ArticlePDF Available

The 2019–2020 Novel Coronavirus (Severe Acute Respiratory Syndrome Coronavirus 2) Pandemic: A Joint American College of Academic International Medicine‑World Academic Council of Emergency Medicine Multidisciplinary COVID‑19 Working Group Consensus Paper


Abstract and Figures

What started as a cluster of patients with a mysterious respiratory illness in Wuhan, China, in December 2019, was later determined to be coronavirus disease 2019 (COVID‑19). The pathogen severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2), a novel Betacoronavirus, was subsequently isolated as the causative agent. SARS‑CoV‑2 is transmitted by respiratory droplets and fomites and presents clinically with fever, fatigue, myalgias, conjunctivitis, anosmia, dysgeusia, sore throat, nasal congestion, cough, dyspnea, nausea, vomiting, and/or diarrhea. In most critical cases, symptoms can escalate into acute respiratory distress syndrome accompanied by a runaway inflammatory cytokine response and multiorgan failure. As of this article’s publication date, COVID‑19 has spread to approximately 200 countries and territories, with over 4.3 million infections and more than 290,000 deaths as it has escalated into a global pandemic. Public health concerns mount as the situation evolves with an increasing number of infection hotspots around the globe. New information about the virus is emerging just as rapidly. This has led to the prompt development of clinical patient risk stratification tools to aid in determining the need for testing, isolation, monitoring, ventilator support, and disposition. COVID‑19 spread is rapid, including imported cases in travelers, cases among close contacts of known infected individuals, and community‑acquired cases without a readily identifiable source of infection. Critical shortages of personal protective equipment and ventilators are compounding the stress on overburdened healthcare systems. The continued challenges of social distancing, containment, isolation, and surge capacity in already stressed hospitals, clinics, and emergency departments have led to a swell in technologically‑assisted care delivery strategies, such as telemedicine and web‑based triage. As the race to develop an effective vaccine intensifies, several clinical trials of antivirals and immune modulators are underway, though no reliable COVID‑19‑specific therapeutics (inclusive of some potentially effective single and multi-drug regimens) have been identified as of yet. With many nations and regions declaring a state of emergency, unprecedented quarantine, social distancing, and border closing efforts are underway. Implementation of social and physical isolation measures has caused sudden and profound economic hardship, with marked decreases in global trade and local small business activity alike, and full ramifications likely yet to be felt. Current state‑of‑science, mitigation strategies, possible therapies, ethical considerations for healthcare workers and policymakers, as well as lessons learned for this evolving global threat and the eventual return to a “new normal” are discussed in this article. Keywords: 2019‑nCoV, coronavirus, COVID‑19, global impact, International Health Security, pandemic, severe acute respiratory syndrome coronavirus 2
Content may be subject to copyright.
© 2020 Journal of Global Infectious Diseases | Published by Wolters Kluwer - Medknow 47
Consensus Paper
Address for correspondence: Dr. Stanislaw P Stawicki,
Department of Research and Innovation, St. Luke’s University Health
Network, 801 Ostrum Street, Bethlehem, Pennsylvania, USA.
Access this article online
Quick Response Code:
This is an open access journal, and arcles are distributed under the terms of the Creave
Commons Aribuon‑NonCommercial‑ShareAlike 4.0 License, which allows others to
remix, tweak, and build upon the work non‑commercially, as long as appropriate credit
is given and the new creaons are licensed under the idencal terms.
For reprints contact:
How to cite this article: Stawicki SP, Jeanmonod R, Miller AC, Paladino L,
Gaieski DF, Yaee AQ, et al. The 2019–2020 Novel coronavirus (Severe
Acute Respiratory Syndrome Coronavirus 2) Pandemic: A Joint
American College of Academic International Medicine-World Academic
Council of Emergency Medicine Multidisciplinary COVID-19 Working
Group Consensus Paper. J Global Infect Dis 2020;XX:XX-XX.
Received: 16 April 2020 Revised: 25 April 2020
Accepted: 04 May 2020 Published: ***
The 2019–2020 Novel Coronavirus (Severe Acute Respiratory
Syndrome Coronavirus 2) Pandemic: A Joint American College
of Academic International Medicine‑World Academic Council
of Emergency Medicine Multidisciplinary COVID‑19 Working
Group Consensus Paper
Stanislaw P Stawicki1,2, Rebecca Jeanmonod1,2, Andrew C Miller1, Lorenzo Paladino1,2, David F Gaieski2, Anna Q Yaffee1, Annelies De Wulf1,
Joydeep Grover 2, Thomas J. Papadimos1, Christina Bloem1, Sagar C Galwankar1,2, Vivek Chauhan2, Michael S. Firstenberg1,2, Salvatore Di Somma2,
Donald Jeanmonod1,2, Sona M Garg1, Veronica Tucci1, Harry L Anderson III1,2, Lateef Fatimah2, Tamara J Worlton1, Siddharth P Dubhashi2, Krystal S Glaze1,
Sagar Sinha2, Ijeoma Nnodim Opara1, Vikas Yellapu1, Dhanashree Kelkar2, Ayman El‑Menyar2, Vimal Krishnan2, S Venkataramanaiah2, Yan Leyfman1,
Hassan Ali Saoud Al Thani2, Prabath WB Nanayakkara2, Sudip Nanda1, Eric Cioè‑Peña1, Indrani Sardesai2, Shruti Chandra2, Aruna Munasinghe2, Vibha Dutta2,
Silvana Teixeira Dal Ponte1, Ricardo Izurieta1, Juan A Asensio1,2, Manish Garg1,2
1Working Group on International Health Security, The American College of Academic International Academic Medicine, Bethlehem, Pennsylvania, 2COVID‑19 Pandemic
Taskforce, World Academic Congress of Emergency Medicine, Tampa, Florida, USA
What started as a cluster of patients with a mysterious respiratory illness in Wuhan, China, in December 2019, was later determined
to be coronavirus disease 2019 (COVID-19). The pathogen severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel
Betacoronavirus, was subsequently isolated as the causative agent. SARS-CoV-2 is transmitted by respiratory droplets and fomites and
presents clinically with fever, fatigue, myalgias, conjunctivitis, anosmia, dysgeusia, sore throat, nasal congestion, cough, dyspnea, nausea,
vomiting, and/or diarrhea. In most critical cases, symptoms can escalate into acute respiratory distress syndrome accompanied by a runaway
inammatory cytokine response and multiorgan failure. As of this article’s publication date, COVID-19 has spread to approximately 200
countries and territories, with over 4.3 million infections and more than 290,000 deaths as it has escalated into a global pandemic. Public
health concerns mount as the situation evolves with an increasing number of infection hotspots around the globe. New information about
the virus is emerging just as rapidly. This has led to the prompt development of clinical patient risk stratication tools to aid in determining
the need for testing, isolation, monitoring, ventilator support, and disposition. COVID-19 spread is rapid, including imported cases in
travelers, cases among close contacts of known infected individuals, and community-acquired cases without a readily identiable source
of infection. Critical shortages of personal protective equipment and ventilators are compounding the stress on overburdened healthcare
systems. The continued challenges of social distancing, containment, isolation, and surge capacity in already stressed hospitals, clinics, and
emergency departments have led to a swell in technologically-assisted care delivery strategies, such as telemedicine and web-based triage.
As the race to develop an eective vaccine intensies, several clinical trials of antivirals and immune modulators are underway, though
no reliable COVID-19-specic therapeutics (inclusive of some potentially eective single and multi-drug regimens) have been identied
as of yet. With many nations and regions declaring a state of emergency, unprecedented quarantine, social distancing, and border closing
eorts are underway. Implementation of social and physical isolation measures has caused sudden and profound economic hardship, with
marked decreases in global trade and local small business activity alike, and full ramications likely yet to be felt. Current state-of-science,
Stawicki, et al.: Joint ACAIM-WACEM Statement on COVID-19
Journal of Global Infectious Diseases ¦ Volume 12 ¦ Issue 2 ¦ April-June 2020
The modern world is increasingly interlinked. With an extensive
network of air, ground, and sea transportation hubs, one can
travel relatively seamlessly between any two places on the planet
within just a few days’ time.[1-8] When this is superimposed on
the ever-present danger of zoonotic-to-human transmission of
both established and emerging infectious agents, the possibility
exists of a rapidly evolving novel pathogen pandemic.[9] Despite
previous planning and preparations, the current 2019 novel
coronavirus disease (COVID-19) pandemic illustrates how even
the most extensive eorts may be inadequate and exemplies
the need to adapt to quickly changing and unpredictable
circumstances.[10-14] The COVID-19 pandemic has revealed
gaps in current preparedness within and between nations. This
narrative review is intended to provide the reader with a high
level overview of what is known, what remains to be elucidated
regarding the COVID-19 pandemic, and to suggest specic steps
for moving forward as a global community.
focus of the cuRRent ARtIcle
Our objective is to provide insight regarding information gaps and
blind spots that may exist in the available literature and relevant
governmental or press reports regarding the SARS-CoV-2
pandemic. As academic organizations of international scope,
the American College of Academic International Medicine and
the World Academic Council of Emergency Medicine (ACAIM-
WACEM) strongly feel that pandemic readiness has been
suboptimal, there are lessons to be learned, and this article
highlights some of the observed gaps in preparedness, based on
state-of-the-art evidence. It is not the goal of the Working Group
to provide another recap of the current state of the COVID-19
pandemic, nor is it our intent to reiterate much of the information
already available on the Internet.
fRom outbReAk to PAndemIc: An oveRvIew of
oRIgIn And humAn PAthogenIcIty of seveRe Acute
ResPIRAtoRy syndRome coRonAvIRus 2
In December 2019, Chinese authorities reported emergence
of a cluster of severe respiratory infections of unknown
etiology in Wuhan (Hubei Province, China).[15-17] Despite
global eorts to slow the spread of the SARS-CoV-2 and
“atten the curve” [Figure 1], including population-level
“social distancing” (physical separation of people so as not to
contract the illness) and drastic travel restriction/quarantine
measures, the disease relentlessly continued to expand its
reach.[18-22] As of the writing of this Position Statement, the
World Health Organization (WHO) has declared COVID-19
a pandemic[23,24] and the United States (US) has declared a
National Emergency.[25,26] With more than 4.3 million people
with documented SARS-CoV-2 infection and more than
290,000 deaths, the malady continues to spread around the
globe.[27,28] The coronavirus responsible for COVID-19 has
been likened to a bulldozer, capable of causing widespread
severe illness and deaths with terrifying speed, and aecting
those who are most vulnerable.[29,30]
seveRe Acute ResPIRAtoRy syndRome coRonAvIRus
2 vIRus
The seventh identified human coronavirus and third novel
coronavirus to emerge in the past 17 years, SARS-CoV-2 was
isolated in January 2020 as the cause of the SARS-like atypical
pneumonia called COVID-19.[31-35] Phylogenetics has indicated
that SARS-CoV-2 is closely related to bat-derived SARS-like
coronaviruses, bat-SL-CoVZC45 and bat-SL-CoVZXC21.[32,34,36]
Human and zoonotic coronaviruses belong to the Sarbecovirus
subgenus of the family Coronaviridae.[37,38] Currently,
there are four genera: Alphacoronavirus, Betacoronavirus,
Figure 1: Schematic representation of “flattening the curve” during
an outbreak. (A) Typical course of a pandemic without targeted
intervention (e.g. physical distancing). This scenario places undue
burden on healthcare institutions and is likely to exceed preoutbreak
capacity (indicated by dashed horizontal line) and resources available
to treat affected patients; (B) modified curve resulting from the prompt
implementation of mitigation measures (e.g. physical distancing). In this
scenario, both the rate of increase of new cases and the peak number
of cases are significantly lower, permitting the existing infrastructure to
reasonably handle the increased demands associated with an outbreak
mitigation strategies, possible therapies, ethical considerations for healthcare workers and policymakers, as well as lessons learned for this
evolving global threat and the eventual return to a “new normal” are discussed in this article.
Keywords: 2019-nCoV, coronavirus, COVID-19, global impact, International Health Security, pandemic, severe acute respiratory
syndrome coronavirus 2
Stawicki, et al.: Joint ACAIM-WACEM Statement on COVID-19
Journal of Global Infectious Diseases ¦ Volume 12 ¦ Issue 2 ¦ April-June 2020 49
Gammacoronavirus, and Deltacoronavirus. Before the current
COVID-19 pandemic, there were six recognized human respiratory
coronaviruses: HCoV-229E (Alphacoronavirus), HCoV-
OC43 (Betacoronavirus), HCoV-NL63 (Alphacoronavirus), and
HKU1 (Betacoronavirus), which often cause mild respiratory
tract infection; and SARS-CoV (Betacoronavirus) and Middle
East respiratory syndrome (MERS-CoV) (Betacoronavirus),
which may lead to severe or even fatal lower respiratory
tract disease.[39] Coronaviruses are well established as being
causative of respiratory, enteric, and systemic infections across
various animal hosts, including sh, birds, mammals, as well as
humans.[40,41] Of interest, the approximately 96% similarity of
the SARS-CoV-2 at the whole-genome level to a bat coronavirus
strongly suggests the latter as the point of origin,[42] although there
is some controversy over this.[43]
PAthogenesIs of seveRe Acute ResPIRAtoRy
syndRome coRonAvIRus 2
Although much still remains to be learned about the
pathogenicity of SARS-CoV-2, the virus appears to spread
primarily via the droplet nuclei or small particles (which can
travel a considerable distance), and requires contact points
within the mouth, nose, eyes, or other parts of the upper
aerodigestive system.[44,45] There is also early evidence of
fecal–oral transmission.[46,47] The mechanism of cellular entry
is being elucidated and is beyond the scope of the current
review. However, it is now understood that SARS-CoV-2
utilizes the angiotensin-converting enzyme 2 (ACE-2)
receptor as its principal entry portal,[48-51] and possibly as
a route of secondary “metastatic” end-organ disease. Of
interest, outside of the kidney, the greatest concentrations
of ACE-2 are found in the lung and the gastrointestinal
tract,[50] with more recent identication on the nasal epithelial
cells.[52] In addition, evidence shows that CD147-spike
protein, furin, as well as GRP78 receptors all may play a role
in viral entry.[53-55] Finally, there is controversy regarding the
possibility that SARS-CoV-2 may be gradually evolving and
increasing in its genetic diversity; a handful of strains have
been discovered that appear to be mutating, but the observed
process appears to be slower than that seen in inuenza.[56,57]
PAthology of PAtIents wIth seveRe Acute
ResPIRAtoRy syndRome coRonAvIRus 2
Pathology studies of patients who underwent partial lobectomy
procedures and were found to have subclinical COVID-19
infections demonstrated proteinaceous and brin exudate
formation, scattered large protein globules, diuse expansion
of alveolar walls and septa, plugs of proliferating broblasts
in the interstitium, macrophage inltration of airspaces, and
type II pneumocyte hyperplasia (sometimes associated with
suspected viral inclusions).[58] Postmortem studies of the lung
tissue demonstrated predominantly lymphocytic inltration,
with copresence of multinucleated giant cells alongside
the large atypical pneumocytes.[59] There was evidence of
pulmonary brosis that was less severe when compared with
SARS, but there was relatively more tissue edema relative to
SARS.[60] Additional microscopic ndings included diuse
alveolar damage and exudative changes.[59] In addition to
large amounts of viscous secretions found within the alveoli,
there is also the suggestion of regional changes aecting other
intrathoracic structures including the heart.[60]
ePIdemIology of seveRe Acute ResPIRAtoRy
syndRome coRonAvIRus 2
The SARS-CoV-2 infection has been estimated to have a
mean incubation period of 5.1–6.4 days[36,61] and a basic
reproduction number in a range of 2.2–3.6.[36,62] The majority
of patients (97.5%) develop symptoms within 11.5 days (95%
condence interval [CI] 8.2–15.6 days).[61] Furthermore, a
nontrivial proportion of patients (2.5%–17.9%) who tested
positive may remain asymptomatic, supporting the hypothesis
that active asymptomatic transmission occurs.[63-66] Even more
striking, the island nation of Iceland conducted extensive
testing, suggesting that 50% of coronavirus cases exhibited no
symptoms.[67] It has been estimated that the overall proportion of
presymptomatic transmission may be as high as 48%–62%,[64,68]
with viral transmission anywhere between 1 and 3 days before
symptom onset,[69] providing a strong rationale for physical
distancing. Interesting clinical correlations have also emerged
about the relationship between the ABO blood group type
and COVID-19 susceptibility,[70,71] but more investigation is
required before more denitive statements can be made in this
area. Finally, familial (e.g., genetic) predisposition cannot be
excluded at this time, with reports of severe presentations and
deaths among close relatives.[72-75] Further investigation into such
multiple cases involving close relatives will be important to our
overall understanding of the SARS-CoV-2 pathophysiological
behavior and clinical disease characteristics.
clInIcAl PResentAtIon And PAtIent
Symptoms of COVID-19 may range from mild to severe,
with sizable yet varied fatality rates of 2.3% in China, 7.2% in
Italy, and 1.0% in South Korea.[76-80] Most adults and children
with COVID-19 develop a mild-to-moderate, u-like illness
with fever, malaise, cough, and/or dyspnea that resolves in
about 1 week.[81] It has been reported by some patients that the
symptoms may be phasic, with relatively asymptomatic spells
interspersed among severely symptomatic periods,[82-85] while
others report that the illness can be likened to “a slow burn” with
symptoms that linger on before worsening.[85,86] Of importance,
fever is not always present in early illness and among the
elderly.[33] Early anosmia and dysgeusia may be present.[87]
Children and teenagers usually exhibit mild symptoms as
severe infection is rare among younger patients, but deaths
in younger age groups have occurred (e.g., infants less than
1 year of age may have higher morbidity and mortality).[88-91]
Anecdotally, seen mainly among children with COVID-19,
Stawicki, et al.: Joint ACAIM-WACEM Statement on COVID-19
Journal of Global Infectious Diseases ¦ Volume 12 ¦ Issue 2 ¦ April-June 2020
erythematous toe lesions have been described. Dubbed
‘COVID toes,’ their clinical signicance or impact are unclear.
Consistent with adult mortality patterns, recent data also show
that children and teenagers with preexisting conditions, such as
asthma, chronic lung disease, cardiovascular disorders, history
of smoking/vaping, or hemoglobinopathies, may be more likely
to experience severe or even fatal COVID-19.[92-97] In addition,
it is now emerging that morbid obesity also constitutes a major
contributor to mortality, with a magnitude of risk that rivals
that of age.[98] Age distribution of COVID-19 cases, compiled
from numerous sources around the globe, is provided in
Figure 2.[79,89,90,99-104]
In terms of symptoms, systemic and pulmonary manifestations
predominate, with an increasing emphasis placed on
gastrointestinal symptoms as both diagnostically and
prognostically important (note, gastrointestinal symptoms
are more prevalent than initially thought).[105-107] In one study
from Wuhan, China, examining >1000 cases of COVID-19,
the predominant symptoms were fever and dry cough, with
80% suffering only from mild-to-moderate disease and
approximately 13% experiencing severe disease.[81] The most
commonly reported symptoms are fever, dry cough, myalgias,
fatigue, pneumonia, and dyspnea. Even a clinical picture
compatible with acute pancreatitis has been described.[108]
High temperature is not always recorded at initial presentation.
In particular, elderly patients can be afebrile in the early stages,
with only chills, with or without respiratory symptoms.[33]
Less common symptoms include the production of sputum,
headache, hemoptysis, and rhinorrhea.[16,47,105,106,109] Other
studies noted that gastrointestinal symptoms, such as
diarrhea (2%–10.1%) and nausea and vomiting (1%–3.6%),
were present in a nontrivial proportion of patients.[16,105,106,109]
Moreover, a signicant proportion of patients presented
initially with those atypical gastrointestinal symptoms.[110]
Anosmia and dysgeusia have recently been reported as early
symptoms associated with COVID-19.[87,111] Of importance,
many frontline healthcare workers (HCWs) and caregivers
report the nding of “red eyes” as one of the manifestations
of COVID-19.[112,113] A detailed listing of signs and symptoms
of COVID-19 is provided in Table 1.[16,33,47,81,85,109,112-121]
A smaller proportion of COVID-19 patients will progress to
develop severe illness (8%–15%) including respiratory failure,
acute respiratory distress syndrome (ARDS), multiple organ
failure, and potentially death.[36,115,121,122] Among those admitted
to the intensive care unit (ICU), mortality ranged from <14%
to >66%, depending on patient-specific factors.[121,123,124]
Common ancillary ndings include lymphocytopenia;[125]
increased neutrophil-to-lymphocyte ratio; decreased
percentages of basophils, eosinophils, and monocytes;[126]
thrombocytopenia (severe disease);[122] elevated lactate
dehydrogenase (LDH), elevated C-reactive protein (CRP),
elevated ferritin, elevated D-dimer, elevated interleukin-6 (IL-
Figure 2: Age distribution of COVID‑19 cases based on composite data
from around the globe[79,89,90,99‑104]
Table 1: Reported symptoms of COVID‑19 infection
Category Symptom Reported
General/systemic Fever 83-98.6%
Malaise and fatigue 11-69.6%
Body aches and myalgias 11-44%
Chills 11%
Cyclical nature of symptoms,
clinical ups and downs
Acute cardiac injury/dysfunction Reported
Acute renal failure Reported
Respiratory Dry cough 46-82%
Productive cough 12-28.2%
Shortness of breath 19-31.2%
Hemoptysis 1-5%
Chest pain 2%
Feeling of “chest pressure” Reported
Silent or exertional hypoxia Reported
HEENT Pharyngitis/pharyngalgia 5-17.4%
Nasal congestion/rhinorrhea 4%
Watery eyes <1%
Cyanotic, “blue lips” Reported
Loss of smell and taste Reported
Conjunctival injection/”red eyes” Reported
Gastrointestinal Loss of appetite 39.9-50%
Diarrhea 2-15%
Nausea and vomiting 1-10.1%
Abdominal pain 2.2%
Pancreatitis Reported
Neurological Headache 6.5-12.1%
Dizziness 9.4%
Confusion 9%
Delirium, especially non-agitated
delirium in the elderly
Encephalopathy Reported
Meningitis Reported
Seizures Reported
More than one sign of symptom was present in 90% of patients; fever,
cough, and shortness of breath were present in 15% of patients. *Range
provided whenever available. HEENT: Head, ears, eyes, nose, and throat.
Data sources[16,33,47,81,85,109,112-121]
Stawicki, et al.: Joint ACAIM-WACEM Statement on COVID-19
Journal of Global Infectious Diseases ¦ Volume 12 ¦ Issue 2 ¦ April-June 2020 51
6);[81] new pulmonary infiltrates on chest radiography or
computed tomography (CT); and no improvement in symptoms
after 3 days of directed treatment.[127] Known contact with
another COVID-19-positive individual may be reported, but the
importance of this will become less relevant with community
spread. Patients at increased risk of mortality include those
with advanced age, medical comorbidities/preexisting
illnesses (e.g., diabetes, hypertension, malignancy), active
tobacco smoking/vaping, morbid obesity, and high sequential
organ failure assessment (SOFA) score.[77,94,95,98,117,118,128]
The time course for mild symptoms may be as short as 1 week,
while severe cases may extend far beyond that.[129] One
retrospective study of 191 hospitalized patients in Wuhan reported
that the median time from illness onset to initiation of mechanical
ventilation was 14.5 days and from onset of illness to day of
discharge was 22 days.[116] Mortality is primarily among middle-
aged and elderly patients with preexisting diseases (malignancy,
cirrhosis, hypertension, coronary heart disease, diabetes, kidney
failure, immunodeficiency, cerebrovascular diseases, and
neurodegenerative diseases) [Figures 3 and 4].[28,79,102,116,127,130-137]
Finally, several countries reported that the mortality rate is
signicantly higher (by approximately a factor of 2) among
men [Figure 5].[138-141] The latter nding may be related to recent
data showing that SARS-CoV-2 is more prevalent in male
children and adolescents (57%) compared to female children and
adolescents (43%), suggesting a more fundamental dierence
between genders, based on immune and/or other mechanistic
Of importance, early testing policies have significantly
inuenced reported mortality rates. For example, in Italy or
the US, where surveillance testing was limited and reserved
for more acutely ill patients, reported mortality has been
signicantly higher than for countries such as the Republic
of Korea or Germany where widespread surveillance testing
captured a greater proportion of patients with less severe
manifestations.[77,142] Variance in mortality gures depends on
the demographic prole of countries and the governmental
response to the pandemic in the initial stages.
bIomARkeRs And otheR PRognostIc coRRelAtes of
Complicated COVID-19 infection carries a high mortality, with
multiorgan dysfunction characterized by respiratory failure,
encephalopathy, acute cardiac injury and cardiac failure,
renal failure, and other end-organ damage.[143,144] In a recently
published paper, retrospective data from a cohort of patients
from Wuhan, China, showed that older age and comorbidities
including diabetes and hypertension, high SOFA scores, and
D-dimer > 1 µg/L are associated with poor prognosis at an early
stage.[128] In the same study, other biomarker abnormalities were
associated with higher incidence of mortality including a low
platelet count, high levels of LDH, and elevated creatinine.[128]
Guo et al.[145] published the MuLBSTA (multilobar inltrates,
lymphocytes ≤0.8 × 109/L, bacterial infection, smoking status,
Figure 3: Mor tality associated with COVID‑19 infections by age.
Composite global data compiled from multiple sources[28,79,102,130‑132]
Figure 4: Mortality rates associated with different comorbid conditions.
Additional factors that may predispose to increased mortality include
morbid obesity, neurodegenerative diseases, and immunocompromised
status. Data from Italy demonstrate that 25.1% of mor talities had 1
comorbid condition, 25.6% had two, and 48.5% had three or more
illnesses. A repor t from China demonstrated 15.4% mortality for those
with ≥2 comorbidities, compared to mor tality of 5.6% for those with one
or no comorbid condition[116,133‑137]
Figure 5: Comparison of composite global mortality rates by patient
Stawicki, et al.: Joint ACAIM-WACEM Statement on COVID-19
Journal of Global Infectious Diseases ¦ Volume 12 ¦ Issue 2 ¦ April-June 2020
hypertension, and age ≥60 years) score, which may help
prognosticate outcomes in COVID-19 patients.[109] The Brescia-
COVID Respiratory Severity Scale (BCRSS) incorporates
four simple data elements into a clinically useful stratication
system: (a) patient wheezing or unable to speak in full
sentences while at rest or with minimal eort; (b) respiratory
rate >22; (c) PaO2 <65 mmHg or SpO2 <90%; and (d) repeat
chest X-ray (CXR) shows signicant pulmonary worsening.[146]
Other prognostic biomarkers including D-dimer, high-sensitivity
troponin I, serum ferritin, LDH, IL-6, and procalcitonin
also showed both clinical and predictive utility.[128,143,147]
Repeated procalcitonin ”typical” assessments may be useful in
determining complicated COVID-19, especially in the setting
of clinical deterioration and bacterial superinfection.[148]
Among early ndings in Wuhan, China, was the appearance
of dysregulated immune response, with observed relatively
higher leukocyte (5.6 vs. 4.9 × 109) and neutrophil (4.3 vs.
3.2 × 109) counts; relatively lower lymphocyte counts (0.8 vs.
1.0 × 109); higher neutrophil-to-lymphocyte ratio (5.5 vs.
3.2); as well as lower percentages of basophils, eosinophils,
and monocytes.[126] Others noted that lymphopenia may
be a part of a COVID-19 clinical signature[125,143,149] and
that thrombocytopenia may be a hallmark of severe
COVID-19 cases.[122,143] Although generally highly sensitive
and nonspecic, CRP, erythrocyte sedimentation rate (ESR),
and ferritin may oer prognostic utility when combined with
other indicators of disease acuity and/or when followed over
time for trending purposes.[121,143,149-151] A plethora of other,
likely nonspecic laboratory derangements were also noted
among nonsurvivors.[143]
In a study utilizing an articial intelligence (AI) approach to
determine the factors most strongly associated with ARDS,
several surprising observations emerged.[152] The rst factor
is elevated levels of alanine aminotransferase (ALT). The
second was the presence of reported myalgias. The nal
strong predictor of respiratory distress was elevated levels of
hemoglobin (possibly related to male gender or undeclared
tobacco use or vaping). Taken together, these three factors
exhibited 70%–80% accuracy in predicting the risk of
ARDS.[152] Finally, observations have been made of the high
prevalence of hypokalemia in COVID-19 patients, apparently
attributable to continuous renal potassium loss associated with
the degradation of ACE-2.[153] It was also noted that the end of
renal potassium loss constitutes a good prognostic sign and
may represent a reliable, in-time, and sensitive biomarker
reflecting the normalization of renin-angiotensin system
pathology of COVID-19.[153]
dIAgnostIc ImAgIng
Although diagnosis of COVID-19 is denitively made through
laboratory testing, diagnostic imaging can be helpful in
supporting the diagnosis or identifying alternative pathology.
CXR is often used as a rst line diagnostic tool in patients
with respiratory complaints, but it lacks sensitivity and
specicity relative to CT in patients with COVID-19 and
often temporally lags CT in ndings.[154] Specically, CXR
may not be able to detect ground-glass opacities (GGO), and
the bibasilar nature of their distribution in COVID-19 may
be obscured by the cardiomediastinal silhouette or in the
area overlying the diaphragm.[154] Both CXR and CT of the
thorax can demonstrate a range of ndings, from “normal
appearance” to “pulmonary consolidations” to “diffuse
multifocal GGO” characteristic of ARDS [Table 2].[65,155-158]
In one study, pulmonary changes on CT were noted in 54%
of asymptomatic cases, compared to 80% in the symptomatic
group.[65] In the same study, asymptomatic cases tended to
have more GGOs whereas symptomatic patients demonstrated
more consolidations.[65] In another study, chest CT was found
to be highly sensitive for COVID-19 diagnosis, and disease
severity on the CT appeared to correlate with both clinical
severity and subsequent recovery.[159] The most “typical” CT
ndings of COVID are changes (usually GGOs or multifocal
inltrates), that are located bilaterally and mainly distributed
in the posterior and peripheral portions of the lungs.[154] For
CXR, the severity of ndings appears to peak at approximately
10–12 days following symptom onset.[65]
In terms of COVID-19-related changes seen on CT scanning,
GGOs were more prevalent than consolidations in 74% of
cases, with the opposite noted in 26% of instances.[65] A
majority of opacities were noted to be peripheral (56%)
or mixed (37%) in distribution, with only 7% being more
central in location.[65] In a study from Japan, the distribution
of “lobes aected,” from 1 to 5, was fairly even (the least
frequent being four lobes involved in 13% of cases and
the most being two lobes involved in 26%).[65] However,
another study from Italy demonstrated that approximately
84% of patients had evidence of four lobes (10%) or ve
lobes (74%) involved.[157] When evaluating available reports,
Table 2: Key computed tomography and chest X‑ray
features of COVID‑19 infection
Finding Computed tomography
radiography (%)
Multifocal lung lesions
with peripheral distribution
>50 41
Ground-glass opacities 40.3-100 33
Consolidation 13-72 47
“Crazy paving” pattern 12-39 -
Interlobular thickening 13-37 -
Linear opacities combined 27-61 -
“Airway abnormalities” 17.7-27
Pleural thickening 48.4
Pleural eusion 3-9.7 3
Pericardial eusion 5-
Lymphadenopathy 58 -
Normal 23 (initially, especially
in asymptomatic
patients, but many
Data compiled from several sources[65,155-158]
Stawicki, et al.: Joint ACAIM-WACEM Statement on COVID-19
Journal of Global Infectious Diseases ¦ Volume 12 ¦ Issue 2 ¦ April-June 2020 53
>2 lobes were found to be aected in 76%–93% of cases,
with bilateral lung involvement in 82%–91% of cases and
slight right lung (60%) predominance.[65,157]
Debate continues regarding the utility of contrast-
enhanced chest CT, with proponents indicating that the
additional information gained from intravenous contrast
administration (e.g., the identification of pulmonary
embolism [PE]) is more important than the associated risks.
Indeed, more and more cases of coincident PE (and other
thrombotic and/or thromboembolic events) with COVID-19
infection are being reported, and many feel that the infection
may predispose to venous thromboembolism.[160,161] If this
is the case, foregoing CT angiography may leave the
patient with unidentified, severe, and potentially treatable
conditions. Opponents of contrast-enhanced chest CT cite
the time delay for terminally cleaning the CT machine in
busy centers when the management is largely clinical; the
risk of contrast nephropathy exacerbating renal failure in
potentially critical patients; the risk of systemic reactions
to contrast medium; as well as the low incidence of findings
that require additional radiographic information.[162-165]
In resource-limited settings, including healthcare facilities
overwhelmed with rapid increases in patient volumes, the use
of point-of-care ultrasonography (POCUS) can be of immense
value. Reports from the most severely aected countries and
regions indicate that there is a good clinical correlation between
CT thorax and pleural ultrasound.[166,167] Mild GGOs visualized
on CT scanning correlate well with scattered B-lines on bedside
ultrasound.[166] As disease progresses and GGOs become
conuent on CT, so, too, will ultrasound B-lines coalesce.[166]
More severe disease will demonstrate peripheral consolidation
and pleural thickening, with progression of consolidation in
cases of advanced illness.[166,167] Because pulmonary ndings
are more common in the posterior portions of the lungs, it is
important to ensure that these areas are adequately visualized
during POCUS examination, which can pose technical
limitations in high acuity patients. Given the need to assess the
peripheral and posterior regions of the lung, the sensitivity and
specicity of POCUS for diagnosis of COVID-19 in dyspneic
real-time scenarios are presently not known. Among other
applications of POCUS is the assessment of intravascular
volume status, including inferior vena cava or subclavian
venous collapsibility measurements.[168,169]
dIAgnostIc confIRmAtoRy vIRAl testIng
Several different diagnostic assays are available due to
emergency use authorizations from the US Food and Drug
Administration (FDA).[170] The testing methodologies consist of
a variation on nucleic acid amplication technology intended
for the in vitro qualitative detection of SARS-CoV-2 viral
ribonucleic acid (RNA). Manufacturers are publishing analytical
reactivity (sensitivity) as low as 80% and as high as 100%. Each
assay reviewed, at the time of this article, only noted SARS-CoV
as a cross-reactive test result (analytical specicity).
The majority of COVID-19 diagnostic assays available
to date require the collection of nasopharyngeal swabs,
which should be submitted to the laboratory in universal or
viral transport media. Sputum and bronchial lavage (BAL)
samples are also acceptable for these tests.[171] It is important
to note that sample collection, handling, and transport
directly impact an assay’s analytical sensitivity.[171] In
addition, a high-sensitivity assay may result in an increased
risk of false positive reporting due to contaminated work
areas (from previously processed positive samples).
Nonetheless, the diagnosis of COVID-19 requires a skilled
clinician who can correlate real-time patient observations
and disease-specic patterns, with the totality of available
diagnostic information (e.g., clinical, laboratory, and
radiographic evidence). For example, patients with
pulmonary disease are often nasal swab negative and only
positive on the sputum or BAL testing, thus necessitating
a high index of clinical suspicion in all pneumonia
patients. Speedy and accurate diagnosis is critical to avoid
delays in the provision of critical medical care, especially
when patients experience rapid pulmonary and systemic
COVID-19 testing algorithms should be used to guide
clinicians on whom to test, when to repeat testing, as well
as alternative testing options (i.e., CT scans of the chest).[172]
Other factors that may aect a COVID-19 testing algorithm
include the clinician’s urgency to receive the result, medical
facility setting, and the availability of testing and collection
resources in the laboratory. Current testing algorithms include
some version of a polymerase chain reaction (PCR) test and/or
other SARS-CoV-2 testing. Due to the high false-negative rates
in some tests, treatment algorithms may opt for approaches that
call for one or more repeat COVID-19 test on the same patient
over multiple days to increase the chances of identifying and/
or conrming a positive. To expand testing capacity, veterinary
laboratories can be retooled to assist in such repeat testing by
running human COVID-19 diagnostics.[173]
Judicious utilization of available diagnostic infrastructure
is of critical importance, especially during the early phases
of the outbreak when testing capacity may not be fully
developed (e.g., before transition to active community
spread takes place) and within active disease hotspots
when resource considerations predominate. Pooled
sampling techniques for COVID-19 surveillance have been
described in crisis situations.[174] Samples from multiple
cases can be tested simultaneously, thereby cutting down
on cost, time, and requirement for reagents, with improved
overall eciency. Revised testing policies warrant such
interventions, especially amid severe shortages of testing
kit supplies.[175] This surveillance strategy is capable of
quickly grading the severity of the disease spread in a given
population and thus providing early warning signals to
public health ocials.[175,176] Negative results of a “sample
pool” will save a lot of resources. However, a positive
Stawicki, et al.: Joint ACAIM-WACEM Statement on COVID-19
Journal of Global Infectious Diseases ¦ Volume 12 ¦ Issue 2 ¦ April-June 2020
result in a pooled test will require further analysis to detect
individual positives. An associated algorithm and testing
optimization graph are provided in Figure 6.[177]
synoPsIs of clInIcAl mAnAgement of covId-19,
wIth focus on PRotocol-dRIven, evIdence-bAsed
The clinical management approach for SARS-CoV-2
infection is an evolving process. Consequently, we would
like to focus our eort in this area on a practical survival
guide for frontline clinical personnel [Appendix A]. In
addition, the Combined ACAIM-WACEM Consortium
created a dedicated resource hub for centralized clinical
protocol storage from around the world, available for
all to access, adopt, and use.[178] Of importance, this
also includes critical intrafacility and interfacility
patient transfer logistics.[179] Finally, there are important
COVID-19 considerations that directly impact the areas of
surgery,[180-182] endoscopy,[183,184] anesthesiology,[180,185] and
related disciplines.[186-188]
Although patients with COVID-19 pneumonia and respiratory
distress share many clinical similarities with patients suering
from other types of severe viral pneumonia, and often meet
the Berlin denition of ARDS, accumulating clinical evidence
suggests that there are important phenotypic dierences in their
presentation.[189] While most patients do not require immediate
intubation on emergency department (ED) arrival, patients
can decompensate quickly depending upon their viral load,
comorbidities, and length of clinical illness among other factors.
A systematic, escalating, stepwise approach to respiratory
support is essential. A patient who arrives to the ED with
hypoxia should immediately be placed on nasal cannula (NC)
or facemask (FM) with appropriate supplemental oxygen
Figure 6: Pooled testing algorithm (top) and optimization curves showing the relationship between the median testing pool size and the median number
of testing kits required (bottom). Algorithm and graph courtesy of Dr. S Venkataramanaiah, Indian Institute of Management, Lucknow[177]
Stawicki, et al.: Joint ACAIM-WACEM Statement on COVID-19
Journal of Global Infectious Diseases ¦ Volume 12 ¦ Issue 2 ¦ April-June 2020 55
surgical mask placed over it may decrease the risk.[198] During
all airway and respiratory maneuvers, extreme caution should
be exercised, and the patient should be closely monitored for
factors that would indicate a need for intubation, including
decreasing or increasing respiratory rate, depressed mental
status, worsening hypoxia despite escalating therapy, and
inability to protect the airway.[190] During these advanced
procedures, it is important to maintain the safety of HCWs by
limiting the number of those directly caring for the patient to
essential personnel and utilizing a negative pressure room (if
available). The following diagram demonstrates a suggested
oxygenation escalation strategy [Figure 8].
When the decision to intubate is undertaken, the most
experienced intubator, dressed in full personal protective
equipment (PPE, that at minimum includes an N95 mask,
protective eye wear, uid impervious gowns, and gloves),
should perform the intubation using video laryngoscopy
if available. Although the Surviving Sepsis Campaign
Guidelines recommend an ARDSNet ventilator strategy in
these patients (tidal volumes of 4–8 ml/kg of predicted body
weight; higher positive end-expiratory pressure [PEEP]
strategy), there is emerging evidence suggesting that more
than one phenotype of COVID-19 respiratory failure
may exist. Gattinoni et al. have recently described two
primary patient groups in this context: (a) L-type with low
elastance (normal compliance), low lung weight, and low
lung recruitability; and (b) H-type with high elastance (low
compliance), high lung weight, and high lung recruitability.[189]
Obviously, the respiratory management strategies in these
two patient types will be markedly dierent. L-type patients
are more likely to respond to NC, HFNC, and NIPPV than
H-type patients. Once intubated, a lower PEEP strategy may
improve outcomes since there is little recruitable lung. H-type
patients should be approached as in a traditional severe ARDS
scenario where one would be treated with an escalating PEEP
strategy. It is important to remember that the observations
from Gattinoni et al. are based on a small cohort of patients
and that the number of primary types of lung injury in the
Figure 7: A schematic depicting the steps of the proning procedure to
improve lung recruitment in COVID‑19 patients; it is recommended that
proning is initiated early in the hospital course, well before considering
noninvasive or invasive ventilator support
levels and their response should be monitored closely. Patients
who present on a spectrum from “normal” to “tachypneic”
with normal oxygen saturation should have an ambulatory
pulse oximetry recorded for a 60-s period to ensure that
exertional (a.k.a., silent or occult) hypoxia does not develop
or worsen.[190,191] For patients with normal oxygenation (or
hyperoxemia), it is critical for a clinical care team to downtitrate
oxygen to preserve precious resources.
Patients with acute hypoxemic respiratory failure who fail NC
and/or FM oxygenation may be considered for a trial of high-ow
NC (HFNC). Some patients can be managed using this strategy
alone and do not require escalation to endotracheal intubation;
however, this approach may be considered controversial by some
provider groups who favor closed-system noninvasive positive
pressure ventilation (NIPPV) instead. When transitioning to NIPPV,
it is essential to utilize a closed loop setup or to place the patient in
a negative pressure room because this approach may increase viral
dispersal into the environment. It should be noted that this specic
area is continuously evolving and recommendations may change.
Small studies have shown that patients with severe COVID-19
infection-related ARDS assisted by mechanical ventilation who do
not respond well to high-positive pressure may respond better to prone
positioning in attempts to increase lung recruitment.[192] The postulated
mechanism is that proning allows recruitment of posterior lung units
and improves ventilation/perfusion matching.[193] Interestingly, this
benet may also extend to COVID-19 patients not yet mechanically
ventilated, who are receiving NC, HFNC, or NIPPV as a maneuver
to improve oxygenation and prevent intubation.[194,195] In one study,
physicians were able to keep invasive mechanical ventilation use to
a minimum using awake prone positioning.[196] Other studies in viral
pneumonia (non-COVID-19) reported similar success with proning
to stave o invasive mechanical ventilation.[197] The awake patient can
turn prone, move about, and turn on their sides. Published algorithms
outline that the progression of patients with persistently low levels
of blood oxygenation on NC can be sequentially scaled to HFNC to
HFNC with proning, then NIPPV, and nally NIPPV with proning in
an attempt to prevent intubation [Figure 7].[197]
The use of HFNC, FM, and NIPPV may pose a risk to providers
because of aerosolization of pathogens. HFNC use with a
Figure 8: Diagram showing the gradual, step‑wise escalation of
supplemental oxygen therapy, from nasal cannula to intubation and
mechanical ventilation
Stawicki, et al.: Joint ACAIM-WACEM Statement on COVID-19
Journal of Global Infectious Diseases ¦ Volume 12 ¦ Issue 2 ¦ April-June 2020
very heterogeneous COVID-19 pulmonary syndrome can be
even more diverse.[189]
With variations in the number of ventilators at different
institutions, there has been a lot of discussion about allocation
of available devices to the most appropriate patients, low-cost
ventilator substitutes, use of manual ventilators for some
patients, and the possibility of ventilating multiple patients
on a single ventilator circuit. Experimental work in a sheep
model by Paladino et al. demonstrated the feasibility of
ventilating four sheep on a single ventilator with a modied
circuit.[199] Algorithms to apply this to two or four humans
during a pandemic have been developed. However, due to
the complexity of such a ventilator circuit, a number of safety
concerns exist and consequently this approach should only be
considered as an “absolute last resort” option.[200] A summary of
the most commonly utilized types of oxygenation/ventilation
support is provided in Table 3.[201]
For patients with profound respiratory failure, conventional
mechanical ventilatory therapies – including salvage therapies
such as prone ventilation, inhaled nitric oxide, or inhaled
prostacyclin – might not be sucient to support physiologic
oxygenation and ventilation. Extracorporeal membrane
oxygenation (ECMO) is an established therapeutic modality
for the treatment of advanced ARDS refractory to maximal
medical therapy.[202,203] Typically, for ARDS, ECMO is used in
a venovenous conguration in which deoxygenated blood is
drained from the venous system and actively pumped through
an “oxygenator membrane” in which a sweep gas diuses out
the carbon dioxide and oxygenates the blood as it is returned to
the body – typically as close to the right heart and pulmonary
arterial tree as possible. This is dierentiated from venoarterial
ECMO in which the oxygenated blood is returned back to the
arterial tree (i.e., the aorta) to augment the cardiac output and
provide a more active, mechanically assisted, supply of oxygen
to the tissue beds and end organs. In essence, venovenous
ECMO is used for isolated pulmonary failure in the setting of
preserved cardiac function while venoarterial ECMO is used
in the setting of cardiac failure with a need for oxygenation
and ventilation support (as opposed to isolated cardiac failure
with preserved pulmonary function in which a ventricular
assist device might be a preferred option).[204] While there is
extensive literature supporting the use of ECMO for ARDS,
regardless of the etiology, there are concerns regarding the
appropriate use of ECMO in COVID-19 infections. Some of
the early data and experiences from China have suggested
poor outcomes with ECMO in these critically ill patients,[116]
with additional concerns raised by anecdotal experiences of
unfavorable outcomes in certain higher-risk populations.[205]
Nevertheless, there is growing advocacy to support the use
of ECMO in centers with experience in this very complex
and resource-intensive modality.[206] Proponents of ECMO
have speculated that poor patient selection, delayed initiation
of therapy, and limited center experiences are the signicant
factors contributing to suboptimal outcomes; hence, they
advocate for ECMO use only by established programs,
specically recommending that new program development
should not be undertaken at this time for the sole purpose
of supporting COVID-19 patients.[207,208] Clearly, while the
use of ECMO in this population is highly controversial, it
is imperative that ECMO providers participate in ongoing
registry and research studies to help better dene the role of
extracorporeal support in this extremely ill and heterogeneous
group of patients [Table 4].
In summary, in those patients with advanced respiratory failure,
failing prone positioning maneuvers, and maximal ventilatory
therapy, who are otherwise reasonable candidates based upon
current risk assessment scoring systems,[209,210] ECMO should
be considered to treat severe COVID-19 pulmonary infections.
This view is supported by the American Thoracic Society and
the Extracorporeal Life Support Organization.[206,211]
end-of-lIfe decIsIons And cARdIoPulmonARy
ResuscItAtIon foR the clInIcIAn
Decisions at the end-of-life, especially those pertaining to
cardiopulmonary resuscitation (CPR), have come to the
forefront during the COVID-19 pandemic.[212,213] Truog et al.[214]
and Di Blasi[215] have highlighted the shortage of ventilators,
basic disinfectants, and PPE and the important discussions
needed on rationing of care, both in regard to equipment
and its association with end-of-life decisions in regard to
COVID-19 patients; Emanuel et al.[216] have highlighted the
fair allocation of resources from an American perspective.
In the United Kingdom (UK), Mahase and Kmietowicz
call for a re-examination of CPR during this crisis.[217] They
discuss the guidance from the National Health Service (NHS)
Foundation Trust at the University Hospitals, Birmingham,
UK, which states:
Table 3: Reported type of oxygenation support required
by patients with COVID‑19 admitted to the intensive care
Modality Percentage of ICU Cases (%)
Mechanical ventilation ~50%
NIPPV ~42%
Hi-ow ~11%
ECMO 2-5%
ECMO: Extracorporeal membrane oxygenation, NIPPV: Noninvasive
positive pressure ventilation; ICU: Intensive care unit
Table 4: Sites for extracorporeal membrane oxygenation
and COVID‑19 references and registry/outcome tracking
and reporting
Extracorporeal Life Support Organization Registry:
Extracorporeal Life Support Organization Registry:
Extracorporeal Life Support Organization COVID-19 Resources: https://
Stawicki, et al.: Joint ACAIM-WACEM Statement on COVID-19
Journal of Global Infectious Diseases ¦ Volume 12 ¦ Issue 2 ¦ April-June 2020 57
“…patients in cardiac arrest outside the emergency department
can be given debrillator treatment if they have a ‘shockable’
rhythm. But if this fails to restart the heart, further resuscitation
is futile.”
There is variation on some of this guidance throughout the UK.
The Birmingham UK NHS Trust Foundation advises providers
to only use one shock, whereas the guidance from the UK
Resuscitation Council advises three shocks.[218] The Council’s
guidance also says that sta should put on full PPE for aerosol-
generating procedures before initiating CPR in patients with
COVID-19. In the US, the Emergency Cardiovascular Care
Committee and ‘Get with the Guidelines’-Resuscitation task
forces of the American Heart Association recently released the
“Interim Guidance for Basic and Advanced Life Support in
Adults, Children, and Neonates with Suspected or Conrmed
COVID-19.”[219] Their guiding principle in developing interim
recommendations was “... to balance the competing interests
of providing timely and high-quality resuscitation to patients
while simultaneously protecting rescuers.”[219] Their general
approach to resuscitation includes (a) maximum protection of
CPR providers by donning appropriate PPE; (b) prioritization
of oxygenation and ventilation approaches that minimize
aerosolization risk; (c) consideration for using mechanical
CPR devices; and (d) evaluation of the appropriateness of CPR
eorts in individual patients. For out-of-hospital cardiac arrest
compressions, only CPR or mechanical CPR and debrillation
should be prioritized; for in-hospital cardiac arrest, emphasis
should be placed on establishing advanced directives for
critically ill COVID-19 patients, placing those at greatest
risk of cardiac arrest in negative pressure rooms if available,
with close monitoring of vital signs for clinical deterioration.
As indicated above, the approach toward CPR and end-of-life
care during this pandemic will vary from country to country
and from organization to organization. It will be dicult to
establish a consistent approach in these times of rapid disease
spread and the ensuing fear. The mindset of providers, the
public, and the families of victims is important during this
crisis. Wax and Christian put it well:
“The psychologic effects of perceived risk to healthcare
providers and the public, especially for those with conrmed or
suspected 2019-nCoV infection, cannot be ignored. Clear and
transparent communication from governments and healthcare
facilities to sta and public will be essential. The Canadian
experience with SARS taught many lessons, and hopefully,
those lessons will serve in keeping health care workers safe
and providing optimal care to patients infected with 2019-
covId 19 And PRegnAncy
The current data about pregnancy and COVID-19 infections
are heavily biased toward the third trimester patients. Specic
guidance and practice advisories for obstetricians are available
and should be followed.[221,222] Pregnant patients may be more
susceptible to infections as they have decreased immunity,
and also they may be more susceptible to respiratory diseases
as functional residual capacity, end-expiratory volume, and
residual volume all decrease as gestation progresses. The
common symptoms associated with COVID-19 are cough,
fever, dyspnea, and lymphopenia, and this remains the same
for pregnant patients. Due to heightened metabolism, relative
anemia, and increased maternal oxygen consumption, it may
be dicult to distinguish normal shortness of breath from
pathologic dyspnea.[223]
Universal testing of symptomatic pregnant females is
variable because of the testing policies that depend on the
overall community burden and resources for COVID-19 in
each country. The United Arab Emirates, as an example, is
oering drive-in tests for the symptomatic pregnant woman
for free, and it takes less than 5 min to complete the sampling
process.[224] A review of 55 reported cases of COVID-19 in
pregnancy has shown promising results compared to the
SARS-CoV and MERS-CoV. Pooled analysis of pregnant
women shows a case-fatality rate of 0%, 18%, and 25% with
COVID-19, SARS, and MERS, respectively.[225] The reported
pregnancy complications associated with COVID-19 are
miscarriage (2%), intrauterine growth retardation (IUGR,
10%), and preterm delivery (39%).[225,226] At the time of this
publication, there is no denitive support for the presence of
vertical transmission,[225,227] although elevated antibody levels
in infants suggest the possibility of such an occurrence.[228,229]
As mentioned above, COVID-19 has been studied mainly in the
setting of late pregnancy. A retrospective study of nine patients
was done in Wuhan, China. All nine patients underwent cesarean
sections. The amniotic uid, breast milk, and respiratory swabs of
infants in six cases were negative.[227] Current COVID-19 guidance
covers all aspects of care during pregnancy, including oce visits,
labor, and the postpartum period.[221] Specic recommendations
include electronic fetal monitoring; epidural analgesia for labor
to minimize the need for general anesthesia if urgent surgery is
needed; avoidance of birthing pools; shortening of the second
stage of labor for women who become hypoxic; cautious use of
intravenous uids (250–500 ml boluses); and maternal stabilization
before delivery.[221] Consensus guidelines from China provide 10
key recommendations for managing pregnancy and labor during
COVID-19 infection.[230] Two sources state that there is no clear
evidence regarding optimal route and timing of delivery and the
decision should be based on obstetric indications and maternal–
fetal status.[225,230] In terms of breastfeeding, the Royal College
of Obstetricians and Gynaecologists, the American College of
Obstetricians and Gynecologists, and the WHO recommend the
practice even in the setting of active COVID-19 maternal infection.
[221,222,231,232] Since there is a risk of viral transmission through
the respiratory tract, aected mothers should wash their hands
and wear a mask while breastfeeding. If the mother is severely
symptomatic, a recommendation would be to pump milk and have
another provider feed the infant.
Therapeutic considerations, including the use of specific
pharmacological agents, are outlined later in the manuscript,
Stawicki, et al.: Joint ACAIM-WACEM Statement on COVID-19
Journal of Global Infectious Diseases ¦ Volume 12 ¦ Issue 2 ¦ April-June 2020
and will depend on the ultimate outcome of ongoing clinical
trials. Current guidelines regarding the safety of various
therapeutic agents during pregnancy should be consulted before
commencing pharmaceutical interventions. Pregnant women
recovering from COVID-19 infection should have at least one
ultrasound to monitor fetal growth due to 10% incidence of
IUGR. Appropriate PPE should be utilized for all labor and
delivery based on the SARS data; delayed umbilical cord
clamping and avoiding skin-to-skin contact are recommended.
Corticosteroids for fetal lung development should be utilized on
a case-by-case basis. Breastfeeding is not currently specically
contraindicated, but appropriate hand-washing and PPE to
include FMs should be utilized.[233,234]
PAtIent fRAIlty, PhysIologIcAl Age,
comoRbIdItIes, And RIsk stRAtIfIcAtIon
Rapid accurate risk stratification is essential for ensuring
appropriate resource allocation and mitigation of morbidity
and mortality.[235-237] In the setting of SARS-CoV-2 infection,
patients at markedly increased risk of mortality include those with
advanced age and medical comorbidity/preexisting illness.[76,77,117]
It is broadly understood that patient frailty, representing a
conglomerate of “physiological age” and “chronological
age,” is among the key outcome determinants.[238-243] Although
COVID-19 tends to be less severe in younger populations, no age
group is truly spared, and mortality among the younger patients
may be related with symptomatic severity of the infection and
comorbid conditions (e.g., morbid obesity, asthma, insulin-
dependent diabetes, and malignancy).[244] In face of a rapidly
evolving pandemic, the simpler and easier it is to implement
a risk stratication protocol for comorbidity-related risk, the
better the ability to quickly and accurately triage patients.[235-237]
It is also well established that certain comorbid conditions may
predispose patients to higher COVID-19 acuity and associated
mortality [Figure 4].[133] The Italian National Health Institute
reported that while only 0.8% of mortalities had no other reported
comorbidity, approximately 25.1% of those who died had one
other illness, 25.6% had two other illnesses, and 48.5% had three
or more preexisting conditions.[133] Both Italy and China report
that hypertension and diabetes are among the most dominant
comorbid factors, along with heart disease.[133,245] Chronic
respiratory conditions including asthma and increased rates of
tobacco use have also been linked with poor outcomes.[245,246]
Finally, it is recognized that immunocompromised status,
malignancy, chronic renal failure, liver disease, and severe
obesity (body mass index >40) may all be associated with
worse prognosis.[247,248] The presence and specic patterns of
comorbidities may help explain emerging ndings of racial
disparities in mortality of patients with COVID-19 in the US,
although the full understanding of these ndings has yet to be
elucidated and requires further investigation.[249]
PhysIcAl dIstAncIng
In the midst of the 1918 Spanish u pandemic, city authorities
in Philadelphia decided to proceed with the Liberty Loan
Parade, bringing approximately 200,000 people together. A few
months later, there were more than 16,000 inuenza deaths in
the city.[250] Early in the COVID-19 pandemic, on February
25, 2020, Mardi Gras celebrations took place in New Orleans,
Louisiana. Within a few weeks, the city experienced the fastest
uptick in COVID-19 cases and deaths in the world.[251,252]
When the travel ban for visitors from Europe to the US was
announced in mid-March 2020, two important factors may
have contributed to the accelerated growth of COVID-19 cases
in major air travel hub cities across the US and the UK. First,
the ban excluded the UK which provided a potential route
for individuals to circumvent the restrictions in place.[253]
Second, witnesses reported widespread lack of preparation,
with airport authorities conducting “zero checks” in Britain,
including travelers from the global COVID-19 hotspot at the
time Italy.[254] Similarly, alarming travel experiences were
reported in the US in the early March 2020, with neither the
major nor the regional airport hubs performing any organized
COVID-19 checks for those returning from Italy.[255] Air travel
can be just as eective in spreading the disease as any large
human gathering, and contact tracing may not be possible given
the intricacies of the air transportation system and the multitude
of global intersection points involved. Similar concerns are
present when examining the cruise ship industry.[256,257]
Physical distancing strategies (PDSs), ranging from less
restrictive social distancing to complete closure of society,
or “shelter-in-place” orders, have been suggested as an
approach to contain and mitigate the severity of the COVID-19
pandemic.[79,258] PDSs are designed to drastically shift social
mixing patterns and are often used in epidemic settings.[259,260]
In this context, they can be likened to “circuit breakers”
that over time assist in stopping the transmission chain and
attening the epidemic curve [Figure 1].[260,261] Since the WHO
declaration of a pandemic, governments around the world have
advised against public gatherings and encouraged people to
stay at home as much as possible.
Containment eorts help prevent transmission of the disease
from documented cases imported by international travelers,
thus mitigating transition toward community spread, where
disease growth in the local setting occurs without the ability
to clearly identify an exposure.[262] Contact tracing of emerging
cases can aid in making containment more eective.[262,263]
This strategy can succeed by decreasing the total percentage
of infected cases during the period required for vaccine
development, thereby helping to atten the curve. Thus,
contract tracing reduces the rate of increase in cases in various
geographic clusters, so the number of cases is spread out over
time and healthcare resources are not overwhelmed.[264]
The mildest form of PDS is social distancing, which requires
people to limit the size of gatherings (recommendations
range from <10 people to <50 people), to maintain
distance between individuals in social spaces
(recommendations range from 1 to 2 m), and to remain at
Stawicki, et al.: Joint ACAIM-WACEM Statement on COVID-19
Journal of Global Infectious Diseases ¦ Volume 12 ¦ Issue 2 ¦ April-June 2020 59
home whenever possible.[265] If any gatherings of more than
10–50 people were absolutely required and could not be
conducted using virtual platforms, relevant steps such as
temperature checks, screening questionnaires, and collection
of contact tracing details must be implemented. Consequences
of noncompliance, combined with lack of adequate contact
tracing, can be severe, including signicant attributable disease
spread and preventable mortality.[260,266-268] Sustained PDS may
reduce the magnitude of the epidemic peak of COVID-19,
may lead to a smaller number of overall cases, and should
be designed to minimize the spread of the disease, especially
by asymptomatic or minimally symptomatic cases.[21,22]
Lowering (and attening) of the epidemic peak is particularly
important as it provides critical time to develop vaccines,
identify eective therapeutics, and reduce the acute pressure on
the healthcare system.[22] To support this point, countries with
eective testing and contact tracing (e.g., Germany, Denmark,
Czech Republic, Greece, Poland, Slovakia, Singapore, United
Arab Emirates, and South Korea) appear to have passed the
peak of their local epidemics well within national health
system capabilities,[80,142,269,270] while countries/locales that had
a delayed response or a public health policy transition from
“herd immunity” to “strict isolation” are seeing more severe
and prolonged peaks, as well as higher case-fatality rates.[271-273]
To better protect the elderly and other vulnerable populations, the
suspension of any nonessential activities involving such groups
should be mandated immediately (including family visitations).
This is most evident in the setting of nursing homes and long-
term care facilities, where susceptible residents are at especially
high risk of contracting and dying from COVID-19.[274] Beyond
this, places of business, food and beverage outlets, shopping
malls, entertainment venues, and all public institutions must
comply with the above-outlined PDS methodologies. Awareness
should be raised regarding common modes of transmission in
public places, including grocery stores, pharmacies, bathrooms,
and elevators.[275-277] In terms of workforce management, PDSs
include working from home, utilization of teleconferencing
for meetings and discussions, staggered shifts/schedules/
hours, staggered meal times, and other necessary precautions
specic to certain industries.[265,278] Educational institutions
and businesses are beginning to utilize AI, virtual reality, and
high delity simulation to help address some of the challenges
associated with COVID-19 disruptions.[279,280] Flexible electronic
learning (e-learning) is being utilized more frequently for
students to ensure uninterrupted curriculum completion during
the remainder of the school year, without the risk of transmitting
the disease.[281,282] At the tertiary and postgraduate levels, some
face-to-face courses and examinations are being transitioned to
video conferencing.[282,283]
In response to the pandemic, Singapore implemented a
“whole of government” and a “whole of nation” approach,
where everyone’s buy-in was crucial. Advertisements and
posters were used to help educate and create awareness in the
community, with simultaneous media/smartphone messaging
and reinforcements.[284] Being socially responsible must become
a way of life during COVID-19, where every person plays their
required part.[265] Persons who are unwell and have symptoms
suggestive of COVID-19 must seek medical consultation and
stay at home. Good personal hygiene practices are crucial
and hand-shaking has been discouraged (e.g., substitute
gestures including the use of elbows or feet are acceptable,
as are friendly facial expressions). In countries and regions
able to successfully manage their COVID-19 outbreaks, the
population was advised to take their body temperature twice a
day to evaluate for fever.[285] Utilization of tele-triaging, online
self-triage tools, or COVID-19 symptom tracker applications
has reduced ED visits. Places of religious worship such as
temples, mosques, synagogues, and churches, where devotees
congregate regularly to practice their faith, have modied their
gathering practices temporarily to help enforce appropriate
PDS.[286] When COVID-19 clusters are contact traced to
religious institutions, rapid interventions and social isolation
and distancing strategies must be put in place immediately.
Scheduling population-wide events, such as elections, is highly
controversial and requires extreme eorts to prevent active
disease spread during the pandemic.[287,288] Remote voting using
secure, blockchain-based approaches may be the safest and
most reliable solution to this challenge.[289,290] A recent example
of PDS for a large event occurred with the South Korean
parliamentary elections where voting booths were frequently
disinfected, citizens wore masks and gloves, people stayed 1 m
apart, and voters underwent temperature checks.
Nonpharmaceutical interventions (NPIs) are inclusive of PDS.
They represent the personal, environmental, and community
expectation standards to reduce spread of infectious disease,
decrease the overall burden on healthcare facilities, and reduce
morbidity and mortality [Table 5].
A summary of common strategies used to limit the spread of
infection is provided in Table 6. Optimally, when an individual
develops symptoms suggestive of infection with SARS-CoV-2,
they should practice self-quarantine for 14 days, which is
thought to be a sucient period to monitor for the development
of the presenting signs and symptoms of COVID-19.[258,291]
Table 5: Summary of the personal‑, environmental‑,
and community‑accepted norms during and outside of a
Category NPIs recommended
NPIs at time of
Personal Voluntary home
isolation when ill
Respiratory etiquette
Hand hygiene
Voluntary home quarantine
facemask use by ill
(source control)
Environmental Routine surface cleaning -
Community - School closures
Mass gathering
Other social distancing
NPIs: Nonpharmaceutical interventions
Stawicki, et al.: Joint ACAIM-WACEM Statement on COVID-19
Journal of Global Infectious Diseases ¦ Volume 12 ¦ Issue 2 ¦ April-June 2020
Individuals who have tested positive for SARS-CoV-2 and
have mild COVID-19 should be in isolation until they are
symptom-free. This eectively separates them from those
unaected. When geographic hotspots appear where the rate
of increase in cases is rapid, partial shutdown, such as what
has occurred in New York City, or the stricter government
lockdown, may be employed.[19,292] One recent controversy
in the US surrounded the recommendation to use facial
coverings to help reduce person-to-person transmission.[293]
This particular recommendation is based on the observations
that SARS-CoV-2 may spread via droplets generated during
ordinary conversations or even during regular breathing
activity and does not require one to cough or sneeze to transmit
the pathogen.[294,295] The initial lack of widespread face covering
usage may explain some of the dierences between observed
US viral spread patterns and those in Asia, where citizenry was
using masks in much higher numbers at baseline (presumably
due to previous experiences with SARS). In response, a
massive US grassroots eort took place to design and distribute
home-made FMs.[296,297]
bIllIons undeR QuARAntIne oR “stAy-At-home
Given that the infectivity of SARS-CoV-2 is signicantly
higher than that of inuenza, and there is much greater
variability in incubation times, challenging questions arise
regarding the logistics of any quarantine and/or containment
effort(s).[61,62] From an outbreak mechanics perspective,
using a conservative set of assumptions, approximately
only one in 100 cases will develop symptoms after
14 days of active monitoring and quarantine.[61] Given
these parameters, an unprecedented decision to eectively
quarantine an entire province of China was made in an
attempt to contain the COVID-19 outbreak.[20,298,299] In the
US, Europe, Russia, and many other countries and regions
around the globe, “stay-at-home” orders have been issued,
eectively conning entire populations to their residences,
with exceptions for certain essential (e.g., healthcare, food
supply, transportation, and public safety) workers, as well as
very limited essential (e.g. shopping, healthcare visits) and
recreational (e.g. exercise in open spaces) activities under the
regime of continuous physical distancing and FM use.[300-303]
While such strategies might be perceived as an appropriate
response to try and contain the spread of a highly contagious
infection, there also must be concurrent collection and
access to timely, transparent, and accurate data, resources,
and action plans. This will limit, or prevent, the spread of
misinformation, opportunistic preying on public fear, and
mass hysteria.[304,305] The decisions to quarantine or otherwise
geographically conne a population must also consider the
larger implications of removing that population from the
global community. Unless such decisions are made on sound
social and medical principles, data, and objective information,
the risk for chaos and panic becomes magnied. Finally, the
appearance of various scams touting “cures for COVID-19”
and engaging in price gouging as it relates to the sales of
toiletries, N95 respirators, and other essential products to
an already vulnerable and fearful communities are of grave
evolvIng contAInment stRAtegIes
Much has been learned about containment strategies, with
relevant experiences from the SARS, MERS, and Ebola virus
disease outbreaks over the past two decades.[309-313] Isolation
of infected patients and quarantine of potentially infectious
individuals are two containment strategies utilized. In general,
mass quarantine can inict signicant social, psychological,
and economic costs while the ability to detect newly infected
individuals is limited. Probabilistic modeling has shown that
the eectiveness of mass quarantine is inversely related to the
ability to eectively isolate all infected individuals within the
population.[314] Given the previous SARS experience, China
initially tried to contain COVID-19 in Wuhan by adopting
isolation methods. There may have been an opportunity to
institute mass quarantine in Wuhan earlier, perhaps 3 or so
weeks before the ocial declaration, which may have resulted
in less vigorous transmission of COVID-19 within Hubei
Province and its spillover to the rest of China.[315] The number
of cases and mortality did not rise exponentially in any other
city of China once mass quarantine plus isolation of infected
individuals were jointly adopted.[316]
This experience represents the rst modern example of a
large-scale containment action and will certainly serve as a
model for planning and preparation that will inuence similar
events in the future. Of note, quarantine is included within the
legal framework of the International Health Regulations.[317]
The 196 member states have a sovereign right to legislate and
to implement legislation for quarantine, even if this involves
restriction of movement of individuals to enhance International
Health Security (IHS).[318,319] To assist governments and various
local authorities in their responses to COVID-19, the WHO has
released the following documents that can help countries plan
Table 6: Summary of measures available to help reduce disease transmission in the context of physical distancing,
starting with widespread, society‑wide educational efforts, and ending with strict quarantine orders
Education LOA SHN Quarantine order
Social media, television, internet
platforms to educate public
For asymptomatic people who have
no COVID-19-positive contacts.
Allowed to leave residence
Individuals with international travel
<14 days but no COVID-19-positive
contacts. Not allowed to leave
Either COVID-19 positive or a PUI
LOA: Leave of absence, SHN: Stay home notice, PUI: Person under investigation
Stawicki, et al.: Joint ACAIM-WACEM Statement on COVID-19
Journal of Global Infectious Diseases ¦ Volume 12 ¦ Issue 2 ¦ April-June 2020 61
containment measures: (a) management of travelers at points
of entry – airports, ports, and ground crossings; (b) rational use
of PPE; (c) quarantine of individuals at mass levels; (d) issuing
national guidance on the use of masks in the community,
during home care and in healthcare settings; (e) infection
prevention and control in healthcare settings; and (f) home
care for COVID-19-positive patients with mild symptoms and
management of contacts.[318,320-323]
humAn And economIc AsPects of the covId-19
The prelude of the COVID-19 pandemic as an IHS threat
was brought into the forefront of attention of both biomedical
research and IHS communities in the early 2000s by the
SARS-CoV outbreak followed by the subsequent MERS-
CoV outbreak.[324-326] What sets the COVID-19 pandemic
apart from previous novel coronavirus outbreaks is both the
magnitude of the current event and the scale of the coordinated
governmental responses, both locally and around the globe.
Unlike previous events that tended to be regionalized, the
speed at which this outbreak has become global is much
more dramatic. Within an extremely short time, the impact
on multiple industries and the global economy has been
catastrophic.[327] For example, many airlines have suspended
nearly all ights to impacted regions.[328] Diverse supply chains,
including those for medical supplies, hospital equipment, and
pharmaceuticals, depend on global integration, often with deep
links with COVID-19-aected regions.[329] In addition to the
inherently deleterious eects of PDS on routine healthcare,
access to elective surgery, oce visits, and dental care in
many aected areas is becoming rationed due to disruptions
in the supply chain of disposables.[330] The crisis extends
well beyond these considerations and includes the impact of
disruptions in the global supply chains that aect basic hospital
supplies, medications, and items that everyone depends on
for daily routine activities. Recent decisions by the US FDA
to suspend overseas inspections of foreign drug, device, and
food producers will likely further exacerbate current supply
chain disruptions and may negatively aect patient safety.[331]
Economic consequences of the COVID-19 pandemic are
dicult to estimate but will certainly reach a magnitude
sufficient to adversely affect economic growth around
the planet for years to come. According to the Center for
Strategic and International Studies, signicant reductions in
gross domestic product (GDP) will be observed around the
globe,[332,333] although it would be premature to declare “how
bad and for how long” economic activity will be negatively
aected.[333] Ultimately, the magnitude of the decline will
be dependent on each individual/regional economy’s GDP
structure (e.g., percentage of GDP attributable to services,
industrial production, nances, and tourism).[333,334] Despite
massive stimulus measures,[335] unemployment claims in the
US skyrocketed past the unprecedented level of 6 million in a
single week,[336] with no sign of immediate slowing. The most
recent precipitous drop across global nancial markets shows
how interconnected our economy is with human health, health
security, and wellness.[337]
One of the most striking phenomena seen during outbreaks
and pandemics, directly linked to social distancing, is a
marked reduction in the quantity, duration, and closeness
of individuals’ interactions outside of their closest circles of
family or friends.[337,338] Subsequently, this reduction in social
interaction leads to further signicant economic slowing,
including freezing of the so-called “gig economy.”[339,340] As
nancial markets attempt to price “fear and risk” into existing
valuation structures, the behavior of global equity markets
will likely uctuate while attempting to account for “various
unanticipated risks.”[341,342] Simple fear-based responses, such
as “hoarding” of toilet paper in the US – a commodity with
limited risk for disruption – illustrate a social reaction that
is founded in fear, misinformation, and a general sense of
individual and social loss of control.[343]
Perhaps, even more concerning is the misallocation and
maldistribution of precious healthcare-suitable PPE.[344,345]
It has been emphasized that although there may not be an
actual shortage of certain types of PPE or other medical
equipment, the maldistribution may result in effective
shortages due to mismatch between regional supply and
demand.[345] This includes industrial-grade N95 respirator
masks that briey became more available for purchase at
local hardware and construction stores than through routine
medical supply chains.[346] In response, large allocations of
such PPE were subsequently donated by industry, private
individuals, veterinarians, and dentists to help alleviate acute
healthcare shortages.[347-350] Nonetheless, a more robust and
reliable production and distribution capacity will be required
to adequately address the acute needs of medical community
as it ghts the COVID-19 pandemic. As astutely pointed out
by Pirkle, “a health system is more than just hospitals.”[351]
Another thought that is important in the context of the
current approach to the COVID-19 pandemic is that the
unprecedented sacrices made to help save lives must not result
in greater downstream loss of life, due to long-term economic
consequences, reduced access to care, loss of healthcare
insurance coverage, migrations, social unrest, crime, and other
forms of violence.[352-358]
The combination of PDS and the diversion of frontline
healthcare personnel to fight COVID-19 resulted in a
signicantly limited access to routine emergency, maintenance,
and follow-up care.[359-361] Under such conditions, the
development and utilization of telemedicine-based services
are critical to allowing high-risk and vulnerable patients
to continue receiving care.[319,362] Further, telemedicine can
provide home-based care to stable COVID-19 patients who
do not require hospitalization.[363] In the past, telemedicine
support has been shown to signicantly reduce the number of
Stawicki, et al.: Joint ACAIM-WACEM Statement on COVID-19
Journal of Global Infectious Diseases ¦ Volume 12 ¦ Issue 2 ¦ April-June 2020
infected people visiting healthcare settings during inuenza
outbreaks.[364] Similar benets could be achieved in the setting
of COVID-19. According to published experiences, there
are important considerations for eective implementation of
telemedicine across multiple domains of healthcare delivery,
including obstetrics,[365] psychiatry,[366] endocrinology,[367]
wound care,[368] rural health,[369] and many other areas. Perhaps,
most relevant to the COVID-19 global context, telemedicine
capabilities can be utilized to institute more eective point-of-
care triage capabilities, cross-border medical expertise sharing,
ongoing large-scale patient follow-up eorts, platform for
quarantined physicians to contribute and remain productive
remotely, as well as dissemination of critical knowledge and
PRotectIng And suPPoRtIng heAlthcARe woRkeRs
The risk of HCW exposure is substantial during the COVID-19
response, especially when faced with limited PPE supplies and
a surging volume of infected patients.[371] Protecting HCWs
is paramount in successful management and containment
of an infectious outbreak. Occupational Safety and Health
Administration and the Centers for Disease Control and
Prevention (CDC) have developed guidelines for protecting
HCWs including using standard precautions and PPE training.
For example, performing as many tasks as possible away from
the bedside in less-contaminated areas is ideal.[100] Limiting
the number of HCWs interacting with COVID-19 patients
and optimizing the number of room entries (e.g., bundling
tasks) are important considerations.[372] One good example
of this strategy is the placement of intravenous infusion
pumps outside of patient room so that nursing sta can adjust
infusion rates without having to enter the actively isolated
environment. Telemedicine, drive-through testing, and the
eventual development of at home test kits and health screening
robots can help decrease the risk to providers.[373,374] This will
allow HCWs to have more capacity to treat the sickest patients
in an eective manner without overwhelming the system. Of
importance, dierent countries, regions, and institutions have
dierent standards for PPE when managing patients with
COVID-19, and this may be partly responsible for dierences
in infection rates among HCWs [Figure 9].[316,375-378]
Emotional support of frontline personnel is very important.
Exposure to potentially large numbers of severely aected
patients, including the repeated witnessing of fatal hypoxic
respiratory failure with concomitant do-not-resuscitate/do not
intubate (DNR/DNI) goals of care discussions where families
rely on the HCW as the intermediary, can be extremely
draining and will lead to burnout.[379-381] The upfront presence
of counseling and other forms of support was deemed of high
importance by both Chinese and Italian healthcare providers
during reective exercises.[17] Adequate logistical support and
accommodations were important in mitigating the psychological
impact of COVID-19 among hospital workers.[17] Moreover,
better and more optimal management of the pandemic in the
community may, to a degree, help protect the overworked
and dangerously exposed frontline personnel.[382] Finally, it
should be noted that due to physician workforce demographics,
especially in countries such as the US and Italy, a signicant
proportion of providers are inherently in high-risk groups for
severe COVID-19 presentations if infected.[383]
For COVID-19, PPE may be divided into four categories: (a)
respiratory, (b) eye, (c) body, and (d) hand. Providers
should wear a ltering face piece (FFP) respirator class 2
or 3 (FFP2 or FFP3), and an FFP3 respirator should always
be used when performing aerosol-generating medical
procedures (AGMPs).[384] Cloth (e.g., cotton or gauze) masks
are not recommended in performing medical care.[385] In
addition, a face shield or goggles that t the contours of the
user’s face and are compatible with the respirator should be
used.[384] Finally, gloves and a long-sleeved water-resistant
gown should be donned.[384]
All PPE, except the N95 respirator (if used for an AGMP), should
be removed before leaving the patient’s room and discarded into
a no-touch receptacle.[386] The N95 respirator (if used) should
be removed after leaving the patient’s room and optimally
discarded into a no-touch waste receptacle (see below for potential
considerations for safely reusing N95 respirators).[386] Hand
hygiene should be performed after removing gloves and gowns,
before removing facial protection, and upon exiting the patient’s
room and removing the N95 respirator (if used).[386] Handling
linen, dishes, cutlery, and waste management require no special
precautions beyond routine practice.[386]
To aid entities in planning the acquisition of PPE materials, the
US CDC has published a PPE burn rate calculator that is free
for public use.[387] Conversely, the European CDC has provided
the following PPE set estimates: suspected case (3-6 sets);
conrmed case, mild symptoms (14–15); and conrmed case,
severe symptoms (15–24).[384]
Figure 9: Comparison of total reported infections versus the number
of infected healthcare workers in three countries affected by high
volumes of COVID‑19 infections. Reported healthcare workers infection
rates ranged from 5.2% in China to 13.5% in Spain as of mid‑March
Stawicki, et al.: Joint ACAIM-WACEM Statement on COVID-19
Journal of Global Infectious Diseases ¦ Volume 12 ¦ Issue 2 ¦ April-June 2020 63
Finally, resource and supply chain disruptions may limit the
supply of vital resources (e.g., N95 respirator masks). There
is no way of determining the maximum possible number of
safe reuses for an N95 respirator as a generic number to be
applied in all cases.[388] Safe N95 reuse is aected by several
variables that impact respirator function and contamination
over time.[388] Some have proposed rotational reuse through
72-h cycles.[389] Others have promoted use of reusable
elastomeric respirators (e.g. respirators with exchangeable
lter cartridges). However, the idea gaining the most traction
seems to be N95 mask disinfection using moist heat (e.g.,
autoclave) or ultraviolet (UV) light.[389]
stRAtegIes to AddRess shoRtAges of essentIAl
suPPlIes And fAcIlItIes
Shortages of N95 masks prompted many institutions to
decontaminate and reuse PPE.[390,391] Others innovate by utilizing
three-dimensional (3D) printing techniques to fabricate PPE,
from face shields to specialized FMs.[392,393] There are also
examples of innovative 3D printing approaches to produce
custom medical equipment, test swabs, and ventilator parts.[392,393]
In this respect, 3D printing can be very versatile and represents
a creative, low-resource approach of addressing critical needs
as it relates to the ongoing pandemic.[394]
Many dierent solutions were proposed to address the acute
ventilator device shortages. One approach describes the
modication of continuous positive airway pressure (CPAP)
and bilevel positive airway pressure (BiPAP) machines that
eectively turns them into low-level ventilators capable of
supporting patients with less severe forms of COVID-19
respiratory failure.[395,396] Another strategy advocates the use
of anesthesia machines as back-up ventilator capacity in
times of COVID-19 surge.[397] Similar paradigms have been
described with the use of veterinary ventilators to increase
the capacity to address the pandemic surge.[398] Novel devices
are also being introduced to help with the acute ventilator
shortage, such as the CPAP device designed by the carmaker
Mercedes-AMG High Performance Powertrains.[399] Finally,
when an insucient number of ventilators places providers
and institutions in a situation where the availability of life-
saving therapy might be at risk, strategies to place more than
one patient on a single ventilator or “co-venting,” have been
described by Paladino et al.,[199] more than a decade ago.
“Co-venting” should be a last resort option as it is not the
ideal method to ventilate patients with lung injury, but rather
a means to save the most lives possible. It is a temporizing
maneuver, supplying the crude minimum to sustain life until
additional ventilators are obtained. Although “co-venting” can
be scaled to help multiple patients, it is recommended to limit
the number to two as the addition of more patients becomes
sequentially more complex and harder to manage. Pressure
cycle modes should be employed to minimize adverse eects
of volutrauma and barotrauma. Additional instructions and
resources on co-venting” can be found on the Health and
Human Services website maintained by the White House
Coronavirus Task Force on “co-venting.”[400] Regardless of the
approach, it must be emphasized that personnel who operate
nonstandard ventilator equipment must be well versed with
the technical parameters, logistical considerations, and any
clinical limitations associated with the device/methodology
being employed.
Facing increasing pressure to deliver critical equipment,
including PPE and ventilators to US hospitals, the Defense
Production Act was recently invoked to compel industrial
manufacturers to make ventilators and other essential
supplies.[401] In another executive order, the US President set
out to empower the executive branch to prevent hoarding
and price gouging of supplies critical to COVID-19 frontline
efforts.[402] Similar efforts should be in place to prevent
intellectual property/patent laws from delaying the availability
of life-saving drugs and technologies due to the imposition of
inherently unethical barriers to production and market entry.
Numerous initiatives around the globe are focusing on
generating much needed capacity to care for and isolate low-
acuity COVID-19 patients while freeing much needed high-
acuity healthcare infrastructure. To this end, a phethora of
highly creative options includes: (a) mobilizing and modifying
non-patient care areas within existing facilities to acutely
serve patient care purposes; (b) re-purposing non-healthcare
facilities and buildings to server various healthcare or ancillary
functions; and (c) mobilizing military, public infrastructure,
and other resources to generate surge capacity for beds and
non-COVID-19 related indications / procedures [656-661]. In
on example, healthcare resource nationalization has been
exercised by the Government of Spain [661].
At times overlooked during pandemics, blood banks
reported acute shortages of blood and blood products
due to decreased donation volume and increased demand
related to COVID-19.[403,404] It must also be emphasized that
critical equipment shortages are not isolated to high-income
countries (HICs) and that such shortages are likely both more
prevalent and more deleterious in low-and-middle income
countries (LMICs) around the globe.
heAlth eQuIty And ethIcAl consIdeRAtIons
Vulnerable and marginalized populations will disproportionately
bear the brunt of this crisis. Underrepresented minorities, low
socioeconomic workers, incarcerated and detained populations,
immigrant and refugee communities, orphans, and housing-
insecure individuals, are all likely to be disproportionately
aected by COVID-19 and the response to its spread.[405-410]
Advocacy for equitable policies, practices, and procedures that
protect our vulnerable populations can help (at least in part)
mitigate this undue burden. In the US, persistent attempts to
dismantle expanded health coverage added another layer of
complexity to the already tense situation characterized by
record unemployment and the vulnerability of underinsured
populations with an already limited access to care.[411] Reports
Stawicki, et al.: Joint ACAIM-WACEM Statement on COVID-19
Journal of Global Infectious Diseases ¦ Volume 12 ¦ Issue 2 ¦ April-June 2020
are emerging of an increasing number of individuals who
died from the illness in their homes, thus contributing to an
under-reporting of mortality and compounding the overall
public health risk.[412] At the same time, Latino and African-
American communities were noted to have signicantly higher
COVID-19 mortality compared to other groups.[413-415]
An unprecedented conuence of social and economic factors
is pushing populations to their breaking point. The COVID-19
outbreak heralded an uptick in hurtful and unfounded anti-
Asian racist sentiment around the world.[416-418] Across the globe,
LMICs face both healthcare and economic devastation.[419-421]
To help ease the situation, the International Monetary Fund
recently announced that it will cancel debt payments for
6 months for 25 LMICs battling COVID-19.[422] It has been
noted that the approach to COVID-19 in Sub-Saharan Africa
cannot be “copied and pasted” based on Chinese or Italian
experiences. Instead, unique solutions will be required that
consider important population structure dierences, high
prevalence of endemic diseases, and already overstretched
health systems with minimal critical care capacity.[423] A
preview of what may come can be seen in Guayaquil, Ecuador,
where bodies of the deceased have been left in the streets in
cardboard cons due to the overwhelmed mortuaries and
insucient healthcare resources in the midst of the local
COVID-19 outbreak.[424,425]
Global health crises, including the COVID-19 pandemic,
bring into the forefront important ethical considerations
as societies struggle with balancing medical capabilities,
available resources, economic factors, and societal well-being.
Dialogue regarding clinical ethics during a Public Health
Emergency of International Concern (PHEIC) should take
place on an ongoing basis beginning long before an outbreak
occurs.[426] The Ebola outbreak of 2014 was a seminal event
highlighting the need for the international medical and public
health communities to discuss and prepare for the ethical
challenges regarding therapies, treatment limitations, duty
to treat, and family-centered care and communications.[426,427]
Key issues to consider in the above contexts include fair
allocation of scarce health resources, PPE availability, patient
condentiality and privacy, social isolation of both aected
patients and providers, ethical framework for research studies,
and professional liability.[428-430] While clinical ethics focuses on
individual patients, public ethics deals with the protection of
community health at large. All of these aspects are discussed
in the following sections.
Outbreaks can occur in any country, regardless of income
level. However, when dealing with LMICs, HICs must avoid
being paternalistic and must be cognizant of the structure of
communities, understand family dynamics and interactions
in aected locations, know the religious implications of
medical interventions/public health actions being proposed,
pay close attention to local and regional traditions, and
understand potential economic consequences regarding any
proposed actions. Transparency of communication is of
great importance, especially in regard to decisions made by
authorities, as there will be community uncertainty of the
eectiveness of treatments, vaccines, and patient outcomes.
In addition, there must be a structured plan to accept survivors
back into the community while avoiding any disease-
associated stigma.[427,431] Moreover, the duty of healthcare
providers to treat the ill may become a contentious issue.[426]
There likely will be medical providers questioning whether
it is their duty to provide care to patients, the act of which
may then jeopardize their lives or the lives of their loved
ones.[432] There is also the question of access to COVID-19
testing, mechanical ventilation, and other services, including
prioritization and allocation challenges given resource
Another evolving ethical development includes the concepts
of information sharing and goals of care discussions while
patients are isolated away from family members in the hospital.
Patients at the end of life, those who are unable to advocate for
themselves, and women in labor are especially vulnerable and
dependent on the clinical sta to relay information back and
forth. As new DNR/DNI orders are initiated, it is crucial for
hospitals to support communication, resources, and protocols
to assist patients, families, and caregivers.
Discussed in previous sections, the issue of quarantine continues
to be highly controversial from ethical perspective.[436,437]
Questions may arise as to whether quarantine is needed, how
should quarantine be implemented, where aected individuals
should be housed, and for how long. The fashion in which
quarantine measures will be introduced to society is very
important.[438] Quarantined populations must have appropriate
access to all the basic human essential rights to continue to live
safely, with access to water, food, energy, healthcare, and the
social infrastructures that dene humanity. As such, restriction
of liberty is always of concern.[439]
Successful control of an outbreak will be dramatically aected
by the ethical perceptions of patients, their families, the local
community, and those providing healthcare.[440] Without
community acceptance of quarantine measures, successful
control will be impossible. Frontline sta who ensure that
critical services (e.g., public transport, telecommunication
infrastructure, supply chains) are functioning and supplies (e.g.,
food, water, healthcare equipment, medications, fuel) keep
owing may also be at increased COVID-19 risk and deserve
support and recognition for their eorts.[441-444] An example of
creative solutions in the area of supply chain logistics includes
the utilization of trains to transport detachable semi-trailers
due to a shortage of truck drivers.[445]
fIeld clInIcAl tRIAls
In times of a pandemic, human vulnerability increases, and
the need to provide clinical care must be balanced with
the need to conduct clinical and epidemiologic research to
improve that care.[426] From an ethical perspective, research
endeavors should be governed by the principles of respect for
Stawicki, et al.: Joint ACAIM-WACEM Statement on COVID-19
Journal of Global Infectious Diseases ¦ Volume 12 ¦ Issue 2 ¦ April-June 2020 65
persons, benecence, and justice.[446] A humanitarian crisis
does not allow for the suspension of the ethical foundations
governing human subjects research, including institutional
review board (IRB) oversight and approval.[447] Indeed, federal
regulations outline more—not fewer—research protections for
such vulnerable populations.[447]
One unique situation in which research may be conducted
without obtaining prior consent is “emergency research.”
As with other exceptions to the IRB review and informed
consent requirements, the denition of “emergency research”
is explicit and narrow.[448] The use of experimental strategies
and interventions was deemed acceptable before the recent
Ebola virus outbreak,[449] and it became evident during the
outbreak that experimental approaches may be necessary, while
recognizing the risks.[450] However, while it is important to
rapidly gain new clinical and therapeutic knowledge during an
outbreak, HICs or technologically advanced countries, which
usually provide the interventions, therapies, vaccines, and
research agendas, must be cautious in how medical research
is conducted during a PHEIC. Particular concerns include
rushed or poor research methods, misinterpretations of big
data, unfair treatment and preventive service allocation, and
safeguards for HCWs.[426]
Serious consideration must be given to SARS-CoV-2/
COVID-19 study design to ensure the collection of impactful
data while maintaining ethical standards, including the
limitations of case studies without comparative control
groups, the challenges of performing randomized, placebo-
controlled studies, and the potential advantages of adaptive
study designs.[451] Specic study design dierences should be
considered in regard to therapies, vaccines, and prophylactic
versus therapeutic intervention groups.
There are important considerations and treatment
limitations identied that tend to be common during most
outbreaks.[426] These include (a) resource scarcity and its
impact on treatments; (b) ability to operationalize goals while
maintaining appropriate oversight by state and local authorities
and triage ocers; (c) potential treatment limitations based
on provider risk; and (d) limiting the use of treatments with a
low probability of benet. Extensive recommendations on the
ethics principles applicable to outbreaks and pandemics have
been made by the Society of Critical Care Medicine.[426,427]
ImPoRtAnt legAl consIdeRAtIons
In addition to the specic ethical concerns discussed above,
pandemics also present unique legal challenges for patients,
law enforcement, and government policy as well as for
healthcare entities and personnel. These legal issues can
be divided into two broad categories: (a) the restriction of
movement and implementation of quarantine policies and (b)
medicolegal consequences for patients, families, physicians,
and allied medical personnel due to overwhelmed systems. This
may include, in the US, violations of the Emergency Medical
Treatment and Labor Act (EMTALA), delays in diagnosis and
treatment, and medical malpractice due to, or exacerbated by,
rationing of available sta and resources.
First, the right to travel has long been asserted as a fundamental
human right, internationally codied in Article 13 of the
Universal Declaration of Human Rights (UDHR) and Article
12 of the International Covenant on Civil and Political
Rights.[452,453] The authority to restrict and regulate the actions
of citizens varies broadly across the globe. Moreover, most
signatories of the UDHR recognize that an individual’s right
to move and travel within and across borders is not absolute.
Moreover, regional or national authorities may threaten to
ne or jail/conne citizenry when their movements or failure
to comply with quarantine measures potentially threaten the
health and welfare of the country or region as a whole.[454]
Isolation and quarantine policies and procedures are designed
to protect the public health and interest during an outbreak and
are often a compelling state interest that can take precedence
over individual liberties. In the US, under Title 42 of the
Code of Federal Regulations Parts 70 and 71, the CDC may
detain, medically examine, and release persons arriving into
the US and traveling between states if there is knowledge of
an infection or suspected risk of transmitting communicable
diseases.[455] State, local, and tribal authorities also have
separate but co-existing powers translating into over 2000
individual departments of public health.[456,457] In the event
of discordant views between federal and state authorities,
the Supreme Court is the nal arbiter and decision-maker in
the US based on the scientic evidence of the individual’s
threat to community welfare, minimizing the restrictiveness
of proposed connement, and respect for due process.[458-461] It
remains to be seen whether individuals will employ principles
of common sense and follow directives of self-quarantine
(or other required measures) to limit the spread of disease or
whether more punitive measures will need to be implemented
by state or federal authorities.[462]
Pandemics overwhelm existing systems in terms of both sta
and fungible medical supplies and equipment.[463-465] With most
hospitals already operating close to capacity, an unexpected
inux of critically ill patients will easily cripple EDs and
ICUs, leading to stang shortages, as emergency physicians,
intensivists, and their support sta fall victim themselves to
the disease or are placed in quarantine.[465-468] In the era of
“just-in-time” supply chains, critical equipment and drugs
are also likely to be in short supply and physicians may have
to make dicult decisions about rationing these supplies
based on triage principles, allocating equipment to patients
with the greatest chance of survival.[469,470] By proxy, these
system-wide problems could aect both COVID-19 patients
and non-COVID-19 patients, including those with various
chronic medical conditions, as outlined in previous sections.
Under the current EMTALA law in the US, emergency physicians
or qualied medical providers are required to perform a medical
screening examination (MSE) and stabilize all patients who walk
in the doors of the ED, irrespective of their ability to pay. During
Stawicki, et al.: Joint ACAIM-WACEM Statement on COVID-19
Journal of Global Infectious Diseases ¦ Volume 12 ¦ Issue 2 ¦ April-June 2020
pandemic surges, delays to MSE are inevitable. Physicians, nurses,
and other personnel trained in dierent specialties, possessing
different skills sets, from general practitioners to surgical
specialists, may be mobilized when stang shortages reach a
critical level. Depending on jurisdiction, Good Samaritan laws are
often not applicable in professional settings like hospitals where
physicians have a preexisting duty to provide care to patients, and
where patients will also be billed for such services.[471] Across the
world, many physicians are agents of the state, and as a result, when
a patient is harmed under their care, the individual physician is not
held nancially liable, although they may be held professionally
or even criminally liable depending on the circumstance.[472]
This unique concept of attempting to make the patient or family
whole under tort law does not take into account systemic failures
but classically rests on individual culpability. Systemic errors,
which can always contribute to individual error, are magnied
during times of medical crisis. Thus, modication of tort law is
needed during pandemics. Options include granting sovereign
immunity to all medical personnel and increasing the agreed
upon standard for malpractice claims from simple negligence to
reckless indierence.[473,474] National and international specialty
organizations must advocate for an equitable legal framework to
protect physicians practicing on the COVID-19 frontlines.
seveRe Acute ResPIRAtoRy syndRome coRonAvIRus
2 theRAPeutIcs
Because SARS-CoV-2 is related to SARS-CoV, certain
known similarities between these two members of the
genus Betacornavirus can be leveraged when developing
therapeutic interventions for COVID-19.[475,476] For example,
although SARS-CoV and SARS-CoV-2 share only 82% of
the RNA sequence, their RNA-dependent RNA polymerase
demonstrates 96% similarity.[477] Another strategy involves
supercomputer-based strategies to estimate the eectiveness
of existing therapeutic molecules (e.g., drugs or synthetic
antibodies) in relation to viral proteins, receptors and functional
complexes.[478,479] Finally, it is well recognized that advanced
COVID-19 infection can be associated with an intense immune
reaction, prompting interest in pharmacologically modulating
such systemic responses.[15,39,291,480-485]
A diverse group of therapeutic agents and classes has been
identied as potentially eective against SARS-CoV-2. Due
to the extensive nature and diversity of these therapeutic
candidates, a full discussion is beyond the scope of this
review. A high-level overview of this topic now follows,
and the reader is invited to consult any denitive materials
referenced below. Table 7 provides a focused outline of
key investigational agents and major takeaway points. To
date, agents considered for clinical investigation in the
context of COVID-19 include protease inhibitors (e.g.,
lopinavir, ritonavir);[501,505,509,540-546] nucleoside analogs (e.g.,
favipiravir, galidesivir, penciclovir, remdesivir, ribavirin);[515,547]
6′-fluorinated aristeromycin analogs;[548,549] acyclovir
fleximer analogs;[550,551] interferon;[38,39,486,510,520-524,552-555]
antimalarials;[231,486-498,556] neuraminidase inhibitors (e.g.,
peramivir, oseltamivir, zanamivir);[39,557,558] corticosteroids
and immunomodulators;[15,39,291,480-485] antilice agent
ivermectin;[559,560] as well as a highly heterogeneous group of
other potential treatments.[528-531,561-575]
Based on recent reports suggesting that countries with mandatory
Bacillus Calmette-Guerin (BCG) inoculations may be experiencing
fewer COVID-19 deaths, there is renewed interest in this old
tuberculosis vaccine.[535,536] The mechanism behind the eectiveness
of a tuberculosis vaccine in the setting of SARS-CoV-2
infection is unclear but may involve BCG’s immune boosting
characteristics.[537] As a result, Germany initiated a clinical trial
of a potential COVID-19 vaccine based on a BCG vaccine.[538]
A similar study in Australia will focus on HCWs and will enroll
approximately 4000 subjects.[538,539] In addition, plasma from
COVID-19-convalescent patients has been advocated by some
as it has been reported to decrease mortality with SARS-CoV
and severe inuenza infections.[525,576] However, plasma collection
during the COVID-19 recovery period must be accurately timed
to effectively capture appropriate antibodies in sufficiently
high concentrations. The ecacy and safety of convalescent
plasma in patients with COVID-19 infection is currently being
evaluated in clinical trials,[577] with some encouraging reports
from small case series.[578] Finally, the identication of SARS-
CoV-2-specic antibodies, both in terms of temporal patterns and
types, could lead to the synthesis of highly specic monoclonal
or polyclonal antibodies against the virus. Such eorts are also
under development and investigation at this time.[533,534,579] Of
importance, the inclusion of specic agents and devices in this
discussion should not be taken as an endorsement or proof of
their ecacy. Despite the wealth of investigational COVID-19
therapies, it must be emphasized that as of the completion of this
article (May 12, 2020), with the exception of marginally eective
remdesivir, early promising reports of some multi-drug approaches,
and mesenchymal stem cell applications, there are no established
therapeutics against SARS-CoV-2 outside of emergency use
authorizations and/or ongoing clinical trials.[500,515,580-582,662,665]
envIRonmentAl PARAmeteR contRols
Airow patterns within healthcare facilities can signicantly
aect the risk of nosocomial transmission of coronaviruses.[583]
The susceptibility to germicidal kill of any microorganism
is determined by its genomic sequence of nucleotides
adenosine [A], cytosine [C], thymine [T], guanine [G], and in
particular, the recurrence of the sequences TT and TTT.[584] At
this time, highly ecient air purication technology (HEAFT)
exists that will reliably deliver a kill/disinfection rate of 145-
log against the airborne SARS-CoV-2 virus[585] (as a reference,
sterility is dened by a 6-log reduction). The kill ability provided
by this technology was intentional as the capture ability
employed by standard hospital high-eciency particulate
arrestance (a.k.a., HEPA) ltration systems, the most common
means of air ltration used in healthcare, cannot provide
comprehensive remediation when pathogen sizes fall within
the range of 0.1–0.3 µ.[586] The approximate size of SARS-
Stawicki, et al.: Joint ACAIM-WACEM Statement on COVID-19
Journal of Global Infectious Diseases ¦ Volume 12 ¦ Issue 2 ¦ April-June 2020 67
CoV-2 is 0.125 µ.[587] Because the HEAFT comprehensively
remediates the COVID-19 airborne virus, it may be useful
in hospitals, nursing facilities, critical care infrastructure,
and frontline modular containment/isolation areas, to protect
patients, HCWs, and those in potential proximity to infected
individuals (e.g., contractors, visitors/families, nonclinical
personnel, and allied healthcare professionals). Because
HEAFT also correlates with surface contamination, high
eciency air purication systems, in permanent or deployable/
portable form, may represent an important adjunct in facilities
caring for high-risk populations, such as geriatric patients and
those with immunosuppressed status.[220] Although standard
Table 7: Novel candidate therapeutics for COVID‑19 by class, mechanism of action, and available evidence. There are
currently no United States Food and Drug Administration approved therapeutics at this time
Therapeutic Class Theoretical mechanism of action Evidence
Antimalarial May act nonspecically at viral
entry or at stages of viral production
Some promising in vitro and in vivo studies, but WHO still
cites inecient evidence for making specic therapeutic
recommendations.[231,486-499] Reportedly used in combination with
azithromycin.[498] On April 8, 2020, the US CDC dropped its
guidance regarding antimalarials, stating “hydroxychloroquine and
chloroquine are under investigation in clinical trials[500]
Lopinavir-Ritonavir Protease
May block viral entry Viral loads decreased in case series.[32,39,501-504] Currently undergoing
clinical trials, but one randomized trial did not demonstrate
dierence in outcomes at 28 days.[505] There is a risk of interactions
with other drugs[506-508] Finally, early data show that multi-therapies
containing lopinavir-ritonavir in combination with other agents
(e.g., lopinavir-ritonavir plus interferon-β1, plus ribavirin) may be
more eective.[662]
remdesivir, ribavirin
May block viral entry; lethal
mutagenesis; inhibition of
nucleotide biosynthesis
Ribavirin has not been shown to be eective and has severe side
eects.[509-512] However, remdesivir has been shown to decrease
viral titers in mice and reduce lung tissue damage.[513] It also has
completed a phase 3 clinical trial for Ebola.[514] Clinical trials
for COVID-19 are ongoing[513,515-519] and preliminary data show
marginal clinical eectiveness of remdesivir (e.g., shortened
hospital length of stay with no dierence in patient mortality for
those treated with the drug).
Interferon Interferon Coronaviruses are thought to have
the ability to suppress counteracting
interferons; using interferon may
inhibit viral replication
Mixed ecacy; not routinely recommended[486,510,520-524] Early
evidence shows that interferon-β1 may be more eective when
combined with other antiviral agents.[662]
Anti-inammatory Reported benet in small observational study but have otherwise
been shown to have negative eects with similar viruses; not
routinely recommended[15,39,291,480,481,483]
Anti-IL-6 agents Prevent T-cell and macrophage
activation to manage cytokine storm
There are anecdotal reports of use; no formal or peer-reviewed
publications in the setting of COVID; not routinely recommended
while under investigation[484,485]
Convalescent serum Blood product Provides anti-viral antibodies that
specically target COVID-19
Theoretical benet in some viral infections,[525]but no eect
observed with Ebola,[526] which was thought to be due to low
antibody titers during recovery period. A 5-patient case series did
demonstrate improvement in symptoms but requires additional
evaluation before any therapeutic recommendations[527]
vitamin C, vitamin D
Vitamin General immune system functioning Some evidence supporting vitamin C use in SARS-CoV to reduce
pneumonia risk;[528,529] However, there is no demonstrated ecacy
in SARS-CoV-2, and thus, it is currently not recommended[528-532]
A clinical trial is ongoing evaluating vitamin C infusion for the
treatment of severe COVID-19 infection. [663] In addition, evidence
is emerging that there may be an association between vitamin D
deciency and more severe COVID-19 illness.[664]
antibody product
Highly specic targeting and
inactivation of SARS-CoV-2
Currently under active clinical investigation, including fast-track
clinical trials[533,534]
BCG Anti-tuberculosis
Unknown Countries with mandatory BCG vaccination have been noted to
have fewer COVID-19 deaths; However, the mechanism of such
protection is not known; eectiveness unclear (posited to be
due to immune boosting activity) and clinical trials are currently
underway to better elucidate any potential benets[535-539]
There are currently no US FDA approved therapeutics at this time. BCG: Bacillus Calmette-Guerin, FDA: Food and Drug Administration, SARS-CoV-2:
Severe acute respiratory syndrome coronavirus 2, CDC: Centers for Disease Control and Prevention, IL: Interleukin
Stawicki, et al.: Joint ACAIM-WACEM Statement on COVID-19
Journal of Global Infectious Diseases ¦ Volume 12 ¦ Issue 2 ¦ April-June 2020
deployment of HEAFT systems across all patient-care areas
is likely unnecessary, housing for at-risk individuals outlined
above may benet from high-eciency air ltration with added
viral kill capacity, especially in common areas (e.g., hallways,
designated buer zones/entry ways/anterooms, meeting, and
dining rooms). It is questionable whether such air ltration
capacity would prevent viral transmission within the close
quarters of a single patient room or small, conned space where
circulating infectious droplets would not likely be eliminated
before reaching another individual.[220] However, makeshift
anterooms, potentially featuring high-eciency air ltration,
can be constructed to help “buer” the external environment
from immediate exposure.[220]
There is some evidence that adjunctive use of UV germicidal
irradiation may provide an additional layer of protection,[588-590]
a potential consideration for high-trac areas, designated
buer zones/entry ways/anterooms, elevators, bathrooms,
and critical healthcare spaces and surfaces. Under such
circumstances, UV lights should be coupled with motion
detectors to temporarily deactivate potentially harmful
UV light as people enter and transit through these areas.
The eectiveness of UV light deployment in this setting is
relatively less well explored than HEAFT, although there is
some evidence of ecacy.[591] Finally, the use of hydrogen
peroxide for viral inactivation has been described. It was
determined that inuenza and coronaviruses are sensitive to
such environmental approaches.[592] Practical implementations
of these ndings remain to be fully elucidated, including the
role of hydrogen peroxide in achieving environmental purity.
lessons leARned And futuRe dIRectIons
There are many lessons learned from the COVID-19 pandemic.
The virus characteristics are similar to previous historical
coronavirus infections, with a relatively stable transmission
rate, deceptively slow incubation time, and a case-fatality
rate that is higher than that of H1N1 inuenza but lower than
that of SARS-CoV or MERS-CoV.[593] It appears that the virus
has largely impacted older patients and those with weakened
immune systems or other risk factors [see earlier sections and
Figures 4 and 5]; however, deaths in younger and previously
healthy individuals do occur.[594]
There response is been a controversy surrounding nonsteroidal
anti-inflammatory agents, with conflicting reports about
potential adverse effects.[595,596] These concerns have not
been substantiated. Used more extensively during the early
pandemic, the benet of corticosteroids has been a subject of
signicant scientic and clinical debate. Although steroids may
provide clinical benet if a patient has ARDS or lung brosis,
they may be harmful by potentially prolonging the duration
of viral shedding.[231]
With regard to frontline healthcare sta preparation, daily
messaging of established best practices for emergency and
critical care is paramount to contain the spread of SARS-CoV-2
and to ensure that optimal clinical management strategies are
followed. It is important that hospitals ensure the presence of
adequate resources (i.e., PPE) and available personnel who
are properly instructed in contact, droplet, and respiratory
precautions. Data-driven and consistently applied protocols for
HCWs to report illness and voluntarily observe ‘sick leave’ and
appropriate quarantine practices (e.g., eective isolation and
its duration) will help decrease nosocomial spread of illness.
Based on input from frontline personnel, it has been reported
that having standardized processes and “best practices”
established early on during the pandemic extremely helpful. In
addition, early respiratory intervention (e.g., proning, orderly
therapeutic escalation as shown in Figure 8) should be initiated
to improve outcomes, reduce endotracheal intubations and ICU
resource utilization.[15]
Future directions include the use of telemedicine for the
evaluation of suspected patients; patient-administered,
provider-supervised accurate point-of-care testing; best
practices for pandemics from thought leaders; deployment
of AI-based analytical systems and modeling; and vaccine
development for COVID-19.[128,370,597,598] With the history of
SARS-CoV, MERS-CoV, and now SARS-CoV-2, the systemic
management approach requires a well-organized, collaborative
eort that utilizes thoughtful innovation, from basic science
laboratories to disaster planning. Scaling production capacity
to meet global needs will require creative solutions, especially
when promising new therapies or tests require mass production
to reach the largest number of people in the shortest amount of
time. Re-tooling of otherwise idle production capacity (e.g.,
transitioning car manufacturing into ventilator production)
is one of such solutions.[401] In one example of cutting edge
innovation, Mayo Clinic in Jacksonville, Florida, deployed
AI-enabled, self-driving vans to ferry COVID-19 tests a
strategy that protects sta from infectious exposure while
ensuring continued service to patients.[599]
In terms of restarting the global economy, healing our
healthcare systems, and re-integrating those who recovered
from COVID-19 into active workforce, several important
considerations must be taken into account. First, rapid
diagnostic testing on a massive scale will be required to
identify and contain new cases and to minimize further
disease spread.[80,142,600] Second, convalescent individuals who
are certied to be fully recovered should be issued some sort
of ocial document that certies their status, followed by
return to active workforce.[601,602] This should be a foundation
of a very ecient system of easily identifying those who are
considered to be “safe from infection” (including those who
are immunized once SARS-CoV-2 vaccine becomes available)
and those who remain “susceptible,”[601] with much more
optimal resultant resource allocation, testing deployment, and
expedited medical management of those aected. Blockchain-
based solutions that allow robust tracking of cases while
preserving individual autonomy and privacy rights will be
most optimal.[289,603] Healthcare systems should quickly and
eciently shift focus toward treating patients with chronic
health conditions and addressing all elective patient concerns
Stawicki, et al.: Joint ACAIM-WACEM Statement on COVID-19
Journal of Global Infectious Diseases ¦ Volume 12 ¦ Issue 2 ¦ April-June 2020 69
that were placed on hold during the pandemic.[604,605] This will
help reduce preventable morbidity and mortality related to non-
COVID-19 conditions, especially chronic medical diseases
and mental health concerns. Appropriate immunization
programs should be seamlessly introduced and eciently
executed, quickly providing an “insurance policy” that will
be needed before any subsequent waves of COVID-19 or
another pandemic emerge. Finally, our preparedness for the
“next pandemic” should be placed high on the global priority
list and should become an inseparable part of mainstream
political agendas. It would not be unreasonable to require
our elected leaders and those aspiring to become elected
leaders, to demonstrate competency in the area of outbreak
preparedness. If anything is to be learned from the current
pandemic, it is that “no one really knows what is going on”
early in the evolution of the process, delays in response are very
likely, and coordinated global action incorporating adaptive
strategies and “lessons learned” is the only way to eectively
tackle these problems.[309,310,606,607] Moving forward, one thing
is certain the COVID-19 pandemic will change how we
shop, travel, socialize, and work for years to come.[608] And
not to be forgotten social distancing may stay with us for
quite some time to ensure that all preventable SARS-CoV-2
transmission is halted.
Summary of the most important “lessons learned thus far
during the COVID-19 pandemic is provided in Table 8,
focusing on the most important, easily implementable, most
Table 8: Summary of some of the most important “lessons learned” regarding the COVID‑19 pandemic; data compiled
from multiple sources
Lesson learned Comment Source
Rapid development, dissemination, and implementation of
diagnostic testing are crucial to allow clinicians to detect the rst
cases of disease during an epidemic and curb early spread. Drive-
thru, rapid diagnostic testing is an eective strategy and may help
implement more sensible and targeted isolation eorts
This worked well in South Korea and has been named
as one of the key factors for reversing the COVID-19
outbreak in that country
Additional positive experience reported by certain local
authorities in Italy
Patients with less severe respiratory failure may benet from
ongoing trial of HFNC or NIPPV, especially when combined with
early proning. However, in the event of clinical deterioration,
prompt endotracheal intubation may be more benecial than
prolonged use of NIV
This statement is experience-based and not validated
It is important to have well-established protocols and practice
guidelines, especially for the ED and critical care settings
This statement is experience-based and not validated
Key supplies, medications and PPE are necessary to stockpile.
Healthcare institutions and systems should prepare accordingly
Such considerations may be most relevant in situations
where the majority of a supply chain is limited to 1-2
sources or countries.[612] This statement is experience-based
and not validated scientically
Nosocomial transmission has been documented as an important
source of spread of this disease. In some studies, up to 40%
of cases were due to nosocomial transmission to uninfected
hospitalized patients, HCWs, or uninfected visitors and family
members. Appropriate PPE, in-hospital isolation measures, and
visitor policies may help decrease likelihood of nosocomial spread
This statement is based on limited available testing data [613]
Alternate strategies to prevent or decrease aerosolization during
nebulization, high-ow nasal cannula, noninvasive ventilation,
and intubation are being explored and may have a role in certain
Viral lters, nonaerosolizing masks, Lucite™ boxes/
shields for intubation, and using surgical masks over NIV
face mask have been suggested
Super-spreaders (or super-carriers) are infected individuals who
remain asymptomatic but retain the ability to infect others
The presence of such individuals highlights the need for
protocolized and highly standardized approach to triage
and management of COVID-19, including large-scale
testing; Super-spreaders are thought to be involved in
multiple transmission aboard cruise ships and/or large
public events
Triage planning is very important for adequate COVID-19
response. It is important to determine, ahead of time, how to
handle patients with complaints of viral illness, detect suspected
cases, conrm the diagnosis, and isolate as required
This statement is experience-based and not validated
Society-wide social distancing, home isolation and quarantine
measures have been shown to suppress viral spread in some
contexts; however, longitudinal eects of these suppression
eorts, if not sustained in the long run, are thought to be limited
There have been good viral suppression eorts seen in
multiple contexts, including China, Singapore, Hong Kong
and South Korea. Some early reversal of that has been
seen in countries that have since loosened restrictions. It
is thought such eorts would be required until an eective
vaccine is widely available
HFNC: High-ow nasal cannula, NIPPV: Noninvasive positive pressure ventilation, PPE: Personal protective equipment, HCWs: Healthcare workers, ED:
Emergency department, NIV: Noninvasive ventilation
Stawicki, et al.: Joint ACAIM-WACEM Statement on COVID-19
Journal of Global Infectious Diseases ¦ Volume 12 ¦ Issue 2 ¦ April-June 2020
impactful, and when possible empirically proven approaches
and strategies.
mIscellAneous toPIcs – Post-covId-19 lung
Previous studies of the SARS-CoV have identied the presence of
a signicant autoimmune component during the resolution phase
of the infection.[621,622] This heightened immune response within
the pulmonary system may lead to severe pneumonia or ARDS.
Moreover, there have been anecdotal reports that SARS-CoV-2
is associated with worsening of existing pulmonary conditions,
such as chronic obstructive pulmonary disease (COPD) and
asthma in convalescent patients. Subsequently, evidence began
emerging regarding residual pulmonary dysfunction among
COVID-19 survivors, mainly aecting those with more severe
disease manifestations.[623,624] SARS-CoV-2 appears to have
anity for nasal goblet and ciliated cells within human airways,
leading to potentially signicant damage.[625] In addition to direct
viral damage to the lung, immune hyper-reactivity may play a
role in further exacerbating pulmonary tissue pathology and
subsequent scarring.[623]
It is also now emerging that there is signicant incidence of
end-organ dysfunction across many body systems, in line with
the associated and previously described organ failure patterns
in the ICU.[626,627] Biochemical evidence of end-organ damage
such as elevations in highly sensitive Troponin, ALT, serum
creatinine, as well as immune system depression all appear to
be prognostically important.[124,125,152,628,629] It is unclear how
these parameters translate into longer-term, postrecovery
disability, and chronic end-organ dysfunction. One important
piece of evidence that has emerged recently is the appearance of
Kawasaki-like vasculitis in children who reportedly recovered
from COVID-19.[666] If conrmed, this development would
corroborate both the pro-inammatory changes secondary to
SARS-CoV-2 infection and the persistence - and potentially
the evolution of - such changes over time. Another important
piece of the puzzle potentially related to the “vasculitis” theory
is the presence of thrombotic and thromboembolic phenomena
in the adult COVID-19 patient population [160,161]. Anecdotally,
these changes may occur well into the convalescent period,
perhaps representing a process similar to the “vasculitis” seen
in the pediatric patient.
Much remains to be learned about SARS-CoV-2 shedding,
including the average duration of postrecovery shedding
and any modulating factors. The reported duration of SARS-
CoV-2 shedding among survivors ranged from 17 to 24 days,
with a median of 20 days.[128] One factor associated with
prolonged viral shedding is the use of corticosteroids.[15,231]
The magnitude and duration of this phenomenon are not
known at present; however, given the above, the CDC is
discouraging corticosteroid use.[291,483] In another report, stool
testing for SARS-CoV-2 using qRT-PCR between 0 and
11 days after symptom onset demonstrated viral persistence
in fecal samples.[63] Similar to Ebola virus disease, there
is anecdotal evidence of SARS-CoV-2 presence in semen
for some time after the acute illness ends. Related to viral
shedding and long-term immune-related behavior, the topic
of recurrent COVID-19 infections warrants a brief mention.
Several cases have been described of patients who reportedly
recovered, as proven by negative conrmatory testing, and
experienced a subsequent short-term relapse of symptoms
and positive viral testing.[630-633] Although exact circumstances
of each case of recurrent infection are unique, it will be
important to determine both viral (e.g. strain dierences)
and host (e.g. immunosuppression) factors associated with
such occurrences, as well as their clinical and epidemiologic
signicance. Finally, potential exists for human-to-animal
transmission for SARS-CoV-2 as demonstrated by anecdotal
reports of household pets testing positive for the virus. This,
in turn, opens the possibility of a long-term, zoonotic SARS-
CoV-2 reservoir and reciprocal animal-to-human transmission.
Implications of such development may be signicant and far
effect of covId-19 on long-RAnge
InteRnAtIonAl medIcAl PRogRAms
COVID-19 has aected international medical programs (IMPs)
signicantly. For instance, on March 12, 2020, the Fulbright
Scholar Award program was put on pause for 60 days by the
Bureau of Educational and Cultural Aairs (ECA) of the US
Department of State.[634] All current Fulbright Scholars who are
overseas have been ordered to return home. The ECA will review
this order every 30 days, and the fall program is in danger of
cancelation. Similarly, the Fogarty International Clinical Research
Scholars and Fellows Program has been temporarily closed.
Many universities have active medical and cultural exchanges
with other countries. Faculty and trainees have been required
to cease programs while abroad, and many returnees were
required to undergo a mandatory 14 days of quarantine upon
arrival back to the home country. This is an example of lost
educational opportunities for both universities and a loss of
funds that were allocated for the opportunity and required
for emergency return travel arrangements. In addition, the
mandatory quarantine contributed to significant loss of
productivity to home departments.[635]
Medical institutions in LMICs may face a loss of staff,
overburdened infrastructure, and limited ability to connect
using high-speed, readily available, and reliable Internet.[636]
This often precludes the use of the primary alternative to direct
person-to-person contact – telemedicine and e-learning.[282,370]
Consequently, despite signicant technological progress in
learning platforms, and increasing use of such platforms in
HICs,[637] partners in LMICs may not be able to take full
advantage of bidirectional information exchanges and various
other virtual educational opportunities.[638,639]
In many cases, students and trainees involved in IMP activities
will not be able to complete or even begin their curricula.
Stawicki, et al.: Joint ACAIM-WACEM Statement on COVID-19
Journal of Global Infectious Diseases ¦ Volume 12 ¦ Issue 2 ¦ April-June 2020 71
Oine digital education may be an alternative solution for this
pandemic, allowing trainees to learn at their own pace, with or
without the need for a working or reliable internet connection.
However, this assumes that appropriate arrangements are in
place and that there was forethought and anticipation of this
PHEIC. The sudden and tectonic changes in medical education
and healthcare in general caused by the COVID-19 pandemic
will not easily allow such a transition. Subsequent systems
strengthening must include better preparedness for similar
events in the future.
The balance of international health equity relies on multilateral
strategic partnering between HICs and LMICs. The current
pandemic has resulted in a return to home base for vast
majority, if not all IMP members, and this will negatively
impact IMP maturation. Global partners will need to nd
creative solutions to keep this important work moving forward.
PsychologIcAl AsPects of the PAndemIc
Posttraumatic stress disorder (PTSD), both among survivors
and relatives of victims, may be another “unseen epidemic”
following the COVID-19 pandemic.[640] Such phenomena
were observed on a large scale in Africa following the
2014–2016 Ebola outbreak.[641] In similar fashion, early
reports from China indicate that the COVID-19 outbreak
has resulted in significant number of new PTSD cases.[642] It
should be expected that PTSD will be increasingly evident
across the affected areas of the globe, and it will be equally
important to ensure that local resources are available to
help individuals cope with the immense emotional stress
of a pandemic. In addition, significant rates of anxiety,
depression, and other mental health disorders are to be
expected, involving both the general population and
healthcare providers.[640,643-646] Perhaps, the most dreaded
mental health consequence is the increase in suicidal
ideation and suicide during the pandemic.[647-649]
The concept of “cabin fever” clearly applies in the current
context of prolonged quarantine or “stay-at-home” orders
and is inherently associated with feelings of isolation,
loneliness, and distress.[650] Common manifestations of “cabin
fever” include restlessness, lack of motivation, diculty
concentrating, irritability, lack of patience, hopelessness,
irregular sleep patterns, lethargy and diculty waking up,
distrust of those nearby, and persistent sadness/depression.[650]
Some strategies that may be potentially useful in coping with
“cabin fever” include spending time outdoors, creating a
structured daily routine, maintaining a social life, engaging in
creative activities, physical exercise, mindfulness strategies,
and ensuring scheduled times away from others.[650] There are
also growing concerns about the potential for domestic abuse
in the presence of home connement, fear and anxiety, and
poor coping mechanisms.[651-653] Finally, in environments where
fear and anxiety are prevalent, there may be greater propensity
toward abusive behaviors from those tasked with enforcing
quarantine or “stay-at-home” orders.[654,655]
ongoIng exPloRAtIon, flexIble AdAPtAtIon, And
evolvIng undeRstAndIng of the covId-19
COVID-19 is an evolving phenomenon. At the weekly ACAIM-
WACEM Global Taskforce meetings, multiple aspects of the
COVID-19 pandemic have been explored including disease
models, disease prevention, pathophysiologic mechanisms,
bedside diagnosis and individual clinical observations, basic
and advanced imaging, clinical testing, and evidence-based
management guidelines, among other topics. Innovative
treatment options are discussed, from combinations of
medications to clinical trials involving monoclonal antibodies
and vaccines, various forms of ultraviolet light therapy including
intratracheal applications and extracorporeal blood irradiation, as
well as convalescent serum therapy, to name just a few. Finally,
non-clinical topics such as socio-economic disruptions, medical
education, social distancing strategies, global health equity,
and post-pandemic future, tend to invoke some of the most
controversial and vibrant discussions.
Due in part to the increased mobility of modern societies, SARS-
CoV-2 has spread rapidly beyond China’s borders and has reached
pandemic levels. The WHO named the crisis as the sixth PHEIC
before its status was upgraded to a global pandemic. Case-fatality
rates remain high, most notably among the elderly and those with
comorbidities. Pandemic preparation and response take time,
so healthcare and public health systems need to move forward
quickly in their eorts to confront this disease around the globe,
actively anticipating new disease hotspots and allocating resources
accordingly. The most important public health interventions
to slow the spread include rapid identication and isolation of
cases, along with early implementations of physical distancing
measures. A serious challenge in responding to COVID-19 is
protecting HCWs and preventing nosocomial infection. Reliably
sustainable supplies of PPE and ventilators are urgently needed.
Novel therapeutics must be studied in expedited but rigorous
clinical investigations to reduce therapeutic ambiguity, potentially
harmful therapeutic applications, and the possibility or undue
pressure from non-expert inuencers. Postpandemic transition to
a new global baseline will require deliberate planning, thoughtful
implementation, and close international coordination.
The Joint ACAIM-WACEM Working Group on COVID-19
would like to thank the following individuals for their generous
support (alphabetically): Praveen Aggarwal, Bonnie Arquilla,
Sanjeev Bhoi, Christine Butts, Basan Cander, Roberto C
Castillo, Pia Daniel, Jessica Evert, Ramon Gist, Diane Gorgas,
Vicente H Gracias, Yves Juillet, Sarathi Kalra, Himanshu
Kataria, Kristiana Kaufmann, Abbas Khan, Prashant Mahajan,
Ron Maio, Marian McDonald, Moshe Michaelson, Alaa-Eldin
A. Mira, Yasumitsu Mizobata, Shella Nagales Liggayu, Mayur
Narayan, Tetsuro Nishimura, Rockefeller Oteng, Jessica
Stawicki, et al.: Joint ACAIM-WACEM Statement on COVID-19
Journal of Global Infectious Diseases ¦ Volume 12 ¦ Issue 2 ¦ April-June 2020
Paulson, Gregory Peck, Alwi Abdul Rahman, Samiddhi
Samarakoon, Richard P Sharpe, Ziad C Sifri, Mamta Swaroop,
Eran Tal-Or, Krima Thakker, Thushara Vidanapathirana, Franz
Yanagawa, Mansour Mohamed Yousef.
Financial support and sponsorship
Conflicts of interest
There are no conicts of interest.
1. Kaewunruen S, Sussman JM, Matsumoto A. Grand challenges in
transportation and transit systems. Frontiers Built Environ 2016;2:4.
2. Rodrigue JP. Globalization and the synchronization of transport
terminals. J Transport Geography 1999;7:255-61.
3. Cai J, Xu B, Chan KK, Zhang X, Zhang B, Chen Z, et al. Roles of
dierent transport modes in the spatial spread of the 2009 inuenza
A (H1N1) pandemic in mainland China. Int J Environ Res Public Health
4. Kulmala I. Tackling the spread of pathogens in transport hubs. Drug
Target Rev 2016;3:46-9.
5. Browne A, Ahmad SS, Beck CR, Nguyen-Van-Tam JS. The roles of
transportation and transportation hubs in the propagation of inuenza
and coronaviruses: A systematic review. J Travel Med 2016;23:tav002.
6. Kulczyński M, Tomaszewski M, Łuniewski M, Olender A. Air transport
and the spread of infectious diseases. World Sci News 2017;76:123-35.
7. Nasir ZA, Campos LC, Christie N, Colbeck I. Airborne biological
hazards and urban transport infrastructure: Current challenges and
future directions. Environ Sci Pollut Res Int 2016;23:15757-66.
8. Goscé L, Johansson A. Analysing the link between public transport
use and airborne transmission: Mobility and contagion in the London
underground. Environ Health 2018;17:84.
9. Gralinski LE, Menachery VD. Return of the coronavirus: 2019-nCoV.
Viruses 2020;12. pii: E135.
10. Rappuoli R, Dormitzer PR. Inuenza: Options to improve pandemic
preparation. Science 2012;336:1531-3.
11. Tomizuka T, Kanatani Y, Kawahara K. Insucient preparedness of
primary care practices for pandemic inuenza and the eect of a
preparedness plan in Japan: A prefecture-wide cross-sectional study.
BMC Fam Pract 2013;14:174.
12. Peeri NC, Shrestha N, Rahman MS, Zaki R, Tan Z, Bibi S, et al.
The SARS, MERS and novel coronavirus (COVID-19) epidemics, the
newest and biggest global health threats: what lessons have we learned?
Int J Epidemiol 2020. pii: dyaa033.
13. Kandel N, Chungong S, Omaar A, Xing J. Health security capacities
in the context of COVID-19 outbreak: an analysis of International
Health Regulations annual report data from 182 countries. Lancet
14. Gudi SK, Tiwari KK. Preparedness and lessons learned from the novel
coronavirus disease. Int J Occup Environ Med 2020;11:1977-108.
15. Che C. What Doctors Treating Covid-19 in Wuhan Say About
Coronavirus; 2020. Available from:
about-the-virus. [Last accessed on 2020 Mar 11].
16. Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, et al. Clinical characteristics
of 138 hospitalized patients with 2019 novel coronavirus-infected
pneumonia in Wuhan, China. JAMA. 2020 17;323:1061-9.
17. Zhu Z, Xu S, Wang H, Liu Z, Wu J, Li G, et al. COVID-19 in Wuhan:
Immediate psychological impact on 5062 Health Workers. medRxiv;
2020 Jan 1.
18. Chinazzi M, Davis JT, Ajelli M, Gioannini C, Litvinova M, Merler S,
et al. The eect of travel restrictions on the spread of the 2019 novel
coronavirus (COVID-19) outbreak. Science 2020. pii: eaba9757.
19. Melendez P. This is What a Coronavirus Lockdown Means in Each
State; 2020. Available from:
washington-and-other-states. [Last accessed on 2020 Mar 31].
20. Li D, Liu Z, Liu Q, Gao Z, Zhu J, Yang J, et al. Estimating the ecacy
of trac blockage and quarantine for the epidemic caused by 2019-
nCoV (COVID-19). medRxiv; 2020 Jan 1.
21. Bergman D, Bethell C, Gombojav N, Hassink S, Stange KC. Physical
Distancing With Social Connectedness; 2020. Available online at:
StangeAFM-674-19%20ms.pdf?sequence=1. Last accessed on April 25,
22. Faherty LJ, Schwartz HL, Ahmed F, Zheteyeva Y, Uzicanin A, Uscher-
Pines L. School and preparedness ocials’ perspectives on social
distancing practices to reduce inuenza transmission during a pandemic:
Considerations to guide future work. Prev Med Rep 2019;14:100871.
23. Zi AL, Zi RM. Fractal kinetics of COVID-19 pandemic. medRxiv;
2020 Jan 1 (updated 2020 Mar 1).
24. Mole B. Pandemic Declared as COVID-19 Blazes across Globe: The
Disease and its Spread are Alarming—So is the Level of Inaction, WHO
Says; 2020. Available from:
covid-19-is-a-pandemic-who-declares/. [Last accessed on 2020 Mar 11].
25. Fox L, Dister C. Schumer, Other Senators to Ask Trump to Issue
National Emergency Declaration for Coronavirus; 2020. Available
emergency-declaration/index.html. [Last accessed on 2020 Mar 11].
26. Cathey L. Government Coronavirus Response: Trump Declares
National Emergency, says he ‘likely’ will get Tested; 2020. Available
[Last accessed on 2020 Mar 16].
27. World-O-Meter. COVID-19 Coronavirus Pandemic; 2020. Available
from: [Last accessed on
2020 Mar 29].
28. World-O-Meter. Coronavirus (COVID-19) Mortality Rate; 2020.
Available from:
coronavirus-death-rate/. [Last accessed on 2020 Mar 30].
29. Achenbach J. Three Months into the Pandemic, here’s how Likely the
Coronavirus is to Infect People; 2020. Available from: https://www.
11ea-b148-e4ce3fbd85b5_story.html. [Last accessed on 2020 Apr 09].
30. Van Beusekom M. US Studies oer Cluses to COVID-19 Swift Spread,
Severity; 2020. Available from:
severity. [Last accessed on 2020 Apr 09].
31. Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, et al. A novel
coronavirus from patients with pneumonia in China, 2019. N Engl J
Med 2020;382:727-33.
32. Young BE, Ong SW, Kalimuddin S, Low JG, Tan SY, Loh J, et al.
Epidemiologic features and clinical course of patients infected with
SARS-CoV-2 in Singapore. JAMA 2020 ;Mar 3.
33. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of
patients infected with 2019 novel coronavirus in Wuhan, China. Lancet
34. Lu R, Zhao X, Li J, Niu P, Yang B, Wu H, et al. Genomic characterisation
and epidemiology of 2019 novel coronavirus: Implications for virus
origins and receptor binding. Lancet 2020;395:565-74.
35. Plapp F. The COVID-19 Pandemic: A Summary; 2020. Available from:
summary. [Last accessed on 2020 Apr 09].
36. Lai CC, Shih TP, Ko WC, Tang HJ, Hsueh PR. Severe acute
respiratory syndrome coronavirus 2 (SARS-CoV-2) and corona virus
disease-2019 (COVID-19): The epidemic and the challenges. Int J
Antimicrobial Agents 2020 ;Feb 17:105924.
37. Ko WC, Rolain JM, Lee NY, Chen PL, Huang CT, Lee PI, et al.
Arguments in favor of remdesivir for treating SARS-CoV-2 infections.
Int J Antimicrobial Agents 2020 ;Mar 6:105933.
38. Khan S, Siddique R, Shereen MA, Ali A, Liu J, Bai Q, et al. The
emergence of a novel coronavirus (SARS-CoV-2), their biology and
therapeutic options. J Clin Microbiol. 2020 Mar 11:00187-20.
39. Wu C, Chen X, Cai Y, Xia J, Zhou X, Xu S, et al. Risk Factors Associated
With Acute Respiratory Distress Syndrome and Death in Patients With
Stawicki, et al.: Joint ACAIM-WACEM Statement on COVID-19
Journal of Global Infectious Diseases ¦ Volume 12 ¦ Issue 2 ¦ April-June 2020 73
Coronavirus Disease 2019 Pneumonia in Wuhan, China. JAMA Intern
Med 2020 ;Mar 13.
40. Totura AL, Bavari S. Broad-spectrum coronavirus antiviral drug
discovery. Expert Opin Drug Discov 2019;14:397-412.
41. Al-Omari A, Rabaan AA, Salih S, Al-Tawq JA, Memish ZA. MERS
coronavirus outbreak: Implications for emerging viral infections. Diagn
Microbiol Infect Dis 2019;93:265-85.
42. Zhang S, Li H, Huang S, You W, Sun H. High-resolution CT features of
17 cases of Corona Virus Disease 2019 in Sichuan Province, China. Eur
Respir J 2020. pii: 2000334.
43. Cyranoski D. Mystery Deepends over Animal Source of Coronavirus;
2020. Available from:
00548-w. [Last accessed on 2020 Mar 19].
44. Brosseau L. Commentary: COVID-19 Transmission Messages Should
Hinge on Science; 2020. Available from: http://www.cidrap.umn.
messages-should-hinge-science. [Last accessed on 2020 Apr 02]
45. Brown L. The Coronavirus Spreads at Least 13 Feet, Travels on
Shoes: CDC; 2020. Available from:
the-coronavirus-can-travel-at-least-13-feet-new-study-shows/. [Last
accessed on 2020 Apr 13].
46. Hindson J. COVID-19: Faecal-Oral Transmission?; 2020. Available
from: [Last
accessed on 2020 Apr 02].
47. Gu J, Han B, Wang J. COVID-19: Gastrointestinal manifestations and
potential fecal-oral transmission. Gastroenterology 2020 ;Mar 3.
48. Xinhua Net. Chinese Scientists Map out Novel Coronavirus’s Entry
Point into Human Cell at Atomic Level; 2020. Available from: http:// [Last
accessed on 2020 Apr 02].
49. Kuster GM, Pster O, Burkard T, Zhou Q, Twerenbold R,
Haaf P, et al. SARS-CoV2: Should inhibitors of the renin–angiotensin
system be withdrawn in patients with COVID-19? Eur Heart J 2020;Mar
20 .
50. R&D Systems. ACE-2: The Receptor for SARS-CoV-2; 2020. Available
receptor-identied. [Last accessed on 2020 Apr 02].
51. Cai G, Cui X, Zhu X, Zhou J. A Hint on the COVID-19 Risk: Population
Disparities in Gene Expression of Three Receptors of SARS-CoV;
Preprints 2020 Feb 27. doi: 10.20944/preprints202002.0408.v1
52. Wu C, Zheng S, Chen Y, Zheng M. Single-cell RNA expression proling
of ACE2, the putative receptor of Wuhan 2019-nCoV, in the nasal tissue.
medRxiv; 2020 Jan 1.
53. AssayGenie. How Furin and ACE2 Interact with the Spike Protein on
SARS-CoV-2; 2020. Available from:
furin-and-ace2-interact-with-the-spike-on-sarscov2. [Last accessed on
2020 Apr 04].
54. Wang K, Chen W, Zhou YS, Lian JQ, Zhang Z, Du P, et al. SARS-
CoV-2 invades host cells via a novel route: CD147-spike protein.
bioRxiv; 2020 Jan 1.
55. Ibrahim IM, Abdelmalek DH, Elshahat ME, Elky AA. COVID-19
spike-host cell receptor GRP78 binding site prediction. J Infect
56. Xi J, et al. Virus strain of a mild COVID-19 patient in Hangzhou
representing a new trend in SARS-CoV-2 evolution related to Furin
cleavage site. medRxiv; 2020.
57. MacLean OA, Orton R, Singer JB, Robertson DL. Response to “On
the origin and continuing evolution of SARS-CoV-2”; 2020. Available
evolution-of-sars-cov-2/418. [Last accessed on 2020 Apr 13].
58. Tian S, Hu W, Niu L, Liu H, Xu H, Xiao SY. Pulmonary Pathology
of Early Phase SARS-COV-2 Pneumonia; Preprints 2020;Mar 2. doi:
59. Hanley B, Lucas SB, Youd E, Swift B, Osborn M. Autopsy in suspected
COVID-19 cases. J Clin Pathol 2020; 73 (5):239-42 .
60. Zhihao Z. Autopsy Report Reveals COVID-19 Mainly Attacks Lungs;
2020. Available from:
WS5e58a9cea31012821727b144.html. [Last accessed on 2020 Apr 05].
61. Lauer SA, Grantz KH, Bi Q, Jones FK, Zheng Q, Meredith HR, et al.
The incubation period of coronavirus disease 2019 (COVID-19) from
publicly reported conrmed cases: Estimation and application. Ann
Intern Med 2020 ;March 10.
62. Resnick B, Animashaun C. Why COVID-19 is Worse than the Flu, in
One Chart; 2020. Available from:
chart. [Last accessed on 2020 Mar 19].
63. Von Beusekom M. Studies Prole Lung Changes in Asymptomatic
COVID-19, Viral Loads in Patient Samples; 2020. Available from: http://le-lung-
changes-asymptomatic-covid-19-viral-loads-patient. [Last accessed on
2020 Mar 19].
64. Diamond F. Asymptomatic Carriers of COVID-19 Make It Tough to
Target; 2020. Available from:
covid-19/asymptomatic-carriers-covid-19-make-it-tough-target. [Last
accessed on 2020 Apr 02].
65. Inui S, Fujikawa A, Jitsu M, Kunishima N, Watanabe S, Suzuki Y, et al.
Chest CT ndings in cases from the cruise ship “diamond princess” with
coronavirus disease 2019 (COVID-19). Radiology 2020;2:e200110.
66. Apoorva M. Infected but Feeling Fine: The Unwitting Coronavirus
Spreaders; 2020. Available from:
health/coronavirus-asymptomatic-transmission.html. [Last accessed on
2020 Apr 05].
67. John T. Iceland lab’s Testing Suggests 50% of Coronavirus Cases have
no Symptoms; 2020. Available from:
europe/iceland-testing-coronavirus-intl/index.html. [Last accessed on
2020 Apr 14].
68. Nishiura H, Linton NM, Akhmetzhanov AR. Serial interval of novel
coronavirus (COVID-19) infections. Int J Infect Dis 2020 ;Mar 4.
69. Haglage A. New CDC Report nds COVID-19 can be Spread 1-3 Days
Before onset of Symptoms. 2020. Available from:
days-before-onset-of-symptoms-174344709.html. [Last accessed on
2020 Apr 09].
70. Zhao J, Yang Y, Huang HP, Li D, Gu DF, Lu XF, et al. Relationship
between the ABO Blood Group and the COVID-19 Susceptibility.
medRxiv; 2020: Jan 1.
71. Gander K. Risk of Getting COVID-19 Could Be Linked to Certain Blood
Types, Coronavirus Study Suggests; 2020. Available from: https://www. [Last
accessed on 2020 Apr 05].
72. Tully T. Coronavirus Ravages 7 Members of a Single Family, Killing 4;
2020. Available from:
new-jersey-family-coronavirus.html. [Last accessed on 2020 Apr 05].
73. Redick G. Ohio Woman Loses 3 Family Members to COVID-19, Urges
Social Distancing for Others; 2020. Available from:
urges-social-distancing-for-others. [Last accessed on 2020 Apr 05].
74. Yeager P. Members of Metro Family Tested Positive for COVID-19,
3 in Critical Condition; 2020. Available from:
3-in-critical-condition/. [Last accessed on 2020 Apr 05].
75. Hogg E. Members of Same St. Louis Family Come Down with
COVID-19; 2020. Available from:
article_05568d18-6d50-11ea-892e-4b1433f11c07.html. [Last accessed
on 2020 Apr 05].
76. Chinese Center for Disease Control and Prevention Novel Coronavirus
Pneumonia Emergency Response Epidemiology, The epidemiological
characteristics of an outbreak of 2019 novel coronavirus
diseases (COVID-19) in China. Zhonghua Liu Xing Bing Xue Za Zhi
77. Livingston E, Bucher K. Coronavirus Disease 2019 (COVID-19) in
Italy. JAMA 2020; 323 (14):1335 .
78. Bicker L. Coronavirus in South Korea: How ‘Trace, Test and Treat’ may
be Saving Lives; 2020. Available from:
world-asia-51836898. [Last accessed on 2020 Mar 13].
79. Craig D. Tale of Two Death Rates: How South Korea and Italy Predict
our COVID-19 Future; 2020. Available from: https://blog.sprucehealth.
covid-19-future/. [Last accessed on 2020 Mar 30].
Stawicki, et al.: Joint ACAIM-WACEM Statement on COVID-19