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COVID-19 Nifedipine Phoshpdiesterase Inhibitors Acetazolamide

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Effective treatments for Coronavirus Disease 2019 (COVID-19) outbreak are urgently needed. While anti-viral approaches and vaccines are being considered immediate countermeasures are unavailable. The aim of this article is to outline a perspective on the pathophysiology of COVID-19 in the context of the currently available clinical data published in the literature. This article appreciates clinical data published on COVID-19 in the context of another respiratory illness - high altitude pulmonary edema (HAPE). Both conditions have significant similarities that portend pathophysiologic trajectories. Following this potential treatment options emerge. Both COVID-19 and HAPE exhibit a decreased ratio of arterial oxygen partial pressure to fractional inspired oxygen with concomitant hypoxia and tachypnea. There also appears to be a tendency for low carbon dioxide levels in both as well. Radiologic findings of ground glass opacities are present in up to 86% of patients with COVID-19 in addition to patchy infiltrates. Patients with HAPE also exhibit patchy infiltrates throughout the pulmonary fields, often in an asymmetric pattern and CT findings reveal increased lung markings and ground glass-like changes as well. Widespread ground-glass opacities are most commonly a manifestation of hydrostatic pulmonary edema. Similarly, elevated fibrinogen levels in both conditions are likely an epiphenomenon of edema formation rather than coagulation activation. Autopsy results of a COVID-19 fatality revealed bilateral diffuse alveolar damage associated with pulmonary edema, pro-inflammatory concentrates, and indications of early-phase acute respiratory distress syndrome (ARDS). HAPE itself is initially caused by an increase in pulmonary capillary pressure and induces altered alveolar-capillary permeability via high pulmonary artery hydrostatic pressures that lead to a protein-rich and mildly hemorrhagic edema. It appears that COVID-19 and HAPE both discretely converge on ARDS. In light of this, a countermeasure that has been shown to be effective in the analogous condition of HAPE is Acetazolamide. Acetazolamide has a myriad of effects on different organ systems, potently reduces hypoxic pulmonary vasoconstriction, improves minute ventilation and expired vital capacity. Other therapeutics to consider that are also directed towards decreased pulmonary pressure include Nifedipine and Phosphodiesterase inhibitors. This review describes COVID-19 in parallel to HAPE. Deranged respiratory parameters that are present in both conditions are highlighted. The utilization of medications found to be effective in HAPE, for the treatment of COVID-19, is proposed. Given the medical emergency of a growing contagion and the thousands of lives at stake, expedient attempts to improve survival are needed. Acetazolamide, Nifedipine and Phosphodiesterase inhibitors may be potential countermeasures.
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Received 03/07/2020
Review began 03/09/2020
Review ended 03/16/2020
Published 03/20/2020
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Acetazolamide, Nifedipine and
Phosphodiesterase Inhibitors: Rationale for
Their Utilization as Adjunctive
Countermeasures in the Treatment of
Coronavirus Disease 2019 (COVID-19)
Isaac Solaimanzadeh
1. Internal Medicine, Interfaith Medical Center, Brooklyn, USA
Corresponding author: Isaac Solaimanzadeh, isolaimanzadeh@interfaithmedical.org
Abstract
Effective treatments for Coronavirus Disease 2019 (COVID-19) outbreak are urgently needed.
While anti-viral approaches and vaccines are being considered immediate countermeasures are
unavailable. The aim of this article is to outline a perspective on the pathophysiology of
COVID-19 in the context of the currently available clinical data published in the literature. This
article appreciates clinical data published on COVID-19 in the context of another respiratory
illness - high altitude pulmonary edema (HAPE). Both conditions have significant similarities
that portend pathophysiologic trajectories. Following this potential treatment options emerge.
Both COVID-19 and HAPE exhibit a decreased ratio of arterial oxygen partial pressure to
fractional inspired oxygen with concomitant hypoxia and tachypnea. There also appears to be a
tendency for low carbon dioxide levels in both as well. Radiologic findings of ground glass
opacities are present in up to 86% of patients with COVID-19 in addition to patchy infiltrates.
Patients with HAPE also exhibit patchy infiltrates throughout the pulmonary fields, often in an
asymmetric pattern and CT findings reveal increased lung markings and ground glass-like
changes as well. Widespread ground-glass opacities are most commonly a manifestation of
hydrostatic pulmonary edema. Similarly, elevated fibrinogen levels in both conditions are likely
an epiphenomenon of edema formation rather than coagulation activation. Autopsy results of a
COVID-19 fatality revealed bilateral diffuse alveolar damage associated with pulmonary edema,
pro-inflammatory concentrates, and indications of early-phase acute respiratory distress
syndrome (ARDS). HAPE itself is initially caused by an increase in pulmonary capillary
pressure and induces altered alveolar-capillary permeability via high pulmonary artery
hydrostatic pressures that lead to a protein-rich and mildly hemorrhagic edema. It appears that
COVID-19 and HAPE both discretely converge on ARDS. In light of this, a countermeasure that
has been shown to be effective in the analogous condition of HAPE is Acetazolamide.
Acetazolamide has a myriad of effects on different organ systems, potently reduces hypoxic
pulmonary vasoconstriction, improves minute ventilation and expired vital capacity. Other
therapeutics to consider that are also directed towards decreased pulmonary pressure include
Nifedipine and Phosphodiesterase inhibitors.
This review describes COVID-19 in parallel to HAPE. Deranged respiratory parameters that are
present in both conditions are highlighted. The utilization of medications found to be effective
in HAPE, for the treatment of COVID-19, is proposed. Given the medical emergency of a
growing contagion and the thousands of lives at stake, expedient attempts to improve survival
are needed. Acetazolamide, Nifedipine and Phosphodiesterase inhibitors may be
potential countermeasures.
1
Open Access Review
Article DOI: 10.7759/cureus.7343
How to cite this article
Solaimanzadeh I (March 20, 2020) Acetazolamide, Nifedipine and Phosphodiesterase Inhibitors: Rationale
for Their Utilization as Adjunctive Countermeasures in the Treatment of Coronavirus Disease 2019
(COVID-19). Cureus 12(3): e7343. DOI 10.7759/cureus.7343
Categories: Infectious Disease, Pulmonology, Public Health
Keywords: coronavirus, covid-19, high altitude pulmonary edema, respiratory care, wuhan
coronavirus, acetazolamide, ground glass opacities, hypoxia, covid-2019, novel coronavirus
Introduction And Background
Effective treatments for Coronavirus Disease 2019 (COVID-19) outbreak are urgently needed.
While anti-viral approaches are being considered and trials as well as vaccines may be
forthcoming, immediate countermeasures are still remiss [1].
In ideal circumstances medications are intentionally designed, profiled and tested to combat
initiators of pathophysiologic processes. However, when that is not available, there may be a
need to consider treatment regimens from analogous disease patterns. Matching clinical
dispositions can be considered in efforts to develop therapeutic interventions. Moreover, dire
outcomes of illness may be overcome with adjunctive measures that do not necessarily cure
underlying disease. Rather, supportive care as well as adjunctive countermeasures may assist
patients in surviving viral illness.
The aim of this article is to outline a perspective on the pathophysiology of COVID-19 in the
context of the currently available clinical data published in the literature. Following a
characterization of the disease vis-a-vis a similar respiratory illness, potential treatment
options may emerge.
Review
Supportive management with specific Respiratory and Ventilator support are current mainstays
of treatment [2]. Sequential progression of respiratory compromise has been observed -
highlighting the primacy of respiratory malfunction in overall clinical demise [3].
Therefore, garnering management approaches from similar respiratory conditions may be
beneficial. Analyzing clinical data reported in published studies reveal striking similarities to
high altitude pulmonary edema (HAPE) as manifested during the acute hypoxic ventilatory
response.
To begin with, in severe cases, both COVID-19 and HAPE exhibit a decreased ratio of arterial
oxygen partial pressure to fractional inspired oxygen (Pao2:FiO2 ratio) with concomitant
hypoxia and tachypnea [4,5]. There also appears to be a tendency for low carbon dioxide levels
in COVID-19 as the median partial pressure of carbon dioxide (PaCO2) level was 34 mmHg
(inter-quartile range: 30-38; normal range: 35-48) in a recent JAMA article describing 138
hospitalized cases [6]. Initial exposure to hypoxia at high altitude leads to an immediate
increase in ventilation that blows off large quantities of carbon dioxide, producing hypocapnia
as well [7]. Furthermore, blood gases of non-acclimatized mountaineers with severe illness
were accompanied by a significant decrease in arterial oxygen due to an increase in alveolar-
arterial oxygen difference, although herein arterial PaCO2 did not change significantly [8]. In
short, hypoxia and hypocapnia are seen in both conditions, but there is more.
Radiologic findings of ground-glass opacities are present in up to 86% of patients with COVID-
19 with 76% having bilateral distribution and 33% peripheral [9]. Notably, lung cavitations,
discrete pulmonary nodules, pleural effusions, and lymphadenopathy were absent [10]. In
addition to this, patchy infiltrates are present [11]. Patients with HAPE also exhibit patchy
infiltrates throughout the pulmonary fields, often in an asymmetric pattern and CT findings
reveal increased lung markings and ground glass-like changes as well [12-14]. It has been
shown that widespread ground-glass opacities are most commonly a manifestation of
2020 Solaimanzadeh et al. Cureus 12(3): e7343. DOI 10.7759/cureus.7343 2 of 6
hydrostatic pulmonary edema and this is a central point to consider going forward [15].
See, all older patients in a familial cluster had elevated fibrinogen levels [16]. In tandem,
markers of fibrin formation were significantly elevated in HAPE and Fibrin generation in that
condition is deliberated as an epiphenomenon of edema formation rather than coagulation
activation [8]. Altogether, these specific pulmonary clinical manifestations exhibit identical
features between both COVID-19 and HAPE.
There certainly is much to ascertain with regard to the precise pathophysiology of COVID-19.
Investigation of virulent properties of COVID-19 as well inflammatory responses and their
effects on Alveolar integrity requires further study. Autopsy results of a COVID-19 fatality
revealed bilateral diffuse alveolar damage associated with pulmonary edema, pro-inflammatory
concentrates, and indications of early-phase acute respiratory distress syndrome (ARDS) [17].
HAPE itself is initially caused by an increase in pulmonary capillary pressure [18]. HAPE
induces altered alveolar-capillary permeability via high pulmonary artery hydrostatic pressures
that lead to a protein-rich and mildly hemorrhagic edema [19]. COVID-19 and HAPE both
discretely converge on ARDS [5,17].
Yet, it can be posited that beginning early treatment may prevent ARDS development.
Regardless of pathophysiologic triggers, stark clinical endpoints are apparent and similar in
nature. Ultimately, distinctive pulmonary specific parameters in severe disease have
comparable patterns (Table 1).
Parameter HAPE COVID-19
Pao2:FiO2 ratio Decreased Decreased
Hypoxia Present Present
Tachypnea Increased Increased
PaCO2 level Decreased Decreased
Ground Glass Opacities on Chest CT Present Present
Patchy Infiltrates on Chest X-RAY Present Present
Fibrinogen levels/Fibrin formation Increased Increased
Alveolar compromise Present Present
Acute Respiratory Distress Syndrome Development in Severe Disease Present Present
TABLE 1: Similar patterns of pulmonary disease between HAPE and COVID-19
HAPE: High altitude pulmonary edema; COVID-19: Coronavirus disease 2019; Pao2:FiO2 ratio: Arterial oxygen partial pressure to
fractional inspired oxygen ratio; PaCO2 level: Partial pressure of carbon dioxide; Chest CT: Computed tomography of chest.
In light of this, a countermeasure that has been shown to be effective in high altitude illness is
Acetazolamide.
Acetazolamide has a myriad of effects on different organ systems [20]. It potently reduces
2020 Solaimanzadeh et al. Cureus 12(3): e7343. DOI 10.7759/cureus.7343 3 of 6
hypoxic pulmonary vasoconstriction [21]. Improved minute ventilation and expired vital
capacity has been shown in climbers taking Acetazolamide as well [22].
Furthermore, over 70% of patients with COVID-19 had elevated lactate dehydrogenase levels
[23]; this too may be connected to hypoxia. Evidently, Acetazolamide has physiologic effects
that delay plasma lactate appearance with no effect on ventilatory threshold [24].
Other therapeutics that have been shown to be effective in the analogous condition of
HAPE and that are directed towards decreased pulmonary pressure include Nifedipine and
Phosphodiesterase inhibitors (Table 2) [25,26].
Acetazolamide 250 mg every 12 hours
Nifedipine 30 mg extended release every 12 hours
Sildenafil 20-50 mg every 8 hours
Tadalafil 10 mg every 12 hours
TABLE 2: Sample medications and dosages utilized in high altitude illness and HAPE
HAPE: High altitude pulmonary edema
Conclusions
This review describes COVID-19 in parallel to HAPE. Deranged respiratory parameters that are
present in both conditions are highlighted. The utilization of medications found to be effective
in HAPE for the treatment of COVID-19 is proposed. Given the medical emergency of a growing
contagion and the thousands of lives at stake, expedient attempts to improve survival are
needed. Acetazolamide, Nifedipine and Phosphodiesterase inhibitors may present an
opportunity for countermeasure development.
Additional Information
Disclosures
Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors
declare the following: Payment/services info: All authors have declared that no financial
support was received from any organization for the submitted work. Financial relationships:
All authors have declared that they have no financial relationships at present or within the
previous three years with any organizations that might have an interest in the submitted work.
Other relationships: All authors have declared that there are no other relationships or
activities that could appear to have influenced the submitted work.
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... In the last few months, as expected, a few authors have proposed the use of PDE inhibitors for the treatment of COVID-19, based on the clinical features observed in this disease, as well as on their analogy to other already known pathologies, for which the use of inhibitors has already been approved (Figure 1). Solaimanzadeh and coauthors [79] propose the use of PDE5 inhibitors, showing the analogy of COVID-19 to HAPE (high altitude pulmonary edema), a respiratory disease in which these molecules have already been clinically tested and used. Given the medical emergency due to the growing contagion and the thousands of lives at stake, drugs like acetazolamide, nifedipine and phosphodiesterase 5 inhibitors represent an opportunity not to be underestimated for SARS-CoV-2 infection [79]. ...
... Solaimanzadeh and coauthors [79] propose the use of PDE5 inhibitors, showing the analogy of COVID-19 to HAPE (high altitude pulmonary edema), a respiratory disease in which these molecules have already been clinically tested and used. Given the medical emergency due to the growing contagion and the thousands of lives at stake, drugs like acetazolamide, nifedipine and phosphodiesterase 5 inhibitors represent an opportunity not to be underestimated for SARS-CoV-2 infection [79]. ...
... As reported in the literature, and also highlighted in this review, an effective inhibitory action on proinflammatory cytokines is also performed by cAMP, through modulation of protein kinase A (PKA) and nuclear factor κB (NF-κΒ) pathways. In a recent commentary, Dalamaga and co-authors [82] hypothesize that the selective inhibition of cAMPspecific PDE4, a widely distributed PDE whose inhibition leads to appreciable anti-inflammatory, Solaimanzadeh and coauthors [79] propose the use of PDE5 inhibitors, showing the analogy of COVID-19 to HAPE (high altitude pulmonary edema), a respiratory disease in which these molecules have already been clinically tested and used. Given the medical emergency due to the growing contagion and the thousands of lives at stake, drugs like acetazolamide, nifedipine and phosphodiesterase 5 inhibitors represent an opportunity not to be underestimated for SARS-CoV-2 infection [79]. ...
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On March 11, 2020, the World Health Organization (WHO) declared the severe acute respiratory syndrome caused by coronavirus 2 (SARS-CoV-2) a global pandemic. As of July 2020, SARS-CoV-2 has infected more than 14 million people and provoked more than 590,000 deaths, worldwide. From the beginning, a variety of pharmacological treatments has been empirically used to cope with the life-threatening complications associated with Corona Virus Disease 2019 (COVID-19). Thus far, only a couple of them and not consistently across reports have been shown to further decrease mortality, respect to what can be achieved with supportive care. In most cases, and due to the urgency imposed by the number and severity of the patients’ clinical conditions, the choice of treatment has been limited to repurposed drugs, approved for other indications, or investigational agents used for other viral infections often rendered available on a compassionate-use basis. The rationale for drug selection was mainly, though not exclusively, based either i) on the activity against other coronaviruses or RNA viruses in order to potentially hamper viral entry and replication in the epithelial cells of the airways, and/or ii) on the ability to modulate the excessive inflammatory reaction deriving from dysregulated host immune responses against the SARS-CoV-2. In several months, an exceptionally large number of clinical trials have been designed to evaluate the safety and efficacy of anti-COVID-19 therapies in different clinical settings (treatment or pre- and post-exposure prophylaxis) and levels of disease severity, but only few of them have been completed so far. This review focuses on the molecular mechanisms of action that have provided the scientific rationale for the empirical use and evaluation in clinical trials of structurally different and often functionally unrelated drugs during the SARS-CoV-2 pandemic.
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In December, 2019, several patients with pneumonia of an unknown cause were detected in Wuhan, China. On January 7, 2020, the causal organism was identified as a new coronavirus, later named as the “2019 novel coronavirus” (2019-nCoV). Genome sequencing found the genetic sequence of 2019-nCoV homologous to that of Severe Acute Respiratory Syndrome-Associated Coronavirus (SARS-CoV). As of January 29, 2020, the virus had been diagnosed in more than 7,000 patients in China and 77 outside this country. It is reported that both symptomatic and asymptomatic patients with 2019-nCov can play a role in disease transmission via airborne and contact. This finding has caused a great concern about the prevention of illness spread. The clinical features of the infection are not specific and are often indistinguishable from those of other respiratory infections, making it difficult to diagnose. Given that the virus has a strong ability to spread between individuals, it is of top priority to identify potential or suspected patients as soon as possible. Or the virus may cause a serious pandemic. Therefore, a precision medicine approach to managing this disease is urgently needed for detecting and controlling the spread of the virus. In this article, we present such an approach to managing 2019-nCoV-related pneumonia based on the unique traits of the virus recently revealed, and on our experience with coronaviruses at West China Hospital in Chengdu, China.
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Therapeutic options in response to the 2019-nCoV outbreak are urgently needed. Here, we discuss the potential for repurposing existing antiviral agents to treat 2019-nCoV infection (now known as COVID-19), some of which are already moving into clinical trials. Therapeutic options in response to the 2019-nCoV outbreak are urgently needed. Here, we discuss the potential for repurposing existing antiviral agents to treat 2019-nCoV infection (now known as COVID-19), some of which are already moving into clinical trials.
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Background: An ongoing outbreak of pneumonia associated with a novel coronavirus was reported in Wuhan city, Hubei province, China. Affected patients were geographically linked with a local wet market as a potential source. No data on person-to-person or nosocomial transmission have been published to date. Methods: In this study, we report the epidemiological, clinical, laboratory, radiological, and microbiological findings of five patients in a family cluster who presented with unexplained pneumonia after returning to Shenzhen, Guangdong province, China, after a visit to Wuhan, and an additional family member who did not travel to Wuhan. Phylogenetic analysis of genetic sequences from these patients were done. Findings: From Jan 10, 2020, we enrolled a family of six patients who travelled to Wuhan from Shenzhen between Dec 29, 2019 and Jan 4, 2020. Of six family members who travelled to Wuhan, five were identified as infected with the novel coronavirus. Additionally, one family member, who did not travel to Wuhan, became infected with the virus after several days of contact with four of the family members. None of the family members had contacts with Wuhan markets or animals, although two had visited a Wuhan hospital. Five family members (aged 36-66 years) presented with fever, upper or lower respiratory tract symptoms, or diarrhoea, or a combination of these 3-6 days after exposure. They presented to our hospital (The University of Hong Kong-Shenzhen Hospital, Shenzhen) 6-10 days after symptom onset. They and one asymptomatic child (aged 10 years) had radiological ground-glass lung opacities. Older patients (aged >60 years) had more systemic symptoms, extensive radiological ground-glass lung changes, lymphopenia, thrombocytopenia, and increased C-reactive protein and lactate dehydrogenase levels. The nasopharyngeal or throat swabs of these six patients were negative for known respiratory microbes by point-of-care multiplex RT-PCR, but five patients (four adults and the child) were RT-PCR positive for genes encoding the internal RNA-dependent RNA polymerase and surface Spike protein of this novel coronavirus, which were confirmed by Sanger sequencing. Phylogenetic analysis of these five patients' RT-PCR amplicons and two full genomes by next-generation sequencing showed that this is a novel coronavirus, which is closest to the bat severe acute respiatory syndrome (SARS)-related coronaviruses found in Chinese horseshoe bats. Interpretation: Our findings are consistent with person-to-person transmission of this novel coronavirus in hospital and family settings, and the reports of infected travellers in other geographical regions. Funding: The Shaw Foundation Hong Kong, Michael Seak-Kan Tong, Respiratory Viral Research Foundation Limited, Hui Ming, Hui Hoy and Chow Sin Lan Charity Fund Limited, Marina Man-Wai Lee, the Hong Kong Hainan Commercial Association South China Microbiology Research Fund, Sanming Project of Medicine (Shenzhen), and High Level-Hospital Program (Guangdong Health Commission).
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Objectives The purpose of this study was to observe the imaging characteristics of the novel coronavirus pneumonia.Methods Sixty-three confirmed patients were enrolled from December 30, 2019 to January 31, 2020. High-resolution CT (HRCT) of the chest was performed. The number of affected lobes, ground glass nodules (GGO), patchy/punctate ground glass opacities, patchy consolidation, fibrous stripes and irregular solid nodules in each patient's chest CT image were recorded. Additionally, we performed imaging follow-up of these patients.ResultsCT images of 63 confirmed patients were collected. M/F ratio: 33/30. The mean age was 44.9 ± 15.2 years. The mean number of affected lobes was 3.3 ± 1.8. Nineteen (30.2%) patients had one affected lobe, five (7.9%) patients had two affected lobes, four (6.3%) patients had three affected lobes, seven (11.1%) patients had four affected lobes while 28 (44.4%) patients had 5 affected lobes. Fifty-four (85.7%) patients had patchy/punctate ground glass opacities, 14 (22.2%) patients had GGO, 12 (19.0%) patients had patchy consolidation, 11 (17.5%) patients had fibrous stripes and 8 (12.7%) patients had irregular solid nodules. Fifty-four (85.7%) patients progressed, including single GGO increased, enlarged and consolidated; fibrous stripe enlarged, while solid nodules increased and enlarged.Conclusions Imaging changes in novel viral pneumonia are rapid. The manifestations of the novel coronavirus pneumonia are diverse. Imaging changes of typical viral pneumonia and some specific imaging features were observed. Therefore, we need to strengthen the recognition of image changes to help clinicians to diagnose quickly and accurately.Key Points• High-resolution CT (HRCT) of the chest is critical for early detection, evaluation of disease severity and follow-up of patients with the novel coronavirus pneumonia.• The manifestations of the novel coronavirus pneumonia are diverse and change rapidly.• Radiologists should be aware of the various features of the disease and temporal changes.
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With the expanding use of molecular assays, viral pathogens are increasingly recognized among critically ill adult patients with community-acquired severe respiratory illness; studies have detected respiratory viral infections (RVIs) in 17–53% of such patients. In addition, novel pathogens including zoonotic coronaviruses like the agents causing Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS) and the 2019 novel coronavirus (2019 nCoV) are still being identified. Patients with severe RVIs requiring ICU care present typically with hypoxemic respiratory failure. Oseltamivir is the most widely used neuraminidase inhibitor for treatment of influenza; data suggest that early use is associated with reduced mortality in critically ill patients with influenza. At present, there are no antiviral therapies of proven efficacy for other severe RVIs. Several adjunctive pharmacologic interventions have been studied for their immunomodulatory effects, including macrolides, corticosteroids, cyclooxygenase-2 inhibitors, sirolimus, statins, anti-influenza immune plasma, and vitamin C, but none is recommended at present in severe RVIs. Evidence-based supportive care is the mainstay for management of severe respiratory viral infection. Non-invasive ventilation in patients with severe RVI causing acute hypoxemic respiratory failure and pneumonia is associated with a high likelihood of transition to invasive ventilation. Limited existing knowledge highlights the need for data regarding supportive care and adjunctive pharmacologic therapy that is specific for critically ill patients with severe RVI. There is a need for more pragmatic and efficient designs to test different therapeutics both individually and in combination.
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Importance In December 2019, novel coronavirus (2019-nCoV)–infected pneumonia (NCIP) occurred in Wuhan, China. The number of cases has increased rapidly but information on the clinical characteristics of affected patients is limited. Objective To describe the epidemiological and clinical characteristics of NCIP. Design, Setting, and Participants Retrospective, single-center case series of the 138 consecutive hospitalized patients with confirmed NCIP at Zhongnan Hospital of Wuhan University in Wuhan, China, from January 1 to January 28, 2020; final date of follow-up was February 3, 2020. Exposures Documented NCIP. Main Outcomes and Measures Epidemiological, demographic, clinical, laboratory, radiological, and treatment data were collected and analyzed. Outcomes of critically ill patients and noncritically ill patients were compared. Presumed hospital-related transmission was suspected if a cluster of health professionals or hospitalized patients in the same wards became infected and a possible source of infection could be tracked. Results Of 138 hospitalized patients with NCIP, the median age was 56 years (interquartile range, 42-68; range, 22-92 years) and 75 (54.3%) were men. Hospital-associated transmission was suspected as the presumed mechanism of infection for affected health professionals (40 [29%]) and hospitalized patients (17 [12.3%]). Common symptoms included fever (136 [98.6%]), fatigue (96 [69.6%]), and dry cough (82 [59.4%]). Lymphopenia (lymphocyte count, 0.8 × 10⁹/L [interquartile range {IQR}, 0.6-1.1]) occurred in 97 patients (70.3%), prolonged prothrombin time (13.0 seconds [IQR, 12.3-13.7]) in 80 patients (58%), and elevated lactate dehydrogenase (261 U/L [IQR, 182-403]) in 55 patients (39.9%). Chest computed tomographic scans showed bilateral patchy shadows or ground glass opacity in the lungs of all patients. Most patients received antiviral therapy (oseltamivir, 124 [89.9%]), and many received antibacterial therapy (moxifloxacin, 89 [64.4%]; ceftriaxone, 34 [24.6%]; azithromycin, 25 [18.1%]) and glucocorticoid therapy (62 [44.9%]). Thirty-six patients (26.1%) were transferred to the intensive care unit (ICU) because of complications, including acute respiratory distress syndrome (22 [61.1%]), arrhythmia (16 [44.4%]), and shock (11 [30.6%]). The median time from first symptom to dyspnea was 5.0 days, to hospital admission was 7.0 days, and to ARDS was 8.0 days. Patients treated in the ICU (n = 36), compared with patients not treated in the ICU (n = 102), were older (median age, 66 years vs 51 years), were more likely to have underlying comorbidities (26 [72.2%] vs 38 [37.3%]), and were more likely to have dyspnea (23 [63.9%] vs 20 [19.6%]), and anorexia (24 [66.7%] vs 31 [30.4%]). Of the 36 cases in the ICU, 4 (11.1%) received high-flow oxygen therapy, 15 (41.7%) received noninvasive ventilation, and 17 (47.2%) received invasive ventilation (4 were switched to extracorporeal membrane oxygenation). As of February 3, 47 patients (34.1%) were discharged and 6 died (overall mortality, 4.3%), but the remaining patients are still hospitalized. Among those discharged alive (n = 47), the median hospital stay was 10 days (IQR, 7.0-14.0). Conclusions and Relevance In this single-center case series of 138 hospitalized patients with confirmed NCIP in Wuhan, China, presumed hospital-related transmission of 2019-nCoV was suspected in 41% of patients, 26% of patients received ICU care, and mortality was 4.3%.
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In this retrospective case series, chest CT scans of 21 symptomatic patients from China infected with the 2019 Novel Coronavirus (2019-nCoV) were reviewed with emphasis on identifying and characterizing the most common findings. Typical CT findings included bilateral pulmonary parenchymal ground-glass and consolidative pulmonary opacities, sometimes with a rounded morphology and a peripheral lung distribution. Notably, lung cavitation, discrete pulmonary nodules, pleural effusions, and lymphadenopathy were absent. Follow-up imaging in a subset of patients during the study time window often demonstrated mild or moderate progression of disease as manifested by increasing extent and density of lung opacities.
Article
Background: In December, 2019, a pneumonia associated with the 2019 novel coronavirus (2019-nCoV) emerged in Wuhan, China. We aimed to further clarify the epidemiological and clinical characteristics of 2019-nCoV pneumonia. Methods: In this retrospective, single-centre study, we included all confirmed cases of 2019-nCoV in Wuhan Jinyintan Hospital from Jan 1 to Jan 20, 2020. Cases were confirmed by real-time RT-PCR and were analysed for epidemiological, demographic, clinical, and radiological features and laboratory data. Outcomes were followed up until Jan 25, 2020. Findings: Of the 99 patients with 2019-nCoV pneumonia, 49 (49%) had a history of exposure to the Huanan seafood market. The average age of the patients was 55·5 years (SD 13·1), including 67 men and 32 women. 2019-nCoV was detected in all patients by real-time RT-PCR. 50 (51%) patients had chronic diseases. Patients had clinical manifestations of fever (82 [83%] patients), cough (81 [82%] patients), shortness of breath (31 [31%] patients), muscle ache (11 [11%] patients), confusion (nine [9%] patients), headache (eight [8%] patients), sore throat (five [5%] patients), rhinorrhoea (four [4%] patients), chest pain (two [2%] patients), diarrhoea (two [2%] patients), and nausea and vomiting (one [1%] patient). According to imaging examination, 74 (75%) patients showed bilateral pneumonia, 14 (14%) patients showed multiple mottling and ground-glass opacity, and one (1%) patient had pneumothorax. 17 (17%) patients developed acute respiratory distress syndrome and, among them, 11 (11%) patients worsened in a short period of time and died of multiple organ failure. Interpretation: The 2019-nCoV infection was of clustering onset, is more likely to affect older males with comorbidities, and can result in severe and even fatal respiratory diseases such as acute respiratory distress syndrome. In general, characteristics of patients who died were in line with the MuLBSTA score, an early warning model for predicting mortality in viral pneumonia. Further investigation is needed to explore the applicability of the MuLBSTA score in predicting the risk of mortality in 2019-nCoV infection. Funding: National Key R&D Program of China.