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Do we know the diagnostic properties of the tests used in COVID-19? A rapid review of recently published literature

Authors:

Abstract

COVID-19 has brought death and disease to large parts of the world. Governments must deploy strategies to screen the population and subsequently isolate the suspect cases. Diagnostic testing is critical for epidemiological surveillance, but the accuracy (sensitivity and specificity) and clinical utility (impact on health outcomes) of the current diagnostic methods used for SARS-CoV-2 detection are not known. I ran a quick search in PubMed/MEDLINE to find studies on laboratory diagnostic tests and rapid viral diagnosis. After running the search strategies, I found 47 eligible articles that I discuss in this review, commenting on test characteristics and limitations. I did not find any papers that report on the clinical utility of the tests currently used for COVID-19 detection, meaning that we are fighting a battle without proper knowledge of the proportion of false negatives that current testing is resulting in. This shortcoming should not be overlooked as it might hamper national efforts to contain the pandemic through testing community-based suspect cases.
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Reviews
Do we know the diagnostic properties of the tests used in
COVID-19? A rapid review of recently published literature
Vivienne C. Bacheleta,*
a Escuela de Medicina, Facultad de Ciencias Médicas, Universidad de Santiago de Chile (USACH), Santiago, Chile
Abstract
COVID-19 has brought death and disease to large parts of the world. Govern-
ments must deploy strategies to screen the population and subsequently isolate
the suspect cases. Diagnostic testing is critical for epidemiological surveillance,
but the accuracy (sensitivity and specificity) and clinical utility (impact on
health outcomes) of the current diagnostic methods used for SARS-CoV-2 de-
tection are not known. I ran a quick search in PubMed/MEDLINE to find
studies on laboratory diagnostic tests and rapid viral diagnosis. After running
the search strategies, I found 47 eligible articles that I discuss in this review,
commenting on test characteristics and limitations. I did not find any papers
that report on the clinical utility of the tests currently used for COVID-19 de-
tection, meaning that we are fighting a battle without proper knowledge of the
proportion of false negatives that current testing is resulting in. This shortcom-
ing should not be overlooked as it might hamper national efforts to contain the
pandemic through testing community-based suspect cases.
Introduction
At the end of 2019, the world was made aware of a lethal new strain
of coronaviruslater to be called SARS-CoV-2—that was causing
death and disease in large segments of the Chinese population,
mainly in the city of Wuhan. By March 11, 2020, the World Health
Organization was declaring that the disease caused by this novel vi-
rus, COVID-19, was a pandemic. At the time this article is being
written, nearly three million cases of COVID-19 and over 200 000
deaths have been reported worldwide. A systematic review found that
for 656 patients, the main manifestations of COVID-19 include fe-
ver, cough, and dyspnea, and 32.8% present acute respiratory dis-
tress syndrome, 20.3% of cases require intensive care unit, and 6.2%
will develop shock1.
This enormous burden on our hospital systems has led to aggressive
strategies aimed at mitigating or suppressing the spread of the virus
in the general population, the intensity of which has been strikingly
disparate among the affected countries2,3. Regardless of the strategies
deployed by national and local governments, the more successful
ones rely on laboratory testing and subsequent isolation of suspect
cases. According to the World Health Organization, laboratory “test-
ing for COVID-19 is critical to tracking the virus, understanding
epidemiology, informing case management, and to suppressing
transmission” (see Technical Guidance). However, information on
which tests the different countries are using to detect cases and con-
duct epidemiological surveillance is not readily available. Even less
information is available on the properties of the diagnostic tests cur-
rently deployed in the field, and press reports have referred to the
problem of false-negative results4.
We are still in the process of understanding SARS-CoV-2. Long in-
cubation time may be responsible for the rapid dissemination and
infectivity of this strain of coronavirus5. However, this was rebutted
*
Corresponding author
vivienne.bachelet@usach.cl
Citation
Bachelet VC. Do we know the diagnostic
properties of the tests used in COVID-19? A rapid
review of recently published
literature. Medwave 2020;20(3):e7891
Doi
10.5867/medwave.2020.03.7891
Submission date
15/4/2020
Acceptance date
26/4/2020
Publication date
28/4/2020
Origin
Not commissioned.
Type of review
Internally peer-reviewed.
Keywords
COVID-19, Diagnosis, Testing, SARS-CoV-
2 / 6
by a recent analysis on a larger dataset of patients that found no sta-
tistically significant differences in the mean incubation time for
SARS-CoV, MERS-CoV, and SARS-CoV-26. Also, many asympto-
matic individuals have tested positive for SARS-CoV-27. Statistical
modeling on the Diamond Princess cruise ship found that 17.9%
(95% confidence interval: 15.2% to 20.2%) of individuals who
tested positive for SARS-CoV-2 were asymptomatic, but this could
be an underestimation given that not all passengers were tested8.
Conversely, a high false-negative rate of nucleic acid test for SARS-
CoV-2 has been reported for the most used diagnostic tool for
COVID-19 screeningthe reverse-transcription polymerase chain
reaction (RT-PCR) assay using oropharyngeal swab samples9-12. In a
letter to the editor, an author describes a case of three consecutive
samples negative for the SARS-CoV-2 nucleic acid, which was finally
confirmed as COVID-19 pneumonia based on the chest computed
tomography scan showing the typical ground-glass opacification and
a fourth RT-PCR test with a positive result13. Thus, many reports
are now advising that the diagnosis of COVID-19 should include
computed tomography images together with PCR testing in highly
suspect cases14,15.
Sampling methods to detect viral nucleic acid in the upper airway
have also been called into question due to the purported high rate of
false negatives7,9. A literature review published in Chinese based on
the prior experiences of severe acute respiratory syndrome corona-
virus, middle east respiratory syndrome coronavirus, and influenza
A, pointed to the lack of uniform recommendations on the method
to collect the upper respiratory tract specimen and found that the
nasopharyngeal aspirate had a higher positive rate within two weeks
of symptom onset, while combined nasal and oropharyngeal swabs
were the least harmful to medical staff during sampling16. Some sug-
gest that samples for testing viral infection should be taken from the
lower respiratory tract of the patients, including sputum and bron-
choalveolar lavage fluid9,17.
Laboratory methods to detect the presence of SARS-CoV-2 in a bi-
ological sample have advantages and disadvantages. Isolation of the
virus can be achieved from cell cultures; rapid antigen tests, serology,
and molecular assays are all either actively deployed in epidemiolog-
ical surveillance or are being currently tested for point-of-care
use17,18. Considering the need to have reliable data on the test prop-
erties of the different methods that are being introduced to control
the COVID-19 pandemic, I decided to undertake a literature review
to know the accuracy and clinical utility of the current screening
methods used for SARS-CoV-2 detection in suspect cases.
Methods
I searched in PubMed/MEDLINE with keywords “covid 19”, “sen-
sitivity”, “screening”, and “detection” (see Table) up to March 26,
2020. I used the following MeSH terms to build the searches: “covid
19”, “detection”, “screening”, “sensitivity”, “rt pcr”, and “diagnosis”.
I then searched the references of the selected articles to find primary
references to diagnostic test properties.
The inclusion criteria were articles reporting on laboratory diagnos-
tic tests and rapid viral diagnosis.
The exclusion criteria were case reports, opinion pieces, letters to the
editor, articles reporting clinical findings, surveillance strategies, im-
aging techniques, epidemiology, mitigation strategies, articles ad-
dressing population subgroups (e.g., pediatrics, pregnant women) or
non-diagnostic outcomes (e.g., mental health), treatment strategies,
and guidelines. Articles in Chinese were also excluded if a reasonable
translation was not possible to obtain. For this rapid review, I also
excluded preprints because of their preliminary nature and lack of
peer validation.
Results
After running the search strategies and screening the titles, 47 articles
were found eligible for abstract screening (Table 1). After assessing
the eligible articles for inclusion and exclusion criteria, I selected 13
papers for full-text review. All these papers were published in the first
quarter of 2020, and only eight complied with the inclusion and ex-
clusion criteria15,19-25. All 47 articles were used for the preparation of
this review, plus further references that were found during the writ-
ing of the review. The main search was done on March 26.
Table 1. Search strategies and results.
Search details
Results
"covid 19"[All Fields] AND "detection"[All Fields]
63
"covid 19"[All Fields] AND "screening"[All Fields]
54
"covid 19"[All Fields] AND "sensitivity"[All Fields]
22
"covid 19"[All Fields] AND "rt pcr"[All Fields]
39
"covid 19"[All Fields] AND "diagnosis"[All Fields]
194
Results a fter removing duplicates
47
Analysis of the findings
The purpose of this review is to know the sensitivity and specificity
of the tests that are currently in use for the detection of SARS-CoV-
2 throughout the world. These tests are in vitro diagnostics that an-
alyze samples taken from the human body (some examples are serum,
sputum, saliva, blood, urine, and feces). Decisions are made based
on the results. Thus, front-line healthcare professionals should know
what the probabilities are for false negatives and false positives, in
other words, the accuracy of the test. A test will give us a correct
result to the extent that it is positive in the presence of disease (true
positive) and negative in the absence of disease (true negative); both
false positives and false negatives will provide misleading infor-
mation26. Screening tests, which are used in the asymptomatic pop-
ulations, should be easy to administer, quick to deliver results, low-
cost, and, most importantly, highly sensitive. Currently, the gold
standard for the detection of the SARS-CoV-2 is RT-PCR because
when the sample picks up a virus or viral fragment, even in minimal
quantities, it should provide a 100% sensitivity. However, due to a
variety of shortcomings that I comment further on, our current
forms of testing for the novel coronavirus may be falling short.
Virus nucleic acid RT-PCR tests
Various forms of RT-PCR testing are the predominant diagnostic
method for COVID-19. While it can detect the presence or absence
of viral nucleic acid and thus directly confirm viral infection in a
3 / 6
human sample, it is prone to several limitations. These tests can only
be processed in certified laboratories, which means that in most
countries, test results are coming out with detrimental delays to pa-
tients, and healthcare and surveillance systems. Furthermore, there
are preanalytical and analytical factors that can compromise the qual-
ity of RT-PCR testing for detecting SARS-CoV-2, thus reducing the
diagnostic accuracy of the test27.
Chan et al. in Hong Kong report the development of a new assay
that targets a different region of the SARS-CoV-2 genome
(RdRp/Hel, S, and N genes) using both in vitro and clinical speci-
mens22. Two hundred seventy-three specimens were collected from
15 Hong Kongese patients (8 males, 7 females; age range 37 to 75
years) with laboratory-confirmed COVID-19. The authors report
that the assay was highly sensitive and specific for the detection of
SARS-CoV-2 RNA in vitro but it was not tested in non-COVID-19
patients. The clinical utility of this new test is not known.
Korean authors developed an easy specimen collection via a self-col-
lected pharyngeal swab to perform an RT-PCR and Trizol-based
RNA purification that they tested in 12 mostly asymptomatic hu-
man volunteers24. The authors provide detailed instructions on how
to collect the throat swab. The positive control with SARS-CoV-2
viral RNAs was extracted from Vero cells infected with a viral clone.
The purpose of this study was to create a highly sensitive detection
protocol to identify true negatives for SARS-CoV-2, but the limited
scope of the validation hampers any possibility of generalizability for
this study.
Liu et al. conducted a retrospective analysis of RT-PCR based viral
nucleic acid test from 4880 suspect cases for COVID-19 occurring
from late January to mid-February in the Renmin Hospital of Wu-
han University20 based on nasal and pharyngeal swabs, and bron-
choalveolar lavage fluid and sputum. The study’s main result was a
38% positive finding for SARS-CoV-2 for that population, which
increased to 57% in the population from the fever clinics. This study
only allows us to determine, for this population, the proportion of
positive tests in a population with a high likelihood of having
COVID-19 based on the presence of respiratory infection symptoms
or close contact with COVID-19 patients. There was no follow-up
on cases to determine whether all positive tests were COVID-19 pa-
tients, nor whether the negative tests were truly disease-free. In other
words, this study does not provide the necessary data to calculate
sensitivity and specificity for the test in this disease-prevalent popu-
lation.
Another group in Korea developed and evaluated Loop-Mediated
Isothermal Amplification (LAMP) assays to detect genomic RNA of
SARS-CoV-2 and found that RT-LAMP assays can detect as low as
100 copies of SARS-CoV-2 RNA, thus providing very high technical
accuracy28. However, the clinical applicability of this technique has
not yet been studied for SARS-CoV-2.
Immunoassays
Immunoassays test specific antibodies in patient blood. Li et al. de-
veloped a point-of-care lateral flow immunoassay test that can detect
IgM and IgG in human blood in 15 minutes25. Interestingly, the test
was applied in eight Chinese sites from six provinces, in both in-
fected and non-infected patients, totaling 522 cases, of which 397
were previously COVID-19 confirmed with PCR test, and 128 were
non-infected patients. Three hundred fifty-two tested positive, re-
sulting in a sensitivity of 88.66%. The specificity was 90.63% (12
false positives). The spectrum of patients is not reported, and neither
is the independence of testing with the gold standard.
Another study sought to describe the time kinetics of the anti-SARS-
CoV-2 IgA, IgM, and IgG antibodies using an ELISA based assay on
208 plasma samples collected from two cohorts of patients: 82 con-
firmed and 58 probable cases from Wuhan and Beijing hospitals
[19]. The median duration of IgM and IgA detection was five days
(range, 3 to 6), while IgG was detected 14 days after symptom onset
(range, 10 to 18), with a positive rate of 85.4%, 92.7%, and 77.9%,
respectively. This study helps to understand the humoral responses
to the virus and thus to situate the immunoassay’s capability to de-
tect any response in a COVID-19 patient.
Limitations of diagnostic test studies
The included studies were all carried out during the COVID-19 ep-
idemic, later defined as a pandemic. It is not the same when these
tests are done for screening purposes (in asymptomatic population)
rather than for diagnostic purposes (to confirm or rule out when
there is a high pretest probability of disease). Establishing the sensi-
tivity or specificity of a test is not necessarily independent of preva-
lence, insofar as the methods by which sampling is done (e.g., spu-
tum or nasopharyngeal swabs) may determine the greater or lesser
likelihood of picking up the virus, which will differ if the population
that is being sampled has more or less advanced disease26.
Many reports refer to the analytical evaluations of tests to detect
SARS-CoV-2 and workflows23,29-31, but these are not useful for the
clinical and epidemiological decision-making process and do not re-
port results in the field with real patients. Most of the published pa-
pers on COVID-19 and diagnosis are not studies conducted in com-
munity-based suspect cases, which could provide pragmatic results
on sensitivity and specificity.
Conclusion and final remarks
Front-line professionals battling the SARS-CoV-2 pandemic should
be aware of the risk of misclassification given the consequences of
missing the disease in infected people. When we know that a screen-
ing test is highly sensitive, then we could confidently rule out the
disease if the test is negative. Do we need to further work up a posi-
tive test result in an asymptomatic person to confirm that it is a true
positive? Probably not, as the central management indication will be
to maintain quarantine if other elements in the history give us a high
pre-test probability for the patient having contracted COVID-19,
such as having traveled to a high-risk country, having had contact
with a known SARS-CoV-2 positive person, or having attended a
crowded and enclosed gathering in the previous days or weeks.
Nonetheless, China has reported that computed tomography scans
are more sensitive for COVID-19 than the RT-PCR tests and, until
4 / 6
recently, it was used as standard practice in diagnosing the disease32.
While several papers describe the molecular diagnostics for this novel
virus9,33,34, my review did not find any that report on the clinical util-
ity of the tests currently used for COVID-19 screening.
There is yet no clear consensus on testing. While RT-PCR testing is
widespread, its limitations include the need for higher-level labora-
tory facilities, proper swab sample techniques, and error-free patient
sample to laboratory result pathways. Likewise, there is a wide variety
of strategies on when to test, with some countries deploying outreach
detection programs that seek to pick up as many cases as possible,
including the asymptomatic ones, to countries that only test in the
hospital. Some countries are even considering handing out COVID-
19 discharge cards based on antibody testing35, which sparked con-
troversy after the World Health Organization stated that “There is
currently no evidence that people who have recovered from COVID-
19 and have antibodies are protected from a second infection”36. Of
course, by the time this article is published, many countries that were
following a screening strategy may have switched over to another
one. To the date of my literature review, there were no large popu-
lation studies that included diseased and healthy persons to provide
us with property statistics for positives in disease and negatives in
health. More research must be done on diagnostic testing for
COVID-19 in the general population as we are still beset by reason-
able uncertainty.
The world is presently in a race to find the solutions that humankind
requires for the diagnosis, prevention, and therapy of this novel coro-
navirus. New papers are coming out each day on any of these critical
questions, many published in high-profile journals. We must not let
ourselves be swayed by an understandable expectation for a quick
success that opens the way for an acritical assessment of the interven-
tions that are being proposed. There have been reports on treatments
in small groups without proper controls37, and many new diagnostic
tests for SARS-CoV-2 are being explored and deployed. Each day,
news articles tout university efforts to mass-produce ventilators and
any new press release is avidly picked up by the mass media and,
regrettably, by high-level authorities as well. Many of these experi-
ments will not stand the test of time, and there might not be enough
evidence to support the continuing use of the tests or interventions.
The research and academic community must insist on following
proper methods and proper reporting even in these times of pain and
suffering, for we must not repeat the mistakes of the past38. The pol-
icymakers and political leaders of this time are called upon to make
decisions for the benefit of their peoples and communities based on
the best available evidence.
Notes
Funding
There were no sources of funding for this review.
Competing interests
The author declares no competing interests with the topic of this article.
Acknowledgments
The author thanks Fernando Lanas, Felipe Cardemil and Carlos Becerra for
their helpful comments.
References
1. Rodriguez-Morales AJ, Cardona-Ospina JA, Gutiérrez-Ocampo E,
Villamizar-Peña R, Holguin-Rivera Y, Escalera-Antezana JP, et al.
Clinical, laboratory and imaging features of COVID-19: A systematic
review and meta-analysis. Travel Med Infect Dis. 2020 Mar
13:101623. | CrossRef | PubMed |
2. Cohen J, Kupferschmidt K. Countries test tactics in 'war' against
COVID-19. Science. 2020 Mar 20;367(6484):1287-1288. | CrossRef
| PubMed |
3. Salathe M, Althaus CL, Neher R, Stringhini S, Hodcroft E, Fellay J, et
al. COVID-19 epidemic in Switzerland: on the importance of testing,
contact tracing and isolation. Swiss Med Wkly. 2020 Mar
19;150:w20225. | CrossRef | PubMed |
4. A 'negative' coronavirus test result doesn't always mean you aren't in-
fected - The Washington Post. The Washington Post. 2020. [Internet]
| Link |
5. Leung C. The difference in the incubation period of 2019 novel coro-
navirus (SARS-CoV-2) infection between travelers to Hubei and non-
travelers: The need for a longer quarantine period. Infect Control Hosp
Epidemiol. 2020 Mar 18:1-3. | CrossRef | PubMed |
6. Jiang X, Rayner S, Luo MH. Does SARS-CoV-2 has a longer incuba-
tion period than SARS and MERS? J Med Virol. 2020 May;92(5):476-
478. | CrossRef | PubMed |
7. Dong X, Cao YY, Lu XX, Zhang JJ, Du H, Yan YQ, et al. Eleven faces
of coronavirus disease 2019. Allergy. 2020 Mar 20. | CrossRef | Pub-
Med |
8. Mizumoto K, Kagaya K, Zarebski A, Chowell G. Estimating the
asymptomatic proportion of coronavirus disease 2019 (COVID-19)
cases on board the Diamond Princess cruise ship, Yokohama, Japan,
2020. Euro Surveill. 2020 Mar;25(10). | CrossRef | PubMed |
9. Wang Y, Kang H, Liu X, Tong Z. Combination of RT-qPCR testing
and clinical features for diagnosis of COVID-19 facilitates manage-
ment of SARS-CoV-2 outbreak. J Med Virol. 2020 Feb 25. | CrossRef
| PubMed |
10. Ye G, Li Y, Lu M, Chen S, Luo Y, Wang S, et al. Experience of differ-
ent upper respiratory tract sampling strategies for detection of
COVID-19. J Hosp Infect. 2020 Mar 12. pii: S0195-6701(20)30111-
0. | CrossRef | PubMed |
11. Li D, Wang D, Dong J, Wang N, Huang H, Xu H, et al. False-Nega-
tive Results of Real-Time Reverse-Transcriptase Polymerase Chain Re-
action for Severe Acute Respiratory Syndrome Coronavirus 2: Role of
Deep-Learning-Based CT Diagnosis and Insights from Two Cases.
Korean J Radiol. 2020 Apr;21(4):505-508. | CrossRef | PubMed |
12. Han H, Luo Q, Mo F, Long L, Zheng W. SARS-CoV-2 RNA more
readily detected in induced sputum than in throat swabs of convales-
cent COVID-19 patients. Lancet Infect Dis. 2020 Mar 12. pii: S1473-
3099(20)30174-2. | CrossRef | PubMed |
13. Hao W, Li M. Clinical diagnostic value of CT imaging in COVID-19
with multiple negative RT-PCR testing. Travel Med Infect Dis. 2020
Mar 13:101627. | CrossRef | PubMed |
14. Lei P, Fan B, Mao J, Wang P. Multiple parameters required for diag-
nosis of COVID-19 in clinical practice. J Infect. 2020 Mar 19. pii:
S0163-4453(20)30142-0. | CrossRef | PubMed |
15. Ai T, Yang Z, Hou H, Zhan C, Chen C, Lv W, et al. Correlation of
Chest CT and RT-PCR Testing in Coronavirus Disease 2019
(COVID-19) in China: A Report of 1014 Cases. Radiology. 2020 Feb
26:200642. | CrossRef | PubMed |
16. Ye B, Fan C, Pan Y, Ding R, Hu HX, Xiang ML. [Which sampling
method for the upper respiratory tract specimen should be taken to
5 / 6
diagnose patient with COVID-19?]. Zhonghua Er Bi Yan Hou Tou
Jing Wai Ke Za Zhi. 2020 Mar 13;55(0):E003. | CrossRef | PubMed |
17. Loeffelholz MJ, Tang YW. Laboratory diagnosis of emerging human
coronavirus infections - the state of the art. Emerg Microbes Infect.
2020 Dec;9(1):747-756. | CrossRef | PubMed |
18. Yuen KS, Ye ZW, Fung SY, Chan CP, Jin DY. SARS-CoV-2 and
COVID-19: The most important research questions. Cell Biosci. 2020
Mar 16;10:40. | CrossRef | PubMed |
19. Guo L, Ren L, Yang S, Xiao M, Chang, Yang F, et al. Profiling Early
Humoral Response to Diagnose Novel Coronavirus Disease (COVID-
19). Clin Infect Dis. 2020 Mar 21. pii: ciaa310. | CrossRef | PubMed
|
20. Liu R, Han H, Liu F, Lv Z, Wu K, Liu Y, et al. Positive rate of RT-
PCR detection of SARS-CoV-2 infection in 4880 cases from one hos-
pital in Wuhan, China, from Jan to Feb 2020. Clin Chim Acta. 2020
Jun;505:172-175. | CrossRef | PubMed |
21. Nguyen T, Duong Bang D, Wolff A. 2019 Novel Coronavirus Disease
(COVID-19): Paving the Road for Rapid Detection and Point-of-Care
Diagnostics. Micromachines (Basel). 2020 Mar 14;11(3). pii: E306. |
CrossRef | PubMed |
22. Chan JF, Yip CC, To KK, Tang TH, Wong SC, Leung KH, et al.
Improved Molecular Diagnosis of COVID-19 by the Novel, Highly
Sensitive and Specific COVID-19-RdRp/Hel Real-Time Reverse
Transcription-PCR Assay Validated In Vitro and with Clinical Speci-
mens. J Clin Microbiol. 2020 Apr 23;58(5). pii: e00310-20. | CrossRef
| PubMed |
23. Konrad R, Eberle U, Dangel A, Treis B, Berger A, Bengs K, et al. Rapid
establishment of laboratory diagnostics for the novel coronavirus
SARS-CoV-2 in Bavaria, Germany, February 2020. Euro Surveill.
2020 Mar;25(9). | CrossRef | PubMed |
24. Won J, Lee S, Park M, Kim TY, Park MG, Choi BY, et al. Develop-
ment of a Laboratory-safe and Low-cost Detection Protocol for SARS-
CoV-2 of the Coronavirus Disease 2019 (COVID-19). Exp Neuro-
biol. 2020 Mar 11. | CrossRef | PubMed |
25. Li Z, Yi Y, Luo X, Xiong N, Liu Y, Li S, et al. Development and clinical
application of a rapid IgM-IgG combined antibody test for SARS-
CoV-2 infection diagnosis. J Med Virol. 2020 Feb 27. | CrossRef |
PubMed |
26. Fletcher RH, Fletcher SW, Fletcher GS. Clinical Epidemiology - The
Essentials. 5th ed. Lippincott Williams & Wilkins; 2014.
27. Lippi G, Simundic AM, Plebani M. Potential preanalytical and analyt-
ical vulnerabilities in the laboratory diagnosis of coronavirus disease
2019 (COVID-19). Clin Chem Lab Med. 2020 Mar 16. | CrossRef |
PubMed |
28. Park GS, Ku K, Baek SH, Kim SJ, Kim SI, Kim BT, et al. Develop-
ment of Reverse Transcription Loop-Mediated Isothermal Amplifica-
tion Assays Targeting SARS-CoV-2. J Mol Diagn. 2020 Apr 7. pii:
S1525-1578(20)30090-8. | CrossRef | PubMed |
29. Pfefferle S, Reucher S, Nörz D, Lütgehetmann M. Evaluation of a
quantitative RT-PCR assay for the detection of the emerging corona-
virus SARS-CoV-2 using a high throughput system. Euro Surveill.
2020 Mar;25(9). | CrossRef | PubMed |
30. Cordes AK, Heim A. Rapid random access detection of the novel
SARS-coronavirus-2 (SARS-CoV-2, previously 2019-nCoV) using an
open access protocol for the Panther Fusion. J Clin Virol. 2020 Feb
28;125:104305. | CrossRef | PubMed |
31. Corman VM, Landt O, Kaiser M, Molenkamp R, Meijer A, Chu DK,
et al. Detection of 2019 novel coronavirus (2019-nCoV) by real-time
RT-PCR. Euro Surveill. 2020 Jan;25(3). | CrossRef | PubMed |
32. Fang Y, Zhang H, Xie J, Lin M, Ying L, Pang P, et al. Sensitivity of
Chest CT for COVID-19: Comparison to RT-PCR. Radiology. 2020
Feb 19:200432. | CrossRef | PubMed |
33. Lippi G, Plebani M. The critical role of laboratory medicine during
coronavirus disease 2019 (COVID-19) and other viral outbreaks. Clin
Chem Lab Med. 2020 Mar 19. | CrossRef | PubMed |
34. Ai JW, Zhang Y, Zhang HC, Xu T, Zhang WH. Era of molecular di-
agnosis for pathogen identification of unexplained pneumonia, lessons
to be learned. Emerg Microbes Infect. 2020 Mar 16;9(1):597-600. |
CrossRef | PubMed |
35. Ministerio de Salud entregar√° carnet sanitario a los recuperados de
COVID-19 - Ministerio de Salud - Gobierno de Chile [Internet] | Link
|
36. "Immunity passports" in the context of COVID-19. In: World Health
Organization. 24 Apr 2020. [Internet] | Link |
37. Gbinigie K, Frie K. Should chloroquine and hydroxychloroquine be
used to treat COVID-19? A rapid review. BJGP Open. 2020 Apr 7. |
CrossRef | PubMed |
38. Bachelet VC. The Tamiflu saga continues: will our conduct change
after the publication of the latest systematic review on benefits and
harms of oseltamivir? Medwave. 2014 May 20;14(4):e5953. | CrossRef
| PubMed |
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... In addition, highthroughput instruments use batched testing to make it cost-effective, which prolongs turnaround times. 6 19 CB-NAAT has been widely employed as a rapid diagnostic test for tuberculosis and for diagnosing rifampin resistance in positive patients using the Xpert MTB/RIF (Cepheid Inc.). [20][21][22] The test has proven especially useful in initiation of treatment of tuberculosis in resource-limited, high-burden Indian rural settings. ...
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Preoperative testing and evaluation for coronavirus disease 2019 (COVID-19) have been an enigmatic challenge for the neurosurgical community during the pandemic. Since the beginning of the pandemic, laboratory diagnostic methods have evolved substantially, and with them has been the necessity for readily available, fast, and accurate preoperative testing methods. In this article, we provide an overview of the various laboratory testing methods that are presently available and a comprehensive literature review how various institutes and neurosurgical communities across the globe are employing them to ensure safe and effective delivery of surgical care to patients. Through this review, we highlight the guiding principles for preoperative testing, which may serve as a road map for other medical institutions to follow. In addition, we provide an Indian perspective of preoperative testing and share our experience in this regard.
... [53]. Furthermore, PCR's limitations include the need for higher-level laboratory facilities, proper swab sample techniques, clinician experience, and error-free patient samples [54,55]. Hence, if clinical suspicion is high, an infection should not be ruled out based on a PCR test only [52]. ...
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Background: The SARS-CoV-2 virus has demonstrated the weakness of many health systems worldwide, creating a saturation and lack of access to treatments. A bottleneck to fight this pandemic relates to the lack of diagnostic infrastructure for early detection of positive cases, particularly in rural and impoverished areas of developing countries. In this context, less costly and fast machine learning (ML) diagnosis-based systems are helpful. However, most of the research has focused on deep-learning techniques for diagnosis, which are computationally and technologically expensive. ML models have been mainly used as a benchmark and are not entirely explored in the existing literature on the topic of this paper. Objective: To analyze the capabilities of ML techniques (compared to deep learning) to diagnose COVID-19 cases based on X-ray images, assessing the performance of these techniques and using their predictive power for such a diagnosis. Methods: A factorial experiment was designed to establish this power with X-ray chest images of healthy, pneumonia, and COVID-19 infected patients. This design considers data-balancing methods, feature extraction approaches, different algorithms, and hyper-parameter optimization. The ML techniques were evaluated based on classification metrics, including accuracy, the area under the receiver operating characteristic curve (AUROC), F1-score, sensitivity, and specificity. Results: The design of experiment provided the mean and its confidence intervals for the predictive capability of different ML techniques, which reached AUROC values as high as 90% with suitable sensitivity and specificity. Among the learning algorithms, support vector machines and random forest performed best. The down-sampling method for unbalanced data improved the predictive power significantly for the images used in this study. Conclusions: Our investigation demonstrated that ML techniques are able to identify COVID-19 infected patients. The results provided suitable values of sensitivity and specificity, minimizing the false-positive or false-negative rates. The models were trained with significantly low computational resources, which helps to provide access and deployment in rural and impoverished areas. Keywords Artificial intelligence; Deep learning; PCR; ROC curve; R software; SARS-CoV-2; X-rays
... Although different types of reverse-transcription polymerase chain reaction (RT-PCR) tests are the predominant diagnostic methods for detecting SARS-CoV-2, the accuracy of these methods for COVID-19 is still unknown (3). False positives are rare for RT-PCR testing when primers and probes are designed appropriately. ...
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After lifting the COVID-19 lockdown restrictions and opening businesses, screening is essential to prevent the spread of the virus. Group testing could be a promising candidate for screening to save time and resources. However, due to the high false-negative rate (FNR) of the RT-PCR diagnostic test, we should be cautious about using group testing because a group's false-negative result identifies all the individuals in a group as uninfected. Repeating the test is the best solution to reduce the FNR, and repeats should be integrated with the group-testing method to increase the sensitivity of the test. The simplest way is to replicate the test twice for each group (the 2Rgt method). In this paper, we present a new method for group testing (the groupMix method), which integrates two repeats in the test. Then we introduce the 2-stage sequential version of both the groupMix and the 2Rgt methods. We compare these methods analytically regarding the sensitivity and the average number of tests. The tradeoff between the sensitivity and the average number of tests should be considered when choosing the best method for the screening strategy. We applied the groupMix method to screening 263 people and identified 2 infected individuals by performing 98 tests. This method achieved a 63% saving in the number of tests compared to individual testing. Our experimental results show that in COVID-19 screening, the viral load can be low, and the group size should not be more than 6; otherwise, the FNR increases significantly. A web interface of the groupMix method is publicly available for laboratories to implement this method.
... The accuracy of available SARS-Cov-2 tests is limited, and they can produce falsepositive or false-negative results. 45 Initial reports of test results in pregnant women admitted for delivery in New York City found 13.7% SARS-CoV-2 positivity by PCR. 46 The rate of positivity in the Brazilian cancer patient population is not known, since they are on average significantly older than pregnant women and probably present more comorbidities and possibly some immunodeficiency. ...
Article
Background Cancer patients configure a risk group for complications or death by COVID‐19. For many of them, postponing or replacing their surgical treatments is not recommended. During this pandemic, surgeons must discuss the risks and benefits of treatment, and patients should sign a specific comprehensive Informed consent (IC). Objectives To report an IC and an algorithm developed for oncologic surgery during the COVID‐19 outbreak. Methods We developed an IC and a process flowchart containing a preoperative symptoms questionnaire and a PCR SARS‐CoV‐2 test and described all perioperative steps of this program. Results Patients with negative questionnaires and tests go to surgery, those with positive ones must wait 21 days and undergo a second test before surgery is scheduled. The IC focused both on risks and benefits inherent each surgery and on the risks of perioperative SARS‐CoV‐2 infections or related complications. Also, the IC discusses the possibility of sudden replacement of medical staff member(s) due to the pandemic; the possibility of unexpected complications demanding emergency procedures that cannot be specifically discussed in advance is addressed. Conclusions During the pandemic, specific tools must be developed to ensure safe experiences for surgical patients and prevent them from having misunderstandings concerning their care.
... 意大利疫情暴发期 间的一项研究采集了前来医院就诊的具有发热及呼 吸道症状的疑似患者的鼻咽拭子并进行病原学分析, 发现SARS-CoV-2感染者占比为2.4%, 其他常见的病 原体包括流感病毒、肠病毒、鼻病毒及其他冠状病 毒等 [51] . 面对大量的呼吸道感染病例, 需要采用创 新、高效的手段应对如此大的检测压力并控制感染 的继续传播 [52] . 有实践证明, 面对大量排查案例可采 用多名测试者样本混合后检测, 尤其是对感染率较低 的人群, 可大大提高检测的效率 [53,54] . ...
... 1 imaging results. [8][9][10][11][12] So far, there is no level I evidence from randomised controlled trials to recommend any specific anti-nCoV treatment, so the management of COVID-19 still is largely supportive (WHO 2020a). 7 Currently, the approach to manage COVID-19 is to control the source of infection; use infection prevention and control measures to lower the risk of transmission; and provide early diagnosis, isolation, and supportive care for affected patients. ...
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The shutdown of dental practices after the announcement of COVID-19 has been implemented worldwide. Aerosol generating procedures and face to face contact with the patients put dental professionals at highest risk of disease transmission. There is a looming risk of increasing severity of dental conditions and burden on treatment providers if required dental treatments are kept on hold for an indefinite time. There is a need for definite guidelines to safely resume dental practice in Nepal, based on international experiences during COVID-19 pandemic and international dental societies recommendations. We have compiled multiple recommendations and guidelines from reputed international organizations and collected evidence from dental professional’s work from China and Italy during COVID-19 crisis and attempted to put forward some recommendations and guidelines that can be followed for a safe dental practice in Nepal.
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The SARS-CoV-2 Coronavirus disease, also known as the COVID-19 pandemic, has engendered the biggest challenge to human life for the last two years. With a rapid increase in the spread of the Omicron variant across the world, and to contain the spread of COVID-19 in general, it is crucial to rapidly identify this viral infection with minimal logistics. To achieve this, a novel plastic optical fiber (POF) U-shaped probe sensing method is presented for accurate detection of SARS-CoV-2, commonly known as the COVID-19 virus, which has the capability to detect new variants such as Omicron. The sample under test can be taken from oropharyngeal or nasopharyngeal via specific POF U-shaped probe with one end that is fed with a laser source while the other end is connected to a photodetector to receive the response and postprocess for decision-making. The study includes detection comparison with two types of POF with diameters of 200 and 500 µm. Results show that detection is better when a smaller-diameter POF is used. It is also seen that the proposed test bed and its envisaged prototype can detect the COVID-19 variants within 15 min of the test. The proposed approach will make the clinical diagnosis faster, cheaper and applicable to patients in remote areas where there are no hospitals or clinical laboratories due to poverty, geographic obstacles, or other factors.
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Objectives Elevated soluble urokinase Plasminogen Activator Receptor (suPAR) is a biomarker associated with adverse outcomes. We aimed to investigate the associations between plasma suPAR levels (testing the cut-offs ⩽4, 4-6, and ⩾6 ng/mL) with risk of 14-day mortality, and with the risk of mechanical ventilation in patients that tested positive for SARS-CoV-2. Methods Observational cohort study of patients presenting with symptoms of COVID-19 at Department of Emergency Medicine, Amager and Hvidovre Hospital, Denmark from March 19th, 2020 to April 3rd, 2020. Plasma suPAR was measured using suPARnostic technologies. Patients were followed for development of mechanical ventilation and mortality for 14 days. Validation of our findings were carried out in a similar sized COVID-19 patient cohort from Mikkeli Central Hospital, Finland. Results Among 386 patients with symptoms of COVID-19, the median (interquartile range) age was 64 years (46-77), 57% were women, median suPAR was 4.0 ng/mL (2.7-5.9). In total, 35 patients (9.1%) died during the 14 days follow-up. Patients with suPAR ⩽4 ng/mL (N = 196; 50.8%) had a low risk of mortality (N = 2; 1.0%; negative predictive value of 99.0%, specificity 55.3%, sensitivity 95.2%, positive predictive value 17.4%). Among patients with suPAR ⩾6 ng/mL (N = 92; 23.8%), 16 died (17.4%). About 99 patients (25.6%) tested positive for SARS CoV-2 and of those 12 (12.1%) developed need for mechanical ventilation. None of the SARS-CoV-2 positive patients with suPAR ⩽4 ng/mL (N = 28; 38.8%) needed mechanical ventilation or died. The Mikkeli Central Hospital validation cohort confirmed our findings concerning suPAR cut-offs for risk of development of mechanical ventilation and mortality. Conclusions Patients with symptoms of COVID-19 and suPAR ⩽4 or ⩾6 ng/mL had low or high risk, respectively, concerning the need for mechanical ventilation or mortality. We suggest cut-offs for identification of risk groups in patients presenting to the ED with symptoms of or confirmed COVID-19.
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Objective. To evaluate the operative capacity of nine serological rapid tests to detect the IgM/IgG antibodies response in serum from patients with SARS-CoV-2 in different clinical stages. Methods. A cross-sectional study of serological rapid tests was designed to compare the performance of the evaluated immunochromatographic tests for the diagnosis of SARS-CoV-2. A total of 293 samples was used, including negatives, asymptomatic, and symptomatic serum samples. Results. The sensitivity of the evaluated tests was low and moderate in the groups of asymptomatic serum samples and the group of serums coming from patients with less than 11 days since the onset of the symptoms. The specificity for the anti-SARS-CoV-2 antibodies tests ranged between 86.5%-99% for IgM and 86.5%-99.5% for IgG. The sensitivity and the likelihood ratio were different according to the study groups. The usefulness of these tests is restricted to symptomatic patients and their sensitivity is greater than 85% after 11 days from the appearance of symptoms. Conclusions. Serological tests are not an adequate strategy for the identification of asymptomatic and pre-symptomatic patients. Serological rapid tests for the detection of specific anti-SARS-CoV-2 antibodies can be used as a diagnostic aid, but diagnosis must be confirmed by RT-PCR. Rapid tests should be reserved for patients with symptoms lasting more than 11 days.
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Background: On the 11 March 2020, the World Health Organization (WHO) declared that COVID-19 was a pandemic. To date, there are no medical treatments for COVID-19 with proven effectiveness. Novel treatments and/or vaccines will take time to be developed and distributed to patients. In light of this, there has been growing interest in the use of existing medications, such as chloroquine (CQ) and hydroxychloroquine (HCQ), as potential treatments of this disease. Aim: To establish the current evidence for the effectiveness of CQ and HCQ in treating COVID-19. Design & setting: A rapid review of the literature was conducted. Method: Electronic searches in PubMed and Google Scholar were conducted on 21 March 2020. A further search was conducted in Google for relevant literature on 28 March 2020. Results: There is limited evidence of in vitro activity of CQ/HCQ against SARS-CoV-2. A number of in vivo clinical trials are underway. The empirical data available from two of these trials reveal conflicting results. Both trials are characterised by small numbers of participants (n = 30 and n = 36) and suffer methodological limitations. No medium or long-term follow-up data is available. Conclusion: At present, there is insufficient evidence to determine whether CQ/HCQ are safe and effective treatments for COVID-19. High quality, adequately powered randomised clinical trials in primary and secondary care settings are urgently required to guide policymakers and clinicians. These studies should report medium- and long-term follow-up results, and safety data.
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Background and aims The outbreak of coronavirus disease 2019 (COVID‐19) caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection has recently spread worldwide and been declared a pandemic. We aim to describe here the various clinical presentations of this disease by examining eleven cases. Methods Electronic medical records of 11 patients with COVID‐19 were collected and demographics, clinical manifestations, outcomes, key laboratory results, and radiological images are discussed. Results The clinical course of the eleven cases demonstrated the complexity of the COVID‐19 profile with different clinical presentations. Clinical manifestations range from asymptomatic cases to patients with mild and severe symptoms, with or without pneumonia. Laboratory detection of the viral nucleic acid can yield false‐negative results, and serological testing of virus specific IgG and IgM antibodies should be used as an alternative for diagnosis. Patients with common allergic diseases did not develop distinct symptoms and severe courses. Cases with a pre‐existing condition of chronic obstructive pulmonary disease or complicated with a secondary bacterial pneumonia were more severe. Conclusion All different clinical characteristics of COVID‐19 should be taken into consideration to identify patients that need to be in strict quarantine for the efficient containment of the pandemic.
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Coronavirus disease 2019, abbreviated to COVID-19 and sustained by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is the latest biological hazard to assume the relevance of insidious worldwide threat. One obvious question that is now engaging the minds of many scientists and healthcare professionals is whether and eventually how laboratory medicine could efficiently contribute to counteract this and other (future) viral outbreaks. Despite there being evidence that laboratory tests are vital throughout many clinical pathways, there are at least three major areas where in vitro diagnos-tics can also provide essential contributions to diagnostic reasoning and managed care of patients with suspected or confirmed SARS-CoV-2 infection. These include etiological diagnosis, patient monitoring, as well as epidemiologic surveillance. Nonetheless, some structural and practical aspects may generate substantial hurdles in providing timely and efficient response to this infectious emergency, which basically include inadequate (insufficient) environment and shortage of technical and human resources for facing enhanced volume of tests on many infected patients, some of whom are with severe disease. Some proactive and reactive strategies may hence be identified to confront this serious healthcare challenge, which entail major investments on conventional laboratory resources, reinforcement of regional networks of clinical laboratories , installation of mobile laboratories, as well as being proactive in establishing laboratory emergency plans.
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We believe a point-of-care (PoC) device for the rapid detection of the 2019 novel Coronavirus (SARS-CoV-2) is crucial and urgently needed. With this perspective, we give suggestions regarding a potential candidate for the rapid detection of the coronavirus disease 2019 (COVID-19), as well as factors for the preparedness and response to the outbreak of the COVID-19.
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Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an ongoing global health emergency. Here we highlight nine most important research questions concerning virus transmission, asymptomatic and presymptomatic virus shedding, diagnosis, treatment, vaccine development, origin of virus and viral pathogenesis.
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Epidemics of Coronavirus Disease 2019 (COVID-19) now have more than 100,000 confirmed cases worldwide. Diagnosis of COVID-19 is currently performed by RT-qPCR methods, but the capacity of RT-qPCR methods is limited by its requirement of high-level facilities and instruments. Here, we developed and evaluated RT-LAMP assays to detect genomic RNA of SARS-CoV-2, the causative virus of COVID-19. RT-LAMP assays in this study can detect as low as 100 copies of SARS-CoV-2 RNA. Cross-reactivity of RT-LAMP assays to other human Coronaviruses was not observed. We also adapted a colorimetric detection method for our RT-LAMP assay so that the tests potentially performed in higher throughput.
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Lockdowns and closings proliferate, but virus testing and contact tracing are lagging.