Jurnal 2
Jurnal 2
Jurnal 2
Major Article
Key Words: Objective: To collate the evidence on the accuracy parameters of all available diagnostic methods for detect-
SARS-CoV-2 ing SARS-CoV-2.
Coronavirus Methods: A systematic review with meta-analysis was performed. Searches were conducted in Pubmed and
Evidence Scopus (April 2020). Studies reporting data on sensitivity or specificity of diagnostic tests for COVID-19 using
Sensitivity
any human biological sample were included.
Specificity
Results: Sixteen studies were evaluated. Meta-analysis showed that computed tomography has high sensi-
tivity (91.9% [89.8%-93.7%]), but low specificity (25.1% [21.0%-29.5%]). The combination of IgM and IgG anti-
bodies demonstrated promising results for both parameters (84.5% [82.2%-86.6%]; 91.6% [86.0%-95.4%],
respectively). For RT-PCR tests, rectal stools/swab, urine, and plasma were less sensitive while sputum (97.2%
[90.3%-99.7%]) presented higher sensitivity for detecting the virus.
Conclusions: RT-PCR remains the gold standard for the diagnosis of COVID-19 in sputum samples. However,
the combination of different diagnostic tests is highly recommended to achieve adequate sensitivity and
specificity.
© 2020 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All
rights reserved.
INTRODUCTION Patients report fever and cough, and most develop chest discom-
fort, difficulty in breathing or pneumonia, being clinically diagnosed
After the first case reports of an acute respiratory syndrome of by imaging tests such as chest X-ray or computed tomography (CT).
unknown etiology in the city of Wuhan, Hubei province (December CT equipment is widespread worldwide and the scan process is rela-
31, 2019), Chinese authorities identified a new coronavirus (SARS- tively simples and quick, which enables rapid screening for suspected
CoV-2) that causes the clinical disease COVID-19. The virus outbreak patients. The typical findings of chest CT images for individuals with
spread quickly, significantly affecting all continents with more than COVID-19 are multifocal bilateral patchy ground-glass opacities or
2 million people infected and thousands of deaths.1,2 Consequently, consolidation with interlobular septal and vascular thickening in the
nations are facing the overwhelming of health care systems and both peripheral areas of the lungs. However, CT findings can change as the
psychological and economic burdens. The lack of effective treatments disease progresses and these manifestations may also be compatible
or prevention strategies has contributed toward the increase in the with other viral pneumonias.4,5
number of cases, enhancing health care expenses with hospitaliza- In this context, the current gold standard for diagnosing COVID-19
tions and palliative therapies. Additionally, there are limited diagnos- is based on a molecular test of the reverse transcription polymerase
tic tests available, which favors the growth of under-reporting of chain reaction (RT-PCR), aimed at detecting the RNA of the virus in
cases.2,3 respiratory samples such as nasopharyngeal swabs or bronchial aspi-
rate.6 The real-time RT-PCR test provides a sensitive (the ability of
the test to correctly identify those patients with the disease 7,8) and
* Address correspondence to Roberto Pontarolo, PhD, Department of Pharmacy, Fed- specific (the ability of the test to correctly identify those patients
eral University of Parana, Av. Lothario Meissner, 632, 80210-170, Curitiba, Parana, Bra-
without the disease 8) method to detect SARS-COV-2, with different
zil.
E-mail address: pontarolo@ufpr.br (R. Pontarolo). diagnosis protocols including sequences of target primers available
Conflict of interest: None to report. in the World Health Organization public database.6,9 However,
https://doi.org/10.1016/j.ajic.2020.07.011
0196-6553/© 2020 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.
22 €ger et al. / American Journal of Infection Control 49 (2021) 21−29
B. Bo
researchers should be aware that this test can also give false nega- the test (eg, sensitivity and/or specificity). We excluded studies pub-
tives if the amount of viral genoma is insufficient or if the correct lished in non-Roman characters.
time-window of viral replication is missed.10 Although the COVID-19
incubation period is estimated to be 5 days, false negative results are Data extraction and bias assessment
common within 7 days of infection. Additionally, RT-PCR process is
time-consuming and shortages in test kit supplies are common The following data were independently extracted by 2 research-
worldwide—especially during the beginning of the epidemic ers: general study details (authors, year of publication, country of ori-
outbreak.11 gin, study design, and sample size), methods, characteristics, and
Other simpler and rapid methods, such as serological testing of IgM diagnostic test results (true positive, TP; true negative, TN; false posi-
and IgG production in response to viral infection, can be used to tive, FP; false negative, FN, sensitivity, specificity, and accuracy).
enhance the detection sensitivity and accuracy of the molecular test or Two reviewers evaluated independently the risk of bias in each
for screening purposes to assess antibody profiles in a large popula- study using the Diagnostic Precision Study Quality Assessment Tool
tion.12,13 Because antibodies are usually detected only 1-3 weeks after (QUADAS-2) recommended by the Cochrane Collaboration. The
the onset of symptoms, these tests are used to assess the overall infec- assessment was performed using the Review Manager Software ver-
tion rate in the community—including the rate of asymptomatic infec- sion 5.3 17
tions—or in remote areas where qPCR assays are not available.12,14
In this scenario, given the limitations of clinical diagnosis alone Statistical analyses
(due to the similarity of the symptoms of COVID-19 infection with
those of other viruses) and the availability of different molecular and The meta-analyses were performed according to the technique
serological tests with both technical advantages and disadvantages, it and type of sample from each study (ie, by subgroups). Sensitivity,
is important to summarize the accuracy parameters of these methods specificity, positive likelihood ratio (PLR) and negative likelihood
and investigate whether they are sufficiently specific or sensitive to ratio (NLR) were measured with a 95% confidence interval based on
fit their role in practice. Few studies addressing the diagnostic perfor- the TP, TN, FP, and FN rates that were extracted from the included
mance of tests for COVID-19 exist, with special focus only on com- studies.
mercially assays available in a given country. In addition, according Sensitivity, defined as the probability that a test result will be pos-
to the different health care settings worldwide, different patterns on itive when the disease exists (true positive rate) was calculated
testing may exist. For instance, the number of daily tests performed as = VP/(VP + FN). Specificity, defined as the probability that a test
per thousand people in Australia or in the United States is around result will be negative when the disease is not present (true negative
1.80, while in Europe is near 1.06 and in South America is lower 0.30 rate) was calculated as = VN/(VN + VP). The PLR is the ratio between
(https://ourworldindata.org/). the probability of a positive test result given the presence of the dis-
Thus, we aimed to perform a systematic review with meta-analy- ease and the probability of a positive test result given the absence of
sis to gather evidence on the features of all available diagnostic test the disease, that is = true positive rate/false positive rate, or expressed
for SARS-CoV-2, including parameters of sensitivity, specificity, posi- as sensitivity/(1-specificity). The NLR is ratio between the probability
tive and negative likelihood ratios and summary receiver operating of a negative test result given the presence of the disease and the
characteristic (SROC) curves, whenever possible. probability of a negative test result given the absence of the disease,
that is = false negative rate/true negative rate, or expressed as (1-sen-
METHODS sitivity)/specificity.
SROC curves based on TP e FP rates were also built whenever pos-
This study was conducted according to Preferred Reporting Items sible to describe the relationship between test sensitivity and speci-
for a Systematic Review and Meta-analysis of Diagnostic Test Accu- ficity. An area under the curve (AUC) close to 1 indicated a good
racy Studies (PRISMA-DTA) statement and Cochrane Collaboration diagnostic performance of the test. All analyses were performed
recommendations.15,16 using the Meta-DiscÓ version 1.4.7.
The heterogeneity of the studies was established by x2 analysis,
Search strategy with inconsistency values (I2) greater than 50% being considered as
moderate heterogeneity, and I2 greater than 75% defined as high het-
Systematic searches were conducted in Pubmed and Scopus with- erogeneity. Outcomes with I2 values greater than 50% were submit-
out limits of time-frame or language (last updated April 2020). The ted to sensitivity analysis (ie, hypothetical removal of studies).
search strategy included the following descriptors: “diagnostic,”
“test,” “assay,” “covid-19,” “sars-cov-2”and other terms combined RESULTS
with Boolean operators AND and OR. The complete strategy is avail-
able in the supplementary material. Manual searches in the referen- A total of 1,089 articles were identified after duplicate removal. Of
ces lists of included studies and in the gray literature (eg, Google these, 1,046 were excluded during the screening phase (title and
Scholar) were also performed. abstract reading), with 43 records being fully appraised. Sixteen stud-
ies were included finally in the systematic review.18-33 We were able
Eligibility criteria to include 14 trials in the quantitative analyses (meta-analysis): the
studies by Corman et al. 22 and Pfefferle et al. 33 did not address the
Titles and abstracts of retrieved articles were screened for eligibil- clinical application of the methods (Fig 1).
ity. Relevant articles were read in full and those fulfilling inclusion All studies included in this review (n = 2,297 patients) were pub-
criteria had their data extracted. Two authors performed all the liter- lished in 2020, designed as retrospective observational cohorts, with
ature selection steps individually and then discussed the differences only one defined as a control-case study.32 Fourteen studies were
with a third author. conducted in China,18-20,22-32 while Italy, 21 Netherlands,22 England,22
Studies were included in this systematic review if they met all the and Germany 33 contributed with one study each.
following eligibility criteria: (i) evaluation of any diagnostic method; All studies presented a test group (patients diagnosed with
(ii) aimed at diagnosis of SARS-CoV-2 (COVID-19); (iii) using any COVID-19), while only 6 trials used a control group (patients negative
human biological sample; and (iv) reporting data on the accuracy of for COVID-19 18,20,21,24,25,33). Patients from the test group were
€ger et al. / American Journal of Infection Control 49 (2021) 21−29
B. Bo 23
previously diagnosed using the (gold standard) PCR technique. The Data on CT of the chest was reported by 6 trials.18,19,23,28,29,31
diagnostic methods were tested for the following samples: nasopha- Meta-analysis showed this method to be sensitive (91.9%, 95% CI
ryngeal swab,20,30,32 nasopharyngeal aspirate,20 throat swab,20,26,30,32 89.8%-93.7%; heterogeneity between trials of I2 = 92.9%), however
blood,21,24,25,27,28,30,32 saliva,20,27 sputum,20,30 urine,20,27,28,30 and with low specificity (25.1%, 95% CI 21.0%-29.5%, I2 = 32.8%; see Figure
stool and rectal swabs.20,27,28,31 Table 1 summarizes the main charac- S1 of the supplementary material for complete results).
teristics of the included studies. Immunological tests (IgM and IgG) were evaluated in 5 trials as a
diagnostic method for COVID-19.21,24,25,27,32 The antibody dosage
Analytical parameters was tested in whole blood samples,21,32 fingerstick blood,24
serum,24,25,27 and plasma.24 Overall, sensitivity and specificity were
Three studies evaluated the optimization of PCR parameters for higher when the combination of IgM and IgG antibodies was evalu-
the detection of SARS-CoV-2.20,22,33 Chan et al. 20 developed and com- ated (see Supplementary Figs S2, S3, and S4), reaching 84.5% (95% CI
pared the performance of 3 new essays of RT-PCR of RNA-dependent 82.2%-86.6%, I2 = 93.2%) and 91.6% (95% CI 86.0%-95.4%, I2 = 0%)
RNA polymerase (RdRp)/helicase (Hel), spike (S) and nucleocapsid respectively. The SROC curves for the immunological diagnostic tests
(N) genes from SARS-CoV-2. Corman et al. 22 assessed several SARS- are shown in Figure 2.
related viral genomic sequences to design the best primer and probe Seven studies addressed the diagnostic test by PCR.20,26-28,30-32
set. Pferfferle et al. 33 investigated a set of primer and probes, target- Meta-analyses were conducted according to the type of sample. Rec-
ing the E gene, for use in an automated system (Cobas 6800 System; tal stool/swab (24.1%, 95% CI 16.7%-33.0%), urine (0.0%, 95% CI 0.0%-
see Table 2). 3.7%), plasma (7.3%, 95% CI 4.1%-11.7%) were less sensitive for detec-
The genes E and RdRp were the most commonly used to detect tion of COVID-19. Sputum (97.2%, 95% CI 90.3%-99.7%), saliva (62.3%,
the COVID-19 virus, both with high analytical sensitivity (technical 95% CI 54.5%-69.6%), nasopharyngeal aspirate/swab and throat swab
limit of detection of 3.2 and 3.6 copies per reaction, respectively). The (73.3%, 95% CI 68.1%-78.0%) were more sensitive for detecting the
detection of the gene N presented lower analytical sensitivity (8.3 virus (Fig S5 in supplementary material). Due to the limited number
copies per reaction). The probe used by these studies is indicated for of PCR studies with a control group, it was not possible to perform
any SARS-CoV infection, including SARS-CoV-2. Process automation statistical analyses on the parameters of specificity, PLR and NLR.
by using the open channel of the Cobas 6800 systems significantly Only the studies by Xie et al. 28 and Yu et al. 30 tested the PCR method
increased the limit of detection. in a control group. In both trials, specificity was 100% for stool, urine,
blood, nasal swab and throat swab samples, while throat swab and
Diagnostic accuracy of tests sputum samples had specificities of 98.6% and 90.0%, respectively
(Table S2 in supplementary material). Sensitivity analyses were per-
Meta-analyses evaluating the parameters of accuracy (sensitivity, formed for all meta-analyses with high heterogeneity results
specificity, PLR and NLR) of the reported tests were performed (I2 > 50%); however, no additional differences were found compared
(Supplementary Table S1), results are shown in Table 3. to the effects of the original analyses (data not shown).
24 €ger et al. / American Journal of Infection Control 49 (2021) 21−29
B. Bo
Table 1
Characteristics of the included studies.
Study Country No. of patients/ No. of control Reference method Evaluated method Sample Marker/gene
samples group patients/ (gene) type
samples
Table 2
Analytical parameters reported by the included studies
Table 3
Meta-analysis of the parameters of accuracy for the different diagnostic techniques
Quality assessment for the detection of SARS-CoV-2 in different samples, including blood,
nasopharyngeal swab, sputum, saliva, urine and feces. We were also
Studies were rated as being of moderate overall methodological able to evaluate qualitatively the main analytical parameters
quality according to QUADAS-2 (see Fig. 3 and 4). The studies by reported in the molecular techniques.
Chan et al. 20 and Pfefferle et al. (29) were not evaluated given the The development of new molecular techniques depends on the
lack of clinical application of the tests (ie, only the analytical perfor- knowledge of the proteomic and genomic composition of the virus or
mance of the methods was assessed). of changes in the hosts’ protein expressions during and after infec-
Around one-quarter of the trials (26%) did not describe the meth- tion.34 Genome sequencing is important for researchers to design pri-
ods of patient selection, and almost half (46%) included previously mers and probes for PCR and other molecular tests. The SARS-CoV-2
diagnosed patients, which may enhance the risk of bias. However, virus has a single-stranded, positive RNA genome of approximately
the majority of the patients included matched the review question 30,000 nucleotides in length that encodes 27 proteins, including an
and were likely to be diagnosed with the evaluated tests (ie, no major RdRP and 4 structural proteins: surface glycoprotein (S), envelope
concerns for the applicability domain). Overall, 80% of the studies protein (E), matrix protein (M) and nucleocapsid protein (N; 34,35. In
properly reported both index and reference standard tests and how the past months, different RT-PCR kits for the detection of SARS-CoV-
they were conducted and interpreted. Only 3 studies (20%) properly 2 have been developed, being able to amplify a small amount of viral
reported the interval between tests, whether patients received differ- genetic material in a sample.36 In this technique, the RNA of the virus
ent index or standard assays, and the complete statistical analyses is reverse-transcribed into complementary DNA strands (cDNA),
performed, thus being judged as having low risk of bias for the flow whose specific regions are amplified. The process usually involves 2
and timing domain. The remaining studies were classified as with an main steps: sequence alignment and primer design, and assay opti-
unclear risk of bias for this domain. mization and testing, especially because this method requires several
temperature changes for each cycle using thermocycling
DISCUSSION equipment.34
We found that in trials evaluating the RdRp/Hel gene, there were
To our knowledge, this is the first systematic review with meta- no cross-reactions with other pathogenic coronaviruses and human
analysis to collate the available evidence on the accuracy parameters respiratory pathogens in cell culture or clinical samples. On the other
of different diagnostic methods (clinical, molecular, and serological) hand, the specific SARS-CoV-2 (RdRp) gene reacted with SARS-CoV in
€ger et al. / American Journal of Infection Control 49 (2021) 21−29
B. Bo 27
a pathogen takes 1-2 weeks to occur. In this context, the use of sero- 3. Adhikari SP, Meng S, Wu YJ, et al. Epidemiology, causes, clinical manifestation and
logical tests for detection in the initial/acute phase of the disease can diagnosis, prevention and control of coronavirus disease (COVID-19) during the
early outbreak period: a scoping review. Infect Dis Poverty. 2020;9:29.
be challenging. A recent study showed that IgM and IgG seroconver- 4. Zhu N, Zhang D, Wang W, et al. A novel coronavirus from patients with pneumonia
sion can occur simultaneously or sequentially in COVID-19, and that in China, 2019. N Engl J Med. 2020;382:727–733.
antibody titers reach a plateau after 6 days.19 In addition, a meta- 5. Ye Z, Zhang Y, Wang Y, Huang Z, Song B. Chest CT manifestations of new coronavi-
rus disease 2019 (COVID-19): a pictorial review. Eur Radiol. 2020;30:4381–4389.
analysis of the accuracy of diagnostic tests marketed in Brazil, taken 6. WHO. WHO Coronavirus Disease (COVID-19) Technical Guidance:Laboratory Testing
from manufacturers' data, showed a range of 10%-40% false-negative for 2019-nCoV in Humans. 2020.. Available at: https://www.who.int/emergencies/
results for detection of SARS-CoV-2 IgM in the acute phase in 8 evalu- diseases/novelcoronavirus-2019/technical-guidance/laboratory-guidance.
Accessed July 27, 2020.
ated tests.41 However, immunological tests have a quick turnaround 7. Theagarajan LN. Group Testing for COVID-19: How to Stop Worrying and Test More. 1.
time and relatively low costs (around £6 per test or USD$ 8-10),42 Cornell University; 2020.
which may represent an important strength for this method, given 8. Lalkhen AG, McCluskey A. Clinical tests: sensitivity and specificity. Contin Educ
Anaesth Crit Care Pain. 2008;8:221–223.
the shortages of RT PCR and its higher price (around £30/test, but
9. Wang YK, Kang H, Liu X, Tong Z. Combination of RT-qPCR testing and clinical fea-
may range from USD$ 25 to 100). Additionally, the participation of tures for diagnosis of COVID-19 facilitates management of SARS-CoV-2 outbreak.
multiple manufacturers in the market can potentially scale the J Med Virol. 2020;92:538–539.
immunological tests to millions of people per day due to their simpler 10. Zou L, Ruan F, Huang M, et al. SARS-CoV-2 viral load in upper respiratory speci-
mens of infected patients. N Engl J Med. 2020;382:1177–1179.
design. This may especially help to improve the detection of the virus 11. Lauer SA, Grantz KH, Bi Q, et al. The incubation period of coronavirus disease 2019
in health care settings where resources are more limited, such as in (COVID-19) from publicly reported confirmed cases: estimation and application.
developing countries.42,43 Ann Intern Med. 2020;172:577–582.
12. Guo L, Ren L, Yang S, et al. Profiling early humoral response to diagnose novel
Our study has some limitations. The included studies differ in terms coronavirus disease (COVID-19). Clin Infect Dis. 2020;71:778–785.
of size, risk of bias, and external validity. We are aware of potential 13. Meyer B, Drosten C, Muller MA. Serological assays for emerging coronaviruses:
introduction of bias caused by studies of poor methodological quality. challenges and pitfalls. Virus Res. 2014;194:175–183.
14. Tang YW, Schmitz JE, Persing DH, Stratton CW. The laboratory diagnosis of COVID-
We found high heterogeneity rates among trials, probably cause by 19 infection: current issues and challenges. J Clin Microbiol. 2020;58:e00512-20.
some differences in the methods, patient characteristics, and samples 15. McInnes MDF, Moher D, Thombs BD, et al. Preferred reporting items for a system-
used. However, we tried to avoid systematic errors by performing sen- atic review and meta-analysis of diagnostic test accuracy studies: the PRISMA-
DTA statement. Jama. 2018;319:388–396.
sitivity analyses, which do not demonstrate significant differences from
16. Higgins J, Green S. Cochrane Handbook for Systematic Reviews of Interventions.
the original analyses. The eligibility criteria and description of the par- Vol Version 5.1.02011.
ticipants is crucial, as the test is only valid under similar circumstances. 17. Whiting PF, Rutjes ASW, Westwood ME, et al. QUADAS-2: a revised tool for the
quality assessment of diagnostic accuracy studies. Ann Intern Med. 2011;155:529–
Sensitivities, specificities, TP, and TN were compared, but these statis-
536.
tics depend on the populations studied, the reference tests used, and 18. Ai T, Yang Z, Hou H, et al. Correlation of chest CT and RT-PCR testing in coronavirus
the specific function of the test. Studies were judged as being of moder- disease 2019 (COVID-19) in China: a report of 1014 cases. Radiology. 2020;296:
ate methodological quality, with few concerns regarding the applicabil- E32–E40.
19. Long C, Xu H, Shen Q, et al. Diagnosis of the coronavirus disease (COVID-19): rRT-
ity of the methods used. The low reporting quality of some studies PCR or CT? Eur J Radiol. 2020;126.
hampered the performance of further analyses. 20. Chan JFW, Yip. CCY, To KKW, et al. Improved molecular diagnosis of COVID-19 by
the novel, highly sensitive and specific COVID-19-RdRp/Hel real-time reverse tran-
scription-polymerase chain reaction assay validated in vitro and with clinical
CONCLUSIONS specimens. J Clin Microbiol. 2020;58:e00310-20.
21. Cassaniti I, Novazzi F, Giardina F, et al. Performance of VivaDiagTM COVID-
19 IgM/IgG Rapid Test is inadequate for diagnosis of COVID-19 in acute patients
RT-PCR remains the gold standard for the diagnosis of COVID-19 in referring to emergency room department. J Med Virol. 2020.
sputum samples. However, depending on the type of sample and stage 22. Corman VM, Landt O, Kaiser M, et al. Detection of 2019 novel coronavirus (2019-
of the disease, other methods are preferable. A combination of clinical, nCoV) by real-time RT-PCR. Euro Surv. 2020;25. 2000045.
23. Li K, Fang Y, Li W, et al. CT image visual quantitative evaluation and clinical classifi-
molecular, and serological diagnostic tests is highly recommended to cation of coronavirus disease (COVID-19). Eur Radiol. 2020;30:4407–4416.
achieve adequate sensitivity and specificity. Automated assays for 24. Li Z, Yi Y, Luo X, et al. Development and clinical application of a rapid IgM-IgG
molecular diagnosis using a 2-target system for detecting SARS-CoV-2 combined antibody test for SARS-CoV-2 infection diagnosis. Clin Infect Dis.
2020;92:1518–1524.
should be used whenever possible to enhance analytical performance. 25. Liu W, Liu L, Kou G, et al. Evaluation of Nucleocapsid and Spike Protein-based ELI-
SAs for detecting antibodies against SARS-CoV-2. J Clin Microbiol. 2020;58:
e00461-20.
Acknowledgments 26. Pan Y, Long L, Zhang D, et al. Potential false-negative nucleic acid testing results for
severe acute respiratory syndrome coronavirus 2 from thermal inactivation of
The authors express their gratitude for research funding to the samples with low viral loads. Clin Chem. 2020;66:794–801.
27. To KKWT, Tsang OTY, Leung WS, et al. Temporal profiles of viral load in pos-
CAPES (Brazilian Federal Agency for Support and Evaluation of Grad- terior oropharyngeal saliva samples and serum antibody responses during
uate Education within the Ministry of Education of Brazil)—Finance infection by SARS-CoV-2: an observational cohort study. Lancet. Infect Dis.
Code 001. 2020;20:565–574.
28. Xie C, Jiang L, Huang G, et al. Comparison of different samples for 2019 novel coro-
navirus detection by nucleic acid amplification tests. Int J Infect Dis. 2020;93:
SUPPLEMENTARY MATERIALS 264–267.
29. Xu X, Yu C, Qu J, et al. Imaging and clinical features of patients with 2019 novel
coronavirus SARS-CoV-2. Eur J Nucl Med Mol Imaging. 2020;47:1275–1280.
Supplementary material associated with this article can be found 30. Yu FY, Yan L, Wang N, et al. Quantitative detection and viral load analysis of SARS-
in the online version at https://doi.org/10.1016/j.ajic.2020.07.011. CoV-2 in infected patients. Clin Infect Dis. 2020;71:793–798.
31. Zhang JC, Wang S, Xue YD. Fecal specimen diagnosis 2019 novel coronavirus
−infected pneumonia. J Med Virol. 2020;92:680–682.
References 32. Zhao Jr JY, Yuan Q, Wang H, et al. Antibody responses to SARS-CoV-2 in patients of
novel coronavirus disease 2019. Clin Infect Dis. 2020;71:2027–2034.
33. Pfefferle S, Reucher S, Norz D, Lutgehetmann M. Evaluation of a quantitative RT-
1. WHO. Coronavirus Disease (COVID-2019) Situation Reports. 2020.. Available at: PCR assay for the detection of the emerging coronavirus SARS-CoV-2 using a high
https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation- throughput system. Euro Surv. 2020;25. 2000152.
reports. Accessed July 27, 2020. 34. Udugama B, Kadhiresan P, Kozlowski HN, et al. Diagnosing COVID-19: the disease
2. Ahn DG, Shin HJ, Kim MH, et al. Current status of epidemiology, diagnosis, thera- and tools for detection. ACS Nano. 2020;14:3822–3835.
peutics, and vaccines for novel coronavirus disease 2019 (COVID-19). J Microbiol 35. Wu A, Peng Y, Huang B, et al. Genome composition and divergence of the novel
Biotechnol. 2020;30:313–324. coronavirus (2019-nCoV) originating in China. Cell Host Microbe. 2020;27:325–328.
€ger et al. / American Journal of Infection Control 49 (2021) 21−29
B. Bo 29
36. Carter LJ, Garner LV, Smoot JW, et al. Assay Techniques and Test Development for 40. Fan L, Liu S. CT and COVID-19: Chinese experience and recommendations concern-
COVID-19 Diagnosis. ACS Cent Sci. 2020;6:591–605. ing detection, staging and follow-up. Eur Radiol. 2020;30:5214–5216.
37. CDC.. CDC 2019-Novel Coronavirus (2019-nCoV) - Real-Time RT-PCR Diagnostic Panel 41. Castro R, Luz PM, Wakimoto MD, Veloso VG, Grinsztejn B, Perazzo H. COVID-19: a
- Catalog # 2019-nCoVEUA-01 1000 Reactions. 2019. Available at: https://www. meta-analysis of diagnostic test accuracy of commercial assays registered in Brazil.
who.int/emergencies/diseases/novelcoronavirus-2019/technical-guidance/labora- Braz J Infect Dis. 2020;24:180–187.
tory-guidance. Accessed July 27, 2020. 42. Wang Y, Wang Y, Chen Y, Qin Q. Unique epidemiological and clinical features of
38. CDC. Interim Guidelines for Collecting, Handling, and Testing Clinical Specimens from the emerging 2019 novel coronavirus pneumonia (COVID-19) implicate special
Persons for Coronavirus Disease 2019 (COVID-19). 2019. Available at: https://www. control measures. J Med Virol. 2020;92:568–576.
cdc.gov/coronavirus/2019-ncov/lab/guidelines-clinical-specimens.html. Accessed 43. FDA. Coronavirus (COVID-19) Update: FDA Authorizes First Antigen Test to Help in the
July 27, 2020. Rapid Detection of the Virus that Causes COVID-19 in Patients. 2020. Available at:
39. Xing YH, Ni W, Wu Q, et al. Prolonged viral shedding in feces of pediatric https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-
patients with coronavirus disease 2019. J Microbiol, Immunol Infect. 2020;53: update-fda-authorizes-first-antigen-test-help-rapid-detection-virus-causes.
473–480. Accessed July 27, 2020.