key: cord-296588-q2716lda
authors: Hanson, Kimberly E; Caliendo, Angela M; Arias, Cesar A; Englund, Janet A; Lee, Mark J; Loeb, Mark; Patel, Robin; El Alayli, Abdallah; Kalot, Mohamad A; Falck-Ytter, Yngve; Lavergne, Valery; Morgan, Rebecca L; Murad, M Hassan; Sultan, Shahnaz; Bhimraj, Adarsh; Mustafa, Reem A
title: Infectious Diseases Society of America Guidelines on the Diagnosis of COVID-19
date: 2020-06-16
journal: Clin Infect Dis
DOI: 10.1093/cid/ciaa760
sha: 
doc_id: 296588
cord_uid: q2716lda

BACKGROUND: Accurate molecular diagnostic tests are necessary for confirming a diagnosis of coronavirus disease 2019 (COVID-19). Direct detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acids in respiratory tract specimens informs patient, healthcare institution and public health level decision-making. The numbers of available SARS-CoV-2 nucleic acid detection tests are rapidly increasing, as is the COVID-19 diagnostic literature. Thus, the Infectious Diseases Society of America (IDSA) recognized a significant need for frequently updated systematic reviews of the literature to inform evidence-based best practice guidance. OBJECTIVE: The IDSA’s goal was to develop an evidence-based diagnostic guideline to assists clinicians, clinical laboratorians, patients and policymakers in decisions related to the optimal use of SARS-CoV-2 nucleic acid amplification tests. In addition, we provide a conceptual framework for understanding molecular diagnostic test performance, discuss the nuance of test result interpretation in a variety of practice settings, and highlight important unmet research needs in the COVID-19 diagnostic testing space. METHODS: IDSA convened a multidisciplinary panel of infectious diseases clinicians, clinical microbiologists, and experts in systematic literature review to identify and prioritize clinical questions and outcomes related to the use of SARS-CoV-2 molecular diagnostics. Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess the certainty of evidence and make testing recommendations. RESULTS: The panel agreed on 15 diagnostic recommendations. CONCLUSIONS: Universal access to accurate SARS-CoV-2 nucleic acid testing is critical for patient care, hospital infection prevention and the public response to the COVID-19 pandemic. Information on the clinical performance of available tests is rapidly emerging, but the quality of evidence of the current literature is considered low to very low. Recognizing these limitations, the IDSA panel weighed available diagnostic evidence and recommends nucleic acid testing for all symptomatic individuals suspected of having COVID-19. In addition, testing is recommended for asymptomatic individuals with known or suspected contact with a COVID-19 case. Testing asymptomatic individuals without known exposure is suggested when the results will impact isolation/quarantine/personal protective equipment (PPE) usage decisions, dictate eligibility for surgery, or inform administration of immunosuppressive therapy. Ultimately, prioritization of testing will depend on institutional-specific resources and the needs of different patient populations.

A c c e p t e d M a n u s c r i p t Background In late December 2019, an outbreak of pneumonia cases of unclear etiology was reported in Wuhan City, Hubei Province, China [1] . Unbiased next generation sequencing (NGS) using lower respiratory tract (LRT) specimens collected from affected patients subsequently identified a novel coronavirus as the cause of illness now known as Coronavirus Disease 2019 .

The entire viral genome was shared online within days and phylogenetic analyses established close relationship to human severe acute respiratory syndrome coronavirus (SARS-CoV) as well as several other SARS-like bat coronaviruses [1, 2] . Based on genetic similarities, the novel coronavirus was officially named SARS-CoV-2 [3] . By March 11 th , 2020, the virus had spread to at least 114 countries and killed more than 4,000 people, prompting the World Health Organization (WHO) to officially declare a global pandemic [4] .

Public availability of the SARS-CoV-2 genome was an essential first step enabling development of accurate molecular diagnostic assays. Nucleic acid amplification tests (NAATs) designed to detect one or more gene sequences specific to SARS-CoV-2 are essential for confirming COVID- To date, multiple commercial test manufacturers and clinical laboratories, including academic medical centers, have received EUA for a SARS-CoV-2-specific molecular diagnostic test. The first home-based test collection kit was also recently granted an EUA [5] . It is important to recognize, however, that EUA guidance differs substantially from the standard FDA approval process. In the setting of a public health emergency, the FDA only requires test developers to establish acceptable analytical accuracy. Clinical test performance (i.e., sensitivity and specificity) has yet to be determined or comprehensively compared across EUA platforms. As a result, most of the NAAT performance data used to inform this guideline was derived from A c c e p t e d M a n u s c r i p t studies evaluating assays not widely used in the U.S. We assumed, therefore, that performance of standard NAAT methods to be comparable across countries (which may or may not be correct).

Given increasing test availability combined with a rapidly growing number of NAAT-focused studies published online or in academic journals, the Infectious Diseases Society of America Table 1 .

At the time of this review, there was little evidence to inform use of serologic testing.

Therefore, the first version of the IDSA diagnostic guideline focuses only on the use of targeted NAAT applied directly respiratory tract specimens. It is anticipated that these guidelines will be frequently updated as substantive new information becomes available; subsequent versions will also address SARS-CoV-2 serology due to the rapidly evolving information and uncertainty of the reliability of serological tests. M a n u s c r i p t

This guideline was developed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach for evidence assessment. In addition, given the need for rapid response to an urgent public health crisis, the methodological approach was modified according to the GIN/McMaster checklist for development of rapid recommendations [6] .

The 

The conflict of interest (COI) review group included two representatives from IDSA who were responsible for reviewing, evaluating and approving all disclosures. All members of the expert panel complied with the COI process for reviewing and managing conflicts of interest, which required disclosure of any financial, intellectual, or other interest that might be construed as constituting an actual, potential, or apparent conflict, regardless of relevancy to the guideline topic. The assessment of disclosed relationships for possible COI was based on the relative weight of the financial relationship (i.e., monetary amount) and the relevance of the relationship (i.e., the degree to which an association might reasonably be interpreted by an independent observer as related to the topic or recommendation of consideration). The COI review group ensured that the majority of the panel and chair was without potential relevant A c c e p t e d M a n u s c r i p t (related to the topic) conflicts. The chair and all members of the technical team were determined to be unconflicted.

Clinical questions were developed into a Population, Intervention, Comparison, Outcomes (PICO) format [7] prior to the first panel meeting (Table s1) . IDSA panel members prioritized questions with available evidence that met the minimum acceptable criteria (i.e., the body of evidence reported on at least test accuracy results can be applied to the population of interest).

Panel members prioritized patient-oriented outcomes related to SARS-CoV-2 testing such as requirement for self-quarantine, eligibility for investigational COVID-19 treatment, timing of elective surgery or procedures, and management of immunosuppressive therapy. We also considered the impact of SARS-CoV-2 results on infection prevention and public health practices, including the use of personal protective equipment (PPE) and contact tracing.

The National Institute of Health and Care Excellence (NICE) and the Center of Disease Control (CDC) highly-sensitive search was reviewed by the methodologist in consultation with the technical team information specialist and was determined to have high sensitivity. An additional term, COVID, was added to the search strategy used in addition to the terms identified in the PICO questions (Table s2) . Ovid Medline and Embase were searched from 2019 through April 20, 2020. Horizon scans were performed daily during the evidence assessment and recommendation process to locate additional grey literature and manuscript preprints from the following sources Litcovid, Medrxiv, SSRN, and Trip database. Reference lists and literature suggested by panelists were reviewed for inclusion. No restrictions were placed on language or study type.

Two reviewers independently screened titles and abstracts, as well as eligible full-text studies.

We included studies reporting data on diagnostic test accuracy (cohort studies, cross sectional A c c e p t e d M a n u s c r i p t studies and case-control studies). When questions compared the performance of different tests (e.g., different testing or sampling methods) or testing strategies, we included studies that provided direct test accuracy data about both tests in the same population. When these direct studies where lacking, we included studies that assessed a single test and compared its results to a reference standard. We did not limit our inclusion to a specific reference standard due to sparsity of data. We also included studies that assessed the prevalence of COVID-19 in different populations. Reviewers extracted relevant information into a standardized data extraction form.

Two reviewers completed data extraction independently and in duplicate. Disagreements were resolved by discussion to reach consensus and in consultation with expert clinician scientists.

Data extracted included general study characteristics (authors, publication year, country, study design), diagnostic index test and reference standard, prevalence of COVID-19, and parameters to determine test accuracy (i.e., sensitivity and specificity of the index test). Accuracy estimates from individual studies were combined quantitatively (pooled) for each test using

OpenMetaAnalyst (http://www.cebm.brown.edu/openmeta/). We had planned to conduct a bivariate analysis for pooling sensitivity and specificity for each of the test comparisons to account for variation within and between studies. However, this was not feasible due to the sparsity of available data and lack of information on specificity in most instances, so we either presented data as a range of the extreme sensitivity and specificity presented in the studies or pooled as proportions to facilitate decision making. We had also planned to use the Breslow-Day test to measure the percentage of total variation across studies due to heterogeneity (I 2 ) but were not able to do that due to the sparsity of data. Forest plots were created for each comparison.

To calculate the absolute differences in effects for different testing or sampling strategies, we applied the results of the sensitivity and specificity to a range of plausible prevalence in the population. We then calculated true positives, true negatives, false positives, and false A c c e p t e d M a n u s c r i p t negatives. To determine the prevalence for each question, we considered the published literature in consultation with the clinical experts. In general, for questions addressing symptomatic individuals we considered the following prevalence: 10% which is typically seen in symptomatic outpatients who have not reached a hospital facility [8] [9] [10] ; 40% which is typically seen in patients meeting clinical definition for COVID-19 who were hospitalized [11, 12] ; and 80% which is typically seen in patients meeting clinical definition for COVID-19 who were admitted to intensive care units. For questions addressing asymptomatic individuals who were exposed to COVID-19, we considered that the prevalence may range from 10% to 50% based on household clusters, nursing home outbreak, active surveillance of passengers quarantined on a cruise ship or passengers of repatriation flights, hospital employees with close contact with COVID-19 positive patients and customers and employees of a restaurant that had a COVID-19

outbreak [13] [14] [15] [16] [17] [18] [19] . For questions addressing asymptomatic individuals, we considered that the prevalence may range from <1% in general population who are not in hotspots to 10% in asymptomatic patients in hotspots [8, 20, 21] .

We conducted the risk of bias assessment for diagnostic test accuracy studies using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 revised tool (Table s3 ) [22] . GRADE framework was used to assess overall certainty by evaluating the evidence for each outcome on the following domains: risk of bias, imprecision, inconsistency, indirectness, and publication bias [23, 24] . GRADE summary of findings tables were developed in GRADEpro Guideline Development Tool [25] .

The panel considered core elements of the GRADE evidence in the decision process, including A c c e p t e d M a n u s c r i p t

As per GRADE methodology, recommendations are labeled as "strong" or "conditional". The words "we recommend" indicate strong recommendations and "we suggest" indicate conditional recommendations. Figure 2 provides the suggested interpretation of strong and weak recommendations for patients, clinicians, and healthcare policymakers. Rarely, low certainty evidence may lead to strong recommendations. In those instances, we followed generally recommended approaches by the GRADE working group, which are outlined in five paradigmatic situations (e.g., avoiding a catastrophic harm) [26] . For recommendations pertaining to good practice statements, appropriate identification and wording choices were followed according to the GRADE working group [27] . A "Good practice statement" represents a message perceived by the guideline panel as necessary to health care practice, that is supported by a large body of indirect evidence difficult to summarize, and indicates that implementing this recommendation would clearly result in large net positive consequences. For recommendations where the comparators are not formally stated, the comparison of interest was implicitly referred to as "not using the test". Some recommendations acknowledge the current "knowledge gap" and aim at avoiding premature favorable recommendations for test use and to avoid encouraging the rapid diffusion of potentially inaccurate tests. Detailed suggestions about the specific research questions that should be addressed are found in Table   2 .

A c c e p t e d M a n u s c r i p t A c c e p t e d M a n u s c r i p t Committee reviewed and approved the guideline prior to dissemination.

Regular, frequent screening of the literature will take place to determine the need for revisions based on the likelihood that new data will have an impact on the recommendations. If necessary, the expert panel will be reconvened to discuss potential changes. In addition, future searches will include critical appraisal of the SARS-CoV-2 serology literature.

Systematic review and horizon scan of the literature identified 2,909 references of which 23

informed the evidence base for these recommendations (Figure s1 ). Characteristics of the included studies can be found in Table s4 . Figure 1 summarizes a testing algorithm for COVID-19 diagnosis guidelines. However, testing is not widely available in some areas. 

 This recommendation does not address testing a combination of specimen types due to lack of evidence.

 The panel considered symptomatic patients to have at least one of the most common symptoms compatible with COVID-19 ( Table 1) .

Thirteen studies informed this recommendation [33] [34] [35] [36] [37] [38] [39] [40] [41] [42] [43] [44] [45] and they provided varying descriptions of specimen type (Supplement C). In an effort to maintain consistency in the analysis of evidence, reported specimen types were grouped into nasopharyngeal (NP), mid-turbinate (MT), nasal, throat, or saliva. In studies that did not define collection techniques for "nasal", we assumed it to mean anterior nasal and not deep-nasal or A c c e p t e d M a n u s c r i p t nasopharyngeal. Saliva collection methods were also inconsistent. Saliva studies incorporating a "coughed-up" sample were excluded from the URTI and ILI analysis under the assumption that they likely included some mixture of pure saliva and sputum. Analyses of "tongue" swabs were also excluded. It is important to note as well, that not all specimens were collected from the same patient at the same time, the time of collection from symptom onset was not provided in all studies and various approaches for establishing SARS-CoV-2 positivity were used to define positive results (i.e., clinical evaluation, detection different gene targets versus nucleic acid sequencing).

A total of 11 reports presented data about test accuracy of a specific sample type(s); eight of these [35, 36, 38-41, 43, 44] provided comparative data for two or more sample collection sites;

and three others [33, 37, 45] provided data for one site only. Studies with comparative data showed a lower sensitivity for oral sampling in comparison to NP, MT, or nasal sampling.

Summary statistics different specimen type are shown in Table 3 . Two studies [38, 39] A c c e p t e d M a n u s c r i p t types are false negative results, which could promote unchecked SARS-CoV-2 transmission. One potential benefit of the alternative methods are the less-invasive nature of nasal, MT and throat swabs or saliva as compared to NP sampling. In addition, the PPE requirements for healthcare providers collecting non-cough inducing specimen types may be less. Lastly, the non-NP sampling is amendable to patient self-collection, which has the potential to further reduce healthcare worker exposure to infectious droplets and possible droplet nuclei.

Additional considerations: Indirect evidence from influenza and respiratory syncytial virus studies suggest that alternative nasal cavity collection sampling methods such as anterior nasal and MT swabs provide comparable sensitivity to NP swabs [46] . Using NP swab collection as the reference method will bias evaluation of the comparator method by definition. Saliva is an easily obtained specimen and there is significant recent interest in its use for SARS-CoV-2 detection. At the time of this literature review we identified a single study assessing true saliva as a specimen type. This is a promising specimen type given the simplicity of collection. The panel anticipates multiple additional studies to follow, which will be included in future guideline updates. The panel considered indirect evidence for nasal swabs and MT swabs from other respiratory viruses in the decision to list these specimen types are preferred over saliva. In addition, saliva is complex matrix and clinical laboratories will need to carefully assess RNA stability during specimen transport and the efficiency of nucleic acid extraction using their own specific methods. We did not identify any studies assessing combinations of specimen types.

Although oropharyngeal swabs or saliva can be utilized for the diagnosis of COVID-19, the available evidence combined with indirect evidence from other respiratory viruses suggests that collection of anterior nares, MT, or NP swabs has higher sensitivity. At the current time, there is little evidence to support use of oropharyngeal swabs or saliva alone. However, future studies of saliva as a specimen type for SARS-Co-2 detection are anticipated.

A c c e p t e d M a n u s c r i p t

Evaluation of alternative collection devices and methods are critically needed as we are facing shortages in test collection supplies such as swabs, transport media and PPE. While NP swab collection is widely used and the primary specimen type for commercial direct SARS-CoV-2 test platforms, based on current available evidence, clinical practice, and availability of testing resources, the panel believes there are comparable alternative methods for sampling the nasal passages. Clinical laboratories will need to validate use of individual specimen types. Future studies of saliva should clearly describe collection methods, specimen transport media and processing requirements. Moving forward, it will be critical to standardize these processes. 9 (0 to 9) 0 (0 to 9) 0 (0 to 9) 0 (0 to 9) 18 (0 to 216) 0 (0 to 18) Explanations: This table is based on applying the sensitivity and specificity estimates to calculate True and false positives and negatives in a hypothetical population of 1000 individuals. *No studies reported on the specificity of oral and NP a. The case-control design leads to a serious study population bias. b. Some studies compared two or more of the specimen types, but no studies compared all specimen types in the same patient population. Studies reported test accuracy results but did not report on patient-important and population-important outcomes based on the results. c. There is serious unexplained heterogeneity. 

 Appropriate specimen collection and transport to the laboratory is critical. General instructions for swab-based SARS-CoV2 testing are shown in Table 4 . Additional resources are available on the IDSA website.

 A clear, step-by-step protocol needs to be presented to patients attempting self-collection.

This could be in the form of a short video or printed pamphlet with illustrations.

 The majority of self-collection studies were performed in the presence of a healthcare worker.

 The available evidence for nasal and MT swabs as alternatives to healthcare personnel collection is based on assessment of symptomatic patients. Data on self-collection in asymptomatic individuals is currently unavailable.

A c c e p t e d M a n u s c r i p t  The panel considered symptomatic patients to have at least one of the most common symptoms compatible with COVID-19 ( Table 1) .

This recommendation is based on three cohort studies (Supplement D). In the first study, test accuracy results were provided for self-collected non-invasive specimens compared to healthcare-collected NP swabs as the standard [39] . For self-collection, participants were provided with instructions and asked to self-collect tongue, nasal, and MT swabs, in that order. Tongue samples were collected with a nylon flocked swab. Nasal samples were collected with a foam swab bilaterally. Mid-turbinate samples were collected with a nylon flocked swab bilaterally. After patient sampling was completed, NP samples were collected by a healthcare worker using a polyester tipped swab on a skinny wire. In the second study, patients attending dedicated COVID-19 collection clinics were offered the option to first self-collect nasal and throat swabs followed by healthcare provider collection of nasal, throat or oropharyngeal swabs [44] ; concordance of results were presented. The third study compared positivity for supervised oral fluid sampling, supervised self-collected deep nasal swabs, unsupervised oral fluid sampling and provider collected NP swabs [43] . In this analysis, any positive test, obtained from any of the reported sampling methods including the index test, was considered to be a true positive. Although the study reported the results for "oral fluid", it is likely these samples were mixed with sputum. Lastly, the panel considered unpublished data submitted to the FDA on home collection, which demonstrated good stability of specimens stored in universal transport media (UTM) during transport from homes to laboratories and comparable quantities of virus in self-collected compared to healthcare provider collected swabs. Summary statistics for self-collected versus health-care worker collected nasal swabs are shown in Table 5 .

The studies used to inform the recommendation were small and heterogeneous. Sources of heterogeneity included variable swab and transport media types as well as use of unilateral versus bilateral nares self-collection. The timing of collection relative to symptom onset is also important but was not well documented in available data. Due to the mentioned concerns with A c c e p t e d M a n u s c r i p t the studies and the lack of direct comparisons between different specimen types in the same patient population, the panel agreed that overall certainty of evidence was low.

Benefits and harms: The panel placed a high value on avoiding the close exposure of healthcare providers to patient droplets and possible droplet nuclei generated during specimen collection.

We assumed that self-collected specimens including anterior nasal swabs, MT swabs and saliva (without cough) would reduce provider exposure and could reduce mask or respirator use. The overall sensitivity of testing when samples were collected by patients was comparable to those collected by healthcare providers.

Other potential benefits of self-collection include increasing the availability of testing outside the healthcare system and increased patient satisfaction with selfcollection. Concerns with self-collection include lack of experience or documentation for actual collection methods by patients; inappropriate sample collection and/or handling could then lead to inaccurate results.

Although data is limited, both healthcare provider collected, and self-collected nasal or MT swabs appear to result in similar rates of detection of SARS-CoV-2. Self-collection of NP swabs is unlikely to be an option as a self-collection method. There are advantages of having multiple strategies to collect clinical specimens, particularly in times of PPE shortages when limiting exposure to healthcare personnel or other patients is important, or when testing in specific populations without access to the healthcare system is required. Further comparative studies of self-collected non-invasive specimens (i.e., nasal, mid-turbinate, and throat swabs, as well as saliva) compared with M a n u s c r i p t Abbreviations: NP = nasopharyngeal; OP = oropharyngeal; MT = nasal mid-turbinate; NS = anterior nares swab.

^C autions: Do NOT use calcium alginate swabs or swabs with wooden shafts, which may contain substances that interfere with nucleic acid amplification. Rayon swabs may not be compatible with all molecular platforms. Clinical laboratories should confirm compatibility of collection devices during assay validation. # Pediatrics: Swab insertion distance will differ for pediatric patients. Swabs with stoppers make estimating distance easier for MT self-collection. Two-sided MT sampling not always performed. 

We identified nine studies that performed both an upper respiratory tract (URT) swab and lower respiratory tract (LRT) sample collection consecutively on the same patient (Supplement E). Two reported on viral load and did not report on sensitivity [47, 48] .

Seven studies reported on sensitivity, of which three had a case control design [35, 49, 50] and one reported results per sample and not per patient [51] . The three cohort studies [43, 52, 53] were used to inform the panel's decision-making process. The sample type varied by study and included throat and nasal swabs for URT sampling and sputum and bronchoalveolar lavage (BAL) fluid specimens for LRT sampling. Summary statistics for URT versus LRT sampling in 3 cohort studies are shown in Table 6 . The timing of specimen collection with regards to clinical course was not reported for all these studies and different diagnostic reference standards were A c c e p t e d M a n u s c r i p t M a n u s c r i p t A c c e p t e d M a n u s c r i p t 0 (0 to 9) 0 (0 to 9) 0 (0 to 6) 0 (0 to 6)

Explanations: This table is based on applying the sensitivity and specificity estimates to calculate True and false positives and negatives in a hypothetical population of 1000 individuals a. Studies reported test accuracy results but did not report on patient-important and population-important outcomes based on the results. b. Considering the lower vs upper limit of the sensitivity confidence interval may lead to different clinical decision, and the low number of patients lead to very serious imprecision c. Typically seen in symptomatic outpatients who have not reached a hospital facility d. Typically seen in patients meeting clinical definition for COVID-19 who were hospitalized e. Certainty of evidence (CoE) M a n u s c r i p t Missing data in the studies included timing of specimen collection in relationship to onset of clinical symptoms and specimen type used for testing. Additionally, the performance and accuracy of different rapid tests was very inconsistent. Given all these issues, the overall certainty of the effect of using rapid tests on patients was very low.

The major benefit of a rapid result is the ability to make clinical decisions while the patient is present in a timely manner and implement interventions to protect others.

A possible harm of rapid tests is the potential for increased numbers of false negative results, which could lead to missed diagnoses and patients not being isolated when they are indeed infected, if sensitivity is lower than non-rapid tests. Diagnostic accuracy should be stratified by duration of symptoms and severity of disease.

Furthermore, the diagnostic reference standard must be clearly defined. Performance characteristics of EUA rapid tests, especially those that are CLIA-waived, should be collected in the field and performed by the non-laboratory staff running the test (which is how they are used in real life). Ideally, studies should assess the impact of rapid results on clinical outcomes, such as time to appropriate treatment or therapeutic intervention.

individuals who are either known or suspected to have been exposed to COVID-19 (conditional recommendation, very low certainty of evidence).

 Known exposure was defined as direct contact with a laboratory confirmed case of COVID-

 Suspected exposure was defined as working or residing in a congregate setting (e.g., longterm care, correctional facility, cruise ship, factory, among others) experiencing a COVID-19

A c c e p t e d M a n u s c r i p t  The risk of contracting SARS-CoV-2 may vary under different exposure conditions.  This recommendation assumes the exposed individual was not wearing appropriate PPE.

 The decision to test asymptomatic patients will be dependent on the availability of testing resources.

Summary of the evidence: We did not identify any studies that directly assessed a strategy of testing versus no testing of asymptomatic individuals exposed to SARS-CoV-2. Therefore, the effect of testing on the pre-specified outcomes could not be directly assessed. We also did not identify test accuracy studies directly assessing the performance of SARS-CoV-2 NAATs in asymptomatic individuals. However, based on evidence that asymptomatic or pre-symptomatic patients may have similar viral loads and shedding compared to those who are symptomatic [15, 62, 63] , the panel agreed that it is reasonable to apply test accuracy data based on symptomatic patients to the asymptomatic populations. Hence, it was essential to determine the pre-test probability or prevalence of COVID-19 in the asymptomatic groups.

We assessed studies that reported the prevalence of COVID-19 among asymptomatic individuals in household clusters [15, 17, 19] , a nursing home outbreak [14] , active surveillance of passengers quarantined on a cruise ship or passengers of repatriation flights [18] , hospital employees with close contact to COVID-19 positive patients [13] , and customers and employees of a restaurant that had a COVID-19 outbreak [16] . Overall, prevalence ranged from 10 to 50% in settings where substantial transmission was suspected prior to testing. Summary statistics for single versus repeated testing are shown in Table 8 and Supplement H. We acknowledge that information on individual exposure was limited in the evidence base. All these limitations led to very low certainty in the evidence overall.

Testing asymptomatic individuals who have been exposed, or suspected to have been exposed, allows for isolation for those who are positive. Whether in an institutional cluster or a wider community outbreak, isolation will help reduce further transmission. There is potential harm in a false negative NAAT result collected from an exposed individual who is A c c e p t e d M a n u s c r i p t actually infected; these individuals may incorrectly consider themselves non-infected, and unknowingly expose others to SARS-CoV-2 as a result. Given the lack of evidence, a negative test post-exposure does not mean quarantine can be discontinued. Some individuals may still be in the incubation phase, subsequently develop active viral shedding, and incorrectly consider themselves non-infected. As a result, a negative post-exposure test cannot necessarily be used to avoid quarantine. A positive result, however, would reinforce the importance of isolation as well as inform contact tracing, cohorting, or other mitigation strategies.

Additional considerations: Diagnostic test performance in asymptomatic individuals has not been established. Assuming an overall test sensitivity between 75%-95% [35, 36, [38] [39] [40] 44] , false negative test results are expected. There is also cost to testing asymptomatic exposed individuals; since quarantine may still be indicated regardless of test results, such testing may add cost without changing practice. Data are limited to define definitions of close contact. Risk stratification of a given exposure can be made in consultation with public health authorities. In addition, the CDC has published guidance on defining healthcare exposures and categorizing exposure risks [64] .The ideal time to test an asymptomatic contact of a known or suspected COVID-19 case is also unknown. Timing also becomes complicated for household contacts with ongoing exposure. The average incubation period for SARS-CoV2 has been determined to be five days [65] . Thus, 5-7 days following exposure may be a reasonable time frame to consider post-exposure testing. In addition, data to inform the definition of a significant exposure or close contact are limited. Considerations when assessing the risk of a known contact include the duration of exposure and the clinical symptoms (e.g., cough) of the person with COVID-19.

with known or suspected exposures should be coordinated with local public health officials.

This indication for testing is especially important in situations where knowledge of asymptomatic or pre-symptomatic infection is essential for determining medical follow-up, defining risks for other vulnerable individuals in the household, congregate setting or hospital.

Special consideration should also be given to healthcare personnel exposed without A c c e p t e d M a n u s c r i p t appropriate PPE in healthcare settings. Definitions of appropriate PPE can be found on the CDC website [66] .

Comparative studies (preferably randomized controlled trials) along with cost-effectiveness analyses of testing strategies in asymptomatic populations are needed. Studies on the ideal time and collection method to test asymptomatic individuals who have been exposed to COVID-19 should be performed. In addition, what constitutes an exposure that would justify testing requires further research. Whether early diagnosis of COVID-19 might provide an opportunity to intervene therapeutically and change the ultimate course of infection (i.e., prevent severe pneumonia) is unknown. If this is shown to be the case, the opportunity for therapeutic intervention might justify screening exposed individuals. This table is based on applying the sensitivity and specificity estimates to calculate True and false positives and negatives in a hypothetical population of 1000 individuals a. Reference standard considered to be nasopharyngeal specimen RT-PCR. b. Studies report test accuracy results but do not report on patient-important outcomes based on these results. c. A small number of patients included. d. We assessed studies that reported the prevalence of COVID-19 among asymptomatic individuals who were exposed to COVID-19 and determined that the prevalence may range from 10% to 50% based on household clusters, nursing home outbreak, active surveillance of passengers quarantined on a cruise ship or passengers of repatriation flights, hospital employees with close contact with COVID-19 positive patients and customers and employees of a restaurant that had a COVID-19 outbreak. e. Certainty of evidence (CoE) 

 Asymptomatic individuals are defined as those with no symptoms or signs of COVID-19.

 A high prevalence of COVID-19 in the community was considered communities with a prevalence of 10%.

A c c e p t e d M a n u s c r i p t  The decision to test asymptomatic patients (including when the prevalence is between 2 and 9%) will be dependent on the availability of testing resources.

We did not identify any studies that directly assessed a strategy of nucleic acid testing for SARS-CoV-2 versus no testing before hospitalization for non-COVID-19 related reasons. We also did not identify test accuracy studies directly assessing the performance of SARS-CoV-2 viral RNA tests in asymptomatic individuals. However, based on existing evidence suggesting that asymptomatic or pre-symptomatic patients may have similar virus loads and shedding as those who are symptomatic [62, 63] , the panel agreed to infer test accuracy for asymptomatic populations before being hospitalized.

It was also essential to determine the pre-test probability or prevalence of the disease in asymptomatic patients admitted to the hospital. We assessed studies that reported prevalence 

 This recommendation defines immunosuppressive procedures as cytotoxic chemotherapy, solid organ or stem cell transplantation, long acting biologic therapy, cellular immunotherapy, or high-dose corticosteroids.

 Testing should ideally be performed as close to the planned treatment/procedure as possible (e.g. within 48-72 hours).

 Many of these patients require frequent, repeated or prolonged visits to receive treatment.

 This recommendation does not address risks or strategies to deal with SARS-CoV-2 transmission in outpatient settings such as infusion centers.

We did not identify any studies that directly assessed a strategy of testing for SARS-CoV-2 versus no testing of asymptomatic individuals before receiving chemotherapy or transplantation. In addition, we were unable to evaluate the risks of delaying necessary treatments or transplants if testing was not available and quarantine/delay of treatment was then required. We also did not identify any test accuracy studies directly assessing the performance of NAAT in asymptomatic individuals. Based on existing evidence supporting that asymptomatic or pre-symptomatic patients may have similar virus loads and A c c e p t e d M a n u s c r i p t shedding as those who are symptomatic [62, 63] , the panel agreed that test accuracy data from symptomatic patients would apply to asymptomatic populations being hospitalized.

It was essential to determine the pre-test probability or prevalence of COVID-19 in asymptomatic patients who will be receiving chemotherapy. We assessed studies that evaluated prevalence of COVID-19 among asymptomatic individuals and patients with cancer to estimate prevalence a between <1 to 10%. We identified three studies reporting data on the prevalence of cancer among COVID-19 patients and the percentage of complications (e.g., ICU admission, death) among these patients. Liang et al [67] showed that the prevalence of cancer among COVID-19 patients to be 1%, which was higher compared to their general population (0.2%). Yu et al [21] showed the prevalence of COVID-19 among patients admitted to the radiation and medical oncology floor to be 0.8%. Lastly, a systematic review conducted by Desai et al. (2020) [68] showed the pooled prevalence of cancer among COVID-19 cases to be 2-3%.

The overall certainty of the evidence about testing effects in immunocompromised individuals was very low due to extremely limited data in this population.

The panel determined that a maximum threshold of <2-5 missed cases per 1000 would be acceptable. Not testing individuals regardless of low versus high prevalence areas would lead to higher numbers of missed cases which the panel considered to exceed the acceptable threshold. The threshold was set very low due to concern about catastrophic outcomes in this population.

Although data is limited, there are reports documenting outbreaks of respiratory viruses in hospitalized immunocompromised hosts [69] . In addition, increased risks of severe adverse respiratory virus-related outcomes in this population are documented [70] . for false negative test results, so caution should be exercised by those who will be in close contact with/exposed to the upper respiratory tract (e.g., anesthesia personnel, ENT procedures).

The decision to test asymptomatic patients will be dependent on the availability of testing resources. 

 The panel defined time-sensitive procedures as medically necessary procedures that need to be done within three months.

 Procedures considered to be aerosol generating are listed in Table 9 .  Decisions about PPE will be dependent on test results because of limited availability of PPE.

However, there is a risk for false negative test results, so caution should be exercised for those who will be in close contact with/exposed to the patient's airways.

 Procedures considered to be aerosol generating are listed in Table 9 .

 The decision to test asymptomatic patients will be dependent on the availability of testing resources.

 This recommendation does not address the need for repeat testing if patients are required to undergo multiple procedures over time.

The panel did not identify any studies that directly assessed a strategy of testing for SARS-CoV-2 versus no testing of asymptomatic individuals before undergoing major surgery or aerosol generating procedures (AGPs). The panel also did not identify test accuracy studies directly assessing the performance of SARS-CoV-2 NAATs in asymptomatic individuals. However, based on existing evidence supporting that asymptomatic or presymptomatic patients may have similar viral loads and shedding as those who are symptomatic, the panel agreed that test accuracy data from symptomatic patients could be applied to asymptomatic populations before surgery.

It was essential to determine the pre-test probability or prevalence of disease in the asymptomatic patients who will undergo surgery. We assessed studies that evaluated the A c c e p t e d M a n u s c r i p t prevalence of COVID-19 among asymptomatic individuals and determined that the range of prevalence would be between <1 to 10% based on assessing rates of infection in asymptomatic individuals in the general population in low prevalence and in "hotspot" areas [8, 20, 21] . The panel recommendation was based on emphasizing the importance of preventing infection in healthcare providers during major time-sensitive surgeries and AGPs. In addition, the limited data showing poor outcomes in COVID-19 positive patients undergoing a major surgical procedure requiring intubation informed decisions to reduce this risk for asymptomatic patients [71] . There are no data that assess the outcome of AGPs in SARS-CoV-2 positive patients.

The benefit of suggesting testing for SARS-CoV-2 in asymptomatic patients undergoing major time-sensitive surgery is that it allows for the identification of infected patients before the procedure; thus allowing surgery to delayed based on the limited data suggesting that patients testing positive may have poor outcomes [71] . This approach also has the potential to inform healthcare workers in terms of PPE use, particularly in areas where PPE is limited. Of note, there is very low certainty evidence from retrospective case series suggesting poor outcomes of time-sensitive surgeries for those with COVID-19. The surgeries included were variable in complexity and it was not clear if the poor outcomes came mostly from major or minor surgeries. However, it is plausible that poor outcomes were driven by the major surgeries.

A potential harm of testing of immunocompetent, asymptomatic patients before a major surgery or AGP is depletion of testing supplies and the diversion of all associated resources away from symptomatic patients. An additional harm of testing is related to the sensitivity of the NAATs for SARS-CoV-2, which will not detect all asymptomatic patients with COVID-19

infection. Therefore, some patients may be missed and healthcare workers at high risk could be exposed. Thus, the panel suggests that healthcare workers at the highest risk during surgical procedures (e.g., those performing intubation or ENT procedures) consider wearing PPE at all times, regardless of test results. This would be especially important in high prevalence areas A c c e p t e d M a n u s c r i p t (i.e., "hotspots"). An additional harm is that false positive tests for SARS-CoV-2 may unnecessarily delay a major time-sensitive surgery.

There is no standard definition of what constitutes a major surgery.

In general, the panel in consultation with surgical colleagues, agreed that major surgeries would be defined as more complicated and/or prolonged surgeries that require general anesthesia and intubation (which is an AGP). Additionally, time-sensitive surgeries/procedures were defined as those for which a delay greater than 3 months would negatively affect outcomes. 

In addition to the clinical questions addressed above, there is significant interest in the use of serologic SARS-CoV-2 tests both for diagnosis and public health surveillance. At the time of our literature review, however, additional data were needed to formulate recommendations. Important areas that need to be addressed include assessment of the sensitivity and specificity of commercial antibody tests, determinations of protective immunity and measures of antibody responses over time. Whether seroconversion can inform return to work or hospital staffing policies needs to be assessed. In the absence of evidence to guide the use of SARS-CoV-2 serologic testing, the IDSA Diagnostics Committee published a serology primer for clinicians which highlights potential benefits, limitations and unmet research needs [73] .

Antigen detection tests may be on the horizon. How these will compare with NAAT needs to be defined. In addition, current NAATs detect viral RNA but cannot distinguish infectious from noninfectious virus. This determination requires viral culture, which is not routinely performed in clinical laboratories for biosafety reasons and is likely less sensitive than NAAT. It will be important to define whether individuals who remain nucleic acid positive after symptom resolution, and potentially seroconversion, are infectious to others because this will have important ramifications for quarantine and reducing restrictions around social distancing. Some "test of cure" algorithms require two sequential negative NAATs, yet some studies describe A c c e p t e d M a n u s c r i p t prolonged RNA positivity. Future studies are required to determine the significance of nucleic acid or antigen shedding after clinical recovery.

Molecular tests designed to detect SARS-CoV-2 nucleic acids are essential both for confirming COVID-19 diagnosis and for public health responses aimed at curbing the pandemic. Several countries have deployed NAAT on a massive scale as the cornerstone of a successful containment strategy. Although the U.S. was hampered by limited test availability early in the outbreak, there are now more than 25 different commercially available SARS-CoV-2 assays and multiple clinical laboratories have developed their own laboratory-developed tests. Aggressive efforts are underway to assure access to testing, but regional differences in availability persist.

Individual medical centers and clinics are likely to have different testing capacity as well.

Furthermore, which test a laboratory or facility chooses to perform will vary based on the resources of a given setting (e.g., near-patient versus high complexity laboratory) and turnaround-time to result requirements (i.e., rapid versus standard).

The primary recommendations set forth in this guideline assume that SARS-CoV-2 testing is available to healthcare providers on the front lines. However, the panel also recognized that resources may vary, and contingency recommendations were developed for situations where NAAT supplies or PPE are limited. Individual institutions will need to prioritize testing based on available resources and unique patient populations. Testing for symptomatic patients should be prioritized. When testing capacity for symptomatic individuals is considered sufficiently robust, testing for asymptomatic individuals should be considered. There will undoubtedly be challenges prioritizing and implementing testing strategies for asymptomatic groups. The strongest recommendation for testing in asymptomatic individuals in this guideline pertains to immunocompromised patients being admitted to the hospital or in advance of immunosuppressive procedures.

A c c e p t e d M a n u s c r i p t Molecular tests have been central to our understanding of SARS-CoV-2. However, much about the biology of SARS-CoV-2 remains unknown. Early experience suggests that SARS-CoV-2 is detectable in the upper respiratory tract, with peak levels typically measurable during the first week of symptoms [48, 62, 74] . RNA detection rates, however, appear to vary from patient to patient and change over time. Some patients with pneumonia, for example, have negative upper respiratory tract samples but positive lower airway samples [35, 75] . Much less it known about the frequency of viral detection in asymptomatic individuals, although the concentration of detectable virus in some people with infection may be quite high [62, 63] . A better understanding of the spectrum of viral load kinetics over time at different anatomic sites is needed to inform decisions about the optimal testing strategies, including when and how to repeat if the first test is negative. Like other respiratory viruses, shedding of viral RNA in respiratory secretions may persist beyond resolution of symptoms and seroconversion [76] .

Whether such patients remain infectious to others is uncertain and this is an important area for future study.

The clinical performance of commercially available SARS-CoV-2 molecular diagnostic tests has not yet been defined and will depend in large part on the biology of the virus. Typically, when tests for the detection of viral respiratory pathogens are submitted to the FDA, both analytical and clinical performance data are provided. Under EUA, however, only analytical data are required. Diagnostic developers may test contrived specimens, by spiking viral RNA or inactivated virus into the desired matrix, rather than using real clinical specimens collected from patients with COVID-19. Thirty contrived positive and 30 negative specimens tested, with 95% sensitivity and 100% specificity required for EUA. Therefore, while we have information regarding the limit of detection of the test and evidence (both in vitro and in silico studies) that the primer design is specific for SARS-CoV-2, there is no information on how each test performs clinically at the time the EUA is issued. Clinical laboratories using commercial EUA tests must verify analytic test performance at some level in their own hands, including evaluation of different specimen types and collection methods (e.g., swab types and transport media).

A c c e p t e d M a n u s c r i p t Clinical performance metrics include sensitivity, which is the ability of the test to correctly identify those with infection, and specificity, the ability of the test to correctly identify those without the disease. In practice, the positive and negative predictive values of the test are also essential for interpreting test results. Estimations of community prevalence and patient pre-test probability combined with knowledge of test sensitivity and specificity are essential for determining the likelihood that an individual has COVID-19. In practice, however, the true prevalence of COVID-19 in the community may not be well-defined and may be underestimated when test availability is limited. In addition, while SARS-CoV-2 RNA tests are highly specific, their respective sensitivities are likely to vary. Recognizing these complexities, estimates of prevalence/pre-test probability and assay sensitivity were varied in our analyses based on the available literature in an attempt to mirror what may be encountered in clinical practice. Going forward, robust prevalence studies are needed. Clinical test performance should also ideally be determined in prospective multicenter studies using a well-defined reference standard as the benchmark for test comparisons. Table 2 outlines the type of clinical studies needed to address the most pressing COVID-19 diagnostic knowledge gaps.

One of the most important problems with current COVID-19 diagnostic literature is the lack of a standard definition to define COVID-19. The studies included in the systematic reviews that informed this guideline used variable case definitions and many classified disease based in part on the results of the index test under investigation. Incorporation of the investigational index test into the diagnostic "gold" standard falsely inflates sensitivity and specificity estimates (i.e. incorporation bias). Table 10 outlines options for defining a confirmed COVID-19 case in diagnostic trials. It is recognized that not all individuals with COVID-19 will have detectable SARS-CoV-2 nucleic acid. Therefore, a "probable" case definition is also proposed. False negative NAAT results may be due to a variety of factors, including assay limit of detection, anatomic location and adequacy of specimen collection, timing of sampling relative to symptom onset, and underlying biology of disease. To fully understand SARS-CoV-2 viral dynamics, studies need to be designed to obtain specimens from multiple sites, ideally from the same A c c e p t e d M a n u s c r i p t patient at the same time. In addition, information on the duration of symptoms (if present), assessment of potential exposures and longitudinal follow-up of outcomes will be essential to define optimal diagnostic test strategies across a variety of patient populations. Nucleic acid sequencing matches SARS-CoV-2 reference sequences

Positive results from at least 2 different NAATs (one of the two may be the index test) OPTION 3

Dual positive results from a single NAAT targeting 2 different genes (cannot be the index test)

Compatible clinical signs and symptoms in a setting with known community transmission, negative reference NAAT and documented SARS-CoV-2 seroconversion.

Compatible clinical signs and symptoms in a setting with known community transmission, negative reference NAAT and positive index test from two different anatomic sites.

Compatible clinical signs and symptoms in a setting with known community transmission, negative reference NAAT and positive SARS-CoV-2-specific serology.

The guideline panel used a methodologically rigorous process to critically appraise the available diagnostic literature and formulate SARS-CoV-2 testing recommendations. The quality of existing evidence, however, was limited and not all of the data used to inform these recommendations had undergone peer-review. Based on low certainty evidence, the IDSA panel recommends nucleic acid testing for all symptomatic individuals suspected of having COVID-19. In addition, testing selected asymptomatic individuals is suggested when the results will have significant impact on isolation/quarantine/PPE usage, dictate eligibility for surgery, or inform use of immunosuppressive therapy. Ultimately, institutional resources will dictate test 

This project was funded by IDSA.

The following list displays what has been reported to the IDSA. To provide thorough transparency, the IDSA requires full disclosure of all relationships, regardless of relevancy to the guideline topic. Evaluation of such relationships as potential conflicts of interest is determined by a review process which includes assessment by the Board of Directors liaison to the Standards and Practice Guideline Committee and, if necessary, the Conflicts of Interest (COI) and Ethics Committee. The assessment of disclosed relationships for possible COI is based on the relative weight of the financial relationship (i.e., monetary amount) and the relevance of the relationship (i.e., the degree to which an association might reasonably be interpreted by an independent observer as related to the topic or recommendation of consideration). The reader of these guidelines should be mindful of this when the list of disclosures is reviewed. K.H. serves as an advisor for BioFire and Quideland and receives

Centers for Disease Control and Prevention. Health care Infection Prevention and Control FAQs for COVID-19

Prevention Strategies for Seasonal Influenza in Health care Settings

Advice on the use of masks in the context of COVID-19

Epidemic-and pandemic-prone acute respiratory diseases -Infection prevention and control in health care

Day Zero, Visby, and Chroma Code; receives research funding from ArcBio and Hologic; and has served as an advisor for Luminex. C.A. receives royalties from UpToDate and receives research funding from Merck

Entasis Pharmaceuticals and the National Institute of Allergy and Infectious Diseases (NIAID)/NIH. J.E. serves as a consultant for Sanofi Pasteur; an advisor/consultant for Meissa Vaccines; and receives research funding from the Centers for

serves as an advisor for Sanofi, Seqirus, and Medicago; has served as an advisor for Pfizer, Sunovion, and MD Brief; and receives research funding from the Canadian Institutes of Health Research and the Medical Research Council (United Kingdom). R.P. receives grants from Shionogi

the Infectious Diseases Society of America (IDSA), the National Board of Medical Examiners, UpToDate, and the Infectious Disease Board Review Course; Y.F.Y. receives honoraria for evidence reviews and teaching from the Evidence Foundation, honoraria for evidence reviews for the American Gastroenterological Association, and serves as a Director for the Evidence Foundation and for the U.S

A Novel Coronavirus from Patients with Pneumonia in China

Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding

The species Severe acute respiratory syndromerelated coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2

Novel coronavirus-2019 events-as-they happen

Adminsitration FaD

Development of rapid guidelines: 3. GIN-McMaster Guideline Development Checklist extension for rapid recommendations

GRADE guidelines: 2. Framing the question and deciding on important outcomes

Spread of SARS-CoV-2 in the Icelandic Population

Preliminary Results of Initial Testing for Coronavirus (COVID-19) in the Emergency Department. The western journal of emergency medicine

Optimizing diagnostic strategy for novel coronavirus pneumonia, a multi-center study in Eastern China

Positive rate of RT-PCR detection of SARS-CoV-2 infection in 4880 cases from one hospital in

SARS-CoV-2 infection in Health Care Workers

Asymptomatic and Presymptomatic SARS-CoV-2 Infections in Residents of a Long-Term Care Skilled Nursing Facility -King County

Clinical Characteristics of 24 Asymptomatic Infections with COVID-19 Screened among Close Contacts in Nanjing

COVID-19 Outbreak Associated with Air Conditioning in Restaurant

Epidemiology and Transmission of COVID-19 in Shenzhen China: Analysis of 391 cases and 1,286 of their close contacts

Estimated effectiveness of symptom and risk screening to prevent the spread of COVID-19

Presymptomatic Transmission of SARS-CoV-2 -Singapore

Universal Screening for SARS-CoV-2 in Women Admitted for Delivery

SARS-CoV-2 transmission in cancer patients of a tertiary hospital in Wuhan

QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies

GRADE guidelines: 21 part 1. Study design, risk of bias, and indirectness in rating the certainty across a body of evidence for test accuracy

GRADE guidelines: 21 part 2. Test accuracy: inconsistency, imprecision, publication bias, and other domains for rating the certainty of evidence and presenting it in evidence profiles and summary of findings tables

Available from gradepro.org

World Health Organization recommendations are often strong based on low confidence in effect estimates

Guideline panels should not GRADE good practice statements

Differential diagnosis of illness in patients under investigation for the novel coronavirus (SARS-CoV-2)

Featuring COVID-19 cases via screening symptomatic patients with epidemiologic link during flu season in a medical center of central Taiwan

Screening and managing of suspected or confirmed novel coronavirus (COVID-19) patients: experiences from a tertiary hospital outside Hubei province

Centers for Disease Control and Prevention. Priorities for testing patients with suspected COVID-19 infection

Comparison of throat swabs and sputum specimens for viral nucleic acid detection in 52 cases of novel coronavirus (SARS-Cov-2) infected pneumonia

Detecting SARS-CoV-2 at point of care: Preliminary data comparing Loop-mediated isothermal amplification (LAMP) to

Detection of SARS-CoV-2 in Different Types of Clinical Specimens

Evaluating the accuracy of different respiratory specimens in the laboratory diagnosis and monitoring the viral shedding of 2019-nCoV infections

Evaluation the auxiliary diagnosis value of antibodies assays for detection of novel coronavirus (SARS-Cov-2) causing an outbreak of pneumonia

Nasal swab sampling for SARS-CoV-2: A convenient alternative in time of nasopharyngeal swab shortage

Patient-collected tongue, nasal, and mid-turbinate swabs for SARS-CoV-2 yield equivalent sensitivity to health care worker collected nasopharyngeal swabs

Quantitative Detection and Viral Load Analysis of SARS-CoV-2 in Infected Patients

Saliva as a non-invasive specimen for detection of SARS-CoV-2

SARS-CoV-2 Viral Load in Upper Respiratory Specimens of Infected Patients

Self-Collected Oral Fluid and Nasal Swabs Demonstrate Comparable Sensitivity to Clinician Collected Nasopharyngeal Swabs for Covid-19 Detection

Self-collection: an appropriate alternative during the SARS-CoV-2 pandemic

Viral Kinetics and Antibody Responses in Patients with

Self-collected compared with professional-collected swabbing in the diagnosis of influenza in symptomatic individuals: A meta-analysis and assessment of validity

Viral Load Kinetics of SARS-CoV-2 Infection in First Two Patients in Korea

Virological assessment of hospitalized patients with COVID-2019

Evaluating the accuracy of different respiratory specimens in the laboratory diagnosis and monitoring the viral shedding of 2019-nCoV infections

Evaluation the auxiliary diagnosis value of antibodies assays for detection of novel coronavirus (SARS-Cov-2) causing an outbreak of pneumonia (COVID-19)

Quantitative Detection and Viral Load Analysis of SARS-CoV-2 in Infected Patients

Viral Kinetics and Antibody Responses in Patients with

Comparison of throat swabs and sputum specimens for viral nucleic acid detection in 52 cases of novel coronavirus (SARS-Cov-2) infected pneumonia

Analysis of factors associated early diagnosis in coronavirus disease

Clinical features and outcomes of 197 adult discharged patients with COVID-19 in Yichang

Rapid colorimetric detection of COVID-19 coronavirus using a reverse tran-scriptional loop-mediated isothermal amplification (RT-LAMP) diagnostic plat-form

Rapid Detection of SARS-CoV-2 Using Reverse transcription RT-LAMP method

Rapid Molecular Detection of SARS-CoV-2 (COVID-19) Virus RNA Using Colorimetric LAMP

Reverse transcription loop-mediated isothermal amplification combined with nanoparticles-based biosensor for diagnosis of

Comparison of Abbott ID Now and Abbott m2000 methods for the detection of SARS-CoV-2 from nasopharyngeal and nasal swabs from symptomatic patients

Comparison of Abbott ID Now, Diasorin Simplexa, and CDC FDA EUA methods for the detection of SARS-CoV-2 from nasopharyngeal and nasal swabs from individuals diagnosed with

SARS-CoV-2 Viral Load in Upper Respiratory Specimens of Infected Patients

Cluster of coronavirus disease 2019 (Covid-19) in the French Alps

Guidance for Risk Assessment and Public Health Management of Healthcare Personnel with Potential Exposure in a Healthcare Setting to Patients with Coronavirus Disease

The Incubation Period of Coronavirus Disease 2019 (COVID-19) From Publicly Reported Confirmed Cases: Estimation and Application

Centers for Disease Control and Prevention. Infection Control Guidance for Healthcare Professionals about Coronavirus (COVID-19). Available at

Cancer patients in SARS-CoV-2 infection: a nationwide analysis in China

COVID-19 and Cancer: Lessons From a Pooled Meta-Analysis

Respiratory viruses in transplant recipients: more than just a cold. Clinical syndromes and infection prevention principles

Respiratory Virus Infections in Hematopoietic Cell Transplant Recipients

Clinical characteristics and outcomes of patients undergoing surgeries during the incubation period of COVID-19 infection

IDSA COVID-19 Antibosy Testing Primer

Viral load of SARS-CoV-2 in clinical samples

Negative Nasopharyngeal and Oropharyngeal Swabs Do Not Rule Out COVID-19

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

A c c e p t e d M a n u s c r i p t