key: cord-0726453-p1zy0fhq
authors: Carrara, Elena; Ong, David S.Y.; Hussein, Khetam; Keske, Siran; Johansson, Anders F.; Presterl, Elisabeth; Tsioutis, Constantinos; Tschudin-Sutter, Sarah; Tacconelli, Evelina
title: ESCMID guidelines on testing for SARS-CoV-2 in asymptomatic individuals to prevent transmission in the healthcare setting
date: 2022-02-03
journal: Clin Microbiol Infect
DOI: 10.1016/j.cmi.2022.01.007
sha: 54b48ae96d3a46bd3f7fe2fba04011d06a85f180
doc_id: 726453
cord_uid: p1zy0fhq

SCOPE: This guideline addresses the indications for direct testing of SARS-CoV-2 in asymptomatic individuals in healthcare facilities with the aim to prevent SARS-CoV-2 transmissions in these settings. The benefit of testing asymptomatic individuals to create a safe environment for patients and healthcare workers must be weighed against potential unintended consequences including delaying necessary treatments due to false positive results and lower quality of care due to strict isolation measures. METHODS: A total of 9 PICOs on the topic of testing asymptomatic individuals was selected by the panel members. Subsequently, a literature search for existing guidelines and systematic reviews was performed on Pubmed, Epistemonikos, and RecMap using relevant filters available in each database. Data about article/recommendation type, setting, target population, intervention, and quality of the evidence were extracted. Credibility of the systematic reviews were evaluated using the AMSTAR-tool, and level of agreement with available recommendation was evaluated with the AGREE II-score. Because the evidence available from systematic reviews was deemed insufficiently updated to formulate relevant recommendations, an additional search targeting relevant guidance documents from major public health institutions and original studies was performed. Provisional recommendations were discussed via web conferences until agreement was reached and final recommendations was formulated according to the GRADE approach. Questions addressed by the guideline and recommendations: Recommendations were formulated regarding systematic testing in asymptomatic individuals upon admission to a healthcare setting, during hospital stay, prior to elective procedures, and prior to scheduled non-surgical procedures. Moreover, recommendations regarding testing of asymptomatic visitors, personal caregivers and healthcare workers in healthcare facilities were presented. Also, recommendations were given on contact tracing in asymptomatic patients or healthcare workers, and the possibility of a negative screening test to shorten the quarantine period. Furthermore, if applicable, recommendations were specified to transmission rate and vaccination coverage.

Transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the healthcare setting can have devastating consequences for both patients and healthcare workers (HCWs) (1) . Additional infection prevention and control (IPC) practices have been universally recommended along with standard measures to prevent the spread of SARS-CoV-2 in both acute care settings and long-term care facilities. Appropriate use of personal protective equipment (PPE), environmental cleaning, adequate room ventilation, social distancing, appropriate patient placement, controlled access to the facilities, and a functioning testing strategy are all essential components of bundled interventions aimed at controlling healthcare transmission of SARS-CoV-2.

This guideline addresses the indications for direct testing of SARS-CoV-2 in asymptomatic individuals in acute care settings and long-term care facilities (LTCFs) with the aim to prevent transmission. This guideline does not include recommendations for the use of different testing methodologies for diagnosing SARS-CoV-2, which is addressed by an ESCMID dedicated guidance document (currently under development). Unless differently specified, positivity of testing refers to molecular detection of SARS-CoV-2 specific RNA in nasopharyngeal swabs.

Although several documents provide recommendations for IPC measures to be implemented in hospitals and the community to reduce SARS-CoV-2 transmission (2-4), the present guidance is the first to specifically address management of testing procedures in asymptomatic individuals accessing healthcare settings (including LTCFs).

The World Health Organization gives a strong recommendation to screen all patients for signs and symptoms at the first point of contact with the healthcare system in order to identify individuals with suspected or confirmed coronavirus disease 2019 (COVID-19) (5) . However, according to estimates from the US Centers for Disease Control and Prevention, 24% of infections are transmitted by the 30% of individuals who will never develop symptoms, and 35% are transmitted during the pre-J o u r n a l P r e -p r o o f symptomatic phase of the infection (6) . Thus, testing policies in asymptomatic individuals may play a key role in controlling transmission, in addition to only screening when there are signs and symptoms suspected for SARS-CoV-2 infection.

The present guidelines have attempted to balance the potential benefit of testing asymptomatic individuals in terms of creating a safe environment for patients and HCWs with potential unintended consequences such as the risk of delaying necessary treatments due to false positive results and the risk of providing lower quality care due to strict isolation measures. Even though there is very little to no evidence on the topic, the panel tried to address the issue on how testing policies should be adapted to different epidemiological settings and/or special patient-populations. The definitions adopted to define these specific scenarios are detailed in Box 1.

The general principles and methodology applied have been described in the first paper of the ESCMID guidelines for COVID-19 related clinical topics (7) . A total of nine PICOs (population, intervention, comparison, outcome) on the topic of testing asymptomatic individuals in the healthcare setting were selected by the panel members by open discussion.

On May 7 th , 2021, a first broad search for systematic reviews was performed on Pubmed, Epistemonikos DB, and RecMap using relevant filters available in each database. A first screening of abstracts and titles was performed by individual panelists, and a second panelist verified a randomly selected set of articles to ensure consistency. Two reviewers independently assessed the full text of eligible papers for inclusion.

A second systematic search targeting recommendations was conducted on December 27 th , 2021 in order to include the must updated versions in the guidelines development.

J o u r n a l P r e -p r o o f Systematic reviews assessing the efficacy of SARS-CoV-2 laboratory screenings in asymptomatic patients and HCWs for reducing transmission in the healthcare setting were included.

Non-systematic reviews, reviews in non-English language, systematic reviews dealing specifically with test accuracy, screening in symptomatic individuals, clinical issues, and public health interventions were excluded. There was no restriction on time of publication.

A single reviewer extracted data and recommendations from included papers to a pre-defined excel file. A second reviewer was selected to double-check the data extracted for each paper and discuss any uncertainties. Relevant data about article/recommendation type, setting, target population, intervention, and quality of the evidence were extracted. Credibility of the systematic review was evaluated using the AMSTAR tool (8) , and level of agreement with available recommendation was evaluated with the AGREE II score (9) . If recommendations were based on evidence and not only expert opinion, the evidence to which the recommendations refer to was also extracted and used in the process of adaptation (rather than accepting the individual recommendations).

After data extraction, each PICO was matched with available recommendations and systematic reviews. Since the evidence available from systematic reviews was deemed insufficiently updated to formulate relevant recommendations, a more extensive search targeting relevant guidance documents from major public health institutions and primary studies relative to specific emergent topics such as vaccination and variants of concern was performed.

A narrative synthesis of the evidence was drafted, and provisional recommendations made by each panelist were then discussed via web conferences to reach agreement on final recommendations according to the GRADE approach (10).

A final set of seven systematic reviews and 15 recommendations (from nine guidance documents) were included in the systematic process. After screening of guidance documents, an additional 14 documents and one guideline document (with 9 recommendations) were considered for the panel discussion. A schematic representation of the selection process is shown in Figure 1 .

The overall quality of the evidence was deemed as low to very low. Only two systematic reviews were rated as 'high quality' (i.e., the panel had high confidence in the results) on the AMSTAR scale, and the remaining five were all judged to be of low to critically low quality (i.e., the panel had scarce confidence in the results). Only eight of the 23 included recommendations were formulated following the GRADE approach. The median and mean AGREE score for the recommendations were 55.3% (IQR 50.2%-70.2%) and 59.2% (+/-11.2%), respectively. Tables summarizing included documents and quality assessment are available as supplementary material (Tables S2-S3 ).

Evidence summary: Evidence was extracted from one systematic review (11) and the guidelines from the Infectious Diseases Society of America (IDSA) (12) , the WHO interim guidance on IPC for LTCFs in the context of COVID-19 (5). The systematic review included 61 studies; the data suggests that at least one-third of SARS-CoV-2 infections are asymptomatic and that nearly three-quarters of individuals who test SARS-CoV-2 positive and have no symptoms at the time of testing remain asymptomatic (11) . Overall, the proportion of asymptomatic carriers of SARS-CoV-2 has been estimated to range from 30% to 85% according to the setting and case mix; a clear understanding of the drivers of transmission is still lacking (11) . Several analyses have reported a very low level of detection (<1%) of asymptomatic patients infected by SARS-CoV-2 at hospital admission (13) . The number of patients to be screened to identify an asymptomatic carrier was estimated to be 425 in the first wave of the pandemic and 1218 in a low incidence phase (14) . According to the IDSA guidelines, J o u r n a l P r e -p r o o f testing of asymptomatic individuals should not be universally recommended when the community transmission rate is low (2). An exception to this recommendation is immunocompromised patients admitted to dedicated wards due to the higher risk of severe COVID-19 compared with the general population. Along the same lines, the WHO recommends testing all residents admitted to long-term care facilities (LTCFs) or after their transfer from other healthcare institutions. Following the CDC recommendation for nursing homes, the panel agreed that 48 hours within transfer might be an acceptable timeframe for testing (15).

Based on the evidence, the panel agreed that, except for these special populations, the efficacy of implementing systematic testing of asymptomatic patients at hospital admission is controversial within the setting of a low community transmission rate of SARS-CoV-2. Testing efficacy highly dependent on the diagnostic test used and brings into question the cost-benefit ratio of such an intervention in low community transmission settings. 

Evidence summary: No systematic review addressing this PICO question was retrieved. The IDSA guidelines (12) and the WHO interim guidance on IPC for LTCFs in the context of COVID-19 (5) were considered while formulating this recommendation, even though both documents addressed repeated testing only in specific contexts (ongoing healthcare transmission in LTCFs) or in specific populations (transplant recipients, patients requiring major surgery).

As for testing on hospital admission, the panel concluded that in-hospital transmission is very likely dependent on the level of community transmission, thus repetitive screening might help in reducing in-hospital spread of SARS-CoV-2. However, the risk of false positive results in settings with low transmission rates counterbalances the potential benefit of conducting systematic repetitive testing in the hospital setting. Additionally, the presence of other IPC measures (reduction of visitors, masking, high rate of vaccination, etc.) could also limit the utility of this measure. (18) . Based on such considerations, the CDC recommend considering pre-procedure screening by authorized nucleic acid or antigen detection assays to further reduce the risk for exposures in healthcare settings and to inform decisions about rescheduling elective procedures (19). In line with this, the IDSA suggests SARS-CoV-2 RNA testing in asymptomatic patients undergoing major surgery (classified as a conditional recommendation based on a very low certainty of evidence) with the aim of deferring non-emergency surgeries in patients testing positive for SARS-CoV-2 and tailoring decisions about PPE for aerosol generating procedures when access to PPE is limited, while pointing to the risk of false negative test results (2). These recommendations were made to prevent both infections of HCWs during surgery and to reduce the risk of adverse outcomes for asymptomatic patients. According to those recommendations testing should be performed as close to the scheduled surgery as possible (e.g., within 48-72 hours). (2). The potential risk of poor clinical outcomes has also resulted in the National Institutes of Health (NIH) recommendation to perform molecular diagnostic testing for SARS-CoV-2 prior to procedures that require anesthesia in patients with cancer (16) and has led to a multidisciplinary consensus statement recommending elective surgery not to be performed within seven weeks of a diagnosis of SARS-CoV-2 infection, unless the risks of deferring surgery outweigh the risk of postoperative morbidity and mortality (20) .

Despite the very low level of evidence, the panel agreed to recommend pre-operative testing of patients prior to elective surgery requiring anesthesia with the aim to prevent transmission in settings with high transmission and/or settings in which access to PPE is limited. The panel J o u r n a l P r e -p r o o f acknowledges the challenges around adherence to full PPE use during prolonged surgeries and the potentially heterogenous use of PPE, which would be in favor of a recommendation to perform testing independently of the local epidemiology. On the other hand, the panel agreed that HCWs should always consider patients as being potentially infected given the potential of screening tests to not detect SARS-CoV-2, especially if extended timeframes (i.e., more than 48 hours) are allowed between testing and surgery, as often is the case due to logistical issues.

 The panel suggests pre-operative testing of asymptomatic patients 48-72 hours prior to elective surgery requiring anesthesia to reduce exposure of HCWs in settings where there is a high transmission rate and/or low vaccination coverage rate and/or access to PPE is limited (conditional recommendation, QoE: very low).

 Pre-operative testing of patients prior to elective surgery requiring anesthesia might be considered in settings with a low transmission rate, high vaccination coverage, and proper access to PPE to identify asymptomatic SARS-CoV-2 infected patients who might be at increased risk of poor outcomes after surgery, independently from their vaccination status (good practice statement).

Evidence summary: No systematic review addressing testing of asymptomatic patients undergoing scheduled ambulatory care and/or invasive non-surgical procedures was retrieved from the initial search. Some recommendations on specific procedures were extracted from the CDC interim ICP recommendations in the healthcare setting (17).

This group of patients can be highly heterogeneous, encompassing patients scheduled for aerosol generating non-surgical procedures (21) , as well as those scheduled for (recurrent) medical consultation and/or treatment for underlying diseases, e.g. cancer, hematological diseases, organ J o u r n a l P r e -p r o o f transplant, chronic dialysis or other chronic diseases at a specialized healthcare facility. According to some case series and retrospective studies, testing can be considered for protecting vulnerable patients, e.g., cancer patients, patients from LTCFs or psychiatric institutions. Testing may be especially considered in institutions or situations where PPE is not available and/or wearing appropriate PPE for all procedures is not possible (22) (23) (24) (25) (26) . However, apart from these special situations, universal testing must be carefully balanced against its potential drawbacks, such as Evidence summary: The evidence was extracted from CDC Interim IPC Recommendations for HCWs to prevent SARS-CoV-2 spread in nursing homes (15) and from ECDC report for contact tracing (4) .

No systematic review on this topic was retrieved. The risk of transmission of SARS CoV-2 from an infected case to an individual mainly depends on the level of exposure risk. High and low risk exposure are usually defined based on the type (direct or indirect) and duration of contact, physical distance from the source, and area of exposure (closed or opened area). If the contact occurs in a healthcare setting, appropriate use of PPE in case of contact also affects the risk of transmission (4).

The decision of testing and applying IPC measures depends therefore on the level of exposure risk.

For high-risk exposure contacts, the CDC recommends implementing isolation in a separated room testing immediately (at least two days after the contact), and active close follow up for symptoms (28). Whenever possible, isolation of high-risk contacts in single rooms is preferred, but cohort isolation according to exposure time might also be considered if not enough single rooms are available. If the first test is negative, the appropriate time for re-testing is not clearly defined for this situation, although based on the evidence from contact tracing for HCWs, and the CDC suggests testing again on the 5-7th day of contact (17). Further comprehensive testing of all residents and staff weekly/bi-weekly depending on testing capacity is recommended (17). For low-risk exposure contacts, the ECDC suggests self-monitoring for development of symptoms, however if the population is vulnerable or transmission is likely to occur testing is recommended (4).

The CDC suggests testing residents of LTCFs who have had high-risk contact with a confirmed COVID-19 case regardless of vaccination status; testing is recommended immediately (at least two days after the contact), and if negative, re-testing at 5-7 days after exposure (15). 

Evidence summary: The evidence was extracted from two international guidelines that provide recommendations regarding cessation of a predefined quarantine period for asymptomatic patients J o u r n a l P r e -p r o o f who have been in contact with a SARS-CoV-2 positive case when they are screened and tested negative for SARS-CoV-2 (4, 29) . No systematic review addressing this topic was retrieved.

Although not specified for hospitalized patients, the CDC guidelines allow reduced duration of postexposure quarantine to seven days after last exposure when an individual remains asymptomatic and has a negative test (29). The specimen may be collected and tested within 48 hours before the time of planned quarantine discontinuation, but quarantine cannot be discontinued earlier than after Day 7.

The ECDC guidelines recommend that a negative RT-PCR test at day 10 can be used to discontinue quarantine earlier, but also recommends that the possibility for early release from quarantine be assessed on a case-by-case basis such as contacts in high-risk settings (4) test is possibly lowest about one week after exposure (30). Furthermore, multiple mathematical models show that appropriately timed testing can make shorter quarantines effective (31) (32) (33) . Earlier cessation of quarantine may reduce both costs and the burden on healthcare systems. In nonhealthcare settings, negative testing of quarantined student contacts of confirmed cases after 9 days did not result in missed COVID-19 cases that became apparent thereafter (34) . With the emergence of variants of concern and possibility of breakthrough infections in vaccinated individuals, testing should be considered in both vaccinated and unvaccinated individuals.

J o u r n a l P r e -p r o o f  The panel recommends that a negative PCR test in an asymptomatic individual at least 7 days after being exposed to a confirmed COVID-19 case can be used to shorten the quarantine period. (Strong recommendation, QoE: low).

Evidence summary: Evidence was extracted from the WHO interim guidance on recommendations for national SARS-CoV-2 testing strategies and diagnostic capacities (19), the WHO living guidance on COVID-19 clinical management (22) (23) (24) (25) . We did not identify any systematic review that directly assessed SARS-CoV-2 testing of visitors or personal caregivers in home-like settings and evidence was extracted from two systematic reviews evaluating indirect data from the general populations (11, 35) . The systematic review by Oran et al. found that the proportion of the general population who tested positive but had no symptoms at the time of testing ranged from 6.3% to 100%, with a median of 65.9% (IQR, 42.8% to 87.0%) (11). Sah et al. found that at the time of testing, 42.8% (95% prediction interval: 5.2 to 91.1%) of cases exhibited no symptoms (35) . According to both these systematic reviews, the proportion of new infections caused by asymptomatic persons remains uncertain.

Widespread testing of asymptomatic individuals in the community is not a currently recommended strategy by the WHO due to the significant costs and the lack of data on its operational effectiveness (19). The WHO recommends testing of asymptomatic individuals for specific groups only, including contacts of confirmed or probable COVID-19 cases and frequently exposed groups such as HCWs and those working at LTCFs (19). Potential harms of testing include inefficient use of testing capacity and false positive results potentially adversely affecting patient care, especially when using rapid point-of-care tests (36) . On the other hand, testing might contribute to create a safer environment, and could be considered as a strategy to attenuate restrictive policies, especially for patients' population who particularly suffer from isolation.

Based on the available indirect evidence, the panel agreed that the efficacy of systematic testing of asymptomatic visitors and caregivers at hospital visit remains highly controversial, especially in settings with a low prevalence of SARS-CoV-2. The panel also agreed that in specific settings with vulnerable patients, including those with a severely compromised immune system, testing visitors or caregivers might be considered. The panel acknowledged that visitor and personal caregiver settings and healthcare resources may be highly variable among countries and healthcare systems, implying that different choices will be appropriate for different settings; clinicians and local policy makers should thus be prepared to make a decision that is consistent with the setting.

 The panel suggests universal testing of asymptomatic visitors at first hospital visit and regularly thereafter (3-7 days) in special circumstances only, including when there is a high level of community transmission or low vaccination rate, especially in healthcare settings where vulnerable patients are admitted, independently from their vaccination status (conditional recommendation, QoE: very low).

Evidence summary: Evidence has been extracted from the WHO interim guidance on IPC for LTCFs in the context of COVID-19 (19), the CDC overview of testing for SARS-CoV-2 (COVID-19) (27), and from two systematic reviews (37, 38) . J o u r n a l P r e -p r o o f 9. Does testing asymptomatic HCWs who have been exposed to SARS-CoV-2 cases reduce transmission of SARS-CoV-2 in the healthcare setting compared to no testing?

Evidence summary: The evidence was extracted from the ECDC technical report on contact tracing, the WHO guidance on infection prevention in long-term care facilities, and two systematic review addressing universal screening (3, 4, 38, 39) . No systematic review specifically assessing the effectiveness of testing versus no testing of asymptomatic HCWs after high-risk exposure was retrieved from the initial search. The available guidelines, mainly based on expert opinion, agree in recommending immediate testing following high-risk contact with SARS-CoV-2 infected individuals to detect asymptomatic infection in HCWs employed in healthcare facilities (4) and nursing homes (3) . During the following 10 to 14 days, HCWs are generally required to self-monitor for symptoms while observing physical distancing and undergo repeat testing at different time points. Although quarantine of strict contacts of SARS-CoV-2 cases is a widely adopted measure to control transmission, HCWs might not always be required to self-isolate due to their role as essential frontline workers. Different recommendations about the need for quarantine have been issued if exposure is at high-risk (28) or if the staff is unvaccinated (40) . However, testing at baseline and after 5-7 days remains strongly advised by major available guidance documents, even in presence of low transmission or high vaccination rate (4, 41).

Two systematic reviews have addressed the utility of mass testing in special settings such as cancer institutions (39) and LTCFs (38) , underlying the importance of testing patients and healthcare workers during outbreak situations independently from the risk of the exposure. This strategy is 

Of note, testing policies should always be implemented after careful consideration of resources, infrastructure capacity, and logistical issues. Healthcare facilities adopting testing policies towards asymptomatic individuals should make appropriate plans on what test should be used and in what context (e.g., facility type and resources, patients' risk factors…). Moreover, when testing policies are implemented, adequate logistics and infrastructure should guarantee that asymptomatic patients who test positive continue to receive the best possible care. If testing capacity is limited, expert consensus from the WHO suggests that testing of symptomatic individuals should be prioritized over testing of asymptomatic individuals (19).

Lastly, all recommendations reported herein are based on limited evidence, and must be re-assessed periodically (at least every 6 months) by changes in the epidemiological scenario due to new viral variants, new emerging evidence on efficacy of IPC measure, vaccination coverage and efficacy among healthcare workers and the public, the vulnerable population admitted to hospital.

J o u r n a l P r e -p r o o f

All authors have no conflict of interest to declare. The project received a grant from ESCMID for medical writing assistance.

All authors contributed to the PICO selection, the literature search, the data extraction and the drafting of the recommendations. E.T. chaired the panel, supervised the work. E.C. and D.Y.O drafted the manuscript. All authors have reviewed and approved the manuscript.

The panel will periodically assess the need for further update of the present document (at least every 6 months). The need for update will consider new PICOs or revision of prior PICOs. The methodology will be the same as the present document. Box 1. Definitions used for epidemiological parameters and special populations.

Community transmission rate: refers to the intensity of transmission of SARS-CoV-2 in the community. Low transmission rate refers to <40 cases per 100,000 inhabitants in 14 days and a test positivity rate <2%. Conversely, high transmission rate is determined by >300 cases per 100,000 in 14 days and a >10% test positivity rate (Adapted from the ECDC thresholds and country classification (42)). Vaccination coverage: refers to the percentage of population with previous SARS-CoV-2 infection or vaccination. High vaccination coverage applies in a population with at least 60% who received full vaccination (includes those with past infection); low vaccination rate refers to a population with less than 60% of the individuals who received full vaccination (includes those with past infection) (43) . Exposure risk: High risk exposure refers to face to face or physical contact with an individual infected by SARS-CoV-2 within two meters more than 15 minutes or direct contact with excretions of a COVID-19 case or being in a closed area (i.e. the same hospital room or waiting room or break room) or travelling with an individual infected by SARS-CoV-2 more than 15 minutes or give care to a COVID-19 case without using proper PPE for HCWs. If the duration of the contact defined above is less than 15 minutes or if the healthcare professional who gives care to a COVID-19 case use proper PPE, the risk is considered low risk exposure (4) . Vulnerable populations: refers to populations where the COVID-19 is known to be associated with worse clinical outcomes (2, 44) and include: people aged 60 years and older; those living in long-term care facilities; people with underlying health conditions, such as hypertension, diabetes, cardiovascular disease, chronic respiratory disease and weakened immune systems (patients undergoing immunosuppressive procedures as cytotoxic chemotherapy, solid organ or stem cell transplantation, biologic therapy, cellular immunotherapy, or high-dose corticosteroids). Non-surgical procedures: refers to all procedures (invasive and not invasive) not involving surgery: physical examination; endoscopy; dental procedures; imaging; treatments to repair the effects of injury, disease or malfunctions, including medicines, physical and radiation therapies (therapeutic procedures); allied health treatments to improve, maintain or restore a person's physical function (rehabilitative procedures); and cosmetic procedures to improve a person's physical appearance for aesthetic reasons. Care givers: refers to individuals, including health professionals, family members, friends, social workers, or members of the clergy, providing care to hospitalized patients who need help taking care of themselves.

Nosocomial transmission and outbreaks of coronavirus disease 2019: the need to protect both patients and healthcare workers

WHO Infection prevention and control guidance for long-term care facilities in the context of COVID-19: interim guidance

ECDC Contact tracing in the European Union: public health management of persons, including healthcare workers, who have had contact with COVID-19 cases -fourth update

WHO Living guidance for clinical management of COVID-19

SARS-CoV-2 Transmission From People Without COVID-19 Symptoms

ESCMID COVID-19 Living Guidelines: Drug treatment and clinical management

GRADE Evidence to Decision (EtD) frameworks for adoption, adaptation, and de novo development of trustworthy recommendations: GRADE-ADOLOPMENT

The Proportion of SARS-CoV-2 Infections That Are Asymptomatic : A Systematic Review

Infectious Diseases Society of America Guidelines on the Diagnosis of COVID-19

Systematic screening on admission for SARS-CoV-2 to detect asymptomatic infections

Performance and feasibility of universal PCR admission screening for SARS-CoV-2 in a German tertiary care hospital

World Health Organization Recommendations for national SARS-CoV-2 testing strategies and diagnostic capacities: interim guidance

SARS-CoV-2 infection, COVID-19 and timing of elective surgery: A multidisciplinary consensus statement on behalf of the Association of Anaesthetists, the Centre for Peri-operative Care, the Federation of Surgical Specialty Associations, the Royal College of Anaesthetists and the

infectionprevention-and-control/covid-19-infection-prevention-and-control-guidance-aerosol-generatingprocedures

COVID-19 infection rates in patients referred for psychiatric admission during a regional surge: The case for universal testing

Should we test asymptomatic children for SARS-CoV-2? Evid Based Dent

Reopening dentistry after COVID-19: Complete suppression of aerosolization in dental procedures by viscoelastic Medusa Gorgo

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Universal COVID-19 testing and a three-space triage protocol is associated with a nine-fold decrease in possible nosocomial infections in an inpatient psychiatric facility

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Reducing COVID-19 quarantine with SARS-CoV-2 testing: a simulation study

Positivity on or After 9 Days Among Quarantined Student Contacts of Confirmed Cases

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A rapid systematic review of measures to protect older people in long-term care facilities from COVID-19

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ECDC Assessing SARS-CoV-2 circulation, variants of concern, non-pharmaceutical interventions and vaccine rollout in the EU/EEA, 15th update

Five reasons why COVID herd immunity is probably impossible

ECDC High-risk groups for COVID-19. Available at

We acknowledge ESCMID for supporting medical writing services.Methodological advice from Luigia Scudeller, project management support from Chiara Speziale and medical writing assistance by Patrick Moore is also acknowledged.J o u r n a l P r e -p r o o f

J o u r n a l P r e -p r o o f Institutions' websites (n = 2) Organisations (n = 1) Citation searching (n = 13)Studies included in the systematic review: n = 7 systematic reviews n= 24 recommendations (from 10 guidelines) Documents added at a second stage n = 3 guidance/consensus, n = 3 review/opinion n = 9 studies

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