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Review| Volume 81, ISSUE 3, P357-371, September 2020

SARS-CoV-2 detection, viral load and infectivity over the course of an infection

Published:June 29, 2020DOI:https://doi.org/10.1016/j.jinf.2020.06.067
SARS-CoV-2 detection, viral load and infectivity over the course of an infection
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      Highlights

      • •
        SARS-CoV-2 viral loads peak from upper respiratory tract samples around symptom onset.
      • •
        Viral loads from sputum samples may be higher than upper respiratory tract samples.
      • •
        Viral loads appear to be similar between asymptomatic and symptomatic patients.
      • •
        The prolonged virus detection in stool samples has unclear clinical significance.
      • •
        Patients may not be infectious for the entire duration of virus detection.

      Summary

      Objectives

      To summarise the evidence on the detection pattern and viral load of SARS-CoV-2 over the course of an infection (including any asymptomatic or pre-symptomatic phase), and the duration of infectivity.

      Methods

      A systematic literature search was undertaken in PubMed, Europe PubMed Central and EMBASE from 30 December 2019 to 12 May 2020.

      Results

      We identified 113 studies conducted in 17 countries. The evidence from upper respiratory tract samples suggests that the viral load of SARS-CoV-2 peaks around symptom onset or a few days thereafter, and becomes undetectable about two weeks after symptom onset; however, viral loads from sputum samples may be higher, peak later and persist for longer. There is evidence of prolonged virus detection in stool samples, with unclear clinical significance.
      No study was found that definitively measured the duration of infectivity; however, patients may not be infectious for the entire duration of virus detection, as the presence of viral ribonucleic acid may not represent transmissible live virus.

      Conclusion

      There is a relatively consistent trajectory of SARS-CoV-2 viral load over the course of COVID-19 from respiratory tract samples, however the duration of infectivity remains uncertain.

      Keywords

      Introduction

      The Coronavirus Disease 2019 (COVID-19) pandemic is a public health emergency of international concern causing a substantial number of cases and deaths globally.
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      COVID-19 presents an unprecedented challenge to governments worldwide due to the transmissibility of the virus, the scale of its impact on morbidity and mortality, the uncertainty regarding the development of long-term immunity in those infected, the current lack of vaccine or treatment options, and the impact on healthcare systems, economies and society.
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      Much remains unknown about COVID-19; however, evidence is emerging at a fast pace.
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      EPPI-Centre, Social Science Research Unit, UCL Institute of Education, University College London, London2020
      Our team at the Health Information and Quality Authority (HIQA) of Ireland has conducted a series of rapid reviews on various public health topics relating to COVID-19. The rapid reviews arose directly from questions posed by policy makers and expert clinicians supporting the Irish National Public Health Emergency Team (NPHET). Hence, the findings of these reviews have informed the national response to the COVID-19 pandemic in Ireland,

      HIQA publishes COVID-19 evidence summaries to support work of the National Public Health Emergency Team [press release]. https://www.hiqa.ie/hiqa-news-updates/hiqa-publishes-covid-19-evidence-summaries-support-work-national-public-health: HIQA, 1 April 2020.

      and have implications for international health policy as well as clinical and public health guidance.
      Understanding the trajectory of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the duration of infectivity is of critical importance to controlling the pandemic.
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      As SARS-CoV-2 is a novel virus in the human population, there is substantial uncertainty regarding virological levels (i.e. detection and viral load) in patients and how this relates to infectivity and disease severity. Information relating to SARS-CoV-2 detection and viral load at different time points of an infection, including in those without any symptoms, will aid with the clinical interpretation of real-time reverse transcriptase polymerase chain reaction (rRT-PCR) test results. Furthermore, information pertaining to the duration of infectivity will help inform public health protocols for quarantine, isolation and contact tracing.
      We defined detection as the presence (i.e. detectability) or absence (i.e. undetectability) of the virus in a sample at a given time. We defined viral load as the quantity (or titre) of virus in a volume of fluid at a given time. For this current article, we summarise the available evidence to address the following two research questions:

      Materials and methods

      We conducted rapid reviews for a broad range of public health topics related to COVID-19 following a standardised protocol,

      Health Information and Quality Authority. Protocol for evidence synthesis support - COVID-19. https://www.hiqa.ie/sites/default/files/2020-04/Protocol-for-evidence-synthesis-support_1-4-COVID-19.pdf: HIQA, 2020.

      in keeping with Cochrane rapid review methodology guidance.
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      Initially, we conducted a systematic literature search of electronic databases (PubMed, EMBASE, Science Direct, Cochrane, National Health Service [NHS] Evidence, and Infectious Diseases Society of America search of infectious disease journals) and pre-print servers (medRxiv, bioRxiv and Health Research Board [HRB] Open) using COVID-19 search terms. The purpose of the initial broad search was to identify all COVID-19 scientific and medical literature to answer a range of research questions. Due to the proliferation of COVID-19 literature, the vast majority of which were not relevant to our research question, we employed a more specific search strategy from 27 March 2020 onwards. Hence, we conducted a systematic literature search of PubMed, Europe PubMed Central and EMBASE from 30 December 2019. The search combined terms for COVID-19 with terms for viral load, detection and infectivity. Only articles including human subjects were included. No language restrictions were applied. The last update for this rapid review was conducted on 12 May 2020. The protocol, which is available online, contains the detailed search strategies.

      Health Information and Quality Authority. Protocol for evidence synthesis support - COVID-19. https://www.hiqa.ie/sites/default/files/2020-04/Protocol-for-evidence-synthesis-support_1-4-COVID-19.pdf: HIQA, 2020.

      All potentially eligible papers, including non-peer-reviewed pre-prints, were exported to Endnote X8.2 and screened for relevance. Any study (regardless of design) that addressed the research question and met the inclusion criteria (Table 1) was included. For each included study, data on the study design, participant demographics and clinically relevant data were extracted. Various validated risk of bias tools were used for quality appraisal of included studies, where appropriate (e.g. Cochrane Risk of Bias (RoB) tool for Randomized Controlled Trials [RCTs]
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      and Risk Of Bias In Non-randomized studies of Interventions tool (ROBINS-I)).
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      For study designs where no universally accepted quality appraisal tool existed (e.g. case series, modelling studies), a de-novo tool, adapted from related tools, was used.

      Health Information and Quality Authority. Protocol for evidence synthesis support - COVID-19. https://www.hiqa.ie/sites/default/files/2020-04/Protocol-for-evidence-synthesis-support_1-4-COVID-19.pdf: HIQA, 2020.

      The findings of the research question were synthesised narratively due to the heterogeneity of study designs and data.
      Table 1Population, Outcomes and Study types (POS) framework for study inclusion.
      PopulationPatients (of any age) infected with COVID-19 with information on either viral load or detection during infection (including in the pre-symptomatic phase) and/or duration of infectivity.
      • •
        Subgroups of interest adults vs children
      OutcomesPrimary outcomes:
      • •
        Ribonucleic Acid (viral load or detection) during infection (the test used [including cut-off if reported], sample site [e.g. upper/lower respiratory, faecal, urine], test timing [number of days symptomatic pre-testing (if relevant)], clinical characteristics of the population (age, comorbidity) and clinical syndrome associated with COVID-19 (asymptomatic, mild illness, pneumonia, severe pneumonia, ARDS, sepsis, septic shock)
      • •
        Duration of virus detection (define start as: first confirmed positive test (or symptom onset); use WHO criteria (where reported) for end of detection, that is, two consecutive negative PCR tests 24 h apart).
      • •
        Period of infectiousness/infectivity (defined as the time interval during which SARS-CoV-2 may be transferred from an infected person to another person).
      Types of StudiesInclude:
      • •
        any study that reports on the viral load or duration of viral detection or infectivity of COVID-19.
      Exclude:
      • •
        studies where COVID-19 was not confirmed with a laboratory test.
      Key: ARDS - acute respiratory distress syndrome; COVID-19 - coronavirus disease 2019; SARS-CoV-2 - severe acute respiratory syndrome coronavirus 2; WHO - World Health Organization.

      Results

      Summary of included studies

      A total of 113 studies were included
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