Comparison of different isolation periods for preventing the spread of COVID-19: a rapid systematic review and a modelling study
Authors: Gao Ya , Zhao Yunli , Zhang Xi , Tian Jinhui , Guyatt Gordon , Hao Qiukui 
Published: January 2023

SummaryBackgroundThe optimal isolation duration for COVID-19 patients remains unclear. To support an update of WHO Living Clinical management guidelines for COVID-19 (https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2022.2), this rapid systematic review and modelling study addresses the effects of different isolation periods for preventing onward transmission leading to hospitalization and death among secondary cases.MethodsWe searched World Health Organization (WHO) COVID-19 database for clinical studies evaluating the impact of isolation periods for COVID-19 patients up to July 28, 2022. We performed random-effects meta-analyses to summarize testing rates of persistent test positivity rates after COVID-19 infection. We developed a model to compare the effects of the five-day isolation and removal of isolation based on a negative antigen test with ten-day isolation on onward transmission leading to hospitalization and death. We assumed that patients with a positive test are infectious and those with a negative test are not. If the test becomes negative, patients will stay negative. The model included estimates of test positivity rates, effective reproduction number, and hospitalization rate or case fatality rate.FindingsTwelve studies addressing persistent test positivity rates including 2799 patients proved eligible. Asymptomatic patients (27.1%, 95% CI: 15.8% to 40.0%) had a significantly lower rapid antigen test (RAT) positive rate than symptomatic patients (68.1%, 95% CI: 40.6% to 90.3%) on day 5. The RAT positive rate was 21.5% (95% CI: 0 to 64.1%; moderate certainty) on day 10. Our modelling study suggested that the risk difference (RD) for asymptomatic patients between five-day isolation and ten-day isolation in hospitalization (2 more hospitalizations of secondary cases per 1000 patients isolated, 95% uncertainty interval (UI) 2 more to 3 more) and mortality (1 more per 1000 patients, 95% UI 0 to 1 more) of secondary cases proved very small (very low certainty). For symptomatic patients, the potential impact of five- versus ten-day isolation was much greater in hospitalizations (RD 19 more per 1000 patients, 95% UI 14 more to 24 more; very low certainty) and mortality (RD 5 more per 1000 patients, 95% UI 4 more to 6 more; very low certainty). There may be no difference between removing isolation based on a negative antigen test and ten-day isolation in the onward transmission leading to hospitalization or death, but the average isolation period (mean difference −3 days) will be shorter for the removal of isolation based on a negative antigen test (moderate certainty).InterpretationFive versus 10 days of isolation in asymptomatic patients may result in a small amount of onward transmission and negligible hospitalization and mortality, but in symptomatic patients concerning transmission and resulting hospitalization and mortality. The evidence is, however, very uncertain.FundingWHO.Research in contextEvidence before this studyIsolating infected patients and quarantining individuals with a high risk of recent infection remain widely used strategies to prevent the spread of SARS-CoV-2. There are no prior systematic reviews to evaluate effects relevant to decisions regarding protocols for ending COVID-19 isolation. Many modelling studies have, however, evaluated impact of five days of isolation or alternative strategies (e.g. 7 days and 10 days) with or without one negative lateral flow device on secondary infections or additional transmission risk. However, none has focused on the most patient-important outcomes - onward transmission leading to hospitalization or death. The optimal isolation duration for COVID-19 patients remains unclear. We searched WHO COVID-19 database for clinical studies evaluating the impact of isolation periods for COVID-19 patients up to July 28, 2022. We performed random-effects meta-analyses to summarize testing rates of persistent test positivity rates after COVID-19 infection. We used a model to compare the effects of the five-day isolation and removal of isolation based on a negative antigen test with ten-day isolation on onward transmission leading to hospitalization and death.Added value of this studyTo our knowledge, this is the first systematic review and modelling study to compare effects of the five-day isolation and removal of isolation based on a negative antigen test with ten-day isolation on most patient-important outcomes - onward transmission leading to hospitalization or death. This study demonstrates that for symptomatic patients the five-day isolation may increase onward transmission and thus hospitalization and mortality of secondary cases compared with the ten-day isolation by a magnitude most would consider important. For asymptomatic patients, the increase in hospitalizations and death may be small enough to be considered unimportant. Removal of isolation based on a negative antigen test will probably shorten the average isolation period compared with isolating all patients for 10 days.Implications of all the available evidenceOur study provides evidence that 5 versus 10 days of isolation in asymptomatic patients may result in a small amount of onward transmission and negligible hospitalization and mortality, but in symptomatic patients concerning transmission and resulting hospitalization and mortality.