ABSTRACT
Objectives This study aims to estimate the prevalence and longevity of detectable SARS-CoV-2 antibodies as well as memory cells T and B after recovery. In addition, the prevalence of COVID-19 reinfection, and the preventive efficacy of previous infection with SARS-CoV-2 were investigated. Methods and analyses A synthesis of existing research was conducted. The Cochrane Library for COVID-19 resources, the China Academic Journals Full Text Database, PubMed, and Scopus as well as preprint servers were searched for studies conducted between 1 January 2020 to 1 April 2021. We included studies with the relevant outcomes of interest. All included studies were assessed for methodological quality and pooled estimates of relevant outcomes were obtained in a meta-analysis using a bias adjusted synthesis method. Proportions were synthesized with the Freeman-Tukey double arcsine transformation and binary outcomes using the odds ratio (OR). Heterogeneity between included studies was assessed using the I2 and Cochran’s Q statistics and publication bias was assessed using Doi plots. Results Fifty-four studies, from 18 countries, with around 12 000 000 individuals, followed up to 8 months after recovery were included. At 6-8 months after recovery, the prevalence of SARS-CoV-2 specific immunological memory remained high; IgG – 90.4% (95%CI 72.2-99.9, I 2 =89.0%, 5 studies), CD4+ - 91.7% (95%CI 78.2 – 97.1, one study), and memory B cells 80.6% (95%CI 65.0-90.2, one study) and the pooled prevalence of reinfection was 0.2% (95%CI 0.0 – 0.7, I 2 = 98.8, 9 studies). Individuals previously infected with SARS-CoV-2 had an 81% reduction in odds of a reinfection (OR 0.19, 95% CI 0.1 - 0.3, I 2 = 90.5%, 5 studies). Conclusion Around 90% of people previously infected with SARS-CoV-2 had evidence of immunological memory to SARS-CoV-2, which was sustained for at least 6-8 months after recovery, and had a low risk of reinfection. Registration PROSPERO: CRD42020201234 What is already known on this topic Individuals who recover from COVID-19 may have immunity against future infection but the proportion who develop immunity is uncertain. Further, there is uncertainty about the proportion of individuals who get reinfected with COVID-19. What this study adds Using data from 54 studies with follow up time up to 8 months after recovery, during the period February 2020-February 2021, we found that, post-COVID-19, up to 90% of individuals had antibodies and memory T and B cells against SARS-CoV-2. We also found a pooled prevalence of reinfection of 0.2%, and that infection conferred an 81% decrease in odds of reinfection with SARS-CoV-2, compared to unimmunized individuals without previous COVID-19. This review of 12 million individuals presents evidence that most individuals who recover from COVID-19 develop immunological memory to SARS-CoV-2, which was still detectable for up to 8 months. Further, reinfection after recovery from COVID-19 was rare during the first 8 months after recovery, with a prevalence below 1%, while prior infection confers protection with an odds ratio of 0.19 and a preventive efficacy of 80% at a baseline prevalence of 5% for COVID-19 in a community. Implications of all the available evidence Individuals with a history of COVID-19 infection have immunity against the disease for up to 8 months, although this period could be longer. These individuals could be prioritized last for COVID-19 vaccinations or considered for single dose vaccinations. Strengths This comprehensive review addresses key questions on prevalent immunological memory and risk of reinfection in individuals with prior confirmed COVID-19 using robust systematic review methods. Limitations Some of the included studies which examined prevalent immunological memory were small studies which were affected by loss to follow up. The review did not examine evidence for immunity against the new divergent variants, which may be more likely to have immune evasion behaviour and may present a higher risk of reinfection. Lastly, the review did not examine the effect of the severity of COVID-19 on both immunological memory and the risk of reinfection.
Subject(s)
COVID-19ABSTRACT
Abstract Background There is an urgent need for an efficacious and safe treatment for COVID19. Several trials testing a variety of therapeutics are on-going. Some in-vitro studies found the anti-malarial drug chloroquine (CQ), and its derivative, hydroxychloroquine (HCQ), are effective against COVID19. However, systematic reviews and meta-analyses of clinical trials in humans have produced conflicting findings on the efficacy and safety of these drugs. Guidelines vary considerably and are hotly debated at political and scientific levels. Therefore, it has become necessary to provide a summary of the effectiveness and safety of these drugs in treating COVID19 infection, using an overview of the existing systematic reviews and meta-analyses. Objective To synthesize the findings presented in systematic reviews and meta-analyses as well as to update the evidence using a meta-analysis in evaluating the efficacy and safety of CQ and HCQ with or without Azithromycin for the treatment of COVID19 infection. Methods The design of this meta-review followed the Preferred Reporting Items for Overviews of Systematic Reviews including harms checklist (PRIO-harms). A comprehensive search included several electronic databases in identifying all systematic reviews and meta-analyses as well as experimental studies which investigated the efficacy and safety of CQ, HCQ with or without antibiotics as COVID19 treatment. Manual searches of the reference list of all included studies and a citation search of the top 20 papers supplemented the search. Findings from the systematic reviews and meta-analyses were reported using a structured summary including tables and forest plots. The updated meta-analysis of experimental studies was carried out using the distributional-assumption-free quality effects model. Risk of bias was assessed using the Assessing the Methodological Quality of Systematic Reviews (AMSTAR) tool for reviews and the MethodologicAl STandard for Epidemiological Research (MASTER) scale for the experimental studies. The main outcomes for both the meta-review and the updated meta-analysis were; mortality, transfer to the intensive care unit (ICU), intubation or the need for mechanical ventilation, worsening of illness, viral clearance and the occurrence of adverse events. Results A total of 13 reviews with 40 primary studies comprising 113,000 participants were included. Most of the primary studies were observational (n=27) and the rest were experimental studies. Two meta-analyses reported a high risk of mortality with similar ORs of 2.5 for HCQ with Azithromycin. However, four other meta-analyses reported contradictory results with two reporting a high risk of mortality (OR ~ 2.2 to 3.0) and the other two reporting no significant association between HCQ with mortality. Most reviews reported that HCQ with or without Azithromycin had no significant effect on virological cure, disease exacerbation or the risk of transfer to the ICU, need for intubation or mechanical ventilation. After exclusion of studies that did not meet the eligibility criteria, the updated meta-analysis contained eight experimental studies (7 RCTs and 1 quasi-experimental trial), with a total of 5279 participants of whom 1856 were on either CQ/HCQ or combined with Azithromycin. CQ/HCQ with or without Azithromycin was significantly associated with a higher risk of adverse events (RR 5.7, 95%CI 2.4-13.7, I2 =55%, n = 5 studies). HCQ was not effective in reducing mortality (RR 1.0, 95%CI 1.0-1.2, I2 =0%, n=6 studies), transfer to the ICU, intubation or need for mechanical ventilation (RR 1.1, 95%CI 0.9-1.4, I2 =0%, n=3 studies) virological cure (RR 1.0, 95%CI 0.9-1.2, I2 =55%, n=5 studies) nor disease exacerbation (RR 1.2, 95%CI 0.3-5.0, I2 =29%, n=3 studies). Conclusion There is conclusive evidence that CQ and HCQ, with or without Azithromycin are not effective in treating COVID-19 or its exacerbation.