The mystery of COVID-19 reinfections: a global systematic review and meta-analysis of 577 cases

Background As the COVID-19 pandemic rages on, reports on disparities in vaccine roll out alongside reinfection and reactivation from previously recovered cases have been emerging. With newer waves and variants of COVID-19, we conducted a systematic review to assess the determinants and disease spectrum of COVID-19 reinfection. Methods A comprehensive search covering relevant databases was conducted for observational studies reporting Polymerase Chain Reaction (PCR) confirmed infection and reinfection cases. Quality assessment tool developed by the National Institute of Health (NIH) for assessment of case series was used. Meta-analyses were performed using RevMan 5.3 for pooled proportions of findings in first infection and reinfection with 95% confidence interval (CI). Results Eighty-one studies reporting 577 cases were included from 22 countries. The mean age of patients was 46.2±18.9 years with males accounting for 45.8% of the study population while 179 (31.0%) cases of comorbidities were reported. The average time duration between first infection and reinfection was 63.6±48.9 days. During first infection and reinfection, fever was the most common symptom (41.4% and 36.4%, respectively) whilst anti-viral therapy was the most common treatment regimen administered (44.5% and 43.0%, respectively). Overall, comparable odds of symptomatic presentation and management were reported in the two infections. However, a higher Intensive Care Unit (ICU) admission rate was observed in reinfection compared to first infection (10 vs 3). Ten deaths were reported with 565 patients fully recovering. Respiratory failure was the most common cause of death (7/10 deaths). Seventy-two studies were determined to be of good quality whilst nine studies were of fair quality. Conclusion As the first global-scale systematic review of its kind, our findings support immunization practices given increased ICU admissions and mortality in reinfections. Our cohort serves as a guide for clinicians and authorities for devising an optimal strategy for controlling the pandemic. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement The author(s) received no specific funding for this work. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study did not require an IRB/ERC approval. All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data generated or analysed during this study are included in this article and its supporting information files. Further enquiries can be directed to the corresponding author.