This study determined the current prevalence of COVID-19 reinfection at global and regional levels. We found an overall proportion of COVID-19 reinfection of 4.2% (95% CI: 3.7–4.8%, n = 52).
Initially, it was debated whether it is possible to have COVID-19 reinfection (103). The expert believed that infection with COVID-19 confers immunity, and that reinfection is less likely in previously infected people (104). However, reinfection with COVID-19 is quite common, and naturally acquired immunity wanes within a few weeks of infection (104). The reinfection was mostly observed with Omicron and its subvariants, which can evade natural immunity (104). In a surveillance study conducted in South Africa, the Omicron variant was associated with an increased reinfection rate (29). In contrast to other human coronaviruses, namely SARS-CoV, initially reported in Guangdong/China in 2002, and MERS-CoV, initially reported in Saudi Arabia in 2012, reinfection has not been reported as these infections were directly contained, leaving no time to document reinfection or recurrence (103). However, reinfection was documented with other common coronaviruses within 4–48 weeks of primary infection (mean period of 37 weeks) (103, 105).
The prevalence of COVID-19 reinfection observed in this meta-analysis was low compared with that found in previous meta-analyses (106, 107). This discrepancy in the prevalence of COVID-19 reinfection can be explained by these meta-analyses conducted early during the pandemic when few studies were available, in addition to the difference in the time of follow-up. A meta-analysis by Camilla et al. included 17 studies, and the follow-up period ranged from 1 to 60 days (106). Another meta-analysis included 14 studies, and the median period from infection to recurrence ranged from 21 to 50 days (107). This systematic review and meta-analysis included 52 relevant studies to determine the current prevalence of COVID-19 reinfection at the global and regional levels and considered a longer follow-up period.
There is a lack of a conventional definition of reinfection, and different authors of the studies included in existing meta-analyses have defined COVID-19 reinfection differently. Some authors have described cases of reinfection as continual viral shedding, whereas to ascertain reinfection, genomic sequencing should be performed to determine whether the second infecting virus is genetically different from the previous (51). Zumrut et al. described a case of re-positivity of COVID-19 PCR after 27 days of a negative test, and it was inconclusive whether it was a reinfection or prolonged viral shedding, as no previous genotyping was performed for the first infection (108). The CDC stated that viral shedding could be prolonged for up to 90 days, but even for severely infected persons, there was no replication-competent virus recovered after 10–20 days (109); The ECDC proposed tests such as whole-genome sequencing and phylogenetic analysis to conclude on reinfection (48), and cases of genetically confirmed reinfection in a period of approximately 2 months from the previous infection have been reported in the literature (110, 111). However, these genetic tests are not extensively available, and if considered widely, many cases of reinfection in many settings would not be recognized.
A higher proportion of recurrence of COVID-19 infection was observed in Africa (4.7%; 95% CI: 1.9–7.5%; n = 3) than that in other regions. This finding is unanticipated, as the incidence of COVID-19 in Africa is lower than that in other regions (17). A review by Dufailu states that the incidence, hospitalization, and mortality rate of COVID-19 were lower in Africa than that in other continents (112).
This high rate of reinfection in Africa, where the pandemic was less severe, can be explained by the high population density in this region and the failure to implement pandemic control measures (112). In addition, the low mortality rate observed in Africa, as well as the low incidence of severe cases of infection, should have led people to disregard restrictive measures and barrier actions against COVID-19, even in cases of previous infection, making reinfection an imminent occurrence (112, 113).
Other factors that should have influenced reinfection secondary to non-compliance with COVID-19 control measures by most of the population in Africa are the low vaccination rate, unsanitary conditions, lack of access to clean water, and lack of awareness (114). A study by Wirsiy et al. published in 2020 mentioned that measures taken in Asia, Europe, and North America, such as physical (social) distance and consistent handwashing, were most difficult to implement in African countries where Internet connectivity was limited, population density, access to water was uneven, and social safety nets were limited (115).
Oceania recorded the lowest prevalence of COVID-19 reinfection at 0.3% (95% CI: 0.2–0.4%; n = 1), but the sample size in this region was too small to predict the true estimates of reinfection.
Studies that used a combined type of specimens for PCR retesting had the highest prevalence of 7.6% (95% CI: 5.8–9.5%; n = 15). The studies that used nasopharyngeal specimens only had a lower prevalence of COVID-19 reinfection (3.4%; 95% CI: 3.7–4.8%; n = 12) compared with those that used only oropharyngeal specimens (6.7%; 95% CI: 4.8–8.5%; n = 8). These findings are the opposite of those observed in a meta-analysis by Azam et al., where the highest prevalence was found in studies that used a nasopharyngeal specimen only and the lowest in oropharyngeal specimens only (107).
These findings also disagree with those of a meta-analysis that assessed the positivity rate of COVID-19 using different types of specimens (116). In the latter study, nasopharyngeal swabs showed a positivity rate of 45%, whereas that of oropharyngeal swabs was 7.6%, and the highest detection rate was found in bronchoalveolar fluids (116). However, in agreement with the findings of this meta-analysis, other studies have shown that nasopharyngeal specimens yield a higher detection rate of COVID-19 than that of nasal or oropharyngeal swabs (117–120).
The discrepancy in these findings can be related to many studies considered in this meta-analysis that did not specify the type of specimen used for PCR retesting; however, this analysis considered throat and oropharyngeal swabs equivalent. Therefore, we hypothesize that combining two or more types of specimens should increase the detection rate of COVID-19, as substantiated by the findings of this study. However, more studies must validate this finding, and further meta-analyses will reduce this disagreement.
The difference between vaccinated and unvaccinated individuals in relation to the COVID-19 reinfection rate was not assessed because there was insufficient necessary information for this analysis. A prospective cohort study published in January 2022 by Sezanur Rahman revealed that new COVID-19 variants that emerged in 2021 could reinfect both naturally infected and vaccinated individuals and that being naturally infected confers better protection against COVID-19 for at least 6 months after primary infection (94). Another systematic review indicated a risk of reinfection with COVID-19 in previously infected patients, including those vaccinated against the disease (121).
The severity of the reinfection was not addressed in this study. A systematic review conducted by Rubaid et al. in 2021 showed that the first infection and reinfection with COVID-19 showed a broadly similar pattern of clinical and management regimen but with a slightly higher severity among reinfected cases, evaluated by the need for mechanical ventilation and intensive care unit admission (122).
This meta-analysis has important implications for public health policies. The evidence of COVID-19 reinfection presented in this review should guide countries that demonstrate high reinfection prevalence to a future better preparedness for epidemic and pandemic diseases. Strategies should be set a priori on how preventive measures should be respected to prevent the spread of epidemics as well as reinfection.
The main strength of our study was the long period covered, which included studies from the first that reported reinfection in individuals pre-infected with COVID-19 until June 2022. This made it the first comprehensive meta-analysis to include many studies to date, which also considered the prevalence of COVID-19 reinfection by geographical area. In addition, most of the studies included in our analysis were of good quality.
The limitations of this study are that there is a difference in the definitions of reinfection used by the authors of the studies included in this meta-analysis, and it was difficult to compare findings across all studies. Additionally, no subgroup analysis was done by vaccination status or by definition of reinfection, and all sources of heterogeneity, such as the age group, were not explored because of a lack of appropriate related information among studies. Furthermore, the variability in sample size across the studies should have affected the prevalence and heterogeneity observed between studies.