SARS-CoV-2 reinfections: Overview of efficacy and duration of natural and hybrid immunity

Abstract

Seroprevalence surveys suggest that more than a third and possibly more than half of the global population has been infected with SARS-CoV-2 by early 2022. As large numbers of people continue to be infected, the efficacy and duration of natural immunity in terms of protection against SARS-CoV-2 reinfections and severe disease is of crucial significance for the future. This narrative review provides an overview on epidemiological studies addressing this issue. National surveys covering 2020–2021 documented that a previous SARS-CoV-2 infection is associated with a significantly reduced risk of reinfections with efficacy lasting for at least one year and only relatively moderate waning immunity. Importantly, natural immunity showed roughly similar effect sizes regarding protection against reinfection across different SARS-CoV-2 variants, with the exception of the Omicron variant for which data are just emerging before final conclusions can be drawn. Risk of hospitalizations and deaths was also reduced in SARS-CoV-2 reinfections versus primary infections. Observational studies indicate that natural immunity may offer equal or greater protection against SARS-CoV-2 infections compared to individuals receiving two doses of an mRNA vaccine, but data are not fully consistent. The combination of a previous SARS-CoV-2 infection and a respective vaccination, termed hybrid immunity, seems to confer the greatest protection against SARS-CoV-2 infections, but several knowledge gaps remain regarding this issue. Natural immunity should be considered for public health policy regarding SARS-CoV-2.

mRNA-based vaccine candidate COReNAPCIN® induces robust humoral and cellular immunity in mice and non-human primates

“…1273 & BNT162b, and a similar situation is expected for convalescent people recovered from COVID-19 [24][25][26][27] . Moreover, due to the high mutation rate and behavior of SARS-CoV-2 circulating between humans and animals, scientists predict COVID-19 will remain a major health challenge probably for the next decade 28,29 .…”

“…However, despite the effectiveness of vaccines against ancestral strain, due to the rapid emergence of variant of concerns (VOCs) and also the observed waning immunity, most probably the majority of vaccinated people will require regular booster doses at least in the next few years to overcome this health threatening issue [21][22][23] . This is true even for people vaccinated with the most effective vaccines; mRNA-1273 & BNT162b, and a similar situation is expected for convalescent people recovered from COVID-19 [24][25][26][27] . Moreover, due to the high mutation rate and behavior of SARS-CoV-2 circulating between humans and animals, scientists predict COVID-19 will remain a major health challenge probably for the next decade 28,29 .…”

Protection of Omicron sub-lineage infection against reinfection with another Omicron sub-lineage

“…These findings, in the context of broader evidence for natural immunity, 2,5-9,20-22 suggest that natural immunity of SARS-CoV-2 variants cluster into two groups: early non-Omicron variants, and Omicron BA.1 and BA.2 sub-lineages. Within each group, there appears to be strong protection against reinfection with an effectiveness that exceeds 85%.…”

“…However, evidence has been consistent that natural immunity, unlike vaccine immunity, wanes slowly with minimal waning for at least several months after primary infection. 2,5-9,20-22…”

“…Ideally, SARS-CoV-2 reinfection is defined as a documented infection ≥90 days after an earlier infection, to avoid misclassification of prolonged infections as reinfections, if a shorter time interval is used. 20-22 Since the Omicron wave started only few weeks ago, this definition could not be used. Analysis of durations of follow-up was conducted to identify the longest time interval possible while maintaining adequate durations of follow-up and precision of estimates.…”