The durability of immunity against reinfection by SARS-CoV-2: a comparative evolutionary study

Abstract

Background Among the most consequential unknowns of the devastating COVID-19 pandemic are the durability of immunity and time to likely reinfection. There are limited direct data on SARS-CoV-2 long-term immune responses and reinfection. The aim of this study is to use data on the durability of immunity among evolutionarily close coronavirus relatives of SARS-CoV-2 to estimate times to reinfection by a comparative evolutionary analysis of related viruses SARS-CoV, MERS-CoV, human coronavirus (HCoV)-229E, HCoV-OC43, and HCoV-NL63. Methods We conducted phylogenetic analyses of the S , M, and ORF1b genes to reconstruct a maximum-likelihood molecular phylogeny of human-infecting coronaviruses. This phylogeny enabled comparative analyses of peak-normalised nucleocapsid protein, spike protein, and whole-virus lysate IgG antibody optical density levels, in conjunction with reinfection data on endemic human-infecting coronaviruses. We performed ancestral and descendent states analyses to estimate the expected declines in antibody levels over time, the probabilities of reinfection based on antibody level, and the anticipated times to reinfection after recovery under conditions of endemic transmission for SARS-CoV-2, as well as the other human-infecting coronaviruses. Findings We obtained antibody optical density data for six human-infecting coronaviruses, extending from 128 days to 28 years after infection between 1984 and 2020. These data provided a means to estimate profiles of the typical antibody decline and probabilities of reinfection over time under endemic conditions. Reinfection by SARS-CoV-2 under endemic conditions would likely occur between 3 months and 5·1 years after peak antibody response, with a median of 16 months. This protection is less than half the duration revealed for the endemic coronaviruses circulating among humans (5–95% quantiles 15 months to 10 years for HCoV-OC43, 31 months to 12 years for HCoV-NL63, and 16 months to 12 years for HCoV-229E). For SARS-CoV, the 5–95% quantiles were 4 months to 6 years, whereas the 95% quantiles for MERS-CoV were inconsistent by dataset. Interpretation The timeframe for reinfection is fundamental to numerous aspects of public health decision making. As the COVID-19 pandemic continues, reinfection is likely to become increasingly common. Maintaining public health measures that curb transmission—including among individuals who were previously infected with SARS-CoV-2—coupled with persistent efforts to accelerate vaccination worldwide is critical to the prevention of COVID-19 morbidity and mortality. Funding US National Science Foundation.

COVID-19 Incidence and hospitalization during the delta surge were inversely related to vaccination coverage among the most populous U.S. Counties

“…These negative findings may be the result of the limited duration of naturally acquired immunity. [27] …”

SARS-CoV-2 breakthrough infections in vaccinated individuals: measurement, causes and impact

“…For example, although there is evidence that the vaccines against SARS-CoV-2 reduce transmission in households 96 , 118 , 119 and communities 120 , it has been argued that sustained high levels of herd immunity against SARS-CoV-2 infection may be an impossible goal for vaccination 2 given that it is a mucosal infection without an obligate stage of dissemination through lymph or blood. In this scenario, even with high vaccine coverage, some combination of waning immunity and antigenic variation will produce enough susceptibility in the population to maintain endemic transmission of SARS-CoV-2 for the foreseeable future, likely similar to what is seen for the four other coronaviruses circulating in the human population 121 . Nevertheless, this situation seems unlikely to produce the same level of disruption that has been seen in the first 1.5 years of the COVID-19 pandemic.…”

Protection and waning of natural and hybrid COVID-19 immunity

“…While a rapid decline in protection against SARS-CoV-2 after two doses of BNT162b2 vaccination has been observed in several studies, [1][2][3] the levels of protection and the presence or extent of waning of natural immunity are still unclear. Several studies have reported a substantial natural immunity six and more months following infection, [4][5][6][7][8] although one recent study 9 reported mRNA based vaccines to have a 5-fold higher protection against hospitalization compared to protection provided by prior infection. Waning in both the humoral and cellular responses of the immune system is well documented in vaccinated and in previously infected persons.…”