Dödligt virus från Kina orsakar panik (SARS-CoV-2, COVID-19)

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.

/.../In particular, our estimate argues strongly against the claim that a long-standing resolution of the epidemic could arise due to herd immunity from natural infection or that mitigation of the long-term risks of morbidity and mortality can be achieved without vaccination. Relying on herd immunity without widespread vaccination jeopardises millions of lives, entailing high rates of reinfection, morbidity, and death. In areas with low vaccination, our data-driven analysis reinforces the need for continued safety practices such as social distancing, proper indoor ventilation, and mask wearing to avoid reinfection as pandemic conditions continue.

/.../Undue public confidence in the long-term durability of immunity following natural infection by SARS-CoV-2 has been shown to contribute to vaccine hesitancy,34 perhaps because of a false equivalence with the long-term immunity after natural recovery from evolutionarily divergent viruses causing diseases such as measles, mumps, and rubella. By contrast, numerous respiratory viruses such as influenza, human rhinoviruses, or coronaviruses can overcome the immunity conferred by previous infections by evolving new variants in the protein domains most frequently surveilled and targeted by the human immune system. Just over a year into the COVID-19 pandemic, novel SARS-CoV-2 variants that can vary in severity of infection and evoke differential immune system responses and that can thwart the durability of immunity started arising.35 Such novel variants probably play a similar evolutionary role in the persistence of lower-severity, endemic human coronaviruses.4 Mitigation of the potential evolution of immune-evading SARS-CoV-2 variants in the near-future might depend crucially on a rapid global deployment of vaccination, which can induce higher immunogenicity than natural infection.