The Potential Future of the COVID-19 Pandemic: Will SARS-CoV-2 Become a Recurrent Seasonal Infection?

There is growing optimism andhopethatbyvirtueofongoing immunization efforts, seasonality (declining infections through August), and naturally acquired immunity, by spring and early summer 2021 in the US there will be a substantial decline in the number of deaths and hospitalizations related to COVID-19. However, this optimism must be tempered by several important factors. The likelihood of achieving herd immunity against SARS-CoV-2 is low simply because not all individuals in the US are eligible to be vaccinated and a quarter of eligible individuals will likely decline to be immunized. Moreover, the vaccines do not provide full immunity against infection, and the currently available vaccines are less effective against variant B.1.351, and possibly other variants. Accordingly, the public and health systems need to plan for the possibility that COVID19 will persist and become a recurrent seasonal disease. Herd immunity is a theoretical construct from infectious disease modeling that posits that in a population in which every individual is equally likely to encounter every other individual, transmission will not be sustained when immunity through past infection, vaccination, or both reaches the level of 1 − (1/R), where R is the number of infections caused by a single infection in a population in which everyone is susceptible.1 Reality diverges from this simple notion. First, because COVID-19 is clearly seasonal, like other coronaviruses, the herd immunity level will be lower in the summer and higher in the winter. Second, herd immunity depends on how much interaction individuals have with one another, which will vary by state or city after social distancing mandates are lifted. Third, nonrandom mixing (individuals are not equally likely to interact with one another) can lead to modifications of the level of immunity required to stop transmission. Despite these factors, some public health officials suggest that achieving winter herd immunity in the presence of new more contagious variants will require more than 70% to 80% of individuals to be immune. Three key considerations will make achieving herd immunity against COVID-19 challenging. First, vaccines will have a reduced effect on preventing infection from the B.1.351 variant. Moderna and Pfizer vaccines have an overall effectiveness against symptomatic disease of approximately 95% for wild-type variants, whereas adenovirus vector vaccines, such as the Janssen/Johnson & Johnson vaccine, have effectiveness closer to 70%. Evidence on vaccine efficacy for preventing infection, however, comes onlyfrom1groupintheAstraZenecatrialthatshowed55% protection against infection as measured through weekly nasal swabs vs 70% protection for symptomatic disease.2 Furthermore, for the 3 vaccines tested against the B.1.351 variant, Janssen, Novavax, and AstraZeneca reported effectiveness estimates for symptomatic disease of 57%,3 49%,4 andastatisticallynonsignificantpercentage,respectively. IftheB.1.351variantbecomesdominant,asimplecalculation suggests that the aggregate effectiveness of vaccines for preventing B.1.351 transmission in the US could be only50%(ie,basedoncurrenteffectivenessof90%toprevent symptomatic disease × 20% reduction of efficacy for preventing infection compared with symptomatic disease and assuming an average reduction in efficacy for B.1.351 of 33% [excluding the statistically insignificant protection from the AstraZeneca vaccine]). Second,notenoughindividualswillreceivethevaccine. Because the vaccines are currently not authorized for use in children, only approximately 75% of US individuals are eligible to be immunized. Perhaps more important in the long run, not all individuals are willing be immunized. Data collected daily through Facebook’s Data for Good initiative provide timely information on the proportion of individualswhorespondyesor“yes,probably”tothequestion,Will you take the vaccine if offered it? These positive responses regarding likelihood of vaccine receipt increased in January 2021 and have reached 71%,5 similar to the 72% response in a nationally representative sample.6 Even with aneffectiveapprovedvaccineforchildren,ifB.1.351orsome other variant becomes dominant, the US can expect vaccine-derived immunity to reach only 37.5% (the estimated potential 50% aggregate efficacy for transmission ×75%ofindividualsreceivingthevaccine) in2021ifallsupply and administration difficulties are overcome. Third, there is concern about the extent to which previous infections from one variant protect individuals from reinfectionwithsomenewvariants.Novavaxreportedthat in a phase 2b clinical trial in South Africa, the COVID-19 incidence rate in the placebo group, predominantly from variant B.1.351, was 3.9% both among individuals with COVID-19 seropositivity and those who were COVID-19 seronegative.7 The interpretation by Novavax of this finding has been that past infection provides no immunity against new variants. If that is true, herd immunity can be achieved only through vaccination. But if B.1.351 spreads widely, vaccine-derived immunity will likely be much lower than the levels required to reach herd immunity by the 2021-2022 northern hemisphere winter. Various models suggest continuing COVID-19 surges are possible even without B.1.351 dominance.8 A winter surge of infection with B.1.351 dominance may occur in 2021-2022.Hospitalizationanddeathrates,however,may be expected to be lower, assuming vaccines remain more effective for preventing symptomatic disease and remaineffectiveforpreventingseverediseaseanddeath.For example, the Janssen vaccine was more than 85% effective against severe disease, even in South Africa, with no hospitalizations or deaths reported in the trial, albeit with VIEWPOINT