Early SARS-CoV-2 reinfections within 60 days highlight the need to consider antigenic variations together with duration of immunity in defining retesting policies

Abstract

The emergence of the SARS-CoV-2 Omicron variant, characterized by a significant antigenic diversity compared to the previous Delta variant, had led to a decrease in antibody efficacy in both convalescent and vaccinees sera resulting in high number of reinfections and breakthrough cases worldwide. However, to date, reinfections are defined by the ECDC as two positive tests >/= 60 days apart, influencing retesting policies after an initial positive test in several European countries. In our manuscript, we illustrate by a clinical case supplemental by epidemiological data that early reinfections do occur within 60 days especially in young, unvaccinated individuals. In older patient groups, unvaccinated and patients with a basic vaccination scheme are more vulnerable to reinfections compared to patients who received a first booster vaccine. For this reason, we consider that the duration of protection offered by a previous infection should be reconsidered, in particular when a shift between consecutive SARS-CoV-2 variants occurs.

Clinical Severity of SARS-CoV-2 Omicron Variant Compared with Delta among Hospitalized COVID-19 Patients in Belgium during Autumn and Winter Season 2021–2022

“…First, it is important to acknowledge the study selection procedures when interpreting the risk estimates. Restricting the analysis to hospitalized patients may hamper both external and internal validity [57,59,60]. Further, the hospitalized patients with available information on the SARS-CoV-2 variant of their infection may not be representative of the hospitalized population.…”

“…Having exhaustive information on the vaccination status, and performing a sensitivity analysis excluding patients with a documented previous infection, enabled us to account, to a large extent, for the gradually changing background immunity in the population. However, the number of documented reinfections, defined as two positive tests in the same individual taken more than 90 days apart, is probably an underestimation given the larger antigenic diversity of Omicron [59]. The effects of undocumented previous infections and the fact that the rate of underascertainment varies considerably over time could potentially hamper the comparison.…”

Protection against Omicron BA.2 reinfection conferred by primary Omicron or pre-Omicron infection with and without mRNA vaccination

“…3 Omicron BA.2 reinfections had been documented using whole genome sequencing as early as 20 days following an Omicron BA.1 primary infection, although such occurrences appeared rare. 16,17 We observed a moderate protection against any (38%) and symptomatic infection (51%) by heterologous pre-Omicron primary infection without vaccination, but a higher estimate for two-dose hybrid immunity (81%). An study from Qatar reported a 46% effectiveness against symptomatic BA.2 infection in individuals with pre-Omicron PI and 55% and 77% if combined with two-or threedose vaccination, respectively.…”

“…We defined reinfections based on a ≥30-day interval between positive tests because of data documenting early reinfections during SARS-CoV-2 variant replacement periods. 16,17 Prolonged viral shedding might have been misclassified as reinfections, 27 but this would tend to underestimate the protection associated with prior BA.1 infection. Reassuringly, sensitivity analysis using the standard ≥90-day interval did not change our estimates of protection.…”

“…3 Omicron BA.2 reinfections had been documented using whole genome sequencing as early as 20 days following an Omicron BA.1 primary infection, although such occurrences appeared rare. 16,17…”