Viral Genetic Evidence and Host Immune Response of a Small Cluster of Individuals with Two Episodes of SARS-CoV-2 Infection

Background: The dynamics underlying severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection remains poorly understood. We added to the registered case reports of reinfection in USA, Belgium/Netherlands, Ecuador and Hong Kong, a small cluster of individuals with two episodes of 2019 coronavirus disease (COVID-19). Virus genomic analysis and the host immune response were used to characterize this group. Methods: Four individuals from Rio de Janeiro, Brazil, with clinical manifestations of COVID-19 on March and again in late May of 2020 were studied. Nasopharyngeal swabs were collected for RT-PCR and viral genome sequencing (BGI-MGI-2000). Plasma samples from the acute and convalescent phases of both infection episodes were accessed to document innate and humoral responses.Findings: After approximately 60 days of the first diagnostic episode of SARS-CoV-2 infection, the four individuals presented new clinical and molecular evidence of COVID-19. Complete SARS-CoV-2 genome sequence provided genetic evidence of reinfection. The individuals presented an enhanced innate response compared to healthy SARS-CoV-2 negative controls. Patients did not develop a neutralizing humoral immunity, possibly remaining susceptible to another episode of COVID-19. The second episode, associated with higher viral loads and clinical symptoms, likely boosted their anti-SARS-CoV-2 humoral response. Interpretation: SARS-CoV-2 reinfection was fully documented by identification of genetically distinct virus sequences in the first and second episodes for two individuals. The quantity of SARS-CoV-2-associated genetic reads and coverage of virus genome ruled out that the initial RT-PCR results were false positive. The identification that some individuals with mild COVID-19 may have controlled SARS-CoV-2 replication without developing detectable humoral immunity, opens the possibility that reinfection may be more frequent than supposed – but weakly documented.