Reinfection with SARS-CoV-2 and Failure of Humoral Immunity: a case report

Abstract

Recovery from COVID-19 is associated with production of anti-SARS-CoV-2 antibodies, but it is uncertain whether these confer immunity. We describe viral RNA shedding duration in hospitalized patients and identify patients with recurrent shedding. We sequenced viruses from two distinct episodes of symptomatic COVID-19 separated by 144 days in a single patient, to conclusively describe reinfection with a new strain harboring the spike variant D614G. With antibody and B cell analytics, we show correlates of adaptive immunity, including a differential response to D614G. Finally, we discuss implications for vaccine programs and begin to define benchmarks for protection against reinfection from SARS-CoV-2.

Evidence of SARS-CoV-2 re-infection with a different genotype

“…4 It is the most comprehensive studied as it documented seroconversion following the first infection, showed drastically different viral genomes with 34 nucleotide differences, and ruled out errors of samples by techniques commonly used for forensic identifications. The present case adds to 13 previously reported cases of re-infection with a different SARS-CoV-2 strain that occurred in China, Belgium, the Netherlands, India, Ecuador and the USA 2 , 5 , 6 , 7 , 8 , 9 (Supplementary Table S2) documented with varying degrees of robustness (Supplementary Table S3). Mean age (± standard deviation) of the 14 cases was 40±20 years (range, 24-89), and patients were mostly immunocompetent individuals (in 12 cases (86%)).…”

Functional importance of the D614G mutation in the SARS-CoV-2 spike protein

“…Early discussions raised concern of possible antigenic drift, suggesting that vaccines targeting S(D614) may offer limited protection against viruses with S(G614) and that antibodies in exposed individuals would not offer cross-protection [ 64 ]. Indeed, though reinfections have been reported with two independent isolates harboring the same S protein variant [ 65 ], recent case reports identified first infection events with D614 virus followed by reinfection with G614 virus [ 66 , 67 ]. However, many studies have shown that humoral immunity is likely protective against both variants.…”

Will SARS-CoV-2 Infection Elicit Long-Lasting Protective or Sterilising Immunity? Implications for Vaccine Strategies (2020)

“…To date, among the few reinfection cases reported, one study found the humoral immune response to be defective during the second infection, suggesting that a failure of the humoral response during the first infection may account for susceptibility to reinfection ( 42 ). In addition, Chen et al demonstrate a positive correlation between the magnitude of NAb titres and disease severity but also report immense heterogeneity between the NAbs generated—with 80.7% patients producing S1 specific NAbs and only 40% patients producing NAbs to both S1 and S2.…”

“…The first challenge studies in macaques showed that SARS-CoV-2 infection may result in the development of protective immunity, when the animals were challenged soon after resolution of the primary infection (39,40). However, a number of cases of reinfection in humans have now been reported a few months after initial infection, challenging the idea of long-lasting protective immunity (41)(42)(43)(44)(45)(46)(47).…”