<scp>SARS</scp> ‐ <scp>CoV</scp> ‐2 Infection With Alpha B.1.1.7 Virus Induced Higher Antibody Responses Than Earlier Non‐ <scp>VOC</scp> Variants During the First Waves of the <scp>COVID</scp> ‐19 Pandemic in Norway

Antibody levels induced by SARS-CoV-2 infection have been reported to be associated with specific symptoms, disease severity, and viral load. In this study we investigated whether antibody responses were associated with virus type (Alpha B.1.1.7 or non-variants of concern (non-VOC)), viral load and clinical outcome in unvaccinated non-hospitalized adults with PCR-confirmed SARS-CoV-2 infection. Serum samples, questionnaires and symptom diaries were collected longitudinally (Day 0-180) between May 2020 and June 2021. IgG levels against ancestral Wuhan antigens and antibodies inhibiting RBD-ACE2 interaction were measured by multiplex immunoassay and flowcytometry, respectively. Antibody neutralization assays were performed with B.1 and B.1.1.7 viruses. Viral load was measured by digital-droplet PCR, and virus isolates were sequenced. Factors influencing IgG levels were investigated using Bayesian multilevel models. Alpha-cases had 2.6-3.2-fold higher IgG levels against RBD, nucleocapsid, and spike on Day 14, and higher antibody-mediated inhibition of ACE2-RBD interaction compared to non-VOC cases. Alpha-cases displayed 1.8- and 5.4-fold higher neutralizing antibody titers than non-VOC cases against B.1 and B1.1.7, respectively, but both non-VOC and Alpha cases displayed the lowest ratio of binding to neutralizing antibodies against their infecting virus type. Alpha cases reported more symptoms than non-VOC cases, but the severity of disease was similar. Nausea was significantly associated with higher IgG levels, while no association was found for viral load, despite Alpha cases having higher viral loads than non-VOC cases. This study shows higher antibody responses induced by the more transmissible Alpha virus compared to earlier non-VOC variants after mild SARS-CoV-2 infection. Reporting of nausea was positively associated with IgG levels.