Potent anti-SARS-CoV-2 Antibody Responses are Associated with Better Prognosis in Hospital Inpatient COVID-19 Disease

Abstract

COVID-19 continues to cause a pandemic, having infected more than 20 million people globally. Successful elimination of the SARS-CoV-2 virus will require an effective vaccine. However, the immune correlates of infection are currently poorly understood. While neutralizing antibodies are believed to be essential for protection against infection, the contribution of the neutralizing antibody response to resolution of SARS-CoV-2 infection has not yet been defined. In this study the antibody responses to the SARS-CoV-2 spike protein and nucleocapsid proteins were investigated in a UK patient cohort, using optimised immunoassays and a retrovirus-based pseudotype entry assay. It was discovered that in severe COVID-19 infections an early antibody response to both antigens was associated with improved prognosis of infection. While not all SARS-CoV-2-reactive sera were found to possess neutralizing antibodies, neutralizing potency of sera was found to be greater in patients who went on to resolve infection, compared with those that died from COVID-19. Furthermore, viral genetic variation in spike protein was found to influence the production of neutralizing antibodies. Infection with the recently described spike protein variant 614G produced higher levels of neutralizing antibodies when compared to viruses possessing the 614D variant. These findings support the assertion that vaccines targeting generation of neutralizing antibodies may be useful at limiting SARS-CoV-2 infection. Assessment of the antibody responses to SARS-CoV-2 at time of diagnosis will be a useful addition to the diagnostic toolkit, enabling stratification of clinical intervention for severe COVID-19 disease.

Immunocompromised children and young people are at no increased risk of severe COVID-19

“…Validated in-house enzyme-linked immunosorbent assays (ELISA) were carried at the virology laboratories of the University of Nottingham to detect SARS-CoV-2 anti-nucleocapsid and anti-spike IgG antibodies, as previously described. 32 All assays were performed on Opentrons OT-2 Precision liquid handling robots (full protocol available on request). Original assay validations were performed on a separate sample set using commercial anti-S1 (Euroimmun) and anti-N assays (Roche) and conducted at the Rare & Imported Pathogens Laboratory at Public Health England using manufacturers’ protocols.…”

Viral infection neutralization tests: A focus on severe acute respiratory syndrome‐coronavirus‐2 with implications for convalescent plasma therapy

“…Exact quantification of nAb has implications for studying duration of immunity (acquired either by natural infection or vaccination), and selection of convalescent plasma (CP) donors, 3 or relative potency 4 and durability 5 of monoclonal antibody therapies. In fact, neutralizing potency of sera was found to be greater in patients who went on to resolve infection, compared with those that died from Covid‐19, 6 and CP therapy is more efficacious in patients receiving units with highest titres of nAb 3 …”

SARS-CoV-2 transmission from the healthcare setting into the home: a prospective longitudinal cohort study

“…Pseudotypes were produced as previously described 13 . Briefly, 1.5 × 106 HEK293T cells were seeded overnight in a 10 cm diameter Primaria-coated dish (Corning).…”