High titers of neutralizing SARS-CoV-2 antibodies six months after symptom onset are associated with increased severity in COVID-19 hospitalized patients

Background: Viral shedding and neutralizing antibody (NAb) dynamics among patients hospitalized with severe coronavirus disease 2019 (COVID-19) and immune correlates of protection have been key questions throughout the pandemic. We investigated the duration of reverse transcriptase-polymerase chain reaction (RT-PCR) positivity, infectious viral shedding and NAb titers as well as the association between NAb titers and disease severity in hospitalized COVID-19 patients in Denmark 2020-2021.

Materials and methods: Prospective single-center observational cohort study of 47 hospitalized COVID-19 patients. Oropharyngeal swabs were collected at eight time points during the initial 30 days of inclusion. Serum samples were collected after a median time of 7 (IQR 5 - 10), 37 (IQR 35 - 38), 97 (IQR 95 - 100), and 187 (IQR 185 - 190) days after symptom onset. NAb titers were determined by an in-house live virus microneutralization assay. Viral culturing was performed in Vero E6 cells.

Results: Patients with high disease severity had higher mean log₂ NAb titers at day 37 (1.58, 95% CI [0.34 -2.81]), 97 (2.07, 95% CI [0.53-3.62]) and 187 (2.49, 95% CI [0.20- 4.78]) after symptom onset, compared to patients with low disease severity. Peak viral load (0.072, 95% CI [- 0.627 - 0.728]), expressed as log₁₀ SARS-CoV-2 copies/ml, was not associated with disease severity. Virus cultivation attempts were unsuccessful in almost all (60/61) oropharyngeal samples collected shortly after hospital admission.

Conclusions: We document an association between high disease severity and high mean NAb titers at days 37, 97 and 187 after symptom onset. However, peak viral load during admission was not associated with disease severity.

Trial registration: The study is registered at https://clinicaltrials.gov/ (NCT05274373).