Long-term clinical, virological and immunological outcomes in patients hospitalized for COVID-19: antibody response predicts long COVID

Abstract

ABSTRACTObjectiveLong-term data following SARS-CoV-2 infection are limited. We aimed to characterize the medium and long-term clinical, virological, and immunological outcomes after hospitalization for COVID-19, and to identify predictors of long-COVID.MethodsProspective, longitudinal study conducted in COVID-19 patients confirmed by RT-PCR. Serial blood and nasopharyngeal samples (NPS) were obtained for measuring SARS-CoV-2 RNA and S-IgG/N-IgG antibodies during hospital stay, and at 1, 2 and 6 months post-discharge. Genome sequencing was performed where appropriate. Patients filled out a COVID19-symptom-questionnaire (CSQ) at 2-month and 6-month visits, and those with highest scores were characterized.ResultsOf 146 patients (60% male, median age 64 years) followed-up, 20.6% required hospital readmission and 5.5% died. At 2-months and 6-months, 9.6% and 7.8% patients, respectively, reported moderate/severe persistent symptoms. SARS-CoV-2 RT-PCR was positive in NPS in 11.8% (median Ct=38) and 3% (median Ct=36) patients at 2-months and 6-months, respectively, but no reinfections were demonstrated.Antibody titers gradually waned, with seroreversion occurring at 6 months in 27 (27.6%) patients for N-IgG and in 6 (6%) for S-IgG. Adjusted 2-month predictors of the highest CSQ scores (OR [95%CI]) were lower peak S-IgG (0.80 [0.66-0.94]) and higher WHO-severity-score (2.57 [1.20-5.86]); 6-month predictors were lower peak S-IgG (0.89 [0.79-0.99]) and female sex (2.41 [1.20-4.82]); no association was found with prolonged viral shedding.ConclusionsLate clinical events and persistent symptoms in the medium and long term occurred in a significant proportion of patients hospitalized for COVID-19. Gender, severity of illness and weaker antibody responses, but not viral shedding, were associated with long-COVID.SummaryThis study characterizes the long-term clinical, virological, and immunological outcomes following COVID-19 hospitalization. We found a significant proportion of late clinical events and persistent symptoms. Gender, severity of illness and weaker antibody responses, but not viral shedding, predicted long-COVID.