Vaccination status and long COVID symptoms among patients hospitalized with COVID-19: the WHF COVID-19 Long-term Study

Abstract Background COVID-19 vaccinations have been found to be effective in reducing the severity of COVID-19 infection and in-hospital deaths; however, insufficient evidence exists about the effect of vaccination on long term morbidity and mortality after hospitalization in patients from low- and middle-income countries. Methods The global WHF COVID-19 Long-Term Follow-up Study recruited 2,504 COVID-19 hospitalized patients from 26 collaborating sites in 16 countries between January 2022 - June 2023. Patients were followed up , at 1, 3, 6, and 9-12 months post-discharge to examine short- and long-term physical and psycho-social outcomes. A standardised questionnaire was used to collect data on demographics, pre-existing comorbidities, COVID-19 symptoms on admission, vaccination status, and outcomes at discharge, including persisting symptoms, new onset hypertension or diabetes, major adverse cardiovascular events (MACE), and mortality. We compared persistent long COVID symptoms, MACE, and mortality outcomes up to one year by COVID-19 vaccination status. Results The majority of study participants were Asians (78%), males (56%) with a mean (SD) age of 59.2 (19.9) years and from low- and middle-income (65%), upper middle-income (20%) and high-income (15%) countries. The most commonly reported comorbidities were hypertension: 54% and diabetes: 38%. Approximately two-thirds of the patients had received at least one dose of COVID-19 vaccination prior to hospitalization. Unvaccinated patients were more likely to present with dyspnea (60% vs 53%, p-value<0.001) and acute respiratory infection (15% vs 9%, p-value<0.001) during hospitalization. Unvaccinated patients also had twice the in-hospital mortality rate, compared with vaccinated patients (6% vs 3%, p-value<0.001). Unvaccinated patients had a greater incidence of MACE (23% vs 18%, p-value=0.016) during hospitalization and across all follow-up visits. Unvaccinated patients also had a higher mortality rate across all follow-up visits (mortality at one year post-discharge 14% vs 10%, p<0.001). At the 9-12 month follow-up, about a quarter of the patients had at least one long COVID symptom, but unvaccinated patients had a higher rate of long COVID symptoms, including fatigue (23% vs 14%, p<0.001), palpitations (17% to 7%, p-value<0.001), and anxiety (13% to 7%, p=0.002). Conclusions Our data highlight the long-term protective effect of COVID-19 vaccination on reducing morbidity and mortality among COVID-19 patients after hospital discharge. However, a substantial proportion of COVID-19 vaccinated patients still showed persistent long COVID symptoms (22%) and mortality (10%). Future research is needed to investigate individual- and health system-level factors contributing to poor health outcomes post-COVID-19 infection.