Symptoms, Course, and Factors Related to Long-Term Morbidity, Including Differences between Infection Strains, in Patients with Long COVID in a Primary Care Clinic in Japan: An Observational Study.

Objectives: The objectives were to investigate the clinical characteristics and course of long COVID, defined as the persistence of symptoms at least one month after the onset of COVID-19, in outpatients and to clarify differences in symptoms between SARS CoV-2 mutant strains. Methods: Our observational study in a primary care institution in Japan included 1053 patients with long COVID who visited our outpatient clinic between April 2021 and March 2023. Symptom distribution, performance status, and patient background at the time of the first outpatient visit were compared between infectious strains (Delta and before group and Omicron group). Background factors and symptoms related to time to remission were also analyzed. Results: The severity of COVID-19 in the acute phase was mild, moderate, and severe in 82.2%, 14.9%, and 2.9% in the Delta and before group; and in 97.6%, 1.7%, and 0.4% in the Omicron group, respectively. Vaccination coverage was significantly different between the Delta and before (37.1%) and Omicron groups (73.1%) ( p < 0.001), probably due to the period of vaccine unavailability in the former group. Symptoms of fatigue and headache occurred most frequently, irrespective of infectious strain. The mean number of symptoms per patient was significantly higher in the Delta and before group than the Omicron group (3.4 vs. 2.7, p < 0.0001). The median time overall to remission of long COVID was 169 days. Cox hazard model analysis identified female sex, high body mass index, and dyspnea (but not infectious strain) as significant factors prolonging the time to remission ( p < 0.05). Conclusions: Differences in the number of symptoms between infectious strains may be related to differences in viral virulence and/or vaccination coverage. However, the clinical course was found to be minimally influenced by the infectious strain. The present results should improve the understanding of prognosis in patients with long COVID from both the clinical and social perspectives.