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

Overview

Journal J Clin Med

Specialty General Medicine

Date 2024 Sep 14

PMID 39274232

Authors

Kenji Baba

Seiko Kawai

Satoshi Iwase

Takahiro Ushida

Yasuhiro Tamura

Mariko Arimoto

Makiko Nojiri

Daisuke Watanabe

Nobutaro Ban

Affiliations

Soon will be listed here.

Abstract

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. 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. 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%) ( < 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, < 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 ( < 0.05). 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.

References

Vlaeyen J, Linton S . Fear-avoidance and its consequences in chronic musculoskeletal pain: a state of the art. Pain. 2000; 85(3):317-332. DOI: 10.1016/S0304-3959(99)00242-0. View

Han Q, Zheng B, Daines L, Sheikh A . Long-Term Sequelae of COVID-19: A Systematic Review and Meta-Analysis of One-Year Follow-Up Studies on Post-COVID Symptoms. Pathogens. 2022; 11(2). PMC: 8875269. DOI: 10.3390/pathogens11020269. View

Watanabe A, Iwagami M, Yasuhara J, Takagi H, Kuno T . Protective effect of COVID-19 vaccination against long COVID syndrome: A systematic review and meta-analysis. Vaccine. 2023; 41(11):1783-1790. PMC: 9905096. DOI: 10.1016/j.vaccine.2023.02.008. View

Bahmer T, Borzikowsky C, Lieb W, Horn A, Krist L, Fricke J . Severity, predictors and clinical correlates of Post-COVID syndrome (PCS) in Germany: A prospective, multi-centre, population-based cohort study. EClinicalMedicine. 2022; 51:101549. PMC: 9289961. DOI: 10.1016/j.eclinm.2022.101549. View

Ando W, Horii T, Uematsu T, Hanaki H, Atsuda K, Otori K . Impact of overlapping risks of type 2 diabetes and obesity on coronavirus disease severity in the United States. Sci Rep. 2021; 11(1):17968. PMC: 8429758. DOI: 10.1038/s41598-021-96720-x. View

Antonelli M, Capdevila Pujol J, Spector T, Ourselin S, Steves C . Risk of long COVID associated with delta versus omicron variants of SARS-CoV-2. Lancet. 2022; 399(10343):2263-2264. PMC: 9212672. DOI: 10.1016/S0140-6736(22)00941-2. View

Vimercati L, De Maria L, Quarato M, Caputi A, Gesualdo L, Migliore G . Association between Long COVID and Overweight/Obesity. J Clin Med. 2021; 10(18). PMC: 8469321. DOI: 10.3390/jcm10184143. View

von Elm E, Altman D, Egger M, Pocock S, Gotzsche P, Vandenbroucke J . The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. J Clin Epidemiol. 2008; 61(4):344-9. DOI: 10.1016/j.jclinepi.2007.11.008. View

Magnusson K, Kristoffersen D, DellIsola A, Kiadaliri A, Turkiewicz A, Runhaar J . Post-covid medical complaints following infection with SARS-CoV-2 Omicron vs Delta variants. Nat Commun. 2022; 13(1):7363. PMC: 9709355. DOI: 10.1038/s41467-022-35240-2. View

10.

Subramanian A, Nirantharakumar K, Hughes S, Myles P, Williams T, Gokhale K . Symptoms and risk factors for long COVID in non-hospitalized adults. Nat Med. 2022; 28(8):1706-1714. PMC: 9388369. DOI: 10.1038/s41591-022-01909-w. View

11.

Komaroff A, Lipkin W . ME/CFS and Long COVID share similar symptoms and biological abnormalities: road map to the literature. Front Med (Lausanne). 2023; 10:1187163. PMC: 10278546. DOI: 10.3389/fmed.2023.1187163. View

12.

Davis H, McCorkell L, Vogel J, Topol E . Long COVID: major findings, mechanisms and recommendations. Nat Rev Microbiol. 2023; 21(3):133-146. PMC: 9839201. DOI: 10.1038/s41579-022-00846-2. View

13.

van Kessel S, Olde Hartman T, Lucassen P, van Jaarsveld C . Post-acute and long-COVID-19 symptoms in patients with mild diseases: a systematic review. Fam Pract. 2021; 39(1):159-167. PMC: 8414057. DOI: 10.1093/fampra/cmab076. View

14.

Hosoya T, Oba S, Komiya Y, Kawata D, Kamiya M, Iwai H . Apple-shaped obesity: A risky soil for cytokine-accelerated severity in COVID-19. Proc Natl Acad Sci U S A. 2023; 120(22):e2300155120. PMC: 10235975. DOI: 10.1073/pnas.2300155120. View

15.

Byambasuren O, Stehlik P, Clark J, Alcorn K, Glasziou P . Effect of covid-19 vaccination on long covid: systematic review. BMJ Med. 2023; 2(1):e000385. PMC: 9978692. DOI: 10.1136/bmjmed-2022-000385. View

16.

Xie Y, Choi T, Al-Aly Z . Postacute Sequelae of SARS-CoV-2 Infection in the Pre-Delta, Delta, and Omicron Eras. N Engl J Med. 2024; 391(6):515-525. PMC: 11687648. DOI: 10.1056/NEJMoa2403211. View

17.

Maslo C, Friedland R, Toubkin M, Laubscher A, Akaloo T, Kama B . Characteristics and Outcomes of Hospitalized Patients in South Africa During the COVID-19 Omicron Wave Compared With Previous Waves. JAMA. 2021; 327(6):583-584. PMC: 8719272. DOI: 10.1001/jama.2021.24868. View

18.

Du M, Ma Y, Deng J, Liu M, Liu J . Comparison of Long COVID-19 Caused by Different SARS-CoV-2 Strains: A Systematic Review and Meta-Analysis. Int J Environ Res Public Health. 2022; 19(23). PMC: 9736973. DOI: 10.3390/ijerph192316010. View

19.

Tsuchida T, Yoshimura N, Ishizuka K, Katayama K, Inoue Y, Hirose M . Five cluster classifications of long COVID and their background factors: A cross-sectional study in Japan. Clin Exp Med. 2023; 23(7):3663-3670. PMC: 10081305. DOI: 10.1007/s10238-023-01057-6. View