Long COVID among the first three waves of COVID-19 in Japan: a multicentre cohort study

Abstract

Objectives: Severe acute respiratory syndrome coronavirus 2 significantly impacts Japan with a high number of infections and deaths reported. Long coronavirus disease (COVID) characterised by persistent symptoms after COVID-19 has gained recognition but varies across studies. This study aimed to investigate the differences in long COVID among patients hospitalised during Japan's first three waves of the pandemic.

Design: Multicentre prospective cohort study.

Setting: 26 medical facilities across Japan between February 2020 and February 2021.

Participants: In total, 1066 hospitalised patients diagnosed with COVID-19 were included with 206, 301 and 559 patients in the first, second and third waves, respectively. Data were collected using electronic data capture and patient-reported outcome forms.

Primary and secondary outcome measures: Long COVID was assessed at 3, 6 and 12 months after COVID-19 diagnosis.

Results: Significant differences were observed between the waves in various baseline and clinical characteristics such as age, body mass index (BMI), comorbidities, the severity of COVID-19, complications and treatment during hospitalisation. Long COVID, particularly dyspnoea, was most prevalent in the first wave. Multivariate logistic regression analysis confirmed a significant positive association between the first wave and long COVID including dyspnoea after adjusting for age, sex, BMI, smoking status and COVID-19 severity.

Conclusions: Patients hospitalised during the first wave had a higher risk of experiencing long COVID, especially dyspnoea, than those hospitalised during the other waves. These findings underscore the need for continued monitoring and managing long COVID in COVID-19 survivors, particularly in those hospitalised during the first wave.

Trial registration number: UMIN000042299.

Keywords: COVID-19; Infection Control.

Figure 1. Number of patients in the present study and newly diagnosed COVID-19 cases in Japan in each COVID-19 wave between January 2020 and March 2021. The first case of COVID-19 was reported in Japan on 16 January 2020. The bar graph represents the number of patients in the present study and the line graph shows the number of patients newly diagnosed with COVID-19 in Japan. The first wave spanned from 29 January 2020 to 13 June 2020, the second wave from 14 June 2020 to 9 October 2020 and the third wave from 10 October 2020 to 28 February 2021. The red, blue and green bar graphs indicate patients diagnosed with COVID-19 during the first, second and third waves, respectively.

Figure 2. Comparison of the prevalence of long COVID and dyspnoea in patients in each COVID-19 wave. (A) Comparison of the proportion of patients in each COVID-19 wave with one or more symptoms of long COVID at 3, 6 and 12 months, respectively, and across all three time points after diagnosis of COVID-19. No significant differences were observed at each time point. However, a significant difference was found in the proportion of patients with one or more symptoms of long COVID across all time points with the highest proportion observed during the first wave. The p value was calculated using the χ² test. (B) Comparison of the proportion of patients in each COVID-19 wave with dyspnoea at 3, 6 and 12 months, respectively, and across all three time points after diagnosis of COVID-19. Significant differences were observed at every time point and across all time points with the highest proportion observed during the first wave in all instances. P values were calculated using the χ² test. Long COVID, long coronavirus disease.

Figure 3. Comparison of the proportion of patients with each symptom of long COVID among infection waves at 3, 6 and 12 months. Only the symptoms with a prevalence of 5% or higher at any one of the three time points in at least one of the three waves are shown. Significant differences were observed in the prevalence of dyspnoea, alopecia, sleeping disorders and headaches at 3 months; dyspnoea and numbness at 6 months; and dyspnoea at 12 months with the first wave exhibiting the highest prevalence. Long COVID, long coronavirus disease.

Figure 4. Risk of prolonged long COVID, presence of dyspnoea and prolonged dyspnoea according to the first wave compared with the second and third waves. Forest plot of adjusted ORs and 95% CIs according to the first wave compared with the second and third waves using multivariate logistic regression analysis. Outcomes were adjusted for the COVID-19 wave, age, sex, BMI, smoking status and severity of COVID-19. Compared with the second and third waves, patients in the first wave exhibited a significantly higher risk of having one or more symptoms of long COVID at all time points as well as experiencing dyspnoea at each or all time points. Long COVID, long coronavirus disease.