A total of 51,822 persons were invited to participate in the study, of whom 18,183 responded to the questionnaire (response rate 35.1%). The response rate was higher in the infected group than in the noninfected group (37.3% vs. 32.9%, difference of 4.4% [95% CI 3.0%–5.8%]). The response rate was higher among female than male persons in all age groups of both infected and noninfected groups. Among male invitees, the difference in response rates between the infected and noninfected groups was large for age groups in their 50s (12.8% [95% CI 8.1%–17.5%]) and 60s (8.5% [95% CI 1.6%–15.4%]) (Table 1).

We excluded 3,473/18,183 respondents for responses of infectious status inconsistent with HER-SYS (answering different infection statuses or different diagnosis date) and reporting a prior infection and 9 because their records were missing data on age or symptoms. A total of 14,710 participants (8,392 cases and 6,318 controls) were eligible for the analysis (Figure 1). Mean age of all participants was 42.4 (SD 11.7) years; 8,502 (57.8%) participants were female and 6,087 (41.4%) male (Table 2). Mean age of case participants was 42.3 (SD 11.6) years; 4,802 (57.2%) case participants were female and 3,535 (42.1%) male. The mean follow-up period from SARS-CoV-2 infection to the response date was 167.9 (SD 14.5) days. Most cases (8,326 [99.2%] patients) demonstrated asymptomatic to mild disease, whereas 66 (0.8%) cases had moderate to severe disease.

The percentage of post–COVID-19 condition for cases was 11.8%, whereas the percentage of persistent symptoms among controls was 5.5% (Figure 2). The prevalence did not differ between cases under follow-up for <6 months (11.6%) and cases under follow-up for >6 months (12.6%). The most frequent post–COVID-19 condition was cough (3.7%), followed by difficulty concentrating (3.1%), hair loss (2.8%), fatigue (2.4%), and brain fog (2.2%). The most frequent persistent symptoms among the controls were sleep disorders (1.3%), followed by cough (0.9%), fatigue (0.7%), and rhinorrhea (0.7%). The age- and sex-adjusted odds ratio (OR) of any persistent symptoms for cases versus controls was 2.33 (95% CI 2.05–2.64). Symptoms with higher OR in cases than controls were ageusia (27.4 [95% CI 6.7–111.8]), muscle weakness (11.8 [95% CI 5.5–25.5]), anosmia (11.6 [95% CI 4.7–28.6]), hair loss (6.5 [95% CI 4.4–9.6]), and brain fog (5.9 [95% CI 3.8–9.0]).

We conducted multivariable logistic regression analysis to investigate the factors associated with post–COVID-19 condition among cases (Table 3). In all 3 models, participants 40–49 years of age had higher odds of having post–COVID-19 condition than those 20–29 years (OR 1.26, 95% CI 1.01–1.57 for model 3); female participants had higher odds of having post–COVID-19 condition than male participants (OR 2.00, 95% CI 1.71–2.34). When models were further adjusted, 2 variables were associated with having post–COVID-19 condition: having any underlying medical conditions (OR 1.36, 95% CI 1.16–1.59, compared with no underlying medical conditions), and severity of acute COVID-19 (mild, OR 2.07, 95% CI 1.18–3.66; moderate, OR 4.49, 95% CI 1.97–10.23, compared with asymptomatic). Those participants vaccinated before infection had lower odds of developing post–COVID-19 condition (OR 0.75, 95% CI 0.60–0.95, compared with unvaccinated). Socioeconomic status, including household income and educational level, was not associated with post–COVID-19 condition.

Among the 992 cases who had experienced any post–COVID-19 condition, 84 (8.5%) answered that the condition was a serious hindrance on their daily lives at the time of response. A total of 402 (40.5%) noted that it was no hindrance, 362 (36.5%) mild hindrance, and 144 (14.5%) moderate hindrance.

We conducted a population-based study using a self-reported questionnaire among adults in Japan who had confirmed SARS-CoV-2 infection during July–August 2022, when the Omicron BA.5 subvariant was dominant. We compared their post–COVID-19 condition with concordant persistent symptoms among noninfected controls. The percentage of post–COVID-19 condition was 11.8% for cases, which was 2.3 times higher than the 5.5% of persistent symptoms noted in controls. The cases had a 6.2% higher prevalence of post–COVID-19 condition than the controls, suggesting that their symptoms were likely associated with SARS-CoV-2 infection.

Population-based studies of infected persons in the United Kingdom (n = 56,003) and the United States (n = 1,480) using smartphone applications reported that the prevalence of post–COVID-19 condition associated with the Omicron variant, defined as symptoms lasting 4 weeks after the infection, was 4.5%–18.7% (12,23). Another population-based study of infected persons in the United States (n = 16,091) showed a prevalence of 11.2% (16) applying the WHO definition of the continuation or development of new symptoms 3 months after the initial SARS-CoV-2 infection, with those symptoms lasting for >2 months with no other explanation (27). Although the definition of post–COVID-19 condition varies among previous studies (12,16,23,27), the proportion shown in our study is consistent with previous results. In those reports, post–COVID-19 condition was less prevalent among those infected during the Omicron variant–dominant wave than those infected during the previous waves with the ancestral strain predominance (16,23). However, although a multicenter prospective cohort study showed a higher proportion of prolonged severe fatigue and multiple symptoms at 3 months during the pre-Delta wave than that during the Delta and Omicron waves, the differences disappeared after accounting for sociodemographics and vaccination status (19). Systematic reviews suggested that vaccination before infection was associated with a lower risk of experiencing post–COVID-19 condition (30,31). Similarly, we found that vaccination before infection was associated with lesser post–COVID-19 condition. An in-depth study would clarify whether the reduced risk for post–COVID-19 condition during the Omicron wave was a result of the differences in strains, the effect of vaccination, or both.

Population-based large cohort studies in the United Kingdom (n = 606,434 and n = 486,149) and Germany (n = 11,710) reported that patients infected with previous-variant SARS-CoV-2 frequently experienced persistent symptoms such as fatigue, shortness of breath, concentration difficulties, memory disturbance, hair loss, and anosmia (5,7,32). Studies on patients infected with the Omicron variant, including a population-based study in the United States (n = 16,091) and hospital-based studies from China (n = 1,829) and India (n = 524), revealed that fatigue, brain fog, cough, and shortness of breath were frequently observed as post–COVID-19 condition (13,16,33). Our findings were comparable with previous results; we observed that post–COVID-19 condition after the Omicron-dominant epidemic frequently included neurologic symptoms such as difficulty concentrating, fatigue, and brain fog, in addition to cough and hair loss. In addition, those neurologic symptoms, as well as ageusia, anosmia, and muscle weakness, were distinctive symptoms among cases, who showed a higher OR than controls. Fatigue and neurocognitive impairment are reportedly related to impaired health recovery and reduced working capacity, even among young and middle-aged adults, after mild infection (7). Our results showed that ≈10% of those who had post–COVID-19 condition had persistent difficulties in daily living 4.5–7 months after the Omicron-dominant wave, which may have led to a deterioration in economic conditions or work productivity. Although background socioeconomic status was not associated with developing post–COVID-19 condition in this study, further investigation is required to evaluate the effect of post–COVID-19 condition on changes in economic conditions, schooling, and employment.

Large-scale population-based cohort studies on infection before the Omicron wave found that post–COVID-19 condition was more common in female persons, smokers, persons with obesity, those with more severe acute COVID-19 symptoms, and those who were deprived or had lower household income (5,7,32). Moreover, hospital-based studies in China (n = 21,799) and South Africa (n = 4,685) showed that the female sex, concurrent conditions, and severe acute illnesses were associated with post–COVID-19 condition in association with the Omicron variant (14,21), which was consistent with our findings. Although the results regarding age are unclear, some studies on the Omicron variant have suggested that the population 18–50 years of age has a higher risk for post–COVID-19 condition (21,34). Our study showed that post–COVID-19 condition for those infected during the Omicron-dominant epidemic was also more prevalent in middle-aged persons. A substantial proportion of the working-age population might have been affected; of 9 million persons infected during July–August 2022 in Japan, 31.2% were in their 30s and 40s (35).

The strengths of this study are the large number of participants including noninfected controls, the population-based approach, and the inclusion of all infected residents registered in the HER-SYS database within a municipality. We compared the infected persons with noninfected persons as a control and assessed the proportion of post–COVID-19 condition after the Omicron-dominant wave.

The first limitation of this study is that the response rate was higher among the infected group than the noninfected group overall. The infected participants may have been more interested in the survey on COVID-19 and post–COVID-19 condition. However, because we did not specify the purpose of the survey to investigate the post–COVID-19 condition but rather informed the participants that we aimed to investigate the effect of the pandemic on their health and daily lives, we believe that the influence of interest in post–COVID-19 condition on the responses to the questionnaire was small. Moreover, the response rate was higher for infected and noninfected female participants and middle-aged infected male participants; this finding could have been because those persons were inherently willing to answer questionnaires more than other persons, or because patients with those attributes (such as female sex and middle age) suffered more from persistent symptoms and had a higher motivation to answer the questionnaire. The results could be biased in both ways; however, we believe the effect was small because the higher odds of having post–COVID-19 condition in our study were consistent with findings from previous studies. Second, although we excluded those who self-reported having SARS-CoV-2 infection, it is possible that some infected persons were included in the controls, causing an underestimation of the difference in persistent symptoms between the cases and controls. Third, because the study was retrospective, recall bias may have occurred. In addition, because we relied on self-reporting, we could not rule out the possibility that the participants’ symptoms were caused by conditions other than COVID-19. However, we estimated the symptoms attributable to COVID-19 by comparing with a noninfected control group. Finally, although this study included all infected persons registered in the nationally established registry system, caution is needed to generalize the results of this single-city analysis to other populations in Japan.

In this population-based study, 11.8% of patients with COVID-19 had post–COVID-19 condition during the Omicron-dominant wave; this rate was 2.3 times higher than the persistent symptoms among noninfected controls. Among the cases, female sex, underlying medical conditions, and severity of acute COVID-19 were associated with having post–COVID-19 condition. We recommend a longer follow-up study of the effects on daily life and socioeconomic status after infection during the Omicron-dominant wave.