Utilizing the self-reported data of a nationwide representative COVID-19 patients in China, our study firstly reported the acute and long symptoms of COVID-19 infection, as well as explored the effects of age, gender and smoking status in the Chinese population. Data showed that the top three acute symptoms of COVID-19 infection were fever, headache and sore throat, for which age groups, gender and smoking status were influencing factors. The rates of hospitalization within 7 days, symptoms disappear within 21 days and long COVID-19 were 3.07%, 68.84% and 19.68%, respectively. Additionally, the primary symptoms of long COVID-19 were muscle weakness and headache, and female and smoking were risk factors for fatigue. Lastly, female, current smokers and those aged 45–54 years and 55–65 years (individuals aged 25–34 years as reference group) were related with more number of symptoms during acute infection period.
In general, our findings on the clinical patterns of acute/long COVID-19 infection in Chinese population were consistent with prior studies from other countries. For acute symptoms of Omicron, the most frequently reported symptoms in our study were fever (69.90%), headache (62.6%), sore throat (54.3%), fatigue (50.8%) and cough (35.1%), while results from the ZOE COVID Study showed that they were runny nose (76.5%), headache (74.7%), sore throat (70.5%), sneezing (63.0%) and persistent cough (49.8%), respectively[19]. Although the main symptoms were similar in the above two studies, the incidence of symptoms was lower in the Chinese study. In addition, the evidence that the clinical severity of infection is lower for omicron than for previously dominant delta variant has been well established[20]. Data from China further booster the evidence that omicron variant to be milder in terms of severity. In our study, the rates of hospital admission within 7 days and recovered within 21 days were 3.1% and 68.8%, respectively. Accordingly, there were 1.9% and 25.0% in the ZOE COVID study. However, the difference in absolute values may be related to population vaccination. The fact that COVID-19 vaccination could promote the recovery of COVID-19 symptoms and reduce intrinsic severity such as hospitalization and death attributable to COVID-19 is indisputable. All individuals in our study were the vaccinated population with at least two doses, while studies from other countries included unvaccinated population[19, 20]. By December 13, 2022, over 90% of the population in China mainland were vaccinated by at least two doses of inactivated vaccines. Given the small sample size of unvaccinated population, there were too many difficulties in including those without vaccination, so our study only focused on the vaccination population.
We found that among Omicron infected individuals, female and smokers had higher proportion of acute symptoms than male and non-smoker. In early period of the outbreak of epidemic, data suggested that severe or deceased COVID-19 cases were more common in male[38–40]. But the high absolute number of male might be related with more exposure chance for COVID-19 viruses, such as frequent social activities and long business trips. However, in the omicron-dominant period, both male and female would face the same risk of infection because non-pharmaceutical public health intervention (NPI) measures—including quarantining and travel restriction—has been revised based on the fact that omicron variant seems to be much more transmissible[18, 21, 41, 42] and less severe[43] than previous variants and high population vaccination rates[35, 36, 44]. Therefore, higher proportion and more number of acute symptoms for female provided a clue that female should be given more attention during omicron prevalence. Similarly, our data also indicated that smokers should be viewed as high risk population susceptible to Omicron symptoms. Extensive previous research has shown smokers were at greater risk of developing severe disease after infection than are non-smokers such as hospital admission, ICU admission and death[45–48], although cigarette smoking on COVID-19 infection are conflicting[49]. This might be related with the evidence that smoking induces substantial lung injury, because harmful substances in tobacco smoke damage epithelial cells and further compromise the epithelial barrier and mucociliary clearance[50]. Lastly, prior evidence have established that disease severity, hospital admission, and death of COVID-19 were dependent on age[22]. In our study, the highest number of Omicron symptoms were reported in the 35–44 years subgroup and Omicron had age-specific symptoms pattern, which might be helpful to better understanding of the different courses in the age groups.
Our data showed that the incidence of long COVID-19 symptoms at 3 months after a first Omicron infection was 19.68% in China mainland, and the main symptoms were muscle weakness, headache, smell/taste disorder and fatigue. The long COVID-19 rates were varied in different studies, which might be related with observation periods of sequelae of COVID-19, virus variants and vaccination status. For example, the UK’s Office for National Statistics found that of triple-vaccinated participants, the socio-demographically adjusted prevalence of self-reported long COVID four to eight weeks after a first COVID-19 infection was 8.5% for Delta and 8.0% for Omicron BA.1. and 9.1% for Omicron BA.2[51]. When they extended follow-up period to 12 to 16 weeks, there were 5.0% for Delta, 4.5% for Omicron BA.1 and 4.2% for Omicron BA.2, respectively. In addition, data from a multicenter prospective cohort study suggested that among the COVID-positive cohort, self-reported prolonged symptoms at 3 months were 52.6% in the pre-Delta group, 41.5% in the Delta and 41.5% in the Omicron, respectively, but not all participants of this study have vaccination (18.4% in the pre-Delta, 74.1% in the Delta and 98.4% in the Omicron)[52]. Moreover, in Eastern India, researchers found that 29.2% self-reported having long COVID symptoms 4 weeks after diagnosis[53], however they also found that the prevalence on long COVID after infection with only Omicron variant was 8.2%[54]. Lastly, prior studies have also supported that vaccination could reduce the risk of the post-acute sequelae of COVID-19[55–57]. Findings from a nationwide cohort study indicated that compared with unvaccinated patients, those with vaccination had significantly lower risk for dyspnoea up to three months after infection[6]. This is in accordance with studies showing that vaccination before COVID-19 breakthrough infection partially reduced the risk of post-acute sequalae[55]. For long COVID-19 symptoms, muscle weakness, smell/taste disorder and fatigue in Chinese people has been repeatedly evident by previous studies including Alpha strain, Delta strain and Omicron strain, even on a small scale or periods longer than one year[58–60].
Our study showed that long COVID-19 symptoms (such as rhinobyon/runny nose, fatigue and mood disorders) were associated with the age groups, which was consistent with prior study[6]. Therefore, it was well established that age was an important indicator for long COVID-19, but we had difficulty in comparing our results with prior studies due to different ranges of age group. Furthermore, data from Chinese population supported that both smoking and female were associated with an risk of fatigue, which was repeatedly reported by previous studies[32, 61–64]. These findings suggested an important clue to guiding future precise recovery management of long COVID-19 sequelae at 3 months.
To our knowledge, this is the largest study to date to firstly report on the symptom patterns of acute and long COVID-19 infection in Chinese mainland, during Omicron period. Strengths of the study include the use of a nationwide representative patients group, which is weighted by age ratios by gender from the Seventh National Census (2020 years) and is also validated by smoking rates from a prior study. The large sample size of over 30 thousand people provide enough statistical power to support stratified analyses. According to the data of the Chinese Center for Disease Control and Prevention, from September 26, 2022 to April 27, 2023, COVID-19 genome effective sequences of 43777 local cases in China mainland were Omicron variants, and all participants in our study was from October 1, 2022 to February 21, 2023[65]. Thus, our study could reflect the property of Omicron variant. However, there are several limitations. Firstly, to improve the accuracy of online survey data, we have limited age range to 25 to 65 years old, which limit the extrapolation of our findings. Secondly, only about 56% of infected patients was diagnosed by objective molecular tests, such as nucleic acid or antigen detection. In the early stages of the COVID-19 epidemic, limited medical resources could not meet testing needs of a large number of symptomatic individuals. In this study, the combination of symptoms and epidemiological history was also viewed as diagnostic criteria of COVID-19, which might bias our results. Thirdly, there may be health seeking bias in the self-reported symptom data, because some participants might be more active in maintaining their health and be more likely to report symptoms than others. Lastly, we also can not distinguish long COVID-19 symptoms from similar clinical manifestations that occur normally or following infections with other pathogens, but our main findings on long COVID-19 are consistent with other studies with a control group.
In conclusion, our findings indicated that omicron variant to be milder in terms of severity in China mainland and the long COVID-19 incidence at 3 months was 19.68% with main symptoms of muscle weakness, headache, smell/taste disorder and fatigue. In addition, current smokers and women had a higher proportion for each acute symptom, and were also associated with more number of symptoms during acute period. For long COVID-19, older age groups (45–54 and 55–65 years) were risk factors for rhinobyon/runny nose, fatigue and mood disorders, while female and smoking also increased an risk of fatigue. Therefore, under background of COVID-19 epidemic no longer listed as PHEIC, more attention should be given to high-risk population (current smokers, women, and the elderly) to control disease burden caused by COVID-19.