In December 2019, novel pneumonia caused by coronavirus disease 2019 (COVID-19) was first reported in Wuhan, Hubei Province, China (1). After implementing strict prevention and treatment protocols of COVID-19, on February 29, 2020, twenty provinces of mainland China announced no domestic COVID-19 cases (2). However, outside China, confirmed cases continued to increase worldwide. As a result, on March 15, 2020, the World Health Organization (WHO) declared the COVID-19 outbreak as a global pandemic (3). With the reversal of the epidemic at home and abroad, China was faced intense pressure due to imported cases (4).

The most severe localized outbreak caused by an imported case occurred in Guangzhou, China. The identified people shared the same RNA sequence as the highly infectious Delta variant strain (B.1.617.2), which was first found in India (5). Transmission associated with this outbreak in Guangdong was faster and more severe than the previous one. To respond to the unprecedented threat, Guangdong Province took a series of rigorous intervention measures, including mass testing, active case finding, community spread management, travel restrictions, and affected area lockdown to contain the spread (6).

The COVID-19 outbreak has substantially negatively impacted people's mental and physical well-being (7–9). Previous studies have shown that during the initial COVID-19 outbreak in China, more than half of the patients endured psychological problems such as anxiety and depression During the post-COVID-19 era, people experienced anxiety and depression accompanied by severe sleep problems (10–14). Several studies have reported a higher prevalence of poor sleep quality and clinical insomnia among healthcare workers worldwide involved in the outbreak control and COVID-19 patient care, compared to other groups of people, as they had to work long hours under intense pressure (15–19). Approximately one-third of medical staff in China endured anxiety, depression, and stress during the early phase of COVID-19(19). Because medical graduate students belong to the medical community, student depression and anxiety soared during the pandemic (20).

Although there have been many empirical studies on the mental health of medical students in China, few studies have surveyed anxiety symptoms, depression symptoms, and poor sleep quality of medical students at Sun Yat-Sen University during the second wave of COVID-19. Therefore, this cross-sectional study aimed to understand the prevalence of anxiety and depression, mental health protective factors, and sleep quality of medical students in China during the second COVID-19 outbreak and to lay the groundwork for further measures for at-risk medical students.

Table 1 presents the participants' general characteristics. Of the 1,336 participants, 636 (47.60%) were men, and 700 (52.40%) were women. Among these participants, 876 (65.57%) were graduate students, 460 (34.43%) were doctoral students. A total of 633 (47.38%) medical students chose a negative coping style. Other detailed sample characteristics, including age, hometown location, family structure, diet for the past 2 weeks, and vaccination status, are presented below.

Figure 1 shows that among the 1,336 participants, 38.85% had potential anxiety symptoms, depressive symptoms, and poor sleep quality. The prevalence of probable anxiety symptoms, depressive symptoms, and poor sleep quality were 27.54%, 27.58%, and 18.19%, respectively. Anxiety and depressive symptoms were present in 10.07% of the participants, while all three health problems occurred in 9.96% of all participants. Poor sleep quality and anxiety symptoms, poor sleep quality, and depression symptoms, represented 1.95% of the total.

In the univariate logistic regression model (Table 2), grade, age (years), family structure, and coping style were significantly associated with the three health problems. Anxiety symptoms were markedly found in the students belonging to the Class of 2019 (p < 0.01), aged over 29 years (p < 0.01), and living in the this province p < 0.01), with a significant between-group difference. The prevalence of anxiety symptoms was significantly higher among students from families with multiple children (p < 0.05). Hometown location (OR = 1.508, 95% CI: 1.173–1.938) and diet for the past 2 weeks (OR = 1.603, 95% CI: 1.122–2.291) were associated with an increased risk of anxiety symptoms. Compared with students in other grades, students in the Class of 2019 reported the highest rate of depression symptoms and poor sleep quality. Students older than 29 and having siblings also had more depressive symptoms and poor sleep quality. Graduates who ate half the time in the canteen were 1.62 times more likely to have depression symptoms than students who ate in the canteen all the time. Those who were not vaccinated were 1.603–1.779 times more likely to have anxiety or depressive symptoms than individuals who had received two vaccine doses. Similarly, hometown was related to medical students' poor sleep quality during the local COVID-19 outbreak. However, gender, classification, diet for the last 2 weeks, and vaccination status were not associated with poor sleep quality (p > 0.05).

Multivariate logistic regression (Table 3) showed that grade (AOR = 1.617–2.147), age (AOR = 0.261–0.591), coping style (AOR = 1.453–6.419), and diet for the past 2 weeks were significantly associated with an increased risk of the three health problems. The classification was a risk factor for anxiety but belonging to a single-child family was a non-risk factor for depression. Individuals' full vaccination status had a protective effect on their mental health. Similarly, a diet based on eating take-out food was a risk factor for poor sleep quality. Graduate students in the Class of 2019 (AOR = 2.177), aged over 29, whose hometown was in the same province, who belonged to a single-child family, and who had a diet based on eating take-out food were more likely to report poor sleep quality.

To the best of our knowledge, this study was the first to investigate the psychological and sleep consequences of the second wave of the COVID-19 pandemic and its influencing factors on medical graduate students from a large general hospital cohort, approximately 2 weeks into the implementation of restrictive government rules, and stringent school, and hospital measures.

Our study has several significant findings. First, mental health and sleep quality problems were prevalent in approximately 38.85% of the participants during the second wave of the COVID-19 epidemic. The prevalence of probable anxiety symptoms, depressive symptoms, and poor sleep quality were 27.54%, 27.58%, and 18.19%, respectively. Second, graduate students in the Class of 2019, older than 29, and residing in this province had a higher prevalence of anxiety, depression, and poor sleep quality symptoms than other students. Third, the prevalence of anxiety symptoms was significantly higher among students with siblings. Graduate students born in non-single-child families also had a higher rate of depressive symptoms and poor sleep quality. There were no significant differences in the prevalence of anxiety symptoms, depressive symptoms, and poor sleep quality according to gender or program classification. Third, positive coping and having siblings were protective factors for anxiety, depression, and poor sleep symptoms in all students. Those whose hometowns were in different provinces and whose diet consisted of eating canteen food only half of the time had an increased risk of probable anxiety symptoms. Fourth, individuals who were not vaccinated were 1.603–1.779 times more likely than individuals who received two shots of a vaccine to have anxiety or depressive symptoms. However, sex, classification, diet over the preceding 2 weeks, and vaccination status were not associated with poor sleep quality. Fifth, multiple factors such as grade, age, program classification, hometown, coping style, and diet over the preceding 2 weeks were also associated with an increased likelihood of all three health problems. Moreover, individuals' completed vaccination status had a protective effect on mental health. Therefore, our study findings could frame appropriate psychological interventions to prevent the occurrence of mental health and sleep problems.

In our study, we used a standardized questionnaire to assess mental health and sleep problems during the second outbreak of the COVID-19 epidemic in China. A previous study showed that 43.77% of Chinese college students had depressive symptoms, and 20.60% had anxiety symptoms during COVID-19(33). Based on a meta-analysis, the prevalence of anxiety ranged from 8.54–88.30%, with a mean of 27.22%, and depression ranged from 13.10%−76.21% with a mean of 32.74%, among 35,160 Chinese medical students (34). A previous study found that 39% of graduate (law and medical school) students in the United States had anxiety, and 32% had depression. However, our survey showed that over 27% of Chinese graduate students had anxiety or depression symptoms. The incidence of both symptoms was similar. The lower incidence of anxiety symptoms may be due to medical students' ability to better adapt to the epidemic and their experience of the first wave of COVID-19.

Our survey revealed no significant differences between men and women in terms of anxiety symptoms, depression symptoms, and sleep disturbances, contrary to other studies (35, 36). However, we found that students in the Class of 2019 (second grade) had the highest risk of mental problems. This increased risk may be due to the students' delayed academic progress and difficulty coping with clinical practice and research as they did not get the opportunity to go to the laboratory or partake in clinical practice because of the sudden onset of the pandemic (37).

A previous study showed that age was negatively correlated with anxiety and depression. However, our study found that graduate students aged above 29 years, had a higher proportion of mental problems during the second wave of COVID-19(38). A possible reason for this finding may be that they face pressure to support their families (39).

We found that students whose hometowns belong to the same province had a higher prevalence of anxiety symptoms than those whose hometowns were in other provinces. This elevated risk may be because the students in this province worry more about their families' risk of contracting the COVID-19 infection.

Our study's findings suggested that 48.3% of students in the Class of 2019 had sleep problems, significantly higher than those from other classes. In addition, more than half of the students aged over 29 years had poor sleep quality. This risk may be due to the increased stress from the ongoing COVID-19 pandemic and academic expectations (40, 41).

It has been reported in the literature that diet and sleep have complex interactions (15). In our study, a good and regular diet, such as eating in the canteen, is a protective factor for sleep. In addition, studies have shown that before and during the COVID-19 emergency, an increase in sleeping hours, sleep latency, and wake-up time impaired sleep quality and exacerbated insomnia symptoms.

We also found that a positive coping style may ensure good sleep and mental health. These involved positive appraisal and thinking, distancing, problem-solving, and help-seeking behaviors. These active coping strategies can enhance mental health by promoting an individual's sense of control over a chaotic environment and creating opportunities to establish satisfying relationships with a support network (42, 43). An increasing amount of evidence suggests that positive coping is a protective factor for mental health. For example, it has been reported that the using a positive coping style could promote university students' academic adjustment and reduce displays of maladaptive behaviors (44). Negative coping techniques were positively related to psychological distress during the COVID-19 outbreak (45). Previous studies have shown that higher negative coping technique scores were related to increased prevalence of anxiety symptoms. In contrast, greater use of positive coping techniques was related to a reduced prevalence of anxiety symptoms. The association between negative coping styles and anxiety symptoms is mediated by sleep quality (46). Our research indicates that positive coping has a powerful protective effect against anxiety and depression symptoms. By adopting proper coping methods and equipping oneself with the necessary coping and stress management skills, associated high levels of perceived stress and anxiety could be mitigated (47).

We found that vaccination status potentially influenced mental health. Unvaccinated students had a high incidence of anxiety and depression symptoms during the second wave of COVID-19. Despite the good safety and efficacy of COVID-19 vaccines made in China, some public skepticism about the vaccines persists (48). They may be concerned about the uncertainty of its effectiveness, side effects, and effective duration (49). It should be noted that mass exposure to media coverage of the COVID-19 or vaccine was associated with an increased risk of probable acute stress and anxiety symptoms (50). Our findings are consistent with COVID-19 related anxiety and fear of infection. Health-related consequences correlated significantly positively with vaccine acceptance (51). In addition, people who refuse the vaccine may pay more attention to daily self-protection. However, a study indicated that very high adherence to personal hygiene factors (such as hand washing, use of disinfectants, wiping down knobs, and surfaces, etc.) predicted f higher anxiety levels (52).

Further, we found that eating at the canteen was more protective from anxiety and depression than eating take-away food. Increasing evidence indicates a strong association between a poor diet and the exacerbation of mood disorders, including anxiety and depression (53). Take-out foods tend to be unhealthy because they are more energy-dense and nutrient-poor than canteen or home-cooked foods. They often contain high quantities of fat, salt, and sugar contents, associated with weight gain and various adverse health outcomes (54). In China, many hot set meals on take-out platforms have the problem of excess energy supply (55). Improving diet quality and subsequent gut health may benefit individuals' mental health (56). Good diet and proper nutrition play essential roles in psychological and physical well-being (57).

This study has several limitations. First, although our sample was large and participants had good educational backgrounds, all the students were initially sampled from one university in Guangzhou, Guangdong province. Hence, it is uncertain whether our findings could be generalized to all students, especially graduate students who lived in local outbreak regions. Second, the duration of the study was short. As the second wave of COVID-19 was short-lived, we only focused on the symptoms that developed during the 2 weeks. Third, no causality could be made between COVID-19 and mental health problems due to the cross-sectional design of our study. Finally, although the measurements used in the current study have good psychometric properties, they are self-reports for screening rather than clinical diagnoses.

This large-scale survey of medical students in China demonstrated that about 38.85% of students had probable depression, anxiety, or poor sleep quality symptoms during the second wave of the COVID-19 epidemic. In addition, multiple factors, such as being unvaccinated, negative coping style, unhealthy diet, grade, age over 29 years, having siblings, having a hometown in the same province, and classification were associated with an increased risk of mental health and sleep problems. These findings may have important implications for prevention, psychosocial interventions, and future research. Notably, mental health services should be made available for graduate students.

The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author/s.

The studies involving human participants were reviewed and approved by Ethics Committee the First Affiliated Hospital of Sun Yat-sen University (number: [2021]771). The patients/participants provided their written informed consent to participate in this study.

HL and LX conceived and designed the questionnaire. HL recruitment and payment of participants. XL, WS, HT, ZD, and JY analyzed the data. LY and HW wrote and revised the paper. All the authors have approved the manuscript and agreed with submission to your esteemed journal.

This work was supported by the National Social Science Fund of China (Grant no. 82073049), and the Scientific and Technological Planning Project of Guangzhou City (Grant no. 201903010093).

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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