Durability and determinants of anti-SARS-CoV-2 spike antibodies following the second and third doses of mRNA COVID-19 vaccine.

OBJECTIVES: To examine the differences in durability and its determinants of humoral immunity following 2- and 3-dose COVID-19 vaccination. METHODS: Throughout the pandemic, we evaluated the anti-spike IgG antibody titers of 2- and 3-dose mRNA vaccine recipients over time among the staff of a medical and research center in Tokyo. Linear mixed models were used to estimate trajectories of antibody titers from 14 to 180 days after the last immune-conferred event (vaccination or infection) and compare antibody waning rates across prior infection and vaccination status, and across background factors in infection-naïve participants. RESULTS: A total of 6901 measurements from 2964 participants (median age, 35 years; 30% male) were analyzed. Antibody waning rate (percentage per 30 days [95% CI]) was slower after 3 doses (25% [23-26]) than 2 doses (36% [35-37]). Participants with hybrid immunity (vaccination and infection) had further slower waning rates: 2-dose plus infection (16% [9-22]); 3-dose plus infection (21% [17-25]). Older age, male sex, obesity, coexisting diseases, immunosuppressant use, smoking, and alcohol drinking were associated with lower antibody titers, whereas these associations disappeared after 3 doses, except for sex (lower in female participants) and immunosuppressant use. Antibody waned slightly faster in older participants, females, and alcohol drinkers after 2 doses, whereas it did not differ after 3 doses across except sex. DISCUSSION: The 3-dose mRNA vaccine conferred higher durable antibody titers, and previous infection modestly enhanced its durability. The antibody levels at a given time point and waning speed after 2 doses differed across background factors; however, these differences mostly diminished after 3 doses.

Omicron BA.1 neutralizing antibody response following Delta breakthrough infection compared with booster vaccination of BNT162b2.

BACKGROUND: Longitudinal data are lacking to compare booster effects of Delta breakthrough infection versus third vaccine dose on neutralizing antibodies (NAb) against Omicron. METHODS: Participants were the staff of a national research and medical institution in Tokyo who attended serological surveys on June 2021 (baseline) and December 2021 (follow-up); in between, the Delta-dominant epidemic occurred. Of 844 participants who were infection-naïve and had received two doses of BNT162b2 at baseline, we identified 11 breakthrough infections during follow-up. One control matched to each case was selected from boosted and unboosted individuals. We compared live-virus NAb against Wild-type, Delta, and Omicron BA.1 across groups. RESULTS: Breakthrough infection cases showed marked increases in NAb titers against Wild-type (4.1-fold) and Delta (5.5-fold), and 64% had detectable NAb against Omicron BA.1 at follow-up, although the NAb against Omicron after breakthrough infection was 6.7- and 5.2-fold lower than Wild-type and Delta, respectively. The increase was apparent only in symptomatic cases and as high as in the third vaccine recipients. CONCLUSIONS: Symptomatic Delta breakthrough infection increased NAb against Wild-type, Delta, and Omicron BA.1, similar to the third vaccine. Given the much lower NAb against Omicron BA.1, infection prevention measures must be continued irrespective of vaccine and infection history while the immune evasive variants are circulating.

Immunogenicity and safety of single booster dose of KD-414 inactivated COVID-19 vaccine in adults: An open-label, single-center, non-randomized, controlled study in Japan.

Although vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease 2019 (COVID-19) induce effective immune responses, vaccination with booster doses is necessary because of waning immunity. We conducted an open-label, non-randomized, single-arm study in adults in Japan to assess the immunogenicity and safety of a single booster dose of the KD-414 purified whole-SARS-CoV-2-virion inactivated vaccine candidate after vaccination with a primary series of BNT162b2. The primary endpoint was serum neutralizing activity at 7 days after booster injection compared with the primary series of BNT162b2. The SARS-CoV-2-structural protein-binding antibody level and T cell response against SARS-CoV-2-Spike (S) peptides were also examined as secondary endpoints, and safety profile assessments were conducted. Twenty subjects who participated in a previous study declined an injection of KD-414 (non-KD-414 group) and received a booster dose of BNT162b2 instead. The non-KD-414 group was compared to the KD-414 group as a secondary outcome. A single dose of KD-414 induced lower serum neutralizing activity against the wild-type virus within 7 days compared to after the primary series of BNT162b2 but significantly induced anti-SARS-CoV-2-S1-receptor-binding domain-binding immunoglobulin G (IgG) antibodies and SARS-CoV-2-S peptide-specific CD4+ and CD8+ T cell responses. Local or systemic symptoms were significantly lower in the participants who received KD-414 than in those who received BNT162b2 as the third COVID-19 vaccine dose. The present data indicate that a single booster dose of KD-414 induces a substantial immune response in BNT162b2-primed individuals and has a good safety profile, thereby supporting further clinical trials to identify rational targets.

Analysis of Previous Infection, Vaccinations, and Anti-SARS-CoV-2 Antibody Titers and Protection Against Infection With the SARS-CoV-2 Omicron BA.5 Variant.

This cohort study examines whether preinfection anti­SARS-CoV-2 spike antibody titer is associated with protection against Omicron BA.5 infection among staff members of a medical and research center in Tokyo, Japan.

Changes in body composition of patients undergoing hemodialysis during the coronavirus disease 2019 pandemic: a retrospective longitudinal study.

Background: The spread of coronavirus disease 2019 (COVID-19) has dramatically altered the lifestyles of many people worldwide. Several studies reported that body weight of young adults increased during the COVID-19 pandemic; however, weight loss has been observed in the elderly population. Therefore, trends in body composition due to the COVID-19 pandemic may vary depending on the characteristics of the population. This study aimed to investigate the changes in body mass index (BMI), muscle mass, and fat mass before and during the COVID-19 pandemic among patients undergoing hemodialysis. Methods: In this retrospective longitudinal study, we enrolled 115 clinically stable outpatients (mean age: 65.7 ± 11.2 years, 62.6% men) who underwent hemodialysis thrice a week. Baseline data were collected between April 2019 and March 2020, before the declaration of the COVID-19 emergency by the Japanese government. The follow-up measurements were performed between July 2020 and March 2021 during the COVID-19 pandemic. Patient characteristics, laboratory data, and BMI measurements were collected from the medical records. Muscle mass and fat mass were measured using bioelectrical impedance analysis. Results: BMI and fat mass among the study participants were significantly higher during the COVID-19 pandemic than before the pandemic (p < 0.01), but no significant change in muscle mass was observed. A restricted cubic spline function showed that the increase in BMI appeared to correlate well with fat mass, but not with muscle mass. Conclusions: BMI and fat mass of patients on hemodialysis significantly increased due to preventive measures against the COVID-19 pandemic in Japan. These findings may provide useful information in making nutritional management decisions for patients undergoing hemodialysis during and after the COVID-19 pandemic.

Underlying medical conditions and anti-SARS-CoV-2 spike IgG antibody titers after two doses of BNT162b2 vaccination: A cross-sectional study.

Patients with underlying medical conditions are at high risk of developing serious symptoms of the coronavirus disease 2019 than healthy individuals; therefore, it is necessary to evaluate the immune response to vaccination among them to formulate precision and personalized vaccination strategies. However, inconsistent evidence exists regarding whether patients with underlying medical conditions have lower anti-SARS-CoV-2 spike IgG antibody titers. We performed a cross-sectional study enrolling 2762 healthcare workers who received second doses of BNT162b2 vaccination from three medical and research institutes between June and July, 2021. Medical conditions were surveyed by a questionnaire, and spike IgG antibody titers were measured with chemiluminescent enzyme immunoassay using serum collected on the median of 62 days after the second vaccination. Multilevel linear regression model was used to estimate geometric mean and ratio of mean (95% confidence interval, CI) for the presence and absence of medical conditions and treatments. Among all participants (median age, 40 years [interquartile range, 30-50]; male proportion, 29.4%), the prevalence of hypertension, diabetes, chronic lung disease, cardiovascular disease, and cancer was 7.5%, 2.3%, 3.8%, 1.8%, and 1.3%, respectively. Patients with treated hypertension had lower antibody titers than those without hypertension; the multivariable-adjusted ratio of mean (95% CI) was 0.86 (0.76-0.98). Patients with untreated and treated diabetes had lower antibody titers than those without diabetes; the multivariable-adjusted ratio of mean (95% CI) was 0.63 (0.42-0.95) and 0.77 (0.63-0.95), respectively. No substantial difference was observed between the presence or absence of chronic lung disease, cardiovascular disease, or cancer. Patients with untreated hypertension and patients with untreated and treated diabetes had lower spike IgG antibody titers than participants without those medical conditions, suggesting that continuous monitoring of antibody titers and further booster shots could be necessary to maintain adaptive immunity in patients with hypertension or diabetes.

The association between experience of COVID-19-related discrimination and psychological distress among healthcare workers for six national medical research centers in Japan.

BACKGROUND: Discrimination is an important determinant of negative mental health outcomes. This study determined the association between the experience of COVID-19-related discrimination and psychological distress among healthcare workers (HCWs) in Japan. METHODS: This cross-sectional study conducted a health survey among 5703 HCWs of six national medical and research centers in Japan from October 2020 to March 2021. COVID-19-related discrimination was defined either when participants or their family members were badmouthed or when they felt discriminated against in some way. We used the Kessler Psychological Distress Scale (K6) to assess the presence of severe psychological distress (≥ 13 points). We used logistic regression models to examine the association between discrimination and psychological distress. We also identified factors associated with discrimination. RESULTS: Of the participants, 484 (8.4%) reported COVID-19-related discrimination and 486 (8.5%) had severe psychological distress. HCWs who were female vs. male (adjusted odds ratio [AOR] = 1.41, 95% confidence interval [CI] = 1.28-1.55), had high vs. low viral exposure (AOR = 2.31, 95% CI = 1.81-2.93), and worked for 11 or more hours/day vs. 8 or less hours/day (AOR = 1.42, 95% CI = 1.35-1.49) were more likely to have experienced COVID-19-related discrimination. The AOR (95% CI) of severe psychological distress was 1.83 (1.29-2.59) among those who experienced discrimination. In the stratified analysis by sociodemographic and job-related factors, all the interactions did not reach statistical significance (p for interaction > 0.20). CONCLUSION: Experience of COVID-19-related discrimination was associated with severe psychological distress among HCWs. During the pandemic, effective measures should be taken to prevent the development of negative mental health outcomes in HCWs who experience discrimination.

Cumulative and undiagnosed SARS-CoV-2 infection among the staff of a medical research centre in Tokyo after the emergence of variants.

To describe the trend of cumulative incidence of coronavirus disease 19 (COVID-19) and undiagnosed cases over the pandemic through the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants among healthcare workers in Tokyo, we analysed data of repeated serological surveys and in-house COVID-19 registry among the staff of National Center for Global Health and Medicine. Participants were asked to donate venous blood and complete a survey questionnaire about COVID-19 diagnosis and vaccine. Positive serology was defined as being positive on Roche or Abbott assay against SARS-CoV-2 nucleocapsid protein, and cumulative infection was defined as either being seropositive or having a history of COVID-19. Cumulative infection has increased from 2.0% in June 2021 (pre-Delta) to 5.3% in December 2021 (post-Delta). After the emergence of the Omicron, it has increased substantially during 2022 (16.9% in June and 39.0% in December). As of December 2022, 30% of those who were infected in the past were not aware of their infection. Results indicate that SARS-CoV-2 infection has rapidly expanded during the Omicron-variant epidemic among healthcare workers in Tokyo and that a sizable number of infections were undiagnosed.

Dyslipidemia and SARS-CoV-2 spike antibody titres after the second and third doses of the BNT162b2 vaccine among healthcare workers in Japan.

OBJECTIVE: This study aimed to examine the sex-associated differences in the relationship between dyslipidemia and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike immunoglobulin (Ig)G antibodies among BNT162b2 vaccine recipients. METHODS: Participants were staff members (aged 21-75 years) of a medical and research institution who underwent an anti-SARS-CoV-2 spike IgG antibody test after the second (n = 1872) and third doses (n = 1075) of the BNT162b2 vaccine. Dyslipidemia was defined as triglyceride level ≥150 mg/dl, high-density lipoprotein-cholesterol level <40 mg/dl, low-density lipoprotein-cholesterol level ≥140 mg/dl, or lipid-lowering medication use. Multivariable linear regression was used to calculate the ratio of means for SARS-CoV-2 spike IgG titre according to dyslipidemia status. RESULTS: The prevalence of dyslipidemia was 38.0% in men and 19.6% in women. The relationship between dyslipidemia and SARS-CoV-2 spike IgG titres after the second dose differed markedly by sex (P for interaction <0.001). In men, dyslipidemia was associated with significantly lower IgG titres: the ratio of means (95% confidence interval) was 0.82 (0.72-0.93). However, this association disappeared after the third dose (0.96 [0.78-1.18]). Of the dyslipidemia components, hypertriglyceridemia was inversely associated with SARS-CoV-2 spike IgG antibody titre after both the second and third doses (ratio of means: 0.82 [0.70-0.95] and 0.73 [0.56-0.95], respectively). In women, IgG titres did not differ according to dyslipidemia or hypertriglyceridemia status after either dose. CONCLUSIONS: These results suggest a detrimental role of hypertriglyceridemia in the humoral immune response to the BNT162b2 vaccine for COVID-19 in men but not in women.

Changes in body composition of patients undergoing hemodialysis during the coronavirus disease 2019 pandemic: a retrospective longitudinal study

Background The spread of coronavirus disease 2019 (COVID-19) has dramatically altered the lifestyles of many people worldwide. Several studies reported that body weight of young adults increased during the COVID-19 pandemic;however, weight loss has been observed in the elderly population. Therefore, trends in body composition due to the COVID-19 pandemic may vary depending on the characteristics of the population. This study aimed to investigate the changes in body mass index (BMI), muscle mass, and fat mass before and during the COVID-19 pandemic among patients undergoing hemodialysis. Methods In this retrospective longitudinal study, we enrolled 115 clinically stable outpatients (mean age: 65.7 ± 11.2 years, 62.6% men) who underwent hemodialysis thrice a week. Baseline data were collected between April 2019 and March 2020, before the declaration of the COVID-19 emergency by the Japanese government. The follow-up measurements were performed between July 2020 and March 2021 during the COVID-19 pandemic. Patient characteristics, laboratory data, and BMI measurements were collected from the medical records. Muscle mass and fat mass were measured using bioelectrical impedance analysis. Results BMI and fat mass among the study participants were significantly higher during the COVID-19 pandemic than before the pandemic (p < 0.01), but no significant change in muscle mass was observed. A restricted cubic spline function showed that the increase in BMI appeared to correlate well with fat mass, but not with muscle mass. Conclusions BMI and fat mass of patients on hemodialysis significantly increased due to preventive measures against the COVID-19 pandemic in Japan. These findings may provide useful information in making nutritional management decisions for patients undergoing hemodialysis during and after the COVID-19 pandemic.

Neutralizing antibodies after three doses of the BNT162b2 vaccine, breakthrough infection, and symptoms during the Omicron-predominant wave.

OBJECTIVES: To investigate the role of immunogenicity after the third vaccine dose against Omicron infection and COVID-19-compatible symptoms of infection. METHODS: First, we examined vaccine effectiveness (VE) of the third dose against the second dose during the Omicron wave among the staff at a tertiary hospital in Tokyo. In a case-control study of third vaccine recipients, we compared the preinfection live-virus neutralizing antibodies (NAb) against Omicron between breakthrough cases and their controls who had close contact with patients with COVID-19. Among these cases, we examined the association between NAb levels and the number of COVID-19-compatible symptoms. RESULTS: Among the 1456 participants for VE analysis, 60 breakthrough infections occurred during the Omicron wave. The third dose VE for infection was 54.6%. Among the third dose recipients, NAb levels against Omicron did not differ between the cases (n = 22) and controls (n = 21). Among the cases, those who experienced COVID-19-compatible symptoms had lower NAb levels against Omicron than those who did not. CONCLUSION: The third vaccine dose was effective in decreasing the risk of SARS-CoV-2 infection during Omicron wave compared with the second dose. Among third dose recipients, higher preinfection NAb levels may not be associated with a lower risk of Omicron infection. Contrarily, they may be associated with fewer symptoms of infection.

Association of COVID-19-related discrimination with subsequent depression and suicidal ideation in healthcare workers.

Previous cross-sectional studies showed that COVID-19-related discrimination against healthcare workers was linked to depression. However, no study has examined the longitudinal association that allows causal interpretations. This prospective cohort study aimed to examine whether COVID-19-related discrimination at baseline is associated with depression and suicidal ideation several months later. Data were collected from October 2020 to July 2021. Multivariable logistic regression was performed. Fixed effects models were used to control for the effect of hospitals (Level 2 variable). Adjustments also included age, sex, living alone, alcohol consumption, exercise, BMI, working hours, comorbidity, and frontline worker status (Level 1 variables). Multiple sensitivity analyses were conducted to examine if the results substantially changed and were robust to unmeasured confounding. Multiple imputation for missing data was conducted via chained equations. As the final sample, 2862 healthcare workers without depression at baseline were studied. A total of 269 individuals (9.4%) experienced COVID-19-related discrimination. Depression was suggested in 205 participants (7.2%), and suicidal ideation in 108 participants (3.8%). In the adjusted models, COVID-19-related discrimination was significantly associated with subsequent depression (OR = 2.18, 95% CI = 1.39 to 2.90) and suicidal ideation (OR = 2.07, 95% CI = 1.22 to 3.50). Multiple sensitivity analyses verified the results. COVID-19-related discrimination results in depression and suicidal ideation in healthcare workers. Interventions to prevent such discrimination against healthcare workers, e.g., anti-discrimination campaigns, are crucial during the COVID-19 pandemic.

Association between γ-Glutamyl Transpeptidase and SARS-CoV-2 Spike Antibody Titers among BNT162b2 Vaccine Recipients.

BACKGROUND: Increased γ-glutamyl transpeptidase (GGT) levels can deplete plasma glutathione, which in turn impairs immune regulation; however, evidence on GGT levels and post-vaccine immunogenicity is lacking. OBJECTIVE: To examine the association between GGT and SARS-CoV-2 spike IgG antibodies. METHODS: Participants were 1479 medical staff (aged 21 to 75 years) who received a SARS-CoV-2 antibody test after their second vaccine and whose GGT levels were measured before the vaccine rollout. Elevated and highly elevated GGT levels were defined as 51-80 and ≥81 U/L, respectively. Multivariable linear regression was used to calculate the means of SARS-CoV-2 spike IgG. RESULTS: In a basic model, both elevated and highly elevated GGT levels were associated with significantly lower antibody titers. The ratio of mean (95% CI) was 0.83 (0.72-0.97) and 0.69 (0.57-0.84) for elevated and highly elevated GGT levels, respectively. However, these associations were largely attenuated after additional adjustment for potential confounders. An inverse association between GGT levels and antibody titers was found in women [0.70 (0.51-0.97)], normal-weight adults [0.71 (0.51-0.98)], and non-drinkers [0.73 (0.46-1.14)] but not in men, overweight adults, and alcohol drinkers. CONCLUSIONS: Circulating GGT concentrations were associated with the humoral immune response after COVID-19 vaccination, but this relationship could be ascribed to confounders such as sex, BMI, and alcohol drinking rather than GGT per se.

Metabolic syndrome and the immunogenicity of Pfizer-BioNTech vaccine: a cross-sectional study in Japanese healthcare workers.

BACKGROUND: The clustering of metabolic abnormalities may weaken vaccine-induced immunity, but epidemiological data regarding SARS-CoV-2 vaccines are scarce. The present study aimed to examine the cross-sectional association between metabolic syndrome (MetS) and humoral immune response to Pfizer-BioNTech vaccine among the staff of a research center for medical care in Japan. METHODS: Participants were the staff (aged 21-75 years) of the National Center of Global Health and Medicine who had completed the second dose of Pfizer-BioNTech vaccine 1-3 months before the survey. MetS was defined according to the Joint Interim Statement. SARS-CoV-2 spike immunoglobulin G (IgG) antibody was measured using quantitative assays. Multivariable linear regression was used to estimate the geometric mean titers (GMT) and geometric mean ratio (GMR) of IgG titers, relative to MetS status. RESULTS: Of 946 participants who received the second vaccine dose, 51 (5.4%) had MetS. Those with MetS had a significantly lower IgG titer (GMT 4125; 95% confidence interval [CI], 2885-5896) than those without MetS (GMT 5348; 95% CI, 3914-7309); the GMR was 0.77 (95% CI 0.64-0.93). Taking those having no MetS component as reference, fully adjusted GMR (95% CI) for those having 1, 2, 3 or ≥ 4 components was 1.00 (0.90, 1.11), 0.89 (0.77, 1.04), 0.86 (0.68, 1.10) and 0.61 (0.45, 0.82), respectively (P trend = 0.024). CONCLUSION: Results suggest that having MetS and a greater number of its components are associated with a weaker humoral immune response to the Pfizer-BioNTech vaccine.

SARS-CoV-2 specific T cell and humoral immune responses upon vaccination with BNT162b2: a 9 months longitudinal study.

The humoral and cellular immune responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) upon the coronavirus disease 2019 (COVID-19) vaccination remain to be clarified. Hence, we aimed to investigate the long-term chronological changes in SARS-CoV-2 specific IgG antibody, neutralizing antibody, and T cell responses during and after receiving the BNT162b2 vaccine. We performed serological, neutralization, and T cell assays among 100 hospital workers aged 22-73 years who received the vaccine. We conducted seven surveys up to 8 months after the second vaccination dose. SARS-CoV-2 spike protein-specific IgG (IgG-S) titers and T cell responses increased significantly following the first vaccination dose. The highest titers were observed on day 29 and decreased gradually until the end of the follow-up period. There was no correlation between IgG-S and T cell responses. Notably, T cell responses were detected on day 15, earlier than the onset of neutralizing activity. This study demonstrated that both IgG-S and T cell responses were detected before acquiring sufficient levels of SARS-CoV-2 neutralizing antibodies. These immune responses are sustained for approximately 6 to 10 weeks but not for 7 months or later following the second vaccination, indicating the need for the booster dose (i.e., third vaccination).

Infection prevention practices and its associated factors among hospital workers in a national medical center designated for COVID-19 in Tokyo, Japan.

BACKGROUND: While healthcare workers (HCWs) are at risk of occupational exposure to SARS-CoV-2 infection, the virus transmission involving them might be exceeding in the non-occupational settings. This study examined the extent of adherence to infection prevention practices (IPPs) against COVID-19 in their daily life and its associated factors among staff members in a national medical center designated for COVID-19 treatment in Tokyo, Japan. METHODS: This cross-sectional study was conducted in July 2020 among 1,228 staff of National Center for Global Health and Medicine (NCGM). We asked participants about their adherence on six IPPs recommended by the WHO in their daily lives, which included wearing masks, maintaining hand and respiratory hygiene, avoiding 3Cs and social distancing. We defined 100% adherence (6 points) to IPPs as good adherence and run logistic regression model to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of IPPs. RESULTS: Nearly 100% of NCGM staff members adhered to four out of six IPPs assessed in this study: washing or sanitizing hands (99.6%), good cough etiquette (99.6%), wearing mask (98.9%), and avoiding 3Cs (98.3%). Doctors (AOR = 2.18, CI: 1.36-3.49) and female staff members (AOR = 1.95, CI: 1.36-3.49) were more likely to adhere to IPPs compared with non-clinical staffs and male counterparts. Good adherence to IPPs tended to increase with older age, with highest adherence among those who were 50 years or above (AOR = 2.53, CI: 1.49-4.29). CONCLUSION: This study revealed that the IPPs among NCGM staff was remarkably good. Older and female staff members, and doctors showed a higher adhere to IPPs compared with their counterparts. Additional effort to improve adherence to IPPs among the younger and male staff members could contribute to reduce infection risk in their daily life, which can eventually prevent nosocomial infection.

Natural inhibitors for severe acute respiratory syndrome coronavirus 2 main protease from Moringa oleifera, Aloe vera, and Nyctanthes arbor-tristis: molecular docking and ab initio fragment molecular orbital calculations.

The novel coronavirus 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread rapidly worldwide, and new drug treatments for COVID-19 are urgently required. To find the potential inhibitors against the main protease (Mpro) of SARS-CoV-2, we investigated the inhibitory potential of naturally occurring compounds from the plants Moringa oleifera, Aloe vera, and Nyctanthes arbor-tristis, using molecular docking, classical molecular mechanics optimizations, and ab initio fragment molecular orbital (FMO) calculations. Of the 35 compounds that we simulated, feralolide from Aloe vera exhibited the highest binding affinity against Mpro. Therefore, we proposed novel compounds based on the feralolide and investigated their binding properties to Mpro. The FMO results indicated that the introduction of a hydroxyl group into feralolide significantly enhances its binding affinity to Mpro. These results provide useful information for developing potent Mpro inhibitors. Supplementary Information: The online version contains supplementary material available at 10.1007/s11224-022-02021-y.

Association of Changes of lifestyle behaviors before and during the COVID-19 pandemic with mental health: a longitudinal study in children and adolescents.

BACKGROUND: We examined the prospective associations of changes in lifestyle behaviors before/during the COVID-19 pandemic, namely physical activity and screen time, with mental health. Furthermore, the impacts of physical activity and screen time on mental health during the pandemic were examined cross-sectionally. METHODS: A two-wave longitudinal study was conducted among 2423 children and adolescents in Shanghai, China. Lifestyle behavior variables (physical activity and screen time) and psychological variables (depressive symptoms, anxiety, and stress) were measured using a self-reported questionnaire in January and March 2020. A series of multivariable logistic regressions were performed to examine the associations between changes in lifestyle behaviors in two waves and psychological problems. The combined associations of physical activity and screen time with psychological problems were also explored using the second wave data. RESULTS: Compared to students with persistently short screen time before and during the COVID-19 pandemic, those with prolonged screen time (OR = 1·36 for depression, OR = 1·48 for anxiety) and those with persistently long screen time (OR = 1·70 for depression, OR = 2·13 for anxiety) reported a higher risk of psychological symptoms. The association between changes in physical activity and psychological symptoms was not statistically significant after adjustment for demographic factors, socioeconomic status, and screen time. During the COVID-19 pandemic, engaging in longer screen time (OR = 1·44 for depression, OR = 1·55 for anxiety) was associated with worsened psychological conditions, while engaging in increased physical activity (OR = 0·58 for depression, OR = 0·66 for anxiety) was associated with better psychological conditions. CONCLUSIONS: Our study suggests that promoting physical activity and limiting leisure screen time during the COVID-19 pandemic are important to prevent and mitigate psychological problems in children and adolescents. Therefore, effective interventions targeting lifestyle behaviors are needed to protect children and adolescents' physical and mental health.