Robust Neutralization of SARS-CoV-2 Variants Including JN.1 and BA.2.87.1 by Trivalent XBB Vaccine-Induced Antibodies (preprint)

Newly emerged SARS-CoV-2 variants like JN.1, and more recently, the hypermutated BA.2.87.1, have raised global concern. We recruited two groups of participants who had BA.5/BF.7 breakthrough infection post three doses of inactivated vaccines: one group experienced subsequent XBB reinfection, while the other received the XBB-containing trivalent WSK-V102C vaccine. Our comparative analysis of their serum neutralization activities revealed that the WSK-V102C vaccine induced stronger antibody responses against a wide range of variants, notably including JN.1 and the highly escaped BA.2.87.1. Furthermore, our investigation into specific mutations revealed that fragment deletions in NTD significantly contribute to the immune evasion of the BA.2.87.1 variant. Our findings emphasize the necessity for ongoing vaccine development and adaptation to address the dynamic nature of SARS-CoV-2 variants.

Enhanced neutralization of SARS-CoV-2 XBB sub-lineages and BA.2.86 by a tetravalent COVID-19 vaccine booster (preprint)

As the SARS-CoV-2 virus continues to evolve, novel XBB sub-lineages such as XBB.1.5, XBB.1.16, EG.5, HK.3 (FLip), and XBB.2.3, as well as the most recent BA.2.86, have been identified and aroused global concern. Understanding the efficacy of current vaccines and the immune system's response to these emerging variants is critical for global public health. In this study, we evaluated the neutralization activities of sera from participants who received COVID-19 inactivated vaccines, or a booster vaccination of the recently approved tetravalent protein vaccine in China (SCTV01E), or had contracted a breakthrough infection with BA.5/BF.7/XBB virus. Comparative analysis of their neutralization profiles against a broad panel of 30 SARS-CoV-2 sub-lineage viruses revealed that strains such as BQ.1.1, CH.1.1, and all the XBB sub-lineages exhibited heightened resistance to neutralization than previous variants, however, despite the extra mutations carried by emerging XBB sub-lineages and BA.2.86, they did not demonstrate significantly increased resistance to neutralization compared to XBB.1.5. Encouragingly, the SCTV01E booster vaccination consistently induced robust and considerably higher neutralizing titers against all these variants than breakthrough infection did. Cellular immunity assays also showed that the SCTV01E booster vaccination elicited a higher frequency of virus-specific memory B cells but not IFN-{gamma} secreting T cells. Our findings underline the importance of developing novel multivalent vaccines to more effectively combat future viral variants.

Potent and broadly neutralizing antibodies against sarbecoviruses induced by sequential COVID-19 vaccination (preprint)

The current SARS-CoV-2 variants strikingly evade all authorized monoclonal antibodies and threaten the efficacy of serum-neutralizing activity elicited by vaccination or prior infection, urging the need to develop antivirals against SARS-CoV-2 and related sarbecoviruses. Here, we identified both potent and broadly neutralizing antibodies from a five-dose vaccinated donor who exhibited cross-reactive serum neutralizing activity against diverse coronaviruses. Through single B cell sorting and sequencing followed by a tailor-made computational pipeline, we successfully selected 86 antibodies with potential cross-neutralizing ability from 684 antibody sequences. Among them, one potently neutralized all SARS-CoV-2 variants that arose prior to Omicron BA.5, and the other three could broadly neutralize all current SARS-CoV-2 variants of concern, SARS-CoV and their related sarbecoviruses (Pangolin-GD, RaTG13, WIV-1, and SHC014). Cryo-EM analysis demonstrates that these antibodies have diverse neutralization mechanisms, such as disassembling spike trimers, or binding to RBM or SD1 to affect ACE2 binding. In addition, prophylactic administration of these antibodies significantly protects nasal turbinate and lung infections against BA.1, XBB.1 and SARS-CoV viral challenge in golden Syrian hamsters, respectively. This study reveals the potential utility of computational process to assist screening cross-reactive antibodies, as well as the potency of vaccine-induced broadly neutralizing antibodies against current SARS-CoV-2 variants and related sarbecoviruses, offering promising avenues for the development of broad therapeutic antibody drugs.

6-month consequences of COVID-19 in patients discharged from hospital: a cohort study.

BACKGROUND: The long-term health consequences of COVID-19 remain largely unclear. The aim of this study was to describe the long-term health consequences of patients with COVID-19 who have been discharged from hospital and investigate the associated risk factors, in particular disease severity. METHODS: We did an ambidirectional cohort study of patients with confirmed COVID-19 who had been discharged from Jin Yin-tan Hospital (Wuhan, China) between Jan 7 and May 29, 2020. Patients who died before follow-up; patients for whom follow-up would be difficult because of psychotic disorders, dementia, or readmission to hospital; those who were unable to move freely due to concomitant osteoarthropathy or immobile before or after discharge due to diseases such as stroke or pulmonary embolism; those who declined to participate; those who could not be contacted; and those living outside of Wuhan or in nursing or welfare homes were all excluded. All patients were interviewed with a series of questionnaires for evaluation of symptoms and health-related quality of life, underwent physical examinations and a 6-min walking test, and received blood tests. A stratified sampling procedure was used to sample patients according to their highest seven-category scale during their hospital stay as 3, 4, and 5-6, to receive pulmonary function test, high resolution CT of the chest, and ultrasonography. Enrolled patients who had participated in the Lopinavir Trial for Suppression of SARS-CoV-2 in China received SARS-CoV-2 antibody tests. Multivariable adjusted linear or logistic regression models were used to evaluate the association between disease severity and long-term health consequences. FINDINGS: In total, 1733 of 2469 discharged patients with COVID-19 were enrolled after 736 were excluded. Patients had a median age of 57·0 years (IQR 47·0-65·0) and 897 (52%) were male and 836 (48%) were female. The follow-up study was done from June 16 to Sept 3, 2020, and the median follow-up time after symptom onset was 186·0 days (175·0-199·0). Fatigue or muscle weakness (52%, 855 of 1654) and sleep difficulties (26%, 437 of 1655) were the most common symptoms. Anxiety or depression was reported among 23% (367 of 1616) of patients. The proportions of 6-min walking distance less than the lower limit of the normal range were 17% for those at severity scale 3, 13% for severity scale 4, and 28% for severity scale 5-6. The corresponding proportions of patients with diffusion impairment were 22% for severity scale 3, 29% for scale 4, and 56% for scale 5-6, and median CT scores were 3·0 (IQR 2·0-5·0) for severity scale 3, 4·0 (3·0-5·0) for scale 4, and 5·0 (4·0-6·0) for scale 5-6. After multivariable adjustment, patients showed an odds ratio (OR) of 1·61 (95% CI 0·80-3·25) for scale 4 versus scale 3 and 4·60 (1·85-11·48) for scale 5-6 versus scale 3 for diffusion impairment; OR 0·88 (0·66-1·17) for scale 4 versus scale 3 and OR 1·76 (1·05-2·96) for scale 5-6 versus scale 3 for anxiety or depression, and OR 0·87 (0·68-1·11) for scale 4 versus scale 3 and 2·75 (1·61-4·69) for scale 5-6 versus scale 3 for fatigue or muscle weakness. Of 94 patients with blood antibodies tested at follow-up, the seropositivity (96·2% vs 58·5%) and median titres (19·0 vs 10·0) of the neutralising antibodies were significantly lower compared with at the acute phase. 107 of 822 participants without acute kidney injury and with an estimated glomerular filtration rate (eGFR) of 90 mL/min per 1·73 m2 or more at acute phase had eGFR less than 90 mL/min per 1·73 m2 at follow-up. INTERPRETATION: At 6 months after acute infection, COVID-19 survivors were mainly troubled with fatigue or muscle weakness, sleep difficulties, and anxiety or depression. Patients who were more severely ill during their hospital stay had more severe impaired pulmonary diffusion capacities and abnormal chest imaging manifestations, and are the main target population for intervention of long-term recovery. FUNDING: National Natural Science Foundation of China, Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, National Key Research and Development Program of China, Major Projects of National Science and Technology on New Drug Creation and Development of Pulmonary Tuberculosis, and Peking Union Medical College Foundation.

Four new eudesmane-type and one new eremophilane-type sesquiterpenes from the whole plant of Carpesium abrotanoides L.

The extract of the whole plant of Carpesium abrotanoides L. yielded five new sesquiterpenes including four eudesmanes (1-4) and one eremophilane (5). The new compounds were characterized by spectroscopic analysis especially 1D and 2D NMR spectroscopy and HRESIMS data. Structurally, both compounds 1 and 2 were sesquiterpene epoxides and 2 owned an epoxy group at C-4/C-15 position to form a spiro skeleton. Compounds 4 and 5 were two sesquiterpenes without lactones and 5 possessed a carboxy group in the molecule. Additionally, all the isolated compounds were preliminarily evaluated for the inhibitory activity against SARS-CoV-2 main protease. As a result, compound 2 showed moderate activity with an IC50 value of 18.79 µM, while other compounds were devoid of noticeable activity (IC50 > 50 µM).

Smoking Status, Nicotine Medication, Vaccination, and COVID-19 Hospital Outcomes: Findings from the COVID EHR Cohort at the University of Wisconsin (CEC-UW) Study.

INTRODUCTION: Available evidence is mixed concerning associations between smoking status and COVID-19 clinical outcomes. Effects of nicotine replacement therapy (NRT) and vaccination status on COVID-19 outcomes in smokers are unknown. METHODS: Electronic health record data from 104 590 COVID-19 patients hospitalized February 1, 2020 to September 30, 2021 in 21 U.S. health systems were analyzed to assess associations of smoking status, in-hospital NRT prescription, and vaccination status with in-hospital death and ICU admission. RESULTS: Current (n = 7764) and never smokers (n = 57 454) did not differ on outcomes after adjustment for age, sex, race, ethnicity, insurance, body mass index, and comorbidities. Former (vs never) smokers (n = 33 101) had higher adjusted odds of death (aOR, 1.11; 95% CI, 1.06-1.17) and ICU admission (aOR, 1.07; 95% CI, 1.04-1.11). Among current smokers, NRT prescription was associated with reduced mortality (aOR, 0.64; 95% CI, 0.50-0.82). Vaccination effects were significantly moderated by smoking status; vaccination was more strongly associated with reduced mortality among current (aOR, 0.29; 95% CI, 0.16-0.66) and former smokers (aOR, 0.47; 95% CI, 0.39-0.57) than for never smokers (aOR, 0.67; 95% CI, 0.57, 0.79). Vaccination was associated with reduced ICU admission more strongly among former (aOR, 0.74; 95% CI, 0.66-0.83) than never smokers (aOR, 0.87; 95% CI, 0.79-0.97). CONCLUSIONS: Former but not current smokers hospitalized with COVID-19 are at higher risk for severe outcomes. SARS-CoV-2 vaccination is associated with better hospital outcomes in COVID-19 patients, especially current and former smokers. NRT during COVID-19 hospitalization may reduce mortality for current smokers. IMPLICATIONS: Prior findings regarding associations between smoking and severe COVID-19 disease outcomes have been inconsistent. This large cohort study suggests potential beneficial effects of nicotine replacement therapy on COVID-19 outcomes in current smokers and outsized benefits of SARS-CoV-2 vaccination in current and former smokers. Such findings may influence clinical practice and prevention efforts and motivate additional research that explores mechanisms for these effects.

Food Sources May Affect the Symptom Rates of COVID-19, an Epidemiological Analysis Based on the Public Data in Gansu Province, China, During the Summer Epidemic Cycle in 2022.

According to the public data collected from the Health Commission of Gansu Province, China, regarding the COVID-19 pandemic during the summer epidemic cycle in 2022, the epidemiological analysis showed that the pandemic spread stability and the symptom rate (the number of confirmed cases divided by the sum of the number of asymptomatic cases and the number of confirmed cases) of COVID-19 were different among 3 main epidemic regions, Lanzhou, Linxia, and Gannan; both the symptom rate and the daily instantaneous symptom rate (daily number of confirmed cases divided by the sum of daily number of asymptomatic cases and daily number of confirmed cases) in Lanzhou were substantially higher than those in Linxia and Gannan. The difference in the food sources due to the high difference of the population ethnic composition in the 3 regions was probably the main driver for the difference of the symptom rates among the 3 regions. This work provides potential values for prevention and control of COVID-19 in different regions.

Cationic crosslinked carbon dots-adjuvanted intranasal vaccine induces protective immunity against Omicron-included SARS-CoV-2 variants.

Mucosal immunity plays a significant role in the first-line defense against viruses transmitted and infected through the respiratory system, such as SARS-CoV-2. However, the lack of effective and safe adjuvants currently limits the development of COVID-19 mucosal vaccines. In the current study, we prepare an intranasal vaccine containing cationic crosslinked carbon dots (CCD) and a SARS-CoV-2 antigen, RBD-HR with spontaneous antigen particlization. Intranasal immunization with CCD/RBD-HR induces high levels of antibodies with broad-spectrum neutralization against authentic viruses/pseudoviruses of Omicron-included variants and protects immunized female BALB/c mice from Omicron infection. Despite strong systemic cellular immune response stimulation, the intranasal CCD/RBD-HR vaccine also induces potent mucosal immunity as determined by the generation of tissue-resident T cells in the lungs and airway. Moreover, CCD/RBD-HR not only activates professional antigen-presenting cells (APCs), dendritic cells, but also effectively targets nasal epithelial cells, promotes antigen binding via sialic acid, and surprisingly provokes the antigen-presenting of nasal epithelial cells. We demonstrate that CCD is a promising intranasal vaccine adjuvant for provoking strong mucosal immunity and might be a candidate adjuvant for intranasal vaccine development for many types of infectious diseases, including COVID-19.

The characteristics and predictive role of lymphocyte subsets in COVID-19 patients.

OBJECTIVE: To investigate the characteristics and predictive roles of lymphocyte subsets in COVID-19 patients. METHOD: We evaluated lymphocyte subsets and other clinical features of COVID-19 patients, and analyzed their potential impacts on COVID-19 outcomes. RESULTS: 1. Lymphocyte subset counts in the peripheral blood of patients with COVID-19 were significantly reduced, especially in patients with severe disease. 2. In patients with non-severe disease, the time from symptom onset to hospital admission was positively correlated with total T cell counts. 3. Among COVID-19 patients who did not reach the composite endpoint, lymphocyte subset counts were higher than in patients who had reached the composite endpoint. 4. The Kaplan-Meier survival curves showed significant differences in COVID-19 patients, classified by the levels of total, CD8+, and CD4+ T cells at admission. CONCLUSION: Our study showed that total, CD8+, and CD4+ T cell counts in patients with COVID-19 were significantly reduced, especially in patients with severe disease. Lower T lymphocyte subsets were significantly associated with a higher occurrence of composite endpoint events. These subsets may help identify patients with a high risk of composite endpoint events.

Efficacy and Safety of Mesenchymal Stem Cells for COVID-19 Infection: A Meta-Analysis and Systematic Review.

BACKGROUND: COVID-19 (coronavirus disease 2019) is a pandemic around the world, and its treatment options often fail to achieve ideal results. There is a lot of controversy in the treatment of COVID-19 with mesenchymal stem cells (MSCs). The study aims to assess the safety and efficacy of mesenchymal treatment of new coronary pneumonia. METHODS: We manually searched electronic databases including PubMed, Embase, Cochrane Library, and Web of Science until 25th July 2022, and Stata 15.0 (StataCorpLLC: College Station, TX, USA) was used to analyze the data. RESULTS: A total of 8 randomized controlled trials were included, involving a total of 345 people, of which 180 were in the MSCs group and 165 were in the placebo group. The analysis results showed that MSCs can reduce mortality in COVID-19 patients compared to placebo [RR (Risk Ratio) = 0.56, 95% CI (Confidence Interval) (0.36, 0.89); p = 0.003]. There was no significant difference between the mesenchymal stem cell group and the placebo group in the incidence of adverse reactions [RR = 0.64, 95% CI (0.34, 1.18); p = 0.281]; In the SpO2/FiO2 (Oxygen Saturation/Fraction of Inspiration O2) [WMD (Weighted Mean Difference) = 9.07, 95% CI (-38.01, 56.15); p = 0.080]; In ICU (Intensive Care Unit) stay [WMD = -1.66, 95% CI (-7.23, 3.91); p = 0.131]. CONCLUSIONS: Mesenchymal stem cells can reduce the mortality of COVID-19 patients.

What contributes to the re-positive nucleic acid test results for the omicron variant of SARS-CoV-2 in the shelter cabin hospital in Shanghai, China?

Background: Despite the increasing reports of re-positive SARS-CoV-2 cases after recovery and discharge from hospitals, our knowledge remains very limited regarding the contributing factors of re-positivity and its roles in the transmission and epidemiology of the Omicron variant. Methods: In this retrospective study, re-positivity is defined as the positive nucleic acid result (Ct < 35) following two consecutive negative results during hospitalization. A total of 751 patients from Shanghai Shelter Cabin Hospital were enrolled and divided with a ratio of about 1:2 into the re-positivity group and the non-re-positivity group. Patients required three consecutive negative results daily as the de-isolation criterion. The follow-up time of discharged patients lasted five weeks. Univariate regression analysis was used to compare variables between the re-positivity and non-re-positivity groups, and the single re-positivity and multiple re-positivity groups, with P < 0.05 defined as the statistical significance of differences. Subsequently, variables with P < 0.2 were subjected to multivariate logistic regression analysis to investigate the odds ratio (OR) of re-positivity and the influencing factors of re-positivity of the Omicron variant. Results: The re-positivity group had a higher proportion of males (68.1% vs 58.1%, p = 0.000), a higher education level (31.9% vs 12.7%, p = 0.007), a longer hospitalization duration (13 days vs 8 days, p = 0.000), and a higher Convidecia vaccination rate (6.0% vs 2.4%, p = 0.011). Further multivariable analysis showed male (OR = 2.168, p = 0.000), Convidecia vaccination (OR = 2.634, p = 0.014), hospitalization duration (OR = 2.146, p = 0.000) and education level (OR = 1.595, p = 0.007) were associated with re-positivity. The average rate of re-positivity was 25% during hospitalization and decreased to 0.4% among discharged patients. Re-positivity was more common in the period with a larger number of hospitalized patients and in larger wards with a larger number of patients. Conclusion: A large number of hospitalized patients, large-sized wards, and gender are significant contributing factors to re-positivity. Division of the shelter cabin hospital into small independent wards and requirement of three consecutive results daily as the de-isolation criterion might be more beneficial to the control and prevention of the spread of the Omicron variant.

Heterologous vaccination with subunit protein vaccine induces a superior neutralizing capacity against BA.4/5‐included SARS‐CoV‐2 variants than homologous vaccination of mRNA vaccine

BA.4 and BA.5 (BA.4/5), the subvariants of Omicron, are more transmissible than BA.1 with more robust immune evasion capability because of its unique spike protein mutations. In light of such situation, the vaccination against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is in desperate need of the third booster. It has been reported that heterologous boosters might produce more effective immunity against wild‐type SARS‐CoV‐2 and the variants. Additionally, the third heterologous protein subunit booster should be considered potentially. In the present study, we prepared a Delta full‐length spike protein sequence‐based mRNA vaccine as the "priming” shot and developed a recombinant trimeric receptor‐binding domain (RBD) protein vaccine referred to as RBD–HR/trimer as a third heterologous booster. Compared to the homologous mRNA group, the heterologous group (RBD–HR/trimer vaccine primed with two mRNA vaccines) induced higher neutralizing antibody titers against BA.4/5‐included SARS‐CoV‐2 variants. In addition, heterologous vaccination exhibited stronger cellular immune response and long‐lasting memory response than the homologous mRNA vaccine. In conclusion, a third heterologous boosting with RBD–HR/trimer following two‐dose mRNA priming vaccination should be a superior strategy than a third homologous mRNA vaccine. The RBD–HR/trimer vaccine becomes an appropriate candidate for a booster immune injection. We prepared a Delta full‐length spike protein sequence‐based mRNA vaccine (Figure A, B) and developed a recombinant trimeric receptor‐binding domain (RBD) protein vaccine (Figure C). Later, the mRNA vaccine was injected as the "priming” shot, and the RBD–HR/trimer vaccine was used as a third heterologous booster (Figure D).

Real-world experience of arbidol for Omicron variant of SARS-CoV-2.

Background: At a crucial time with the rapid spread of Omicron severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus variant globally, we conducted a study to evaluate the efficacy and safety of arbidol tablets in the treatment of this variant. Methods: From Mar 26 to April 26, 2022, we conducted a prospective, open-labeled, controlled, and investigator-initiated trial involving adult patients with confirmed Omicron variant infection. Patients with asymptomatic or mild clinical status were stratified 1:2 to receive either standard-of-care (SOC) or SOC plus arbidol tablets (oral administration of 200 mg per time, three times a day for 5 days). The primary endpoint was the negative conversion rate within the first week. Results: A total of 367 patients were enrolled in the study; 246 received arbidol tablet treatment, and 121 were in the control group. The negative conversion rate of SARS-CoV-2 within the first week in patients receiving arbidol tablets was significantly higher than that of the SOC group [47.2% (116/246) vs. 35.5% (43/121); odds ratio (OR), 1.619; 95% confidence interval (CI): 1.034-2.535; P=0.035]. Compared to those in the SOC group, patients receiving arbidol tablets had a shorter negative conversion time [median 8.3 vs. 10.0 days; hazard ratio (HR), 0.645; 95% CI: 0.516-0.808; P<0.001], and a shorter duration of hospitalization (median 11.4 vs. 13.7 days; HR, 1.214; 95% CI: 0.966-1.526; P<0.001). Moreover, the addition of arbidol tablets led to better recovery of declined blood lymphocytes, CD3+, CD4+, and CD8+ cell counts. The most common adverse event (AE) was transaminase elevation in patients treated with arbidol tablets (3/246, 1.2%). No one withdrew from the study due to AEs or disease progression. Conclusions: As a whole, arbidol may represent an effective and safe treatment in asymptomatic-mild patients suffering from Omicron variant during the pandemic of coronavirus disease 2019 (COVID-19).

Prevalence of Myopia in Children Before, During, and After COVID-19 Restrictions in Hong Kong.

Importance: Childhood myopia increased during the COVID-19 pandemic. Limited evidence exists about whether myopia development was reversed or worsened after the lockdown. Objective: To determine the prevalence of myopia and its associated factors before, during, and after COVID-19 restrictions. Design, Setting, and Participants: This population-based, repeated cross-sectional study evaluated children aged 6 to 8 years from the Hong Kong Children Eye Study between 2015 and 2021 in 3 cohorts: before COVID-19 (2015-2019), during COVID-19 restrictions (2020), and after COVID-19 restrictions were lifted (2021). Exposures: All the children received ocular examinations, including cycloplegic autorefraction and axial length. Data about the children's lifestyle, including time spent outdoors, near-work time, and screen time, were collected from a standardized questionnaire. Main Outcomes and Measures: The main outcomes were the prevalence of myopia, mean spherical equivalent refraction, axial length, changes in lifestyle, and the associated factors over 7 years. Data were analyzed using descriptive statistics, logistic regression, and generalized estimating equations. Results: Of 20 527 children (mean [SD] age, 7.33 [0.89] years; 52.8% boys and 47.2% girls), myopia prevalence was stable from 2015 to 2019 (23.5%-24.9%; P = .90) but increased to 28.8% (P < .001) in 2020 and 36.2% (P < .001) in 2021. The mean (SD) time spent outdoors was much lower in 2020 (0.85 [0.53] h/d; P < .001) and 2021 (1.26 [0.48] h/d; P < .001) compared with pre-COVID-19 levels (1.40 [0.47]-1.46 [0.65] h/d). The trend was reversed for total near-work time and screen time. High myopia prevalence was associated with the COVID-19 pandemic (odds ratio [OR], 1.40; 95% CI, 1.28-1.54; P < .001), younger age (OR, 1.84; 95% CI, 1.76-1.93; P < .001), male sex (OR, 1.11; 95% CI, 1.03-1.21; P = .007), lower family income (OR, 1.05; 95% CI, 1.00-1.09; P = .04), and parental myopia (OR, 1.61; 95% CI, 1.52-1.70; P < .001). During the pandemic, mean (SD) near-work and screen times in children from lower-income families were 5.16 (2.05) h/d and 3.44 (1.97) h/d, more than from higher-income families (4.83 [1.85] and 2.90 [1.61] h/d, respectively). Conclusions and Relevance: The findings of this cross-sectional study revealed that after COVID-19 restrictions were lifted in Hong Kong, myopia prevalence among children was higher than before the pandemic, and lifestyle did not return to pre-COVID-19 levels. Younger children and those from low-income families were at a higher risk of myopia development during the pandemic, suggesting that collective efforts for myopia control should be advocated for these groups.

Sentiment analysis and causal learning of COVID-19 tweets prior to the rollout of vaccines.

While the impact of the COVID-19 pandemic has been widely studied, relatively fewer discussions about the sentimental reaction of the public are available. In this article, we scrape COVID-19 related tweets on the microblogging platform, Twitter, and examine the tweets from February 24, 2020 to October 14, 2020 in four Canadian cities (Toronto, Montreal, Vancouver, and Calgary) and four U.S. cities (New York, Los Angeles, Chicago, and Seattle). Applying the RoBERTa, Vader and NRC approaches, we evaluate sentiment intensity scores and visualize the results over different periods of the pandemic. Sentiment scores for the tweets concerning three anti-epidemic measures, "masks", "vaccine", and "lockdown", are computed for comparison. We explore possible causal relationships among the variables concerning tweet activities and sentiment scores of COVID-19 related tweets by integrating the echo state network method with convergent cross-mapping. Our analyses show that public sentiments about COVID-19 vary from time to time and from place to place, and are different with respect to anti-epidemic measures of "masks", "vaccines", and "lockdown". Evidence of the causal relationship is revealed for the examined variables, assuming the suggested model is feasible.

Myopia control and prevention: From lifestyle to low-concentration atropine. The 2022 Josh Wallman Memorial Lecture.

The purpose of this study was to explore the findings from the Hong Kong Children Eye Study and the Low Concentration Atropine for Myopia Progression (LAMP-1) Study. The incidence of myopia among schoolchildren in Hong Kong more than doubled during the COVID-19 pandemic, with outdoor time decreased significantly and screen time increased. The change in lifestyle during the COVID-19 pandemic aggravated myopia development. Low-concentration atropine (0.05%, 0.025% and 0.01%) is effective in reducing myopia progression with a concentration-related response. This concentration-dependent response was maintained throughout a 3-year follow-up period, and all low concentrations were well tolerated. An age-dependent effect was observed in each treatment group with 0.05%, 0.025% and 0.01% atropine. Younger age was associated with a poor treatment response to low-concentration atropine. Additionally, low-concentration atropine induced choroidal thickening along a concentration-dependent response throughout the treatment period. During the third year, continued atropine treatment achieved a better effect across all concentrations compared with the washout regimen. Stopping treatment at an older age and receiving lower concentration were associated with a smaller rebound effect. However, differences in the rebound effect were clinically small across all the three concentrations studied.

Trimeric protein vaccine based on Beta variant elicits robust immune response against BA.4/5-included SARS-CoV-2 Omicron variants.

The current Coronavirus Disease 2019 (COVID-19) pandemic, induced by newly emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variants, posed great threats to global public health security. There is an urgent need to design effective next­generation vaccines against Omicron lineages. Here, we investigated the immunogenic capacity of the vaccine candidate based on the receptor binding domain (RBD). An RBDß-HR self-assembled trimer vaccine including RBD of Beta variant (containing K417, E484 and N501) and heptad repeat (HR) subunits was developed using an insect cell expression platform. Sera obtained from immunized mice effectively blocked RBD-human angiotensin-converting enzyme 2 (hACE2) binding for different viral variants, showing robust inhibitory activity. In addition, RBDß-HR/trimer vaccine durably exhibited high titers of specific binding antibodies and high levels of cross-protective neutralizing antibodies against newly emerging Omicron lineages, as well as other major variants including Alpha, Beta, and Delta. Consistently, the vaccine also promoted a broad and potent cellular immune response involving the participation of T follicular helper (Tfh) cells, germinal center (GC) B cells, activated T cells, effector memory T cells, and central memory T cells, which are critical facets of protective immunity. These results demonstrated that RBDß-HR/trimer vaccine candidates provided an attractive next-generation vaccine strategy against Omicron variants in the global effort to halt the spread of SARS-CoV-2.

Care patterns and Traditional Chinese Medicine constitution as factors of depression and anxiety in patients with systemic sclerosis: A cross-sectional study during the COVID-19 pandemic.

Objective: Care patterns and Traditional Chinese Medicine (TCM) constitution affects the emotion and health of patients with systemic sclerosis (SSc) while the prevalence of COVID-19 may aggravate such patients' emotion and health. We investigated the depression and anxiety levels of patients with SSc during the pandemic to identify the correlation between care patterns, TCM constitution, and patients' emotion. Materials and methods: This was a cross-sectional study. Patients with SSc and healthy individuals were surveyed using the patient health questionnaire-9, generalized anxiety disorder-7, and constitution in Chinese medicine questionnaire and a modified care pattern questionnaire. Factors correlated with depression and anxiety were screened using univariate and multivariate logistic regression analyses. Results: A total of 273 patients with SSc and 111 healthy individuals were included in the analysis. The proportion of patients with SSc who were depressed was 74.36%, who had anxiety was 51.65%, and who experienced disease progression during the pandemic was 36.99%. The proportion of income reduction in the online group (56.19%) was higher than that in the hospital group (33.33%) (P = 0.001). Qi-deficiency [adjusted odds ratio (OR) = 2.250] and Qi-stagnation (adjusted OR = 3.824) constitutions were significantly associated with depression. Remote work during the outbreak (adjusted OR = 1.920), decrease in income (adjusted OR = 3.556), and disease progression (P = 0.030) were associated with the occurrence of depression. Conclusion: Chinese patients with SSc have a high prevalence of depression and anxiety. The COVID-19 pandemic has changed the care patterns of Chinese patients with SSc, and work, income, disease progression, and change of medications were correlates of depression or anxiety in patients with SSc. Qi-stagnation and Qi-deficiency constitutions were associated with depression, and Qi-stagnation constitution was associated with anxiety in patients with SSc. Trial registration: http://www.chictr.org.cn/showproj.aspx?proj=62301, identifier ChiCTR2000038796.