Mental health status and related factors influencing healthcare workers during the COVID-19 pandemic: a systematic review and meta-analysis (preprint)

Background: The mental health of healthcare workers during the coronavirus-2019 pandemic was seriously affected, and the risk of mental health problems was high. The present study sought to systematically evaluate the mental health problems of healthcare workers worldwide during the pandemic and to determine the latest global frequency of COVID-19 associated mental health problems. Methods: Data in the Cumulative Index to Nursing and Allied Health Literature (CINAHL), EMBASE, Elsevier, MEDLINE, PubMed, PsycINFO and the Web of Science before November 11, 2022, were systematically searched. Cohort, case-control and cross-sectional studies were included. The meta-analysis used a random effects model to synthesize the comprehensive prevalence rate of mental health problems. Subgroup analyses were performed based on time of data collection; whether the country was or was not developed; continent; doctors and nurses; doctors/nurses vs. other healthcare workers; and psychological evaluation scale. Results: A total of 161 studies were included, including 341,014 healthcare workers worldwide, with women accounting for 82.8%. Occupationally, 16.2% of the healthcare workers were doctors, 63.6% were nurses and 13.3% were other medical staff. During the pandemic, 47% (95% confidence interval [CI], 35-60%) of healthcare workers reported job burnout, 38% (95% CI, 35-41%) experienced anxiety, 34% (95% CI 30-38%) reported depression, 30% (95% CI, 29-31%) had acute stress disorder, and 26% (95% CI, 21-31%) had post-traumatic stress disorder. Conclusions: The study found that there were common mental health problems among health care workers during the COVID-19 pandemic. The most common was job burnout, followed by anxiety, depression, acute stress and post-traumatic stress disorder. Although the global pandemic has been brought under control, its long-term impact on the mental health of healthcare workers cannot be ignored. Additional research is required to develop measures to prevent, monitor and treat psychological disorders among healthcare workers.

RAMEN identifies effective indicators for severe COVID and Long COVID patients (preprint)

The outbreak of the COVID-19 pandemic caused catastrophic socioeconomic consequences and fundamentally reshaped the lives of billions across the globe. Our current understanding of the relationships between clinical variables (demographics, symptoms, follow-up symptoms, comorbidities, treatments, lab results, complications, and other clinical measurements) and COVID-19 outcomes remains obscure. Various computational approaches have been employed to elucidate the relationships between different COVID-19 clinical variables and their contributions to the disease outcomes. However, it is often challenging to capture the indirect relationships, as well as the direction of those relationships, with the conventional pairwise correlation methods. Graphical models (e.g., Bayesian networks) can address these limitations but are computationally expensive, which substantially limits their applications in reconstructing relationship networks ofumpteen clinical variables. In this study, we have developed a method named RAMEN, which employs Genetic Algorithm and random walks to infer the Bayesian relationship network between clinical variables. We applied RAMEN to a comprehensive COVID-19 dataset, Biobanque Quebecoise de la COVID-19 (BQC19). Most of the clinical variables in our reconstructed Bayesian network associated with COVID-19 severity, or long COVID, are supported by existing literature. We further computationally verified the effectiveness of the RAMEN method with statistical examinations of the multi-omics measurements (Clinical variables, RNA-seq, and Somascan) of the BQC19 data and simulations. The accurate inference of the relationships between clinical variables and disease outcomes powered by RAMEN will significantly advance the development of effective and early diagnostics of severe COVID-19 and long COVID, which can help save millions of lives.

COVID-19 testing and vaccine willingness: Cross-sectional survey in a culturally diverse community in Sydney, Australia (preprint)

Objective The current study examined patterns in COVID-19 testing and vaccination intentions across multiple language groups in Greater Western Sydney, Australia. Methods Participants completed a cross-sectional survey available from March 21 to July 9, 2021 in Sydney, Australia. Surveys were available in English or translated (11 languages). Participants could complete surveys independently or with support from bilingual staff. Logistic regression models using post-stratification weighted frequencies identified factors associated with testing and vaccination intentions. Results Most of the 708 participants (88%, n=622) were not born in Australia; 31% reported that they did not speak English well or at all (n=220); 70% had no tertiary qualifications (n=497); and 41% had inadequate health literacy (n=290). Most participants reported high testing intention (77.2%, n=546), with differences observed across language groups (p<0.001). The most frequently reported barrier to testing was concerns about infection at the clinic (26.1%). Half (53.0%) reported willingness to get a COVID-19 vaccine if recommended to them (n=375); 18% were unwilling (n=127), and the remainder unsure (29%, n=205). These proportions varied significantly by language group (p<0.001). Participants were more likely to be unwilling/hesitant if they were female (p=0.02) or did not use Australian commercial information sources (p=0.01). Concerns about side effects (30.4%, n=102) and safety (23.9%, n=80), were key reported barriers to vaccination. Conclusion Different language groups have unique and specific needs to support uptake of COVID-19 testing and vaccination. Health services must work collaboratively with culturally and linguistically diverse communities to provide tailored support to encourage COVID-19 testing and vaccination. Lay summary 708 adults living in Sydney, Australia, who did not speak English as their main language at home took part in a survey about COVID-19 vaccination and testing. Participants could complete the survey online (English/translated) or with support from bilingual staff. The survey was available in 11 languages. Three quarters of participants (77%) reported they would get tested for COVID-19 if they had symptoms ‘no matter what.’ The most common barrier was concern about getting infected at the testing clinic. 53% of participants reported that they would get a COVID-19 vaccine if it was recommended to them. 18% reported that they wouldn’t get the vaccine, and 29% were unsure. The main barriers were concerns about vaccine side effects and safety. Intentions to get tested for COVID-19 or to get vaccinated varied significantly across language groups. Participants who were female, or who did not use Australian commercial information sources were more likely to be unwilling or unsure about getting a COVID-19 vaccine. Different language groups have unique and specific needs to support uptake of COVID-19 testing and vaccination. Health services must work collaboratively with culturally and linguistically diverse communities to provide tailored support to encourage COVID-19 testing and vaccination.

Main COVID-19 information sources in a culturally and linguistically diverse community in Sydney, Australia: A cross-sectional survey (preprint)

BackgroundLittle is known about COVID-19 information-seeking experiences for culturally and linguistically diverse groups in Australia. MethodsParticipants were recruited using a cross-sectional survey from March 21 to July 9, 2021, translated into 11 languages, and with supporting bilingual staff. Linear regression models identified factors associated with difficulty finding easy-to-understand COVID-19 information. ResultsAcross 708 participants (88% born overseas, 31% poor English proficiency), difficulty finding easy-to-understand COVID-19 information was rated 4.13 for English materials (95%CI: 3.85 to 4.41) and 4.36 for translated materials (95%CI: 4.07 to 4.66) (1 easy to 10 hard). Participants who were older (p<0.001), had inadequate health literacy (Mean Difference (MD)=-1.43, 95%CI -2.03 to - 0.82, p<0.001), or poor English proficiency (MD=-1.9, 95%CI-2.51 to -1.29, p<0.001) found it harder to find easy-to-understand English-language COVID-19 information. Those who had greater difficulty finding easy-to-understand translated COVID-19 information were younger (p=0.004), had poor English proficiency (MD=-1.61, 95%CI -2.29 to -0.9, p<0.001), university education (MD=0.77, 95%CI 0.00 to 1.53, p=0.05), and had spent longer living in Australia (p=0.001). They were more likely to rely on friends and family for COVID-19 information (p=0.02). There was significant variation in information-seeking experiences across language groups (ps<0.001). ConclusionsEasy-to-understand and accessible COVID-19 information is needed to meet the needs of people in culturally and linguistically diverse communities. This approach should involve working alongside these communities to tailor messages and leverage existing communication channels.

Collateral positives of COVID-19 for culturally and linguistically diverse communities in Western Sydney, Australia (preprint)

Issues addressed: To investigate whether culturally and linguistically diverse communities in Western Sydney have experienced any positive effects during the COVID19 pandemic, and if so, what these were. Methods: A cross sectional survey with ten language groups was conducted from 21st March to 9th July 2021 in Sydney, Australia. Participants were recruited through bilingual multicultural health staff and health care interpreter service staff and answered a question, In your life, have you experienced any positive effects from the COVID-19 pandemic? Differences were explored by demographic variables. Free text responses were thematically coded using the Content Analysis method. Results: 707 people completed the survey, aged 18 to >70, 49% males and 51% females. Only 161 (23%) of those surveyed reported any positive impacts. There were significant differences in the proportion of those who reported positives based on age (p=0.004), gender (p=0.013), language (p=0.003), health literacy (p=0.014), English language proficiency (p=0.003), education (p=<0.001) and whether participants had children less than 18 years at home (p=0.001). Reporting of positive impacts ranged from 12% for people aged seventy years or older to 30% for the 30-49 year age group. Reporting of positive impacts for different language groups ranged from 9% to 42%. 18% of men reported positive impacts compared to 27% of women, and 18% of people with inadequate health literacy reported positive impacts compared to 26% with adequate health literacy. Content Analysis of open ended responses showed that, of those that did report positives, the top themes were Family time (44%), Improved self care (31%) and, Greater connection with others (17%). Conclusions: From 21st March to July 9th, 2021, few surveyed participants reported finding any positives because of the COVID19 pandemic. This finding is in stark contrast to related research in Australia in a population dominated by adults with English as their first language, carried out in June 2020, in which many more people experienced positives. So what: The needs of people from culturally and linguistically diverse backgrounds must inform future responses to community crises to facilitate an equitable effect of any collateral positives that may arise.

Psychological, social and financial impact of COVID-19 on culturally and linguistically diverse communities: a cross-sectional Australian study (preprint)

Objective: This study aimed to explore the psychological, social, and financial impacts of COVID-19 on culturally and linguistically diverse communities in Australia. Design: Cross-sectional survey informed by the Framework for Culturally Competent Health Research conducted between March and July, 2021. Setting: Participants were recruited from Greater Western Sydney, New South Wales, Australia. Participants: 708 community members who speak a language other than English at home participated (mean age: 45.4years [range 18 to 91]; 88% [n=622] born outside of Australia). Outcome measures: Fifteen items regarding impacts of COVID-19, adapted from validated scales, previous surveys or co-designed in partnership with Multicultural Health and interpreter service staff. Logistic regression models (using post-stratification weighted frequencies) identified factors associated with psychological, social, and financial impacts. Surveys were available in English or translated (11 languages). Results: Even prior to the COVID-19 outbreak in Sydney, 25% of the sample reported feeling nervous or stressed most/all of the time and 22% felt lonely or alone most/all of the time. One quarter of participants reported negative impacts on their spousal relationships as a result of COVID-19 and most parents reported that their children were less active (64%), had more screen time (63%), and were finding school harder (45%). Mean financial burden was 2.9/5 (95%CI=2.8 to 2.9). Regression analyses consistently showed distinct impact patterns for different language groups and more negative outcomes for those with comorbidities. Conclusion: Culturally and linguistically diverse communities experience significant psychological, social and financial impacts of COVID-19, with distinct impact patterns across language groups. A whole-of-government approach with policy and sustainable infrastructure is needed to co-design innovative, tailored and culturally-safe COVID-19 support packages.

Comparison of reported main COVID-19 information sources in national and culturally and linguistically diverse communities in Australia (preprint)

BackgroundTo manage the COVID-19 pandemic effectively, governments need clear and effective communication. This is a challenge for culturally diverse communities as groups may have different informational needs and information-seeking behaviours. In this paper we present the frequency of information sources for COVID-19 in a culturally diverse area of Sydney, Australia. MethodsThis study reports findings from two surveys. The first recruited participants across 10 languages between March 21 and July 9, 2021. The second provides a point of reference, and was an Australian, nationally-representative sample of English-speaking participants between November 4 - 18, 2020. ResultsFor the survey in culturally and linguistically diverse communities, of 708 participants, mean age was 45.4 years (SE 0.78), and 51% of respondents were female. Across all language groups, 54.7% of participants used Australian official or public broadcasters to find out about COVID-19 (n=421). Australian commercial information sources (54.1%, n=417), social media (51.6%, n=397), and family and friends in Australia (32.7%, n=252) were common sources. Patterns varied substantially across language groups. In the nationally representative survey (n=2313), 67% of participants (n=1540) used Australian official or public broadcasters, with lower proportions for social media (31.9%, n=738) and friends, family or other personal sources (23.1%; n=533). ConclusionAlmost 50% of participants from culturally and linguistically diverse communities did not report using Australian official or public broadcaster as main sources of information. Instead Australian commercial information sources, friends and family, overseas sources and social media were common. Though a crude comparison of the two datasets, this data can guide policy decisions for communication to different community groups. Further analysis is needed to interpret this data. Better understanding of how diverse communities seek and receive COVID-19 health information is imperative as we manage the current COVID-19 outbreak in the Sydney region.

Cross-neutralizing antibodies bind a SARS-CoV-2 cryptic site and resist to circulating variants (preprint)

The emergence of numerous variants of SARS-CoV-2, the causative agent of COVID-19, has presented new challenges to the global efforts to control the still ravaging COVID-19 pandemic. Here, we obtain two cross-neutralizing antibodies (7D6 and 6D6) that target Sarbecoviruses’ receptor binding domain (RBD) with sub-picomolar affinities and potently neutralize authentic SARS-CoV-2. Crystal structures show that both antibodies bind a cryptic site different from that recognized by existing antibodies and highly conserved across Sarbecovirus isolates. Binding of these two antibodies to the RBD clashes with the adjacent N-terminal domain and disrupts the viral spike. Significantly, both antibodies confer good mutation resistance to the currently circulating SARS-CoV-2 variants. Thus, our results have direct relevance to public health as options for passive antibody therapeutics and even active prophylactics, and can also inform the design of pan-sarbecovirus vaccines.

Network of “drug-target-SARS-CoV-2 Related Genes” Through Integrated Analysis of Pharmacology and Geo Database (preprint)

BackgroundCoronavirus Disease 2019 (COVID-19) respiratory disease rapidly caused a global pandemic and social and economic disruption. The combination of Traditional Chinese medicine (TCM) and Conventional Western medicine (CWM) is more effective for COVID-19 treatment. Moreover, TCM and CWM are important data source for developing new drug targets and promote strategies treat SARS-CoV-2 infections. However, many studies have analyzed the therapeutic mechanism of CWM or TCM alone for COVID-19, it is still unclear the interaction mechanism between TCM and CWM on COVID-19.MethodsThis paper integrates network pharmacology and GEO database to mine and identify COVID-19 molecular therapeutic targets, providing potential targets and new ideas for COVID-19 gene therapy and new drug development. It includes: 1) using TCMSP, TTD, PubChem and CTD databases to analyze drug interactions and associated phenotypes for SARS-CoV-2, to correlate drug and disease interaction mechanisms to screen key drug targets; 2) using GEO database to correlate differential genes and drug targets to screen potential antiviral gene therapy targets, to construct regulatory network and key points of SARS-CoV-2 therapeutic drugs; 3) using computer simulation of molecular docking to screen virus-related proteins for new drugs. ResultsIntegrated analysis of network pharmacology discovered that baicalein, estrone and quercetin are the pivotal active ingredients in TCM and CWM. Combining drug target genes in pharmacology database and virus induced genes in GEO database, the result showed the core hub genes related to COVID-19: STAT1, IL1B, IL6, IL8, PTGS2 and NFKBIA, and these genes were significantly downregulated in A549 and NHBE cells by SARS-CoV-2 infection. Moreover, chemical interaction and molecular docking analysis of hub genes showed that folic acid might as be potential therapeutic drug for COVID-19 treatment, and SARS-CoV-2 nucleocapsid phosphoprotein was a potential drug target. The network of “drug-target-SARS-CoV-2 related genes” provide noval potential compounds and targets for further studies of SARS-CoV-2.ConclusionsIntegrated analysis of network pharmacology and big data mining provided noval potential compounds and targets for further studies of SARS-CoV-2. Our research implied folic acid and SARS-CoV-2 N as therapeutic target in TCM and CWM. Our research also suggests that targeting SARS-CoV-2 N protein is likely to be a common mechanism of TCM and CWM. On the one hand, the identification of pivotal genes provides a target for COVID-19 molecular therapy, on the other hand, it provides ideas for the analysis of interaction mechanism between virus and host.

Celebrex adjuvant therapy on COVID-19: An experimental study (preprint)

Background: The world is under serious threat with the spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes the coronavirus disease 2019 (COVID-19). However, there is no effective drug for the treatment of COVID-19. Based on analyses of available data, we deduced that the excessive prostaglandins E2 (PGE2) accumulation mediated by cyclooxygenase-2 (COX-2) was the key pathological basis of COVID-19. Methods: The urine PGE2 levels were measured by mass spectrometry. An experimental study about Celebrex to treat COVID-19 was conducted based on routine treatment. A total of 44 confirmed COVID-19 patients were enrolled (Experimental group n=37, Control group n=7). Patients in experimental group were given Celebrex once or twice a day (0.2 g/time) for 7-14 days. The dosage or duration was modified for individuals. Clinical outcomes of Celebrex adjuvant therapy were evaluated by vital signs, laboratory tests, and computed tomography upon the discontinuance of Celebrex. Results: We found that the concentrations of PGE2 in urine samples of COVID-19 patients were significantly higher than that of healthy individuals (mean value is 170 ng/ml vs 18.8 ng/ml, p<0.01) and positively correlated with the progression of COVID-19. Among the experimental group (ordinary n=29, severe n=7, critical n=1), 25 cases were treated with full dose and 11 cases with half dose of Celebrex, and 1 case with Ibuprofen. The remission rate were 100%, 82% and 57% in full dose, half dose and control group respectively. Celebrex significantly reduced the PGE2 levels and promoted recovery of ordinary or severe COVID-19. Conclusion: Our study suggests that Celebrex adjuvant treatment may be helpful for the therapy of COVID-19.

Characterization of the SARS-CoV-2 Spike in an Early Prefusion Conformation (preprint)

Pandemic coronavirus disease 2019 (COVID-19) is caused by the emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), for which there are no efficacious vaccines or therapeutics that are urgently needed. We expressed three versions of spike (S) proteins--receptor binding domain (RBD), S1 subunit and S ectodomain--in insect cells. RBD appears monomer in solutions, whereas S1 and S associate into homotrimer with substantial glycosylation. The three proteins confer excellent antigenicity with six convalescent COVID-19 patient sera. Cryo-electron microscopy (cryo-EM) analyses indicate that the SARS-CoV-2 S trimer dominate in a unique conformation distinguished from the classic prefusion conformation of coronaviruses by the upper S1 region at lower position ~15 [A] proximal to viral membrane. Such conformation is proposed as an early prefusion state for the SARS-CoV-2 spike that may broaden the knowledge of coronavirus and facilitate vaccine development.