RCoV19: A One-stop Hub for SARS-CoV-2 Genome Data Integration, Variants Monitoring, and Risk Pre-warning (preprint)

The Resource for Coronavirus 2019 (RCoV19) is an open-access information resource dedicated to providing valuable data on the genomes, mutations, and variants of the Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this updated implementation of RCoV19, we have made significant improvements and advancements over the previous version. Firstly, we have implemented a highly refined genome data curation model. This model now features an automated integration pipeline and optimized curation rules, enabling efficient daily updates of data in RCoV19. Secondly, we have developed a global and regional lineage evolution monitoring platform, alongside an outbreak risk pre-warning system. These additions provide a comprehensive understanding of SARS-CoV-2 evolution and transmission patterns, enabling better preparedness and response strategies. Thirdly, we have developed a powerful interactive mutation spectrum comparison module. This module allows users to compare and analyze mutation patterns, assisting in the detection of potential new lineages. Furthermore, we have incorporated a comprehensive knowledgebase on mutation effects. This knowledgebase serves as a valuable resource for retrieving information on the functional implications of specific mutations. In summary, RCoV19 serves as a vital scientific resource, providing access to valuable data, relevant information, and technical support in the global fight against COVID-19.

Systematic Review and Meta-Analysis of Olfactory and Gustatory Dysfunction in Coronavirus Disease 2019 Patients (preprint)

Background: We performed a meta-analysis to assess the risk factors for olfactory and gustatory dysfunction in patients with COVID-19.Methods: Three databases (PubMed, Embase, and Cochrane Library) were searched for studies published between December 01, 2019 to May 31, 2021. Select random effects model or fixed effects model to pool data based on heterogeneity. The results were reported as odds ratios or standardized mean differences and the corresponding 95% confidence intervals. Heterogeneity was reported as I2.Findings: Twenty-six studies with a total of 13813 patients were included. The pooled data indicated that sex (OR, 1.47; 95% CI, 0.93-2.31), age (SMD, -5.80; 95% CI, −13.35-1.75), smoking (OR, 2.04; 95% CI, 0.72-5.79), and comorbidity (OR, 1.21; 95% CI, 0.58-2.53) had no effect on gustatory dysfunction in COVID-19 patients. Elderly patients with COVID-19 were more prone to olfactory dysfunction (SMD, -5.22; 95% CI, −8.28- −2.16). COVID-19 patients with nasal congestion (OR, 3.41;95%CI, 2.30-5.06) and rhinorrhea (OR, 2.35; 95%CI, 1.60-3.45) are more likely to suffer from olfactory dysfunction.Interpretation: These findings emphasize that elderly COVID-19 patients are more likely to suffer from olfactory dysfunction. Symptoms of nasal congestion and rhinorrhea may affect the recognition of olfactory dysfunction. Funding Information: No funding received.Declaration of Interests: The authors declare that they have no competing interests.

Increased complement activation is a distinctive feature of severe SARS-CoV-2 infection. (preprint)

Complement activation has been implicated in the pathogenesis of severe SARS-CoV-2 infection. However, it remains to be determined whether increased complement activation is a broad indicator of critical illness (and thus, no different in COVID-19). It is also unclear which pathways are contributing to complement activation in COVID-19, and, if complement activation is associated with certain features of severe SARS-CoV-2 infection, such as endothelial injury and hypercoagulability. To address these questions, we investigated complement activation in the plasma from patients with COVID-19 prospectively enrolled at two tertiary care centers. We compared our patients to two non-COVID cohorts: (a) patients hospitalized with influenza, and (b) patients admitted to the intensive care unit (ICU) with acute respiratory failure requiring invasive mechanical ventilation (IMV). We demonstrate that circulating markers of complement activation (i.e., sC5b-9) are elevated in patients with COVID-19 compared to those with influenza and to patients with non-COVID-19 respiratory failure. Further, the results facilitate distinguishing those who are at higher risk of worse outcomes such as requiring ICU admission, or IMV. Moreover, the results indicate enhanced activation of the alternative complement pathway is most prevalent in patients with severe COVID-19 and is associated with markers of endothelial injury (i.e., Ang2) as well as hypercoagulability (i.e., thrombomodulin and von Willebrand factor). Our findings identify complement activation to be a distinctive feature of COVID-19, and provide specific targets that may be utilized for risk prognostication, drug discovery and personalized clinical trials.

Working conditions and health status of 6,317 front line public health workers across five provinces in China during the COVID-19 epidemic: a cross-sectional study (preprint)

Background: Public health workers at the Chinese Centre for Disease Control and Prevention (China CDC) and primary health care institutes (PHIs) were among the main workers who implemented prevention, control, and containment measures. However, their efforts and health status have not been well documented. We aimed to investigate the working conditions and health status of front line public health workers in China during the COVID-19 epidemic. Methods: : Between 18 February and 1 March 2020, we conducted an online cross-sectional survey of 2,313 CDC workers and 4,004 PHI workers in five provinces across China experiencing different scales of COVID-19 epidemic. We surveyed all participants about their work conditions, roles, burdens, perceptions, mental health, and self-rated health using a self-constructed questionnaire and standardised measurements (i.e., Patient Health Questionnaire and General Anxiety Disorder scale). To examine the independent associations between working conditions and health outcomes, we used multivariate regression models controlling for potential confounders. Results: : The prevalence of depression, anxiety, and poor self-rated health was 21.3%, 19.0%, and 9.8%, respectively, among public health workers (27.1%, 20.6%, and 15.0% among CDC workers and 17.5%, 17.9%, and 6.8% among PHI workers). The majority (71.6%) made immense efforts in both field and non-field work. Nearly 20.0% have worked all night for more than 3 days, and 45.3% had worked throughout the Chinese New Year holiday. Three risk factors and two protective factors were found to be independently associated with all three health outcomes in our final multivariate models: working all night for >3 days (multivariate odds ratio [ORm]=1.67~1.75, p <0.001), concerns about infection at work (ORm=1.46~1.89, p <0.001), perceived troubles at work (ORm=1.10~1.28, p <0.001), initiating COVID-19 prevention work after January 23 (ORm=0.78~0.82, p =0.002~0.008), and ability to persist for > 1 month at the current work intensity (ORm=0.44~0.55, p <0.001). Conclusions: : Chinese public health workers made immense efforts and personal sacrifices to control the COVID-19 epidemic and faced the risk of mental health problems. Efforts are needed to improve the working conditions and health status of public health workers and thus maintain their morale and effectiveness during the fight against COVID-19.

Difficulties of Prevention and Control Staff in COVID-19 Outbreak: A Cross-sectional Study Based on Five Provinces (preprint)

Objectives: The aim of this study is to address the difficulties encountered by epidemic control staff in the early and middle stages of their efforts to combat COVID-19, compare the gaps among different types of institutions, and identify shortcomings in epidemic control. Methods: Using multi-stage sampling, a survey of primary (“primary-urban” and “primary-rural”) and non-primary (“CDC”) public health workers involved in the prevention and control of COVID-19 in five provinces, including Hubei, Guangdong, Sichuan, Jiangsu and Gansu, was conducted from 18 February to 1 March 2020 through a self-administered questionnaire.Results: A total of 9475 outbreak prevention and control workers were surveyed, of which 40.0% were from the primary-rural, 27.0% were from the primary-urban and 33.0% were CDC. Resources shortage was reported at 27.9%, with the primary-rural being the worst affected (OR=1.201, 95%CI: 1.073-1.345). Difficulties in data processing were reported at 31.5%, with no significant differences among institutions. Communication and coordination difficulties were reported at 29.8%, with the CDC being the most serious (the rural primary: OR=0.520, 95%CI: 0.446-0.606; the primary-urban: OR=0.533, 95%CI: 0.454-0.625). Work object difficulties were reported at 20.2%, with the primary-urban being the worst (OR=1.368, 95%CI: 1.199-1.560). Psychological distress was reported at 48.8%, with no significant differences among institutions.Conclusions: Psychological distress is the most serious problem in the prevention and control of COVID-19, and the resources shortage in primary-rural, communication and coordination difficulties in CDC, and difficulties in working with the target population in the primary-urban deserve attention. This study will provide a scientific basis for improving the national public health emergency management system, especially for reducing the urban-rural differences in emergency response capacity.

The global landscape of SARS-CoV-2 genomes, variants, and haplotypes in 2019nCoVR (preprint)

On 22 January 2020, the National Genomics Data Center (NGDC), part of the China National Center for Bioinformation (CNCB), created the 2019 Novel Coronavirus Resource (2019nCoVR), an open-access SARS-CoV-2 information resource. 2019nCoVR features a comprehensive integration of sequence and clinical information for all publicly available SARS-CoV-2 isolates, which are manually curated with value-added annotations and quality evaluated by our in-house automated pipeline. Of particular note, 2019nCoVR performs systematic analyses to generate a dynamic landscape of SARS-CoV-2 genomic variations at a global scale. It provides all identified variants and detailed statistics for each virus isolate, and congregates the quality score, functional annotation, and population frequency for each variant. It also generates visualization of the spatiotemporal change for each variant and yields historical viral haplotype network maps for the course of the outbreak from all complete and high-quality genomes. Moreover, 2019nCoVR provides a full collection of SARS-CoV-2 relevant literature on COVID-19 (Coronavirus Disease 2019), including published papers from PubMed as well as preprints from services such as bioRxiv and medRxiv through Europe PMC. Furthermore, by linking with relevant databases in CNCB-NGDC, 2019nCoVR offers data submission services for raw sequence reads and assembled genomes, and data sharing with National Center for Biotechnology Information. Collectively, all SARS-CoV-2 genome sequences, variants, haplotypes and literature are updated daily to provide timely information, making 2019nCoVR a valuable resource for the global research community. 2019nCoVR is accessible at https://bigd.big.ac.cn/ncov/.

Circulating Mitochondrial DNA is an Early Indicator of Severe Illness and Mortality from COVID-19 (preprint)

Mitochondrial DNA (MT-DNA) are intrinsically inflammatory nucleic acids released by damaged solid organs. Whether the appearance of cell-free MT-DNA is linked to poor COVID-19 outcomes remains undetermined. Here, we quantified circulating MT-DNA in prospectively collected, cell-free plasma samples from 97 subjects with COVID-19 at the time of hospital presentation. Circulating MT-DNA were sharply elevated in patients who eventually died, required ICU admission or intubation. Multivariate regression analysis revealed that high circulating MT-DNA levels is an independent risk factor for all of these outcomes after adjusting for age, sex and comorbidities. Additionally, we found that circulating MT-DNA has a similar or superior area-under-the curve when compared to clinically established measures of systemic inflammation, as well as emerging markers currently of interest as investigational targets for COVID-19 therapy. These results show that high circulating MT-DNA levels is a potential indicator for poor COVID-19 outcomes.

The nexus between COVID-19, temperature and exchange rate in Wuhan city: New findings from partial and multiple wavelet coherence.

This study attempts to document the nexus between weather, COVID-19 outbreak in Wuhan and the Chinese economy. We used daily average temperature (hourly data), daily new confirmed cases of COVID-19 in Wuhan, and RMB (Chinese currency) exchange rate to represent the weather, COVID-19 outbreak and the Chinese economy, respectively. The methodology of Wavelet Transform Coherence (WTC), Partial Wavelet Coherence (PWC) and Multiple Wavelet Coherence (MWC) is employed to analyze the daily data collected from 21st January 2020 to 31st March 2020. The results have revealed a significant coherence between the series at different time-frequency combinations. The overall results suggest the insignificance of an increase in temperature to contain or slow down the new COVID-19 infections. The RMB exchange rate and the COVID-19 showed an out phase coherence at specific time-frequency spots suggesting a negative but limited impact of the COVID-19 outbreak in Wuhan on the Chinese export economy. Our results are contrary to many earlier studies which suggest a significant role of temperature in slowing down the COVID-19 spread. These results can have important policy implications for the containment of COVID-19 spread and macro-economic management with respect to changes in the weather.