Evolutionary adaptation of bovine coronavirus (BCoV): Screening of natural recombinations across the complete genomes.

Bovine coronavirus (BCoV) is a member of pathogenic Betacoronaviruses that has been circulating for several decades in multiple host species. Given the similarity between BCoV and human coronaviruses, the current study aimed to review the complete genomes of 107 BCoV strains available on the GenBank database, collected between 1983 and 2017 from different countries. The maximum-likelihood based phylogenetic analysis revealed three main BCoV genogroups: GI, GII, and GIII. GI is further divided into nine subgenogroups: GI-a to GI-i. The GI-a to GI-d are restricted to Japan, and GI-e to GI-i to the USA. The evolutionary relationships were also inferred using phylogenetic network analysis, revealing two major distinct networks dominated by viruses identified in the USA and Japan, respectively. The USA strains-dominated Network Cluster includes two sub-branches: France/Germany and Japan/China in addition to the United States, while Japan strains-dominated Network Cluster is limited to Japan. Twelve recombination events were determined, including 11 intragenogroup (GI) and one intergenogroup (GII vs. GI-g). The breakpoints of the recombination events were mainly located in ORF1ab and the spike glycoprotein ORF. Interestingly, 10 of 12 recombination events occurred between Japan strains, one between the USA strains, and one from intercontinental recombination (Japan vs. USA). These findings suggest that geographical characteristics, and population density with closer contact, might significantly impact the BCoV infection and co-infection and boost the emergence of more complex virus lineages.

Genetic comparison of transmissible gastroenteritis coronaviruses.

Transmissible gastroenteritis virus (TGEV) is a porcine coronavirus that threatens animal health and remains elusive despite years of research efforts. The systematical analysis of all available full-length genomes of TGEVs (a total of 43) and porcine respiratory coronaviruses PRCVs (a total of 7) showed that TGEVs fell into two independent evolutionary phylogenetic clades, GI and GII. Viruses circulating in China (until 2021) clustered with the traditional or attenuated vaccine strains within the same evolutionary clades (GI). In contrast, viruses latterly isolated in the USA fell into GII clade. The viruses circulating in China have a lower similarity with that isolated latterly in the USA all through the viral genome. In addition, at least four potential genomic recombination events were identified, three of which occurred in GI clade and one in GII clade. TGEVs circulating in China are distinct from the viruses latterly isolated in the USA at either genomic nucleotide or antigenic levels. Genomic recombination serves as a factor driving the expansion of TGEV genomic diversity.

Computational Screening of Inhibitory Compounds for SARS-Cov-2 3CL Protease with a Database Consisting of Approved and Investigational Chemicals.

Computational screening is one of the fundamental techniques in drug discovery. Each compound in a chemical database is bound to the target protein in virtual, and candidate compounds are selected from the binding scores. In this work, we carried out combinational computation of docking simulation to generate binding poses and molecular mechanics calculation to estimate binding scores. The coronavirus infectious disease has spread worldwide, and effective chemotherapy is strongly required. The viral 3-chymotrypsin-like (3CL) protease is a good target of low molecular-weight inhibitors. Hence, computational screening was performed to search for inhibitory compounds acting on the 3CL protease. As a preliminary assessment of the performance of this approach, we used 51 compounds for which inhibitory activity had already been confirmed. Docking simulations and molecular mechanics calculations were performed to evaluate binding scores. The preliminary evaluation suggested that our approach successfully selected the inhibitory compounds identified by the experiments. The same approach was applied to 8820 compounds in a database consisting of approved and investigational chemicals. Hence, docking simulations, molecular mechanics calculations, and re-evaluation of binding scores including solvation effects were performed, and the top 200 poses were selected as candidates for experimental assays. Consequently, 25 compounds were chosen for in vitro measurement of the enzymatic inhibitory activity. From the enzymatic assay, 5 compounds were identified to have inhibitory activities against the 3CL protease. The present work demonstrated the feasibility of a combination of docking simulation and molecular mechanics calculation for practical use in computational virtual screening.

Numerical Analysis of Three-dimensional Nanodisk Array-based Surface Plasmon Resonance Biosensors for SARS-CoV-2 Detection.

With continuous mutations of SARS-CoV-2 virus, new highly contagious and fast-spreading variants have emerged, including Delta and Omicron. The popular label-free immunosensor based on surface plasmon resonance (SPR) technique can be used for real-time monitoring of the ligand-analyte or antibody-antigen interactions occurring on the sensor surface. In this work, an SPR-based biosensor combined with a nanodisk array was presented to enhance the sensitivity toward virus detection. The nanodisk arrays were employed to enhance the adsorption of molecules for better detection by increasing the SPR field. Four optimal sensing configurations of silver or gold nanodisks on gold thin films with different aspect ratios were achieved through systematic optimization of all parameters to yield the best sensor performance. The resonance angle can be modulated simply by the aspect ratio of nanodisk array. The sensitivity of the optimized sensors has been improved, and the detection limit is smaller than that of bare gold-based sensor. The multi-jump resonance angle curves at tiny refractive index can clearly distinguish the difference of trace concentrations, which is very important for the accurate detection of trace substances. Supplementary Information: The online version contains supplementary material available at 10.1007/s11468-023-01802-3.

Influencing Factors of Mental Health Status of Dentists Under COVID-19 Epidemic.

Objective: To investigate dentists' psychological status and influencing factors in Shaanxi Province during the COVID-19 epidemic and assess their perceived wellness. Methods: The study was conducted among dentists from Shaanxi Province in China. The basic information was collected through the network questionnaire star platform. Depression, Anxiety, and Stress Scales (DASS-42) and Perceived Wellness Survey (PWS) were used to assess subjects' psychological status and perceived wellness. Univariate linear regression analysis and multivariate analysis were performed on the influencing factors of depression, anxiety, and stress, and t-test and analysis of variance were used to analyze the perceived wellness results. Results: The results demonstrated that 33.2% of the surveyed dentists were in a state of depression, 37.1% were anxious, and 34.4% reported stress among 256 subjects. Linear Regression analysis results showed that: "years of working," "the impact of COVID-19 on their life, work, and sleep," "worrying about occupational exposure/virus infection," "lacking the awareness of prevention and control measures," "overtime work during the epidemic," "worrying about participating in the supporting work," and "continuous exhaustion from work" were significant contributors to depression, anxiety, and stress status. In addition, the results of PWS found that each dimension of PWS was correlated with depression, anxiety, and stress state, which indicates the individual's physical and mental health state was associated with multiple factors. Conclusion: COVID-19 has significantly impacted dentists' mental health in Shaanxi Province. With these findings, we aim to educate and promote targeted interventions that can be utilized to improve dentists' mental health by analyzing the influencing factors.

Development of functional anti-Gn nanobodies specific for SFTSV based on next-generation sequencing and proteomics.

Severe fever with thrombocytopenia syndrome (SFTS) is an acute infectious disease caused by novel bunyavirus (SFTSV), with a mortality rate of 6.3% ~ 30%. To date, there is no specific treatment for SFTS. Previously, we demonstrated that SFTSV surface glycoprotein (Glycoprotein N, Gn) was a potential target for the development of SFTS vaccine or therapeutic antibodies, and anti-Gn neutralizing antibodies played a protective role in SFTS infection. Compared with traditional antibodies, nanobodies from camelids have various advantages, including small molecular weight, high affinity, low immunogenicity, convenient production by gene engineering, etc. In this study, we combined next-generation sequencing (NGS) with proteomics technology based on affinity purification-mass spectrometry (AP-MS) and bioinformatics analysis to high-throughput screen monoclonal anti-Gn nanobodies from camel immunized with Gn protein. We identified 19 anti-Gn monoclonal nanobody sequences, of which six sequences were selected for recombinant protein expression and purification. Among these six anti-Gn nanobodies, nanobody 57,493 was validated to be highly specific for Gn. The innovative high-throughput technical route developed in this study could also be expanded to the production of nanobodies specific for other viruses like SARS-CoV-2.

[Change in serum IgG antibody during the recovery stage of Omicron variant infection in children: an analysis of 110 cases]. / 110ä¾‹å„¿ç«¥å¥¥å¯†å ‹æˆŽå˜å¼‚æ ªæ„ŸæŸ“æ¢å¤æœŸè¡€æ¸ IgG抗体变化.

OBJECTIVES: To investigate the serum level of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific RBD IgG antibody (SARS-CoV-2 IgG antibody for short) in children with SARS-CoV-2 Omicron variant infection during the recovery stage, as well as the protective effect of SARS-CoV-2 vaccination against Omicron infection. METHODS: A retrospective analysis was performed on 110 children who were diagnosed with coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 Omicron variant infection in Tianjin of China from January 8 to February 7, 2022. According to the status of vaccination before diagnosis, they were divided into a booster vaccination (3 doses) group with 2 children, a complete vaccination (2 doses) group with 90 children, an incomplete vaccination (1 dose) group with 5 children, and a non-vaccination group with 13 children. The clinical data and IgG level were compared among the 4 groups. RESULTS: The complete vaccination group had a significantly higher age than the non-vaccination group at diagnosis (P<0.05), and there was a significant difference in the route of transmission between the two groups (P<0.05). There were no significant differences among the four groups in sex, clinical classification, and re-positive rate of SARS-CoV-2 nucleic acid detection (P>0.05). All 97 children were vaccinated with inactivated vaccine, among whom 85 children (88%) were vaccinated with BBIBP-CorV Sinopharm vaccine (Beijing Institute of Biological Products, Beijing, China). At 1 month after diagnosis, the booster vaccination group and the complete vaccination group had a significantly higher level of SARS-CoV-2 IgG antibody than the non-vaccination group (P<0.05), and at 2 months after diagnosis, the complete vaccination group had a significantly higher level of SARS-CoV-2 IgG antibody than the non-vaccination group (P<0.05). For the complete vaccination group, the level of SARS-CoV-2 IgG antibody at 2 months after diagnosis was significantly lower than that at 1 month after diagnosis (P<0.05). CONCLUSIONS: Vaccination with inactivated SARS-CoV-2 vaccine has a protective effect against Omicron infection in children. For children vaccinated with 2 doses of the vaccine who experience Omicron infection, there may be a slight reduction in the level of SARS-CoV-2 IgG antibody at 2 months after diagnosis. Citation:Chinese Journal of Contemporary Pediatrics, 2022, 24(7): 736-741.

Implications of the COVID-19 pandemic for urban informal housing and planning interventions: Evidence from Singapore.

The outbreak of the COVID-19 pandemic revealed the crucial role of social distancing and hygiene practices in reducing virus transmission and thus revealed the high risk of infection in urban informal housing. Through an empirical study of Singapore's infectious situation and antiepidemic measures, this paper shows that the number of infected migrant workers living in dormitories was three hundred times greater than the number of infected local urban residents, not only because of the migrants' 'vulnerable' position but also because their living conditions fostered widespread transmission of the virus. The dwelling conditions of migrant dormitories, such as overcrowded living spaces, widely shared sanitation facilities, and poor hygiene practices, present great challenges to standard prevention strategies and control measures. Adverse health impacts resulting from the lockdown of dormitories during the COVID-19 pandemic suggest the importance of planning intervention in the dwelling conditions of informal housing, and indicate a need for the governments' active reforms of building codes and health care systems to promote the health of disadvantaged groups and then create more inclusive and healthy cities for all the society.

Drug-Target Network Study Reveals the Core Target-Protein Interactions of Various COVID-19 Treatments.

The coronavirus disease 2019 (COVID-19) pandemic has caused a dramatic loss of human life and devastated the worldwide economy. Numerous efforts have been made to mitigate COVID-19 symptoms and reduce the death rate. We conducted literature mining of more than 250 thousand published works and curated the 174 most widely used COVID-19 medications. Overlaid with the human protein-protein interaction (PPI) network, we used Steiner tree analysis to extract a core subnetwork that grew from the pharmacological targets of ten credible drugs ascertained by the CTD database. The resultant core subnetwork consisted of 34 interconnected genes, which were associated with 36 drugs. Immune cell membrane receptors, the downstream cellular signaling cascade, and severe COVID-19 symptom risk were significantly enriched for the core subnetwork genes. The lung mast cell was most enriched for the target genes among 1355 human tissue-cell types. Human bronchoalveolar lavage fluid COVID-19 single-cell RNA-Seq data highlighted the fact that T cells and macrophages have the most overlapping genes from the core subnetwork. Overall, we constructed an actionable human target-protein module that mainly involved anti-inflammatory/antiviral entry functions and highly overlapped with COVID-19-severity-related genes. Our findings could serve as a knowledge base for guiding drug discovery or drug repurposing to confront the fast-evolving SARS-CoV-2 virus and other severe infectious diseases.

A Dual Role of Complement Activation in the Development of Fulminant Hepatic Failure Induced by Murine-Beta-Coronavirus Infection.

With the epidemic of betacoronavirus increasing frequently, it poses a great threat to human public health. Therefore, the research on the pathogenic mechanism of betacoronavirus is becoming greatly important. Murine hepatitis virus strain-3 (MHV-3) is a strain of betacoronavirus which cause tissue damage especially fulminant hepatic failure (FHF) in mice, and is commonly used to establish models of acute liver injury. Recently, MHV-3-infected mice have also been introduced to a mouse model of COVID-19 that does not require a Biosafety Level 3 (BSL-3) facility. FHF induced by MHV-3 is a type of severe liver damage imbalanced by regenerative hepatocellular activity, which is related to numerous factors. The complement system plays an important role in host defense and inflammation and is involved in first-line immunity and/or pathogenesis of severe organ disorders. In this study, we investigated the role of aberrant complement activation in MHV-3 infection-induced FHF by strategies that use C3-deficient mice and intervene in the complement system. Our results showed that mice deficient in C3 had more severe liver damage, a higher viral load in the liver and higher serum concentrations of inflammatory cytokines than wild-type controls. Treatment of C57BL/6 mice with C3aR antagonist or anti-C5aR antibody reduced liver damage, viral load, and serum IFN-γ concentration compared with the control group. These findings indicated that complement system acts as a double-edged sword during acute MHV-3 infection. However, its dysregulated activation leads to sustained inflammatory responses and induces extensive liver damage. Collectively, by investigating the role of complement activation in MHV-3 infection, we can further understand the pathogenic mechanism of betacoronavirus, and appropriate regulation of immune responses by fine-tuning complement activation may be an intervention for the treatment of diseases induced by betacoronavirus infection.

Elevated SARS-CoV-2 in peripheral blood and increased COVID-19 severity in American Indians/Alaska Natives.

Epidemiological data across the United States show health disparities in COVID-19 infection, hospitalization, and mortality by race/ethnicity. While the association between elevated SARS-CoV-2 viral loads (VLs) (i.e. upper respiratory tract (URT) and peripheral blood (PB)) and increased COVID-19 severity has been reported, data remain largely unavailable for some disproportionately impacted racial/ethnic groups, particularly for American Indian or Alaska Native (AI/AN) populations. As such, we determined the relationship between SARS-CoV-2 VL dynamics and disease severity in a diverse cohort of hospitalized patients. Results presented here are for study participants (n = 94, ages 21-88 years) enrolled in a prospective observational study between May and October 2020 who had SARS-CoV-2 viral clades 20A, C, and G. Based on self-reported race/ethnicity and sample size distribution, the cohort was stratified into two groups: (AI/AN, n = 43) and all other races/ethnicities combined (non-AI/AN, n = 51). SARS-CoV-2 VLs were quantified in the URT and PB on days 0-3, 6, 9, and 14. The strongest predictor of severe COVID-19 in the study population was the mean VL in PB (OR = 3.34; P = 2.00 × 10-4). The AI/AN group had the following: (1) comparable co-morbidities and admission laboratory values, yet more severe COVID-19 (OR = 4.81; P = 0.014); (2) a 2.1 longer duration of hospital stay (P = 0.023); and (3) higher initial and cumulative PB VLs during severe disease (P = 0.025). Moreover, self-reported race/ethnicity as AI/AN was the strongest predictor of elevated PB VLs (ß = 1.08; P = 6.00 × 10-4) and detection of SARS-CoV-2 in PB (hazard ratio = 3.58; P = 0.004). The findings presented here suggest a strong relationship between PB VL (magnitude and frequency) and severe COVID-19, particularly for the AI/AN group.

Genetic Characteristics of Porcine Hemagglutinating Encephalomyelitis Coronavirus: Identification of Naturally Occurring Mutations Between 1970 and 2015.

Porcine hemagglutinating encephalomyelitis virus (PHEV) is a Betacoronavirus characterized by neurological symptoms and a worldwide prevalence. Although PHEV is one of the earliest discovered porcine coronaviruses, it remains poorly studied. The full-length genome of the earliest PHEV strain collected in 1970 in the United States (PHEV/67 N/US/1970) was determined in October 2020. Using this virus as a prototype, we comparatively analyzed all available PHEV full-length sequences during 1970-2015. In phylogenetic trees based on PHEV full-length or spike glycoprotein open reading frame genomic sequences, PHEV/67 N/US/1970 was sorted into a clade different from that of viruses isolated in the United States in 2015. Intriguingly, United States and Belgium viruses isolated in 2015 and 2005, respectively, revealed multiple deletion mutation patterns compared to the strain PHEV/67 N/US/1970, leading to a truncated or a non-functional NS2A coding region. In addition, the genomic similarity analysis showed a hypervariability of the spike glycoprotein coding region, which can affect at least eight potential linear B cell epitopes located in the spike glycoprotein. This report indicates that PHEVs in the United States underwent a significant genetic drift, which might influence PHEV surveillance in other countries.

Flow of goods to the shock of COVID-19 and toll-free highway policy: Evidence from logistics data in China

Using high-frequency logistics data from China, this paper quantitatively examines the negative impact of the COVID-19 pandemic on logistics. Meanwhile, our research focuses on the toll-free highway policy during the COVID-19 pandemic, analyzing the promoting effect of this policy on road freight in China. Three main conclusions are drawn from the study. Firstly, the COVID-19 pandemic led to an average daily drop of 0.67% in road freight volume and an increase of 0.48% in logistic cost compared to the pre-pandemic period. Secondly, the toll-free highway policy had a significant offset effect of pandemic on freight volume and price, stimulating the resumption of work and production. However, the dynamic effect shows that the toll-free highway policy is only temporarily effective rather than the long term. Thirdly, the effectiveness of the toll-free highway policy is moderated by the severity of the epidemic and the transportation distance. This paper contributes to research on economy recovery and transportation policy under the COVID-19 pandemic shock.

Construction of Orthogonal Modular Proteinaceous Nanovaccine Delivery Vectors Based on mSA-Biotin Binding.

Proteinaceous nanovaccine delivery systems have significantly promoted the development of various high-efficiency vaccines. However, the widely used method of coupling the expression of scaffolds and antigens may result in their structural interference with each other. Monovalent streptavidin (mSA) is a short monomer sequence, which has a strong affinity for biotin. Here, we discuss an orthogonal, modular, and highly versatile self-assembled proteinaceous nanoparticle chassis that facilitates combinations with various antigen cargos by using mSA and biotin to produce nanovaccines. We first improved the yield of these nanoparticles by appending a short sugar chain on their surfaces in a constructed host strain. After confirming the strong ability to induce both Th1- and Th2-mediated immune responses based on the plasma cytokine spectrum from immunized mice, we further verified the binding ability of biotinylated nanoparticles to mSA-antigens. These results demonstrate that our biotinylated nanoparticle chassis could load both protein and polysaccharide antigens containing mSA at a high affinity. Our approach thus offers an attractive technology for combining nanoparticles and antigen cargos to generate various high-performance nanovaccines. In particular, the designed mSA connector (mSA containing glycosylation modification sequences) could couple with polysaccharide antigens, providing a new attractive strategy to prepare nanoscale conjugate vaccines.

Establishing and evaluating physician-pharmacist collaborative clinics to manage patients with type 2 diabetes in primary hospitals in Hunan province: study protocol of a multi-site randomized controlled trial in the era of COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic has exerted an unprecedented and universal impact on global health system, resulting in noticeable challenges in traditional chronic disease care, of which diabetes was reported to be most influenced by the reduction in healthcare resources in the pandemic. China has the world's largest diabetes population, and current diabetes management in China is unsatisfactory, particularly in rural areas. Studies in developed countries have demonstrated that physician-pharmacist collaborative clinics are efficient and cost-effective for diabetes management, but little is known if this mode could be adapted in primary hospitals in China. The aim of this proposed study is to develop and evaluate physician-pharmacist collaborative clinics to manage type 2 diabetes mellitus (T2DM) in primary hospitals in Hunan province. METHODS: A multi-site randomized controlled trial will be conducted to evaluate the effectiveness and cost-effectiveness of the physician-pharmacist collaborative clinics compared with usual care for Chinese patients with T2DM. Six primary hospitals will participate in the study, which will recruit 600 eligible patients. Patients in the intervention group will receive services from both physicians and pharmacists in the collaborative clinics, while the control group will receive usual care from physicians. Patients will be followed up at the 3rd, 6th, 9th and 12th month. Comparison between the two groups will be conducted by assessing the clinical parameters, process indicators and costs on diabetes. A satisfaction survey will also be carried out at the end of the study. DISCUSSION: If effective, the physician-pharmacist collaborative clinics can be adapted and used in primary hospitals of China to improve glycemic control, enhance medication adherence, decrease incidence of complications and reduce patients' dependence on physicians. Findings from the present study are meaningful for developing evidence-based diabetes care policy in rural China, especially in the COVID-19 pandemic era. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2000031839 , Registered 12 April 2020.

A highly immunogenic live-attenuated vaccine candidate prevents SARS-CoV-2 infection and transmission in hamsters.

The highly pathogenic and readily transmissible SARS-CoV-2 has caused a global coronavirus pandemic, urgently requiring effective countermeasures against its rapid expansion. All available vaccine platforms are being used to generate safe and effective COVID-19 vaccines. Here, we generated a live-attenuated candidate vaccine strain by serial passaging of a SARS-CoV-2 clinical isolate in Vero cells. Deep sequencing revealed the dynamic adaptation of SARS-CoV-2 in Vero cells, resulting in a stable clone with a deletion of seven amino acids (N679SPRRAR685) at the S1/S2 junction of the S protein (named VAS5). VAS5 showed significant attenuation of replication in multiple human cell lines, human airway epithelium organoids, and hACE2 mice. Viral fitness competition assays demonstrated that VAS5 showed specific tropism to Vero cells but decreased fitness in human cells compared with the parental virus. More importantly, a single intranasal injection of VAS5 elicited a high level of neutralizing antibodies and prevented SARS-CoV-2 infection in mice as well as close-contact transmission in golden Syrian hamsters. Structural and biochemical analysis revealed a stable and locked prefusion conformation of the S trimer of VAS5, which most resembles SARS-CoV-2-3Q-2P, an advanced vaccine immunogen (NVAX-CoV2373). Further systematic antigenic profiling and immunogenicity validation confirmed that the VAS5 S trimer presents an enhanced antigenic mimic of the wild-type S trimer. Our results not only provide a potent live-attenuated vaccine candidate against COVID-19 but also clarify the molecular and structural basis for the highly attenuated and super immunogenic phenotype of VAS5.

Transmission of COVID-19 from community to healthcare agencies and back to community: a retrospective study of data from Wuhan, China.

BACKGROUND: The early spatiotemporal transmission of COVID-19 remains unclear. The community to healthcare agencies and back to community (CHC) model was tested in our study to simulate the early phase of COVID-19 transmission in Wuhan, China. METHODS: We conducted a retrospective study. COVID-19 case series reported to the Municipal Notifiable Disease Report System of Wuhan from December 2019 to March 2020 from 17 communities were collected. Cases from healthcare workers (HW) and from community members (CM) were distinguished by documented occupations. Overall spatial and temporal relationships between HW and CM COVID-19 cases were visualised. The CHC model was then simulated. The turning point separating phase 1 and phase 2 was determined using a quadratic model. For phases 1 and 2, linear regression was used to quantify the relationship between HW and CM COVID-19 cases. RESULTS: The spatial and temporal distributions of COVID-19 cases between HWs and CMs were closely correlated. The turning point was 36.85±18.37 (range 15-70). The linear model fitted well for phase 1 (mean R2=0.98) and phase 2 (mean R2=0.93). In phase 1, the estimated [Formula: see text]s were positive (from 18.03 to 94.99), with smaller [Formula: see text]s (from 2.98 to 15.14); in phase 2, the estimated [Formula: see text]s were negative (from -4.22 to -81.87), with larger [Formula: see text]s (from 5.37 to 78.12). CONCLUSION: Transmission of COVID-19 from the community to healthcare agencies and back to the community was confirmed in Wuhan. Prevention and control measures for COVID-19 in hospitals and among HWs are crucial and warrant further attention.