The Infection of Healthcare Workers and the Reinfection of Patients by Omicron Variant - Jiangsu Province, China, December 2022 to January 2023.

What is already known about this topic?: Healthcare workers (HCWs) and previously infected patients (PIPs) may experience a wave of epidemic following the modification of the country's coronavirus disease (COVID)-zero policy in China. What is added by this report?: As of early January 2023, the initial wave of the COVID-19 pandemic among HCWs had effectively subsided, with no statistically significant differences observed in infection rates compared to those of their co-occupants. The proportion of reinfections among PIPs was relatively low, particularly in those with recent infections. What are the implications for public health practice?: Medical and health services have resumed normal operations. For patients who have recently experienced severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, appropriate relaxation of policies may be considered.

Management of SARS-CoV-2 Omicron Variant Community Screenings in Shanghai, China: A Cross-Sectional Study.

Background: Community screening for SARS-CoV-2 Omicron variant plays a significant role in controlling the spread of infection. However, loopholes may exist in the current management of community screening in Shanghai, China. The objective of this study was to discover loopholes in the management of community screening for SARS-CoV-2 Omicron variant in Shanghai, China and provide targeted solutions. Methods: The cross-sectional study was carried out April 4 to April 30, 2021, among residential committee directors from the Putuo District, Pudong District, and Minhang District of Shanghai, China. Data were collected using a self-designed questionnaire about the management of nucleic acid testing (NAT) sampling in communities through the network platform powered by www.wjx.cn. Results: A total of 203 residential committee directors responded to the survey. Of them, 47.3% were not accepted training and 40.4% were not aware of cross-infection. Comparison among sampling sites and communities, high-risk group contained lower proportion of community training (P = 0.093~0.200), higher awareness of cross-infection (P = 0.039~0.777), more medical workers (P = 0.007~0.724) and more tests performed (P = 0.001~0.992). Larger communities had more medical workers, sampling sites, sampling tables (P = 0.000) and higher awareness of cross-infection (P = 0.009), but lower proportion of community training (P = 0.051). Conclusion: Overall, community training and awareness of infection control were inadequate. Government or institutions should organize the community training and raise the awareness of infection control. Significant differences exist in NAT management patterns between sampling sites, as well as communities of different sizes. Residential community directors minimize high-risk sampling point settings in the future. Special personnel designated by the government or institutions should tour to guide each sampling site.

Polypharmacology of ambroxol in the treatment of COVID-19.

The pandemic of coronavirus disease 2019 (COVID-19) by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still underway. Due to the growing development of severe symptoms, it is necessary to promote effective therapies. Ambroxol [2-amino-3,5-dibromo-N-(trans-4-hydroxycyclohexyl) benzylamine] has long been used as one of the over-the-counter mucolytic agents to treat various respiratory diseases. Therefore, we focused on the mechanism of action of ambroxol in COVID-19 treatment. In vitro and in silico screening revealed that ambroxol may impede cell entry of SARS-CoV-2 by binding to neuropilin-1. Ambroxol could also interact with multiple inflammatory factors and signaling pathways, especially nuclear factor kappa B (NF-κB), to interfere cytokines cascade activated by SARS-CoV-2 internalization. Furthermore, multipathways and proteins, such as the cell cycle and matrix metalloproteinases (MMPs), were identified as significant ambroxol-targeting pathways or molecules in PBMC and lung of severe COVID-19 patients by bioinformatics analysis. Collectively, these results suggested that ambroxol may serve as a promising therapeutic candidate for the treatment of severe SARS-CoV-2 infection.

Individual bat viromes reveal the co-infection, spillover and emergence risk of potential zoonotic viruses (preprint)

Bats are reservoir hosts for many zoonotic viruses. Despite this, relatively little is known about the diversity and abundance of viruses within bats at the level of individual animals, and hence the frequency of virus co-infection and inter-species transmission. Using an unbiased meta-transcriptomics approach we characterised the mammalian associated viruses present in 149 individual bats sampled from Yunnan province, China. This revealed a high frequency of virus co-infection and species spillover among the animals studied, with 12 viruses shared among different bat species, which in turn facilitates virus recombination and reassortment. Of note, we identified five viral species that are likely to be pathogenic to humans or livestock, including a novel recombinant SARS-like coronavirus that is closely related to both SARS-CoV-2 and SARS-CoV, with only five amino acid differences between its receptor-binding domain sequence and that of the earliest sequences of SARS-CoV-2. Functional analysis predicts that this recombinant coronavirus can utilize the human ACE2 receptor such that it is likely to be of high zoonotic risk. Our study highlights the common occurrence of inter-species transmission and co-infection of bat viruses, as well as their implications for virus emergence.

Result of SARS-CoV-2 nucleic acid test for aerosol in a designated COVID-19 hospital

OBJECTIVE: To collect aerosol from isolation wards of a designated COVID-19 hospital and conduct the nucleic acid test so as to provide scientific basis for prevention and control of COVID-19. METHODS: The air aerosol specimens were collected from layout sites in the isolation wards of the hospital by using bioaerosol collector, and the COVID-19 nucleic acid test was carried out for all of the specimens by using fluorescent polymerase chain reaction(PCR) and digital PCR. RESULTS: A total of 86 aerosol samples were collected, all of which were tested negative for the fluorescent PCR, the result of the digital PCR test showed that 14 air aerosol samples were tested positive for COVID-19 nucleic acid, with the detection rate 16.28%. The toilets of the patients and taking-off area of protective supplies of healthcare workers were the major places where the specimens were tested positive. The positive rate of nucleic acid test was significantly higher in in intensive care units than in common wards, however, there was no significant difference in the positive rate of nucleic acid among the aerosol specimens in different wards(?-2=7.871, P=0.248);there was no significant difference in the positive rate of nucleic acid of aerosol between the patients with CT value more than 30 and the patients with CT value no more than 30(?-2=0.232, P=0.630). CONCLUSION: There are still viral nucleic acids in the air aerosol of the isolation wards during the middle and late disease course of the COVID-19 patients, but the copy number of novel coronavirus is not large in the specimens. The detection rate of the viral nucleic acid is high in the aerosol of the wards that are crowed and poorly ventilated and are associated with the cases. It is necessary for the health care workers to take good care of themselves, keep the environment well ventilated and do a good job in environmental cleaning and disinfection and air purification.

Role of tannic acid against SARS-cov-2 cell entry by targeting the interface region between S-protein-RBD and human ACE2

Coronavirus disease 2019 (COVID-19) was caused by a new coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 utilizes human angiotensin converting enzyme 2 (hACE2) as the cellular receptor of its spike glycoprotein (SP) to gain entry into cells. Consequently, we focused on the potential of repurposing clinically available drugs to block the binding of SARS-CoV-2 to hACE2 by utilizing a novel artificial-intelligence drug screening approach. Based on the structure of S-RBD and hACE2, the pharmacophore of SARS-CoV-2-receptor-binding-domain (S-RBD) -hACE2 interface was generated and used to screen a library of FDA-approved drugs. A total of 20 drugs were retrieved as S-RBD-hACE2 inhibitors, of which 16 drugs were identified to bind to S-RBD or hACE2. Notably, tannic acid was validated to interfere with the binding of S-RBD to hACE2, thereby inhibited pseudotyped SARS-CoV-2 entry. Experiments involving competitive inhibition revealed that tannic acid competes with S-RBD and hACE2, whereas molecular docking proved that tannic acid interacts with the essential residues of S-RBD and hACE2. Based on the known antiviral activity and our findings, tannic acid might serve as a promising candidate for preventing and treating SARS-CoV-2 infection.

Role of COVID-19 Vaccines in SARS-CoV-2 Variants.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is a threat to the health of the global population. As the result of a global effort in the determination of origin, structure, and pathogenesis of SARS-CoV-2 and its variants, particularly such the variant of concern as Delta Variant and Omicron Variant, the understanding of SARS-CoV-2 are deepening and the development of vaccines against SARS-CoV-2 are ongoing. Currently, AstraZeneca-Vaxzevria/SII-Covishield vaccine, Janssen-Ad26.COV2.S vaccine, Moderna-mRNA-1273 vaccine, Pfizer BioNTech-Comirnaty vaccine and Sinovac-CoronaVac vaccine have been listed as WHO Emergency Use Listing (EUL) Qualified Vaccines by WHO. Because of the antigen escape caused by the mutation in variants, the effectiveness of vaccines, which are currently the main means of prevention and treatment, has been affected by varying degrees. Herein, we review the current status of mutations of SARS-CoV-2 variants, the different approaches used in the development of COVID-19 vaccines, and COVID-19 vaccine effectiveness against SARS-CoV-2 variants.

Tuftsin: A Natural Molecule Against SARS-CoV-2 Infection.

Coronavirus disease 2019 (COVID-19) continuously progresses despite the application of a variety of vaccines. Therefore, it is still imperative to find effective ways for treating COVID-19. Recent studies indicate that NRP1, an important receptor of the natural peptide tuftsin (released from IgG), facilitates SARS-CoV-2 infection. Here, we found 91 overlapping genes between tuftsin targets and COVID-19-associated genes. We have demonstrated that tuftsin could also target ACE2 and exert some immune-related functions. Molecular docking results revealed that tustin could combine with ACE2 and NRP1 in stable structures, and their interacted regions cover the binding surfaces of S1-protein with the two receptors. Using surface plasmon resonance (SPR) analysis, we confirmed that tuftsin can bind ACE2 and NRP1 directly. Importantly, using SPR-based competition assay we have shown here that tuftsin effectively prevented the binding of SARS-CoV-2 S1-protein to ACE2. Collectively, these data suggest that tuftsin is an attractive therapeutic candidate against COVID-19 and can be considered for translational as well as clinical studies.

Environmental sampling of the severe acute respiratory syndrome coronavirus 2 Delta variant in the inpatient wards of a hospital in Nanjing.

BACKGROUND: Little is known about severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta variant of concern (VOC)-contaminated environmental surfaces and air in hospital wards admitting COVID-19 cases. Our study was designed to identify high-risk areas of Delta VOC contamination in the hospital and provide suggestions to in-hospital infection control. We analyzed the SARS-CoV-2 Delta VOC contamination in the air and environmental surface samples collected from a hospital in Nanjing, China. METHODS: We collected data on clinical features, laboratory tests, swab tests, and hospital wards, identified the factors associated with environmental contamination, and analyzed patients' hygiene behaviors during hospitalization. RESULTS: A total of 283 environmental surface and air samples were collected from a hospital admitting 36 COVID-19 patients. Twelve swab samples from ten patients were positive. Toilet seats had the highest contamination rate (11.8%), followed by bedside tables (8.2%), garbage bins (5.9%), and bedrails (1.6%). The median time of symptom onset to surface sampling was shorter in the positive environment group than in the negative environment group (11 vs. 18 days; P=0.001). The results indicated that environmental surface contamination was associated with positive anal swabs [odds ratio (OR) 27.183; 95% CI: 2.359-226.063; P=0.003] and the time from symptom onset to surface sampling (OR 0.801; 95% CI: 0.501-0.990; P=0.046). The survey revealed that 33.3% of the patients never cleaned or disinfected their bedside tables or toilets, and 8.3% of them only cleaned their bedside tables or toilets. More than half of the patients often (25%) or always (30.6%) put the used masks on their bedside tables. Only 16.7% of the patients threw the masks into the specific garbage bin for used masks. CONCLUSIONS: The SARS-CoV-2 Delta VOC was detected on environmental surfaces, especially toilet seats and bedside tables, within a median time of 11 days after symptom onset. Our study provided potential predictors for environmental surface contamination, including positive anal swabs and the time from symptom onset to sampling. Disinfecting high-risk environmental surfaces should be emphasized in hospital wards, especially for patients in the early stage of COVID-19.

Genomic Characterization of Diverse Bat Coronavirus HKU10 in Hipposideros Bats.

Bats have been identified as natural reservoirs of a variety of coronaviruses. They harbor at least 19 of the 33 defined species of alpha- and betacoronaviruses. Previously, the bat coronavirus HKU10 was found in two bat species of different suborders, Rousettus leschenaultia and Hipposideros pomona, in south China. However, its geographic distribution and evolution history are not fully investigated. Here, we screened this viral species by a nested reverse transcriptase PCR in our archived samples collected over 10 years from 25 provinces of China and one province of Laos. From 8004 bat fecal samples, 26 were found to be positive for bat coronavirus HKU10 (BtCoV HKU10). New habitats of BtCoV HKU10 were found in the Yunnan, Guangxi, and Hainan Provinces of China, and Louang Namtha Province in Laos. In addition to H. pomona, BtCoV HKU10 variants were found circulating in Aselliscus stoliczkanus and Hipposideros larvatus. We sequenced full-length genomes of 17 newly discovered BtCoV HKU10 strains and compared them with previously published sequences. Our results revealed a much higher genetic diversity of BtCoV HKU10, particularly in spike genes and accessory genes. Besides the two previously reported lineages, we found six novel lineages in their new habitats, three of which were located in Yunnan province. The genotypes of these viruses are closely related to sampling locations based on polyproteins, and correlated to bat species based on spike genes. Combining phylogenetic analysis, selective pressure, and molecular-clock calculation, we demonstrated that Yunnan bats harbor a gene pool of BtCoV HKU10, with H. pomona as a natural reservoir. The cell tropism test using spike-pseudotyped lentivirus system showed that BtCoV HKU10 could enter cells from human and bat, suggesting a potential interspecies spillover. Continuous studies on these bat coronaviruses will expand our understanding of the evolution and genetic diversity of coronaviruses, and provide a prewarning of potential zoonotic diseases from bats.