This study describes results of PCR and viral RNA testing for SARS-CoV-2 in bronchoalveolar fluid, sputum, feces, blood, and urine specimens from patients with COVID-19 infection in China to identify ...possible means of non-respiratory transmission.
The launch of the new journal, Biosafety and Health, presents me with a unique opportunity to recount the progress of laboratory biosafety (LB) in China and my contribution to this area over the past ...30 years. Since the severe acute respiratory syndrome epidemic in 2003, China has constructed a primary network of high-level biosafety laboratories at different levels and established an expert team on LB. Furthermore, a series of LB management documents, including laws, regulations, standards, and guidelines, have been developed and published. This gradually maturing LB system has played a pivotal role in emerging infectious disease control and prevention, as well as in research, which in turn contributes to public health. In recent years, international collaboration between China and other countries has also been accelerated. Despite these achievements, we are still facing many challenges and opportunities in the field of LB. Sustainable LB development requires the joint efforts of the entire society and continuous international cooperation to safeguard global public health.
•Since the SARS epidemic, China has constructed a biosafety laboratories network and set up an expert team on LB.•A series of LB management documents, including laws, regulations, standards, and guidelines, have been published.•In recent years, international collaboration between China and other countries has also been accelerated.•In future, infrastructure, regulatory system and human resource should be enhanced to improve China’s LB system.
Neutralizing antibodies could potentially be used as antivirals against the coronavirus disease 2019 (COVID-19) pandemic. Here, we report isolation of four human-origin monoclonal antibodies from a ...convalescent patient, all of which display neutralization abilities. The antibodies B38 and H4 block binding between the spike glycoprotein receptor binding domain (RBD) of the virus and the cellular receptor angiotensin-converting enzyme 2 (ACE2). A competition assay indicated different epitopes on the RBD for these two antibodies, making them a potentially promising virus-targeting monoclonal antibody pair for avoiding immune escape in future clinical applications. Moreover, a therapeutic study in a mouse model validated that these antibodies can reduce virus titers in infected lungs. The RBD-B38 complex structure revealed that most residues on the epitope overlap with the RBD-ACE2 binding interface, explaining the blocking effect and neutralizing capacity. Our results highlight the promise of antibody-based therapeutics and provide a structural basis for rational vaccine design.
Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) causes the infectious disease COVID-19 (coronavirus disease 2019), which was first reported in Wuhan, China, in December 2019. Despite ...extensive efforts to control the disease, COVID-19 has now spread to more than 100 countries and caused a global pandemic. SARS-CoV-2 is thought to have originated in bats; however, the intermediate animal sources of the virus are unknown. In this study, we investigated the susceptibility of ferrets and animals in close contact with humans to SARS-CoV-2. We found that SARS-CoV-2 replicates poorly in dogs, pigs, chickens, and ducks, but ferrets and cats are permissive to infection. Additionally, cats are susceptible to airborne transmission. Our study provides insights into the animal models for SARS-CoV-2 and animal management for COVID-19 control.
An outbreak of coronavirus disease 2019 (COVID-19)
, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
, has spread globally. Countermeasures are needed to treat and prevent ...further dissemination of the virus. Here we report the isolation of two specific human monoclonal antibodies (termed CA1 and CB6) from a patient convalescing from COVID-19. CA1 and CB6 demonstrated potent SARS-CoV-2-specific neutralization activity in vitro. In addition, CB6 inhibited infection with SARS-CoV-2 in rhesus monkeys in both prophylactic and treatment settings. We also performed structural studies, which revealed that CB6 recognizes an epitope that overlaps with angiotensin-converting enzyme 2 (ACE2)-binding sites in the SARS-CoV-2 receptor-binding domain, and thereby interferes with virus-receptor interactions by both steric hindrance and direct competition for interface residues. Our results suggest that CB6 deserves further study as a candidate for translation to the clinic.
Abstract
Background
Train travel is a common mode of public transport across the globe; however, the risk of coronavirus disease 2019 (COVID-19) transmission among individual train passengers remains ...unclear.
Methods
We quantified the transmission risk of COVID-19 on high-speed train passengers using data from 2334 index patients and 72 093 close contacts who had co-travel times of 0–8 hours from 19 December 2019 through 6 March 2020 in China. We analyzed the spatial and temporal distribution of COVID-19 transmission among train passengers to elucidate the associations between infection, spatial distance, and co-travel time.
Results
The attack rate in train passengers on seats within a distance of 3 rows and 5 columns of the index patient varied from 0 to 10.3% (95% confidence interval CI, 5.3%–19.0%), with a mean of 0.32% (95% CI, .29%–.37%). Passengers in seats on the same row (including the adjacent passengers to the index patient) as the index patient had an average attack rate of 1.5% (95% CI, 1.3%–1.8%), higher than that in other rows (0.14% 95% CI, .11%–.17%), with a relative risk (RR) of 11.2 (95% CI, 8.6–14.6). Travelers adjacent to the index patient had the highest attack rate (3.5% 95% CI, 2.9%–4.3%) of COVID-19 infection (RR, 18.0 95% CI, 13.9–23.4) among all seats. The attack rate decreased with increasing distance, but increased with increasing co-travel time. The attack rate increased on average by 0.15% (P = .005) per hour of co-travel; for passengers in adjacent seats, this increase was 1.3% (P = .008), the highest among all seats considered.
Conclusions
COVID-19 has a high transmission risk among train passengers, but this risk shows significant differences with co-travel time and seat location. During disease outbreaks, when traveling on public transportation in confined spaces such as trains, measures should be taken to reduce the risk of transmission, including increasing seat distance, reducing passenger density, and use of personal hygiene protection.
The transmission risk of coronavirus disease 2019 (COVID-19) in train passengers is heterogeneous by co-travel time and seat location, with the highest risk seen among passengers adjacent to an index patient. Measures should be taken to prevent COVID-19 transmission on trains.
SARS-CoV-2, a β-coronavirus, has rapidly spread across the world, highlighting its high transmissibility, but the underlying morphogenesis and pathogenesis remain poorly understood. Here, we ...characterize the replication dynamics, cell tropism and morphogenesis of SARS-CoV-2 in organotypic human airway epithelial (HAE) cultures. SARS-CoV-2 replicates efficiently and infects both ciliated and secretory cells in HAE cultures. In comparison, HCoV-NL63 replicates to lower titers and is only detected in ciliated cells. SARS-CoV-2 shows a similar morphogenetic process as other coronaviruses but causes plaque-like cytopathic effects in HAE cultures. Cell fusion, apoptosis, destruction of epithelium integrity, cilium shrinking and beaded changes are observed in the plaque regions. Taken together, our results provide important insights into SARS-CoV-2 cell tropism, replication and morphogenesis.
The outbreak of COVID-19 has become a worldwide pandemic. The pathogenesis of this infectious disease and how it differs from other drivers of pneumonia is unclear. Here we analyze urine samples from ...COVID-19 infection cases, healthy donors and non-COVID-19 pneumonia cases using quantitative proteomics. The molecular changes suggest that immunosuppression and tight junction impairment occur in the early stage of COVID-19 infection. Further subgrouping of COVID-19 patients into moderate and severe types shows that an activated immune response emerges in severely affected patients. We propose a two-stage mechanism of pathogenesis for this unusual viral infection. Our data advance our understanding of the clinical features of COVID-19 infections and provide a resource for future mechanistic and therapeutics studies.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of coronavirus disease 2019 (COVID-19), which has become a public health emergency of international concern
. ...Angiotensin-converting enzyme 2 (ACE2) is the cell-entry receptor for severe acute respiratory syndrome coronavirus (SARS-CoV)
. Here we infected transgenic mice that express human ACE2 (hereafter, hACE2 mice) with SARS-CoV-2 and studied the pathogenicity of the virus. We observed weight loss as well as virus replication in the lungs of hACE2 mice infected with SARS-CoV-2. The typical histopathology was interstitial pneumonia with infiltration of considerable numbers of macrophages and lymphocytes into the alveolar interstitium, and the accumulation of macrophages in alveolar cavities. We observed viral antigens in bronchial epithelial cells, macrophages and alveolar epithelia. These phenomena were not found in wild-type mice infected with SARS-CoV-2. Notably, we have confirmed the pathogenicity of SARS-CoV-2 in hACE2 mice. This mouse model of SARS-CoV-2 infection will be valuable for evaluating antiviral therapeutic agents and vaccines, as well as understanding the pathogenesis of COVID-19.
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