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Background: The newly emerged SARS-CoV-2 possesses shared antigenic epitopes with other human coronaviruses. We investigated if COVID-19 vaccination or SARS-CoV-2 infection may boost cross-reactive antibodies to other human coronaviruses., Methods: Prevaccination and postvaccination sera from SARS-CoV-2 naïve healthy subjects who received three doses of the mRNA vaccine (BioNTech, BNT) or the inactivated vaccine (CoronaVac, CV) were used to monitor the level of cross-reactive antibodies raised against other human coronaviruses by enzyme-linked immunosorbent assay. In comparison, convalescent sera from COVID-19 patients with or without prior vaccination history were also tested. Pseudoparticle neutralization assay was performed to detect neutralization antibody against MERS-CoV., Results: Among SARS-CoV-2 infection-naïve subjects, BNT or CV significantly increased the anti-S2 antibodies against Betacoronaviruses (OC43 and MERS-CoV) but not Alphacoronaviruses (229E). The prevaccination antibody response to the common cold human coronaviruses did not negatively impact the postvaccination antibody response to SARS-CoV-2. Cross-reactive antibodies that binds to the S2 protein of MERS-CoV were similarly detected from the convalescent sera of COVID-19 patients with or without vaccination history. However, these anti-S2 antibodies do not possess neutralizing activity in MERS-CoV pseudoparticle neutralization tests., Conclusions: Our results suggest that SARS-CoV-2 infection or vaccination may potentially modulate population immune landscape against previously exposed or novel human coronaviruses. The findings have implications for future sero-epidemiological studies on MERS-CoV., (© 2024 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.)

Objectives: We compared the risk of environmental contamination among patients with COVID-19 who received high-flow nasal cannula (HFNC), noninvasive ventilation (NIV), and conventional oxygen therapy (COT) via nasal cannula for respiratory failure., Methods: Air was sampled from the hospital isolation rooms with 12 air changes/hr where 26 patients with COVID-19 received HFNC (up to 60 l/min, n = 6), NIV (n = 6), or COT (up to 5 l/min of oxygen, n = 14). Surface samples were collected from 16 patients during air sampling., Results: Viral RNA was detected at comparable frequency in air samples collected from patients receiving HFNC (3/54, 5.6%), NIV (1/54, 1.9%), and COT (4/117, 3.4%) (P = 0.579). Similarly, the risk of surface contamination was comparable among patients receiving HFNC (3/46, 6.5%), NIV (14/72, 19.4%), and COT (8/59, 13.6%) (P = 0.143). An increment in the cyclic thresholds of the upper respiratory specimen prior to air sampling was associated with a reduced SARS-CoV-2 detection risk in air (odds ratio 0.83 [95% confidence interval 0.69-0.96], P = 0.027) by univariate logistic regression., Conclusion: No increased risk of environmental contamination in the isolation rooms was observed in the use of HFNC and NIV vs COT among patients with COVID-19 with respiratory failure. Higher viral load in the respiratory samples was associated with positive air samples., Competing Interests: Declarations of competing interest The authors have no competing interests to declare., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: The epidemiological advantage of Omicron variant is evidenced by its rapid spread and the ability to outcompete prior variants. Among Omicron sublineages, early outbreaks were dominated by BA.1, while BA.2 has gained dominance since February 2022. The relative pathogenicity and transmissibility of BA.1 and BA.2 have not been fully defined., Methods: We compared viral loads and clinical signs in Syrian hamsters after infection with BA.1, BA.2, or D614G variant. A competitive transmission model and next-generation sequencing were used to compare the relative transmission potential of BA.1 and BA.2., Results: BA.1 and BA.2 caused no apparent clinical signs, while D614G caused more than 10% weight loss. Higher viral loads were detected in nasal wash samples and nasal turbinate and lung tissues from BA.1-inoculated hamsters compared with BA.2-inoculated hamsters. No aerosol transmission was observed for BA.1 or BA.2 under the experimental condition in which D614G transmitted efficiently. BA.1 and BA.2 were able to transmit among hamsters via direct contact; however, BA.1 transmitted more efficiently than BA.2 under the competitive transmission model. No recombination was detected from direct contacts exposed simultaneously to BA.1 and BA.2., Conclusions: Omicron BA.1 and BA.2 demonstrated attenuated pathogenicity and reduced transmission potential in hamsters compared with early SARS-CoV-2 strains., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Several animal models have been developed to study the pathophysiology of SARS-CoV-2 infection and to evaluate vaccines and therapeutic agents for this emerging disease. Similar to infection with SARS-CoV-1, infection of Syrian hamsters with SARS-CoV-2 results in moderate respiratory disease involving the airways and lung parenchyma but does not lead to increased mortality. Using a combination of immunohistochemistry and transmission electron microscopy, we showed that the epithelium of the conducting airways of hamsters was the primary target for viral infection within the first 5 days of infection, with little evidence of productive infection of pneumocytes. At 6 days postinfection, antigen was cleared but parenchymal damage persisted, and the major pathological changes resolved by day 14. These findings are similar to those previously reported for hamsters with SARS-CoV-1 infection. In contrast, infection of K18-hACE2 transgenic mice resulted in pneumocyte damage, with viral particles and replication complexes in both type I and type II pneumocytes together with the presence of convoluted or cubic membranes; however, there was no evidence of virus replication in the conducting airways. The Syrian hamster is a useful model for the study of SARS-CoV-2 transmission and vaccination strategies, whereas infection of the K18-hCE2 transgenic mouse results in lethal disease with fatal neuroinvasion but with sparing of conducting airways.

Background: Transmission of SARS-CoV-2 from humans to other mammals, including pet animals, has been reported. However, with the exception of farmed mink, there is no previous evidence that these infected animals can infect humans, resulting in sustained human-to-human transmission. Following a confirmed SARS-CoV-2 infection of a pet shop worker, animals in the shop and the warehouse supplying it were tested for evidence of SARS-CoV-2 infection., Methods: In this case study, viral swabs and blood samples were collected from animals in a pet shop and its corresponding warehouse in Hong Kong. Nasal swab or saliva samples from human COVID-19 patients epidemiologically linked to the pet shop and from subsequent local cases confirmed to be infected by SARS-CoV-2 delta variant were collected. Oral swabs were tested by quantitative RT-PCR (RT-qPCR) for SARS-CoV-2 and blood samples were serologically tested by a surrogate virus neutralisation test and plaque reduction neutralisation test. The SARS-CoV-2 RT-qPCR positive samples were sequenced by next generation viral full genome sequencing using the ISeq sequencing platform (Illumina), and the viral genomes were phylogenetically analysed., Findings: Eight (50%) of 16 individually tested Syrian hamsters in the pet shop and seven (58%) of 12 Syrian hamsters in the corresponding warehouse were positive for SARS-CoV-2 infection in RT-qPCR or serological tests. None of the dwarf hamsters (n=75), rabbits (n=246), guinea pigs (n=66), chinchillas (n=116), and mice (n=2) were confirmed positive for SARS-CoV-2 in RT-qPCR tests. SARS-CoV-2 viral genomes deduced from human and hamster cases in this incident all belong to the delta variant of concern (AY.127) that had not been circulating locally before this outbreak. The viral genomes obtained from hamsters were phylogenetically related with some sequence heterogeneity. Phylogenetic dating suggests infection in these hamsters occurred around Oct 14, 2021 (95% CI Sept 15 to Nov 9, 2021). Multiple zoonotic transmission events to humans were detected, leading to onward human-to-human transmission., Interpretation: Pet hamsters can be naturally infected with SARS-CoV-2. The virus can circulate among hamsters and lead to human infections. Both genetic and epidemiological results strongly suggest that there was more than one hamster-to-human transmission event in this study. This incident also led to onward human transmission. Importation of SARS-CoV-2-infected hamsters was a likely source of this outbreak., Funding: US National Institutes of Health, Research Grants Council of Hong Kong, Food and Health Bureau, and InnoHK., Competing Interests: Declaration of interests GML is an official expert adviser to the Hong Kong Government on COVID-19. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The number of people infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to increase worldwide, but despite extensive research, there remains significant uncertainty about the predominant routes of SARS-CoV-2 transmission. We conducted a mechanistic modeling and calculated the exposure dose and infection risk of each passenger in a two-bus COVID-19 outbreak in Hunan province, China. This outbreak originated from a single pre-symptomatic index case. Some human behavioral data related to exposure including boarding and alighting time of some passengers and seating position and mask wearing of all passengers were obtained from the available closed-circuit television images/clips and/or questionnaire survey. Least-squares fitting was performed to explore the effect of effective viral load on transmission risk, and the most likely quanta generation rate was also estimated. This study reveals the leading role of airborne SARS-CoV-2 transmission and negligible role of fomite transmission in a poorly ventilated indoor environment, highlighting the need for more targeted interventions in such environments. The quanta generation rate of the index case differed by a factor of 1.8 on the two buses and transmission occurred in the afternoon of the same day, indicating a time-varying effective viral load within a short period of five hours., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein is the main target for neutralizing antibodies. These antibodies can be elicited through immunization or passively transferred as therapeutics in the form of convalescent-phase sera or monoclonal antibodies (MAbs). Potently neutralizing antibodies are expected to confer protection; however, it is unclear whether weakly neutralizing antibodies contribute to protection. Also, their mechanism of action in vivo is incompletely understood. Here, we demonstrate that 2B04, an antibody with an ultrapotent neutralizing activity (50% inhibitory concentration [IC 50 ] of 0.04 μg/ml), protects hamsters against SARS-CoV-2 in a prophylactic and therapeutic infection model. Protection is associated with reduced weight loss and viral loads in nasal turbinates and lungs after challenge. MAb 2B04 also blocked aerosol transmission of the virus to naive contacts. We next examined three additional MAbs (2C02, 2C03, and 2E06), recognizing distinct epitopes within the receptor binding domain of spike protein that possess either minimal (2C02 and 2E06, IC 50 > 20 μg/ml) or weak (2C03, IC 50 of 5 μg/ml) virus neutralization capacity in vitro . Only 2C03 protected Syrian hamsters from weight loss and reduced lung viral load after SARS-CoV-2 infection. Finally, we demonstrated that Fc-Fc receptor interactions were not required for protection when 2B04 and 2C03 were administered prophylactically. These findings inform the mechanism of protection and support the rational development of antibody-mediated protection against SARS-CoV-2 infections. IMPORTANCE The ongoing coronavirus disease 2019 (COVID-19) pandemic, caused by SARS-CoV-2, has resulted in the loss of millions of lives. Safe and effective vaccines are considered the ultimate remedy for the global social and economic disruption caused by the pandemic. However, a thorough understanding of the immune correlates of protection against this virus is lacking. Here, we characterized four different monoclonal antibodies and evaluated their ability to prevent or treat SARS-CoV-2 infection in Syrian hamsters. These antibodies varied in their ability to neutralize the virus in vitro . Prophylactic administration of potent and weakly neutralizing antibodies protected against SARS-CoV-2 infection, and this effect was Fc receptor independent. The potent neutralizing antibody also had therapeutic efficacy and eliminated onward aerosol transmission. In contrast, minimally neutralizing antibodies provided no protection against infection with SARS-CoV-2 in Syrian hamsters. Combined, these studies highlight the significance of weakly neutralizing antibodies in the protection against SARS-CoV-2 infection and associated disease.

Surrogate neutralization assays for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that can be done without biosafety level 3 containment and in multiple species are desirable. We evaluate a recently developed surrogate virus neutralization test (sVNT) in comparison to 90% plaque reduction neutralization tests (PRNT 90 ) in human, canine, cat, and hamster sera. With PRNT 90 as the reference, sVNT had sensitivity of 98.9% and specificity of 98.8%. Using a panel of immune sera corresponding to other coronaviruses, we confirm the lack of cross-reactivity to other coronaviruses in SARS-CoV-2 sVNT and PRNT 90 , except for cross-reactivity to SARS-CoV-1 in sVNT., (Copyright © 2021 American Society for Microbiology.)

Understanding the transmission mechanism of SARS-CoV-2 is a prerequisite to effective control measures. To investigate the potential modes of SARS-CoV-2 transmission, 21 COVID-19 patients from 12-47 days after symptom onset were recruited. We monitored the release of SARS-CoV-2 from the patients' exhaled breath and systematically investigated environmental contamination of air, public surfaces, personal necessities, and the drainage system. SARS-CoV-2 RNA was detected in 0 of 9 exhaled breath samples, 2 of 8 exhaled breath condensate samples, 1 of 12 bedside air samples, 4 of 132 samples from private surfaces, 0 of 70 samples from frequently touched public surfaces in isolation rooms, and 7 of 23 feces-related air/surface/water samples. The maximum viral RNA concentrations were 1857 copies/m 3 in the air, 38 copies/cm 2 in sampled surfaces and 3092 copies/mL in sewage/wastewater samples. Our results suggest that nosocomial transmission of SARS-CoV-2 can occur via multiple routes. However, the low detection frequency and limited quantity of viral RNA from the breath and environmental specimens may be related to the reduced viral load of the COVID-19 patients on later days after symptom onset. These findings suggest that the transmission dynamics of SARS-CoV-2 differ from those of SARS-CoV in healthcare settings., (Copyright © 2020 Elsevier B.V. All rights reserved.)

An outbreak of COVID-19 occurred on the Diamond Princess cruise ship in January and February 2020 in Japan. We analysed information on the cases of infection to infer whether airborne transmission of SARS-CoV-2, the causative agent of COVID-19, had occurred between cabins. We infer from our analysis that most infections in passengers started on 28 January and were completed by 6 February, except in those who shared a cabin with another infected passenger. The distribution of the infected cabins was random, and no spatial cluster of the infected can be identified. We infer that the ship's central air-conditioning system for passenger's cabins did not play a role in SARS-CoV-2 transmission, i.e. airborne transmission did not occur between cabins during the outbreak, suggesting that the sufficient ventilation was provided. We also infer that the ship's cabin drainage system did not play a role. Most transmission appears to have occurred in the public areas of the cruise ship, likely due to crowding and insufficient ventilation in some of these areas. [Display omitted] • No cross-room transmission between cabins during the quarantine period. • Most infections occurred before quarantine. • The central air-conditioning system and drainage system of cabins did not play a role. • SARS-CoV-2 transmission in public areas may explain the outbreak. • Intervention in public areas, such as sufficient ventilation, is important. [ABSTRACT FROM AUTHOR]

Respiratory and fecal aerosols play confirmed and suspected roles, respectively, in transmitting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). An extensive environmental sampling campaign of both toilet and non-toilet environments was performed in a dedicated hospital building for patients with coronavirus disease 2019 (COVID-19), and the associated environmental factors were analyzed. In total, 107 surface samples, 46 air samples, two exhaled condensate samples, and two expired air samples were collected within and beyond four three-bed isolation rooms. The data of the COVID-19 patients were collected. The building environmental design and the cleaning routines were reviewed. Field measurements of airflow and CO 2 concentrations were conducted. The 107 surface samples comprised 37 from toilets, 34 from other surfaces in isolation rooms, and 36 from other surfaces outside the isolation rooms in the hospital. Four of these samples were positive, namely two ward door handles, one bathroom toilet seat cover, and one bathroom door handle. Three were weakly positive, namely one bathroom toilet seat, one bathroom washbasin tap lever, and one bathroom ceiling exhaust louver. Of the 46 air samples, one collected from a corridor was weakly positive. The two exhaled condensate samples and the two expired air samples were negative. The fecal-derived aerosols in patients' toilets contained most of the detected SARS-CoV-2 in the hospital, highlighting the importance of surface and hand hygiene for intervention. Unlabelled Image • All SARS-CoV-2-positive surface samples were associated with patients' toilets. • Only one of 46 air samples was weakly positive for SARS-CoV-2. • All four exhaled condensate or expired air samples were negative for SARS-CoV-2. • Fecal-derived aerosols contained most of the detected SARS-CoV-2 virus. • Regular disinfection of toilet surfaces is an important COVID-19 intervention. [ABSTRACT FROM AUTHOR]

An escalating pandemic by the novel SARS-CoV-2 virus is impacting global health and effective therapeutic options are urgently needed. We evaluated the in vitro antiviral effect of compounds that were previously reported to inhibit coronavirus replication and compounds that are currently under evaluation in clinical trials for SARS-CoV-2 patients. We report the antiviral effect of remdesivir, lopinavir, homorringtonine, and emetine against SARS-CoV-2 virus in Vero E6 cells with the estimated 50% effective concentration at 23.15 μM, 26.63 μM, 2.55 μM and 0.46 μM, respectively. Ribavirin or favipiravir that are currently evaluated under clinical trials showed no inhibition at 100 μM. Synergy between remdesivir and emetine was observed, and remdesivir at 6.25 μM in combination with emetine at 0.195 μM may achieve 64.9% inhibition in viral yield. Combinational therapy may help to reduce the effective concentration of compounds below the therapeutic plasma concentrations and provide better clinical benefits. • Remdesivir inhibits SARS-CoV-2 replication in Vero-E6 cells with EC 50 at 23.15 μM. • Lopinavir but not ritonavir inhibits SARS-CoV-2 replication with EC 50 at 26.63 μM. • Homoharringtonine and emetine inhibits SARS-CoV-2 replication with EC 50 at 2.55 and 0.46 μM, respectively. • Combination of remdesivir and emetine showed synergistic effect in vitro. [ABSTRACT FROM AUTHOR]