Nirmatrelvir/ritonavir use in patients with COVID-19 on hemodialysis: a case series

Patients undergoing hemodialysis (HD) are particularly vulnerable to coronavirus disease 2019 (COVID-19) and are at increased risk of developing severe infection. However, given the exclusion of such patients from clinical trials, there are limited data regarding the effectiveness of the antiviral drug nirmatrelvir/ritonavir (N/R) in patients on HD. We prescribed N/R to four patients on HD with COVID-19 after obtaining informed consent. Their clinical symptoms were improved at approximately 3 days after N/R administration. The viral load was reduced after approximately 10 days. The main adverse effects were nausea and vomiting. Rational dosage adjustment obtained good tolerance but did not influence the efficacy. These results suggest that N/R may be a promising agent for patients on HD with COVID-19.

Antiviral Nanobiologic Therapy Remodulates Innate Immune Responses to Highly Pathogenic Coronavirus.

Highly pathogenic coronavirus (CoV) infection induces a defective innate antiviral immune response coupled with the dysregulated release of proinflammatory cytokines and finally results in acute respiratory distress syndrome (ARDS). A timely and appropriate triggering of innate antiviral response is crucial to inhibit viral replication and prevent ARDS. However, current medical countermeasures can rarely meet this urgent demand. Here, an antiviral nanobiologic named CoVR-MV is developed, which is polymerized of CoVs receptors based on a biomimetic membrane vesicle system. The designed CoVR-MV interferes with the viral infection by absorbing the viruses with maximized viral spike target interface, and mediates the clearance of the virus through its inherent interaction with macrophages. Furthermore, CoVR-MV coupled with the virus promotes a swift production and signaling of endogenous type I interferon via deregulating 7-dehydrocholesterol reductase (DHCR7) inhibition of interferon regulatory factor 3 (IRF3) activation in macrophages. These sequential processes re-modulate the innate immune responses to the virus, trigger spontaneous innate antiviral defenses, and rescue infected Syrian hamsters from ARDS caused by SARS-CoV-2 and all tested variants.

Virus diversity, wildlife-domestic animal circulation and potential zoonotic viruses of small mammals, pangolins and zoo animals.

Wildlife is reservoir of emerging viruses. Here we identified 27 families of mammalian viruses from 1981 wild animals and 194 zoo animals collected from south China between 2015 and 2022, isolated and characterized the pathogenicity of eight viruses. Bats harbor high diversity of coronaviruses, picornaviruses and astroviruses, and a potentially novel genus of Bornaviridae. In addition to the reported SARSr-CoV-2 and HKU4-CoV-like viruses, picornavirus and respiroviruses also likely circulate between bats and pangolins. Pikas harbor a new clade of Embecovirus and a new genus of arenaviruses. Further, the potential cross-species transmission of RNA viruses (paramyxovirus and astrovirus) and DNA viruses (pseudorabies virus, porcine circovirus 2, porcine circovirus 3 and parvovirus) between wildlife and domestic animals was identified, complicating wildlife protection and the prevention and control of these diseases in domestic animals. This study provides a nuanced view of the frequency of host-jumping events, as well as assessments of zoonotic risk.

A SARS-CoV-2-specific CAR-T-cell model identifies felodipine, fasudil, imatinib, and caspofungin as potential treatments for lethal COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced cytokine storm is closely associated with coronavirus disease 2019 (COVID-19) severity and lethality. However, drugs that are effective against inflammation to treat lethal COVID-19 are still urgently needed. Here, we constructed a SARS-CoV-2 spike protein-specific CAR, and human T cells infected with this CAR (SARS-CoV-2-S CAR-T) and stimulated with spike protein mimicked the T-cell responses seen in COVID-19 patients, causing cytokine storm and displaying a distinct memory, exhausted, and regulatory T-cell phenotype. THP1 remarkably augmented cytokine release in SARS-CoV-2-S CAR-T cells when they were in coculture. Based on this "two-cell" (CAR-T and THP1 cells) model, we screened an FDA-approved drug library and found that felodipine, fasudil, imatinib, and caspofungin were effective in suppressing the release of cytokines, which was likely due to their ability to suppress the NF-κB pathway in vitro. Felodipine, fasudil, imatinib, and caspofungin were further demonstrated, although to different extents, to attenuate lethal inflammation, ameliorate severe pneumonia, and prevent mortality in a SARS-CoV-2-infected Syrian hamster model, which were also linked to their suppressive role in inflammation. In summary, we established a SARS-CoV-2-specific CAR-T-cell model that can be utilized as a tool for anti-inflammatory drug screening in a fast and high-throughput manner. The drugs identified herein have great potential for early treatment to prevent COVID-19 patients from cytokine storm-induced lethality in the clinic because they are safe, inexpensive, and easily accessible for immediate use in most countries.

Utility of monocyte distribution width in the differential diagnosis between simple and complicated diverticulitis: a retrospective cohort study.

BACKGROUND: Colonic diverticulitis is a leading cause of abdominal pain. The monocyte distribution width (MDW) is a novel inflammatory biomarker with prognostic significance for coronavirus disease and pancreatitis; however, no study has assessed its correlation with the severity of colonic diverticulitis. METHODS: This single-center retrospective cohort study included patients older than 18 years who presented to the emergency department between November 1, 2020, and May 31, 2021, and received a diagnosis of acute colonic diverticulitis after abdominal computed tomography. The characteristics and laboratory parameters of patients with simple versus complicated diverticulitis were compared. The significance of categorical data was assessed using the chi-square or Fisher's exact test. The Mann-Whitney U test was used for continuous variables. Multivariable regression analysis was performed to identify predictors of complicated colonic diverticulitis. Receiver operator characteristic (ROC) curves were used to test the efficacy of inflammatory biomarkers in distinguishing simple from complicated cases. RESULTS: Of the 160 patients enrolled, 21 (13.125%) had complicated diverticulitis. Although right-sided was more prevalent than left-sided colonic diverticulitis (70% versus 30%), complicated diverticulitis was more common in those with left-sided colonic diverticulitis (61.905%, p = 0.001). Age, white blood cell (WBC) count, neutrophil count, C-reactive protein (CRP) level, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and MDW were significantly higher in the complicated diverticulitis group (p < 0.05). Logistic regression analysis indicated that the left-sided location and the MDW were significant and independent predictors of complicated diverticulitis. The area under the ROC curve (AUC) was as follows: MDW, 0.870 (95% confidence interval [CI], 0.784-0.956); CRP, 0.800 (95% CI, 0.707-0.892); NLR, 0.724 (95% CI, 0.616-0.832); PLR, 0.662 (95% CI, 0.525-0.798); and WBC, 0.679 (95% CI, 0.563-0.795). When the MDW cutoff was 20.38, the sensitivity and specificity were maximized to 90.5% and 80.6%, respectively. CONCLUSIONS: A large MDW was a significant and independent predictor of complicated diverticulitis. The optimal cutoff value for MDW is 20.38 as it exhibits maximum sensitivity and specificity for distinguishing between simple and complicated diverticulitis The MDW may aid in planning antibiotic therapy for patients with colonic diverticulitis in the emergency department.

Discovery of novel Mamastroviruses in Bactrian camels and dromedaries reveals complex recombination history.

Virus emergence may occur through interspecies transmission and recombination of viruses coinfecting a host, with potential to pair novel and adaptive gene combinations. Camels are known to harbor diverse ribonucleic acid viruses with zoonotic and epizootic potential. Among them, astroviruses are of particular interest due to their cross-species transmission potential and endemicity in diverse host species, including humans. We conducted a molecular epidemiological survey of astroviruses in dromedaries from Saudi Arabia and Bactrian camels from Inner Mongolia, China. Herein, we deployed a hybrid sequencing approach coupling deep sequencing with rapid amplification of complementary deoxyribonucleic acid ends to characterize two novel Bactrian and eight dromedary camel astroviruses, including both partial and complete genomes. Our reported sequences expand the known diversity of dromedary camel astroviruses, highlighting potential recombination events among the astroviruses of camelids and other host species. In Bactrian camels, we detected partially conserved gene regions bearing resemblance to human astrovirus types 1, 4, and 8 although we were unable to recover complete reading frames from these samples. Continued surveillance of astroviruses in camelids, particularly Bactrian species and associated livestock, is highly recommended to identify patterns of cross-species transmission and to determine any epizootic threats and zoonotic risks posed to humans. Phylogenomic approaches are needed to investigate complex patterns of recombination among the astroviruses and to infer their evolutionary history across diverse host species.

Overcome social anxiety disorder and develop visionary leadership in uncertain environments: The important role of psychological resilience.

Uncertainty is the main feature of the business environment in the post-coronavirus disease 2019 (COVID-19) era. People taking leadership positions in an uncertain environment constantly encounter unprecedented risks and challenges. Many of them have difficulties adapting to such an environment and thus experience severe anxiety, showing the symptoms of social anxiety disorder (SAD), failing to exert effective leadership in social interaction contexts. How can leaders overcome SAD and effectively motivate their subordinates in an uncertain environment? This study explores the important role of psychological resilience. Using sample data collected from 82 leaders and 363 subordinates of eight enterprises in China from May to June 2020, the current study reveals that a high degree of psychological resilience enables leaders to maintain intrinsic motivated at work in an uncertain environment. Leaders with a high degree of psychological resilience perform better in identifying the organizations' vision and displaying visionary leadership than those with a low degree. The current study enriches the knowledge of leaders' psychological well-being and effective leadership in the post-COVID-19 era.

Lineage-mosaic and mutation-patched spike proteins for broad-spectrum COVID-19 vaccine.

SARS-CoV-2 spread in humans results in continuous emergence of new variants, highlighting the need for vaccines with broad-spectrum antigenic coverage. Using inter-lineage chimera and mutation-patch strategies, we engineered a recombinant monomeric spike variant (STFK1628x) that contains key regions and residues across multiple SAR-CoV-2 variants. STFK1628x demonstrated high immunogenicity and mutually complementary antigenicity to its prototypic form (STFK). In hamsters, a bivalent vaccine composed of STFK and STFK1628x elicited high titers of broad-spectrum neutralizing antibodies to 19 circulating SARS-CoV-2 variants, including Omicron sublineages BA.1, BA.1.1, BA.2, BA.2.12.1, BA.2.75, and BA.4/5. Furthermore, this vaccine conferred robust protection against intranasal challenges by either SARS-CoV-2 ancestral strain or immune-evasive Beta and Omicron BA.1. Strikingly, vaccination with the bivalent vaccine in hamsters effectively blocked within-cage virus transmission of ancestral SARS-CoV-2, Beta variant, and Omicron BA.1 to unvaccinated sentinels. Thus, our study provided insight and antigen candidates for the development of next-generation COVID-19 vaccines.

Overcome social anxiety disorder and develop visionary leadership in uncertain environments: The important role of psychological resilience

Uncertainty is the main feature of the business environment in the post-coronavirus disease 2019 (COVID-19) era. People taking leadership positions in an uncertain environment constantly encounter unprecedented risks and challenges. Many of them have difficulties adapting to such an environment and thus experience severe anxiety, showing the symptoms of social anxiety disorder (SAD), failing to exert effective leadership in social interaction contexts. How can leaders overcome SAD and effectively motivate their subordinates in an uncertain environment? This study explores the important role of psychological resilience. Using sample data collected from 82 leaders and 363 subordinates of eight enterprises in China from May to June 2020, the current study reveals that a high degree of psychological resilience enables leaders to maintain intrinsic motivated at work in an uncertain environment. Leaders with a high degree of psychological resilience perform better in identifying the organizations' vision and displaying visionary leadership than those with a low degree. The current study enriches the knowledge of leaders' psychological well-being and effective leadership in the post-COVID-19 era.

A Heterologous Challenge Rescues the Attenuated Immunogenicity of SARS-CoV-2 Omicron BA.1 Variant in Syrian Hamster Model.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant is becoming a dominant circulator and has several mutations in the spike glycoprotein, which may cause shifts of immunogenicity, so as to result in immune escape and breakthrough infection among the already infected or vaccinated populations. It is unclear whether infection with Omicron could generate adequate cross-variant protection. To investigate this possibility, we used Syrian hamsters as an animal model for infection of SARS-CoV-2. The serum from Omicron BA.1 variant-infected hamsters showed a significantly lower neutralization effect against infection of the same or different SARS-CoV-2 variants than the serum from Beta variant-infected hamsters. Furthermore, the serum from Omicron BA.1 variant-infected hamsters were insufficient to protect against rechallenge of SARS-CoV-2 Prototype, Beta and Delta variants and itself. Importantly, we found that rechallenge with different SARS-CoV-2 lineages elevated cross-variant serum neutralization titers. Overall, our findings indicate a weakened immunogenicity feature of Omicron BA.1 variant that can be overcome by rechallenge of a different SARS-CoV-2 lineages. Our results may lead to a new guideline in generation and use of the vaccinations to combat the pandemic of SARS-CoV-2 Omicron variant and possible new variants. IMPORTANCE The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant causes breakthrough infections among convalescent patients and vaccinated populations. However, Omicron does not generate robust cross-protective responses. Here, we investigate whether heterologous SARS-CoV-2 challenge is able to enhance antibody response in a sensitive animal model, namely, Syrian hamster. Of note, a heterologous challenge of Beta and Omicron BA.1 variant significantly broadens the breadth of SARS-CoV-2 neutralizing responses against the prototype, Beta, Delta, and Omicron BA.1 variants. Our findings confirm that vaccination strategy with heterologous antigens might be a good option to protect against the evolving SARS-CoV-2.

Utility of monocyte distribution width for diagnosing colonic diverticulitis in the emergency department: a retrospective cohort study (preprint)

Background Colonic diverticulitis is a leading cause of abdominal pain. The monocyte distribution width (MDW) is a novel inflammatory biomarker with prognostic significance for coronavirus disease and pancreatitis; however, no study has assessed its correlation with the severity of colonic diverticulitis. Methods This single-center retrospective cohort study included patients older than 18 years who presented to the emergency department between November 1, 2020, and May 31, 2021, and received a diagnosis of acute colonic diverticulitis after abdominal computed tomography. The characteristics and laboratory parameters of patients with simple versus complicated diverticulitis were compared. The significance of categorical data was assessed using the chi-square or Fisher’s exact test. The Mann–Whitney U test was used for continuous variables. Multivariate regression analysis was performed to identify predictors of complicated colonic diverticulitis. Receiver operator characteristic (ROC) curves were used to test the efficacy of inflammatory biomarkers in distinguishing simple from complicated cases. Results Of the 160 patients enrolled, 21 (13.125%) had complicated diverticulitis. Although right-sided was more prevalent than left-sided colonic diverticulitis (70% versus 30%), complicated diverticulitis was more common in those with left-sided colonic diverticulitis (61.905%, p = 0.001). Age, white blood cell (WBC) count, neutrophil count, C-reactive protein (CRP) level, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and MDW were significantly higher in the complicated diverticulitis group (p < 0.05). Logistic regression analysis indicated that the left-sided location and the MDW were significant and independent predictors of complicated diverticulitis. The area under the ROC curve (AUC) was as follows: MDW, 0.870 (95% confidence interval [CI], 0.784–0.956); CRP, 0.800 (95% CI, 0.707–0.892); NLR, 0.724 (95% CI, 0.616–0.832); PLR, 0.662 (95% CI, 0.525–0.798); and WBC, 0.679 (95% CI, 0.563–0.795). The MDW had the largest AUC for diagnosing complicated diverticulitis; when the MDW cutoff was 20.38, the sensitivity and specificity were maximized to 90.5% and 80.6%, respectively. Conclusions Patients with complicated diverticulitis were significantly older and predominantly had left-sided colonic diverticulitis. A large MDW was a significant and independent predictor of complicated diverticulitis. The MDW may aid in planning antibiotic therapy for patients with colonic diverticulitis in the emergency department.

Nasal irrigation efficiently attenuates SARS-CoV-2 Omicron infection, transmission and lung injury in the Syrian hamster model.

Recently, a new variant lineage of SARS-CoV-2, namely Omicron, became the dominant global circulating strain. The multiple antigenic mutations of Omicron largely decrease the efficiency of current vaccines and neutralizing antibodies, which highlights the need for more potent and reachable medical countermeasures. Here, we hypothesize that direct viral clearance by nasal irrigation might be a convenient and alternative option, and perform proof-of-concept experiments in the Syrian hamster model. Interestingly, Omicron shows a different dynamic in the changes of viral RNA, viral titers, and proinflammatory cytokines in nasal rinsing samples when compared with the prototype. Meanwhile, the levels of viral load and proinflammatory cytokines in nasal rinsing samples can indicate the severity of lung injury. Of note, daily nasal irrigation efficiently attenuates inflammation and lung injury in Omicron-infected hamsters by decreasing the viral loads in the respiratory tract organs. Moreover, daily nasal irrigation effectively suppresses viral transmission by close contact.

Infection, pathology and interferon treatment of the SARS-CoV-2 Omicron BA.1 variant in juvenile, adult and aged Syrian hamsters.

The new predominant circulating SARS-CoV-2 variant, Omicron, can robustly escape current vaccines and neutralizing antibodies. Although Omicron has been reported to have milder replication and disease manifestations than some earlier variants, its pathogenicity in different age groups has not been well elucidated. Here, we report that the SARS-CoV-2 Omicron BA.1 sublineage causes elevated infection and lung pathogenesis in juvenile and aged hamsters, with more body weight loss, respiratory tract viral burden, and lung injury in these hamsters than in adult hamsters. Juvenile hamsters show a reduced interferon response against Omicron BA.1 infection, whereas aged hamsters show excessive proinflammatory cytokine expression, delayed viral clearance, and aggravated lung injury. Early inhaled IFN-α2b treatment suppresses Omicron BA.1 infection and lung pathogenesis in juvenile and adult hamsters. Overall, the data suggest that the diverse patterns of the innate immune response affect the disease outcomes of Omicron BA.1 infection in different age groups.

The neutralizing breadth of antibodies targeting diverse conserved epitopes between SARS-CoV and SARS-CoV-2.

Antibody therapeutics for the treatment of COVID-19 have been highly successful. However, the recent emergence of the Omicron variant has posed a challenge, as it evades detection by most existing SARS-CoV-2 neutralizing antibodies (nAbs). Here, we successfully generated a panel of SARS-CoV-2/SARS-CoV cross-neutralizing antibodies by sequential immunization of the two pseudoviruses. Of the potential candidates, we found that nAbs X01, X10, and X17 offer broad neutralizing potential against most variants of concern, with X17 further identified as a Class 5 nAb with undiminished neutralization against the Omicron variant. Cryo-electron microscopy structures of the three antibodies together in complex with each of the spike proteins of the prototypical SARS-CoV, SARS-CoV-2, and Delta and Omicron variants of SARS-CoV-2 defined three nonoverlapping conserved epitopes on the receptor-binding domain. The triple-antibody mixture exhibited enhanced resistance to viral evasion and effective protection against infection of the Beta variant in hamsters. Our findings will aid the development of antibody therapeutics and broad vaccines against SARS-CoV-2 and its emerging variants.

Acute Polyserositis with Cardiac Tamponade and Bilateral Refractory Pleural Effusion after ChAdOx1 nCoV-19 Vaccination.

The association of SARS-CoV-2 messenger ribonucleic acid vaccines with pericarditis in young adults has been reported. However, data regarding other types of vaccines are extremely limited. We presented a 94-year-old man with rapidly progressive dyspnea and fatigue six days after his first ChAdOx1 nCoV-19 vaccination. Impending cardiac tamponade and bilateral pleural effusion were found. Hence, massive yellowish pericardial and pleural effusion were drained. However, the pleural effusion persisted and pigtail catheters were inserted bilaterally. After serial studies including surgical pleural biopsy, acute polyserositis (pericarditis and pleurisy) was diagnosed. Anti-inflammatory treatment with colchicine and prednisolone was administered. All effusions resolved accordingly. This rare case sheds light on the presentation of ChAdOx1 nCoV-19 vaccine-related acute polyserositis. In conclusion, awareness of this potential adverse event may facilitate the diagnosis for unexplained pericardial or pleural effusion after vaccination.

Investigation and Analysis of the Effect of Knowledge, Attitude, and Behavior of Gastrointestinal Endoscopy Nurses on Occupational Protection Against COVID-19.

The purpose of this study was to investigate the effects of knowledge, attitude, and behavior (KAB) of gastrointestinal endoscopy nurses on occupational protection against COVID-19. We analyzed the influencing factors on KAB to provide a reference for the training of nurses on occupational protection in endoscopic centers. A convenience sample of 400 endoscopy nurses from 26 provinces and cities in China was surveyed using a questionnaire to determine their KAB about occupational protection against COVID-19. Job title was an influencing factor of endoscopy nurses' attitude toward occupational protection against COVID-19. The type of hospital, whether nurses had received training on COVID-19, number of training courses received, and nurses' satisfaction with the workload in their endoscopic center were the influencing factors for occupational protective behavior. Study participants had good knowledge of occupational protection against COVID-19. Their overall attitude was positive, but their protective behavior needs further improvement. Feasible interventions to strengthen the occupational protective behavior of endoscopy nurses during the COVID-19 epidemic are suggested to improve the overall occupational protection level of endoscopy nurses.

Utility of Monocyte Distribution Width for Diagnosing Colonic Diverticulitis in the Emergency Department (preprint)

BackgroundColonic diverticulitis is a leading cause of abdominal pain. The monocyte distribution width (MDW) is a novel inflammatory biomarker with prognostic significance for coronavirus disease and pancreatitis; however, no study has assessed its correlation with the severity of colonic diverticulitis.MethodsThis single-center retrospective cohort study included patients older than 18 years who presented to the emergency department between November 1, 2020, and May 31, 2021, and received a diagnosis of acute colonic diverticulitis after abdominal computed tomography. The characteristics and laboratory parameters of patients with simple versus complicated diverticulitis were compared. The significance of categorical data was assessed using the chi-square or Fisher’s exact test. The Mann–Whitney U test was used for continuous variables. Multivariate regression analysis was performed to identify predictors of complicated colonic diverticulitis. Receiver operator characteristic (ROC) curves were used to test the efficacy of inflammatory biomarkers in distinguishing simple from complicated cases.ResultsOf the 160 patients enrolled, 21 (13.125%) had complicated diverticulitis. Although right-sided was more prevalent than left-sided colonic diverticulitis (70% versus 30%), complicated diverticulitis was more common in those with left-sided colonic diverticulitis (61.905%, p = 0.001). Age, white blood cell (WBC) count, neutrophil count, C-reactive protein (CRP) level, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and MDW were significantly higher in the complicated diverticulitis group (p < 0.05). Logistic regression analysis indicated that left-sided location and the MDW were significant and independent predictors of complicated diverticulitis. The area under the ROC curve (AUC) was as follows: MDW, 0.870 (95% confidence interval [CI], 0.784–0.956); CRP, 0.800 (95% CI, 0.707–0.892); NLR, 0.724 (95% CI, 0.616–0.832); PLR, 0.662 (95% CI, 0.525–0.798); and WBC, 0.679 (95% CI, 0.563–0.795). The MDW had the largest AUC for diagnosing complicated diverticulitis; when the MDW cutoff was 20.38, the sensitivity and specificity were maximized to 90.5% and 80.6%, respectively.ConclusionsPatients with complicated diverticulitis were significantly older and predominantly had left-sided colonic diverticulitis. A large MDW was a significant and independent predictor of complicated diverticulitis. The MDW may aid in planning antibiotic therapy for patients with colonic diverticulitis in the emergency department.

Three SARS-CoV-2 antibodies provide broad and synergistic neutralization against variants of concern, including Omicron.

The rapidly spreading Omicron variant is highly resistant to vaccines, convalescent sera, and neutralizing antibodies (nAbs), highlighting the urgent need for potent therapeutic nAbs. Here, a panel of human nAbs from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) convalescent patients show diverse neutralization against Omicron, of which XMA01 and XMA04 maintain nanomolar affinities and excellent neutralization (half maximal inhibitory concentration [IC50]: ∼20 ng/mL). nAb XMA09 shows weak but unattenuated neutralization against all variants of concern (VOCs) as well as SARS-CoV. Structural analysis reveals that the above three antibodies could synergistically bind to the receptor-binding domains (RBDs) of both wild-type and Omicron spikes and defines the critical determinants for nAb-mediated broad neutralizations. Three nAbs confer synergistic neutralization against Omicron, resulting from the inter-antibody interaction between XMA04 and XMA01(or XMA09). Furthermore, the XMA01/XMA04 cocktail provides synergistic protection against Beta and Omicron variant infections in hamsters. In summary, our results provide insights for the rational design of antibody cocktail therapeutics or universal vaccines against Omicron.

Cross-species tropism and antigenic landscapes of circulating SARS-CoV-2 variants.

Mutations in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike receptor-binding domain (RBD) may alter viral host tropism and affect the activities of neutralizing antibodies. Here, we investigated 153 RBD mutants and 11 globally circulating variants of concern (VOCs) and variants of interest (VOIs) (including Omicron) for their antigenic changes and cross-species tropism in cells expressing 18 ACE2 orthologs. Several RBD mutations strengthened viral infectivity in cells expressing ACE2 orthologs of non-human animals, particularly those less susceptible to the ancestral strain. The mutations surrounding amino acids (aas) 439-448 and aa 484 are more likely to cause neutralization resistance. Strikingly, enhanced cross-species infection potential in the mouse and ferret, instead of the neutralization-escape scores of the mutations, account for the positive correlation with the cumulative prevalence of mutations in humans. These findings present insights for potential drivers of circulating SARS-CoV-2 variants and provide informative parameters for tracking and forecasting spreading mutations.

Surveillance of Rodent Pests for SARS-CoV-2 and Other Coronaviruses, Hong Kong.

We report surveillance conducted in 217 pestiferous rodents in Hong Kong for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We did not detect SARS-CoV-2 RNA but identified 1 seropositive rodent, suggesting exposure to a virus antigenically similar to SARS-CoV-2. Potential exposure of urban rodents to SARS-CoV-2 cannot be ruled out.