Characterization of RBD-specific cross-neutralizing antibodies responses against SARS-CoV-2 variants from COVID-19 convalescents.

Introduction: The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has been posing a severe threat to global public health. Although broadly neutralizing antibodies have been used to prevent or treat corona virus disease 2019 (COVID-19), new emerging variants have been proven resistant to these antibodies. Methods: In this study, we isolated receptor binding domain (RBD)-specific memory B cells using single-cell sorting method from two COVID-19 convalescents and expressed the antibody to test their neutralizing activity against diverse SARS-CoV-2 variants. Then, we resolved antibody-RBD complex structures of potent RBD-specific neutralizing antibodies by X-ray diffraction method. Finally, we analyzed the whole antibody repertoires of the two donors and studied the evolutionary pathway of potent neutralizing antibodies. Results and discussion: We identified three potent RBD-specific neutralizing antibodies (1D7, 3G10 and 3C11) from two COVID-19 convalescents that neutralized authentic SARS-CoV-2 WH-1 and Delta variant, and one of them, 1D7, presented broadly neutralizing activity against WH-1, Beta, Gamma, Delta and Omicron authentic viruses. The resolved antibody-RBD complex structures of two antibodies, 3G10 and 3C11, indicate that both of them interact with the external subdomain of the RBD and that they belong to the RBD-1 and RBD-4 communities, respectively. From the antibody repertoire analysis, we found that the CDR3 frequencies of the light chain, which shared high degrees of amino acid identity with these three antibodies, were higher than those of the heavy chain. This research will contribute to the development of RBD-specific antibody-based drugs and immunogens against multiple variants.

Trajectories of Sexual Risk Behaviors and the Associated Factors Among Young Men Who Have Sex With Men in China.

Background: Young men who have sex with men (YMSM) are at high risk of HIV infection that accounts for an increasing proportion of new human immunodeficiency virus (HIV) infections in China. However, little is known about the trajectories of sexual risk behaviors in this population. The study aimed to investigate longitudinal patterns of sexual risk behaviors among YMSM in China. Methods: Study data were collected from a prospective cohort study among 460 YMSM from 2017 to 2020. Based on the predicted HIV infection risk scores, distinct sexual risk behaviors trajectories of YMSM were estimated and plotted using the group-based censored normal model to identify the predictors of trajectories change over time. Results: Three sexual risk behaviors trajectories were identified: a decreasing low-risk group (7.6%), an intermediate-risk group (67.4%), and an ascending high-risk group (25.0%).Compared to the decreasing low-risk group, intermediate-risk group membership was associated with being from rural areas, current smoker and higher depressive symptoms; ascending high-risk group membership was associated with an education level of high school or lower, being from rural areas, younger age at sex debut with a man, current smoker, higher depressive symptoms and sexual minority stress. Conclusions: Sexual risk behaviors among YMSM changed over time within different trajectories. Identifying YMSM belonging to high-risk trajectories before HIV infection is vital for the intervention and may reduce HIV transmission.

Exploring Rapid and Effective Screening Methods for Anti-SARS-CoV-2 Neutralizing Antibodies in COVID-19 Convalescent Patients and Longitudinal Vaccinated Populations.

Assessing the duration of neutralizing antibodies (nAbs) following SARS-CoV-2 infection or vaccination is critical to evaluate the protective immunity and formulate public health strategies. In this study, SARS-CoV-2 Ab ELISA (enzyme-linked immunosorbent assay), chemiluminescent microparticle immunoassay (CMIA), as well as pseudovirus neutralization test (PVNT) were performed in two cohorts, convalescent patients (CP) from coronavirus disease 2019 (COVID-19) and BBIBP-CorV vaccinated population. It was found that nAbs and binding antibodies emerged at 14 days post the 1st dose of vaccination, reached peaks at 28 days after 2nd dose vaccination and then gradually declined over time. CP-6M (convalescent patients up to 6 months) from COVID-19 presented stronger nAbs or binding antibodies responses than vaccinees 90 days or 180 days after 2nd dose vaccination. CMIA or SARS-CoV-2 Ab ELISA correlated well with PVNT with high consistency in the two cohorts. It shown that nAbs and binding antibodies can keep 6 months both in CP and vaccinees. Most importantly, our data show the application of using CMIA and SARS-CoV-2 Ab ELISA as rapid screening tests for nAb titer and could be used as alternative strategies for quickly evaluating SARS-CoV-2 nAbs responses in vaccine research.

Case Report: Next-Generation Sequencing in Diagnosis of Pneumonia Due to Pneumocystis jirovecii and Cytomegalovirus in a Patient With HIV Infection.

Background: Pulmonary infections remain a significant cause of morbidity and mortality in immunocompromised patients. The pathogens spectrum of pulmonary infection that can affect patients with human immunodeficiency virus (HIV) is wide such as bacterial, fungal, viral, parasitic organisms, and so on. The risk of multi-pathogenic pneumonia is higher in HIV-infected patients. However, the fast and accurate diagnosis of multi-pathogenic pneumonia is challenging because of the limitations of current conventional tests. Case Presentation: Here, we report a case of pneumonia due to Pneumocystis jirovecii and cytomegalovirus (CMV) in a 22-year-old male with newly diagnosed HIV infection. Blood tests revealed a low CD4 count, a chest computed tomography (CT) scan showed extensive ground-glass opacities in the bilateral lung with multiple cavity lesions in the left upper lung. Microscopic examination of stained sputum and bronchoalveolar lavage fluid (BALF) smear specimens did not find any pathogens. There was also no evidence of pathogens known to cause pneumonia in bacteria and fungi culture tests and virus antibodies such as EBV, CMV, and COVID-19. The nucleic acid of CMV in blood was reported by quantitative PCR. Next-generation sequencing (NGS) analysis of BALF specimens identified a large number of P. jirovecii and CMV reads, and confirmed the diagnosis of pneumonia due to P. jirovecii and CMV. Following the patient's treatment with anti-PCP and anti-CMV, the patient was cured and discharged. Conclusions: This case highlights the combined application of NGS in the clinical diagnosis of multi-pathogenic pneumonia in an HIV-infected patient. NGS is proposed as an important adjunctive diagnostic approach for identifying pathogens of multi-pathogenic pneumonia in HIV-infected patients.

Sharing CD4+ T Cell Loss: When COVID-19 and HIV Collide on Immune System.

COVID-19 is a distinctive infection characterized by elevated inter-human transmission and presenting from absence of symptoms to severe cytokine storm that can lead to dismal prognosis. Like for HIV, lymphopenia and drastic reduction of CD4+ T cell counts in COVID-19 patients have been linked with poor clinical outcome. As CD4+ T cells play a critical role in orchestrating responses against viral infections, important lessons can be drawn by comparing T cell response in COVID-19 and in HIV infection and by studying HIV-infected patients who became infected by SARS-CoV-2. We critically reviewed host characteristics and hyper-inflammatory response in these two viral infections to have a better insight on the large difference in clinical outcome in persons being infected by SARS-CoV-2. The better understanding of mechanism of T cell dysfunction will contribute to the development of targeted therapy against severe COVID-19 and will help to rationally design vaccine involving T cell response for the long-term control of viral infection.

Safety of protease inhibitors and Arbidol for SARS-CoV-2 pneumonia in Zhejiang Province, China.

The aim of this study was to evaluate the safety of an antiviral regimen of protease inhibitors combined with Arbidol (umifenovir) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia patients. The genomic sequence of SARS-CoV-2 is highly homologous to that of SARS-CoV (Zhou et al., 2020). Previously published basic and clinical research on anti-SARS-CoV treatment found that lopinavir/ritonavir (LPV/r) could improve the prognosis of SARS patients (Chan et al., 2003; Chu et al., 2004). Darunavir (DRV) is another protease inhibitor that blocks the binding of SARS-CoV-2 to human angiotensin-converting enzyme 2 (Omotuyi et al., 2020). The broad-spectrum antiviral drug Arbidol (umifenovir) also shows in vitro anti-SARS-CoV activity (Khamitov et al., 2008).

Epidemiological, clinical and virological characteristics of 74 cases of coronavirus-infected disease 2019 (COVID-19) with gastrointestinal symptoms.

OBJECTIVE: The SARS-CoV-2-infected disease (COVID-19) outbreak is a major threat to human beings. Previous studies mainly focused on Wuhan and typical symptoms. We analysed 74 confirmed COVID-19 cases with GI symptoms in the Zhejiang province to determine epidemiological, clinical and virological characteristics. DESIGN: COVID-19 hospital patients were admitted in the Zhejiang province from 17 January 2020 to 8 February 2020. Epidemiological, demographic, clinical, laboratory, management and outcome data of patients with GI symptoms were analysed using multivariate analysis for risk of severe/critical type. Bioinformatics were used to analyse features of SARS-CoV-2 from Zhejiang province. RESULTS: Among enrolled 651 patients, 74 (11.4%) presented with at least one GI symptom (nausea, vomiting or diarrhoea), average age of 46.14 years, 4-day incubation period and 10.8% had pre-existing liver disease. Of patients with COVID-19 with GI symptoms, 17 (22.97%) and 23 (31.08%) had severe/critical types and family clustering, respectively, significantly higher than those without GI symptoms, 47 (8.14%) and 118 (20.45%). Of patients with COVID-19 with GI symptoms, 29 (39.19%), 23 (31.08%), 8 (10.81%) and 16 (21.62%) had significantly higher rates of fever >38.5°C, fatigue, shortness of breath and headache, respectively. Low-dose glucocorticoids and antibiotics were administered to 14.86% and 41.89% of patients, respectively. Sputum production and increased lactate dehydrogenase/glucose levels were risk factors for severe/critical type. Bioinformatics showed sequence mutation of SARS-CoV-2 with m6A methylation and changed binding capacity with ACE2. CONCLUSION: We report COVID-19 cases with GI symptoms with novel features outside Wuhan. Attention to patients with COVID-19 with non-classic symptoms should increase to protect health providers.