Multivalent S2-subunit Vaccines Provide Broad Protection Against Clade 1 Sarbecoviruses (preprint)

The continuing emergence of immune evasive SARS-CoV-2 variants and the previous SARS-CoV-1 outbreak have accentuated the need for broadly protective sarbecovirus vaccines. Targeting the conserved S2-subunit of SARS-CoV-2 is a particularly promising approach to elicit broad protection. Here, expanding on our previous work with S2-based vaccines, we developed a nanoparticle vaccine displaying multiple copies of the SARS-CoV-1 S2 subunit. This vaccine alone, or as a cocktail with a SARS-CoV-2 S2 subunit vaccine, protected transgenic K18-hACE2 mice from challenges with Omicron subvariant XBB as well as several sarbecoviruses identified as having pandemic potential including the bat sarbecovirus WIV1, BANAL-236, and a pangolin sarbecovirus. Challenge studies in Fc-g receptor knockout mice revealed that antibody-based cellular effector mechanisms played a role in protection elicited by these vaccines. These results demonstrate that our S2-based vaccines provide broad protection against clade 1 sarbecoviruses and offer insight into the mechanistic basis for protection.

Mutability and hypermutation antagonize immunoglobulin codon optimality (preprint)

The efficacy of polyclonal antibody responses is inherently linked to paratope diversity, as generated through V(D)J recombination and somatic hypermutation (SHM). These processes arose in early jawed vertebrates; however, little is known about how immunoglobulin diversity, mutability, and hypermutation have evolved in tandem with another more ubiquitous feature of protein-coding DNA - codon optimality. Here, we explore these relationships through analysis of germline IG genes, natural V(D)J repertoires, serum VH usage, and monoclonal antibody (mAb) expression, each through the lens of multiple optimality metrics. Strikingly, proteomic serum IgG sequencing showed that germline IGHV codon optimality positively correlated with VH representation after influenza vaccination, and in vitro, codon deoptimization of mAbs with synonymous amino acid sequences caused consistent expression loss. Germline V genes exhibit a range of codon optimality that is maintained by functionality, and inversely related to mutability. SHM caused a load-dependent deoptimization of IGH VDJ repertoires within human tonsils, bone marrow, and lymph nodes (including SARS-CoV-2-specific clones from mRNA vaccinees), influenza-infected mice, and zebrafish. Comparison of natural mutation profiles to true random suggests the presence of selective pressures that constrain deoptimization. These findings shed light on immunoglobulin evolution, providing unanticipated insights into the antagonistic relationship between variable region diversification, codon optimality, and antibody secretion; ultimately, the need for diversity takes precedence over that for the most efficient expression of the antibody repertoire.

Effect of Multimedia E-Book Use on the Information Literacy of Nursing Students and Health Communication in Student-Led Large- and Small-Group Community Health Education Sessions

The integration of digital technology into healthcare is critical for health communication. This study analyzed a group of nursing students who applied multimedia health education e-books to different groups of varying sizes to explore the efficiency of implementing health communication and nursing information literacy in the nursing industry. If medical personnel can make appropriate use of technology, combine medical operations with information systems, and disseminate the purpose of health to groups of different sizes properly, the quality of patient care will improve. Thirty-two junior nursing students at the college level were divided into three groups, each subject to a 3-week internship. After the internship, a questionnaire survey was conducted. Additionally, nine nursing students were interviewed in a 45-min semistructured format. Regarding the effectiveness of nursing students using multimedia e-books to implement health communication and the development of nursing information literacy, the statistical analysis results demonstrated no significant differences between large groups and small groups. However, their 5-point Likert scale average values were all greater than 4, indicating that regardless of group size, their feedback on using e-books was positive. This means multimedia e-books can effectively help nursing students practice health communication application effectiveness and develop nursing information literacy.

Establishing an integrated prevention and control system to ensure zero nosocomial infections – an analysis of the logistics support in controlling nosocomial infections during the hospital's fight against the COVID-19 epidemic Aufbau eines integrierten Präventions- und Kontrollsystems zur Gewährleistung der Null-Strategie zur Prävention nosokomialer Infektionen – eine Analyse der logistischen Unterstützung zur Prävention nosokomialer Infektionen während des Kampfes des Krankenhauses gegen die COVID-19-Epidemie

Aim: To analyze the role of the logistics support services in nosocomial infection control during emergency periods, with a focus on job responsibilities including the organization of vehicle parking, supply of hospital meals, washing of medical bedding and clothing, disposal and management of medical sewage and waste, elevator services, disinfection of air conditioning systems, disinfection and cleaning of ambulances, management of hospital buildings, storage of sterilization supplies, reception and delivery of oxygen cylinders and protection of staff health as examples. Methods: The adjustment and optimization of the emergency support system and working mode as part of hospitals' response to major public emergencies were summarized, and the vital supporting role of the logistics support services in nosocomial infection control was analyzed. Results: The logistics support services played a crucial role in ensuring the high-performance operations of the hospitals and control of nosocomial infections, resulting in the excellent outcome of "zero infection” among hospital staff. Conclusion: Establishing a safe, flexible and efficient system for the logistics support services is important in ensuring an effective response by hospitals to health emergencies.

Chest computed tomography and pulmonary function analysis of coronavirus disease 2019 survivors in 1 month follow-up period after cure and discharge

OBJECTIVE: The objective is to explore the chest computed tomography (CT) and pulmonary function findings of coronavirus disease 2019 (COVID-19) survivors 1 month after discharge. METHODS: We retrospectively analyzed the chest CT and pulmonary function findings of 158 (COVID-19) survivors who were discharged and followed up at Wuhan Red Cross Hospital from April 9 to May 10, 2020. RESULTS: Follow-up chest CT revealed that pulmonary lesions in all patients were clearly absorbed and dissipated. One month after discharge, 125 (79.1%) patients had residual imaging abnormalities, mainly light ground-glass opacities (44.9%) and light patchy shadows (38.6%). Other features included fibrous cord lesions in 90 cases (57.0%), pulmonary nodules in 46 cases (29.1%), pleural thickening in 44 cases (27.8%), and mediastinal lymphadenopathy in 81 cases (51.3%). Among 158 COVID-19 survivors, 124 were tested for pulmonary function. Pulmonary function tests revealed pulmonary function impairment in 10 patients (8.1%), restrictive ventilation dysfunction in 16 (12.9%), and pulmonary diffusion dysfunction in 48 (38.7%). Residual lung lesions and pleural thickening were negatively correlated with DLCO% (P < 0.05). CONCLUSION: COVID-19 patients have characteristic findings on chest CT and pulmonary function testing. Identifying these findings is helpful to dynamically monitor the disease prognosis.

Source tracing of the COVID-19 infection case in Guangxi, China

The study describing the process of discovery and source tracing of a native case of coronavirus disease 2019 (COVID-19) infection on Jan 2021, in Guangxi, China, to provide methodology for source investigation better in the future. Following the Epidemiological Investigation Plan for COVID-19 (version 7), information of the native COVID-19 case and related close contacts were collected. Real time reverse transcription-quantitative polymerase chain reaction was performed to detect the nucleic acids of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in samples collected from the infection case, related close contacts, and the environment, combined with serum specific antibody detection. The positive nucleic acid samples were undergone whole genome sequencing, phylogenetic analysis and analyses of variation of amino acids. The whole genome sequence from the native case and the imported asymptomatic infected case from Indonesia containing 25 nucleotide mutation sites belong to L-Lineage European Branch II. 3. The imported asymptomatic case was the source of infection of this native case. The possible route of infection was that native case was exposed to contaminated environment by imported case, due to improper personal protective equipment. A focus on local outbreaks of COVID-19 caused by SARS-CoV-2-infected people from outside China is needed.

Establishing an integrated prevention and control system to ensure zero nosocomial infections - an analysis of the logistics support in controlling nosocomial infections during the hospital's fight against the COVID-19 epidemic.

Aim: To analyze the role of the logistics support services in nosocomial infection control during emergency periods, with a focus on job responsibilities including the organization of vehicle parking, supply of hospital meals, washing of medical bedding and clothing, disposal and management of medical sewage and waste, elevator services, disinfection of air conditioning systems, disinfection and cleaning of ambulances, management of hospital buildings, storage of sterilization supplies, reception and delivery of oxygen cylinders and protection of staff health as examples. Methods: The adjustment and optimization of the emergency support system and working mode as part of hospitals' response to major public emergencies were summarized, and the vital supporting role of the logistics support services in nosocomial infection control was analyzed. Results: The logistics support services played a crucial role in ensuring the high-performance operations of the hospitals and control of nosocomial infections, resulting in the excellent outcome of "zero infection" among hospital staff. Conclusion: Establishing a safe, flexible and efficient system for the logistics support services is important in ensuring an effective response by hospitals to health emergencies.

Site of vulnerability on SARS-CoV-2 spike induces broadly protective antibody to antigenically distinct omicron SARS-CoV-2 subvariants (preprint)

The rapid evolution of SARS-CoV-2 Omicron variants has emphasized the need to identify antibodies with broad neutralizing capabilities to inform future monoclonal therapies and vaccination strategies. Herein, we identify S728-1157, a broadly neutralizing antibody (bnAb) targeting the receptor-binding site (RBS) and derived from an individual previously infected with SARS-CoV-2 prior to the spread of variants of concern (VOCs). S728-1157 demonstrates broad cross-neutralization of all dominant variants including D614G, Beta, Delta, Kappa, Mu, and Omicron (BA.1/BA.2/BA.2.75/BA.4/BA.5/BL.1). Furthermore, it protected hamsters against in vivo challenges with wildtype, Delta, and BA.1 viruses. Structural analysis reveals that this antibody targets a class 1 epitope via multiple hydrophobic and polar interactions with its CDR-H3, in addition to common class 1 motifs in CDR-H1/CDR-H2. Importantly, this epitope is more readily accessible in the open and prefusion state, or in the hexaproline (6P)-stabilized spike constructs, as compared to diproline (2P) constructs. Overall, S728-1157 demonstrates broad therapeutic potential, and may inform target-driven vaccine design against future SARS-CoV-2 variants.

Prediction of Survival Time after Terminal Extubation: the Balance between Critical Care Unit Utilization and Hospice Medicine in the COVID-19 Pandemic Era (preprint)

Background We established 1-hour and 1-day survival models after terminal extubation to optimize ventilator use and achieve a balance between critical care for COVID-19 and hospice medicine.Methods Data were obtained from patients with end-of-life status at terminal extubation from 2015 to 2020. The associations between APACHE II scores and parameters with survival time were analyzed. Parameters with a p-value ≤ 0.2 in univariate analysis were included in multivariate models. Cox proportional hazards regression analysis was used for the multivariate analysis of survival time at 1 hour and 1 day.Results Of the 140 enrolled patients, 76 (54.3%) died within 1 hour and 35 (25%) survived beyond 24 hours. No spontaneous breathing trial (SBT) within the past 24 hours, minute ventilation (MV) ≥ 12 L/min, and APACHE II score ≥ 25 were associated with shorter survival in the 1-hour regression model. Lower MV, SpO2 ≥ 96% and SBT were related to longer survival in the 1-day model. Hospice medications did not influence survival time.Conclusion An APACHE II score of ≥ 25 at 1 hour and SpO2 ≥ 96% at 1 day were strong predictors of disposition of patients to intensivists. These factors can help to objectively tailor pathways for post-extubation transition and rapidly allocate intensive care unit resources without sacrificing the quality of palliative care in the era of COVID-19.Trial registration They study was retrospectively registered. IRB No.: 202101929B0

Safety and immunogenicity of SARS-CoV-2 vaccine MVC-COV1901 in Taiwanese adolescents: A double-blind, randomized, placebo-controlled phase 2 trial (preprint)

Adolescents and children play important role in SARS-CoV-2 transmission and epidemiology. MVC-COV1901 is a subunit SARS-CoV-2 vaccine based on stabilized spike protein adjuvanted with CpG 1018 and aluminum hydroxide that has been approved for use in adults in Taiwan. In this study, we have investigated the safety and immunogenicity of two doses of MVC-COV1901 in adolescents. Healthy adolescents from age of 12 to 17 years were randomly assigned to receive two intramuscular doses of either MVC-COV1901 or placebo at 28 days apart. Adverse events were mostly mild and were similar in MVC-COV1901 and placebo groups with the most commonly reported adverse events being pain/tenderness and malaise/fatigue. All immunogenicity endpoints in the adolescent group were non-inferior to the endpoints seen in the young adult and placebo groups. The results here advocate the use of MVC-COV1901 in adolescents in the ongoing efforts to control the pandemic. ClinicalTrials.gov registration NCT04951388.

Randomized controlled study of a diagnosis and treatment plan for moderate coronavirus disease 2019 that integrates Traditional Chinese and Western Medicine.

OBJECTIVE: To investigate the clinical efficacy and safety of a diagnosis and treatment plan for moderate coronavirus disease 2019 (COVID-19) that integrates traditional Chinese (TCM) and western medicine. METHODS: One hundred twenty patients with moderate COVID-19 were randomized 1∶2 to the control group ( = 40) and experimental group ( = 80). Both groups received conventional western medicine treatment, and the experimental group also received TCM decoction. Over a 2-week period from diagnosis, we observed the time to clinical recovery (TTCR), rate of improvement on lung computed tomography (CT) imaging, time to defervescence, cough remission time, hospital discharge rate, average hospitalization stay, modified Medical Research Council (mMRC) scale score, clinical cure rate, laboratory findings, incidence of progression to severe or critical disease, and adverse events. RESULTS: Among 120 enrolled patients, 108 completed the study. The baseline data did not differ between the experimental and control groups (all > 0.05). After treatment, the TTCR, rate of lung CT imaging improvement, time to defervescence, cough remission time, hospital discharge rate, average hospitalization stay (among discharged patients), mMRC scale score, clinical cure rate, and rates of normal values for laboratory findings were better in the experimental group than in the control group ( < 0.05 or < 0.01). The incidence of progression to severe or critical disease and the incidence of adverse events did not differ between the two groups ( > 0.05). CONCLUSION: The diagnosis and treatment plan integrating Chinese and western medicine showed improved clinical efficacy compared with western medicine alone for patients with moderate COVID-19 and is worthy of clinical promotion and application.

Safety and immunogenicity of SARS-CoV-2 vaccine MVC-COV1901 in adolescents in Taiwan: A double-blind, randomized, placebo-controlled phase 2 trial (preprint)

Background: MVC-COV1901 is a subunit SARS-CoV-2 vaccine based on the prefusion spike protein S-2P and adjuvanted with CpG 1018 and aluminum hydroxide. Although MVC-COV1901 has been licensed for emergency use for adults in Taiwan, the safety and immunogenicity of MVC-COV1901 in adolescents remained unknown. As young people play an important role in SARS-CoV-2 transmission and epidemiology, a vaccine approved for adolescents and eventually, children, will be important in mitigating the COVID-19 pandemic. Methods: This study is a prospective, double-blind, multi-center phase 2 trial evaluating the safety, tolerability and immunogenicity of two doses of the SARS-CoV-2 vaccine MVC-COV1901 in adolescents. Healthy adolescents from age of 12 to 17 years were recruited and randomly assigned (6:1) to receive two intramuscular doses of either MVC-COV1901 or placebo at 28 days apart. The primary outcomes were safety and immunogenicity from the day of first vaccination (Day 1) to 28 days after the second vaccination (Day 57), and immunogenicity of MVC COV1901 in adolescents as compared to young adult vaccinees in terms of neutralizing antibody titers and seroconversion rate. The secondary outcomes were safety and immunogenicity of MVC-COV1901 as compared to placebo in adolescents in terms of immunoglobulin titers and neutralizing antibody titers over the study period. Results: Between July 21, 2021 and December 22, 2021, a total of 399 adolescent participants were included for safety evaluation after enrollment to receive at least one dose of either MVC-COV1901 (N=341) or placebo (N=58). Of these, 334 and 46 participants went on to receive two doses of either MVC-COV1901 or placebo, respectively, and were included in the per protocol set (PPS) for immunogenicity analysis. Adverse events were mostly mild and were similar in MVC-COV1901 and placebo groups. The most commonly reported adverse events were pain/tenderness and malaise/fatigue. All immunogenicity endpoints in the adolescent group were non-inferior to the endpoints seen in the young adult and placebo groups. Conclusions: The safety and immunogenicity data presented here showed that MVC-COV1901 has similar safety profile and non-inferior immunogenicity in adolescents compared to young adults.

Twin girls infected with SARS-CoV-2

This article reports the diagnosis and treatment of twin girls who were diagnosed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Hunan Province, China. The twin girls, aged 1 year and 2 months, were admitted on January 29, 2020 due to fever for one day and cough and sneezing for two days respectively. Both recovered after symptomatic treatment. The two girls had mild symptoms and rapid recovery, suggesting that children with SARS-CoV-2 infection may be mild and have a good prognosis. There were differences in the clinical symptoms and imaging findings between the twin girls, suggesting that SARS-CoV-2 infection has diverse clinical features in children.

Using cold atmospheric plasma treated-air for COVID-19 disinfection in cold-chain environment

This study applied surface discharge plasma treated-air to deactivate the pseudovirus with the SARS-CoV-2S protein in a cold-chain environment. The results of experiments show that the capability of infection of either the dried or the wet COVID-19 pseudovirus are inhibited after exposure to plasma treated-air regardless of whether it is attached to flakes of plastic or a copper sheet. Moreover, various plasma-generated reactive species provide it with an advantage over conventional ozone in deactivating the wet pseudovirus in a cold-chain environment. Our findings provide a potential disinfecting strategy to combat the spread of SARS-CoV-2 through cold-chain systems. [ABSTRACT FROM AUTHOR] Copyright of Journal of Physics: D Applied Physics is the property of IOP Publishing and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Cross neutralization of emerging SARS-CoV-2 variants of concern by antibodies targeting distinct epitopes on spike (preprint)

Several severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have arisen that exhibit increased viral transmissibility and partial evasion of immunity induced by natural infection and vaccination. To address the specific antibody targets that were affected by recent viral variants, we generated 43 monoclonal antibodies (mAbs) from 10 convalescent donors that bound three distinct domains of the SARS-CoV-2 spike. Viral variants harboring mutations at K417, E484 and N501 could escape most of the highly potent antibodies against the receptor binding domain (RBD). Despite this, we identified 12 neutralizing mAbs against three distinct regions of the spike protein that neutralize SARS-CoV-2 and the variants of concern, including B.1.1.7 (alpha), P.1 (gamma) and B.1.617.2 (delta). Notably, antibodies targeting distinct epitopes could neutralize discrete variants, suggesting different variants may have evolved to disrupt the binding of particular neutralizing antibody classes. These results underscore that humans exposed to wildtype (WT) SARS-CoV-2 do possess neutralizing antibodies against current variants and that it is critical to induce antibodies targeting multiple distinct epitopes of the spike that can neutralize emerging variants of concern.

Epidemiological characteristics of 147 patients infected with SARS-CoV-2 in Chengdu

Objective: Analysis of the epidemiological characteristics and trend of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection were conducted in Chengdu.

COVID-19 Infection Induces Substantial Memory B Cell Maturation to Non-Neutralizing Viral Targets (preprint)

Dissecting the evolution of memory B cells (MBCs) against SARS-CoV-2 is critical for understanding antibody recall upon secondary exposure. Here, we utilized single-cell sequencing to profile SARS-CoV-2-reactive B cell subsets in 42 COVID-19 patients. We isolated thousands of B cells in multiple distinct subsets specific to the SARS-CoV-2 spike, endemic coronavirus (HCoV) spikes, nucleoprotein (NP), and open reading frame 8 (ORF8). Spike-specific cells were enriched in the memory compartment of acutely infected and convalescent patients 1.5–5 months post-infection. With severe acute infection, we identified substantial populations of endemic HCoV-reactive antibody-secreting cells with highly mutated variable genes, indicative of preexisting immunity. Finally, MBCs exhibited maturation to NP and ORF8 over time relative to spike, especially in older patients. Monoclonal antibodies against these targets were non-neutralizing and non-protective in vivo. These findings reveal considerable antibody adaptation to non-neutralizing antigens during infection, emphasizing the importance of vaccination for inducing neutralizing spike-specific MBCs.Trial Registration Number: This clinical trial was registered at ClinicalTrials.gov with identifier NCT04340050, and clinical information for patients included in the study is detailed in Table S1–S3.Funding: This project was funded in part by the National Institute of Allergy and Infectious Disease (NIAID); National Institutes of Health (NIH) grant numbers U19AI082724 (P.C.W.), U19AI109946 (P.C.W.), U19AI057266 (P.C.W.), the NIAID Centers of Excellence for Influenza Research and Surveillance (CEIRS) grant numbers HHSN272201400005C(P.C.W.). N.W.A. was supported by the Multi-disciplinary Training program in Cancer Research (MTCR) - NIH T32 CA009594. A.J. and R.P.J were supported by federal funds from the NIAID, NIH, and Department of Health and Human Services under Contract HHSN272201700060C. F.K and F.A. were funded by the NIAID CEIRS contractHHSN272201400008C, Collaborative Influenza Vaccine Innovation Centers (CIVIC) contract 75N93019C00051 and the generous support of the JPB foundation, the Open Philanthropy Project (#2020-215611) and other philanthropic donations. Y.K. and P.H.were funded by the Research Program on Emerging and Re-emerging Infectious Disease grant (JP19fk0108113) and the Japan Program for Infectious Diseases Research and Infrastructure (JP20fk0108272) from the Japan Agency for Medical Research and Development (AMED), NIAID CEIRS contract HHSN272201400008C, and CIVIC contract 75N93019C00051. D.F., C.N, Y.D., and P.D.H, were supported by NIAID contracts HHSN272201700060C and 75N93019C00062. M.S.D. and E.S.W. were supported by NIH grants R01 AI157155 and F30 AI152327, respectively.Conflict of Interest: Several antibodies generated from this work are being used by Now Diagnostics in Springdale, AR for the development of a diagnostic test. M.S.D. is a consultant for Inbios, Vir Biotechnology, NGM Biopharmaceuticals, and Carnival Corporation, and on the Scientific Advisory Boards of Moderna and Immunome. The Diamond laboratory has received funding support in sponsored research agreements from Moderna, Vir Biotechnology, and Emergent BioSolutions.Ethical Approval: All studies were performed with the approval of the University of Chicago institutional review board IRB20-0523 and University of Chicago, University of Wisconsin-Madison, and Washington University in St. Louis institutional biosafety committees. Informed consent was obtained after the research applications and possible consequences of the studies were disclosed to study subjects.

Transcriptomic Characteristics and Impaired Immune Function of Patients Who Retest Positive for SARS-CoV-2 RNA (preprint)

Background: The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has gradually become a global public health crisis. Some patients who have recovered from COVID-19 subsequently tested positive again for SARS-CoV-2 after discharge (retesting-positive, RTP). However, the underlying mechanism is unknown.Methods: Here, 30 RTP patients, 20 convalescent patients, and 20 healthy controls were enrolled for analysis of the immunological characteristics of their peripheral blood mononuclear cells (PBMCs). Furthermore, we sought to comprehensively characterize the transcriptional changes in the three groups by transcriptome sequencing.Findings: It was found that the absolute numbers of CD4+ T cells, CD8+ T cells, and NK cells were not decreased remarkably, while the expression of activation markers on these cells was significantly decreased in RTP patients. Furthermore, the percentage of granzyme B-producing T cells was also decreased in RTP patients compared with that in convalescent patients. Moreover, the high expression of inhibitor of differentiation-1 (ID1) and the low expression of IFITM10 may be associated with the insufficient activation of immune cells and RTP occurrence.Interpretation: Our findings provide insights into the impaired immune function and pathogenesis of RTP occurrence in COVID-19, which may contribute to the development of immunotherapy for RTP patients.Funding Statement: This work was supported by China National Center for Biotechnology Development (2020YFC0843800 and 2020YFC0846800), Ministry of Science and Technology of China (2020TFC0844100), and China Postdoctoral Science Foundation (2020T130112ZX).Declaration of Interests: The authors declare no potential conflict of interest.Ethics Approval Statement: The studies were approved by the Ethics Committee of the First Affiliated Hospital of the University of Science & Technology of China (2020-XG(H)-005) and Peking University First Hospital (2020-Research-112) for Emerging Infectious Diseases. Experiments were conducted in accordance with the ethical guidelines of the 1975 Declaration of Helsinki, the Principles of Good Clinical Practice, and the guidelines of China’s regulatory requirements.

Distinct B cell subsets give rise to antigen-specific antibody responses against SARS-CoV-2 (preprint)

Discovery of durable memory B cell (MBC) subsets against neutralizing viral epitopes is critical for determining immune correlates of protection from SARS-CoV-2 infection. Here, we identified functionally distinct SARS-CoV-2-reactive B cell subsets by profiling the repertoire of convalescent COVID-19 patients using a high-throughput B cell sorting and sequencing platform. Utilizing barcoded SARS-CoV-2 antigen baits, we isolated thousands of B cells that segregated into discrete functional subsets specific for the spike, nucleocapsid protein (NP), and open reading frame (ORF) proteins 7a and 8. Spike-specific B cells were enriched in canonical MBC clusters, and monoclonal antibodies (mAbs) from these cells were potently neutralizing. By contrast, B cells specific to ORF8 and NP were enriched in naïve and innate-like clusters, and mAbs against these targets were exclusively non-neutralizing. Finally, we identified that B cell specificity, subset distribution, and affinity maturation were impacted by clinical features such as age, sex, and symptom duration. Together, our data provide a comprehensive tool for evaluating B cell immunity to SARS-CoV-2 infection or vaccination and highlight the complexity of the human B cell response to SARS-CoV-2.

SARS-CoV-2 infection severity is linked to superior humoral immunity against the spike (preprint)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently causing a global pandemic. The antigen specificity and kinetics of the antibody response mounted against this novel virus are not understood in detail. Here, we report that subjects with a more severe SARS-CoV-2 infection exhibit a larger antibody response against the spike and nucleocapsid protein and epitope spreading to subdominant viral antigens, such as open reading frame 8 and non-structural proteins. Subjects with a greater antibody response mounted a larger memory B cell response against the spike, but not the nucleocapsid protein. Additionally, we revealed that antibodies against the spike are still capable of binding the D614G spike mutant and cross-react with the SARS-CoV-1 receptor binding domain. Together, this study reveals that subjects with a more severe SARS-CoV-2 infection exhibit a greater overall antibody response to the spike and nucleocapsid protein and a larger memory B cell response against the spike.