A Dual-Approach Strategy to Optimize the Safety and Efficacy of Anti-Zika Virus Monoclonal Antibody Therapeutics.

Antibody-dependent enhancement of infection (ADE) is clinically relevant to Dengue virus (DENV) infection and poses a major risk to the application of monoclonal antibody (mAb)-based therapeutics against related flaviviruses such as the Zika virus (ZIKV). Here, we tested a two-tier approach for selecting non-cross-reactive mAbs combined with modulating Fc glycosylation as a strategy to doubly secure the elimination of ADE while preserving Fc effector functions. To this end, we selected a ZIKV-specific mAb (ZV54) and generated three ZV54 variants using Chinese hamster ovary cells and wild-type (WT) and glycoengineered ΔXF Nicotiana benthamiana plants as production hosts (ZV54CHO, ZV54WT, and ZV54ΔXF). The three ZV54 variants shared an identical polypeptide backbone, but each exhibited a distinct Fc N-glycosylation profile. All three ZV54 variants showed similar neutralization potency against ZIKV but no ADE activity for DENV infection, validating the importance of selecting the virus/serotype-specific mAbs for avoiding ADE by related flaviviruses. For ZIKV infection, however, ZV54CHO and ZV54ΔXF showed significant ADE activity while ZV54WT completely forwent ADE, suggesting that Fc glycan modulation may yield mAb glycoforms that abrogate ADE even for homologous viruses. In contrast to the current strategies for Fc mutations that abrogate all effector functions along with ADE, our approach allowed the preservation of effector functions as all ZV54 glycovariants retained antibody-dependent cellular cytotoxicity (ADCC) against the ZIKV-infected cells. Furthermore, the ADE-free ZV54WT demonstrated in vivo efficacy in a ZIKV-infection mouse model. Collectively, our study provides further support for the hypothesis that antibody-viral surface antigen and Fc-mediated host cell interactions are both prerequisites for ADE, and that a dual-approach strategy, as shown herein, contributes to the development of highly safe and efficacious anti-ZIKV mAb therapeutics. Our findings may be impactful to other ADE-prone viruses, including SARS-CoV-2.

Prioritization of potential causative genes for schizophrenia in placenta.

Our earlier work has shown that genomic risk for schizophrenia converges with early life complications in affecting risk for the disorder and sex-biased neurodevelopmental trajectories. Here, we identify specific genes and potential mechanisms that, in placenta, may mediate such outcomes. We performed TWAS in healthy term placentae (N = 147) to derive candidate placental causal genes that we confirmed with SMR; to search for placenta and schizophrenia-specific associations, we performed an analogous analysis in fetal brain (N = 166) and additional placenta TWAS for other disorders/traits. The analyses in the whole sample and stratifying by sex ultimately highlight 139 placenta and schizophrenia-specific risk genes, many being sex-biased; the candidate molecular mechanisms converge on the nutrient-sensing capabilities of placenta and trophoblast invasiveness. These genes also implicate the Coronavirus-pathogenesis pathway and showed increased expression in placentae from a small sample of SARS-CoV-2-positive pregnancies. Investigating placental risk genes for schizophrenia and candidate mechanisms may lead to opportunities for prevention that would not be suggested by study of the brain alone.

Effects of brief exposure to campus environment on students' physiological and psychological health

Experiences in natural environments can enhance human wellbeing and promote the recovery of physiological and psychological health. During the COVID-19 pandemic, university students' activity off-campus was limited, thus, the campus environment was particularly important for the recovery of students' physiological and psychological health. Although the benefits of sustained natural exposure are obvious for people's physiological and psychological health, the effects of brief exposure on physiological and psychological are unclear. In the present study, four types of campus environments, including square space, dense forest space, sparse forest space, and waterfront space, were selected to explore the transient recovery effects of different types of campus environments. Sixty university students were recruited, measuring their systolic blood pressure, diastolic blood pressure, and heart rate as physical parameters to assess stress recovery. Respondents also reported scores about their personal feelings in questionnaires to evaluate their psychological states. Both physiological and psychological indicators responded to the brief natural exposure (5 min), and physiological and psychological health was restored. However, only the recovery amounts of psychological indicators were significantly different in waterfront space, dense forest space, and sparse forest space. These results indicate that being compare with other spaces, the brief exposure in the waterfront space was the most beneficial to students' psychological health recovery. This recovery was attributed to the great role played by the sense of escape, but after the brief exposure, the attraction and compatibility of the environment would hinder the psychological health recovery. In conclusion, according to tests on both physiological and psychological aspects, the waterfront environment on campus is the best choice for students' transient health recovery.

Lessons from China's Experience: Legal Analysis of Health Risks and Medical Obstacles of Personnel in COVID-19 Control Areas.

Purpose: Individuals in controlled areas often face restrictions on their personal freedom, and if they are unable to receive medical treatment when needed, it can significantly increase their health risks. However, current epidemic prevention and control policies do not provide clear guidelines on how to ensure individuals in controlled areas to seek medical attention when faced with health problems. By implementing specific measures that local governments must take in order to protect the health of those in controlled areas, the risks to their health can be greatly reduced. Patients and Methods: Our research utilizes a comparative approach to analyze the measures adopted by various regions for safeguarding the health of individuals in control areas, and the diverse outcomes they produce. We conduct empirical analysis and present examples of severe health risks that individuals in control areas face due to inadequate health protection measures. Furthermore, we conduct a critical evaluation of China's legal management of control areas, identifying both its principles and shortcomings. Results: The lack of unified legal regulations has led some local governments to make some shortcomings in making decisions on epidemic prevention and control. Specifically, some governments have neglected to provide adequate medical protection for individuals in controlled areas, limited the authority of specific implementers of prevention policies, and failed to establish fair punishment mechanisms. These shortcomings have a direct impact on the health of those in controlled areas and can even lead to tragic outcomes. Conclusion: Effective management of individuals in control areas during public health emergencies is crucial in reducing health risks. To achieve this, China needs to establish unified regulations and requirements, particularly with regards to medical protection, for individuals in control areas. Such measures can be achieved through the improvement of legislation, which can significantly reduce health risks faced by individuals in control areas during public health emergencies.

A novel plant-made monoclonal antibody enhances the synergetic potency of an antibody cocktail against the SARS-CoV-2 Omicron variant.

This study describes a novel, neutralizing monoclonal antibody (mAb), 11D7, discovered by mouse immunization and hybridoma generation, against the parental Wuhan-Hu-1 RBD of SARS-CoV-2. We further developed this mAb into a chimeric human IgG and recombinantly expressed it in plants to produce a mAb with human-like, highly homogenous N-linked glycans that has potential to impart greater potency and safety as a therapeutic. The epitope of 11D7 was mapped by competitive binding with well characterized mAbs, suggesting that it is a Class 4 RBD-binding mAb that binds to the RBD outside the ACE2 binding site. Of note, 11D7 maintains recognition against the B.1.1.529 (Omicron) RBD, as well neutralizing activity. We also provide evidence that this novel mAb may be useful in providing additional synergy to established antibody cocktails, such as Evusheld™ containing the antibodies tixagevimab and cilgavimab, against the Omicron variant. Taken together, 11D7 is a unique mAb that neutralizes SARS-CoV-2 through a mechanism that is not typical among developed therapeutic mAbs and by being produced in ΔXFT Nicotiana benthamiana plants, highlights the potential of plants to be an economic and safety-friendly alternative platform for generating mAbs to address the evolving SARS-CoV-2 crisis.

Dialogic communication on local government social media during the first wave of COVID-19: Evidence from the health commissions of prefecture-level cities in China.

Although some scholars have explored the level and determinants of Dialogic Communication on Government Social Media (DCGSM), none have conducted their studies in the context of public crisis. The current study contributes to the understanding on DCGSM by 16,822 posts crawled from the official Sina Weibo accounts of 104 Chinese health commissions in prefecture-level cities during the first wave of the COVID-19 pandemic. Results show that Chinese local government agencies have great variations in their DCGSM during the pandemic and the overall performance is poor. Furthermore, Chinese local governments prefer to conserve visitors and generate return visits, rather than dialogic loops development and the usefulness of information enhancement. The findings suggest that both public pressure and peer pressure contribute to the DCGSM of Chinese local governments during the public health crisis. In addition, the effect of public pressure is stronger than that of the peer pressure, indicating that local government agencies have experienced more demand-pull DCGSM.

SARS-CoV-2 Spike Protein Downregulates Cell Surface α7nAChR through a Helical Motif in the Spike Neck.

A deficiency of the functional α7 nicotinic acetylcholine receptor (α7nAChR) impairs neuronal and immune systems. The SARS-CoV-2 spike protein (S12) facilitates virus cell entry during COVID-19 infection and can also independently disrupt cellular functions. Here, we found that S12 expression significantly downregulated surface expression of α7nAChR in mammalian cells. A helical segment of S12 (L1145-L1152) in the spike neck was identified to be responsible for the downregulation of α7nAChR, as the mutant S12AAA (L1145A-F1148A-L1152A) had minimal effects on surface α7nAChR expression. This S12 segment is homologous to the α7nAChR intracellular helical motif known for binding chaperone proteins RIC3 and Bcl-2 to promote α7nAChR surface expression. Competition from S12 for binding these proteins likely underlies suppression of surface α7nAChR. Considering the critical roles of α7nAChR in cellular functions, these findings provide a new perspective for improving mRNA vaccines and developing treatment options for certain symptoms related to long COVID.

Predicting COVID-19 vaccination intentions: the roles of threat appraisal, coping appraisal, subjective norms, and negative affect.

BACKGROUND: As a new disease, communities possess little natural immunity to COVID-19 and vaccines are considered critical to preventing and reducing the incidence of severe illness. This study, inspired by Protection Motivation Theory (PMT), examines the relationship between citizens' threat appraisal, coping appraisal, subjective norms, negative affect, and their COVID-19 vaccination intentions. METHODS: A sample of 340 citizens from two main cities in Mainland China, Xi'an and Wuxi, was used for data analysis. Structural Equation Modeling (SEM) was employed with latent and observed variables to test hypotheses. Data were analyzed using AMOS 24.0. RESULTS: Several findings extend current understanding. Firstly, our proposed model explains 73% of the variance in vaccination intentions. Secondly, perceived severity only indirectly shapes COVID-19 vaccination intentions through negative affect. Thirdly, negative affect and response costs are negatively related to COVID-19 vaccination intentions. Finally, Perceived probability, subjective norms, response efficacy and self-efficacy are positively related to COVID-19 vaccination intentions; among them, self-efficacy contributes the most, followed by response efficacy and subjective norms, and lastly perceived probability. CONCLUSION: Theoretically, this study increases current understanding about subjective norms and affective responses. We provoke a certain amount of thought about the role of affect response in relation to threat appraisal and vaccination intentions. Specifically, governments must be vigilant that citizens' negative affect, such as fear, may cause vaccine hesitation.

Seroepidemiology of pertussis in the east of China: Estimates of incidence of infection in adolescents and adults pre- and post-COVID-19.

Introduction: The dramatic decrease in the number of reported cases of pertussis during COVID-19 pandemic has been underestimated. The objective was to compare the estimated incidence rate of pertussis in populations pre- and post-COVID-19 pandemic by analyzing the anti-pertussis toxin (anti-PT) IgG and anti-filamentous hemagglutininant (anti-FHA) IgG antibodies in healthy Chinese population from 2018 to 2021. Methods: All serum samples (N = 1,000) were collected from healthy population (aged ≥ 15 years) who attended an annual monitoring project of antibody levels in Jiangsu province in 2018-2021 were measured by ELISA. Results: The positive rates of anti-PT IgG and anti-FHA IgG antibodies were 11.4% (114/1,000) and 20.2% (202/1,000) (≥40 IU/ml), the GMC were 17.25 (95% CI: 15.49-19.03) IU/mL and 24.94 (95% CI: 22.73-27.16) IU/mL in the study population, respectively. The percentage of participants with anti-PT IgG antibodies higher than 40 IU/mL was 5.20% (11/212) in 2018, 5.5% (19/348) in 2019, 21.2% (46/217) in 2020 and 17.0% (38/223) in 2021, respectively. The non-detectable rate (<5 IU/mL) of anti-PT IgG antibodies was 16.9, 17.7, 28.1, and 37.3% in 2018, 2019, 2020, and 2021, respectively. We assumed that the infection occurred within 58.6 days, and based on the overall proportion (2.9%) of individuals with anti-PT IgG antibody ≥100 IU/ml, the incidence rate (/100) was estimated by the formula to be 18.08 (95% CI: 12.40-26.11). In addition, the estimated incidence of Post-COVID-19 was higher than that of Pre-COVID-19 (36.33/100 vs. 12.84/100), and the difference was statistically significant (p < 0.05). Conclusions: Our results suggest a high rate of under-reporting of pertussis in Jiangsu Province both pre- and post-COVID-19 pandemic, and there are a large number of adults of childbearing age who are susceptible to pertussis. It seems imperative that vaccination of adolescents and adults should be considered for inclusion in vaccination programs.

Comparison of chest CT features between progressive and nonprogressive patients with COVID-19 pneumonia: A meta-analysis.

OBJECTIVE: The aim of this study was to compare the radiographic features of patients with progressive and nonprogressive coronavirus disease 2019 (COVID-19) pneumonia. METHODS: PubMed, Embase, and Cochrane Library databases were searched from January 1, 2020, to February 28, 2022, by using the keywords: "COVID-19", "novel Coronavirus", "2019-novel coronavirus", "CT", "radiology" and "imaging". We summarized the computed tomography manifestations of progressive and nonprogressive COVID-19 pneumonia. The meta-analysis was performed using the Stata statistical software version 16.0. RESULTS: A total of 10 studies with 1092 patients were included in this analysis. The findings of this meta-analysis indicated that the dominating computed tomography characteristics of progressive patients were a crazy-paving pattern (odds ratio [OR] = 2.10) and patchy shadowing (OR = 1.64). The dominating lesions distribution of progressive patients were bilateral (OR = 11.62), central mixed subpleural (OR = 1.37), and central (OR = 1.36). The other dominating lesions of progressive patients were pleura thickening (OR = 2.13), lymphadenopathy (OR = 1.74), vascular enlargement (OR = 1.39), air bronchogram (OR = 1.29), and pleural effusion (OR = 1.29). Two patterns of lesions showed significant links with the progression of disease: nodule (P = .001) and crazy-paving pattern (P = .023). Four lesions distribution showed significant links with the progression of disease: bilateral (P = .004), right upper lobe (P = .003), right middle lobe (P = .001), and left upper lobe (P = .018). CONCLUSION: Nodules, crazy-paving pattern, and/or new lesions in bilateral, upper and middle lobe of right lung, and lower lobe of left lung may indicate disease deterioration. Clinicians should formulate or modify treatment strategies in time according to these specific conditions.

Manual severity evaluation methods for novel coronavirus pneumonia based on computed tomography imaging

Computed tomography (CT) examination plays an indispensable role in the diagnosis of coronavirus disease-2019 (COVID-19). Many studies have evaluated the severity of COVID-19 based on CT images, with the severity of COVID-19 being evaluated either manually or by using artificial intelligence. In this review, the recently reported methods for manually evaluating COVID-19 severity based on CT images are summarized and divided into three categories: evaluation based on the extent of abnormalities;evaluation based on the characteristics of abnormalities;and evaluation based on both the extent and characteristics of abnormalities.

The effect of short music videos on needs satisfaction and separation anxiety of children's family members during COVID-19: The example of TikTok

Objective To investigate the effect of short music videos on needs satisfaction and separation anxiety of the family members of children with congenital heart disease (CHD) in the cardiac intensive care unit (CICU) during the COVID-19 pandemic. Methods Eighty-seven children's family members were divided into the study group and the control group between February 2020 and March 2021. During the COVID-19 pandemic, the participants in the control group were visited by telephone, while the participants in the study group used the TikTok short music video application and WeChat as communication tools. After the intervention, the critical care family needs inventory (CCFNI) and separation anxiety scale (SAS) for all participants were recorded and analyzed. Results There were no statistically significant differences in general characteristics or preintervention data between the two groups. However, the two dimensions of the support scale and information scale of the CCFNI in the study group were significantly different from those in the control group after the intervention (P = 0.008, and P = 0.021, respectively). There were significant differences in the three dimensions of the SAS between the two groups (P = 0.004, P = 0.007, and P = 0.041, respectively). Conclusion The visiting system of the ICU changed during the COVID-19 pandemic, and the use of the TikTok short music video application and WeChat was conducive to optimizing the CICU ward visiting process, reducing the separation anxiety of the family members of children in the CICU, and improving their needs satisfaction.

Variations in Sulfur and Nitrogen Oxidation Rates in Summer Aerosols from 2014 to 2020 in Wuhan, China

To date, research regarding the changes of the sulfur and nitrogen rates in Wuhan during the summer is limited. In this study, we analyzed the air quality in Wuhan, China, using water-soluble ion, gaseous precursor, and weather data. A Spearman correlation analysis was then performed to investigate the temporal changes in air quality characteristics and their driving factors to provide a reference for air pollution control in Wuhan. The results indicate that SO2 in the atmosphere at Wuhan undergoes secondary conversion and photo-oxidation, and the conversion degree of SO2 is higher than that of NO2. During the summers of 2016 and 2017, secondary inorganic atmospheric pollution was more severe than during other years. The fewest oxidation days occurred in summer 2020 (11 days), followed by the summers of 2017 and 2014 (25 and 27 days, respectively). During the study period, ion neutralization was the strongest in summer 2015 and the weakest in August 2020. The aerosols in Wuhan were mostly acidic and NH4+ was an important neutralizing component. The neutralization factors of all cations showed little change in 2015. K+, Mg2+, and Ca2+ level changes were the highest in 2017 and 2020. At low temperature, high humidity, and low wind speed conditions, SO2 and NO2 were more easily converted into SO42− and NO3−.

Epidemiology and genetic characterization of human metapneumovirus in pediatric patients from Hangzhou China.

Human metapneumovirus (HMPV), which is distributed worldwide, is a significant viral respiratory pathogen responsible for causing acute respiratory tract infections (ARTIs) in children. The aim of the present study was to investigate the epidemiological and genetic characteristics of HMPV in pediatric patients in Hangzhou China following the peak of onset of coronavirus disease 2019 (COVID-19). A total of 1442 throat swabs were collected from the pediatric patients with a diagnosis of ARTI from November 2020 to March 2021. The following viruses were detected by real-time polymerase chain reaction analysis: HMPV, RSV, adenovirus, hPIV1-3, influenza A, and influenza B. A two-step method was used to amplify the F genes of the HMPV-positive samples. Following sequencing, phylogenetic analyses were conducted using the MEGA version 7 software package. Among the 1442 samples, 103 (7.14%) were positive for HMPV. No significant differences were observed in the gender distribution. The highest incidence of HMPV occurred in children older than 6 years and the lowest was noted in children younger than 6 months. Lower respiratory tract infections were diagnosed at a higher rate than upper respiratory tract infections in HMPV-infected children. Only 10 HMPV-infected children (5.41%) were inpatients compared with 93 outpatients (7.39%). Co-infection was observed in 31 HMPV-positive samples including 24 samples of double infection and seven samples of triple infection. A total of 61F gene fragments of HMPV, which were approximately 727 bp in length were successfully sequenced. All the HMPVs belonged to the genotype B and were clustered into subgenotypes B1 (1.6%, 1/61) and B2 (98.4%, 60/61). A total of four specific amino acid substitutions were noted as follows: aa280, aa296, aa392, and aa396. These substitutions were present between sequences derived from the subgenotypes B1 and B2 in the fusion open reading frame from position 244 to 429. In conclusion, the present study provided significant information regarding the epidemiological and genetic characteristics of HMPV in children living in Hangzhou. Following the first peak of the COVID-19 pandemic, HMPV was considered an important viral respiratory pathogen present in children with ARTI.

COVID-19 Pandemic: Insights into Interactions between SARS-CoV-2 Infection and MAFLD.

COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become an ongoing global health pandemic. Since 2019, the pandemic continues to cast a long shadow on all aspects of our lives, bringing huge health and economic burdens to all societies. With our in-depth understanding of COVID-19, from the initial respiratory tract to the later gastrointestinal tract and cardiovascular systems, the multiorgan involvement of this infectious disease has been discovered. Metabolic dysfunction-associated fatty liver disease (MAFLD), formerly named nonalcoholic fatty liver disease (NAFLD), is a major health issue closely related to metabolic dysfunctions, affecting a quarter of the world's adult population. The association of COVID-19 with MAFLD has received increasing attention, as MAFLD is a potential risk factor for SARS-CoV-2 infection and severe COVID-19 symptoms. In this review, we provide an update on the interactions between COVID-19 and MAFLD and its underlying mechanisms.

Does Citizen Engagement With Government Social Media Accounts Differ During the Different Stages of Public Health Crises? An Empirical Examination of the COVID-19 Pandemic.

Background: The COVID-19 pandemic has created one of the greatest challenges to humankind, developing long-lasting socio-economic impacts on our health and wellbeing, employment, and global economy. Citizen engagement with government social media accounts has proven crucial for the effective communication and management of public health crisis. Although much research has explored the societal impact of the pandemic, extant literature has failed to create a systematic and dynamic model that examines the formation mechanism of citizen engagement with government social media accounts at the different stages of the COVID-19 pandemic. This study fills this gap by employing the Heuristic-Systematic Model and investigating the effects of the heuristic clues including social media capital, information richness, language features, dialogic loop, and the systematic clue including content types, on citizen engagement with government social media across three different stages of the pandemic, employing the moderating role of emotional valence. Methods: The proposed model is validated by scraping 16,710 posts from 22 provincial and municipal government micro-blog accounts in the Hubei province, China. Results: Results show that the positive effects of social media capital on citizen engagement were observed at all stages. However, the effects of information richness, language features, dialogic loop, and content types, and the moderating effect of emotional valence, varied across the different pandemic development stages. Conclusions: The findings provide suggestions for the further effective use of government social media, and better cope with crises. Government agencies should pay attention to the content and form of information shared, using technical means to analyze the information needs of citizens at different stages of public health emergencies, understanding the content most concerned by citizens, and formulating the content type of posts.

How Official Social Media Affected the Infodemic among Adults during the First Wave of COVID-19 in China.

The COVID-19 pandemic has demonstrated that social media can impact society both positively (e.g., keeping citizens connected and informed) and negatively (e.g., the deliberate spreading of misinformation). This study aims to examine the underlying mechanisms of the relationship between official social media accounts and the infodemic, experienced during the first wave of COVID-19 in China. A theoretical model is proposed to examine how official social media accounts affected the infodemic during this period. In total, 1398 questionnaire responses were collected via WeChat and Tencent QQ, two leading Chinese social media platforms. Data analysis was conducted using Partial Lease Squares Structural Equation Modeling (PLS-SEM), moderation effect analysis, and mediation effect analysis. Results indicate that the Information Quality (IQ) of Official social media accounts (ß = -0.294, p < 0.001) has a significant negative effect on the infodemic. Mediation effect analysis revealed that both social support (ß = -0.333, 95% Boot CI (-0.388, -0.280)) and information cascades (ß = -0.189, 95% Boot CI (-0.227, -0.151)) mediate the relationship between IQ and the infodemic. Moderation effect analysis shows that private social media usage (F = 85.637, p < 0.001) positively moderates the relationship between IQ and the infodemic, while health literacy has a small negative moderation effect on the relationship between IQ and the infodemic. Our findings show that, in the context of Chinese media, official social media accounts act as a major source of information for influencing the infodemic through increasing social support and reducing information cascades for citizens.

Potential for a Plant-Made SARS-CoV-2 Neutralizing Monoclonal Antibody as a Synergetic Cocktail Component.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a public health crisis over the last two years. Monoclonal antibody (mAb)-based therapeutics against the spike (S) protein have been shown to be effective treatments for SARS-CoV-2 infection, especially the original viral strain. However, the current mAbs produced in mammalian cells are expensive and might be unaffordable for many. Furthermore, the emergence of variants of concern demands the development of strategies to prevent mutant escape from mAb treatment. Using a cocktail of mAbs that bind to complementary neutralizing epitopes is one such strategy. In this study, we use Nicotiana benthamiana plants in an effort to expedite the development of efficacious and affordable antibody cocktails against SARS-CoV-2. We show that two mAbs can be highly expressed in plants and are correctly assembled into IgG molecules. Moreover, they retain target epitope recognition and, more importantly, neutralize multiple SARS-CoV-2 variants. We also show that one plant-made mAb has neutralizing synergy with other mAbs that we developed in hybridomas. This is the first report of a plant-made mAb to be assessed as a potential component of a SARS-CoV-2 neutralizing cocktail. This work may offer a strategy for using plants to quickly develop mAb cocktail-based therapeutics against emerging viral diseases with high efficacy and low costs.

SARS-CoV-2 Spike Protein-Induced Interleukin 6 Signaling Is Blocked by a Plant-Produced Anti-Interleukin 6 Receptor Monoclonal Antibody.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the current COVID-19 pandemic, has caused more than 4.5 million deaths worldwide. Severe and fatal cases of COVID-19 are often associated with increased proinflammatory cytokine levels including interleukin 6 (IL-6) and acute respiratory distress syndrome. In this study, we explored the feasibility of using plants to produce an anti-IL-6 receptor (IL-6R) monoclonal antibody (mAb) and examined its utility in reducing IL-6 signaling in an in vitro model, which simulates IL-6 induction during SARS-CoV-2 infection. The anti-IL6R mAb (IL6RmAb) was quickly expressed and correctly assembled in Nicotiana benthamiana leaves. Plant-produced IL6RmAb (pIL6RmAb) could be enriched to homogeneity by a simple purification scheme. Furthermore, pIL6RmAb was shown to effectively inhibit IL-6 signaling in a cell-based model system. Notably, pIL6RmAb also suppressed IL-6 signaling that was induced by the exposure of human peripheral blood mononuclear cells to the spike protein of SARS-CoV-2. This is the first report of a plant-made anti-IL-6R mAb and its activity against SARS-CoV-2-related cytokine signaling. This study demonstrates the capacity of plants for producing functionally active mAbs that block cytokine signaling and implies their potential efficacy to curb cytokine storm in COVID-19 patients.