Insight into the mechanisms of coronaviruses evading host innate immunity

The SARS-CoV-2 induced coronavirus disease (COVID-19) has recently caused a pandemic. Patients with COVID-19 presented with a wide spectrum of symptoms for the disease, from entirely asymptomatic to full-blown pneumonia and multiorgan failures. More evidence emerged, showing the production of interferons (IFNs) in the severe cases were significantly lower than their milder counterparts, suggesting linkage of COVID-19 to impaired innate immunity. This review presents a brief overview of how coronaviruses evade innate immunity, based on the information from SARS-CoV and MERS-CoV. The coronaviruses manage to block, escape, or dampen the innate immune response by antagonizing double-stranded RNA (dsRNA) sensor, stimulator of IFN genes (STING) and mitochondrial antiviral-signaling protein (MAVS) pathways, epigenetic modification, posttranslational modifications, and host mRNA translation. We provide novel insights into a comprehensive therapy to combat SARS-CoV-2 infection.

Insight into the mechanisms of coronaviruses evading host innate immunity.

The severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) induced coronavirus disease 2019 (COVID-19) has recently caused a pandemic. Patients with COVID-19 presented with a wide spectrum of symptoms for the disease, from entirely asymptomatic disease to full-blown pneumonia and multiorgan failures. More evidence emerged, showing the production of interferons (IFNs) in the severe cases were significantly lower than their milder counterparts, suggesting linkage of COVID-19 to impaired innate immunity. This review presents a brief overview of how coronaviruses evade innate immunity, according to the current studies about SARS-CoV and middle-east respiratory syndrome-coronavirus (MERS-CoV). The coronaviruses manage to block, escape, or dampen the innate immune response by antagonizing double-stranded RNA (dsRNA) sensor, mitochondrial antiviral-signaling protein (MAVS) and stimulator of IFN genes (STING) pathways, epigenetic modification, posttranslational modifications, and host mRNA translation. We provide novel insights into a comprehensive therapy to combat SARS-CoV-2 infection.

Construction of tourism resilience system and high-quality tourism development under the epidemic crisis

China's economic system has entered a new stage of high-quality development from a high-speed growth. As a strategic pillar industry in China, realizing high-quality transformation is an inevitable choice for the tourism industry to respond to the call of the country and enhance industrial competitiveness. However, the repeated shocks of the COVID-19 epidemic have had a wide-ranging impact on socio-economic development and cross-regional flows, and various foreseeable and unforeseen security risks also threaten the normal operation of the tourism system. How to face the uncertainty of the development environment, how to adapt to changes in the external environment, and how to deal with the interference of risk factors and further release the vitality of the industry have become important issues that need to be resolved in the process of promoting high-quality development of the tourism industry.

Repeated COVID-19 Relapse of an Imported Patient Infected with SARS-CoV-2 Delta Variant of Concern.

BACKGROUND: Repeated re-positive of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) B.1.617.2 (Delta) variants of concern (VOC) in recovered coronavirus disease 2019 (COVID-19) patients have not been reported yet. METHODS: We reported a rare case of repeated COVID-19 relapse during the post-discharge surveillance. RESULTS: This case had long-term viral shedding for 79 days. CONCLUSIONS: This case highlights that longer observation and isolation periods need be considered for patients with SARS-CoV-2 delta VOC infection.

Clinical features and viral etiology of acute respiratory infection in an outpatient fever clinic during COVID-19 pandemic in a tertiary hospital in Nanjing, China.

BACKGROUND: Clinical feature and viral etiology for acute respiratory infection (ARI) in the community was unknown during coronavirus disease 2019 (COVID-19) pandemic. OBJECTIVE: In a retrospective study, we aimed to characterize the clinical feature and etiology for the ARI patients admitted to the outpatient fever clinic in Nanjing Drum Tower Hospital between November 2020 and March 2021. METHODS: Fifteen common respiratory pathogens were tested using pharyngeal swabs by multiplex reverse transcriptase-polymerase chain reaction assays. RESULTS: Of the 242 patients, 56 (23%) were tested positive for at least one viral agent. The predominant viruses included human rhinovirus (HRV) (5.4%), parainfluenza virus type III (PIV-III) (5.0%), and human coronavirus-NL63 (HCoV-NL63) (3.7%). Cough, sputum, nasal obstruction, and rhinorrhea were the most prevalent symptoms in patients with viral infection. Elderly and the patients with underlying diseases were susceptible to pneumonia accompanied with sputum and chest oppression. Three (5.4%) patients in virus infection group, whereas 31 (16.7%) in non-viral infection group (p = 0.033), were empirically prescribed with antiviral agents. Among 149 patients who received antibiotic therapy, 30 (20.1%) patients were later identified with viral infection. CONCLUSION: Our study indicated the importance of accurate diagnosis of ARI, especially during the COVID-19 pandemic, which might facilitate appropriate clinical treatment.

Impact of the COVID-19 pandemic on research on marine plastic pollution – A bibliometric-based assessment

Fighting the COVID-19 pandemic has led to a dramatic increase in plastic waste, which has had a huge impact on the environment, including the marine environment. This work is aimed to evaluate the pattern of national research cooperation, research hotspots, and research evolution before and during the epidemic by systematically reviewing the publications on marine plastic pollution during 2015-2019 (before the pandemic) 2020-2022 (during the pandemic) using the Systematic Literature Review and Latent Semantic Analysis. The results show (i) Compared to pre-pandemic, publications on marine pollution during the COVID-19 pandemic declined briefly and then increased sharply. (ii) Compared with before the pandemic, the national cooperation model has changed during the pandemic, and four major research centers have been formed: Central European countries centered on Italy;Nordic countries centered on United Kingdom;South Korea;Asia and Africa centered on India A developing country and a Pacific Rim country centered on United States and China. (iii) The knowledge map of keyword clustering does not change significantly before and during the COVID-19: ecosystem, spatial distribution, environmental governance and biodegradation. However, there are differences in the sub-category research of the four types of keywords. (iv) The impact of marine plastics on organisms and the governance of marine plastic pollution have become a branch of knowledge that has evolved rapidly during the pandemic. The governance of marine plastic pollution and microplastics are expected to become an important research direction.

Correction: Health Perceptions and Misconceptions Regarding COVID-19 in China: Online Survey Study.

[This corrects the article DOI: 10.2196/21099.].

The Impact of China's Paired Assistance Policy on the COVID-19 Crisis-An Empirical Case Study of Hubei Province.

To control the coronavirus pandemic (COVID-19), China implemented the Paired Assistance Policy (PAP). Local responders in 16 cities in Hubei Province were paired with expert teams from 19 provinces and municipalities. Fully supported by the country's top-down political system, PAP played a significant role in alleviating the COVID-19 pandemic in Hubei Province and China as a whole. In this study, we examined PAP using a two-way fixed effects model with the cumulative number of medical support personnel and cumulative duration as measurements. The results show personnel and material support played an active role in the nation's response to the COVID-19 public health crisis.

Visualizing the Knowledge Base and Research Hotspot of Public Health Emergency Management: A Science Mapping Analysis-Based Study

Public health emergency management has been one of the main challenges of social sustainable development since the beginning of the 21st century. Research on public health emergency management is becoming a common focus of scholars. In recent years, the literature associated with public health emergency management has grown rapidly, but few studies have used a bibliometric analysis and visualization approach to conduct deep mining and explore the characteristics of the public health emergency management research field. To better understand the present status and development of public health emergency management research, and to explore the knowledge base and research hotspots, the bibliometric method and science mapping technology were adopted to visually evaluate the knowledge structure and research trends in the field of public health emergency management studies. From 2000 to 2020, a total of 3723 papers related to public health emergency management research were collected from the Web of Science Core Collection as research data. The five main research directions formed are child prevention, mortality from public health events, public health emergency preparedness, public health emergency management, and coronavirus disease 2019 (COVID-19). The current research hotspots and frontiers are climate change, COVID-19 and related coronaviruses. Further research is needed to focus on the COVID-19 and related coronaviruses. This study intends to contribute inclusive support to related academia and industry in the aspects of public health emergency management and public safety research, as well as research hotspots and future research directions.

Clinical features and prognosis of COVID-19 patients with metabolic syndrome: A multicenter, retrospective study Características clínicas y pronóstico de los pacientes con COVID-19 y síndrome metabólico: un estudio multicéntrico y retrospectivo

Background Few studies have investigated the impacts of metabolic syndrome (MS) on coronavirus disease 2019 (COVID-19). We described the clinical features and prognosis of confirmed COVID-19 patients with MS during hospitalization and after discharge. Methods Two hundred and thirty-three COVID-19 patients from the hospitals in 8 cities of Jiangsu, China were retrospectively included. Clinical characteristics of COVID-19 patients were described and risk factors of severe illness were analyzed by logistic regression analysis. Results Forty-five (19.3%) of 233 COVID-19 patients had MS. The median age of COVID-19 patients with MS was significantly higher than non-MS patients (53.0 years vs. 46.0 years, P = 0.004). There were no significant differences of clinical symptoms, abnormal chest CT images, and treatment drugs between two groups. More patients with MS had severe illness (33.3% vs. 6.4%, P < 0.001) and critical illness (4.4% vs. 0.5%, P = 0.037) than non-MS patients. The proportions of respiratory failure and acute respiratory distress syndrome in MS patients were also higher than non-MS patients during hospitalization. Multivariate analysis showed that concurrent MS (odds ratio [OR] 7.668, 95% confidence interval [CI] 3.062–19.201, P < 0.001) and lymphopenia (OR 3.315, 95% CI 1.306–8.411, P = 0.012) were independent risk factors of severe illness of COVID-19. At a median follow-up of 28 days after discharge, bilateral pneumonia was found in 95.2% of MS patients, while only 54.7% of non-MS patients presented bilateral pneumonia. Conclusions 19.3% of COVID-19 patients had MS in our study. COVID-19 patients with MS are more likely to develop severe complications and have worse prognosis. More attention should be paid to COVID-19 patients with MS.

Clinical features and prognosis of COVID-19 patients with metabolic syndrome: A multicenter, retrospective study.

Background: Few studies have investigated the impacts of metabolic syndrome (MS) on coronavirus disease 2019 (COVID-19). We described the clinical features and prognosis of confirmed COVID-19 patients with MS during hospitalization and after discharge. Methods: Two hundred and thirty-three COVID-19 patients from the hospitals in 8 cities of Jiangsu, China were retrospectively included. Clinical characteristics of COVID-19 patients were described and risk factors of severe illness were analyzed by logistic regression analysis. Results: Forty-five (19.3%) of 233 COVID-19 patients had MS. The median age of COVID-19 patients with MS was significantly higher than non-MS patients (53.0 years vs. 46.0 years, P = 0.004). There were no significant differences of clinical symptoms, abnormal chest CT images, and treatment drugs between two groups. More patients with MS had severe illness (33.3% vs. 6.4%, P < 0.001) and critical illness (4.4% vs. 0.5%, P = 0.037) than non-MS patients. The proportions of respiratory failure and acute respiratory distress syndrome in MS patients were also higher than non-MS patients during hospitalization. Multivariate analysis showed that concurrent MS (odds ratio [OR] 7.668, 95% confidence interval [CI] 3.062-19.201, P < 0.001) and lymphopenia (OR 3.315, 95% CI 1.306-8.411, P = 0.012) were independent risk factors of severe illness of COVID-19. At a median follow-up of 28 days after discharge, bilateral pneumonia was found in 95.2% of MS patients, while only 54.7% of non-MS patients presented bilateral pneumonia. Conclusions: 19.3% of COVID-19 patients had MS in our study. COVID-19 patients with MS are more likely to develop severe complications and have worse prognosis. More attention should be paid to COVID-19 patients with MS.

Antecedentes: Pocos estudios han investigado el impacto del síndrome metabólico (SM) en la enfermedad por coronavirus 2019 (COVID-19). Describimos las características clínicas y el pronóstico de los pacientes con COVID-19 confirmados con SM durante la hospitalización y después del alta. Métodos: Se incluyó de forma retrospectiva a 233 pacientes con COVID-19 de los hospitales de 8 ciudades de Jiangsu (China). Se describieron sus características clínicas y se analizaron los factores de riesgo de enfermedad grave mediante un análisis de regresión logística. Resultados: De los 233 pacientes, 45 (19,3%) tenían EM. La mediana de edad de estos pacientes con EM fue significativamente mayor que la de los pacientes sin él (53,0 años frente a 46,0 años; p = 0,004). No hubo diferencias significativas en cuanto a los síntomas clínicos, las imágenes de TC torácica anormales y los fármacos de tratamiento entre los 2 grupos. Hubo más pacientes con EM que tuvieron enfermedades graves (33,3% frente a 6,4%; p < 0,001) y críticas (4,4% frente a 0,5%; p = 0,037) que los pacientes sin EM. Las proporciones de insuficiencia respiratoria y síndrome de dificultad respiratoria aguda en los pacientes con EM también fueron mayores que en los pacientes sin EM durante la hospitalización. El análisis multivariante mostró que la EM concurrente (odds ratio [OR] 7,668; intervalo de confianza [IC] del 95%: 3,062-19,201; p < 0,001) y la linfopenia (OR 3,315; IC del 95%: 1,306-8,411; p = 0,012) eran factores de riesgo independientes de COVID-19 grave. En una mediana de seguimiento de 28 días tras el alta, se encontró neumonía bilateral en el 95,2% de los pacientes con EM, mientras que solo la presentaron el 54,7% de los pacientes sin EM. Conclusiones: El 19,3% de los pacientes con COVID-19 tenían EM en nuestro estudio. Los pacientes con COVID-19 y EM son más propensos a desarrollar complicaciones graves y tienen peor pronóstico. Se debe prestar más atención a los pacientes con COVID-19 y EM.

The latent period of coronavirus disease 2019 with SARS-CoV-2 B.1.617.2 Delta variant of concern in the postvaccination era.

INTRODUCTION: Emerging variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have resulted in new challenges for epidemic prevention and control worldwide. However, little is known about the latent period of coronavirus disease by the SARS-CoV-2 Delta variant of concern (VOC) in the postvaccination era. METHODS: The epidemiology and clinical data of cases with confirmed SARS-CoV-2 Delta VOC infection were retrospective collected. Dates of the first positive PCR test were collected to estimate the distribution of latent period. RESULTS: Of the 40 patients, 16 were male (40%). The median age of patients was 47.5 years. The median latent period of patients was 6.0 days (interquartile range [IQR], 4.0-9.0 days) and the longest latent period was 13.0 days after exposure. The latent periods were longer in male patients compared to female patients (median, 8.5 days vs. 5.0 days, p = .041). The median latent period was comparable among fully vaccinated cases (6.5 days), no vaccinated cases (7.5 days), and partially vaccinated cases (5.5 days). CONCLUSIONS: The median latent period of SARS-CoV-2 Delta VOC infection was 6.0 days. The latent period between vaccinated and non-vaccinated patients was not significantly different. The 14-day quarantine program is sufficient to prevent the transmission of COVID-19 by Delta VOC in the postvaccination era.

The Third dose of CoronVac vaccination induces broad and potent adaptive immune responses that recognize SARS-CoV-2 Delta and Omicron variants.

The waning humoral immunity and emerging contagious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants resulted in the necessity of the booster vaccination of coronavirus disease 2019 (COVID-19). The inactivated vaccine, CoronaVac, is the most widely supplied COVID-19 vaccine globally. Whether the CoronaVac booster elicited adaptive responses that cross-recognize SARS-CoV-2 variants of concern (VoCs) among 77 healthy subjects receiving the third dose of CoronaVac were explored. After the boost, remarkable elevated spike-specific IgG and IgA responses, as well as boosted neutralization activities, were observed, despite 3.0-fold and 5.9-fold reduced neutralization activities against Delta and Omicron strains compared to that of the ancestral strain. Furthermore, the booster dose induced potent B cells and memory B cells that cross-bound receptor-binding domain (RBD) proteins derived from VoCs, while Delta and Omicron RBD-specific memory B cell recognitions were reduced by 2.7-fold and 4.2-fold compared to that of ancestral strain, respectively. Consistently, spike-specific circulating follicular helper T cells (cTfh) significantly increased and remained stable after the boost, with a predominant expansion towards cTfh17 subpopulations. Moreover, SARS-CoV-2-specific CD4+ and CD8+ T cells peaked and sustained after the booster. Notably, CD4+ and CD8+ T cell recognition of VoC spike was largely preserved compared to the ancestral strain. Individuals without generating Delta or Omicron neutralization activities had comparable levels of CD4+ and CD8+ T cells responses as those with detectable neutralizing activities. Our study demonstrated that the CoronaVac booster induced broad and potent adaptive immune responses that could be effective in controlling SARS-CoV-2 Delta and Omicron variants.

Research on comprehensive recovery of liner schedule and container flow with hard time windows constraints.

COVID-19 has had a huge impact on the global container market. Many liner companies have adopted a blank sailing for some voyages to adjust capacity, and vessel schedule reliability continues to be sluggish. From the perspective of the container liner company, this paper studies the integrated recovery of liner schedule and container flow under the background of suspension of shipping service. With the goal of minimizing the total cost of the liner company, the hard time window constraints of the container flow on the suspended routes are set to construct the integrated recovery problem.The increased carbon emission cost during the restoration of the container flow is taken into account.A mixed integer nonlinear programming model is established, and the adaptive mutation particle swarm optimization (AMPSO) is used to solve the model. The results show that the total cost of the model is reduced by 10.66% compared with the total cost of the shipping schedule recovery model that did not consider the recovery of container flow.

Identifying Predictors of COVID-19 Mortality Using Machine Learning.

(1) Background: Coronavirus disease 2019 (COVID-19) is a dominant, rapidly spreading respiratory disease. However, the factors influencing COVID-19 mortality still have not been confirmed. The pathogenesis of COVID-19 is unknown, and relevant mortality predictors are lacking. This study aimed to investigate COVID-19 mortality in patients with pre-existing health conditions and to examine the association between COVID-19 mortality and other morbidities. (2) Methods: De-identified data from 113,882, including 14,877 COVID-19 patients, were collected from the UK Biobank. Different types of data, such as disease history and lifestyle factors, from the COVID-19 patients, were input into the following three machine learning models: Deep Neural Networks (DNN), Random Forest Classifier (RF), eXtreme Gradient Boosting classifier (XGB) and Support Vector Machine (SVM). The Area under the Curve (AUC) was used to measure the experiment result as a performance metric. (3) Results: Data from 14,876 COVID-19 patients were input into the machine learning model for risk-level mortality prediction, with the predicted risk level ranging from 0 to 1. Of the three models used in the experiment, the RF model achieved the best result, with an AUC value of 0.86 (95% CI 0.84-0.88). (4) Conclusions: A risk-level prediction model for COVID-19 mortality was developed. Age, lifestyle, illness, income, and family disease history were identified as important predictors of COVID-19 mortality. The identified factors were related to COVID-19 mortality.

A Lateral Flow Immunoassay Coupled with a Spectrum-Based Reader for SARS-CoV-2 Neutralizing Antibody Detection.

As of August 2021, there have been over 200 million confirmed case of coronavirus disease 2019 caused by severe acute respiratory syndrome coronavirus and more than 4 million COVID-19-related deaths globally. Although real-time polymerase chain reaction is considered to be the primary method of detection for SARS-CoV-2 infection, the use of serological assays for detecting COVID-19 antibodies has been shown to be effective in aiding with diagnosis, particularly in patients who have recovered from the disease and those in later stages of infection. Since it has a high detection rate and few limitations compared to conventional enzyme-linked immunosorbent assay protocols, we used a lateral flow immunoassay as our diagnostic tool of choice. Since lateral flow immunoassay results interpreted by the naked eye may lead to erroneous diagnoses, we developed an innovative, portable device with the capacity to capture a high-resolution reflectance spectrum as a means of promoting diagnostic accuracy. We combined this spectrum-based device with commercial lateral flow immunoassays to detect the neutralizing antibody in serum samples collected from 30 COVID-19-infected patients (26 mild cases and four severe cases). The results of our approach, lateral flow immunoassays coupled with a spectrum-based reader, demonstrated a 0.989 area under the ROC curve, 100% sensitivity, 95.7% positive predictive value, 87.5% specificity, and 100% negative predictive value. As a result, our approach exhibited great value for neutralizing antibody detection. In addition to the above tests, we also tested plasma samples from 16 AstraZeneca-vaccinated (ChAdOx1nCoV-19) patients and compared our approach and enzyme-linked immunosorbent assay results to see whether our approach could be applied to vaccinated patients. The results showed a high correlation between these two approaches, indicating that the lateral flow immunoassay coupled with a spectrum-based reader is a feasible approach for diagnosing the presence of a neutralizing antibody in both COVID-19-infected and vaccinated patients.

The impact of COVID-19 on the cascade of care of HCV in the US and China.

BACKGROUND AND OBJECTIVES: The COVID-19 pandemic imperiled the global health system. We aimed to determine the impact of COVID-19 on the care continuum of HCV-infected patients. MATERIAL AND METHODS: Two hundred and fifty-six patients who were prescribed a course of DAA therapy at three tertiary medical centers in the US and China between January 1, 2019 to June 30, 2020 were included. We assessed the proportions of patients who completed DAA therapy and had HCV RNA testing during and after the end of therapy. We also assessed the impact of utilization of telemedicine. RESULTS: The proportion of patients undergoing HCV RNA testing during DAA treatment decreased from >81.7% before pandemic to 67.8% during the pandemic (P=0.006), with a more prominent decrease in the US. There were significant decreases in HCV RNA testing >12 (P<0.001) and >20 weeks (P<0.001) post-treatment during COVID-19 era. Compared to pre-COVID period, post-treatment clinic encounters during COVID-19 era decreased significantly in China (Xi'an: 13.6% to 7.4%; Nanjing: 16.7% to 12.5%) but increased in the US (12.5% to 16.7%), mainly due to the use of telemedicine. There was a 4-fold increase in utilization of telemedicine in the US. CONCLUSIONS: COVID-19 pandemic carried profound impact on care for HCV patients in both the US and China. HCV cure rate assessment decreased by half during COVID era but the proportion of patients finishing DAA therapy was not significantly affected. Increased utilization of telemedicine led to increased compliance with DAA therapy but did not encourage patients to have their laboratory assessment for HCV cure.

Pressure, state and response:configurational analysis of antecedents of hotel employees' career prospect perceptions following the COVID-19 pandemic crisis

The unexpected COVID-19 pandemic will reduce the attractiveness of hospitality occupations for a considerable period of time. There is still a lack of research on the combined effects of pressure, state and response with respect to hotel employees ' perceptions of their career prospects as a result of the major public health crisis. This study applied complexity theory and the pressure-state-response (PSR) model to examine the combined and interactive effects of PSR factors on employees' career prospect perceptions by means of fuzzy-set qualitative comparative analysis(fsQCA). Our sample consisted of employees (N=1090) at star-rated hotels in southeast coastal areas of China. A number of conclusions emerged from this study. First, from an analysis of necessary conditions, hotel employees developed low career prospects in the case of high hotel operation losses, high employee job adjustments, and low income levels. Hotel safety incentives and employee safety participation provided the basic conditions for forming high career prospects.In the particular case of COVID-19 prevention and control in China, employee safety compliance and hotel safety control are necessary conditions with respect to perceptions of high or low career prospects. Second, the sufficient conditions analysis for perceptions of low career prospects yielded four configurations. In terms of pressure factors, hotel operation losses and high employee job adjustments were the main causes of negative prospect perceptions;perceived risk and negative emotion further aggravated such perceptions. With respect to state factors, frontline employees with low incomes and low positions had weak adaptability and flexibility, and they were more likely to have perceptions of low career prospects. Even some older employees who had worked in hotels for a long time had such low perceptions. With regard to response factors, the lack of hotel safety incentives and employee safety participation were the main reasons that led to perceptions of low career prospects. Third, the sufficient conditions analysis for perceptions of high career prospects gave rise to five configurations. Compared with frontline employees, senior managers who worked in higher position, had higher incomes, and with long working years had greater adaptability to the impact of COVID-19, and they had perceptions of higher career prospects. Under the same pandemic pressure factors, higher hotel safety incentives and employee safety participation had a positive effect on perceptions of career prospects. In conclusion, the present study offers the following suggestions for management. First, as a result of COVID-19, it is necessary for hotel managers to consider alleviating and adjusting their employees' work stress;they should reduce the impact of pressure factors related to their employees perceptions of career prospects. Second, to achieve hierarchical control of their employees career prospects, hotel managers need to implement differentiated management for different types of employees. Finally, hotels should create a positive atmosphere of safety with respect to preventing and controlling COVID-19 and enhancing the level of risk response of their staff.

Dynamic SARS-CoV-2-specific B-cell and T-cell responses following immunization with an inactivated COVID-19 vaccine.

OBJECTIVE: The dynamic adaptive immune responses elicited by the inactivated virus vaccine CoronaVac remain elusive. METHODS: In a prospective cohort of 100 healthcare professionals naïve for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who received two doses of CoronaVac, we analysed SARS-CoV-2-specific humoral and cellular responses at four different timepoints, including before vaccination (T1), 2 weeks after the first dose (T2), 2 weeks after the booster dose (T3), and 8-10 weeks after the booster dose (T4). SARS-CoV-2-specific antibodies, serum neutralizing activities, peripheral B cells, CD4+ and CD8+ T cells and their memory subsets were simultaneously measured in this cohort. RESULTS: SARS-CoV-2 spike-specific IgG responses reached a peak (geometric mean titre (GMT) 54827, 30969-97065) after two doses and rapidly declined (GMT 502, 212-1190) at T4, whereas suboptimal IgA responses were detected (GMT 5, 2-9). Spike-specific circulating B cells (0.60%, 0.46-0.73% of total B cells) and memory B cells (1.18%, 0.92-1.44% of total memory B cells) were effectively induced at T3 and sustained over time (0.33%, 0.23-0.43%; 0.87%, 0.05-1.67%, respectively). SARS-CoV-2-specific circulating CD4+ T cells (0.57%, 0.47-0.66%) and CD8+ T cells (1.29%, 1.04-1.54%) were detected at T3. At T4, 0.78% (0.43-1.20%) of memory CD4+ T cells and 0.68% (0.29-1.30%) of memory CD8+ T cells were identified as SARS-CoV-2-specific, while 0.62% (0.51-0.75%) of CD4+ T cells and 0.47% (0.38-0.58%) of CD8+ T cells were SARS-CoV-2-specific terminally differentiated effector memory cells. Furthermore, age and interval between doses affected the magnitude of CoronaVac-induced immune responses. SARS-CoV-2 memory CD4+ T cells were strongly associated with both receptor binding domain (RBD)-specific memory B cells (r 0.87, p <0.0001) and SARS-CoV-2-specific memory CD8+ T cells (r 0.48, p <0.0001). CONCLUSIONS: CoronaVac induced robust circulating and memory B cell and T cell responses. Our study offers new insight into the underlying immunobiology of inactivated virus vaccines in humans and may have implications for vaccine strategies in the future.