The Oral Inactivated Porcine Epidemic Diarrhea Virus Presenting in the Intestine Induces Mucosal Immunity in Mice with Alginate–Chitosan Microcapsules

Simple Summary Porcine epidemic diarrhea virus (PEDV) is an α coronavirus that causes major disease outbreaks, producing up to 100% mortality rates in piglets during the first 7 days after birth. In this study, we used microcapsules with inactivated PEDV fed to mice by oral administration to improve the effectiveness of the oral delivery method for protection against PEDV infection, and avoided digestive degradation in the acidic environment of the stomach. In addition, the PEDV microcapsules displayed remarkable storage tolerance to maintain the quality of the PEDV antigen. The PEDV microcapsules delivered the inactivated virus into the gut, stimulating the specific mucosal immune response in mice, which could directly neutralize the enterovirus. Abstract The porcine epidemic diarrhea virus, PEDV, which causes diarrhea, vomiting and death in piglets, causes huge economic losses. Therefore, understanding how to induce mucosal immune responses in piglets is essential in the mechanism and application against PEDV infection with mucosal immunity. A method of treatment in our research was used to make an oral vaccine that packaged the inactive PEDV with microencapsulation, which consisted of sodium alginate and chitosan, and adapted the condition of the gut in mice. The in vitro release experiment of microcapsules showed that inactive PEDV was not only easily released in saline and acid solutions but also had an excellent storage tolerance, and was suitable for use as an oral vaccine. Interestingly, both experimental groups with different doses of inactive virus enhanced the secretion of specific antibodies in the serum and intestinal mucus, which caused the effective neutralization against PEDV in the Vero cell by both IgG and IgA, respectively. Moreover, the microencapsulation could stimulate the differentiation of CD11b+ and CD11c+ dendritic cells, which means that the microencapsulation was also identified as an oral adjuvant to help phagocytosis of dendritic cells in mice. Flow cytometry revealed that the B220+ and CD23+ of the B cells could significantly increase antibody production with the stimulation from the antigens' PEDV groups, and the microencapsulation could also increase the cell viability of B cells, stimulating the secretion of antibodies such as IgG and IgA in mice. In addition, the microencapsulation promoted the expression of anti-inflammatory cytokines, such as IL-10 and TGF-β. Moreover, proinflammatory cytokines, such as IL-1, TNF-α, and IL-17, were inhibited by alginate and chitosan in the microencapsulation groups compared with the inactivated PEDV group. Taken together, our results demonstrate that the microparticle could play the role of mucosal adjuvant, and release inactivated PEDV in the gut, which can effectively stimulate mucosal and systemic immune responses in mice.

An inactivated recombinant rabies virus chimerically expressed RBD induces humoral and cellular immunity against SARS-CoV-2 and RABV.

Many studies suggest that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can infect various animals and transmit among animals, and even to humans, posing a threat to humans and animals. There is an urgent need to develop inexpensive and efficient animal vaccines to prevent and control coronavirus disease 2019 (COVID-19) in animals. Rabies virus (RABV) is another important zoonotic pathogen that infects almost all warm-blooded animals and poses a great public health threat. The present study constructed two recombinant chimeric viruses expressing the S1 and RBD proteins of the SARS-CoV-2 Wuhan01 strain based on a reverse genetic system of the RABV SRV9 strain and evaluated their immunogenicity in mice, cats and dogs. The results showed that both inactivated recombinant viruses induced durable neutralizing antibodies against SARS-CoV-2 and RABV and a strong cellular immune response in mice. Notably, inactivated SRV-nCoV-RBD induced earlier antibody production than SRV-nCoV-S1, which was maintained at high levels for longer periods. Inactivated SRV-nCoV-RBD induced neutralizing antibodies against both SARS-CoV-2 and RABV in cats and dogs, with a relatively broad-spectrum cross-neutralization capability against the SARS-CoV-2 pseudoviruses including Alpha, Beta, Gamma, Delta, and Omicron, showing potential to be used as a safe bivalent vaccine candidate against COVID-19 and rabies in animals.

Efficacy of SARS-CoV-2 vaccines and the dose-response relationship with three major antibodies: a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: The efficacy of SARS-CoV-2 vaccines in preventing severe COVID-19 illness and death is uncertain due to the rarity of data in individual trials. How well the antibody concentrations can predict the efficacy is also uncertain. We aimed to assess the efficacy of these vaccines in preventing SARS-CoV-2 infections of different severities and the dose-response relationship between the antibody concentrations and efficacy. METHODS: We did a systematic review and meta-analysis of randomised controlled trials (RCTs). We searched PubMed, Embase, Scopus, Web of Science, Cochrane Library, WHO, bioRxiv, and medRxiv for papers published between Jan 1, 2020 and Sep 12, 2022. RCTs on the efficacy of SARS-CoV-2 vaccines were eligible. Risk of bias was assessed using the Cochrane tool. A frequentist, random-effects model was used to combine efficacy for common outcomes (ie, symptomatic and asymptomatic infections) and a Bayesian random-effects model was used for rare outcomes (ie, hospital admission, severe infection, and death). Potential sources of heterogeneity were investigated. The dose-response relationships of neutralising, spike-specific IgG and receptor binding domain-specific IgG antibody titres with efficacy in preventing SARS-CoV-2 symptomatic and severe infections were examined by meta-regression. This systematic review is registered with PROSPERO, CRD42021287238. FINDINGS: 28 RCTs (n=286 915 in vaccination groups and n=233 236 in placebo groups; median follow-up 1-6 months after last vaccination) across 32 publications were included in this review. The combined efficacy of full vaccination was 44·5% (95% CI 27·8-57·4) for preventing asymptomatic infections, 76·5% (69·8-81·7) for preventing symptomatic infections, 95·4% (95% credible interval 88·0-98·7) for preventing hospitalisation, 90·8% (85·5-95·1) for preventing severe infection, and 85·8% (68·7-94·6) for preventing death. There was heterogeneity in the efficacy of SARS-CoV-2 vaccines against asymptomatic and symptomatic infections but insufficient evidence to suggest whether the efficacy could differ according to the type of vaccine, age of the vaccinated individual, and between-dose interval (p>0·05 for all). Vaccine efficacy against symptomatic infection waned over time after full vaccination, with an average decrease of 13·6% (95% CI 5·5-22·3; p=0·0007) per month but can be enhanced by a booster. We found a significant non-linear relationship between each type of antibody and efficacy against symptomatic and severe infections (p<0·0001 for all), but there remained considerable heterogeneity in the efficacy, which cannot be explained by antibody concentrations. The risk of bias was low in most studies. INTERPRETATION: The efficacy of SARS-CoV-2 vaccines is higher for preventing severe infection and death than for preventing milder infection. Vaccine efficacy wanes over time but can be enhanced by a booster. Higher antibody titres are associated with higher estimates of efficacy but precise predictions are difficult due to large unexplained heterogeneity. These findings provide an important knowledge base for interpretation and application of future studies on these issues. FUNDING: Shenzhen Science and Technology Programs.

The Oral Inactivated Porcine Epidemic Diarrhea Virus Presenting in the Intestine Induces Mucosal Immunity in Mice with Alginate-Chitosan Microcapsules.

The porcine epidemic diarrhea virus, PEDV, which causes diarrhea, vomiting and death in piglets, causes huge economic losses. Therefore, understanding how to induce mucosal immune responses in piglets is essential in the mechanism and application against PEDV infection with mucosal immunity. A method of treatment in our research was used to make an oral vaccine that packaged the inactive PEDV with microencapsulation, which consisted of sodium alginate and chitosan, and adapted the condition of the gut in mice. The in vitro release experiment of microcapsules showed that inactive PEDV was not only easily released in saline and acid solutions but also had an excellent storage tolerance, and was suitable for use as an oral vaccine. Interestingly, both experimental groups with different doses of inactive virus enhanced the secretion of specific antibodies in the serum and intestinal mucus, which caused the effective neutralization against PEDV in the Vero cell by both IgG and IgA, respectively. Moreover, the microencapsulation could stimulate the differentiation of CD11b+ and CD11c+ dendritic cells, which means that the microencapsulation was also identified as an oral adjuvant to help phagocytosis of dendritic cells in mice. Flow cytometry revealed that the B220+ and CD23+ of the B cells could significantly increase antibody production with the stimulation from the antigens' PEDV groups, and the microencapsulation could also increase the cell viability of B cells, stimulating the secretion of antibodies such as IgG and IgA in mice. In addition, the microencapsulation promoted the expression of anti-inflammatory cytokines, such as IL-10 and TGF-ß. Moreover, proinflammatory cytokines, such as IL-1, TNF-α, and IL-17, were inhibited by alginate and chitosan in the microencapsulation groups compared with the inactivated PEDV group. Taken together, our results demonstrate that the microparticle could play the role of mucosal adjuvant, and release inactivated PEDV in the gut, which can effectively stimulate mucosal and systemic immune responses in mice.

Hospital Strain and COVID-19 Fatality - England, April 2020-March 2022.

What is already known about this topic?: During the coronavirus disease 2019 (COVID-19) pandemic, tremendous efforts have been made in countries to suppress epidemic peaks and strengthen hospital services to avoid hospital strain and ultimately reduce the risk of death from COVID-19. However, there is limited empirical evidence that hospital strain increases COVID-19 deaths. What is added by this report?: We found the risk of death from COVID-19 was linearly associated with the number of patients currently in hospitals, a measure of hospital strain, before the Omicron period. This risk could be increased by a maximum of 188.0%. What are the implications for public health practice?: These findings suggest that any (additional) effort to reduce hospital strain would be beneficial during early large COVID-19 outbreaks and possibly also others alike. During an Omicron outbreak, vigilance remains necessary to prevent excess deaths caused by hospital strain as happened in Hong Kong Special Administrative Region, China.

The difference of primary school teachers' online teaching satisfaction in subject and educational level.

The growth of online education requires high-quality online teaching. Teachers' satisfaction with online teaching is of great significance for improving online teaching effectiveness. This study was to explore the primary school teachers' online teaching satisfaction during the spread of COVID-19 from Shanghai, who have experienced online teaching, and explore whether there were differences of teachers' online teaching satisfaction in subject and educational level. 939 teachers from Shanghai participated in the study. The non-parametric Mann-Whitney U test and Kruskal-Wallis test of variance were performed. Results showed that teachers' online teaching satisfaction was at a high level. Moreover, there was a significant difference in teachers' subject and educational level on online teaching satisfaction. In terms of subject differences of teachers, there were significant differences in resource suitability (RS) among teachers of different subjects. Therefore, it is recommended that each subject should develop the online teaching resources to support teachers' online teaching. In terms of the differences in teachers' educational levels, there were no significant differences between the satisfaction of college-level teachers on non-technical variables such as content selectivity (CS) and teachers with undergraduate and graduate degrees, and only on technical variables such as self-efficacy (SE), resource suitability (RS), ease of use (EU), and intention to use (IU). Given the national context in China, the difference in educational levels may be more reflected in the age of the teachers. For teachers with college educational level, due to their older age, rather than simply enhancing motivation and improving learning ability to increase online teaching satisfaction, emphasis should be placed on providing appropriate teaching service support to help improve online teaching effectiveness. The findings provide new empirical evidence, strategies and Chinese experience for promoting teachers' online teaching satisfaction.

Establishment and application of ERA-LFD method for rapid detection of feline calicivirus.

Feline calicivirus (FCV) has a single-stranded, positive-sense RNA genome, and it is responsible for many infectious respiratory diseases in cats. In addition, more worryingly, highly virulent strains of FCV can cause high mortality in felines. Therefore, a rapid and reliable diagnosis tool plays an important role in controlling the outbreak of FCV. In this study, enzymatic recombinase amplification (ERA) assay combined with lateral flow dipstick (LFD) was developed for the detection of FCV, targeting a relatively conversed position of FCV-ORF1. The results showed that the optimal reaction condition was at 40 °C for 30 min. ERA-LFD method was highly sensitive with the detection limit as low as 3.2 TCID50 of FCV RNA per reaction. The specificity analysis demonstrated no cross-reactivity with feline parvovirus (FPV), feline herpesvirus (FHV) and feline infectious peritonitis virus (FIPV). ERA-LFD was highly repeatable and reproducible, with the intra-assay and inter-assay coefficients of variation for this method both less than 7%. The general test showed that all the recombinant plasmids with known mutant sites and FCV strains with different mutant sites stored in our laboratory were all detected by this method. Of the 23 samples, 14 samples were tested positive for FCV by ERA-LFD and RT-qPCR, respectively. In summary, ERA-LFD assay was a fast, accurate and convenient diagnosis tool for the detection of FCV. KEY POINTS: • The detection principle of ERA-LFD was introduced. • Almost all the currently known FCV strains can be detected. • ERA-LFD is easy to operate and can be used for field detection.

Characteristics and Containment of 74 Imported COVID-19 Outbreaks: Experiences, Lessons, and Implications - China, 2020-2021.

What is already known about this topic?: After the initial coronavirus disease 2019 (COVID-19) outbreak in Wuhan, China, the outbreaks during the dynamic-zero policy period in the mainland of China have not been systematically documented. What is added by this report?: We summarized the characteristics of 74 imported COVID-19 outbreaks between March 19, 2020 and December 31, 2021. All outbreaks of early severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants were successfully contained with the aid of nucleic acid testing, modern communication technologies, and non-pharmacological interventions. What are the implications for public health practice?: These findings provide us with confidence for the containment of future emerging infectious diseases alike at early stages to prevent pandemics or to win time to gain experience, develop vaccines and drugs, vaccinate people, and wait for the possible lessening of the virus' pathogenicity.

Prevalence of Post-traumatic Stress Disorder Status Among Healthcare Workers and Its Impact on Their Mental Health During the Crisis of COVID-19: A Cross-Sectional Study.

Objective: After the unprecedented coronavirus disease 2019 (COVID-19) outbreak, the health status of the general population has suffered a huge threat, and the mental health of front-line healthcare providers has also encountered great challenges. Therefore, this study aims to: (1) investigate the prevalence and influencing factors of post-traumatic stress disorder (PTSD) among healthcare providers, and (2) verify the moderating role of self-efficacy in the influence of PTSD on mental health. Methods: A cross-sectional study was conducted using an online survey of 1993 participants. The presence of depression, anxiety, self-efficacy, and PTSD was evaluated using screening tests from March 1. Sociodemographic and COVID-19-related data were also collected. A data analysis was performed using descriptive statistics, Pearson's correlation coefficient, and multiple linear regression. Results: The prevalence of PTSD among healthcare providers was 9.3%. PTSD was negatively correlated with self-efficacy (r = -0.265, P < 0.01), anxiety (r = -0.453, P < 0.01), and depression (r = 0.708, P < 0.01). Profession, daily working hours, maximum continuous working days, and daily sleep time were influencing factors of PTSD. A binary logistic regression analysis showed that physicians (OR = 2.254, 95% CI = 1.298, 3.914) and nurses (OR = 2.176, 95% CI = 1.337, 3.541) were more likely to experience PTSD than other healthcare providers. Conclusion: Self-efficacy has a moderating effect on the influence of PTSD on anxiety and depression. This suggests that health managers need to respond to the current psychological crisis of healthcare providers, implement appropriate psychological interventions, and minimize the psychological harm caused by COVID-19.

Decreased influenza vaccination coverage among Chinese healthcare workers during the COVID-19 pandemic.

BACKGROUND: Healthcare workers (HCWs) were the priority group for influenza vaccination, in China during the 2020/2021 and 2021/2022 influenza seasons. However, vaccination rates in HCWs have always been low. This study investigated influenza vaccination status among Chinese HCWs and analyzed the factors driving vaccination. METHODS: We provided electronic questionnaires to HCWs from January 27, 2022 to February 21, 2022, using the WeChat platform "Breath Circles". HCWs who received the link could also forward it to their colleagues. Binary logistic regression models were used to analyze vaccination-associated factors among HCWs. RESULTS: Among the 1697 HCWs surveyed, vaccination coverage was 43.7% (741/1697) during the 2020/2021 influenza season, and 35.4% (600/1697) during the 2021/2022 influenza season, as of February 21, 2022. Additionally, 22.7% (385/1697) and 22.1% (358/1697) of HCWs reported that their workplaces implemented a free vaccination policy for all employees during the 2020/2021 and 2021/2022 influenza seasons. HCWs who were required to be vaccinated according to hospital regulations, and whose hospitals implemented the free influenza vaccine policy were more likely to be vaccinated (2020/2021 and 2021/2022; P < 0.05). In addition, the economic level of the HCWs' province (2021/2022, P < 0.05) and the HCWs' knowledge about vaccination and willingness to get vaccinated, such as active learning about vaccines (2020/2021, P < 0.05), supportive attitude toward vaccination for all HCWs (2020/2021 and 2021/2022; P < 0.05), also had an impact on vaccine coverage. CONCLUSIONS: A free influenza vaccination policy and workplace required vaccination are effective in improving influenza vaccination coverage among HCWs. Influenza vaccination coverage of Chinese HCWs remained low and showed a downward trend after the COVID-19 outbreak. Further effective measures, such as advocacy campaigns, free vaccine policies, and on-site vaccination could be implemented to improve influenza vaccination coverage.

Release of microplastics and nanoplastics in water from disposable surgical masks after disinfection.

During the COVID-19 pandemic, disposable surgical masks were generally disinfected and reused due to mask shortages. Herein, the role of disinfected masks as a source of microplastics (MPs) and nanoplastics (NPs) was investigated. The amount of MPs and NPs released from masks disinfected by UV ranged from 1054 ± 106 to 2472 ± 70 and from 2.55 ± 0.22 × 109 to 6.72 ± 0.27 × 109 particles/piece, respectively, comparable to that of the undisinfected masks, and the MPs were changed to small-sized particles. The amount of MPs and NPs released after alcohol and steam treatment were respectively lower and higher than those from undisinfected masks, and MPs were shifted to small-sized particles. The amount of MPs and NPs released in water after autoclaving was lower than for undisinfected masks. In all, the amount of fibers released after disinfection decreased greatly, and certain disinfection processes were found to increase the amount of small-sized NPs released from masks into aqueous environments.

Economic burden of healthcare-associated infection due to carbapenem-resistant gram-negative bacilli in a tertiary general hospital of Qinghai Province

OBJECTIVE: To explore the prevalence of carbapenem-resistant gram-negative bacilli(CRO) infection and the economic burden in a tertiary general hospital of Qinghai province. METHODS: The clinical data, length of hospital stay and costs of hospitalization were retrospectively collected from the patients with Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa hospital-acquired infection who were hospitalized in Qinghai Provincial Hospital from Jan 2017 to Dec 2017. The patients were divided into the drug-resistant group and the non drug-resistant group according to the result of drug susceptibility testing. The length of hospital stay and hospitalization cost were compared between the two groups of patients. RESULTS: A total of 521 patients were involved in the study, 120 of who had CRO infection(the drug-resistant group), and 40 had carbapenem-sensitive organisms infection(the non drug-resistant group). The median length of hospital stay of the drug-resistant group was 19 days, the median total hospitalization cost was 31 292 yuan;the median length of hospital stay of the non drug-resistant group was 15 days, the median total hospitalization cost was 22 610 yuan, and there were significant differences between the two groups(P<0.05). Stratified analysis showed that the median length of hospital stay of the patients with carbapenem-resistant K.pneumoniae infection was 17 days, the medial total hospitalization cost 25 227 yuan, the length of hospital stay of the non drug-resistant group was 14 day, the median total hospitalization cost 20 326 yuan;the median lengths of hospital stay of the patients with respiratory tract infection and the patients with bloodstream infection were respectively 19 days and 30 days in the drug-resistant group, the median total hospitalization costs were respectively 30 315 yuan and 30 050 yuan;the median lengths of hospital stay of the patients with respiratory tract infection and the patients with bloodstream infection were respectively 15 days and 13 days in the non drug-resistant group, the median total hospitalization costs were respectively 21 562 yuan and 24 853 yuan, and there were significant differences(P<0.05). CONCLUSION: The hospital-acquired CRO infection may lead to the increase of length of hospital stay and hospitalization cost of the hospitalized patients as well as the economic burden. It is necessary to take effective measures to reduce the incidence of hospital-acquired CRO infection.

Prevalence of Post-traumatic Stress Disorder Status Among Healthcare Workers and Its Impact on Their Mental Health During the Crisis of COVID-19: A Cross-Sectional Study

Objective After the unprecedented coronavirus disease 2019 (COVID-19) outbreak, the health status of the general population has suffered a huge threat, and the mental health of front-line healthcare providers has also encountered great challenges. Therefore, this study aims to: (1) investigate the prevalence and influencing factors of post-traumatic stress disorder (PTSD) among healthcare providers, and (2) verify the moderating role of self-efficacy in the influence of PTSD on mental health. Methods A cross-sectional study was conducted using an online survey of 1993 participants. The presence of depression, anxiety, self-efficacy, and PTSD was evaluated using screening tests from March 1. Sociodemographic and COVID-19-related data were also collected. A data analysis was performed using descriptive statistics, Pearson's correlation coefficient, and multiple linear regression. Results The prevalence of PTSD among healthcare providers was 9.3%. PTSD was negatively correlated with self-efficacy (r = −0.265, P < 0.01), anxiety (r = −0.453, P < 0.01), and depression (r = 0.708, P < 0.01). Profession, daily working hours, maximum continuous working days, and daily sleep time were influencing factors of PTSD. A binary logistic regression analysis showed that physicians (OR = 2.254, 95% CI = 1.298, 3.914) and nurses (OR = 2.176, 95% CI = 1.337, 3.541) were more likely to experience PTSD than other healthcare providers. Conclusion Self-efficacy has a moderating effect on the influence of PTSD on anxiety and depression. This suggests that health managers need to respond to the current psychological crisis of healthcare providers, implement appropriate psychological interventions, and minimize the psychological harm caused by COVID-19.

Identifying Japanese Encephalitis Virus Using Metatranscriptomic Sequencing, Xinjiang, China.

The treat of infectious disease epidemics has increased the critical need for continuous broad-ranging surveillance of pathogens with outbreak potential. Using metatranscriptomic sequencing of blood samples, we identified several cases of Japanese encephalitis virus infection from Xinjiang Uyghur Autonomous Region, China. This discovery highlights the risk for known viral diseases even in nonendemic areas.

Impact of air temperature and containment measures on mitigating the intrahousehold transmission of SARS-CoV-2: a data-based modelling analysis.

OBJECTIVES: Air temperature has been considered a modifiable and contributable variable in COVID-19 transmission. Implementation of non-pharmaceutical interventions (NPIs) has also made an impact on COVID-19 transmission, changing the transmission pattern to intrahousehold transmission under stringent containment measures. Therefore, it is necessary to re-estimate the influence of air temperature on COVID-19 transmission while excluding the influence of NPIs. DESIGN, SETTING AND PARTICIPANTS: This study is a data-based comprehensive modelling analysis. A stochastic epidemiological model, the ScEIQR model (contactable susceptible-exposed-infected-quarantined-removed), was established to evaluate the influence of air temperature and containment measures on the intrahousehold spread of COVID-19. Epidemic data on COVID-19, including daily confirmed cases, number of close contacts, etc, were collected from the National Health Commission of China. OUTCOME MEASURES: The model was fitted using the Metropolis-Hastings algorithm with a cost function based on the least squares method. The LOESS (locally weighted scatterplot smoothing) regression function was used to assess the relationship between air temperature and rate of COVID-19 transmission within the ScEIQR model. RESULTS: The ScEIQR model indicated that the optimal temperature for spread of COVID-19 peaked at 10℃ (50℉), ranging from 5℃ to 14℃ (41℉-57.2℉). In the fitted model, the fitted intrahousehold transmission rate (ß') of COVID-19 was 10.22 (IQR 8.47-12.35) across mainland China. The association between air temperature and ß' of COVID-19 suggests that COVID-19 might be seasonal. Our model also validated the effectiveness of NPIs, demonstrating that diminishing contactable susceptibility (Sc) and avoiding delay in diagnosis and hospitalisation (η) were more effective than contact tracing (κ and ρ). CONCLUSIONS: We constructed a novel epidemic model to estimate the effect of air temperature on COVID-19 transmission beyond implementation of NPIs, which can inform public health strategy and predict the transmission of COVID-19.

Evaluation of Clinical and Immune Responses in Recovered Children with Mild COVID-19.

The coronavirus disease 2019 (COVID-19) has spread globally and variants continue to emerge, with children are accounting for a growing share of COVID-19 cases. However, the establishment of immune memory and the long-term health consequences in asymptomatic or mildly symptomatic children after severe acute respiratory syndrome coronavirus 2 infection are not fully understood. We collected clinical data and whole blood samples from discharged children for 6-8 months after symptom onset among 0-to-14-year-old children. Representative inflammation signs returned to normal in all age ranges. The infants and young children (0-4 years old) had lung lesions that persisted for 6-8 months and were less responsive for antigen-specific IgG secretion. In the 5-to-14-year-old group, lung imaging abnormalities gradually recovered, and the IgG-specific antibody response was strongest. In addition, we found a robust IgM+ memory B cell response in all age. Memory T cells specific for the spike or nucleocapsid protein were generated, with no significant difference in IFN-γ response among all ages. Our study highlights that although lung lesions caused by COVID-19 can last for at least 6-8 months in infants and young children, most children have detectable residual neutralizing antibodies and specific cellular immune responses at this stage.

Suppression and Activation of Intracellular Immune Response in Initial Severe Acute Respiratory Syndrome Coronavirus 2 Infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently the most important emerging pathogen worldwide, but its early transcriptional dynamics and host immune response remain unclear. Herein, the expression profiles of viral interactions with different types of hosts were comprehensively dissected to shed light on the early infection strategy of SARS-CoV-2 and the host immune response against infection. SARS-CoV-2 was found to exhibit a two-stage transcriptional strategy within the first 24 h of infection, comprising a lag phase that ends with the virus being paused and a log phase that starts when the viral load increases rapidly. Interestingly, the host innate immune response was found not to be activated (latent period) until the virus entered the log stage. Noteworthy, when intracellular immunity is suppressed, SARS-CoV-2 shows a correlation with dysregulation of metal ion homeostasis. Herein, the inhibitory activity of copper ions against SARS-CoV-2 was further validated in in vitro experiments. Coronavirus disease 2019-related genes (including CD38, PTX3, and TCN1) were also identified, which may serve as candidate host-restricted factors for interventional therapy. Collectively, these results confirm that the two-stage strategy of SARS-CoV-2 effectively aids its survival in early infection by regulating the host intracellular immunity, highlighting the key role of interferon in viral infection and potential therapeutic candidates for further investigations on antiviral strategies.