Integrated histopathology, spatial and single cell transcriptomics resolve cellular drivers of early and late alveolar damage in COVID-19 (preprint)

The most common cause of death due to COVID-19 remains respiratory failure. Yet, our understanding of the precise cellular and molecular changes underlying lung alveolar damage is limited. Here, we integrate single cell transcriptomic data of COVID-19 donor lungs with spatial transcriptomic data stratifying histopathological stages of diffuse alveolar damage (DAD). We identify changes in cellular composition across progressive DAD, including waves of molecularly distinct macrophages and depleted epithelial and endothelial populations throughout different types of tissue damage. Predicted markers of pathological states identify immunoregulatory signatures, including IFN-alpha and metallothionein signatures in early DAD, and fibrosis-related collagens in organised DAD. Furthermore, we predict a fibrinolytic shutdown via endothelial upregulation of SERPINE1/PAI-1. Cell-cell interaction analysis revealed macrophage-derived SPP1/osteopontin signalling as a key regulator during early DAD. These results provide the first comprehensive, spatially resolved atlas of DAD stages, highlighting the cellular mechanisms underlying pro-inflammatory and pro-fibrotic pathways across alveolar damage progression.

COVID-19 breakthrough infection after four doses of the vaccines: a case report

The COVID-19 vaccines provide a high degree of protection against severe disease, hospitalisation, and death. However, no vaccine claimed 100% effectiveness and it is expected that a small proportion of vaccinated individuals may develop a breakthrough infection due to individual differences, virus variants and other factors. We conducted an epidemiological investigation and analysis of an imported case who had finished four doses of vaccination, and in order to provide a relevant reference for regular epidemic prevention and control in the post-pandemic era.

Characteristics and containment of the outbreak caused by the SARS-CoV-2 Omicron variants in Shanghai, China: a retrospective study

Objective: The study aimed to describe the characteristics and containment of the Omicron variants in Shanghai compared with the previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants in China. Methods: We summarized the data retrieved from the Shanghai Municipal Health Commission from January to June 2022 and the National Health Commission of the People's Republic of China from March 2020 to August 2021. Epidemiological analysis was utilized to describe the differences among SARS-CoV-2 variants and the infection situation in the outbreaks in China. Results: The Omicron variants had the characteristics of high insidiousness, rapid transmission, high infectivity, and short incubation period, which were consistent with the characteristics of outbreaks caused by Omicron in other regions in China and abroad. There were 568978 asymptomatic infections in Shanghai from Feburary 26 to June 30, 2022, accounting for 90.73% of the SARS-CoV-2 infections in this outbreak wave. It's significantly different from a total of 23277 SARS-CoV-2 infections in China between March 31, 2020 and August 8, 2021, of which 41.97% of the cases were asymptomatic infections. Conclusions: Compared with previous outbreaks emerged in China, the Omicron outbreak in Shanghai was characterized by multiple point dissemination, wide coverage, a large number of close contacts of confirmed infections and asymptomatic carriers, and difficult source tracing. The lessons from Shanghai's response to Omicron showed that the dynamic zero-COVID policy is still the most suitable response to the virus which can quickly find the infections and curb the transmission route.

Moderating Role of Peer Pressure and Positive Learning Environment Between Career Calling and Academic Procrastination in Chinese Medical Students During Controlled COVID-19 Pandemic: A Cross-Sectional Study.

Purpose: The COVID-19 pandemic sets specific circumstances that may accelerate academic procrastination behavior of medical students. Career calling is a protective factor that fights against academic procrastination and may further improve medical students' mental health and academic achievement. This study aims to determine the status of Chinese medical students' academic procrastination during controlled COVID-19 pandemic. Moreover, the study investigates the relationships and mechanisms among career calling, peer pressure, a positive learning environment, and academic procrastination. Patients and Methods: Data were collected from several Chinese medical universities through an anonymous cross-sectional survey of 3614 respondents (effective response rate = 60.0%). Using online questionnaires to collect the data and IBM SPSS Statistics 22.0 for statistical analysis. Results: The average score of academic procrastination of Chinese medical students was 2.62±0.86. This study proved the usage of peer pressure and positive learning environment as moderating roles of relationship between career calling and academic procrastination. Career calling was negatively correlated with academic procrastination (r = -0.232, p < 0.01), while it was positively correlated with peer pressure (r = 0.390, p < 0.01) and a positive learning environment (r = 0.339, p < 0.01). Moreover, academic procrastination was negatively correlated with peer pressure (r = -0.279, p < 0.01) and a positive learning environment (r = -0.242, p < 0.01). Peer pressure was positively correlated with a positive learning environment (r = 0.637, p < 0.01). Conclusion: The findings emphasize the importance of constructive peer pressure and a positive learning environment that discourages academic procrastination. Educators should highlight medical career calling education by offering related courses to fight against academic procrastination.

Sleep quality was associated with adverse reactions after coronavirus disease 2019 vaccination among healthcare workers: A longitudinal paired study.

Background: Many countries have currently relied on various types of vaccines for the public to control the coronavirus disease 2019 (COVID-19) pandemic. The adverse reactions (ARs) after vaccination may affect vaccination coverage and confidence. However, whether sleep quality was associated with ARs after vaccination remains unclear. Methods: We designed a longitudinal paired study within a hospital setting. We collected data about the side effects within 7 days after two doses of scheduled vaccination among healthcare workers (HCWs). All HCWs were asked to complete a sleep survey indexed by the Pittsburgh Sleep Quality Index (PSQI) before vaccination and after a 1-month follow-up. Then, we explored the relationship between sleep quality before or after vaccination and the occurrence of ARs. Results: A total of 345 HCWs were recruited to receive COVID-19 vaccination. The sleep quality became worse after vaccination. All local and systemic reactions were mild or moderate in severity (32.46%), and no serious adverse event was reported. Binary logistic regression showed participants with poor sleep quality (PSQI > 5) than good sleep quality (PSQI ≤ 5) before the two doses of vaccination, respectively, exhibited 1.515 and 1.107 times risk of ARs after each vaccination (both p < 0.001). Conclusion: There is an apparently complex bidirectional relationship between sleep quality and COVID-19 vaccination adverse effects. Poor sleep quality significantly increases the risk of mild ARs after vaccination, while vaccination may cause a temporary decline in sleep quality.

A persistent neutrophil-associated immune signature characterizes post-COVID-19 pulmonary sequelae.

Interstitial lung disease and associated fibrosis occur in a proportion of individuals who have recovered from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection through unknown mechanisms. We studied individuals with severe coronavirus disease 2019 (COVID-19) after recovery from acute illness. Individuals with evidence of interstitial lung changes at 3 to 6 months after recovery had an up-regulated neutrophil-associated immune signature including increased chemokines, proteases, and markers of neutrophil extracellular traps that were detectable in the blood. Similar pathways were enriched in the upper airway with a concomitant increase in antiviral type I interferon signaling. Interaction analysis of the peripheral phosphoproteome identified enriched kinases critical for neutrophil inflammatory pathways. Evaluation of these individuals at 12 months after recovery indicated that a subset of the individuals had not yet achieved full normalization of radiological and functional changes. These data provide insight into mechanisms driving development of pulmonary sequelae during and after COVID-19 and provide a rational basis for development of targeted approaches to prevent long-term complications.

Epidemiological and virological surveillance of influenza viruses in China during 2020-2021.

BACKGROUND: During the coronavirus disease 2019 (COVID-19) pandemic, seasonal influenza activity declined globally and remained below previous seasonal levels, but intensified in China since 2021. Preventive measures to COVID-19 accompanied by different epidemic characteristics of influenza in different regions of the world. To better respond to influenza outbreaks under the COVID-19 pandemic, we analyzed the epidemiology, antigenic and genetic characteristics, and antiviral susceptibility of influenza viruses in the mainland of China during 2020-2021. METHODS: Respiratory specimens from influenza like illness cases were collected by sentinel hospitals and sent to network laboratories in Chinese National Influenza Surveillance Network. Antigenic mutation analysis of influenza virus isolates was performed by hemagglutination inhibition assay. Next-generation sequencing was used for genetic analyses. We also conducted molecular characterization and phylogenetic analysis of circulating influenza viruses. Viruses were tested for resistance to antiviral medications using phenotypic and/or sequence-based methods. RESULTS: In the mainland of China, influenza activity recovered in 2021 compared with that in 2020 and intensified during the traditional influenza winter season, but it did not exceed the peak in previous years. Almost all viruses isolated during the study period were of the B/Victoria lineage and were characterized by genetic diversity, with the subgroup 1A.3a.2 viruses currently predominated. 37.8% viruses tested were antigenically similar to reference viruses representing the components of the vaccine for the 2020-2021 and 2021-2022 Northern Hemisphere influenza seasons. In addition, China has a unique subgroup of 1A.3a.1 viruses. All viruses tested were sensitive to neuraminidase inhibitors and endonuclease inhibitors, except two B/Victoria lineage viruses identified to have reduced sensitivity to neuraminidase inhibitors. CONCLUSIONS: Influenza activity increased in the mainland of China in 2021, and caused flu season in the winter of 2021-2022. Although the diversity of influenza (sub)type decreases, B/Victoria lineage viruses show increased genetic and antigenic diversity. The world needs to be fully prepared for the co-epidemic of influenza and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus globally.

A proposed artificial intelligence workflow to address application challenges leveraged on algorithm uncertainty.

Artificial Intelligence (AI) has achieved state-of-the-art performance in medical imaging. However, most algorithms focused exclusively on improving the accuracy of classification while neglecting the major challenges in a real-world application. The opacity of algorithms prevents users from knowing when the algorithms might fail. And the natural gap between training datasets and the in-reality data may lead to unexpected AI system malfunction. Knowing the underlying uncertainty is essential for improving system reliability. Therefore, we developed a COVID-19 AI system, utilizing a Bayesian neural network to calculate uncertainties in classification and reliability intervals of datasets. Validated with four multi-region datasets simulating different scenarios, our approach was proved to be effective to suggest the system failing possibility and give the decision power to human experts in time. Leveraging on the complementary strengths of AI and health professionals, our present method has the potential to improve the practicability of AI systems in clinical application.

A persistent neutrophil-associated immune signature characterises post-COVID19 pulmonary sequelae (preprint)

Persistent interstitial lung changes with associated symptoms occur in a proportion of individuals that have recovered from severe acute respiratory syndrome coronavirus-2 (SARS-COV-2) infection through unknown mechanisms. We studied individuals with severe COVID-19 longitudinally following recovery from acute illness. Subjects with interstitial lung changes at 3-6 months post-recovery had an upregulated neutrophil-associated immune signature including increased chemokines, proteases and markers of neutrophil extracellular traps detectable systemically. Similar pathways were enriched in the upper airway with a concomitant augmentation of antiviral type-I interferon signalling. Interaction analysis of the peripheral phosphoproteome identified enriched kinases critical for neutrophil inflammatory pathways. Repeat sampling indicated that full normalisation of radiological and functional changes has not yet been reached in many individuals by 12 months post-recovery. These data provide functional insight into mechanisms driving pulmonary sequelae of COVID-19 and provide a rational basis for development of future targeted approaches to prevent long-term complications.

Epidemiological and Virological Surveillance of Seasonal Influenza Viruses - China, 2020-2021.

INTRODUCTION: During the coronavirus disease 2019 (COVID-19) pandemic, the circulation of seasonal influenza virus declined globally and remained below previous seasonal levels. We analyzed the results of the epidemiology, antigenic, and genetic characteristics, and antiviral susceptibilities of seasonal influenza viruses isolated from the mainland of China during October 5, 2020 through September 5, 2021, to better assess the risk of influenza during subsequent influenza season in 2021-2022. METHODS: Positive rates of influenza virus detection during this period were based on real-time polymerase chain reaction (PCR) detection by the Chinese National Influenza Surveillance Network laboratories, and isolated viruses from influenza positive samples were submitted to the Chinese National Influenza Center. Antigenic analyses for influenza viruses were conducted using the hemagglutination inhibition assay. Next-generation sequencing was used for genetic analyses. Viruses were tested for resistance to antiviral medications using a phenotypic assay and next-generation sequencing. RESULTS: In southern China, the influenza positivity rate was elevated especially after March 2021 and was higher than the same period the previous year with the COVID-19 pandemic. In northern China, influenza positive rate peaked at Week 18 in 2021 and has declined since then. Nearly all isolated viruses were B/Victoria lineage viruses during the study period, and 37.3% of these viruses are antigenically similar to the reference viruses representing the vaccine components for the 2020-2021 and 2021-2022 Northern Hemisphere influenza season. All seasonal influenza viruses were susceptible to neuraminidase inhibitors and endonuclease inhibitors. CONCLUSIONS: Influenza activity has gradually increased in the mainland of China in 2021, although the intensity of activity is still lower than before the COVID-19 pandemic. The diversity of circulating influenza types/subtypes decreased, with the vast majority being B/Victoria lineage viruses. The surveillance data from this study suggest that we should strengthen influenza surveillance during the upcoming traditional influenza season. It also provided evidence for vaccine recommendations and prevention and control of influenza and clinical use of antiviral drugs.

Malaria Surveillance of Entry People During the COVID-19 Epidemic - Guangdong Province, China, October 2020-May 2021.

WHAT IS ALREADY KNOWN ABOUT THIS TOPIC?: Malaria control was affected by the coronavirus disease 2019 (COVID-19) pandemic. This study conducted active case finding for key flights and key populations to determine malaria transmission. WHAT IS ADDED BY THIS REPORT?: Surveillance for malaria was conducted for entry personnel coming from areas affected by malaria. It is estimated that at least 100,000 tests were conducted in Guangdong Province; 154 cases were confirmed during the surveillance. WHAT ARE THE IMPLICATIONS FOR PUBLIC HEALTH PRACTICE?: To maintain the malaria elimination status, comprehensively maintaining a sensitive and effective surveillance response system is especially important.

Effectiveness of inactivated SARS-CoV-2 vaccines against the Delta variant infection in Guangzhou: a test-negative case-control real-world study.

The effectiveness of inactivated SARS-CoV-2 vaccines against the Delta variant, which has been associated with greater transmissibility and virulence, remains unclear. We conducted a test-negative case-control study to explore the vaccine effectiveness (VE) in real-world settings. We recruited participants aged 18-59 years who consisted of SARS-CoV-2 test-positive cases (n = 74) and test-negative controls (n = 292) during the outbreak of the Delta variant in May 2021 in Guangzhou city, China. Vaccination status was compared to estimate The VE of SARS-CoV-2 inactivated vaccines. A single dose of inactivated SARS-CoV-2 vaccine yielded the VE of only 13.8%. After adjusting for age and sex, the overall VE for two-dose vaccination was 59.0% (95% confidence interval: 16.0% to 81.6%) against coronavirus disease 2019 (COVID-19) and 70.2% (95% confidence interval: 29.6-89.3%) against moderate COVID-19 and 100% against severe COVID-19 which might be overestimated due to the small sample size. The VE of two-dose vaccination against COVID-19 reached 72.5% among participants aged 40-59 years, and was higher in females than in males against COVID-19 and moderate diseases. While single dose vaccination was not sufficiently protective, the two-dose dosing scheme of the inactivated vaccines was effective against the Delta variant infection in real-world settings, with the estimated efficacy exceeding the World Health Organization minimal threshold of 50%.

Deployment of workforce in global health: what should be the priorities for China?

BACKGROUND: China has increasingly emerged as an important player in global health. However, compared to developed countries, China still lacks a sufficient health workforce for global health engagement with the necessary competencies required. The world has recognized that to solve global health issues, the role of China needs to be strengthened. The priorities for the deployment of the Chinese workforce in global health remain unclear. This study aims to identify the priorities of the deployment of Chinese global health workforce by exploring the core competencies for Chinese global health workforce, factors influencing the deployment and the approach of deployment. METHODS: Quantitative descriptive statistical analysis was applied to analyze the quantitative data. A total of 148 key respondents from 10 provinces in China conducting global health projects over the last 3 years were selected as the study subjects. A structured questionnaire was developed to collect the data on four aspects, including general information, core competencies, factors influencing deployment, and mode of deployment. The questionnaire was distributed to the respondents through an online survey. All original data were exported to Microsoft Excel 2010 to calculate the frequencies and percentages of each option. A descriptive analysis was carried out of the priorities of deployment of the Chinese global health workforce. RESULTS: More than half of the respondents (51.4%, 76/148) regarded "communication" as the most important competency of the Chinese global health workforce, while a large proportion of participants from Chinese embassies (50.0%, 6/12) and international organizations (75.0%, 12/16) believed that "professional skills" were paramount. In addition, 58.1% (86/148) of the participants agreed that incentive factors (salary, professional position, etc.) were the main factors that influenced deployment, whereas 75% (12/16) of participants from international organizations emphasized "security" as the most important determinant. In addition, 60.8% (90/148) of the participants thought that the deployment of staff should be based on the needs of the global health project implementation. CONCLUSIONS: This study highlights the deployment priorities of the Chinese global health workforce, including strengthening communication and professional skills, focusing on personal security and incentives, and catering to the project implementation. This study also highlights the importance of Chinese agencies in developing global health mindsets through global health practices and proactive integration within the global community.

A COVID-19 Outbreak Emerging in a Food Processing Company - Harbin City, Heilongjiang Province, China, January-February 2021.

What is already known about this topic? The coronavirus disease 2019 (COVID-19) epidemic in China had been effectively controlled for several months, but as the ambient temperature dropped, large gathering-initiated epidemics occurred in northern China, including Hebei, Liaoning, and Jilin provinces. What is added by this report? A sudden epidemic emerged in Wangkui County, Suihua City, Heilongjiang Province, on January 9, 2021. An asymptomatically-infected resident of Harbin City returned from Suihua and triggered a large-scale outbreak in the Zhengda Food Processing Company in Harbin, Heilongjiang. The epidemic was associated with widespread community transmission inside and outside the company, eventually leading to 260 persons being infected (87.8% of 296 patients in Harbin). What are the implications for public health practice? This study demonstrates the importance of screening for infections in the COVID-19 prevention and control system, shares experiences identifying and managing asymptomatic infections, and recommends food processing enterprises like the Zhengda Company to improve preventative measures. Our evidence-based epidemiological analyses provide methods for finding high-risk settings and evaluating epidemic situations when many asymptomatic patients are identified in a short period of time.

SARS-CoV-2 Spike Protein Dictates Syncytium-mediated Lymphocyte Elimination (preprint)

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus is highly contagious and causes lymphocytopenia, but the underlying mechanisms are poorly understood. We demonstrate here that heterotypic cell-in-cell structures with lymphocytes inside multinucleate syncytia are prevalent in the lung tissues of coronavirus disease 2019 (COVID-19) patients. These unique cellular structures are a direct result of SARS-CoV-2 infection, as the expression of the SARS-CoV-2 spike glycoprotein is sufficient to induce a rapid (approximately 45.1 nm/sec) membrane fusion to produce syncytium, which could readily internalize multiple lines of lymphocytes to form typical cell-in-cell structures, remarkably leading to the death of internalized cells. This membrane fusion is dictated by a bi-arginine motif within the polybasic S1/S2 cleavage site, which is frequently present in the surface glycoprotein of most highly contagious viruses. Moreover, candidate anti-viral drugs could efficiently inhibit spike glycoprotein processing, membrane fusion, and cell-in-cell formation. Together, we delineate a molecular and cellular rationale for SARS-CoV-2 pathogenesis and identify novel targets for COVID-19 therapy.

An Investigation of a Confirmed Imported Case of COVID-19 Infected Abroad - Qingpu District, Shanghai Municipality, China, November 15, 2020.

SUMMARY: What is already known about this topic? A passenger who was from the United States was taken to the hotel for the required isolation on November 13, 2020. During the quarantine she was diagnosed as the COVID-19 patient on November 15, 2020. Controlling the importation of COVID-19 remains a major challenge.What is added by this report? In this study, an epidemiological investigation was conducted for a confirmed case of COVID-19, including the treatment records in the hospital and 14-day travel trajectory before the onset of disease.What are the implications for public health practice? This study described an epidemiological investigation and management process on an imported case of COVID-19 and analyzed the test results, aiming to provide useful warnings to strengthen the capacity of public health system in response to the importation.