Safety of inactivated COVID-19 vaccines in autoimmune encephalitis: a real-world cross-sectional survey

Objective To assess safety data of the inactivated COVID-19 vaccines in a real-world sample of people with autoimmune encephalitis (pwAE). Methods A cross-sectional study was performed between 1 March and 30 April 2022. We invited pwAE from our previous ONE-WC (Outcome of Autoimmune Encephalitis Study in Western China) registration study database, to attend neurological clinics, at West China Hospital to participate in a face-to-face survey using a custom-designed questionnaire for this study. The ONE-WC study began in October 2011 and prospectively enrolled pwAE from four large comprehensive neurological centers in Sichuan province, China. Results Of the 387 pwAE, 240 (62.0%) completed the questionnaire. Half the 240 participants (121, 50.4%) reported receiving at least one dose of COVID-19 vaccine, which in all but two patients received inactivated COVID-19 vaccine. Among vaccinated pwAE, the median age was 35 years (range 15-69) and 57.8% of them were women. The most frequent reasons that unvaccinated individuals reported for not receiving the COVID-19 vaccine were concern about vaccine-induced relapse of AE (50.4%) and advice from a physician to delay vaccination (21.0%). Small proportions of vaccinated individuals reported adverse events after the first dose (11.5%) or the second dose (10.2%), and none of the adverse events was serious. Across the entire sample, one individual reported relapsing within 30 days after the first dose and three individuals reported relapsing more than 120 days after the first dose. Conclusions This real-world survey indicates an overall favorable safety profile of the inactivated COVID-19 vaccine for pwAE.

The Impact of COVID-19 on Primary Health Care and Antibiotic Prescribing in Rural China: Qualitative Study (preprint)

Background: Primary health care (PHC) system is designated to be responsible for epidemic control and prevention during the outbreak of COVID-19 in China, while COVID-19 suspected cases in PHC are required to be transferred to specialist fever clinics at higher level hospitals. This study aims to understand to impact of COVID-19 on PHC delivery and antibiotic prescribing at community level in the rural areas of central China.Methods: Qualitative semi-structured interviews were conducted with 18 PHC practitioners and seven patients recruited from two township health centres and nine village clinics in two rural residential areas of Anhui province. Interviews were transcribed verbatim and thematically analysed.Results: Practitioners’ and patients’ views and perspectives on COVID-19 impacts on PHC services and antibiotic prescribing are organised into four broad themes. PHC practitioners took on a key public health role of tracing, screening and educating in rural areas, while their original role in seeing and treating patients was reduced since government required patients to be diverted. The additional work, risk, and financial pressure that PHC practitioners faced placed considerable strain on them, particularly those working in the village clinics. PHC largely diminished that related to the difficulty of PHC workforce with limited medical training and the high number of elderly patients in rural areas, and as a result of epidemic, rural patients found it more difficult to access health care. Antibiotic prescribing practices for non-COVID-19 respiratory tract infections remained unchanged and were not seen as relevant to practitioners’ knowledge of COVID-19, although overall antibiotic treatments were reduced because fewer patients were attending rural PHC clinics. Conclusions: Our study identified the considerable impact of COVID-19 epidemic on PHC in rural China. Since COVID-19 epidemic control work has been designated as a long-term task in China, rural PHC clinics now face the challenge of how to balance their principal clinical and prevention and public health roles and, in the case of the village clinics, remain financially viable.

Human Taste Cells Express ACE2: A Portal for SARS-CoV-2 Infection (preprint)

Loss and changes in taste and smell are well-reported symptoms of SARS-CoV-2 infection. The virus targets cells for entry by high affinity binding of its spike protein to cell-surface angiotensin-converting enzyme- 2 (ACE2). It was not known whether ACE2 is expressed on taste receptor cells (TRCs) nor if TRCs are infected directly. Using an in-situ hybridization (ISH) probe and an antibody specific to ACE2, it seems evident that ACE2 is present on a subpopulation of specialized TRCs, namely, PLC{beta}2 positive, Type II cells in taste buds in taste papillae. Fungiform papillae (FP) of a SARS-CoV-2+ patient exhibiting symptoms of COVID-19, including taste changes, were biopsied. Based on ISH, replicating SARS-CoV-2 was present in Type II cells of this patient. Therefore, taste Type II cells provide a portal for viral entry that predicts vulnerabilities to SARS-CoV-2 in the oral cavity. The continuity and cell turnover of the FP taste stem cell layer of the patient were disrupted during infection and had not fully recovered 6 weeks post symptom onset. Another patient suffering post-COVID-19 taste disturbances also had disrupted stem cells. These results indicate that a COVID-19 patient who experienced taste changes had replicating virus in their taste buds and that SARS-CoV-2 infection results in deficient stem cell turnover needed for differentiation into TRCs.

Genomic epidemiology of SARS-CoV-2 in the United Arab Emirates reveals novel virus mutation, patterns of co-infection and tissue specific host responses (preprint)

Background: The United Arab Emirates is a major business hub with substantial amount of international travel. Like many other countries, it was greatly affected by the COVID-19 pandemic since late January 2020, with recurring waves of infection. This study aimed at combining genomic and epidemiological data to unravel the source of SARS-CoV-2 introduction, transmission and evolution in the country. Methods: We performed meta-transcriptomic sequencing of 1,067 nasopharyngeal swab samples collected from qRT-PCR positive COVID-19 patients in Abu Dhabi, UAE, between May 9th and June 29th 2020. We investigated the genetic diversity and transmission dynamics of the viral population and analyzed the infection and transmission potential of novel genomic clusters. Within-host SARS-CoV-2 genetic variation was analyzed to determine the occurrence and prevalence of multiple infections. Finally, we evaluated innate host responses during the prolonged period of local infection. Results: All globally known SARS-CoV-2 clades were identified within the UAE sequenced strains, with a higher occurrence of European and East Asian clades. We defined 5 subclades based on 11 unique genetic variants within the UAE strains, which were associated with no significantly different viral loads. Multiple infection of different SARS-CoV-2 strains was observed for at least 5% of the patients. We also discovered an enrichment of cytosine-to-uracil mutation among the viral population collected from the nasopharynx, that is different from the adenosine-to-inosine change previously observed in the bronchoalveolar lavage fluid samples. This observation is accompanied with an upregulation of APOBEC4, an under-studied putative cytidine-uridine editing enzyme in the infected nasopharynx. Conclusions: The genomic epidemiological and molecular biological knowledge obtained in the study provides new insights for the SARS-CoV-2 evolution and transmission. We highlight the importance of sustained surveillance of the virus mutation using genomic sequencing as a public health strategy. Keywords: SARS-CoV-2, meta-transcriptomic sequencing, novel mutations and subclades, co-infection, cyosine depletion, host RNA editing

The impact of COVID-19 on primary health care and antibiotic prescribing in rural China: qualitative study (preprint)

Introduction Primary health care (PHC) system is designated to be responsible for epidemic control and prevention during the outbreak of COVID-19 in China, while COVID-19 suspected cases in PHC are required to be transferred to specialist fever clinics at higher level hospitals. This study aims to understand to impact of COVID-19 on PHC delivery and antibiotic prescribing at community level in the rural areas of central China. Methods Qualitative semi-structured interviews were conducted with 18 PHC practitioners and seven patients recruited from two township health centres (THCs) and nine village clinics (VCs) in two rural residential areas of Anhui province. Interviews were transcribed verbatim and thematically analysed. Results Practitioners' and patients' views and perspectives on COVID-19 impacts on PHC services and antibiotic prescribing are organised into four broad themes: switch from PHC to epidemic prevention and control, concerns and challenges faced by those delivering PHC, diminished PHC, and COVID-19 as a different class of illness. Conclusion The COVID-19 epidemic has had a considerable impact on the roles of rural PHC clinics in China that shifted to public health from principal medical, and highlighted the difficulties in rural PHC including inadequately trained practitioners, additional work and financial pressure, particularly in VCs. Antibiotic prescribing practices for non-COVID-19 respiratory tract infections remained unchanged since the knowledge of COVID-19 was not seen as relevant to practitioners' antibiotic treatment practices, although overall rates were reduced because fewer patients were attending rural PHC clinics. Since COVID-19 epidemic control work has been designated as a long-term task in China, rural PHC clinics now face the challenge of how to balance their principal clinical and public health roles and, in the case of the VCs, remain financially viable. Keywords COVID-19, antibiotic treatment, township health centre, village clinic, epidemic prevention and control

Dynamic changes in serum IL-6, IL-8, and IL-10 predict the outcome of ICU patients with severe COVID-19.

BACKGROUND: Biomarkers to prognosticate the outcomes and guide the treatment of patients with severe coronavirus disease 2019 (COVID-19) are currently required. We aimed to investigate whether the dynamic variation of cytokines was associated with the survival of patients admitted to the intensive care unit (ICU). METHODS: A retrospective study was performed on 40 patients with COVID-19 admitted to the ICU in Wuhan, China. Demographic, clinical, and laboratory variables were collected, and serum cytokines were kinetically assessed. A multivariable-adjusted generalized linear regression model was used to analyze the differences in serum cytokine levels between survivors and non-survivors. RESULTS: Among the 40 patients included, we found a positive correlation between multiple cytokines. Serum levels of interleukin (IL)-6, IL-10, and tumor necrosis factor alpha (TNFα) in non-survivors were consistently elevated compared to those in the survivors. Kinetic variations in IL-6, IL-8, and IL-10 were associated with a fatal outcome in patients with severe COVID-19, independent of sex, age, absolute lymphocyte count, direct bilirubin, hypertension, chronic obstructive pulmonary disease, and cancer as well as the use of glucocorticoids and tocilizumab. CONCLUSIONS: Dynamic changes in serum IL-6, IL-8, and IL-10 levels were associated with survival in patients in the ICU, and could serve as a predictive biomarker to determine the therapeutic options for patients with severe COVID-19.

Genomic Epidemiology of SARS-CoV-2 in the United Arab Emirates Reveals Novel Insights into the Virus Mutation, Co-Infection and Host-Dependent RNA Editing (preprint)

Background: The United Arab Emirates is a major business hub with substantial amount of international travel. Like many other countries, it was greatly affected by the COVID-19 pandemic since late January 2020, with recurring waves of infection. This study aimed at combining genomic and epidemiological data to unravel the source of SARS-CoV-2 introduction, transmission and evolution in the country.Methods: We performed meta-transcriptomic sequencing of 1,067 nasopharyngeal swab samples collected from qRT-PCR positive COVID-19 patients in Abu Dhabi, UAE, between May 9th and June 29th 2020. We investigated the genetic diversity and transmission dynamics of the viral population and analyzed the infection and transmission potential of novel genomic clusters. Within-host SARS-CoV-2 genetic variation was analyzed to determine the occurrence and prevalence of multiple infections. Finally, we evaluated innate host responses during the prolonged period of local infection.Findings: All globally known SARS-CoV-2 clades were identified within the UAE sequenced strains, with a higher occurrence of European and East Asian clades. We defined 5 subclades based on 11 unique genetic variants within the UAE strains, which were associated with higher viral loads (p<0.001). Multiple infection of different SARS-CoV-2 strains was observed for at least 5% of the patients. We also observed a host-defense mechanism via RNA editing, likely mediated by APOBEC3 rather than ADAR in nasopharyngeal samples.Interpretation: The SARS-CoV-2 epidemic in the UAE was founded by international importation followed by local transmission, leading to prevalent multiple infection and large subclade descendances. While RNA editing mechanisms mutate the viral population, newly arisen genetic variation can contribute to a heavier viral burden. Meta-transcriptomic sequencing can help to determine the transmission patterns of SARS-CoV-2.Funding: Department of Health of Abu Dhabi, UAE and National Natural Science Foundation of China.Declaration of Interests: None to declareEthics Approval Statement: The study was approved by the Abu Dhabi COVID19 Research IRB Committee (approval number DOH/CVDC/2020/1945).

A Single-Center Retrospective and Descriptive Study of Hepatobiliary and Pancreatic Surgical Oncology during the COVID-19 Epidemic (preprint)

Objective: In the battle against COVID-19, most medical resources in China have been directed to infected patients in Wuhan. Thus, patients with hepatobiliary pancreatic tumors who are not suffering from COVID-19 are often not given timely and effective anti-cancer treatments. In this study, we aimed to describe clinical characteristics, treatment, and outcomes of patients with hepatobiliary and pancreatic oncology from our department, which retained normal working during the COVID-19 epidemic. We also sought to formulate a set of standardized hospitalization and treatment processes.Methods: A retrospective and descriptive study was conducted involving patients hospitalized from February 1, 2020, to February 29, 2020 (Return to work after the Spring Festival), at our Department of Hepatobiliary and Pancreatic Surgical Oncology. Results: The study included 92 patients from 12 provinces in the north of China who underwent surgical resection at our Department of Hepatobiliary and Pancreatic Surgical Oncology during the COVID-19 epidemic. Robotic surgery was performed on 82% (75/92) of patients, while the rest underwent laparoscopic (2/92) and open surgery (15/92). Eighty-six patients had malignant tumor, and six had emergency benign diseases. Only five patients had severe pancreatic fistula, and three had biliary fistula after operation. Conclusions: The standardized hospitalization and treatment processes described in this study could prevent cross-infection of patients and still ensure timely treatment of patients with hepatobiliary and pancreatic cancers. These study findings will guide the management of surgical oncology departments and treatment of patients with hepatobiliary and pancreatic oncology during serious epidemics.

Initial Study of Human Genetic Contribution to COVID-19 Severity and Susceptibility (preprint)

The COVID-19 pandemic has accounted for more than five million infections and hundreds of thousand deaths worldwide in the past six months. The patients demonstrate a great diversity in clinical and laboratory manifestations and disease severity. Nonetheless, little is known about the host genetic contribution to the observed inter-individual phenotypic variability. Here, we report the first host genetic study in China by deeply sequencing and analyzing 332 COVID-19 patients categorized by varying levels of severity from the Shenzhen Third Peoples Hospital. Upon a total of 22.2 million genetic variants, we conducted both single-variant and gene-based association tests among five severity groups including asymptomatic, mild, moderate, severe and critical ill patients after the correction of potential confounding factors. The most significant gene locus associated with severity is located in TMEM189-UBE2V1 involved in the IL-1 signaling pathway. The p.Val197Met missense variant that affects the stability of the TMPRSS2 protein displays a decreasing allele frequency among the severe patients compared to the mild and the general population. We also identified that the HLA-A*11:01, B*51:01 and C*14:02 alleles significantly predispose the worst outcome of the patients. This initial study of Chinese patients provides a comprehensive view of the genetic difference among the COVID-19 patient groups and highlighted genes and variants that may help guide targeted efforts in containing the outbreak. Limitations and advantages of the study were also reviewed to guide future international efforts on elucidating the genetic architecture of host-pathogen interaction for COVID-19 and other infectious and complex diseases.

Analysis on clinical features of death patients with COVID-19: a retrospective, single-center study from Wuhan, China (preprint)

Background An ongoing global pandemic of pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused thousands of deaths in China since December, 2019. We aimed to describe the clinical course of patients died of SARS-CoV-2 infection.Methods In this retrospective study, we reviewed 194 patients with SARS-CoV-2 infection, who died consecutively between Feb 3 to 24, 2020 in Tongji Hospital (Wuhan, China). Basic demographic and clinical information, laboratory findings, complications and treatments were extracted from electronic medical records of Hospital Information System. Unpaired t test was employed to evaluate the statistical differences of the serum level of high-sensitive cardiac troponin I (hs-cTnI) among different age or sex groups. The relationship between hs-cTnI and inflammatory cytokines were estimated using Spearman correlation analysis.Results The death patients aged 69.62 ± 10.98, in which 68.6% were male. 74.7% patients had underlying chronic illnesses. The most common symptoms were fever (83%), cough (69.3%), and dyspnea (65.6%). Decreased lymphocyte count (91.4%), elevated level of hs-cTnI (82.9%) and inflammatory parameters in serum were commonly seen. The hs-cTnI level was significantly higher in the group aged 60–79 and male patients. A week positive correlation was observed between hs-cTnI values and D-dimer values (r = 0.343, p༜0.05). Acute respiratory distress syndrome was the main complication. Assisted respiration, antimicrobial drugs, glucocorticoids and immune globulin were the major treatments.Conclusion Most non-survivors with SARS-CoV-2 infection were old with chronic illnesses, complicated by multiple organ dysfunction. Prevention is better than cure in high-risk population.

Emotional responses and coping strategies of nurses and nursing college students during COVID-19 outbreak (preprint)

Background: Affected by a Corona Virus Disease 2019 (COVID-19) outbreak, Since December 2019, there have been more than 76,000 cases of COVID-19 in China, causing more than 3,000 medical staff infections. Due to COVID-19 spreads quickly, is highly contagious, and can be fatal in severe cases, and there are no specific medicines, it poses a huge threat to the life and health of nurses and has a large impact on their emotional responses and coping strategies. Methods: This study conducted an online questionnaire survey from February 1 to 9, 2020 to investigate the current state of emotional responses and coping strategies of nurses and college nursing students in Anhui Province. This study used a modified Brief COPE (Carver, 1997) and a emotional responses scale. Results: The results found that women showed more severe anxiety and fear than men. Participants from cities showed more anxiety and fear than participants from rural, but rural participants showed more sadness than urban participants. The closer COVID-19 is to the participants, the stronger the anxiety and anger. Compared with Nursing college students, nurses have stronger emotional responses and are more willing to use Problem-focused coping. People may have a cycle of "the more fear, the more problem-focused coping". And people may "The more angry, the more emotion-focused coping", "the more problem-focused coping, the more anxious, the more angry, the more sadness". Conclusion: COVID-19 is a pressure source with great influence, both for individuals and for the social public groups. Different individuals and groups may experience different levels of psychological crisis, and those nurses at the core of the incident are affected. Hospitals should focus on providing psychological support to nurses and providing timely psychological assistance and training in coping strategies. Improving nurses' ability to regulate emotions and effective coping strategies, providing a strong guarantee for resolutely winning the battle against epidemic prevention and control.

Overview of theory about pathogenesis, prevention and treatment of epidemic diseases in internal classic of Huangdi

A review. Yibing(epidemic disease) is a kind of epidemic and infectious disease. There was theory about pathogenesis,prevention and treatment of Yibing in Internal Classic of Huangdi, which still enlightens us today. It concerns three aspects in pathogenesis of Yibing: heaven(climatic conditions), human(vital Qi) and pathogen. The etiol. and pathogenesis of Yibing can be analyzed according to the onset time.