[Evaluation of COVID-19 Antigen Test Kit Assay Analytical and Clinical Performance].

Objective To rapidly screen patients with novel coronavirus pneumonia (COVID-19) infection including asymptomatic ones. Method Established a rapid detection test kit, and evaluated analytical and clinical performance of it. Result The minimum limit of detection of the reagent was 9.75×102 TCID50/mL; there was no cross-reaction and interference in the high-concentration samples of 29 common respiratory pathogens tested. The diagnostic sensitivity of clinical samples was 98.56%, specificity was 99.00%, and the total coincidence rate was 98.85%; the consistency test Kappa value is 0.974 5. The stratified analysis of positive samples with different Ct values showed that the coincidence rate within each stratum was greater than 95%. Conclusion This COVID-19 antigen test kit with excellent detection performance, fast detection speed, and portable operation. It can be used as a supplementary method for existing nucleic acid detection methods for early screening of new coronavirus.

A survey on the public's discrimination rate of typical rumors during the coronavirus disease 2019 epidemic. / æ–°åž‹å† çŠ¶ç— æ¯’è‚ºç‚Žæµè¡ŒæœŸé—´å ¬ä¼—å¯¹å ¸åž‹è°£è¨€æ­£ç¡®ç”„åˆ«çŽ‡çš„è°ƒæŸ¥.

OBJECTIVES: During the epidemic of coronavirus disease-2019 (COVID-19), the wide spread of rumors caused significant public hazards. This study aims to understand the situation of discrimination for typical COVID-19 rumors by the public and related factors. METHODS: An anonymous online survey was carried out using Questionnaire Star. The contents included participants' gender, age, education level, the COVID-19 information sources, and the judgmental questions about 14 representative COVID-19 rumors. The discrimination rate and 95% confidence interval of 14 rumors were estimated, and the association of discrimination rate with gender, age, and education level was analyzed by binary logistic regression. RESULTS: A total of 2 087 valid questionnaires were collected. The participants were mainly female (62.7%) and below 35 years old (63.4%); the education level was predominantly college/bachelor's degree (47.3%) and master's degree or above (39.1%); the participants, who accessed to COVID-19 information included internet media, accounted for 91%. The participants with different gender, age, and education level had significant differences in the distribution of COVID-19 information sources (all P<0.01). The participants' discrimination rate for 14 rumors ranged from 67.4% to 98.6%, with 4 rumors less than 80%. Women's discrimination rate of 9 rumors was significantly higher than men's (all P<0.05). There was no significant difference in the discrimination rate of rumors among the different age groups (all P>0.05), but the differences in the discrimination rate of other rumors among the different age groups varied according to the rumor. Compared to those with high school or less education levels, the discrimination rates were also higher in the respondents with high education levels (P<0.05). CONCLUSIONS: A few publics are still unable to identify typical rumors during the COVID-19 epidemic. There are associations among genders, age, and the education levels with the discrimination of some rumors. The government authorities should strengthen the true information regarding COVID-19, and therefore enhance the public's ability to identify rumors.

ACE2 and COVID-19 Susceptibility and Severity.

Sick, male, and older populations are more vulnerable to COVID-19. However, it remains unclear whether a common mechanism exists across different demographic characteristics. SARS-CoV-2 infection is initiated by the specific binding of the viral spike protein to angiotensin-converting enzyme 2 (ACE2). This study analyzed the demographics of pulmonary ACE2 expression, Mendelian randomization (MR) of ACE2 and COVID-19, and comparative tropism of SARS-CoV-2. The key features of SARS-CoV-2 tropism, including pulmonary ACE2 expression and ACE2-expressing cell types, showed distinct subphenotypes associated with the demographics of vulnerable COVID-19 populations, suggesting a hypothesis centered on "ACE2" to explain their interplay. Next, by integrating multiple COVID-19 cohorts of genome-wide association studies (GWASs) and cis-expression quantitative trait loci (cis-eQTLs) of ACE2, MR analysis demonstrated that ACE2 played a causal role in COVID-19 susceptibility and severity, suggesting ACE2 as a promising target for early COVID-19 treatment. Next, by analyzing the expression of host cell receptors using single-cell RNA sequencing (scRNA-seq) data of human lung tissues, comparative tropism analysis showed that SARS-CoV-2 and other respiratory viruses, but not non-respiratory viruses, had remarkably overlapping and enriched cellular tropism in alveolar type 2 (AT2) cells. This finding indicates the possibility of coinfection with SARS-CoV-2 and other respiratory viruses, perhaps implying sociovirology at the cellular level. Moreover, the binding of viral entry proteins to the compatible host cell receptors is under strong natural selection pressure. Therefore, comparative tropism might reveal the footprint of natural selection that shapes the virus population, which provides a novel perspective for understanding zoonotic spillover events.

Hydroxychloroquine/chloroquine and the risk of acute kidney injury in COVID-19 patients: a systematic review and meta-analysis.

OBJECTIVES: Hydroxychloroquine/chloroquine has been widely used as part of the standard treatment for patients with coronavirus disease 2019 (COVID-19). We conducted a systematic review and meta-analysis to determine whether hydroxychloroquine/chloroquine increases the risk of acute kidney injury (AKI) in COVID-19 patients. METHODS: PubMed and Embase were searched for related publications from inception to Dec 31, 2021, including randomized controlled trials (RCTs) and non-randomized studies of interventions (NRSIs) comparing the risk of AKI and/or increased creatinine in COVID-19 patients receiving hydroxychloroquine/chloroquine and other controls (active treatment and placebo). We conducted separate meta-analyses for RCTs and NRSIs based on fixed-effect model, with odds ratios (ORs) being considered as effect sizes. RESULTS: We included 21 studies in the analysis, with 12 were RCTs. Based on the RCTs, compared to placebo, the OR was 1.19 (95% confidence interval [CI]: 0.86, 1.64; p = .30, n = 4, moderate quality) for AKI and 1.00 (95%CI: 0.64, 1.56; p = .99, n = 5, moderate quality) for increased creatinine for patients received hydroxychloroquine/chloroquine treatment; compared to active treatment, the odds was 1.28 (95%CI: 0.65, 2.53; p = .47, n = 2, low quality) for AKI and 0.64 (95%CI: 0.13, 3.20; p = .59, n = 1, low quality) for increased creatine. Evidence from NRSIs showed slightly increased odds of AKI, with low quality. CONCLUSION: Based on current available studies which were graded as low to moderate quality, there is insufficient evidence to conclude that hydroxychloroquine/chloroquine use is associated with increased risk of AKI or raised creatinine. Abbreviations: AKI: acute kidney injury; COVID-19: Coronavirus Disease 2019; RCT: randomized controlled trials; NRSI: non-randomized studies of interventions; OR: odds ratios; ROBIS-I: Risk Of Bias In Non-randomized Studies - of Interventions.

COVID-19-Related Rumor Content, Transmission, and Clarification Strategies in China: Descriptive Study.

BACKGROUND: Given the permeation of social media throughout society, rumors spread faster than ever before, which significantly complicates government responses to public health emergencies such as the COVID-19 pandemic. OBJECTIVE: We aimed to examine the characteristics and propagation of rumors during the early months of the COVID-19 pandemic in China and evaluated the effectiveness of health authorities' release of correction announcements. METHODS: We retrieved rumors widely circulating on social media in China during the early stages of the COVID-19 pandemic and assessed the effectiveness of official government clarifications and popular science articles refuting those rumors. RESULTS: We show that the number of rumors related to the COVID-19 pandemic fluctuated widely in China between December 1, 2019 and April 15, 2020. Rumors mainly occurred in 3 provinces: Hubei, Zhejiang, and Guangxi. Personal social media accounts constituted the major source of media reports of the 4 most widely distributed rumors (the novel coronavirus can be prevented with "Shuanghuanglian": 7648/10,664, 71.7%; the novel coronavirus is the SARS coronavirus: 14,696/15,902, 92.4%; medical supplies intended for assisting Hubei were detained by the local government: 3911/3943, 99.2%; asymptomatically infected persons were regarded as diagnosed COVID-19 patients with symptoms in official counts: 322/323, 99.7%). The number of rumors circulating was positively associated with the severity of the COVID-19 epidemic (ρ=0.88, 95% CI 0.81-0.93). The release of correction articles was associated with a substantial decrease in the proportion of rumor reports compared to accurate reports. The proportions of negative sentiments appearing among comments by citizens in response to media articles disseminating rumors and disseminating correct information differ insignificantly (both correct reports: χ12=0.315, P=.58; both rumors: χ12=0.025, P=.88; first rumor and last correct report: χ12=1.287, P=.26; first correct report and last rumor: χ12=0.033, P=.86). CONCLUSIONS: Our results highlight the importance and urgency of monitoring and correcting false or misleading reports on websites and personal social media accounts. The circulation of rumors can influence public health, and government bodies should establish guidelines to monitor and mitigate the negative impact of such rumors.

Tissue resident memory T cells in the respiratory tract

Owing to their capacity to rapidly spread across the population, airborne pathogens represent a significant risk to global health. Indeed, several of the past major global pandemics have been instigated by respiratory pathogens. A greater understanding of the immune cells tasked with protecting the airways from infection will allow for the development of strategies that curb the spread and impact of these airborne diseases. A specific subset of memory T-cell resident in both the upper and lower respiratory tract, termed tissue-resident memory (Trm), have been shown to play an instrumental role in local immune responses against a wide breadth of both viral and bacterial infections. In this review, we discuss factors that influence respiratory tract Trm development, longevity, and immune surveillance and explore vaccination regimes that harness these cells, such approaches represent exciting new strategies that may be utilized to tackle the next global pandemic.

Safety and immunogenicity of COVID-19 vaccination in patients with non-alcoholic fatty liver disease (CHESS2101): A multicenter study.

BACKGROUND & AIMS: The development of COVID-19 vaccines has progressed with encouraging safety and efficacy data. Concerns have been raised about SARS-CoV-2 vaccine responses in the large population of patients with non-alcoholic fatty liver disease (NAFLD). The study aimed to explore the safety and immunogenicity of COVID-19 vaccination in NAFLD. METHODS: This multicenter study included patients with NAFLD without a history of SARS-CoV-2 infection. All patients were vaccinated with 2 doses of inactivated vaccine against SARS-CoV-2. The primary safety outcome was the incidence of adverse reactions within 7 days after each injection and overall incidence of adverse reactions within 28 days, and the primary immunogenicity outcome was neutralizing antibody response at least 14 days after the whole-course vaccination. RESULTS: A total of 381 patients with pre-existing NAFLD were included from 11 designated centers in China. The median age was 39.0 years (IQR 33.0-48.0 years) and 179 (47.0%) were male. The median BMI was 26.1 kg/m2 (IQR 23.8-28.1 kg/m2). The number of adverse reactions within 7 days after each injection and adverse reactions within 28 days totaled 95 (24.9%) and 112 (29.4%), respectively. The most common adverse reactions were injection site pain in 70 (18.4%), followed by muscle pain in 21 (5.5%), and headache in 20 (5.2%). All adverse reactions were mild and self-limiting, and no grade 3 adverse reactions were recorded. Notably, neutralizing antibodies against SARS-CoV-2 were detected in 364 (95.5%) patients with NAFLD. The median neutralizing antibody titer was 32 (IQR 8-64), and the neutralizing antibody titers were maintained. CONCLUSIONS: The inactivated COVID-19 vaccine appears to be safe with good immunogenicity in patients with NAFLD. LAY SUMMARY: The development of vaccines against coronavirus disease 2019 (COVID-19) has progressed rapidly, with encouraging safety and efficacy data. This study now shows that the inactivated COVID-19 vaccine appears to be safe with good immunogenicity in the large population of patients with non-alcoholic fatty liver disease.

Cellular Tropism of SARS-CoV-2 across Human Tissues and Age-related Expression of ACE2 and TMPRSS2 in Immune-inflammatory Stromal Cells.

Recently, emerging evidence has indicated that COVID-19 represents a major threat to older populations, but the underlying mechanisms remain unclear. The pathogen causing COVID-19 is acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 infection depends on the key entry factors, angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2). Recognizing the importance of ACE2 and TMPRSS2 for the cellular tropism of SARS-CoV-2, we analyzed and presented the landscape of cell-type identities for ACE2+ TMPRSS2+ cells across different human tissues and the age-related alterations in ACE2 and TMPRSS2 expression across different cell types. Additionally, most of the post-acute COVID-19 sequelae could attribute to the ACE2-expressing organ systems. Therefore, these SARS-CoV-2 tropism data should be an essential resource for guiding clinical treatment and pathological studies, which should draw attention toward the prioritization of COVID-19 research in the future. Notably, we discovered the age-related expression of ACE2 and TMPRSS2 in the immune-inflammatory stromal cells, implying the potential interplay between COVID-19, stromal cells, and aging. In this study, we developed a novel and practical analysis framework for mapping the cellular tropism of SARS-CoV-2. This approach was built to aid the identification of viral-specific cell types and age-related alterations of viral tropism, highlighting the power of single-cell RNA sequencing (scRNA-seq) to address viral pathogenesis systematically. With the rapid accumulation of scRNA-seq data and the continuously increasing insight into viral entry factors, we anticipate that this scRNA-seq-based approach will attract broader interest in the virus research communities.

Severe Acute Respiratory Syndrome Coronavirus-2 Infection in Children With Liver Transplant and Native Liver Disease: An International Observational Registry Study.

OBJECTIVE: Increased mortality risk because of severe acute respiratory syndrome coronavirus-2 (SARS-CoV2) infection in adults with native liver disease (LD) and liver transplant (LT) is associated with advanced age and comorbid conditions. We aim to report outcomes for children with LD and LT enrolled in the NASPGHAN/SPLIT SARS-CoV2 registry. METHODS: In this multicenter observational cohort study, we collected data from 91 patients <21 years (LD 44, LT 47) with laboratory-confirmed SARS-CoV2 infection between April 21 and September 17, 2020. RESULTS: Patients with LD were more likely to require admission (70% vs 43% LT, P = 0.007) and pediatric intensive care unit (PICU) management (32% vs 4% LT, P = 0.001). Seven LD patients required mechanical ventilation (MV) and 2 patients died; no patients in the LT cohort died or required MV. Four LD patients presented in pediatric acute liver failure (PALF), 2 with concurrent multisystem inflammatory syndrome in children (MIS-C); all recovered without LT. Two LD patients had MIS-C alone and 1 patient died. Bivariable logistic-regression analysis found that patients with nonalcoholic fatty LD (NAFLD) (odds ratio [OR] 5.6, P = 0.02) and LD (OR 6.1, P = 0.01, vs LT) had higher odds of severe disease (PICU, vasopressor support, MV, renal replacement therapy or death). CONCLUSIONS: Although not directly comparable, LT recipients had lower odds of severe SARS-CoV2 infection (vs LD), despite immunosuppression burden. NAFLD patients reported to the registry had higher odds of severe SARS-CoV2 disease. Future controlled studies are needed to evaluate effective treatments and further stratify LD and LT patients with SARS-CoV2 infection.

Extrapulmonary complications of COVID-19: A multisystem disease?

The outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been recently declared a pandemic by the World Health Organization. In addition to its acute respiratory manifestations, SARS-CoV-2 may also adversely affect other organ systems. To date, however, there is a very limited understanding of the extent and management of COVID-19-related conditions outside of the pulmonary system. This narrative review provides an overview of the current literature about the extrapulmonary manifestations of COVID-19 that may affect the urinary, cardiovascular, gastrointestinal, hematological, hematopoietic, neurological, or reproductive systems. This review also describes the current understanding of the extrapulmonary complications caused by COVID-19 to improve the management and prognosis of patients with COVID-19.

Association and Interaction Between Serum Interleukin-6 Levels and Metabolic Dysfunction-Associated Fatty Liver Disease in Patients With Severe Coronavirus Disease 2019.

Background and Aim: Circulating levels of interleukin (IL)-6, a well-known inflammatory cytokine, are often elevated in coronavirus disease-2019 (COVID-19). Elevated IL-6 levels are also observed in patients with metabolic dysfunction-associated fatty liver disease (MAFLD). Our study aimed to describe the association between circulating IL-6 levels and MAFLD at hospital admission with risk of severe COVID-19. Methods: A total of 167 patients with laboratory-confirmed COVID-19 from three Chinese hospitals were enrolled. Circulating levels of IL-2, IL-4, IL-6, IL-10, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ were measured at admission. All patients were screened for fatty liver by computed tomography. Forty-six patients were diagnosed as MAFLD. Results: Patients with MAFLD (n = 46) had higher serum IL-6 levels (median 7.1 [interquartile range, 4.3-20.0] vs. 4.8 [2.6-11.6] pg/mL, p = 0.030) compared to their counterparts without MAFLD (n = 121). After adjustment for age and sex, patients with MAFLD had a ~2.6-fold higher risk of having severe COVID-19 than those without MAFLD. After adjustment for age, sex and metabolic co-morbidities, increased serum IL-6 levels remained associated with higher risk of severe COVID-19, especially among infected patients with MAFLD (adjusted-odds ratio 1.14, 95% CI 1.05-1.23; p = 0.002). There was a significant interaction effect between serum IL-6 levels and MAFLD for risk of severe COVID-19 (p for interaction = 0.008). Conclusions: Patients with MAFLD and elevated serum IL-6 levels at admission are at higher risk for severe illness from COVID-19.