The ratio between SARS-CoV-2 RNA viral load and culturable viral titer differs depending on stage of infection (preprint)

Analysis of incident, longitudinal RNA viral loads in saliva and nasal swabs and culturable viral titers in nasal swabs collected twice-daily by a tricenarian male infected with SARS-CoV-2 revealed the ratio between viral load and viral titer can be five orders of magnitude higher during early infection than late infection.

Daily SARS-CoV-2 Nasal Antigen Tests Miss Infected and Presumably Infectious People Due to Viral Load Differences among Specimen Types.

In a recent household transmission study of SARS-CoV-2, we found extreme differences in SARS-CoV-2 viral loads among paired saliva, anterior nares swab (ANS), and oropharyngeal swab specimens collected from the same time point. We hypothesized these differences may hinder low-analytical-sensitivity assays (including antigen rapid diagnostic tests [Ag-RDTs]) by using a single specimen type (e.g., ANS) from reliably detecting infected and infectious individuals. We evaluated daily at-home ANS Ag-RDTs (Quidel QuickVue) in a cross-sectional analysis of 228 individuals and a longitudinal analysis (throughout infection) of 17 individuals enrolled early in the course of infection. Ag-RDT results were compared to reverse transcription-quantitative PCR (RT-qPCR) results and high, presumably infectious viral loads (in each, or any, specimen type). The ANS Ag-RDT correctly detected only 44% of time points from infected individuals on cross-sectional analysis, and this population had an inferred limit of detection of 7.6 × 106 copies/mL. From the longitudinal cohort, daily Ag-RDT clinical sensitivity was very low (<3%) during the early, preinfectious period of the infection. Further, the Ag-RDT detected ≤63% of presumably infectious time points. The poor observed clinical sensitivity of the Ag-RDT was similar to what was predicted based on quantitative ANS viral loads and the inferred limit of detection of the ANS Ag-RDT being evaluated, indicating high-quality self-sampling. Nasal Ag-RDTs, even when used daily, can miss individuals infected with the Omicron variant and even those presumably infectious. Evaluations of Ag-RDTs for detection of infected or infectious individuals should be compared with a composite (multispecimen) infection status to correctly assess performance. IMPORTANCE We reveal three findings from a longitudinal study of daily nasal antigen rapid diagnostic test (Ag-RDT) evaluated against SARS-CoV-2 viral load quantification in three specimen types (saliva, nasal swab, and throat swab) in participants enrolled at the incidence of infection. First, the evaluated Ag-RDT showed low (44%) clinical sensitivity for detecting infected persons at all infection stages. Second, the Ag-RDT poorly detected (≤63%) time points that participants had high and presumably infectious viral loads in at least one specimen type. This poor clinical sensitivity to detect infectious individuals is inconsistent with the commonly held view that daily Ag-RDTs have near-perfect detection of infectious individuals. Third, use of a combination nasal-throat specimen type was inferred by viral loads to significantly improve Ag-RDT performance to detect infectious individuals.

PACT inhibits the replication of SARS-CoV-2 through the blockage of GSK-3ß-N-nsp3 cascade.

The protein activator of protein kinase R (PKR) (PACT) has been shown to play a crucial role in stimulating the host antiviral response through the activation of PKR, retinoic acid-inducible gene I, and melanoma differentiation-associated protein 5. Whether PACT can inhibit viral replication independent of known mechanisms is still unrevealed. In this study, we show that, like many viruses, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) hijacks GSK-3ß to facilitate its replication. GSK-3ß-induced phosphorylation on N protein increased the interaction between N protein and nsp3. Thus, GSK-3ß-N-nsp3 cascade promotes viral replication. Although SARS-CoV-2 can sabotage the activation of AKT, the upstream proteins suppressing the activation of GSK-3ß, we found that the host can use PACT, another protein kinase, instead of AKT to decrease the activity of GSK-3ß and the interaction between PACT and GSK-3ß is enhanced upon viral infection. Moreover, PACT inhibited the activity of GSK-3ß independent of its well-studied double-stranded RNA binding and PKR activating ability. In summary, this study identified an unknown function of PACT in inhibiting SARS-CoV-2 replication through the blockage of GSK-3ß-N-nsp3 cascade.

Bat ASC2 suppresses inflammasomes and ameliorates inflammatory diseases.

Bats are special in their ability to live long and host many emerging viruses. Our previous studies showed that bats have altered inflammasomes, which are central players in aging and infection. However, the role of inflammasome signaling in combating inflammatory diseases remains poorly understood. Here, we report bat ASC2 as a potent negative regulator of inflammasomes. Bat ASC2 is highly expressed at both the mRNA and protein levels and is highly potent in inhibiting human and mouse inflammasomes. Transgenic expression of bat ASC2 in mice reduced the severity of peritonitis induced by gout crystals and ASC particles. Bat ASC2 also dampened inflammation induced by multiple viruses and reduced mortality of influenza A virus infection. Importantly, it also suppressed SARS-CoV-2-immune-complex-induced inflammasome activation. Four key residues were identified for the gain of function of bat ASC2. Our results demonstrate that bat ASC2 is an important negative regulator of inflammasomes with therapeutic potential in inflammatory diseases.

Profile identification and characterization of risk perceptions and preventive behaviors during the COVID-19 pandemic: A latent profile analysis.

In a public health crisis, communication plays a vital role in making sure policies and recommendations from the government level get disseminated accurately to its people and is only considered as effective when the public accepts, supports, complies to, and engages in policies or behaves as per governments' recommendations. Adopting the multivariate audience segmentation strategy for health communication, this study uses a data-driven analytical method to (1) identify audience segments of public health crisis communication in Singapore based on knowledge, risk perception, emotional responses, and preventive behaviors; and (2) characterize each audience segment according to demographic factors, personality traits, information processing styles, and health information preferences. Results (N = 2033) from a web-based questionnaire executed in August 2021 have identified three audience segments: the less-concerned (n = 650), the risk-anxious (n = 142), and the risk-majority (n = 1,241). This study offers insights to how audiences of public health crisis communication perceive, process, and respond to information directed to them during the pandemic, thereby informing policy makers to tailor more targeted public health communication interventions in promoting positive attitude and behavior change.

Extreme differences in SARS-CoV-2 viral loads among respiratory specimen types during presumed pre-infectious and infectious periods.

SARS-CoV-2 viral-load measurements from a single-specimen type are used to establish diagnostic strategies, interpret clinical-trial results for vaccines and therapeutics, model viral transmission, and understand virus-host interactions. However, measurements from a single-specimen type are implicitly assumed to be representative of other specimen types. We quantified viral-load timecourses from individuals who began daily self-sampling of saliva, anterior-nares (nasal), and oropharyngeal (throat) swabs before or at the incidence of infection with the Omicron variant. Viral loads in different specimen types from the same person at the same timepoint exhibited extreme differences, up to 109 copies/mL. These differences were not due to variation in sample self-collection, which was consistent. For most individuals, longitudinal viral-load timecourses in different specimen types did not correlate. Throat-swab and saliva viral loads began to rise as many as 7 days earlier than nasal-swab viral loads in most individuals, leading to very low clinical sensitivity of nasal swabs during the first days of infection. Individuals frequently exhibited presumably infectious viral loads in one specimen type while viral loads were low or undetectable in other specimen types. Therefore, defining an individual as infectious based on assessment of a single-specimen type underestimates the infectious period, and overestimates the ability of that specimen type to detect infectious individuals. For diagnostic COVID-19 testing, these three single-specimen types have low clinical sensitivity, whereas a combined throat-nasal swab, and assays with high analytical sensitivity, was inferred to have significantly better clinical sensitivity to detect presumed pre-infectious and infectious individuals.

Prevalence and factors associated with flares following COVID-19 mRNA vaccination in patients with rheumatoid arthritis, psoriatic arthritis and spondyloarthritis: a national cohort study (preprint)

Objective To determine prevalence and factors associated with flares post Coronavirus disease 2019 (COVID-19) mRNA vaccination in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and spondyloarthritis (SpA). Methods A retrospective multi-centre study was conducted (January 2021 to February 2022). Data were collected during index visit, defined as first post-vaccine visit in which the patient had a physician-defined flare, or if at least three months had elapsed since first vaccine dose, whichever came first. Factors associated with flares were identified using mixed effects Cox regression and expressed as hazard ratio (HR) and 95% confidence interval (CI). Results Total of 2377 patients were included (1563 RA, 415 PsA and 399 SpA). Among patients with RA, PsA and SpA, 21.3%, 24.1% and 21.8% experienced a flare respectively. Of those who experienced a flare, only 10.2%, 11.0% and 14.9% were severe in patients with RA, PsA and SpA respectively. Patients with low or moderate/ high disease were more likely to flare compared to those in remission in patients with RA only (HR: 1.68, 95% CI: 1.22 – 2.31; HR: 2.28, 95% CI: 1.50 – 3.48, respectively). Receiving the Moderna vaccine was associated with a higher HR of flare compared to the Pfizer vaccine in patients with PsA only (HR: 2.21, 95% CI: 1.20 – 4.08). Patients who had two vaccine doses were found to be less likely to flare (HR: 0.08, 95% CI: 0.06 – 0.10). HRs of flares were not significantly different among RA, PsA and SpA. Conclusion About one-fifth of patients experienced a disease flare post COVID-19 mRNA vaccination, but most flares were non-severe. Patients with active disease prior to vaccination should be monitored closely for disease flares, especially in patients with RA.

Index Cases First Identified by Nasal-Swab Rapid COVID-19 Tests Had More Transmission to Household Contacts Than Cases Identified by Other Test Types (preprint)

Importance: At-home rapid COVID-19 tests utilize nasal-swab specimens and require high viral loads to reliably give positive results. Longitudinal studies from the onset of infection have found infectious virus can present in oral specimens days before nasal. Detection and initiation of infection-control practices may therefore be delayed when nasal-swab rapid tests are used, resulting in greater exposure and transmission to contacts. Objective: We assessed whether index cases first identified by rapid nasal-swab COVID-19 tests had more transmission to household contacts than index cases who used other test types (tests with higher analytical sensitivity but longer turnaround times, and/or that utilize non-nasal specimen types). Design: In this observational cohort study, members of households with a recent COVID-19 case were screened for infection at least daily by RT-qPCR on one or more self-collected upper-respiratory specimen types. Participants reported demographic/medical information (including COVID-19 testing), symptom and exposure information, and household infection-control practices. A two-level random intercept model was used to assess the association between the infection outcome of household contacts and each covariable (household size, race/ethnicity, age, vaccination status, viral variant, infection-control practices, and whether a rapid nasal-swab test was used to initially identify the household index case). Setting: Southern California, September 2020-June 2021 and November 2021-March 2022. Participants: Cohort of 370 individuals from 85 households. Main Outcome(s) and Measure(s): Transmission was quantified by adjusted secondary attack rates (aSAR) and adjusted odds ratios (aOR). Results: An aSAR of 53.6% (95%CI 38.8-68.3%) was observed among households where the index case first tested positive by a rapid nasal-swab COVID-19 test, which was significantly higher than the aSAR for households where the index case utilized another test type (27.2% [19.5-35.0%], P=0.003 pairwise comparisons of predictive margins). We observed an aOR of 4.90 (95%CI 1.65-14.56) for transmission to household contacts when a nasal-swab rapid test was used to identify the index case, compared to other test types. Conclusions and Relevance: Use of nasal-swab rapid COVID-19 tests for initial detection of infection and initiation of infection control may not limit transmission as well as other test types.

Role of the extracellular matrix in COVID-19.

An outbreak of coronavirus disease 2019 (COVID-19) has spread globally, with over 500 million cases and 6 million deaths to date. COVID-19 is associated with a systemic inflammatory response and abnormalities of the extracellular matrix (ECM), which is also involved in inflammatory storms. Upon viral infection, ECM proteins are involved in the recruitment of inflammatory cells and interference with target organ metabolism, including in the lungs. Additionally, serum biomarkers of ECM turnover are associated with the severity of COVID-19 and may serve as potential targets. Consequently, understanding the expression and function of ECM, particularly of the lung, during severe acute respiratory syndrome of the coronavirus 2 infection would provide valuable insights into the mechanisms of COVID-19 progression. In this review, we summarize the current findings on ECM, such as hyaluronic acid, matrix metalloproteinases, and collagen, which are linked to the severity and inflammation of COVID-19. Some drugs targeting the extracellular surface have been effective. In the future, these ECM findings could provide novel perspectives on the pathogenesis and treatment of COVID-19.

Post-mRNA vaccine flares in autoimmune inflammatory rheumatic diseases: Results from the COronavirus National Vaccine registry for ImmuNe diseases SINGapore (CONVIN-SING).

BACKGROUND: Studies of flares of autoimmune inflammatory rheumatic diseases (AIIRD) after COVID-19 mRNA vaccination are limited by small sample size, short follow up or at risk of selection bias. METHODS: A national retrospective cohort study of consecutive AIIRD patients ≥12 years old, across 8 hospitals who received at least one dose of a COVID-19 mRNA vaccine. Patients were included from the date of 1st vaccine dose and censored at the time of flare or on the date of the clinic visit at least 3 months from cohort entry, whichever came first. Predictors of flare were determined by Cox proportional hazards analysis. FINDINGS: 4627 patients (73% Chinese, 71% female) of median (IQR) age 61 (48, 70) years were included; 42% Rheumatoid arthritis, 14% Systemic lupus erythematosus and 11% Psoriatic arthritis. 47% were in remission, 41% low disease activity, 10% moderate disease activity and 1% in high disease activity. 18% patients flared, of which 11.7% were within the 3-month period of interest. 11.8% patients improved. Median (IQR) time-to-flare was 60 (30, 114) days. 25% flares were self-limiting, 61% mild-moderate and 14% severe. Older patients (53-65 years and >66 years) had a lower risk of flare [HR 0.6 (95% CI 0.5-0.8) and 0.7 (0.6-0.8) respectively]. Patients with inflammatory arthritis and with active disease had a higher risk of flare [HR 1.5 (1.2-2.0) and 1.4 (1.2-1.6), respectively]. Treatment with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), immunosuppression and prednisolone was also associated with an increased risk of flare [HR 1.5 (1.1-2), 1.2 (1.1-1.4) and 1.5 (1.2-1.8) for prednisolone ≤7.5 mg respectively]. INTERPRETATION: There was a moderately high rate of AIIRD flares after mRNA vaccination but also improvement in several patients. Severe flares and hospitalisation were rare. Thus, vaccination remains safe and highly recommended.

Setting Up a Transfusion Laboratory for Covid-19 Samples: An Experience from a New Teaching Hospital

University Putra Malaysia (UPM) Teaching Hospital or Hospital Pengajar UPM (HPUPM) is a new 400-bed teaching hospital that started operations in 2019 and initially did not manage COVID-19 patients. However, due to a surge of COVID-19 patients in Malaysia in 2021, HPUPM needs to manage COVID-19 patients in various categories, including those needing intensive care. This paper explored the experience of setting up the transfusion laboratory for COVID-19 samples within a short notice, including the development of the protocol, challenges, and lessons learnt during the whole process. [ FROM AUTHOR]

Effects of mobile health interventions on health-related outcomes in older adults with type 2 diabetes: A systematic review and meta-analysis.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a chronic metabolic condition that is associated with multiple comorbidities. Apart from pharmacological approaches, patient self-management remains the gold standard of care for diabetes. Improving patients' self-management among the elderly with mobile health (mHealth) interventions is critical, especially in times of the COVID-19 pandemic. However, the extent of mHealth efficacy in managing T2DM in the older population remains unknown. Hence, the present review examined the effectiveness of mHealth interventions on cardiometabolic outcomes in older adults with T2DM. METHODS: A systematic search from the inception till May 31, 2021, in the MEDLINE, Embase, and PubMed databases was conducted, and 16 randomized controlled trials were included in the analysis. RESULTS: The results showed significant benefits on glycosylated hemoglobin (HbA1c) (mean difference -0.24%; 95% confidence interval [CI]: -0.44, -0.05; p = 0.01), postprandial blood glucose (-2.91 mmol/L; 95% CI: -4.78, -1.03; p = 0.002), and triglycerides (-0.09 mmol/L; 95% CI: -0.17, -0.02; p = 0.010), but not on low-density lipoprotein cholesterol (-0.06 mmol/L; 95% CI: -0.14, 0.02; p = 0.170), high-density lipoprotein cholesterol (0.05 mmol/L; 95% CI: -0.03, 0.13; p = 0.220), and blood pressure (systolic blood pressure -0.82 mm Hg; 95% CI: -4.65, 3.00; p = 0.670; diastolic blood pressure -1.71 mmHg; 95% CI: -3.71, 0.29; p = 0.090). CONCLUSIONS: Among older adults with T2DM, mHealth interventions were associated with improved cardiometabolic outcomes versus usual care. Its efficacy can be improved in the future as the current stage of mHealth development is at its infancy. Addressing barriers such as technological frustrations may help strategize approaches to further increase the uptake and efficacy of mHealth interventions among older adults with T2DM.

Post-mRNA vaccine flares in autoimmune inflammatory rheumatic diseases: Results from the COronavirus national vaccine registry for ImmuNe diseases Singapore (CONVIN-SING)

Background Studies of flares of autoimmune inflammatory rheumatic diseases (AIIRD) after COVID-19 mRNA vaccination are limited by small sample size, short follow up or at risk of selection bias. Methods A national retrospective cohort study of consecutive AIIRD patients ≥12 years old, across 8 hospitals who received at least one dose of a COVID-19 mRNA vaccine. Patients were included from the date of 1st vaccine dose and censored at the time of flare or on the date of the clinic visit at least 3 months from cohort entry, whichever came first. Predictors of flare were determined by Cox proportional hazards analysis. Findings 4627 patients (73% Chinese, 71% female) of median (IQR) age 61 (48, 70) years were included;42% Rheumatoid arthritis, 14% Systemic lupus erythematosus and 11% Psoriatic arthritis. 47% were in remission, 41% low disease activity, 10% moderate disease activity and 1% in high disease activity. 18% patients flared, of which 11.7% were within the 3-month period of interest. 11.8% patients improved. Median (IQR) time-to-flare was 60 (30, 114) days. 25% flares were self-limiting, 61% mild-moderate and 14% severe. Older patients (53–65 years and >66 years) had a lower risk of flare [HR 0.6 (95% CI 0.5–0.8) and 0.7 (0.6–0.8) respectively]. Patients with inflammatory arthritis and with active disease had a higher risk of flare [HR 1.5 (1.2–2.0) and 1.4 (1.2–1.6), respectively]. Treatment with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), immunosuppression and prednisolone was also associated with an increased risk of flare [HR 1.5 (1.1–2), 1.2 (1.1–1.4) and 1.5 (1.2–1.8) for prednisolone ≤7.5 mg respectively]. Interpretation There was a moderately high rate of AIIRD flares after mRNA vaccination but also improvement in several patients. Severe flares and hospitalisation were rare. Thus, vaccination remains safe and highly recommended.

Morning SARS-CoV-2 Testing Yields Better Detection of Infection Due to Higher Viral Loads in Saliva and Nasal Swabs upon Waking.

Optimizing specimen collection methods to achieve the most reliable SARS-CoV-2 detection for a given diagnostic sensitivity would improve testing and minimize COVID-19 outbreaks. From September 2020 to April 2021, we performed a household-transmission study in which participants self-collected specimens every morning and evening throughout acute SARS-CoV-2 infection. Seventy mildly symptomatic participants collected saliva, and of those, 29 also collected nasal swab specimens. Viral load was quantified in 1,194 saliva and 661 nasal swab specimens using a high-analytical-sensitivity reverse transcription-quantitative PCR (RT-qPCR) assay. Viral loads in both saliva and nasal swab specimens were significantly higher in morning-collected specimens than in evening-collected specimens after symptom onset. This aspect of the biology of SARS-CoV-2 infection has implications for diagnostic testing. We infer that morning collection would have resulted in significantly improved detection and that this advantage would be most pronounced for tests with low to moderate analytical sensitivity. Collecting specimens for COVID-19 testing in the morning offers a simple and low-cost improvement to clinical diagnostic sensitivity of low- to moderate-analytical-sensitivity tests. IMPORTANCE Our findings suggest that collecting saliva and nasal swab specimens in the morning immediately after waking yields higher SARS-CoV-2 viral loads than collection later in the day. The higher viral loads from morning specimen collection are predicted to significantly improve detection of SARS-CoV-2 in symptomatic individuals, particularly when using moderate- to low-analytical-sensitivity COVID-19 diagnostic tests, such as rapid antigen tests.

Heterogeneity and Risk-of-Biases are No Longer the Issues to Conclude the Effectiveness of Baricitinib in Reducing COVID-19 Related Mortality: A Systematic Review and Meta-Analysis of Eight Randomised Controlled Trials (preprint)

BackgroundDue to high heterogeneity and risk of bias (RoB) in previously published meta-analysis, a concrete conclusion on the efficacy of baricitinib in reducing mortality in COVID-19 patients was unable to form. MethodsSearch engines PubMed/MEDLINE, ScienceDirect and other sources like preprints and reference lists were searched with appropriate keywords. The included evidence was graded with GRADEpro. The RoB, heterogeneity and meta-analysis were studied through RevMan 5.4.1 software. The heterogeneity was evaluated based on the generated p-value or I{superscript 2} test. ResultsEight (8) RCTs were included in current analysis. Five studies had low RoB. Based on grading the evidence, the inclusion and exclusion of high RoB articles led to moderate and high certainty of evidence, respectively. Based on 8 RCTs (with high RoB), baricitinib statistically significantly reduced mortality where the risk ratio (RR) = 0.84 [95% CI: 0.76 to 0.92; p = 0.0002; I2 = 23%; p = 0.25]. The heterogeneity was insignificant but the RoB was high. We did subgroup analysis of low and high RoB articles and found out baricitinib statistically significantly reduced mortality with the RR = 0.68 [95% CI: 0.56 to 0.82; p < 0.0001; I2 = 0%; p = 0.85] and RR = 0.89 [95% CI: 0.80 to 0.99; p = 0.04; I2 = 0%; p = 0.43], respectively. The heterogeneity was 0% with insignificant p-values in both subgroup analyses. The percentage of mortality reduction was 31.31% and 7.79%, respectively whereas it was 13.95% in main group analysis. ConclusionWith the presence of optimal sample size of 3944 from 5 low RoB studies which represents a minimum of 300 million population of people and with 0% of heterogeneity, the effectiveness of baricitinib in reducing the mortality in COVID-19 patients is concretely proven.

Establishment of a Captive Cave Nectar Bat (Eonycteris spelaea) Breeding Colony in Singapore.

Bats are known natural reservoirs of several highly pathogenic zoonotic viruses, including Hendra virus, Nipah virus, rabies virus, SARS-like coronaviruses, and suspected ancestral reservoirs of SARS-CoV-2 responsible for the ongoing COVID-19 pandemic. The capacity to survive infections of highly pathogenic agents without severe disease, together with many other unique features, makes bats an ideal animal model for studying the regulation of infection, cancer, and longevity, which is likely to translate into human health outcomes. A key factor that limits bat research is lack of breeding bat colonies. To address this need, a captive bat colony was established in Singapore from 19 wild-caught local cave nectar bats. The bats were screened for specific pathogens before the start of captive breeding. Custom-made cages and an optimized diet inclusive of Wombaroo dietary formula, liquid diet, and supplement of fruits enabled the bats to breed prolifically in our facility. Cages are washed daily and disinfected once every fortnight. Bats are observed daily to detect any sick bat or abnormal behavior. In addition, bats undergo a thorough health check once every 3 to 4 mo to check on their overall wellbeing, perform sampling, and document any potential pregnancy. The current colony houses over 80 bats that are successfully breeding, providing a valuable resource for research in Singapore and overseas.

Human adenovirus (HAdV) infection in children with acute respiratory tract infections in Guangzhou, China, 2010-2021: a molecular epidemiology study.

BACKGROUND: Human adenovirus (HAdV) infection can cause a variety of diseases. It is a major pathogen of pediatric acute respiratory tract infections (ARIs) and can be life-threatening in younger children. We described the epidemiology and subtypes shifting of HAdV among children with ARI in Guangzhou, China. METHODS: We conducted a retrospective study of 161,079 children diagnosed with acute respiratory illness at the Guangzhou Women and Children's Medical Center between 2010 and 2021. HAdV specimens were detected by real-time PCR and the hexon gene was used for phylogenetic analysis. RESULTS: Before the COVID-19 outbreak in Guangzhou, the annual frequency of adenovirus infection detected during this period ranged from 3.92% to 13.58%, with an epidemic peak every four to five years. HAdV demonstrated a clear seasonal distribution, with the lowest positivity in March and peaking during summer (July or August) every year. A significant increase in HAdV cases was recorded for 2018 and 2019, which coincided with a shift in the dominant HAdV subtype from HAdV-3 to HAdV-7. The latter was associated with a more severe disease compared to HAdV-3. The average mortality proportion for children infected with HAdV from 2016 to 2019 was 0.38% but increased to 20% in severe cases. After COVID-19 emerged, HAdV cases dropped to 2.68%, suggesting that non-pharmaceutical interventions probably reduced the transmission of HAdV in the community. CONCLUSION: Our study provides the foundation for the understanding of the epidemiology of HAdV and its associated risks in children in Southern China.

A single-center, cross-sectional study of cross-professional faculties' perception to virtual class under different scenarios: A stepwise approach.

BACKGROUND: Virtual teaching in medical education is rising with the increased need caused by the recent pandemic. However, evaluations of the perception of clinical teachers across professions for setting a virtual class in different teaching scenarios are limited. This study aims to identify cross-professional clinical teachers' perception of virtual classes and the acceptability of the virtual class-specific checklist for setting a virtual class. METHODS: We conducted a cross-sectional study to investigate clinical teachers' need to set and teach a virtual class and then designed a virtual class-specific checklist with five essential steps and a related training program in July 2021. After the training, 186 participants were randomly enrolled in October 2021 to evaluate their perceptions about setting virtual classes and the acceptability of the virtual class-specific checklist using an online assessment questionnaire. RESULTS: In our institution, the number of faculty-led virtual classes has recently been on the increase. Our study revealed that most teachers agreed that virtual classes could break space and time limitations, but that the Internet environment could affect the fluency of the virtual class. They further agreed that the essential five steps in the checklist should vary depending on the type of teaching scenario. Most clinical teachers, with the exception of those who teach in the operating room, considered the operating room as the most difficult scenario for setting virtual classes. CONCLUSION: Faculty training for setting virtual classes is essential, and the essential virtual class-specific five steps are suitable for different teachers and teaching scenarios. However, the virtual class-specific checklist should be further adjusted according to the limitations caused by emerging innovative virtual teaching technology.

Multi-omics integrated analysis reveals a specific phenotype of CD8+ T cell may contribute to immunothromosis via Th17 response in severe and critical COVID-19 (preprint)

T lymphocyte reduction and immunosenescence frequently occur in severe and critical coronavirus disease 2019 (COVID-19) patients, which may cause immunothrombosis and numerous sequelae. This study integrated analyzed multi-omics data from healthy donors, pneumonia, COVID-19 patients (mild & moderate, severe, and critical), and convalescences, including clinical, laboratory test, PBMC bulk RNA-seq, PBMC scRNA-seq and TCR-seq, BAL scRNA-seq, and lung proteome. We revealed that there are certain associations among T lymphocyte reduction, CD8+ T cell senescence, Th17 immune activation, and immunothrombosis. A specific phenotype (S. P.) CD8+ T cells were identified in severe and critical COVID-19 patients in both PBMC and BAL scRNA-seq, which showed highly TCR homology with terminal effector CD8+ T cells and senescent CD8+ T cells. Pseudotime analysis showed that the S. P. CD8+ T cells were located in the transition trajectory from mild to severe disease. Which may be activated by terminal effector CD8+ T cells or senescent CD8+ T cells, thereby promoting Th17 cell differentiation. This phenomenon was absent in healthy donors, mild and moderate COVID-19 patients, or convalescences. Our findings are an important reference for avoiding the conversion of patients with mild to severe diseases and provide insight into the future prevention and control of COVID-19 and its variants.

Patient and learner experience in a new set up of a multidisciplinary dermatology-rheumatology clinic care model for psoriatic arthritis.

OBJECTIVES: We described the set-up of a new multidisciplinary psoriatic arthritis-psoriasis (PsA-PsO) clinic incorporating service, education, and research between rheumatologists and dermatologists for PsA. We describe the patients' and learners' experience of this shared-care model. METHODS: A PsA-PsO clinic was newly set up in 2019. Each patient was first seen by a trainee, followed by both a dermatologist and a rheumatologist simultaneously in the same consultation room. We collected patients' and learners' experience through self-administered surveys. RESULTS: From May 2019 to January 2020, we collected data from 44 visits (55% new referrals, 45% follow up) from 30 patients: 22.7% were referred for diagnostic doubts, 77.3% were for therapeutic issues. Eight of the 10 patients referred for diagnosis had PsA confirmed. Medication changes occurred in 63.6% of visits; 63.6% of patients continued follow up in the PsA-PsO clinic, and 36.4% were discharged back to the original respective care. The median (interquartile range) rating of patient satisfaction of the care was 8 (7-8) out of 10; 96.1% of patients would "probably" or "definitely recommend" the care to others. From 20 learners, 95% reported the experience as "extremely" or "very" beneficial to training. The PsA-PsO clinic was suspended during the COVID-19 pandemic from February 2020 because of lack of available staff. The service was resumed gradually from May 2021. CONCLUSION: Despite challenges, we report the set-up of a new care model between dermatologists and rheumatologists for care of patients with psoriatic disease. The care model was well received by patients. Learners from various levels reported benefit from the learning experience.