YouTube Videos for Public Health Literacy? A Machine Learning Pipeline to Curate Covid-19 Videos (preprint)

The COVID-19 pandemic has highlighted the dire necessity to improve public health literacy for societal resilience. YouTube, the largest video-sharing social media platform, provides a vast repository of user-generated health information in a multi-media-rich format which may be easier for the public to understand and use if major concerns about content quality and accuracy are addressed. This study develops an automated solution to identify, retrieve and shortlist medically relevant and understandable YouTube videos that domain experts can subsequently review and recommend for disseminating and educating the public on the COVID-19 pandemic and similar public health outbreaks. Our approach leverages domain knowledge from human experts and machine learning and natural language processing methods to provide a scalable, replicable, and generalizable approach that can also be applied to enhance the management of many health conditions.

The impact of wearing powered air purifying respirators or N95 masks on the olfactory function in healthcare workers: A randomized controlled trial

Background: With the Coronavirus disease 2019 epidemic, wearing a mask has become routine to prevent and control the virus's spread, especially for healthcare workers. However, the impact of long-term mask wear on the human body has not been adequately investigated. This study aimed to investigate whether Powered Air Purifying Respirators and N95 masks impact the olfaction in healthcare workers. Methods: We recruited fifty-six healthcare workers and randomly divided them into 2 groups, wearing a powered air purifying respirator (PAPR) (experiment group, N = 28) and an N95 mask (control group, N = 28). Olfactory discrimination and threshold tests were performed before and after wearing the masks. SPSS 26.0 (SPSS Inc., Chicago, Illinois) software was used for the statistical analyses. Results: There was a statistical difference in the olfactory threshold test after wearing the mask in both PAPR Group (Z = –2.595, P = .009) and N95 Group (Z = –2.120, P = .034), with no significant difference between the 2 (χ2 = 0.29, P = .589). There was no statistical difference in the discrimination test scores in both 2 groups after wearing the masks. Conclusion: Wearing a mask affects the healthcare workers' olfaction, especially odor sensitivity. Healthcare workers have a higher olfactory threshold after long-term mask wear, whether wearing PAPRs or N95 masks.

Factors associated with negative conversion of viral RNA in hospitalized children infected with SARS-CoV-2 Omicron Variant in Shanghai, China:a retrospective analysis (preprint)

Objectives: This study aimed to identify the related risk factors and potential predictors of SARS-CoV-2 RNA negative conversion by describing the dynamics of viral shedding in infected children admitted to two hospitals from Shanghai during Omicron variant outbreak. Methods: This retrospective cohort included laboratory-confirmed cases of SARS-CoV-2 infection from Shanghai between March 28 and May 31, 2022. Clinical characteristics, personal vaccination, household vaccination rates were collected through electronic health records and telephone interviews. Results: The total of 603 pediatric cases confirmed with COVID-19 was included in this study. Both Univariate and multivariate analysis were performed to filter independent factors for the duration to viral RNA negative conversion. Data on cases re-detected SARS-CoV-2after showing negative results on RT-PCR test (intermittent negative status) were also analyzed. The median duration of virus shedding was 12(Interquartile Qange,IQR: 10-14) days. The severity of clinical outcome, personal vaccination-2doses, household vaccination rates, abnormal defecation were factors indecently affecting negative conversion of SARS-CoV-2 RNA, suggesting that patient who had abnormal defecation or with more severe condition would delay virological clearance, while patient accepted 2 doses vaccination or with higher household vaccination rates would accelerate virological clearance. Loss of appetite (Odds Ratio (OR) :5.343; 95%CI: 3.307-8.632) and abnormal defecation (OR:2.840; 95%CI: 1.736-4.645) were significantly associated with intermittent negative status. Conclusion: These findings could provide clues for early identification of pediatric patients with prolonged viral shedding, enriching the evidence for development of prevention and control strategies especially the vaccination policies for children and adolescents.

Factors associated with negative conversion of viral RNA in hospitalized children infected with SARS-CoV-2 Omicron Variant in Shanghai, China (preprint)

Abstract Objectives: This study aimed to identify the related risk factors and potential predictors of SARS-CoV-2 RNA negative conversion by describing the dynamics of viral shedding in infected children admitted to two hospitals from Shanghai during Omicron variant outbreak. Methods: This retrospective cohort included laboratory-confirmed cases of SARS-CoV-2 infection from Shanghai between March 28 and May 31, 2022. Clinical characteristics, personal vaccination, household vaccination rates were collected through electronic health records and telephone interviews. Results: The total of 603 pediatric cases confirmed with COVID-19 was included in this study. Both Univariate and multivariate analysis were performed to filter independent factors for the duration to viral RNA negative conversion. Data on cases re-detected SARS-CoV-2 after showing negative results on RT-PCR test (intermittent negative status) were also analyzed. The median duration of virus shedding was 12(Interquartile Qange,IQR: 10-14) days. The severity of clinical outcome, personal vaccination-2doses, household vaccination rates, abnormal defecation were factors indecently affecting negative conversion of SARS-CoV-2 RNA, suggesting that patient who had abnormal defecation or with more severe condition would delay virological clearance, while patient accepted 2 doses vaccination or with higher household vaccination rates would accelerate virological clearance. Loss of appetite (Odds Ratio (OR) :5.343; 95%CI: 3.307-8.632) and abnormal defecation (OR:2.840; 95%CI: 1.736-4.645) were significantly associated with intermittent negative status. Conclusion: These findings could provide clues for early identification of pediatric patients with prolonged viral shedding, enriching the evidence for development of prevention and control strategies especially the vaccination policies for children and adolescents.

Antiplatelet therapy for patients with COVID-19: Systematic review and meta-analysis of observational studies and randomized controlled trials

Background Hyperinflammation and coagulopathy are hallmarks of COVID-19 and synergistically contribute to illness progression. Antiplatelet agents have been proposed as candidate drugs for COVID-19 treatment on the basis of their antithrombotic and anti-inflammatory properties. A systematic review and meta-analysis that included early observational studies and recent randomized controlled trials (RCTs) was performed to summarize and compare evidence on this issue. Methods PubMed, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched to identify studies published up to Nov 7, 2021, and the results of registered clinical trials were followed up to Mar 30, 2022. We included RCTs and observational studies assessing the effect of antiplatelet therapy in adult patients with COVID-19. Data on baseline patient characteristics, interventions, controls, and outcomes were extracted by two independent reviewers. The primary outcome was mortality. Data were pooled using a random-effects model. Results Twenty-seven studies were included, of which 23 observational studies were pooled in a meta-analysis, and the remaining four RCTs (ACTIV-4B, RECOVERY, ACTIV-4a, and REMAP-CAP) were narratively synthesized. Based on 23 observational studies of 87,824 COVID-19 patients, antiplatelet treatment favors a lower risk of mortality [odds ratio (OR) 0.72, 95% confidence interval (CI) 0.61–0.85;I2 = 87.0%, P < 0.01]. The narrative synthesis of RCTs showed conflicting evidence, which did not support adding antiplatelet therapy to the standard care, regardless of the baseline illness severity and concomitant anticoagulation intensity. Conclusion While the rationale for using antiplatelet treatment in COVID-19 patients is compelling and was supported by the combined result of early observational studies, evidence from RCTs did not confirm this approach. Several factors that could explain this inconsistency were highlighted alongside perspectives on future research directions.

Aerosol Characteristics during the COVID-19 Lockdown in China: Optical Properties, Vertical Distribution, and Potential Source

The concentration changes of aerosols have attracted wide-ranging attention during the COVID-19 lockdown (CLD) period, but the studies involving aerosol optical properties (AOPs) are relatively insufficient, mainly AOD (fine-mode AOD (AODf) and coarse-mode AOD (AODc)), aerosol absorption optical depth (AAOD), and aerosol extinction coefficient (AEC). Here, the remote-sensing observations, Modern-Era Retrospective analysis for Research and Applications, Version 2 (MERRA-2) products, backward-trajectory, and potential-source-contribution models are used to assess the impact of AOPs, vertical distribution, and possible sources on the atmosphere environment in North China Plain (NCP), Central China (CC), Yangtze River Delta (YRD), Pearl River Delta (PRD), and Sichuan Basin (SB) during the CLD period. The results demonstrate that both AOD (MODIS) and near-surface AEC (CALIPSO, <2 km) decreased in most areas of China. Compared with previous years (average 2017–2019), the AOD (AEC) of NCP, CC, YRD, PRD, and SB reduced by 3.33% (10.76%), 14.36% (32.48%), 10.80% (29.64%), 31.44% (22.68%), and 15.50% (8.44%), respectively. In addition, MODIS (AODc) and MERRA-2 (AODc) decreased in the five study areas compared with previous years, so the reduction in dust activities also contributed to improving regional air quality during the epidemic. Despite the reduction of anthropogenic emissions (AODf) in most areas of China during the CLD periods, severe haze events (AODf > 0.6) still occurred in some areas. Compared to previous years, there were increases in BC, OC (MERRA-2), and national raw coal consumption during CLD. Therefore, emissions from some key sectors (raw coal heating, thermal power generation, and residential coal) did not decrease, and this may have increased AODf during the CLD. Based on backward -rajectory and potential source contribution models, the study area was mainly influenced by local anthropogenic emissions, but some areas were also influenced by northwestern dust, Southeast Asian biomass burning, and marine aerosol transport. This paper underscores the importance of emissions from the residential sector and thermal power plants for atmospheric pollution in China and suggests that these sources must be taken into account in developing pollution-mitigation plans. [ FROM AUTHOR] Copyright of Remote Sensing is the property of MDPI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Terpyridyl ruthenium complexes as visible spectral probe for poly(A) RNA and bifunctional TAR RNA binders and HIV-1 reverse transcriptase inhibitors

HIV-1 reverse transcriptase (RT) inhibitors play essential role in anti-HIV therapy. The vast majority of them target the enzymes, while very few are able to bind to the viral RNA. Here we designed and synthesized two new terpyridyl Ru(II) complexes with HIV-1 TAR RNA binding groups. The complex RuTz2 exhibited a remarkable selectivity for poly(A) RNA over calf thymus DNA, total RNA and yeast transfer RNA, generated significant visible spectral response and inhibited the reverse transcription of poly(A) RNA to poly(dT) cDNA by M-MuLV RT. Moreover, RuTz2 was found to target the HIV-1 TAR RNA tightly and selectively by molecular recognition of hydrogen bonds, further stabilize the Ru(II)-RNA binding complex by electrostatic attraction, and efficiently inhibit the HIV-1 RT. These terpyridyl Ru(II) complexes also showed low toxicity to normal cells, which would greatly reduce its harmful side-effect on normal cells in drug application. This work also provides valuable drug design strategies for AIDS and other RT related diseases researches, such as HCV, EBOV and SARS-CoV-2.

COVID-19 vaccine and Menstrual conditions in female: data analysis of the Vaccine Adverse Event Reporting System (preprint)

Background: In reports of adverse reactions following vaccination with the coronavirus disease 2019(COVID-19) vaccines, there have been fewer reports of concern for menstrual disorders in female. Objective: Our study used Vaccine Adverse Event Reporting System(VAERS)to investigate and analyze the relationship between COVID-19 Vaccines and menstrual disorders in female. Methods: We collected reports of menstrual disorders in VAERS from July 2, 1990 to November 12, 2021, and performed a stratified analysis. The potential relationship between COVID-19 vaccine and reports of menstrual disorders was evaluated using the Reporting Odds Ratio (ROR) method. Results: A total of 14,431 reports of menstrual disorders were included in the study, and 13,118 were associated with COVID-19 vaccine. The ROR was 7.83 (95% confidence interval [95%CI]:7.39-8.28). The most commonly reported event was Menstruation irregular (4998 reports), and a higher percentage of female aged 30-49 years reported menstrual disorders (42.55%) after exposure to COVID-19 Vaccines. Both for all reports of menstrual disorders (ROR=5.82;95%CI:4.93-6.95) and excluding reports of unknown age (ROR=13.02;95%CI:10.89-15.56), suggest that female age may be associated with menstrual disorders after vaccination with the COVID-19 Vaccines. Conclusion: Our study suggests a potential safety signal among female who received the COVID-19 vaccine, which may cause menstrual disorders in young adult female (30-49 years old). However, due to the well-known limitations of spontaneous reporting data, it is challenging to directly define menstrual disorders as an adverse event of the COVID-19 Vaccines, and reports of adverse reactions to COVID-19 Vaccines in this age group should continue to be tracked.

White Blood Cell Variability and Clinical Outcomes in Hospitalized Patients With COVID-19 (preprint)

Background: Inflammation parameters, such as white blood cell (WBC) counts, are closely related to the severity and mortality of Coronavirus disease 2019 (COVID-19). Nevertheless, the association between inflammation fluctuation and clinical outcomes in patients with COVID‐19 is not clear.Methods: We performed a secondary analysis of the ORCHID trial. Inflammation fluctuation was assessed by WBC variability indices (SD [standard deviation], and CV [coefficient of variation]). Cox regression was used to compute the hazard ratio for WBC variability and associated hospitalization and death over 28 days.Results: During the 28 days post-randomization, 46 (10.8%) patients died, and 345 (81.4%) patients were discharged. In multivariable analysis, a worse clinical outcome, including decreased risk of hospital discharge (SD: HR: 2.32; P<0.001; CV: 1.72; P=0.001) and increased mortality (SD: HR: 1.51; P=0.002; CV: 1.35; P=0.006), was found with increased WBC variability. Furthermore, WBC variability had moderate performances in predicting discharge (C-index, SD: 0.705; CV: 0.703), and all-cause death over 28 days (C-index, SD: 0.632, CV: 0.688). Sensitivity analyses that involved changing 28-day mortality to in-hospital mortality, recalculating the WBC indices by using the lowest WBC value, and using the competing risk model generated confirmatory results. Most of the interactions between sex, age (>65), hydroxychloroquine treatment group, and WBC variability indices were not significant (P>0.05).Conclusion: In conclusion, our results showed that COVID-19 patients with higher WBC variability had lower discharge rates and higher mortality. Our study contributes to our understanding of the relationship between inflammation and COVID-19-related adverse outcomes.Clinical trial registration: URL: https://clinicaltrials.gov. Unique identifier: NCT04332991.

Reference-based comparison of adaptive immune receptor repertoires (preprint)

B- and T-cell receptor (immune) repertoires can represent an individual’s immune history. While current repertoire analysis methods aim to discriminate between health and disease states, they are typically based on only a limited number of parameters (e.g., clonal diversity, germline usage). Here, we introduce immuneREF: a quantitative multi-dimensional measure of adaptive immune repertoire (and transcriptome) similarity that allows interpretation of immune repertoire variation by relying on both repertoire features and cross-referencing of simulated and experimental datasets. immuneREF is implemented in an R package and was validated based on detection sensitivity of immune repertoires with known similarities and dissimilarities. To quantify immune repertoire similarity landscapes across health and disease, we applied immuneREF to >2400 datasets from individuals with varying immune states (healthy, [autoimmune] disease and infection [Covid-19], immune cell population). Importantly we discovered, in contrast to the current paradigm, that blood-derived immune repertoires of healthy and diseased individuals are highly similar for certain immune states, suggesting that repertoire changes to immune perturbations are less pronounced than previously thought. In conclusion, immuneREF implements population-wide analysis of immune repertoire similarity and thus enables the study of the adaptive immune response across health and disease states.

The Delivery of Nitric Oxide in the Cardiovascular System: Implication for Clinical Diagnosis and Therapy (preprint)

Nitric oxide (NO) is a key molecule in cardiovascular homeostasis and its abnormal delivery is highly associated with the occurrence and development of cardiovascular disease (CVD). The assessment and manipulation of NO delivery is crucial to the diagnosis and therapy of CVD, such as endothelial dysfunction, atherosclerotic progression, pulmonary hypertension, and cardiovascular manifestations of Coronavirus (COVID-19). However, due to the low concentration and fast reaction characteristics of NO in cardiovascular system, the clinical applications centered on the NO delivery are challenging. In this tutorial review, we first summarized the methods to estimate the in vivo NO delivery process based on the clinical images and mathematical modeling to assess the endothelial function and vulnerability of atherosclerotic plaque. Then, the emerging bioimaging technologies that have the potential to directly measure the arterial NO concentration were discussed, including the Raman spectroscopy and electrochemical sensor. Aside from the diagnostic methods, therapies aimed at controlling NO delivery to regulate CVD were reviewed, including the inhaled NO therapy to treat the pulmonary hypertension and COVID-19, stem cell therapy and NO-releasing platform to treat endothelial dysfunction and atherosclerosis.

Safety, Immunogenicity, and Efficacy of COVID-19 Vaccine in Children and Adolescents: A Systematic Review (preprint)

AimTo identify the safety, immunogenicity, and protective efficacy of COVID-19 vaccine in children and adolescents. MethodsWe conducted a systematic review. Databases including PubMed, Web of Science, WHO COVID-19 database, and CNKI were searched on 23 July 2021. International Clinical Trials Registry Platform (ICTRP) was also searched to collect ongoing trials. We included published researches or ongoing clinical trials related to the safety, immunogenicity, and efficacy of COVID-19 vaccine in children or adolescents (aged [≤]18 years). Meta-analysis was performed if the consistency of the included studies was high. If not, descriptive analyses were performed. ResultsEight published studies with 2851 children or adolescents and 28 ongoing clinical trials were included. Among eight published studies, two (25.0%) were RCTs, two (25.0%) case series, and four (50.0%) case reports. The results showed selected COVID-19 vaccines had a good safety profile in children and adolescents. Injection site pain, fatigue, headache, and chest pain were the most common adverse events. Some studies reported a few cases of myocarditis and pericarditis. Two RCTs showed that the immune response to BNT162b2 in adolescents aged 12-15 years was non-inferior to that in young people aged 16-25 years, while a stronger immune response was detected with 3g CoronaVac injection. Only one single RCT showed the efficacy of BNT162b2 was 100% (95% CI: 75.3 to 100). Of the 28 ongoing clinical trials, twenty-three are interventional studies. Fifteen countries are conducting interventional clinical trials of COVID-19 vaccines in children and adolescents. Among them, China (10, 43.5%) and United Stated (9, 39.1%) were the top two countries with the most trials. BNT162b2 was the most common vaccine, which is under testing. ConclusionSome of the COVID-19 vaccines have potential protective effects in children and adolescents, but awareness is needed to monitor possible adverse effects after injection. Clinical trials of the COVID-19 vaccine in children and adolescents with long follow-up, large sample size, and different vaccines are still urgently needed.

Clinical value of blood markers to assess the severity of coronavirus disease 2019.

BACKGROUND: Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is threatening the world with the symptoms of seasonal influenza. This study was conducted to investigate the patient characteristics and clinical value of blood markers to assess the severity of coronavirus disease 2019 (COVID-19). METHODS: 187 patients, diagnosed with COVID-19 (non-severe and severe cases) and admitted to hospital between January 27th and March 8th of 2020, were enrolled in the present study. RESULTS: A higher proportion of clinical symptoms, including cough, expectoration, myalgia, and fatigue were observed in the non-severe group. The level of white blood cell count, neutrophils, CRP, IL-6 and IL-8 were significantly increased, while the platelet count was remarkedly decreased in the severe group. The risk model based on lymphocyte, IL-6, IL-8, CRP and platelet counts had the highest area under the receiver operator characteristic curve (AUROC). The baseline of IL-6, IL-8 and CRP was positively correlated with other parameters except in the cases of lymphocyte, hemoglobin and platelet counts. The baseline of the platelet count was negatively correlated with other parameters except in the lymphocyte and hemoglobin counts. Additionally, there was no connection between the severity of COVID-19 and cultures of blood, sputum or catheter secretion. CONCLUSIONS: The present study suggested that high leucocyte and low platelets counts were independent predictive markers of the severity of COVID-19.

Associations Between the Use of Non-Steroidal Anti-Inflammatory Drugs and Adverse Outcomes Among Patients with COVID-19: A Systematic Review and Meta-Analysis (preprint)

Background: There are concerns that the use of non-steroidal anti-inflammatory drugs (NSAIDs) may increase the risk of adverse outcomes in COVID-19 patients. Therefore, this study aimed to synthesize the existing evidence on associations between the use of NSAIDs and adverse outcomes among patients with COVID-19.Methods: Systematic search of WHO COVID-19 Database, Medline, The Cochrane Library, Web of Science, Embase, China Biology Medicine disc, China National Knowledge Infrastructure, and Wanfang Database for all articles published from January 1, 2020, to August 10, 2021, as well as a supplementary search of Google Scholar. We included comparative observational studies and randomized controlled trials that enrolled patients with COVID-19 who took NSAIDs before or after diagnosis of COVID-19. Data extraction and quality assessment of methodology of included studies were completed by two reviewers independently. We conducted a meta-anlysis on the main outcomes, as well as selected subgroup analyses stratified by the type of NSAID.Fingings: Fifteen non-randomized studies evaluating 24700 adult COVID-19 patients were identified. The use of NSAIDs in patients with COVID-19, compared with no use of NSAIDs, was not significantly associated with an elevated mortality (odds ratio [OR]=0.94, 95% confidence interval [CI]: 0.87 to 1.02), or an increased probability of ICU admission (OR=1.35, 95% CI: 0.73 to 2.49), requiring mechanical ventilation (OR=1.23, 95% CI: 0.71 to 2.13), or administration of supplemental oxygen (OR=0.99, 95% CI: 0.91 to 1.08). The subgroup analyses revealed that the use of ibuprofen (OR=1.22, 95% CI: 0.32 to 4.60), etoricoxib (OR=0.36, 95% CI: 0.02 to 6.49) or celecoxib (zero deaths in both groups) were not associated with an increased risk of death in COVID-19 patients, compared with not using any NSAID.Interpretation: Fever is one of the main clinical symptoms of COVID-19. According to our findings, NSAIDs such as ibuprofen can be used to treat fever in COVID-19 patients safely.Funding: None to declare. Declaration of Interest: None to declare.

Prevalence use of nonsteroidal anti-inflammatory drugs in the general population with COVID-19 and associated COVID-19 risk, hospitalization, severity, death, and safety outcomes: A systematic review and meta-analysis (preprint)

Introduction: Recent reports of potential harmful effects of nonsteroidal anti-inflammatory drugs (NSAIDs) in patients with Corona Virus Disease 2019 (COVID-19) have provoked great concern. Therefore, the safety of NSAIDs is still questioned. Methods: We searched the PubMed, EMBASE, Cochrane Library and Web of Science databases from December 2019 to January 2021 to examine use prevalence for NSAIDs in general, as well as associated COVID-19 risk and outcomes. This study has been registered with PROSPERO (CRD42019132063) Results: We included 25 studies with a total of 101,215 COVID-19 patients. The use of NSAIDs in COVID-19 patients reached 19%. Exposure to NSAIDs was not associated with significantly increased risk of developing COVID-19 (odds ratio [OR]=0.98, 95% confidence interval [CI]: 0.78-1.24; I2=82%), hospitalization (OR=1.06, 95%CI: 0.76-1.48; I2=81%), mechanical ventilation (OR=0.71, 95%CI: 0.47-1.06; I2=38%), and length of hospital stay. Moreover, use of NSAIDs was significantly associated with better outcomes, including severity of COVID-19 (OR=0.79, 95%CI: 71-0.89; I2=0%) and death (OR=0.68, 95%CI: 0.52-0.89; I2=85%) in patients with COVID-19. Regarding safety outcomes, exposure to NSAIDs was associated with increased risk of stroke (OR=2.32, 95%CI: 1.04-5.2; I2=0%), but not with myocardial infraction (OR=1.49; p=0.66; I2=0%), overt thrombosis (OR=0.76, p=0.50; I2=28%) and major bleeding (p=0.61). Conclusion: Based on current evidence, exposure to NSAIDs is not linked to increased odds or exacerbation of COVID-19 in the general COVID-19 population. Furthermore, administration of NSAIDs might have better outcomes and survival benefits in the general COVID-19 population, although potentially increasing the risk of stroke. Use of NSAIDs might be safe and beneficial in COVID-19. Future observational and randomized control trials are needed for further confirmation.

Prevalence use of nonsteroidal anti-inflammatory drugs in the general population with COVID-19 and associated COVID-19 risk, hospitalization, severity, death, and safety outcomes: A systematic review and meta-analysis (preprint)

Introduction: Recent reports of potential harmful effects of nonsteroidal anti-inflammatory drugs (NSAIDs) in patients with Corona Virus Disease 2019 (COVID-19) have provoked great concern. Therefore, the safety of NSAIDs is still questioned.Methods We searched the PubMed, EMBASE, Cochrane Library and Web of Science databases from December 2019 to January 2021 to examine use prevalence for NSAIDs in general, as well as associated COVID-19 risk and outcomes. This study has been registered with PROSPERO (CRD42019132063)Results We included 25 studies with a total of 101,215 COVID-19 patients. The use of NSAIDs in COVID-19 patients reached 19%. Exposure to NSAIDs was not associated with significantly increased risk of developing COVID-19 (odds ratio [OR] = 0.98, 95% confidence interval [CI]: 0.78–1.24; I2 = 82%), hospitalization (OR = 1.06, 95%CI: 0.76–1.48; I2 = 81%), mechanical ventilation (OR = 0.71, 95%CI: 0.47–1.06; I2 = 38%), and length of hospital stay. Moreover, use of NSAIDs was significantly associated with better outcomes, including severity of COVID-19 (OR = 0.79, 95%CI: 71–0.89; I2 = 0%) and death (OR = 0.68, 95%CI: 0.52–0.89; I2 = 85%) in patients with COVID-19. Regarding safety outcomes, exposure to NSAIDs was associated with increased risk of stroke (OR = 2.32, 95%CI: 1.04–5.2; I2 = 0%), but not with myocardial infraction (OR = 1.49; p = 0.66; I2 = 0%), overt thrombosis (OR = 0.76, p = 0.50; I2 = 28%) and major bleeding (p = 0.61).Conclusion Based on current evidence, exposure to NSAIDs is not linked to increased odds or exacerbation of COVID-19 in the general COVID-19 population. Furthermore, administration of NSAIDs might have better outcomes and survival benefits in the general COVID-19 population, although potentially increasing the risk of stroke. Use of NSAIDs might be safe and beneficial in COVID-19. Future observational and randomized control trials are needed for further confirmation.

Perspectives on Frailty Screening, Management and Its Implementation Among Acute Care Providers in Singapore: A Qualitative Study (preprint)

Background Frailty has emerged to be a public health concern among aging populations. COVID-19 pandemic has reminded how the frailest individuals are particularly exposed to adverse outcomes. It is important to identify and manage frailty to delay functional decline and reduce unnecessary health utilizations. Our study explored understanding on frailty and practice of frailty screening among different acute care professionals in Singapore, (2) identify barriers and facilitators concerning frailty screening, management and its implementation.Methods A qualitative study using focus group discussion among nurses and individual interviews among physicians from four departments (Accident & Emergency, Anaethesia, General Surgery, Orthopedics) in three acute hospitals from the three public health clusters in Singapore. Participants were recruited through a combination of purposive, convenience and snowball approach with a directed approach by using NVIVO 12.0 to analyse the data. Result Frailty was mainly but inadequately understood as a physical and age-related concept. Screening for frailty in acute care was considered necessary to reduce adverse health outcomes. Specific issues related to screening, management and implementation identified were: cooperation from patient/caregivers, acceptance from healthcare workers/hospital managers, need for dedicated resources, guidelines for follow-up management and consensus on the scope of measurement for different specialties. Conclusion Our findings indicated the need for 1) education program for patients/care givers and stakeholders 2) hospital wide push to adopt and develop a uniform frailty screening tool and process and 3) applying relevant guidelines, developing whole of hospital approach and process for the management of frail patients.

Low serum vitamin D level and COVID-19 infection and outcomes, a multivariate meta-analysis (preprint)

Objective: This study aimed to determine whether serum vitamin D is independently associated with COVID-19 infection and outcomes in patients with COVID-19. Methods: We identified relevant studies by searching the PubMed, Embase, and medRxiv databases from December 2019 to October 1, 2020. Odds ratios (ORs) were pooled using random-effects models. Only reports with multivariate adjusted results were included to avoid the impact of potential confounding factors. Results: A total of six studies with 377,265 patients were identified. Overall, in the categorical analysis, a low serum vitamin D level was associated with an increased risk of COVID-19 infection (OR: 1.47, 95% CI: 1.09- 1.97, I2=81%), hospitalization (OR: 1.83, 95% CI: 1.22-2.74, I2=0%), but not in-hospital death (OR: 2.73, 95% CI: 0.27-27.61). Notably, when vitamin D level was analyzed as a continuous variable, each 5 ng/ml increase in vitamin D level was not associated with any increased risk of COVID-19 infection (OR: 1.04, 95% CI: 0.96-1.12, I2=74%) or in-hospital death (OR: 1.02, 95% CI: 0.93-1.12). Conclusions: Low serum vitamin D is associated with an increased risk of COVID-19 infection and hospitalization. In-hospital death showed a tendency to be increased in COVID-19 patients with low vitamin D levels. The ongoing clinical trials for evaluation of vitamin D supplementation will be key to the validation of this adjunctive treatment for COVID-19 patients.

Inflammation Level Severity and Death in Patients With COVID-19: A Rapid Systematic Review and Meta-Analysis (preprint)

Background: An association among the use of angiotensin-converting-enzyme(ACE) inhibitors and angiotensin-receptor blockers(ARBs) with the clinical outcomes of coronavirus disease 2019 (COVID-19) is unclear. Methods: PubMed, EMBASE, and the preprint databases MedRxiv and BioRxiv were searched for relevant studies that assessed the association among inflammation level, application of ACEI/ARB, infection severity and death in patients with COVID-19. Odd risks(OR) and 95% confidence interval (CI) were combined using random-effects or fixed models depending on heterogeneity. Results: Eleven studies were included with a total of 33,483 patients. Our review showed ACEI/ARB therapy might be associated with the reduced inflammatory factor (interleukin-6) and elevated level of immune cells(CD3, CD8). Meta-analysis showed no significant increase in the risk of COVID-19 infection(OR:0.95, 95%CI:0.89-1.05) in patients receiving ACEI/ARB therapy, and ACEI/ARB therapy was associated with a decreased risk of severe COVID-19 (OR:0.75, 95%CI: 0.59-0.96) and mortality (OR:0.52, 95%CI: 0.35-0.79). Subgroup analyses showed that, among the general population, application of ACEI/ARB therapy was associated with reduced risks of all-cause death(OR:0.31, 95%CI: 0.13-0.75), and the risk of severe COVID-19(OR:0.79, 95%CI: 0.60-1.05) infection and COVID-19 infection(OR:0.85, 95% CI: 0.66-1.08) were not increased. Among patients with hypertension, the use of an ACEI/ARB was associated with a lower severity of COVID-19(OR:0.73, 95%CI: 0.51-1.03) and lower mortality(OR:0.57, 95%CI: 0.37-0.87), without evidence of an increased risk of COVID-19 infection(OR:1.00, 95%CI: 0.90-1.12). Conclusion: On the basis of the available evidence, this is the first meta-analysis showed that, in general population, the use of ACEI/ARB therapy was safe without an increased risk of COVID-19 infection and with a decreasing trend of severe COVID-19 infection and lower mortality. In patients with hypertension, the use of ACEI/ARB therapy should be encouraged, without increased risk of COVID-19 inflection, and better prognosis (a decreasing trends of severe COVID-19 and reduced all-cause death). Overall, ACEI/ARB therapy should be continued in patients who are at risk for, or have COVID-19, either in general population or hypertension patients. Our results need to be interpreted with caution considering the potential for residual confounders, and more well-designed studies that control the clinical confounders are necessary to confirm our findings. Key Words COVID-19; ACEI/ARB; SARS-COV-2; pneumonia; infectious disease; lung, hypertension