The relationship between fear of COVID-19 and health anxiety among families with COVID-19 infected: The mediating role of metacognitions, intolerance of uncertainty and emotion regulation.

The current study aimed to investigate the mediating role of metacognitions, intolerance of uncertainty and emotion regulation in the relationship between fear of COVID-19 (FC-19) and health anxiety, among families with COVID-19 infected. Participants were 541 individuals from family members of patients with COVID-19 (F = 52.3%, mean age = 41.3 ± 13.2 years). Data were collected with a packet including sociodemographic and risk factors, the Fear of COVID-19 Scale, the Short Health Anxiety Inventory, the Metacognitions Questionnaire 30, the Intolerance of Uncertainty Scale-12 and the Emotion Regulation Questionnaire. Structural equation modelling analyses revealed a full mediation of metacognitions (i.e., positive beliefs about worry, negative beliefs about thoughts concerning uncontrollability and danger, cognitive confidence and beliefs about the need to control thoughts), intolerance of uncertainty and expressive suppression in the relation between FC-19 and health anxiety. Moreover, the strongest indirect links were found between FC-19 and health anxiety through negative beliefs about thoughts concerning uncontrollability and danger and intolerance of uncertainty. These associations were independent of gender and risk status. The final model accounted for 71% of the variance of health anxiety. These findings suggest that particularly metacognitions, intolerance of uncertainty and expressive suppression play a full mediational role in the relation between FC-19 and health anxiety.

Implications of early respiratory support strategies on disease progression in critical COVID-19: a matched subanalysis of the prospective RISC-19-ICU cohort.

BACKGROUND: Uncertainty about the optimal respiratory support strategies in critically ill COVID-19 patients is widespread. While the risks and benefits of noninvasive techniques versus early invasive mechanical ventilation (IMV) are intensely debated, actual evidence is lacking. We sought to assess the risks and benefits of different respiratory support strategies, employed in intensive care units during the first months of the COVID-19 pandemic on intubation and intensive care unit (ICU) mortality rates. METHODS: Subanalysis of a prospective, multinational registry of critically ill COVID-19 patients. Patients were subclassified into standard oxygen therapy ≥10 L/min (SOT), high-flow oxygen therapy (HFNC), noninvasive positive-pressure ventilation (NIV), and early IMV, according to the respiratory support strategy employed at the day of admission to ICU. Propensity score matching was performed to ensure comparability between groups. RESULTS: Initially, 1421 patients were assessed for possible study inclusion. Of these, 351 patients (85 SOT, 87 HFNC, 87 NIV, and 92 IMV) remained eligible for full analysis after propensity score matching. 55% of patients initially receiving noninvasive respiratory support required IMV. The intubation rate was lower in patients initially ventilated with HFNC and NIV compared to those who received SOT (SOT: 64%, HFNC: 52%, NIV: 49%, p = 0.025). Compared to the other respiratory support strategies, NIV was associated with a higher overall ICU mortality (SOT: 18%, HFNC: 20%, NIV: 37%, IMV: 25%, p = 0.016). CONCLUSION: In this cohort of critically ill patients with COVID-19, a trial of HFNC appeared to be the most balanced initial respiratory support strategy, given the reduced intubation rate and comparable ICU mortality rate. Nonetheless, considering the uncertainty and stress associated with the COVID-19 pandemic, SOT and early IMV represented safe initial respiratory support strategies. The presented findings, in agreement with classic ARDS literature, suggest that NIV should be avoided whenever possible due to the elevated ICU mortality risk.

Corticosteroids in SARS-COV2 infection: certainties and uncertainties in clinical practice.

INTRODUCTION: The SARS-COV-2 pandemic is a worldwide public health problem due to the large medical burden and limited number of therapies available. Corticosteroids have a rather unclear efficacy in viral non-SARS-COV-2 pneumonias and therefore their use is not universally recommended. In SARS-COV-2 pneumonia however, it is expected that they can reduce the deleterious consequences of the virus-related systemic inflammation. AREAS COVERED: a MEDLINE search covering the period 1995-2020 was completed to identify relevant papers. SARS-COV-2 pathogenesis is very complex and is represented by the interplay of many cytokine-driven inflammation pathways. Its most severe form so called cytokine storm, is an exaggerate reaction of the host infected by the virus rapidly resulting in multiple organ dysfunction (MODS). Corticosteroids have the potential to blunt the inflammation response in such patients, but their efficacy is not the same for all patients. Further on the certainties and uncertainties regarding the efficacy of this therapy in SARS-COV-2 pneumonia are discussed. EXPERT OPINION: In patients with severe SARS-COV-2 pneumonia, corticosteroids can be efficacious, but it is still not clear if they can be safely used in patients with comorbid cardiovascular disease or how the optimal duration of therapy can be established.

A qualitative examination of graduating nurses' response to the Covid-19 pandemic.

BACKGROUND: Currently, graduating nurses face pandemic-related uncertainty including gaps in risk perception, unexpected Covid-19 moral dilemmas, and distress surrounding personal health risk. RESEARCH QUESTION/AIM/OBJECTIVES/METHOD: The purpose of this basic qualitative descriptive study is to describe the willingness of graduating nurses to provide care during the Covid-19 pandemic. PARTICIPANTS AND RESEARCH CONTEXT: One week prior to graduation, students were required to submit a written assignment describing willingness to practice in light of the ongoing pandemic. ETHICAL CONSIDERATIONS: This study was approved by an Institutional Review Board. FINDINGS/RESULTS: Eighty-four (n = 84) assignments were used for analysis. Of these, 82% (n = 69) of the graduating nurses describe a willingness to voluntarily care for Covid-19 patients. After summarizing narrative responses, two themes emerged including self-assessment of personal and familial risk and conflicting obligations. DISCUSSION: The assessment of risk to self and family are key in determining whether graduating nurses will care for Covid-19 patients. Conflicting obligations may contribute to stress and uncertainty potentially leading to early burnout. CONCLUSION: Findings from this study can inform academicians of the need to adequality prepare graduating nurses for Covid-19-associated risks and ethical decision making. Organizations should alter residencies and orientation to support the needs of new nurses.

Convalescent plasma or hyperimmune immunoglobulin for people with COVID-19: a living systematic review.

BACKGROUND: Convalescent plasma and hyperimmune immunoglobulin may reduce mortality in patients with viral respiratory diseases, and are being investigated as potential therapies for coronavirus disease 2019 (COVID-19). A thorough understanding of the current body of evidence regarding benefits and risks of these interventions is required.  OBJECTIVES: Using a living systematic review approach, to assess whether convalescent plasma or hyperimmune immunoglobulin transfusion is effective and safe in the treatment of people with COVID-19; and to maintain the currency of the evidence. SEARCH METHODS: To identify completed and ongoing studies, we searched the World Health Organization (WHO) COVID-19 Global literature on coronavirus disease Research Database, MEDLINE, Embase, the Cochrane COVID-19 Study Register, the Epistemonikos COVID-19 L*OVE Platform, and trial registries. Searches were done on 17 March 2021. SELECTION CRITERIA: We included randomised controlled trials (RCTs) evaluating convalescent plasma or hyperimmune immunoglobulin for COVID-19, irrespective of disease severity, age, gender or ethnicity. For safety assessments, we also included non-controlled non-randomised studies of interventions (NRSIs) if 500 or more participants were included. We excluded studies that included populations with other coronavirus diseases (severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS)), as well as studies evaluating standard immunoglobulin. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methodology. To assess bias in included studies, we used the Cochrane 'Risk of Bias 2' tool for RCTs, and for NRSIs, the assessment criteria for observational studies, provided by Cochrane Childhood Cancer. We rated the certainty of evidence, using the GRADE approach, for the following outcomes: all-cause mortality, improvement and worsening of clinical status (for individuals with moderate to severe disease), development of severe clinical COVID-19 symptoms (for individuals with asymptomatic or mild disease), quality of life (including fatigue and functional independence), grade 3 or 4 adverse events, and serious adverse events. MAIN RESULTS: We included 13 studies (12 RCTs, 1 NRSI) with 48,509 participants, of whom 41,880 received convalescent plasma. We did not identify any completed studies evaluating hyperimmune immunoglobulin. We identified a further 100 ongoing studies evaluating convalescent plasma or hyperimmune immunoglobulin, and 33 studies reporting as being completed or terminated. Individuals with a confirmed diagnosis of COVID-19 and moderate to severe disease Eleven RCTs and one NRSI investigated the use of convalescent plasma for 48,349 participants with moderate to severe disease. Nine RCTs compared convalescent plasma to placebo treatment or standard care alone, and two compared convalescent plasma to standard plasma (results not included in abstract). Effectiveness of convalescent plasma We included data on nine RCTs (12,875 participants) to assess the effectiveness of convalescent plasma compared to placebo or standard care alone.  Convalescent plasma does not reduce all-cause mortality at up to day 28 (risk ratio (RR) 0.98, 95% confidence interval (CI) 0.92 to 1.05; 7 RCTs, 12,646 participants; high-certainty evidence). It has little to no impact on clinical improvement for all participants when assessed by liberation from respiratory support (RR not estimable; 8 RCTs, 12,682 participants; high-certainty evidence). It has little to no impact on the chance of being weaned or liberated from invasive mechanical ventilation for the subgroup of participants requiring invasive mechanical ventilation at baseline (RR 1.04, 95% CI 0.57 to 1.93; 2 RCTs, 630 participants; low-certainty evidence). It does not reduce the need for invasive mechanical ventilation (RR 0.98, 95% CI 0.89 to 1.08; 4 RCTs, 11,765 participants; high-certainty evidence). We did not identify any subgroup differences.  We did not identify any studies reporting quality of life, and therefore, do not know whether convalescent plasma has any impact on quality of life. One RCT assessed resolution of fatigue on day 7, but we are very uncertain about the effect (RR 1.21, 95% CI 1.02 to 1.42; 309 participants; very low-certainty evidence).  Safety of convalescent plasma We included results from eight RCTs, and one NRSI, to assess the safety of convalescent plasma. Some of the RCTs reported on safety data only for the convalescent plasma group.  We are uncertain whether convalescent plasma increases or reduces the risk of grade 3 and 4 adverse events (RR 0.90, 95% CI 0.58 to 1.41; 4 RCTs, 905 participants; low-certainty evidence), and serious adverse events (RR 1.24, 95% CI 0.81 to 1.90; 2 RCTs, 414 participants; low-certainty evidence).  A summary of reported events of the NRSI (reporting safety data for 20,000 of 35,322 transfused participants), and four RCTs reporting safety data only for transfused participants (6125 participants) are included in the full text. Individuals with a confirmed diagnosis of SARS-CoV-2 infection and asymptomatic or mild disease We identified one RCT reporting on 160 participants, comparing convalescent plasma to placebo treatment (saline).  Effectiveness of convalescent plasma We are very uncertain about the effect of convalescent plasma on all-cause mortality (RR 0.50, 95% CI 0.09 to 2.65; very low-certainty evidence). We are uncertain about the effect of convalescent plasma on developing severe clinical COVID-19 symptoms (RR not estimable; low-certainty evidence).  We identified no study reporting quality of life.  Safety of convalescent plasma We do not know whether convalescent plasma is associated with a higher risk of grade 3 or 4 adverse events (very low-certainty evidence), or serious adverse events (very low-certainty evidence). This is a living systematic review. We search weekly for new evidence and update the review when we identify relevant new evidence. Please refer to the Cochrane Database of Systematic Reviews for the current status of this review. AUTHORS' CONCLUSIONS: We have high certainty in the evidence that convalescent plasma for the treatment of individuals with moderate to severe disease does not reduce mortality and has little to no impact on measures of clinical improvement. We are uncertain about the adverse effects of convalescent plasma. While major efforts to conduct research on COVID-19 are being made, heterogeneous reporting of outcomes is still problematic. There are 100 ongoing studies and 33 studies reporting in a study registry as being completed or terminated. Publication of ongoing studies might resolve some of the uncertainties around hyperimmune immunoglobulin therapy for people with any disease severity, and convalescent plasma therapy for people with asymptomatic or mild disease.

Treatment of severe acute ulcerative colitis in SARS-CoV-2 infected patients: report of three cases and discussion of treatment options.

In the wake of the coronavirus disease 2019 (COVID-19) pandemic, it is unclear how asymptomatic severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-infected patients who present with acute severe ulcerative colitis (UC) can be treated effectively and safely. Standard treatment regimens consist of steroids, immunomodulatory drugs, and biological therapies, but therapeutic decision-making becomes challenging as there are uncertainties about how to deal with these drugs in patients with COVID-19 and active UC. Importantly, guidelines for this particular group of patients with UC are still lacking. To inform therapeutic decision-making, we describe three consecutive cases of patients with active UC and COVID-19 and discuss their treatments based on theoretical knowledge, currently available evidence and clinical observations. Three patients were identified through our national inflammatory bowel disease network [Initiative on Crohn's and Colitis (ICC)] for whom diagnosis of SARS-CoV-2-infection was established by reverse transcription-polymerase chain reaction (RT-PCR) testing in nasopharynx, stools, and/or biopsies. Acute severe UC was diagnosed by clinical parameters, endoscopy, and histopathology. Clinical guidelines for SARS-CoV-2-negative patients advocate the use of steroids, calcineurin inhibitors, or tumor necrosis factor alpha (TNF-α)-antagonists as induction therapy, and experiences from the current three cases show that steroids and TNF-α-antagonists could also be used in patients with COVID-19. This could potentially be followed by TNF-α-antagonists, vedolizumab, or ustekinumab as maintenance therapy in these patients. Future research is warranted to investigate if, and which, immunomodulatory drugs should be used for COVID-19 patients that present with active UC. To answer this question, it is of utmost importance that future cases of patients with UC and COVID-19 are documented carefully in international registries, such as the SECURE-IBD registry.

Illness uncertainty among patients with COVID-19 in the Mobile Cabin Hospital.

AIMS: To investigate the status and influencing factors of illness uncertainty among patients with coronavirus disease 2019 (COVID-19) in the mobile cabin hospital. DESIGN: A cross-sectional study. METHODS: 114 patients with COVID-19 admitted to a mobile cabin hospital in Wuhan, Hubei Province, in February 2020 were enrolled by a convenience sampling method. The Chinese version of the Mishel Illness Uncertainty Scale (MUIS) was used to assess patients' degree of illness uncertainty, and multiple regression analysis was used to explore the influencing factors. RESULTS: The average total score of MUIS (Chinese version) was 52.22 ± 12.51, indicating a moderate level of illness uncertainty. The dimension unpredictability turned out to have the highest mean score: 2.88 ± 0.90. The multiple stepwise regression analysis showed that female (t = 2.462, p = .015), monthly family income not less than RMB 10,000 (t = -2.095, p = .039), and disease duration of 28 days or more (t = 2.249, p = .027) were independent influencing factors of illness uncertainty. CONCLUSION: Patients with COVID-19 are at a moderate level of illness uncertainty. Medical staffs should pay more attention to female patients, patients with lower monthly family income, patients with the prolonged disease, and take targeted interventions to help them reduce illness uncertainty. IMPACT: Facing the brand new and unknown infectious disease, patients confirmed of COVID-19 suffer from immense physical and psychological stress, where illness uncertainty is a major stressor that troubles patients. The present study surveys illness uncertainty among patients with COVID-19 in the mobile cabin hospital with results revealing a moderate level. Study results will benefit nurses in any setting where care for patients with COVID-19 is provided, public policymakers and future researchers.

Changes in Emergency Department Patient Volume and Acuity Associated with Early Stages of the COVID-19 Pandemic in a Unique Environment.

INTRODUCTION: Hospitals and emergency departments (EDs) faced profound uncertainty during the COVID-19 pandemic. Early concerns regarding demand far exceeding capacity were balanced by anecdotal reports of decreased patient visits, including those for specific high-acuity conditions. This study sought to identify changes in ED volume and acuity, within a specific managed care environment, associated with the onset of the pandemic. METHODS: Data from patient visits to 2 San Diego, California, EDs-within an integrated health-care system-were extracted from the electronic health record. Daily patient visits, hospital admissions from the ED, Emergency Severity Index scores, and mode of arrival were compared between two 28-day periods, with the 28 days following a "stay at home" order issued by the governor of California and a control period of the same dates in 2019. RESULTS: These EDs observed a significant decrease in daily visits (42% compared to the previous year) associated with the pandemic. An increased rate of hospital admissions (16.6%-21.6%) was suggestive of an overall increase in acuity; however, changes in the distribution of Emergency Severity Index scores were less pronounced. The overall number of admissions declined significantly. Although overall ambulance traffic decreased, the proportion of patients arriving by ambulance was unchanged. CONCLUSION: Patient volume in 2 EDs dropped significantly in association with a statewide response to the COVID-19 pandemic. There was also a shift in acuity as measured by the proportion of patients admitted to the hospital, but overall admissions declined, suggesting sicker patients also did not seek care.

Predicting Risk of Hospital Admission in Patients With Suspected COVID-19 in a Community Setting: Protocol for Development and Validation of a Multivariate Risk Prediction Tool.

BACKGROUND: During the pandemic, remote consultations have become the norm for assessing patients with signs and symptoms of COVID-19 to decrease the risk of transmission. This has intensified the clinical uncertainty already experienced by primary care clinicians when assessing patients with suspected COVID-19 and has prompted the use of risk prediction scores, such as the National Early Warning Score (NEWS2), to assess severity and guide treatment. However, the risk prediction tools available have not been validated in a community setting and are not designed to capture the idiosyncrasies of COVID-19 infection. OBJECTIVE: The objective of this study is to produce a multivariate risk prediction tool, RECAP-V1 (Remote COVID-19 Assessment in Primary Care), to support primary care clinicians in the identification of those patients with COVID-19 that are at higher risk of deterioration and facilitate the early escalation of their treatment with the aim of improving patient outcomes. METHODS: The study follows a prospective cohort observational design, whereby patients presenting in primary care with signs and symptoms suggestive of COVID-19 will be followed and their data linked to hospital outcomes (hospital admission and death). Data collection will be carried out by primary care clinicians in four arms: North West London Clinical Commissioning Groups (NWL CCGs), Oxford-Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC), Covid Clinical Assessment Service (CCAS), and South East London CCGs (Doctaly platform). The study involves the use of an electronic template that incorporates a list of items (known as RECAP-V0) thought to be associated with disease outcome according to previous qualitative work. Data collected will be linked to patient outcomes in highly secure environments. We will then use multivariate logistic regression analyses for model development and validation. RESULTS: Recruitment of participants started in October 2020. Initially, only the NWL CCGs and RCGP RSC arms were active. As of March 24, 2021, we have recruited a combined sample of 3827 participants in these two arms. CCAS and Doctaly joined the study in February 2021, with CCAS starting the recruitment process on March 15, 2021. The first part of the analysis (RECAP-V1 model development) is planned to start in April 2021 using the first half of the NWL CCGs and RCGP RSC combined data set. Posteriorly, the model will be validated with the rest of the NWL CCGs and RCGP RSC data as well as the CCAS and Doctaly data sets. The study was approved by the Research Ethics Committee on May 27, 2020 (Integrated Research Application System number: 283024, Research Ethics Committee reference number: 20/NW/0266) and badged as National Institute of Health Research Urgent Public Health Study on October 14, 2020. CONCLUSIONS: We believe the validated RECAP-V1 early warning score will be a valuable tool for the assessment of severity in patients with suspected COVID-19 in the community, either in face-to-face or remote consultations, and will facilitate the timely escalation of treatment with the potential to improve patient outcomes. TRIAL REGISTRATION: ISRCTN registry ISRCTN13953727; https://www.isrctn.com/ISRCTN13953727. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/29072.

Interleukin-6 receptor blockade in patients with COVID-19: placing clinical trials into context.

The pleiotropic cytokine interleukin-6 (IL-6) has been implicated in the pathogenesis of COVID-19, but uncertainty remains about the potential benefits and harms of targeting IL-6 signalling in patients with the disease. The efficacy and safety of tocilizumab and sarilumab, which block the binding of IL-6 to its receptor, have been tested in adults with COVID-19-related acute respiratory illness in randomised trials, with important differences in trial design, characteristics of included patients, use of co-interventions, and outcome measurement scales. In this Series paper, we review the clinical and methodological heterogeneity of studies of IL-6 receptor antagonists, and consider how this heterogeneity might have influenced reported treatment effects. Timing from clinical presentation to treatment, severity of illness, and concomitant use of corticosteroids are among the factors that might have contributed to apparently inconsistent results. With an understanding of the sources of variability in these trials, available evidence could be applied to guide clinical decision making and to inform the enrichment of future studies.

A predictive model of clinical deterioration among hospitalized COVID-19 patients by harnessing hospital course trajectories.

From early March through mid-May 2020, the COVID-19 pandemic overwhelmed hospitals in New York City. In anticipation of ventilator shortages and limited ICU bed capacity, hospital operations prioritized the development of prognostic tools to predict clinical deterioration. However, early experience from frontline physicians observed that some patients developed unanticipated deterioration after having relatively stable periods, attesting to the uncertainty of clinical trajectories among hospitalized patients with COVID-19. Prediction tools that incorporate clinical variables at one time-point, usually on hospital presentation, are suboptimal for patients with dynamic changes and evolving clinical trajectories. Therefore, our study team developed a machine-learning algorithm to predict clinical deterioration among hospitalized COVID-19 patients by extracting clinically meaningful features from complex longitudinal laboratory and vital sign values during the early period of hospitalization with an emphasis on informative missing-ness. To incorporate the evolution of the disease and clinical practice over the course of the pandemic, we utilized a time-dependent cross-validation strategy for model development. Finally, we validated our prediction model on an external validation cohort of COVID-19 patients served in a demographically distinct population from the training cohort. The main finding of our study is the identification of risk profiles of early, late and no clinical deterioration during the course of hospitalization. While risk prediction models that include simple predictors at ED presentation and clinical judgement are able to identify any deterioration vs. no deterioration, our methodology is able to isolate a particular risk group that remain stable initially but deteriorate at a later stage of the course of hospitalization. We demonstrate the superior predictive performance with the utilization of laboratory and vital sign data during the early period of hospitalization compared to the utilization of data at presentation alone. Our results will allow efficient hospital resource allocation and will motivate research in understanding the late deterioration risk group.

Nurses' uncertainty about medical gloves safety during the COVID-19 pandemic.

BACKGROUND: Nurses, as the largest group of health professionals, are at the frontline of the healthcare system in response to COVID-19 epidemic. This study aimed to evaluate the nurses' certainty and satisfaction with medical gloves when exposed to coronavirus in Fars province, south of Iran. METHODS: Using convenience sampling, 400 hospital nurses during the COVID-19 outbreak were selected from eight hospitals of Shiraz University of Medical Sciences (SUMS). A questionnaire about glove reliability, including protection in tasks, durability, integrity and tear resistance, feeling fearful, and focusing on duties, and the nurses' anxiety regarding their infection with coronavirus was distributed to the selected nurses to complete. 375 questionnaires were completed (response rate of 93.75%). Among the participants, 180 (48%) were in the corona section and 195 (52%) were hardly possible to have contact with coronavirus pneumonia patients. RESULTS: The mean score (SD) of anxiety about infection with COVID-19 for nurses in the COVID-19 section and those in the non-COVID-19 section were 6.08 (2.8) and 4.56 (2.58), respectively (p<0.05). The mean duration of gloves usage in a day was almost similar in the two groups (about 5h), but the number of glove replacements was significantly higher among the nurses in the corona section (6 times) compared to those in the non-corona section (3 times). The two groups were also significantly different regarding glove protection in daily tasks and glove durability. CONCLUSION: The nurses in the corona section had more concerns about medical gloves as a type of personal protective equipment. In addition to health education on controlling and preventing the spread of diseases, raising awareness about the reliability of personal protective equipment can improve nurses' performance.

Rationales and uncertainties for aspirin use in COVID-19: a narrative review.

OBJECTIVES: To review the pathophysiology of COVID-19 disease, potential aspirin targets on this pathogenesis and the potential role of aspirin in patients with COVID-19. DESIGN: Narrative review. SETTING: The online databases PubMed, OVID Medline and Cochrane Library were searched using relevant headlines from 1 January 2016 to 1 January 2021. International guidelines from relevant societies, journals and forums were also assessed for relevance. PARTICIPANTS: Not applicable. RESULTS: A review of the selected literature revealed that clinical deterioration in COVID-19 is attributed to the interplay between endothelial dysfunction, coagulopathy and dysregulated inflammation. Aspirin has anti-inflammatory effects, antiplatelet aggregation, anticoagulant properties as well as pleiotropic effects on endothelial function. During the COVID-19 pandemic, low-dose aspirin is used effectively in secondary prevention of atherosclerotic cardiovascular disease, prevention of venous thromboembolism after total hip or knee replacement, prevention of pre-eclampsia and postdischarge treatment for multisystem inflammatory syndrome in children. Prehospital low-dose aspirin therapy may reduce the risk of intensive care unit admission and mechanical ventilation in hospitalised patients with COVID-19, whereas aspirin association with mortality is still debatable. CONCLUSION: The authors recommend a low-dose aspirin regimen for primary prevention of arterial thromboembolism in patients aged 40-70 years who are at high atherosclerotic cardiovascular disease risk, or an intermediate risk with a risk-enhancer and have a low risk of bleeding. Aspirin's protective roles in COVID-19 associated with acute lung injury, vascular thrombosis without previous cardiovascular disease and mortality need further randomised controlled trials to establish causal conclusions.

Prevalence and prognostic associations of cardiac abnormalities among hospitalized patients with COVID-19: a systematic review and meta-analysis.

Although most patients recover from COVID-19, it has been linked to cardiac, pulmonary, and neurologic complications. Despite not having formal criteria for its diagnosis, COVID-19 associated cardiomyopathy has been observed in several studies through biomarkers and imaging. This study aims to estimate the proportion of COVID-19 patients with cardiac abnormalities and to determine the association between the cardiac abnormalities in COVID-19 patients and disease severity and mortality. Observational studies published from December 1, 2019 to September 30, 2020 were obtained from electronic databases (PubMed, Embase, Cochrane Library, CNKI) and preprint servers (medRxiv, bioRxiv, ChinaXiv). Studies that have data on prevalence were included in the calculation of the pooled prevalence, while studies with comparison group were included in the calculation of the odds ratio. If multiple tests were done in the same study yielding different prevalence values, the largest one was used as the measure of prevalence of that particular study. Metafor using R software package version 4.0.2 was used for the meta-analysis. A total of 400 records were retrieved from database search, with 24 articles included in the final analysis. Pooled prevalence of cardiac abnormalities in 20 studies was calculated to be 0.31 [95% Confidence Intervals (CI) of (0.23; 0.41)], with statistically significant heterogeneity (percentage of variation or I-squared statistic I2 = 97%, p < 0.01). Pooled analysis of 19 studies showed an overall odds ratio (OR) of 6.87 [95%-CI (3.92; 12.05)] for cardiac abnormalities associated with disease severity and mortality, with statistically significant heterogeneity (I2 = 85%, between-study variance or tau-squared statistic τ2 = 1.1485, p < 0.01). Due to the high uncertainty in the pooled prevalence of cardiac abnormalities and the unquantifiable magnitude of risk (although an increased risk is certain) for severity or mortality among COVID-19 patients, much more long-term prognostic studies are needed to check for the long-term complications of COVID-19 and formalize definitive criteria of "COVID-19 associated cardiomyopathy".

Bronchodilator reversibility testing in post-COVID-19 patients undergoing pulmonary rehabilitation.

BACKGROUND: The usefulness of bronchodilators in coronavirus diseases 2019 (COVID-19) survivors is still uncertain, especially for patients with a concomitant obstructive lung disease. We aimed at verifying the level of bronchodilator reversibility in COVID-19 patients undergoing multidisciplinary pulmonary rehabilitation after the acute phase. METHODS: We enrolled 105 consecutive patients referring to the Pulmonary Rehabilitation Unit of Istituti Clinici Scientifici Maugeri Spa SB, IRCCS of Telese Terme, Benevento, Italy after being discharged from the COVID-19 acute care ward and after recovering from acute COVID-19 pneumonia. All subjects performed a spirometry before and after inhalation of salbutamol 400 µg to determine the bronchodilation response within 48 h of admission to the unit. RESULTS: All patients had suffered from a moderate to severe COVID-19, classified 3 or 4 according to the WHO classification, Seventeen patients had concomitant obstructive lung disease (14 suffering from COPD and 3 from asthma). FEV1 after salbutamol improved on average by 41.7 mL in the entire examined sample, by 29.4 mL in subjects without concomitant obstructive lung diseases, by 59.3 mL in COPD patients and by 320.0 mL in asthma patients. Mean FVC after salbutamol improved by 65.7 mL in the entire examined sample, by 52.5 mL in subjects without concomitant obstructive lung diseases, by 120.0 mL in COPD patients, and by 200.0 mL in asthma patients. CONCLUSIONS: This study suggests that a treatment with bronchodilators must always be taken into consideration in post-COVID-19 patients because it can induce a functional improvement that, even if small, can facilitate the breathing of these patients.

COVID-19 Vaccination in Patients with Autoimmune Inflammatory Rheumatic Diseases: Clinical Guidance of the Korean College of Rheumatology.

The coronavirus disease 2019 (COVID-19) pandemic has caused more than 100 million infections and 2 million deaths worldwide. In up to 20% of cases, COVID-19 infection can take a severe, life-threatening course. Therefore, preventive measures such as mask-wearing, hand hygiene, and social distancing are important. COVID-19 vaccines that use novel vaccine technology can prevent up to 95% of infections. However, the uncertainty regarding the efficacy and safety of vaccination in patients with autoimmune inflammatory rheumatic disease (AIIRD), who are immunocompromised due to underlying immune dysfunction and concomitant immunosuppressive treatment, warrants clear guidance. A task force of the Korean College of Rheumatology formulated a set of vaccination guidance based on the currently available data and expert consensus. The currently available COVID-19 vaccines are considered to be safe and effective. Every patient with AIIRD should receive one of the available COVID-19 vaccines unless contraindicated for medical reasons such as prior allergy/anaphylaxis to the COVID-19 vaccine or its components. Patients should continue immunosuppressive treatment for their underlying AIIRD, including biological and targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs). Corticosteroids should be reduced to the lowest dose possible without aggravating the AIIRD. To improve the vaccine response, methotrexate can be withheld for 1-2 weeks after each vaccination, and the timing of rituximab and abatacept infusion should be adjusted if clinically acceptable. Rheumatologists should play a leading role in educating and vaccinating patients with AIIRD.

Allergische Reaktionen auf COVID-19-Impfungen ­ Was HNO-Ärzte wissen sollten ­ Teil 1: Allgemeine Aspekte von Allergien auf Impfstoffe, immunologische Grundlagen von Allergien auf Impfstoffe, Immunmechanismen von allergischen und pseudoallergischen Reaktionen, Teil 2: Charakteristiken der mRNA-Impfstoffe BNT162b2 und mRNA-1273 zur Prophylaxe von COVID-19 und assoziierte Immunphänomene, Teil 3: Praktische Aspekte der Prophylaxe, Diagnostik und Therapie von Allergien auf COVID-19-Impfstoffe.

With BNT162b2 (approved in the EC on 27th of December 2020) and mRNA-1273 (approved in the EC on 6th of January 2021) for the first time ever two RNA-vaccines received conditional approval within the EC in order to effectively combat the SARS-COV2 pandemic. The emergence of sporadic cases of anaphylaxis following vaccination with these new compounds and the identification of PEGs (polyethylenglycols) as potential, widely used but yet usually unknown culprits have led to uncertainty among treating physicians and patients. The aim of this article series is to summarize current available pathophysiological and clinical information (part 1), to describe the characteristics of the vaccines (part 2) and to provide practical solutions for diagnosis and treatment of potential allergy against mRNACovid19 vaccines.

Heterogeneous Recommendations for School Attendance in Children With Chronic Kidney Diseases During the COVID-19 Pandemic in Europe.

Introduction: After worldwide closures due to the COVID-19 pandemic, schools have reopened in most European countries in late 2020. Consequently, for children with chronic diseases the risks of COVID-19 have to be weighed against the long-time risks of missing school. Methods: To evaluate the impact of chronic diseases on school attendance for children in Europe during the COVID-19 pandemic we conducted a survey among members of the European Society for Pediatric Nephrology (ESPN) between September and November 2020. We asked for current forms of schooling, the existence of national guidelines, parental concerns, and the pediatric nephrologists recommendations for school attendance for specific virtual patients with chronic kidney disease (CKD). Results: Recommendations varied widely among pediatric nephrologists. A minority stated that specific recommendations for COVID-19 risk in children with kidney diseases existed in their country from local health authorities (9 of 29 countries; 31%) and/or national pediatric nephrology societies (9 of 29 countries; 31%). Over 90% of physicians have experienced parents keeping their children out of school against medical advice of their health providers and about 50% have experienced their patients being refused by school authorities. Consequently, 25% of all pediatric nephrologists estimated that more than 10% of their patients will not attend school regularly. Conclusion: COVID-19 causes educational deficits in the already vulnerable population of children with CKD. As the evidence for the course of COVID-19 in children with chronic diseases grows, rapidly adapted recommendations from pediatric societies could help reduce uncertainty among doctors, patients, and parents.

Recommendations for the use of COVID-19 vaccines in patients with immune-mediated kidney diseases.

Coronavirus Disease 19 (COVID-19) vaccine platforms are becoming available and are the most promising strategy to curb the spread of SARS-CoV-2 infections. However, numerous uncertainties exist regarding the pros and cons of vaccination, especially in patients with (immune-mediated) kidney diseases on immunosuppressive drugs. Here, members of the Immunonephrology Working Group (IWG) of the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) discuss thirteen frequently-asked questions regarding safety and efficacy of the most promising vaccine candidates. Post-marketing surveillance should be performed to estimate the rate of vaccine response (humoral and cellular) of different vaccine platforms, and surveillance of disease activity following administration of COVID-19 vaccines. Some of the candidates induce signaling pathways which also promote autoimmune kidney diseases, e.g. type I interferons in systemic lupus erythematosus. Efficacy estimates would thus far favor the use of selected COVID-19 vaccines, such as BNT162b2, mRNA-1273 or Gam-COVID-Vac. Humoral immune response after vaccination should be monitored using appropriate assays. Even in the absence of neutralizing antibodies patients might be protected by a sufficient cellular immune response capable to reduce severity of COVID-19. A reduced vaccine response after the use of CD20-depleting agents is anticipated, and it is particularly important to discuss strategies to improve vaccine response with these patients. Distancing and shielding measures remain important as not all vaccines fully protect from coronavirus infection. In-depth information about the most pressing vaccine questions is essential to reduce vaccine hesitancy of patients.

Cardiovascular biomarkers in patients with COVID-19.

The coronavirus disease 2019 (COVID-19) pandemic has increased awareness that severe acute respiratory distress syndrome coronavirus-2 (SARS-CoV-2) may have profound effects on the cardiovascular system. COVID-19 often affects patients with pre-existing cardiac disease, and may trigger acute respiratory distress syndrome (ARDS), venous thromboembolism (VTE), acute myocardial infarction (AMI), and acute heart failure (AHF). However, as COVID-19 is primarily a respiratory infectious disease, there remain substantial uncertainty and controversy whether and how cardiovascular biomarkers should be used in patients with suspected COVID-19. To help clinicians understand the possible value as well as the most appropriate interpretation of cardiovascular biomarkers in COVID-19, it is important to highlight that recent findings regarding the prognostic role of cardiovascular biomarkers in patients hospitalized with COVID-19 are similar to those obtained in studies for pneumonia and ARDS in general. Cardiovascular biomarkers reflecting pathophysiological processes involved in COVID-19/pneumonia and its complications have a role evaluating disease severity, cardiac involvement, and risk of death in COVID-19 as well as in pneumonias caused by other pathogens. First, cardiomyocyte injury, as quantified by cardiac troponin concentrations, and haemodynamic cardiac stress, as quantified by natriuretic peptide concentrations, may occur in COVID-19 as in other pneumonias. The level of those biomarkers correlates with disease severity and mortality. Interpretation of cardiac troponin and natriuretic peptide concentrations as quantitative variables may aid in risk stratification in COVID-19/pneumonia and also will ensure that these biomarkers maintain high diagnostic accuracy for AMI and AHF. Second, activated coagulation as quantified by D-dimers seems more prominent in COVID-19 as in other pneumonias. Due to the central role of endothelitis and VTE in COVID-19, serial measurements of D-dimers may help physicians in the selection of patients for VTE imaging and the intensification of the level of anticoagulation from prophylactic to slightly higher or even therapeutic doses.