International Severe Acute Respiratory And Emerging Infections Consortium Research Articles

The association between non-communicable diseases and COVID-19 severity and mortality among infected hospitalized healthcare workers in 29 countries: a cohort study

Background Due to occupational exposure, healthcare workers (HCWs) have a higher risk of Coronavirus Disease 2019(COVID-19) infection than the general population. Non-communicable diseases (NCDs) may increase the risk of COVID-19-related morbidity and mortality among HCWs, potentially reducing the available health workforce. We examined the association between NCDs and COVID-19 disease severity and mortality among infected HCWs. Methods This cohort study used data from the International Severe Acute Respiratory and Emerging Infections Consortium (ISARIC) database. HCWs hospitalized between January 2020 and January 2023 due to clinically suspected or laboratory-confirmed COVID-19 were eligible for inclusion. Variables collected included demographic data, comorbidities, and hospitalization outcomes. Descriptive statistics were reported using mean/standard deviation (SD), median/interquartile range (IQR), or frequencies and proportions. For each NCD, the relative risk of death, adjusted for age and sex, was calculated using log-binomial regression as well as the population-attributable fraction. Results There were 17,502 HCWs, 95.7% of whom had a confirmed COVID-19 diagnosis. The majority were female (66.5%) and the mean age (SD) was 49.8 (14.3) years. Roughly, half (51.42%) of HCWs had no comorbidities, 29.28% had one comorbidity, 14.68% had 2 comorbidities and <5% had ≥3 comorbidities. The most common comorbidities were diabetes mellitus (49.40%) and cardiovascular disease (36.90%). Approximately one-fifth of the HCWs had severe COVID-19 (16.95%) and 10.68% of the HCWs with COVID-19 died. Being ≥45 years old, male gender, smoking, obesity, and certain NCDs increased the risk of COVID-19 severity and mortality. Obesity and diabetes mellitus were the leading risk factors in terms of the population-attributable risk for COVID-19 severity (6.89%) and mortality (36.00%) respectively. Conclusions Many HCWs with COVID-19 had one or more NCDs. Obesity and diabetes mellitus increased COVID-19 severity and mortality risk. Reducing the prevalence of obesity and diabetes mellitus would yield the biggest reduction in COVID-19-related morbidity and mortality among HCWs.

Changes in hospital mortality in patients with cancer during the COVID-19 pandemic (ISARIC-CCP-UK): a prospective, multicentre cohort study

Patients with cancer are at greater risk of dying from COVID-19 than many other patient groups. However, how this risk evolved during the pandemic remains unclear. We aimed to determine, on the basis of the UK national pandemic protocol, how factors influencing hospital mortality from COVID-19 could differentially affect patients undergoing cancer treatment. We also examined changes in hospital mortality and escalation of care in patients on cancer treatment during the first 2 years of the COVID-19 pandemic in the UK. We conducted a prospective cohort study of patients aged older than 19 years and admitted to 306 health-care facilities in the UK with confirmed SARS-CoV-2 infection, who were enrolled in the International Severe Acute Respiratory and emerging Infections Consortium (ISARIC) WHO Clinical Characterisation Protocol (CCP) across the UK from April 23, 2020, to Feb 28, 2022; this analysis included all patients in the complete dataset when the study closed. The primary outcome was 30-day in-hospital mortality, comparing patients on cancer treatment and those without cancer. The study was approved by the South Central-Oxford C Research Ethics Committee in England (Ref: 13/SC/0149) and the Scotland A Research Ethics Committee (Ref 20/SS/0028), and is registered on the ISRCTN Registry (ISRCTN66726260). 177 871 eligible adult patients either with no history of cancer (n=171 303) or on cancer treatment (n=6568) were enrolled; 93 205 (52·4%) were male, 84 418 (47·5%) were female, and in 248 (13·9%) sex or gender details were not specified or data were missing. Patients were followed up for a median of 13 (IQR 6-21) days. Of the 6568 patients receiving cancer treatment, 2080 (31·7%) died at 30 days, compared with 30 901 (18·0%) of 171 303 patients without cancer. Patients aged younger than 50 years on cancer treatment had the highest age-adjusted relative risk (hazard ratio [HR] 5·2 [95% CI 4·0-6·6], p<0·0001; vs 50-69 years 2·4 [2·2-2·6], p<0·0001; 70-79 years 1·8 [1·6-2·0], p<0·0001; and >80 years 1·5 [1·3-1·6], p<0·0001) but a lower absolute risk (51 [6·7%] of 763 patients <50 years died compared with 459 [30·2%] of 1522 patients aged >80 years). In-hospital mortality decreased for all patients during the pandemic but was higher for patients on cancer treatment than for those without cancer throughout the study period. People with cancer have a higher risk of mortality from COVID-19 than those without cancer. Patients younger than 50 years with cancer treatment have the highest relative risk of death. Continued action is needed to mitigate the poor outcomes in patients with cancer, such as through optimising vaccination, long-acting passive immunisation, and early access to therapeutics. These findings underscore the importance of the ISARIC-WHO pandemic preparedness initiative. National Institute for Health Research and the Medical Research Council.

Symptomology following COVID-19 among adults in Alberta, Canada: an observational survey study

ObjectiveFatigue, headache, problems sleeping and numerous other symptoms have been reported to be associated with long COVID. However, many of these symptoms coincide with symptoms reported by the general population,...

Event rates and incidence of post-COVID-19 condition in hospitalised SARS-CoV-2 positive children and young people and controls across different pandemic waves: exposure-stratified prospective cohort study in Moscow (StopCOVID)

BackgroundLong-term health outcomes in children and young people (CYP) after COVID-19 infection are not well understood and studies with control groups exposed to other infections are lacking. This study aimed to investigate the incidence of post-COVID-19 condition (PCC) and incomplete recovery in CYP after hospital discharge and compare outcomes between different SARS-CoV-2 variants and non-SARS-CoV-2 infections.MethodsA prospective exposure-stratified cohort study of individuals under 18 years old in Moscow, Russia. Exposed cohorts were paediatric patients admitted with laboratory-confirmed COVID-19 infection between April 2 and December 11, 2020 (Wuhan variant cohort) and between January 12 and February 19, 2022 (Omicron variant cohort). CYP admitted with respiratory and intestinal infections, but negative lateral flow rapid diagnostic test and PCR-test results for SARS-CoV-2, between January 12 and February 19, 2022, served as unexposed reference cohort. Comparison between the ‘exposed cohorts’ and ‘reference cohort’ was conducted using 1:1 matching by age and sex. Follow-up data were collected via telephone interviews with parents, utilising the long COVID paediatric protocol and survey developed by the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC). The WHO case definition was used to categorise PCC.ResultsOf 2595 CYP with confirmed COVID-19, 1707 (65.7%) participated in follow-up interviews, with 1183/1707 (69%) included in the final ‘matched’ analysis. The median follow-up time post-discharge was 6.7 months. The incidence of PCC was significantly higher in the Wuhan variant cohort (89.7 cases per 1000 person-months, 95% CI 64.3–120.3) compared to post-infection sequalae in the reference cohort (12.2 cases per 1000 person-months, 95% CI 4.9–21.9), whereas the difference with the Omicron variant cohort and reference cohort was not significant. The Wuhan cohort had higher incidence rates of dermatological, fatigue, gastrointestinal, sensory, and sleep manifestations, as well as behavioural and emotional problems than the reference cohort. The only significant difference between Omicron variant cohort and reference cohort was decreased school attendance. When comparing the Wuhan and Omicron variant cohorts, higher incidence of PCC and event rates of fatigue, decreased physical activity, and deterioration of relationships was observed. The rate of incomplete recovery was also significantly higher in the Wuhan variant cohort than in both the reference and the Omicron variant cohorts.ConclusionsWuhan variant exhibited a propensity for inducing a broad spectrum of physical symptoms and emotional behavioural changes, suggesting a pronounced impact on long-term health outcomes. Conversely, the Omicron variant resulted in fewer post-infection effects no different from common seasonal viral illnesses. This may mean that the Omicron variant and subsequent variants might not lead to the same level of long-term health consequences as earlier variants.

Assessment of the state of children after COVID-19 and other acute respiratory infections using the ISARIC COVID-19 survey

Introduction. The state of children had suffered from COVID-19 causes various persistent symptoms affecting on patient well-being and quality of life which is a significant healthcare issue. &#x0D; The aim of the work. To assess health and well-being of children following COVID-19 and other acute respiratory infections. &#x0D; Materials and methods. This is a case-control study including children with history of PCR-confirmed COVID-19 (n = 261) and other acute respiratory infections (n = 198). Patients were assessed 6 months and 1 year after the infection using the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) COVID-19 questionnaire for children. The prevalence of symptoms including fatigue, weakness, lack of energy, as well as the emotional well-being, social relationships, and social activity of children was evaluated. &#x0D; Results. Children with history of COVID-19 in six months had significantly higher rates of weakness and decreased school attendance compared to children with other acute respiratory infections. 12 months after infection, children in the case group were significantly more likely to experience poor concentration, weakness, a decreased sense of belonging and school attendance. However, 12 months after infection, control group had significantly higher rates of fatigue. &#x0D; Conclusion. Children with a history of mild COVID-19 and other acute respiratory infections may experience ongoing health problems for 1 year after the infection, requiring greater attention from healthcare professionals and family members.

Implementation of Recommendations on the Use of Corticosteroids in Severe COVID-19

Research diversity and representativeness are paramount in building trust, generating valid biomedical knowledge, and possibly in implementing clinical guidelines. To compare variations over time and across World Health Organization (WHO) geographic regions of corticosteroid use for treatment of severe COVID-19; secondary objectives were to evaluate the association between the timing of publication of the RECOVERY (Randomised Evaluation of COVID-19 Therapy) trial (June 2020) and the WHO guidelines for corticosteroids (September 2020) and the temporal trends observed in corticosteroid use by region and to describe the geographic distribution of the recruitment in clinical trials that informed the WHO recommendation. This prospective cohort study of 434 851 patients was conducted between January 31, 2020, and September 2, 2022, in 63 countries worldwide. The data were collected under the auspices of the International Severe Acute Respiratory and Emerging Infections Consortium (ISARIC)-WHO Clinical Characterisation Protocol for Severe Emerging Infections. Analyses were restricted to patients hospitalized for severe COVID-19 (a subset of the ISARIC data set). Corticosteroid use as reported to the ISARIC-WHO Clinical Characterisation Protocol for Severe Emerging Infections. Number and percentage of patients hospitalized with severe COVID-19 who received corticosteroids by time period and by WHO geographic region. Among 434 851 patients with confirmed severe or critical COVID-19 for whom receipt of corticosteroids could be ascertained (median [IQR] age, 61.0 [48.0-74.0] years; 53.0% male), 174 307 (40.1%) received corticosteroids during the study period. Of the participants in clinical trials that informed the guideline, 91.6% were recruited from the United Kingdom. In all regions, corticosteroid use for severe COVID-19 increased, but this increase corresponded to the timing of the RECOVERY trial (time-interruption coefficient 1.0 [95% CI, 0.9-1.2]) and WHO guideline (time-interruption coefficient 1.9 [95% CI, 1.7-2.0]) publications only in Europe. At the end of the study period, corticosteroid use for treatment of severe COVID-19 was highest in the Americas (5421 of 6095 [88.9%]; 95% CI, 87.7-90.2) and lowest in Africa (31 588 of 185 191 [17.1%]; 95% CI, 16.8-17.3). The results of this cohort study showed that implementation of the guidelines for use of corticosteroids in the treatment of severe COVID-19 varied geographically. Uptake of corticosteroid treatment was lower in regions with limited clinical trial involvement. Improving research diversity and representativeness may facilitate timely knowledge uptake and guideline implementation.

428. Risk Stratification and Clinical Outcomes in a Mixed Vaccination Cohort of COVID-19 Patients Admitted in a Tertiary Hospital Using ISARIC 4C Scores

Abstract Background The risk of clinical deterioration and death with the use of prognostic tools remain necessary for strategic planning among COVID-19 patients. The International Severe Acute Respiratory and Emerging Infections Consortium (ISARIC) developed and validated Coronavirus Clinical Characterization Consortium (4C) scores to predict clinical deterioration and mortality. ISARIC 4C scores uses readily available clinical parameters. With the increasing uptake of COVID-19 vaccine, there is a need to evaluate these tools. The study examined a cohort of fully vaccinated (FV), partially vaccinated (PV) and unvaccinated (UV) COVID-19 patients and determined their clinical outcomes and stratified risks using ISARIC 4C scores. Methods We reviewed medical records of confirmed COVID-19 patients admitted to a single tertiary hospital between May 2021 and April 2022. Vaccination status were classified as FV, PV and UV. The primary outcome was in-hospital mortality. Baseline data were collected and predictors recorded upon admission were used to calculate the 4C scores. Multiple logistic regression analysis was used to determine the association of vaccination status and 4C Deterioration and Mortality scores with in-hospital mortality. STATA 14 was used for data analysis and p&amp;lt; 0.05 was considered statistically significant. Results A total of 301 confirmed COVID-19 patients were included and 46.5% were fully vaccinated. FV patients had significantly lower CRP (p&amp;lt; 0.0001), had higher mean oxygen saturation (p&amp;lt; 0.0001), had lower mean mortality score (p=0.004), had lower mean % risk for deterioration (p&amp;lt; 0.0001) and had significantly lower 30-day mortality (&amp;lt; 0.0001) compared to those UV and PV. Patient who died had significantly higher mean age (p=0.001), lower mean lymphocyte ratio (p=0.0004), had significantly higher mean deterioration and mortality score (p&amp;lt; 0.0001). Being fully vaccinated was associated with lower risk for mortality (OR=0.4, 95%CI=0.2 to 0.7). Conclusion Fully vaccinated patients were at lower risk for deterioration and mortality. High ISARIC 4C scores were also significantly associated with higher risk for mortality. Risk stratification tools should be utilized in COVID-19 management as they provide a helpful means to identify patients at risk for worse outcomes. Disclosures All Authors: No reported disclosures

Utility of the 4C ISARIC mortality score in hospitalized COVID-19 patients at a large tertiary Saudi Arabian center.

The International Severe Acute Respiratory and Emerging Infections Consortium (ISARIC) 4C mortality score has been used before as a valuable tool for predicting mortality in COVID-19 patients. We aimed to address the utility of the 4C score in a well-defined Saudi population with COVID-19 admitted to a large tertiary referral hospital in Saudi Arabia. A retrospective study was conducted that included all adults COVID‑19 patients admitted to the Armed Forces Hospital Southern Region (AFHSR), between January 2021 and September 2022. The receiver operating characteristic (ROC) curve depicted the diagnostic performance of the 4C Score for mortality prediction. A total of 1,853 patients were enrolled. The ROC curve of the 4C score had an area under the curve of 0.73 (95% CI: 0.702-0.758), p<0.001. The sensitivity and specificity with scores >8 were 80% and 58%, respectively, the positive and negative predictive values were 28% and 93%, respectively. Three hundred and sixteen (17.1%), 638 (34.4%), 814 (43.9%), and 85 (4.6%) patients had low, intermediate, high, and very high values, respectively. There were significant differences between survivors and non-survivors with regard to all variables used in the calculation of the 4C score. Multivariable logistic regression analysis revealed that all components of the 4C score, except gender and O2 saturation, were independent significant predictors of mortality. Our data support previous international and Saudi studies that the 4C mortality score is a reliable tool with good sensitivity and specificity in the mortality prediction of COVID-19 patients. All components of the 4C score, except gender and O2 saturation, were independent significant predictors of mortality. Within the 4C score, odds ratios increased proportionately with an increase in the score value. Future multi-center prospective studies are warranted.

External validation of the ISARIC 4C Mortality Score to predict in-hospital mortality among patients with COVID-19 in a Canadian intensive care unit: a single-centre historical cohort study.

With uncertain prognostic utility of existing predictive scoring systems for COVID-19-related illness, the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) 4C Mortality Score was developed by the International Severe Acute Respiratory and Emerging Infection Consortium as a COVID-19 mortality prediction tool. We sought to externally validate this score among critically ill patients admitted to an intensive care unit (ICU) with COVID-19 and compare its discrimination characteristics to that of the Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores. We enrolled all consecutive patients admitted with COVID-19-associated respiratory failure between 5 March 2020 and 5 March 2022 to our university-affiliated and intensivist-staffed ICU (Jewish General Hospital, Montreal, QC, Canada). After data abstraction, our primary outcome of in-hospital mortality was evaluated with an objective of determining the discriminative properties of the ISARIC 4C Mortality Score, using the area under the curve of a logistic regression model. A total of 429 patients were included, 102 (23.8%) of whom died in hospital. The receiver operator curve of the ISARIC 4C Mortality Score had an area under the curve of 0.762 (95% confidence interval [CI], 0.717 to 0.811), whereas those of the SOFA and APACHE II scores were 0.705 (95% CI, 0.648 to 0.761) and 0.722 (95% CI, 0.667 to 0.777), respectively. The ISARIC 4C Mortality Score is a tool that had a good predictive performance for in-hospital mortality in a cohort of patients with COVID-19 admitted to an ICU for respiratory failure. Our results suggest a good external validity of the 4C score when applied to a more severely ill population.

Characteristics and outcomes of an international cohort of 600 000 hospitalized patients with COVID-19.

We describe demographic features, treatments and clinical outcomes in the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) COVID-19 cohort, one of the world's largest international, standardized data sets concerning hospitalized patients. The data set analysed includes COVID-19 patients hospitalized between January 2020 and January 2022 in 52 countries. We investigated how symptoms on admission, co-morbidities, risk factors and treatments varied by age, sex and other characteristics. We used Cox regression models to investigate associations between demographics, symptoms, co-morbidities and other factors with risk of death, admission to an intensive care unit (ICU) and invasive mechanical ventilation (IMV). Data were available for 689 572 patients with laboratory-confirmed (91.1%) or clinically diagnosed (8.9%) SARS-CoV-2 infection from 52 countries. Age [adjusted hazard ratio per 10 years 1.49 (95% CI 1.48, 1.49)] and male sex [1.23 (1.21, 1.24)] were associated with a higher risk of death. Rates of admission to an ICU and use of IMV increased with age up to age 60years then dropped. Symptoms, co-morbidities and treatments varied by age and had varied associations with clinical outcomes. The case-fatality ratio varied by country partly due to differences in the clinical characteristics of recruited patients and was on average 21.5%. Age was the strongest determinant of risk of death, with a ∼30-fold difference between the oldest and youngest groups; each of the co-morbidities included was associated with up to an almost 2-fold increase in risk. Smoking and obesity were also associated with a higher risk of death.The size of our international database and the standardized data collection method make this study a comprehensive international description of COVID-19 clinical features. Our findings may inform strategies that involve prioritization of patients hospitalized with COVID-19 who have a higher risk of death.

Relevance of prediction scores derived from the SARS-CoV-2 first wave, in the evolving UK COVID-19 second wave, for safe early discharge and mortality: a PREDICT COVID-19 UK prospective observational cohort study

ObjectiveProspectively validate prognostication scores, SOARS and 4C Mortality Score, derived from the COVID-19 first wave, for mortality and safe early discharge in the evolving pandemic with SARS-CoV-2 variants (B.1.1.7 replacing...

International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC). A new collaborative global platform for global clinical trials targeting post-COVID19 patients.

Background: In response to the pandemic caused by COVID-19, World Health Organization (WHO), together with International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC), developed research protocols facilitating global collaboration and accelerating the understanding of the disease, to identify the potential symptoms and persistent sequelae in infected individuals, which can be used in different areas of health, that is, in primary care, at a hospital or outpatient level, both public and private. Objective: To describe the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) protocol as a new global collaborative platform for global clinical trials targeting post-COVID-19 patients. Methods: The standardized forms were developed from the COVID-19 Clinical Characterization Protocol (PCC) by the ISARIC/WHO working group composed of specialist researchers with experience in clinical research in different areas of medicine and public health, especially outbreaks and infectious diseases. Conclusion: It is expected that the creation of a database composed of different populations from all over the world will help in the characterization of risk factors, in the best form of clinical intervention and in the best prevention strategies for physical, neurological and psychosocial sequelae in the medium and long term in post-COVID-19 patients.

Extended coagulation profile of children with Long Covid: a prospective study

Emerging data suggests that endotheliopathy changes can be associated with post covid condition (PCC) in adults. Research on the matter in children is lacking. We analyzed an extended coagulation profile including biomarkers of endothelial damage in children with PCC and compared it with a control group of children that fully recovered post- SARS-CoV-2 infection. A case-control study enrolling children below 18 years of age with previous microbiologically confirmed SARS-CoV-2 infection in a pediatric post-covid unit in Italy ≥ 8 weeks after the initial infection. Samples were taken at 8 and 12 weeks after the SARS-CoV-2 diagnosis and analyzed for coagulation profiling (fibrinogen, prothrombin time, international normalized ratio, activated partial thromboplastin time, d-dimers, factor VIII coagulant activity, plasma von Willebrand factor (VWF) antigen and VWF ristocetin cofactor (RC)). We compared coagulation profiles in samples from children identified with PCC (at least one, or three or more symptoms, which could not be explained by an alternative diagnosis, at the 8- and 12-week follow-up assessment using the pediatric Long Covid International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) survey. Seventy-five children were enrolled, 49.3% were females, the median age was 10.2 (IQR 4.9) years. Forty-six (61%) of the children had at least one persisting symptom at the eight weeks post-onset, (PCC8); 39/75 (52%) had persistent symptoms for more than 12 weeks (PCC12) and 15/75(32%) had at least three persisting symptoms (PCC ≥ 3) at 12 weeks. Children with PCC presented more frequently with abnormal D-Dimer levels above the reference range compared to children that had fully recovered at the 8–12 weeks (39.1% vs. 17.2%, p = 0.04), and 12 week follow up or more (41% vs. 17.2%, p = 0.05), and in children with three or more symptoms at 12 weeks follow up compared to those that had recovered (64.3% vs. 22.2%, p = 0.002). For the other coagulation profiles, there were abnormal values detected for VWF, FVIII, RC and Fibrinogen but no significant differences between children with PCC compared to controls. Although the majority of children in our cohort showed coagulation profile within or close to normal ranges, we found that a higher proportion of children with PCC, and specifically those with a more severe spectrum characterized with three or more persisting symptoms, had abnormal D-dimer levels compared to other children that fully recovered from an acute SARS-CoV-2 infection.

Paediatric COVID-19 mortality: a database analysis of the impact of health resource disparity

BackgroundThe impact of the COVID-19 pandemic on paediatric populations varied between high-income countries (HICs) versus low-income to middle-income countries (LMICs). We sought to investigate differences in paediatric clinical outcomes and...

ISARIC-COVID-19 dataset: A Prospective, Standardized, Global Dataset of Patients Hospitalized with COVID-19

The International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) COVID-19 dataset is one of the largest international databases of prospectively collected clinical data on people hospitalized with COVID-19. This dataset was compiled during the COVID-19 pandemic by a network of hospitals that collect data using the ISARIC-World Health Organization Clinical Characterization Protocol and data tools. The database includes data from more than 705,000 patients, collected in more than 60 countries and 1,500 centres worldwide. Patient data are available from acute hospital admissions with COVID-19 and outpatient follow-ups. The data include signs and symptoms, pre-existing comorbidities, vital signs, chronic and acute treatments, complications, dates of hospitalization and discharge, mortality, viral strains, vaccination status, and other data. Here, we present the dataset characteristics, explain its architecture and how to gain access, and provide tools to facilitate its use.

Mapping of SARS-CoV-2 IgM and IgG in gingival crevicular fluid: Antibody dynamics and linkage to severity of COVID-19 in hospital inpatients

Mapping of SARS-CoV-2 IgM and IgG in gingival crevicular fluid: Antibody dynamics and linkage to severity of COVID-19 in hospital inpatients

EFFICACY OF REMDESIVIR VERSUS REMDESIVIR PLUS TOCILIZUMAB IN MODERATE TO SEVERE COVID-19 PATIENTS ADMITTED IN THE CRITICAL CARE UNIT OF A TERTIARY CARE HOSPITAL IN WEST BENGAL, INDIA

Background And Aims: Severe corona virus infection is often associated with hyper immune response and liberation of inammatory cytokines. Anti-interleukin-6 receptor monoclonal antibody like tocilizumab might be effective in corona virus infection. Present study was designed to assess the effect of adding tocilizumab to remdesivir and other supportive therapy in management of critically ill covid-19 patients. Methods: This Randomized open-level clinical trial was done in 50 critically ill Covid-19 patients (from December 2020 to February 2021). They were randomly allocated in two group; to receive either injection remdesivir (Group R) or injection remdesivir plus tocilizumab (Group RT) intravenously. Patients were assessed using daily record sheets capturing data on the six-category ordinal scale and safety prole from day-1 to day28 or discharge or death. Other clinical data were recorded using the WHO International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) case record form. Primary endpoint with respect to the efcacy of the drugs was based on proportion of patients achieving clinical improvement dened as a two point reduction in six point ordinal scale from patients admission status or live discharge from the hospital, which ever came rst. Results: Baseline characteristics were identical in both R and RT group. Biomarkers, C reactive protein, IL-6 and serum ferritin levels were signicantly more in RT group as compared to R group on day 1,3 and 7. But C reactive protein (CRP), serum ferritin and IL-6 levels from day 1 to day 7 gradually decreased in RT group and increased in R group. Conclusion: In spite of higher levels of biomarkers morbidity and mortality of patients did not increase in RT group; use of tocilizumab might be responsible for the gradual reduction in the level of biomarkers in this group.

Use of an extended KDIGO definition to diagnose acute kidney injury in patients with COVID-19: A multinational study using the ISARIC-WHO clinical characterisation protocol.

Acute kidney injury (AKI) is one of the most common and significant problems in patients with Coronavirus Disease 2019 (COVID-19). However, little is known about the incidence and impact of AKI occurring in the community or early in the hospital admission. The traditional Kidney Disease Improving Global Outcomes (KDIGO) definition can fail to identify patients for whom hospitalisation coincides with recovery of AKI as manifested by a decrease in serum creatinine (sCr). We hypothesised that an extended KDIGO (eKDIGO) definition, adapted from the International Society of Nephrology (ISN) 0by25 studies, would identify more cases of AKI in patients with COVID-19 and that these may correspond to community-acquired AKI (CA-AKI) with similarly poor outcomes as previously reported in this population. All individuals recruited using the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC)-World Health Organization (WHO) Clinical Characterisation Protocol (CCP) and admitted to 1,609 hospitals in 54 countries with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection from February 15, 2020 to February 1, 2021 were included in the study. Data were collected and analysed for the duration of a patient's admission. Incidence, staging, and timing of AKI were evaluated using a traditional and eKDIGO definition, which incorporated a commensurate decrease in sCr. Patients within eKDIGO diagnosed with AKI by a decrease in sCr were labelled as deKDIGO. Clinical characteristics and outcomes-intensive care unit (ICU) admission, invasive mechanical ventilation, and in-hospital death-were compared for all 3 groups of patients. The relationship between eKDIGO AKI and in-hospital death was assessed using survival curves and logistic regression, adjusting for disease severity and AKI susceptibility. A total of 75,670 patients were included in the final analysis cohort. Median length of admission was 12 days (interquartile range [IQR] 7, 20). There were twice as many patients with AKI identified by eKDIGO than KDIGO (31.7% versus 16.8%). Those in the eKDIGO group had a greater proportion of stage 1 AKI (58% versus 36% in KDIGO patients). Peak AKI occurred early in the admission more frequently among eKDIGO than KDIGO patients. Compared to those without AKI, patients in the eKDIGO group had worse renal function on admission, more in-hospital complications, higher rates of ICU admission (54% versus 23%) invasive ventilation (45% versus 15%), and increased mortality (38% versus 19%). Patients in the eKDIGO group had a higher risk of in-hospital death than those without AKI (adjusted odds ratio: 1.78, 95% confidence interval: 1.71 to 1.80, p-value < 0.001). Mortality and rate of ICU admission were lower among deKDIGO than KDIGO patients (25% versus 50% death and 35% versus 70% ICU admission) but significantly higher when compared to patients with no AKI (25% versus 19% death and 35% versus 23% ICU admission) (all p-values <5 × 10-5). Limitations include ad hoc sCr sampling, exclusion of patients with less than two sCr measurements, and limited availability of sCr measurements prior to initiation of acute dialysis. An extended KDIGO definition of AKI resulted in a significantly higher detection rate in this population. These additional cases of AKI occurred early in the hospital admission and were associated with worse outcomes compared to patients without AKI.

Prevalence of bacterial coinfection and patterns of antibiotics prescribing in patients with COVID-19: a systematic review and meta-analysis

IntroductionEvidence on prevalence of bacterial coinfection in Coronavirus Disease 2019 (COVID-19) is controversial; previous global viral respiratory pandemics reported high prevalence of bacterial coinfection, which was associated with increased risk of morbidity and mortality (1). Data on Prevalence of antibiotic prescribing in COVID-19 indicates high antibiotic prescribing, causing a potential setback in antimicrobial stewardship and potential increase in antimicrobial resistance (2). The study protocol was registered in the international register of systematic reviews, PROSPERO, under the following ID: CRD42021261734AimTo determine the prevalence of bacterial coinfection and antibiotic prescribing in COVID-19 patientsMethodsSystematic review and meta-analysis was conducted using Covidence. Data were extracted by one reviewer. Proportion data was pooled using random effects meta-analysis approach using STATA 17; and stratified based on region and study design. Data Source: OVID MEDLINE, OVID EMBASE, Cochrane and MedRxiv between January 2020 and June 2021. Study Eligibility: English language studies of laboratory-confirmed COVID-19 patients which reported (a) prevalence of bacterial coinfection and/or (b) prevalence of antibiotic prescribing with no restrictions to study designs or healthcare setting. Participants: Adults with RT-PCR confirmed diagnosis of COVID-19ResultsA total of 1058 studies were screened, of which 22 studies were eligible. Retrospective cohort studies accounted for the majority of the studies involved (n = 18, 81%), whilst prospective cohort studies accounted for the remaining (n=4, 18%). Of the 22 studies included, 3 (13%) studies were pre-prints, whilst the remaining (n=19, 86%) were peer-reviewed. A total of 13 (59%) studies were conducted in multicentre settings, whilst the remaining (n=9, 40%) were conducted in single centre settings. All of the studies included were conducted in hospital setting, whether it be in a normal, isolation or an intensive care ward. Twenty-one out of 22 studies have been rated “Good” rating during the quality assessment process. Pooled estimates for the prevalence of bacterial co-infection and antibiotic use were 5.62% (95% CI 2.26 – 10.31) and 61.77% (CI 50.95 – 70.90), respectively.ConclusionThe prevalence of bacterial coinfection amongst COVID-19 patients is low (5.62%) when compared with previous pandemics, yet antibiotic prescribing in COVID-19 patients was high (61.77%) indicating the need for stronger antimicrobial stewardship to reduce the global threat of AMR. Prescribing of antibiotics in COVID-19 should be based on clinical and/or laboratory evidence of bacterial coinfection. Key strengths of this review, is that it included a comprehensive search strategy spanning over several databases, including both pre-prints and peer-reviewed studies. Limitations in this review was that during the screening process, a significant number of studies have been excluded due to not meeting the inclusion criteria, therefore, bacterial coinfection and antibiotic use may be under- or over-reported. In addition, disproportionate representation from North America and failure to include studies from regions other than Europe and Asia, can limit the generalizability of the results to other regions impacted by COVID-19References(1) Morris DE, Cleary DW, Clarke SC. Secondary bacterial infections associated with influenza pandemics. Front Microbiol. 2017;8:1041.(2) International Severe Acute Respiratory and Emerging Infections Consortium (ISARIC). COVID-19 Clinical data report. 19May 2020.

Association of body mass index with COVID-19 related in-hospital death

BackgroundPatients with extreme body mass indices (BMI) could have an increased risk of death while hospitalized for COVID-19.MethodsThe database of the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) was used to assess the time to in-hospital death with competing-risks regression by sex and between the categories of BMI.ResultsData from 12,137 patients (age 60.0 ± 16.2 years, 59% males, BMI 29.4 ± 6.9 kg/m2) of 48 countries were available. By univariate analysis, underweight patients had a higher risk of mortality than the other patients (sub-hazard ratio (SHR) 1.75 [1.44–2.14]). Mortality was lower in normal (SHR 0.69 [0.58–0.85]), overweight (SHR 0.53 [0.43–0.65]) and obese (SHR 0.55 [0.44–0.67]) than in underweight patients. Multivariable analysis (adjusted for age, chronic pulmonary disease, malignant neoplasia, type 2 diabetes) confirmed that in-hospital mortality of underweight patients was higher than overweight patients (females: SHR 0.63 [0.45–0.88] and males: 0.69 [0.51–0.94]).ConclusionEven though these findings do not imply changes in the medical care of hospitalized patients, they support the use of BMI category for the stratification of patients enrolled in interventional studies where mortality is recorded as an outcome.