Biomarker-Concordant Steroid Administration in Severe Coronavirus Disease-2019.

BACKGROUND: Although corticosteroids have become the standard of care for patients with coronavirus disease-2019 (COVID-19) on supplemental oxygen, there is growing evidence of differential treatment response. This study aimed to evaluate if there was an association between biomarker-concordant corticosteroid treatment and COVID-19 outcomes. METHODS: This registry-based cohort study included adult COVID-19 hospitalized patients between January 2020 and December 2021 from 109 institutions. Patients with available C-reactive protein (CRP) levels within 48 h of admission were evaluated. Those on steroids before admission, stayed in the hospital for <48 h, or were not on oxygen support were excluded. Corticosteroid treatment was biomarker-concordant if given with high baseline CRP ≥150 mg/L or withheld with low CRP (<150 mg/L) and vice-versa was considered discordant (low CRP with steroids, high CRP without steroids). Hospital mortality was the primary outcome. Sensitivity analyses were conducted using varying CRP level thresholds. The model interaction was tested to determine steroid effectiveness with increasing CRP levels. RESULTS: Corticosteroid treatment was biomarker-concordant in 1778 (49%) patients and discordant in 1835 (51%). The concordant group consisted of higher-risk patients than the discordant group. After adjusting for covariates, the odds of in-hospital mortality were significantly lower in the concordant group than the discordant (odds ratio [95% confidence interval (C.I.)] = 0.71 [0.51, 0.98]). Similarly, adjusted mortality difference was significant at the CRP thresholds of 100 and 200 mg/L (odds ratio [95% C.I.] = 0.70 [0.52, 0.95] and 0.57 [0.38, 0.85], respectively), and concordant steroid use was associated with lower need for invasive ventilation for 200 mg/L threshold (odds ratio [95% C.I.] = 0.52 [0.30, 0.91]). In contrast, no outcome benefit was observed at CRP threshold of 50. When the model interaction was tested, steroids were more effective at reducing mortality as CRP levels increased. CONCLUSION: Biomarker-concordant corticosteroid treatment was associated with lower odds of in-hospital mortality in severe COVID-19.

Discharge Disposition and Loss of Independence Among Survivors of COVID-19 Admitted to Intensive Care: Results From the SCCM Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS).

OBJECTIVES: To describe incidence and risk factors of loss of previous independent living through nonhome discharge or discharge home with health assistance in survivors of intensive care unit (ICU) admission for coronavirus disease 2019 (COVID-19). DESIGN: Multicenter observational study including patients admitted to the ICU from January 2020 till June 30, 2021. HYPOTHESIS: We hypothesized that there is a high risk of nonhome discharge in patients surviving ICU admission due to COVID-19. SETTING: Data were included from 306 hospitals in 28 countries participating in the SCCM Discovery Viral Infection and Respiratory Illness Universal Study COVID-19 registry. PATIENTS: Previously independently living adult ICU survivors of COVID-19. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was nonhome discharge. Secondary outcome was the requirement of health assistance among patients who were discharged home. Out of 10 820 patients, 7101 (66%) were discharged alive; 3791 (53%) of these survivors lost their previous independent living status, out of those 2071 (29%) through nonhome discharge, and 1720 (24%) through discharge home requiring health assistance. In adjusted analyses, loss of independence on discharge among survivors was predicted by patient age ≥ 65 years (adjusted odds ratio [aOR] 2.78, 95% confidence interval [CI] 2.47-3.14, P < .0001), former and current smoking status (aOR 1.25, 95% CI 1.08-1.46, P = .003 and 1.60 (95% CI 1.18-2.16), P = .003, respectively), substance use disorder (aOR 1.52, 95% CI 1.12-2.06, P = .007), requirement for mechanical ventilation (aOR 4.17, 95% CI 3.69-4.71, P < .0001), prone positioning (aOR 1.19, 95% CI 1.03-1.38, P = .02), and requirement for extracorporeal membrane oxygenation (aOR 2.28, 95% CI 1.55-3.34, P < .0001). CONCLUSIONS: More than half of ICU survivors hospitalized for COVID-19 are unable to return to independent living status, thereby imposing a significant secondary strain on health care systems worldwide.

Development and Validation of an Acute Respiratory Distress Syndrome Prediction Model in Coronavirus Disease 2019: Updated Lung Injury Prediction Score.

OBJECTIVE: To develop and validate an updated lung injury prediction score for coronavirus disease 2019 (COVID-19) (c-LIPS) tailored for predicting acute respiratory distress syndrome (ARDS) in COVID-19. PATIENTS AND METHODS: This was a registry-based cohort study using the Viral Infection and Respiratory Illness Universal Study. Hospitalized adult patients between January 2020 and January 2022 were screened. Patients who qualified for ARDS within the first day of admission were excluded. Development cohort consisted of patients enrolled from participating Mayo Clinic sites. The validation analyses were performed on remaining patients enrolled from more than 120 hospitals in 15 countries. The original lung injury prediction score (LIPS) was calculated and enhanced using reported COVID-19-specific laboratory risk factors, constituting c-LIPS. The main outcome was ARDS development and secondary outcomes included hospital mortality, invasive mechanical ventilation, and progression in WHO ordinal scale. RESULTS: The derivation cohort consisted of 3710 patients, of whom 1041 (28.1%) developed ARDS. The c-LIPS discriminated COVID-19 patients who developed ARDS with an area under the curve (AUC) of 0.79 compared with original LIPS (AUC, 0.74; P<.001) with good calibration accuracy (Hosmer-Lemeshow P=.50). Despite different characteristics of the two cohorts, the c-LIPS's performance was comparable in the validation cohort of 5426 patients (15.9% ARDS), with an AUC of 0.74; and its discriminatory performance was significantly higher than the LIPS (AUC, 0.68; P<.001). The c-LIPS's performance in predicting the requirement for invasive mechanical ventilation in derivation and validation cohorts had an AUC of 0.74 and 0.72, respectively. CONCLUSION: In this large patient sample c-LIPS was successfully tailored to predict ARDS in COVID-19 patients.

A Path to Real-World Evidence in Critical Care Using Open-Source Data Harmonization Tools.

COVID-19 highlighted the need for use of real-world data (RWD) in critical care as a near real-time resource for clinical, research, and policy efforts. Analysis of RWD is gaining momentum and can generate important evidence for policy makers and regulators. Extracting high quality RWD from electronic health records (EHRs) requires sophisticated infrastructure and dedicated resources. We sought to customize freely available public tools, supporting all phases of data harmonization, from data quality assessments to de-identification procedures, and generation of robust, data science ready RWD from EHRs. These data are made available to clinicians and researchers through CURE ID, a free platform which facilitates access to case reports of challenging clinical cases and repurposed treatments hosted by the National Center for Advancing Translational Sciences/National Institutes of Health in partnership with the Food and Drug Administration. This commentary describes the partnership, rationale, process, use case, impact in critical care, and future directions for this collaborative effort.

Coronavirus Disease 2019 in Pediatric Oncology Patients: A Matched-Cohort Analysis of the SCCM Discovery Viral Infection and Respiratory Illness Universal Study COVID-19 Registry.

BACKGROUND: There is a paucity of multicenter data describing the impact of coronavirus disease 2019 (COVID-19) on hospitalized pediatric oncology patients. Using a large, multicenter, Society of Critical Care Medicine (SCCM) Discovery Viral Infection and Respiratory Illness University Study (VIRUS) database, we aimed at assessing outcomes of COVID-19 infection in this population. METHOD: This is a matched-cohort study involving children below 18 years of age hospitalized with COVID-19 between March 2020 and January 2021. Using the VIRUS; COVID-19 Registry database, children with oncologic diseases were compared with propensity score matched (age groups, sex, race, and ethnicity) cohort of children without oncologic diseases for the prevalence of Multisystem Inflammatory Syndrome in Children (MIS-C), intensive care unit (ICU) admission, interventions, hospital, and ICU length of stay. RESULTS: The number of children in the case and control groups was 45 and 180, respectively. ICU admission rate was similar in both groups ([47.7 vs 51.7%], P =0.63). The proportion of children requiring noninvasive and invasive mechanical ventilation, and its duration were similar between groups, same as hospital mortality. Interestingly, MIS-C was significantly lower in the oncology group compared with the control (2.4 vs 24.6%; P =0.0002). CONCLUSIONS: In this study using a multicenter VIRUS database, ICU admission rate, interventions, and outcomes of COVID-19 were similar in children with the oncologic disease compared with control patients. The incidence of MIS-C is lower in oncologic patients.

Hospital Variation in Management and Outcomes of Acute Respiratory Distress Syndrome Due to COVID-19.

OBJECTIVES: To describe hospital variation in use of "guideline-based care" for acute respiratory distress syndrome (ARDS) due to COVID-19. DESIGN: Retrospective, observational study. SETTING: The Society of Critical Care Medicine's Discovery Viral Infection and RESPIRATORY ILLNESS UNIVERSAL STUDY COVID-19 REGISTRY. PATIENTS: Adult patients with ARDS due to COVID-19 between February 15, 2020, and April 12, 2021. INTERVENTIONS: Hospital-level use of "guideline-based care" for ARDS including low-tidal-volume ventilation, plateau pressure less than 30 cm H2O, and prone ventilation for a Pao2/Fio2 ratio less than 100. MEASUREMENTS AND MAIN RESULTS: Among 1,495 adults with COVID-19 ARDS receiving care across 42 hospitals, 50.4% ever received care consistent with ARDS clinical practice guidelines. After adjusting for patient demographics and severity of illness, hospital characteristics, and pandemic timing, hospital of admission contributed to 14% of the risk-adjusted variation in "guideline-based care." A patient treated at a randomly selected hospital with higher use of guideline-based care had a median odds ratio of 2.0 (95% CI, 1.1-3.4) for receipt of "guideline-based care" compared with a patient receiving treatment at a randomly selected hospital with low use of recommended therapies. Median-adjusted inhospital mortality was 53% (interquartile range, 47-62%), with a nonsignificantly decreased risk of mortality for patients admitted to hospitals in the highest use "guideline-based care" quartile (49%) compared with the lowest use quartile (60%) (odds ratio, 0.7; 95% CI, 0.3-1.9; p = 0.49). CONCLUSIONS: During the first year of the COVID-19 pandemic, only half of patients received "guideline-based care" for ARDS management, with wide practice variation across hospitals. Strategies that improve adherence to recommended ARDS management strategies are needed.

Evaluation of the discrimination and calibration of predictive scores of mortality in ECMO for patients with COVID-19.

BACKGROUND: The criteria for the selection of COVID-19 patients that could benefit most from ECMO organ support are yet to be defined. In this study, we evaluated the predictive performance of ECMO mortality predictive models in patients with COVID-19. We also performed a cost-benefit analysis depending on the mortality predicted probability. We conducted a retrospective cohort study in COVID-19 patients who received ECMO at two tertiary care hospitals between March 2020 to July 2021. MATERIALS AND METHODS: We evaluated the discrimination (C-statistic), calibration (Cox calibration), and accuracy of the prediction of death due to severe ARDS in V-V ECMO score (PRESERVE), the Respiratory Extracorporeal Membrane Oxygenation Survival Score (RESP) score, and the PREdiction of Survival on ECMO Therapy-Score (PRESET) score. In addition, we compared the RESP score with Plateau pressure instead of Peak pressure. RESULTS: We included a total of 36 patients, 29 (80%) of them male and with a median (IQR) APACHE of 10 (8-15). The PRESET score had the highest discrimination (AUROCs 0.81 [95%CI 0.67-0.94]) and calibration (calibration-in-the-large 0.5 [95%CI -1.4 to 0.3]; calibration slope 2.2 [95%CI 0.7/3.7]). The RESP score with Plateau pressure had higher discrimination than the conventional RESP score. The cost per QALY in the USA, adjusted to life expectancy, was higher than USD 100 000 in patients older than 45 years with a PRESET > 10. CONCLUSION: The PRESET score had the highest predictive performance and could help in the selection of patients that benefit most from this resource-demanding and highly invasive organ support.

Variations in Administrative Approvals During the COVID-19 Pandemic at Participating Sites in the Society of Critical Care Medicine Discovery Network Viral Infection and Respiratory Illness Universal Study: COVID-19 Registry: A Cross-Sectional Study.

There is a paucity of literature regarding administrative approvals required for clinical studies during a pandemic. We aimed to evaluate variation in duration of administrative approvals within the Viral Infection and Respiratory illness Universal Study (VIRUS): A Global COVID-19 Registry. DESIGN SETTING AND SUBJECTS: Survey analysis of 188 investigators who participated in the VIRUS: COVID-19 registry, a prospective, observational global registry database of 287 sites. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: For each study site approved through December 8, 2020, we assessed the duration in days: 1) from institutional review board (IRB) submission to IRB approval, 2) from IRB approval to Research Electronic Data Capture (REDCap) access, 3) from REDCap access to first patient data entry in REDCap, and 4) total duration from IRB submission to first patient data entry in REDCap. Analysis of variance and Wilcoxon rank-sum test were used to compare time durations. Of 287 sites, 188 sites (United States = 155, non-United States = 33) provided complete administrative data. There was considerable variability in duration from IRB submission to first patient data entry with median (interquartile range) of 28 days (16-50 d), with differences not significantly different by country (United States: 30 [17-50] vs non-United States: 23 d [8-46 d]; p = 0.08) or previous "multisite trial experience" (experienced: 27 [15-51] vs not experienced: 29 d [13-47 d]; p = 0.67). The U.S. sites had a higher proportion of female principal investigators (n = 77; 50%), compared with non-U.S. sites (n = 7; 21%; p = 0.002). Non-U.S. sites had a significantly shorter time to first patient data entry after REDCap access: 7 (1-28) versus 3 days (1-6 d) (p = 0.02). CONCLUSIONS: In this Society of Critical Care Medicine global VIRUS: COVID-19 Registry, we identified considerable variability in time from IRB submission to first patient data entry with no significant differences by country or prior multicenter trial experience. However, there was a significant difference between US and non-U.S. sites in the time from REDCap access to first data entry.

Improved air quality leads to enhanced vegetation growth during the COVID-19 lockdown in India.

The direct effect of pandemic induced lockdown (LD) on environment is widely explored, but its secondary impacts remain largely unexplored. Therefore, we assess the response of surface greenness and photosynthetic activity to the LD-induced improvement of air quality in India. Our analysis reveals a significant improvement in air quality marked by reduced levels of aerosols (AOD, -19.27%) and Particulate Matter (PM 2.5, -23%) during LD (2020)from pre-LD (March-September months for the period 2017-2019). The vegetation exhibits a positive response, reflected by the increase in surface greenness [Enhanced Vegetation Index (EVI, +10.4%)] and photosynthetic activity [Solar Induced Fluorescence (SiF, +11%)], during LD from pre-LD that coincides with two major agricultural seasons of India; Zaid (March-May) and Kharif (June-September). In addition, the croplands show a higher response [two-fold in EVI (14.45%) and four-fold in SiF (17.7%)] than that of forests. The prolonged growing period (phenology) and high rate of photosynthesis (intensification) led to the enhanced greening during LD owing to the reduced atmospheric pollution. This study, therefore, provides new insights into the response of vegetation to the improved air quality, which would give ideas to counter the challenges of food security in the context of climate pollution, and combat global warming by more greening.

Association of dementia and patient outcomes among COVID-19 patients: A multi-center retrospective case-control study.

Background: We conducted a retrospective cohort study on COVID-19 patients with and without dementia by extracting data from the HCA Healthcare Enterprise Data Warehouse between January-September 2020. Aims: To describe the role of patients' baseline characteristics specifically dementia in determining overall health outcomes in COVID-19 patients. Methods: We grouped in-patients who had ICD-10 codes for dementia (DM) with age and gender-matched (1:2) patients without dementia (ND). Our primary outcome variables were in-hospital mortality, length of stay, Intensive Care Unit (ICU) admission, ICU-free days, mechanical ventilation (MV) use, MV-free days and 90-day re-admission. Results: Matching provided similar age and sex in DM and ND groups. BMI (median, 25.8 vs. 27.6) and proportion of patients who had smoked (23.3 vs. 31.3%) were lower in DM than in ND patients. The median (IQR) Elixhauser Comorbidity Index was higher in dementia patients 7 (5-10) vs. 5 (3-7, p < 0.01). Higher mortality was observed in DM group (30.8%) vs. ND group (26.4%, p < 0.01) as an unadjusted univariate analysis. The 90-day readmission was not different (32.1 vs. 31.8%, p = 0.8). In logistic regression analysis, the odds of dying were not different between patients in DM and ND groups (OR = 1.0; 95% CI 0.86-1.17), but the odds of ICU admissions were significantly lower for dementia patients (OR = 0.58, 95% CI 0.51-0.66). Conclusions: Our data showed that COVID-19 patients with dementia did not fare substantially worse, but in fact, fared better when certain metrics were considered.

The impact of violence on healthcare workers' mental health in conflict based settings amidst COVID-19 pandemic, and potential interventions: A narrative review.

Healthcare workers (HCWs) have faced an increased amount of mental health struggles amidst the COVID-19 pandemic. However, those in conflict-based settings with fragile healthcare systems meet additional challenges. This study reviews violence, conflict and mental health among HCWs in five countries: Syria, Palestine, Yemen, Afghanistan and Lebanon. Our study reports that HCWs are targeted by violence, bombings, mistreatment and different forms of abuse, including verbal and physical. With the additional burdens of the pandemic including prolonged working hours, limited resources and insufficient humanitarian aid, the healthcare workers fall victim to increased levels of burnout and mental illnesses. The situation leads to dire consequences on their personal lives and professional development, compelling them to quit their job or country all together. Although healthcare workers remain resilient in these conflict-based settings, immediate interventions are required to prevent violence against them and cater to their rapidly declining mental health.

COVID-19 Misinformation: A Potent Co-Factor in the COVID-19 Pandemic

COVID-19, the biggest global health crisis of our times was complicated by an equally potent co-factor: the misinformation infodemic. A confluence of unique factors led to the emergence of the crisis of misinformation, including the widespread reach of social media, the lack of credible sources and strategies for information dissemination, and the sticky and virulent nature of the misinformation campaigns. One of the primary targets of the misinformation campaign was the COVID-19 vaccine effort, leading to significant impediments to implementing an effective and successful vaccination campaign. The time to act is now and will need a concerted multipronged approach with a close partnership between scientists, public health agencies, government agencies, and social media companies to foster accuracy in the exchange of health information in social media and curb the menace of misinformation. This paper aims to review the scope of the problem and examine strategies to help mitigate it.

The Association of Latitude and Altitude with COVID-19 Symptoms: A VIRUS: COVID-19 Registry Analysis.

Background: Better delineation of COVID-19 presentations in different climatological conditions might assist with prompt diagnosis and isolation of patients. Objectives: To study the association of latitude and altitude with COVID-19 symptomatology. Methods: This observational cohort study included 12267 adult COVID-19 patients hospitalized between 03/2020 and 01/2021 at 181 hospitals in 24 countries within the SCCM Discovery VIRUS: COVID-19 Registry. The outcome was symptoms at admission, categorized as respiratory, gastrointestinal, neurological, mucocutaneous, cardiovascular, and constitutional. Other symptoms were grouped as atypical. Multivariable regression modeling was performed, adjusting for baseline characteristics. Models were fitted using generalized estimating equations to account for the clustering. Results: The median age was 62 years, with 57% males. The median age and percentage of patients with comorbidities increased with higher latitude. Conversely, patients with comorbidities decreased with elevated altitudes. The most common symptoms were respiratory (80%), followed by constitutional (75%). Presentation with respiratory symptoms was not associated with the location. After adjustment, at lower latitudes (<30º), patients presented less commonly with gastrointestinal symptoms (p<.001, odds ratios for 15º, 25º, and 30º: 0.32, 0.81, and 0.98, respectively). Atypical symptoms were present in 21% of the patients and showed an association with altitude (p=.026, odds ratios for 75, 125, 400, and 600 meters above sea level: 0.44, 0.60, 0.84, and 0.77, respectively). Conclusions: We observed geographic variability in symptoms of COVID-19 patients. Respiratory symptoms were most common but were not associated with the location. Gastrointestinal symptoms were less frequent in lower latitudes. Atypical symptoms were associated with higher altitude.

Association of Early Steroid Administration With Outcomes of Children Hospitalized for COVID-19 Without Multisystem Inflammatory Syndrome in Children.

Importance: There is limited evidence for therapeutic options for pediatric COVID-19 outside of multisystem inflammatory syndrome in children (MIS-C). Objective: To determine whether the use of steroids within 2 days of admission for non-MIS-C COVID-19 in children is associated with hospital length of stay (LOS). The secondary objective was to determine their association with intensive care unit (ICU) LOS, inflammation, and fever defervescence. Design, Setting, and Participants: This cohort study analyzed data retrospectively for children (<18 years) who required hospitalization for non-MIS-C COVID-19. Data from March 2020 through September 2021 were provided by 58 hospitals in 7 countries who participate in the Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS) COVID-19 registry. Exposure: Administration of steroids within 2 days of admission. Main Outcomes and Measures: Length of stay in the hospital and ICU. Adjustment for confounders was done by mixed linear regression and propensity score matching. Results: A total of 1163 patients met inclusion criteria and had a median (IQR) age of 7 years (0.9-14.3). Almost half of all patients (601/1163, 51.7%) were male, 33.8% (392/1163) were non-Hispanic White, and 27.9% (324/1163) were Hispanic. Of the study population, 184 patients (15.8%) received steroids within 2 days of admission, and 979 (84.2%) did not receive steroids within the first 2 days. Among 1163 patients, 658 (56.5%) required respiratory support during hospitalization. Overall, patients in the steroids group were older and had greater severity of illness, and a larger proportion required respiratory and vasoactive support. On multivariable linear regression, after controlling for treatment with remdesivir within 2 days, country, race and ethnicity, obesity and comorbidity, number of abnormal inflammatory mediators, age, bacterial or viral coinfection, and disease severity according to ICU admission within first 2 days or World Health Organization ordinal scale of 4 or higher on admission, with a random intercept for the site, early steroid treatment was not significantly associated with hospital LOS (exponentiated coefficient, 0.94; 95% CI, 0.81-1.09; P = .42). Separate analyses for patients with an LOS of 2 days or longer (n = 729), those receiving respiratory support at admission (n = 286), and propensity score-matched patients also showed no significant association between steroids and LOS. Early steroid treatment was not associated with ICU LOS, fever defervescence by day 3, or normalization of inflammatory mediators. Conclusions and Relevance: Steroid treatment within 2 days of hospital admission in a heterogeneous cohort of pediatric patients hospitalized for COVID-19 without MIS-C did not have a statistically significant association with hospital LOS.

SARS-CoV-2 With Concurrent Respiratory Viral Infection as a Risk Factor for a Higher Level of Care in Hospitalized Pediatric Patients.

OBJECTIVE: As of early 2021, there have been over 3.5 million pediatric cases of SARS-CoV-2, including 292 pediatric deaths in the United States. Although most pediatric patients present with mild disease, they are still at risk for developing significant morbidity requiring hospitalization and intensive care unit (ICU) level of care. This study was performed to evaluate if the presence of concurrent respiratory viral infections in pediatric patients admitted to the hospital with SARS-CoV-2 was associated with an increased rate of ICU level of care. DESIGN: A multicenter, international, noninterventional, cross-sectional study using data provided through The Society of Critical Care Medicine Discovery Network Viral Infection and Respiratory Illness Universal Study database. SETTING: The medical ward and ICU of 67 participating hospitals. PATIENTS: Pediatric patients younger than 18 years hospitalized with SARS-CoV-2. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 922 patients were included. Among these patients, 391 required ICU level care and 31 had concurrent non-SARS-CoV-2 viral coinfection. In a multivariate analysis, after accounting for age, positive blood culture, positive sputum culture, preexisting chronic medical conditions, the presence of a viral respiratory coinfection was associated with need for ICU care (odds ratio, 3.6; 95% confidence interval, 1.6-9.4; P < 0.01). CONCLUSIONS: This study demonstrates an association between concurrent SARS-CoV-2 infection with viral respiratory coinfection and the need for ICU care. Further research is needed to identify other risk factors that can be used to derive and validate a risk-stratification tool for disease severity in pediatric patients with SARS-CoV-2.