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.

Association of latitude and altitude with adverse outcomes in patients with COVID-19: The VIRUS registry.

BACKGROUND: The coronavirus disease 2019 (COVID-19) course may be affected by environmental factors. Ecological studies previously suggested a link between climatological factors and COVID-19 fatality rates. However, individual-level impact of these factors has not been thoroughly evaluated yet. AIM: To study the association of climatological factors related to patient location with unfavorable outcomes in patients. METHODS: In this observational analysis of the Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study: COVID-19 Registry cohort, the latitudes and altitudes of hospitals were examined as a covariate for mortality within 28 d of admission and the length of hospital stay. Adjusting for baseline parameters and admission date, multivariable regression modeling was utilized. Generalized estimating equations were used to fit the models. RESULTS: Twenty-two thousand one hundred eight patients from over 20 countries were evaluated. The median age was 62 (interquartile range: 49-74) years, and 54% of the included patients were males. The median age increased with increasing latitude as well as the frequency of comorbidities. Contrarily, the percentage of comorbidities was lower in elevated altitudes. Mortality within 28 d of hospital admission was found to be 25%. The median hospital-free days among all included patients was 20 d. Despite the significant linear relationship between mortality and hospital-free days (adjusted odds ratio (aOR) = 1.39 (1.04, 1.86), P = 0.025 for mortality within 28 d of admission; aOR = -1.47 (-2.60, -0.33), P = 0.011 for hospital-free days), suggesting that adverse patient outcomes were more common in locations further away from the Equator; the results were no longer significant when adjusted for baseline differences (aOR = 1.32 (1.00, 1.74), P = 0.051 for 28-day mortality; aOR = -1.07 (-2.13, -0.01), P = 0.050 for hospital-free days). When we looked at the altitude's effect, we discovered that it demonstrated a non-linear association with mortality within 28 d of hospital admission (aOR = 0.96 (0.62, 1.47), 1.04 (0.92, 1.19), 0.49 (0.22, 0.90), and 0.51 (0.27, 0.98), for the altitude points of 75 MASL, 125 MASL, 400 MASL, and 600 MASL, in comparison to the reference altitude of 148 m.a.s.l, respectively. P = 0.001). We detected an association between latitude and 28-day mortality as well as hospital-free days in this worldwide study. When the baseline features were taken into account, however, this did not stay significant. CONCLUSION: Our findings suggest that differences observed in previous epidemiological studies may be due to ecological fallacy rather than implying a causal relationship at the patient level.

SARS-CoV-2 infection increases risk of acute kidney injury in a bimodal age distribution.

BACKGROUND: Hospitalized patients with SARS-CoV2 develop acute kidney injury (AKI) frequently, yet gaps remain in understanding why adults seem to have higher rates compared to children. Our objectives were to evaluate the epidemiology of SARS-CoV2-related AKI across the age spectrum and determine if known risk factors such as illness severity contribute to its pattern. METHODS: Secondary analysis of ongoing prospective international cohort registry. AKI was defined by KDIGO-creatinine only criteria. Log-linear, logistic and generalized estimating equations assessed odds ratios (OR), risk differences (RD), and 95% confidence intervals (CIs) for AKI and mortality adjusting for sex, pre-existing comorbidities, race/ethnicity, illness severity, and clustering within centers. Sensitivity analyses assessed different baseline creatinine estimators. RESULTS: Overall, among 6874 hospitalized patients, 39.6% (n = 2719) developed AKI. There was a bimodal distribution of AKI by age with peaks in older age (≥60 years) and middle childhood (5-15 years), which persisted despite controlling for illness severity, pre-existing comorbidities, or different baseline creatinine estimators. For example, the adjusted OR of developing AKI among hospitalized patients with SARS-CoV2 was 2.74 (95% CI 1.66-4.56) for 10-15-year-olds compared to 30-35-year-olds and similarly was 2.31 (95% CI 1.71-3.12) for 70-75-year-olds, while adjusted OR dropped to 1.39 (95% CI 0.97-2.00) for 40-45-year-olds compared to 30-35-year-olds. CONCLUSIONS: SARS-CoV2-related AKI is common with a bimodal age distribution that is not fully explained by known risk factors or confounders. As the pandemic turns to disproportionately impacting younger individuals, this deserves further investigation as the presence of AKI and SARS-CoV2 infection increases hospital mortality risk.

Characterization and Outcomes of Hospitalized Children With Coronavirus Disease 2019: A Report From a Multicenter, Viral Infection and Respiratory Illness Universal Study (Coronavirus Disease 2019) Registry.

OBJECTIVES: Multicenter data on the characteristics and outcomes of children hospitalized with coronavirus disease 2019 are limited. Our objective was to describe the characteristics, ICU admissions, and outcomes among children hospitalized with coronavirus disease 2019 using Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study: Coronavirus Disease 2019 registry. DESIGN: Retrospective study. SETTING: Society of Critical Care Medicine Viral Infection and Respiratory Illness Universal Study (Coronavirus Disease 2019) registry. PATIENTS: Children (< 18 yr) hospitalized with coronavirus disease 2019 at participating hospitals from February 2020 to January 2021. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was ICU admission. Secondary outcomes included hospital and ICU duration of stay and ICU, hospital, and 28-day mortality. A total of 874 children with coronavirus disease 2019 were reported to Viral Infection and Respiratory Illness Universal Study registry from 51 participating centers, majority in the United States. Median age was 8 years (interquartile range, 1.25-14 yr) with a male:female ratio of 1:2. A majority were non-Hispanic (492/874; 62.9%). Median body mass index (n = 817) was 19.4 kg/m2 (16-25.8 kg/m2), with 110 (13.4%) overweight and 300 (36.6%) obese. A majority (67%) presented with fever, and 43.2% had comorbidities. A total of 238 of 838 (28.2%) met the Centers for Disease Control and Prevention criteria for multisystem inflammatory syndrome in children, and 404 of 874 (46.2%) were admitted to the ICU. In multivariate logistic regression, age, fever, multisystem inflammatory syndrome in children, and pre-existing seizure disorder were independently associated with a greater odds of ICU admission. Hospital mortality was 16 of 874 (1.8%). Median (interquartile range) duration of ICU (n = 379) and hospital (n = 857) stay were 3.9 days (2-7.7 d) and 4 days (1.9-7.5 d), respectively. For patients with 28-day data, survival was 679 of 787, 86.3% with 13.4% lost to follow-up, and 0.3% deceased. CONCLUSIONS: In this observational, multicenter registry of children with coronavirus disease 2019, ICU admission was common. Older age, fever, multisystem inflammatory syndrome in children, and seizure disorder were independently associated with ICU admission, and mortality was lower among children than mortality reported in adults.

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.

Risk Factors for Critical Coronavirus Disease 2019 and Mortality in Hospitalized Young Adults: An Analysis of the Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS) Coronavirus Disease 2019 Registry.

IMPORTANCE: Even with its proclivity for older age, coronavirus disease 2019 has been shown to affect all age groups. However, there remains a lack of research focused primarily on the young adult population. OBJECTIVES: To describe the epidemiology and outcomes of coronavirus disease 2019 and identify the risk factors associated with critical illness and mortality in hospitalized young adults. DESIGN SETTINGS AND PARTICIPANTS: A retrospective cohort study of the Society of Critical Care Medicine's Viral Infection and Respiratory Illness Universal Study registry. Patients 18-40 years old, hospitalized from coronavirus disease 2019 from March 2020 to April 2021, were included in the analysis. MAIN OUTCOMES AND MEASURES: Critical illness was defined as a composite of mortality and 21 predefined interventions and complications. Multivariable logistic regression was used to assess associations with critical illness and mortality. RESULTS: Data from 4,005 patients (152 centers, 19 countries, 18.6% non-U.S. patients) were analyzed. The median age was 32 years (interquartile range, 27-37 yr); 51% were female, 29.4% Hispanic, and 42.9% had obesity. Most patients (63.2%) had comorbidities, the most common being hypertension (14.5%) and diabetes (13.7%). Hospital and ICU mortality were 3.2% (129/4,005) and 8.3% (109/1,313), respectively. Critical illness occurred in 25% (n = 996), and 34.3% (n = 1,376) were admitted to the ICU. Older age (p = 0.03), male sex (adjusted odds ratio, 1.83 [95% CI, 1.2-2.6]), and obesity (adjusted odds ratio, 1.6 [95% CI, 1.1-2.4]) were associated with hospital mortality. In addition to the above factors, the presence of any comorbidity was associated with critical illness from coronavirus disease 2019. Multiple sensitivity analyses, including analysis with U.S. patients only and patients admitted to high-volume sites, showed similar risk factors. CONCLUSIONS: Among hospitalized young adults, obese males with comorbidities are at higher risk of developing critical illness or dying from coronavirus disease 2019.

Coronavirus Disease 2019-Associated PICU Admissions: A Report From the Society of Critical Care Medicine Discovery Network Viral Infection and Respiratory Illness Universal Study Registry.

OBJECTIVES: To compare clinical characteristics and outcomes of children admitted to the PICU for severe acute respiratory syndrome coronavirus 2-related illness with or without multisystem inflammatory syndrome in children. The secondary objective was to identify explanatory factors associated with outcome of critical illness defined by a composite index of in-hospital mortality and organ system support requirement. DESIGN: Retrospective cohort study. SETTING: Thirty-eight PICUs within the Viral Infection and Respiratory Illness Universal Study registry from March 2020 to January 2021. PATIENTS: Children less than 18 years with severe acute respiratory syndrome coronavirus 2-related illness with or without multisystem inflammatory syndrome in children. MEASUREMENTS AND MAIN RESULTS: Of 394 patients, 171 (43.4%) had multisystem inflammatory syndrome in children. Children with multisystem inflammatory syndrome in children were more likely younger (2-12 yr vs adolescents; p < 0.01), Black (35.6% vs 21.9%; p < 0.01), present with fever/abdominal pain than cough/dyspnea (p < 0.01), and less likely to have comorbidities (33.3% vs 61.9%; p < 0.01) compared with those without multisystem inflammatory syndrome in children. Inflammatory marker levels, use of inotropes/vasopressors, corticosteroids, and anticoagulants were higher in multisystem inflammatory syndrome in children patients (p < 0.01). Overall mortality was 3.8% (15/394), with no difference in the two groups. Diagnosis of multisystem inflammatory syndrome in children was associated with longer duration of hospitalization as compared to nonmultisystem inflammatory syndrome in children (7.5 d[interquartile range, 5-11] vs 5.3 d [interquartile range, 3-11 d]; p < 0.01). Critical illness occurred in 164 patients (41.6%) and was more common in patients with multisystem inflammatory syndrome in children compared with those without (55.6% vs 30.9%; p < 0.01). Multivariable analysis failed to show an association between critical illness and age, race, sex, greater than or equal to three signs and symptoms, or greater than or equal to two comorbidities among the multisystem inflammatory syndrome in children cohort. Among nonmultisystem inflammatory syndrome in children patients, the presence of greater than or equal to two comorbidities was associated with greater odds of critical illness (odds ratio 2.95 [95% CI, 1.61-5.40]; p < 0.01). CONCLUSIONS: This study delineates significant clinically relevant differences in presentation, explanatory factors, and outcomes among children admitted to PICU with severe acute respiratory syndrome coronavirus 2-related illness stratified by multisystem inflammatory syndrome in children.