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.

Neurologic Manifestations of Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Hospitalized Patients During the First Year of the COVID-19 Pandemic.

To describe the prevalence, associated risk factors, and outcomes of serious neurologic manifestations (encephalopathy, stroke, seizure, and meningitis/encephalitis) among patients hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. DESIGN: Prospective observational study. SETTING: One hundred seventy-nine hospitals in 24 countries within the Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study COVID-19 Registry. PATIENTS: Hospitalized adults with laboratory-confirmed SARS-CoV-2 infection. INTERVENTIONS: None. RESULTS: Of 16,225 patients enrolled in the registry with hospital discharge status available, 2,092 (12.9%) developed serious neurologic manifestations including 1,656 (10.2%) with encephalopathy at admission, 331 (2.0%) with stroke, 243 (1.5%) with seizure, and 73 (0.5%) with meningitis/encephalitis at admission or during hospitalization. Patients with serious neurologic manifestations of COVID-19 were older with median (interquartile range) age 72 years (61.0-81.0 yr) versus 61 years (48.0-72.0 yr) and had higher prevalence of chronic medical conditions, including vascular risk factors. Adjusting for age, sex, and time since the onset of the pandemic, serious neurologic manifestations were associated with more severe disease (odds ratio [OR], 1.49; p < 0.001) as defined by the World Health Organization ordinal disease severity scale for COVID-19 infection. Patients with neurologic manifestations were more likely to be admitted to the ICU (OR, 1.45; p < 0.001) and require critical care interventions (extracorporeal membrane oxygenation: OR, 1.78; p = 0.009 and renal replacement therapy: OR, 1.99; p < 0.001). Hospital, ICU, and 28-day mortality for patients with neurologic manifestations was higher (OR, 1.51, 1.37, and 1.58; p < 0.001), and patients had fewer ICU-free, hospital-free, and ventilator-free days (estimated difference in days, -0.84, -1.34, and -0.84; p < 0.001). CONCLUSIONS: Encephalopathy at admission is common in hospitalized patients with SARS-CoV-2 infection and is associated with worse outcomes. While serious neurologic manifestations including stroke, seizure, and meningitis/encephalitis were less common, all were associated with increased ICU support utilization, more severe disease, and worse outcomes.

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.

Association of hypothyroidism with outcomes in hospitalized adults with COVID-19: Results from the International SCCM Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS): COVID-19 Registry.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) is associated with high rates of morbidity and mortality. Primary hypothyroidism is a common comorbid condition, but little is known about its association with COVID-19 severity and outcomes. This study aims to identify the frequency of hypothyroidism in hospitalized patients with COVID-19 as well as describe the differences in outcomes between patients with and without pre-existing hypothyroidism using an observational, multinational registry. METHODS: In an observational cohort study we enrolled patients 18 years or older, with laboratory-confirmed severe acute respiratory syndrome coronavirus-2 infection between March 2020 and February 2021. The primary outcomes were (1) the disease severity defined as per the World Health Organization Scale for Clinical Improvement, which is an ordinal outcome corresponding with the highest severity level recorded during a patient's index COVID-19 hospitalization, (2) in-hospital mortality and (3) hospital-free days. Secondary outcomes were the rate of intensive care unit (ICU) admission and ICU mortality. RESULTS: Among the 20,366 adult patients included in the study, pre-existing hypothyroidism was identified in 1616 (7.9%). The median age for the Hypothyroidism group was 70 (interquartile range: 59-80) years, and 65% were female and 67% were White. The most common comorbidities were hypertension (68%), diabetes (42%), dyslipidemia (37%) and obesity (28%). After adjusting for age, body mass index, sex, admission date in the quarter year since March 2020, race, smoking history and other comorbid conditions (coronary artery disease, hypertension, diabetes and dyslipidemia), pre-existing hypothyroidism was not associated with higher odds of severe disease using the World Health Organization disease severity index (odds ratio [OR]: 1.02; 95% confidence interval [CI]: 0.92, 1.13; p = .69), in-hospital mortality (OR: 1.03; 95% CI: 0.92, 1.15; p = .58) or differences in hospital-free days (estimated difference 0.01 days; 95% CI: -0.45, 0.47; p = .97). Pre-existing hypothyroidism was not associated with ICU admission or ICU mortality in unadjusted as well as in adjusted analysis. CONCLUSIONS: In an international registry, hypothyroidism was identified in around 1 of every 12 adult hospitalized patients with COVID-19. Pre-existing hypothyroidism in hospitalized patients with COVID-19 was not associated with higher disease severity or increased risk of mortality or ICU admissions. However, more research on the possible effects of COVID-19 on the thyroid gland and its function is needed in the future.