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Type I interferon (IFN) is critical in our defense against viral infections. Increased type I IFN pathway activation is a genetic risk factor for systemic lupus erythematosus (SLE), and a number of common risk alleles contribute to the high IFN trait. We hypothesized that these common gain-of-function IFN pathway alleles may be associated with protection from mortality in acute COVID-19. We studied patients admitted with acute COVID-19 (756 European-American and 398 African-American ancestry). Ancestral backgrounds were analyzed separately, and mortality after acute COVID-19 was the primary outcome. In European-American ancestry, we found that a haplotype of interferon regulatory factor 5 (IRF5) and alleles of protein kinase cGMP-dependent 1 (PRKG1) were associated with mortality from COVID-19. Interestingly, these were much stronger risk factors in younger patients (OR=29.2 for PRKG1 in ages 45-54). Variants in the IRF7 and IRF8 genes were associated with mortality from COVID-19 in African-American subjects, and these genetic effects were more pronounced in older subjects. Combining genetic information with blood biomarker data such as C-reactive protein, troponin, and D-dimer resulted in significantly improved predictive capacity, and in both ancestral backgrounds the risk genotypes were most relevant in those with positive biomarkers (OR for death between 14 and 111 in high risk genetic/biomarker groups). This study confirms the critical role of the IFN pathway in defense against COVID-19 and viral infections, and supports the idea that some common SLE risk alleles exert protective effects in anti-viral immunity. BackgroundWe find that a number of IFN pathway lupus risk alleles significantly impact mortality following COVID-19 infection. These data support the idea that type I IFN pathway risk alleles for autoimmune disease may persist in high frequency in modern human populations due to a benefit in our defense against viral infections. Translational SignificanceWe develop multivariate prediction models which combine genetics and known biomarkers of severity to result in greatly improved prediction of mortality in acute COVID-19. The specific associated alleles provide some clues about key points in our defense against COVID-19.
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IntroductionPatients infected with novel COVID-19 virus have a spectrum of illnesses ranging from asymptomatic to death. Data has shown that age, gender and obesity are strongly correlated with poor outcomes in COVID-19 positive patients. Bariatric surgery is the only treatment that provides significant, sustained weight loss in the severely obese. We look at whether prior bariatric surgery correlates with increased risk of hospitalization and outcome severity after COVID-19 infection. MethodsA cross-sectional retrospective analysis of a COVID-19 database from a single, NYC-based, academic institution was conducted. A cohort of COVID-19 positive patients with a history of bariatric surgery (n=124) were matched in a 4:1 ratio to a control cohort of COVID-19 positive patients who were eligible for bariatric surgery (BMI [≥]40 kg/m2 or BMI [≥]35 kg/m2 with a comorbidity) (n=496). A comparison of outcomes, including mechanical ventilation requirements and deceased at discharge, was done between cohorts using Chi-square test or Fishers exact test. Additionally, overall length of stay and duration of time in ICU were compared using Wilcoxon Rank Sum test. Conditional logistic regression analyses were done to determine both unadjusted (UOR) and adjusted odds ratios (AOR). ResultsA total of 620 COVID-19 positive patients were included in this analysis. The categorization of bariatric surgeries included 36% Roux-en-Y Gastric Bypass (RYGB, n=45), 35% laparoscopic adjustable gastric banding (LAGB, n=44), and 28% laparoscopic sleeve gastrectomy (LSG, n=35). The body mass index (BMI) for the bariatric group was 36.1 kg/m2 (SD=8.3), which was significantly lower than the control group, 41.4 kg/m2 (SD=6.5) (p<0.0001). There was also less burden of diabetes in the bariatric group (32%) compared to the control group (48%) (p=0.0019). Patients with a history of bariatric surgery were less likely to be admitted through the emergency room (UOR=0.39, p=0.0001), less likely to have had a ventilator used during the admission (UOR=0.42, p=0.028), had a shorter length of stay in both the ICU (p=0.033) and overall (UOR=0.44, p=0.0002), and were less likely to be deceased at discharge compared to the control group (OR=0.42, p=0.028). ConclusionA history of bariatric surgery significantly decreases the risk of emergency room admission, mechanical ventilation, prolonged ICU stay, and death in patients with COVID-19.
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Early reports showed high mortality from Covid-19; by contrast, the current outbreaks in the southern and western United States are associated with fewer deaths, raising hope that treatments have improved. However, in Texas for instance, 63% of diagnosed cases are currently under 50, compared to only 52% nationally in March-April. Current demographics in Arizona and Florida are similar. Therefore, whether decreasing Covid-19 mortality rates are a reflection of changing demographics or represent improvements in clinical care is unknown. We assessed outcomes over time in a single health system, accounting for changes in demographics and clinical factors. Methods We analyzed biweekly mortality rates for admissions between March 1 and June 20, 2020 in a single health system in New York City. Outcomes were obtained as of July 14, 2020. We included all hospitalizations with laboratory-confirmed Covid-19 disease. Patients with multiple hospitalizations (N=157, 3.3%) were included repeatedly if they continued to have laboratory-confirmed disease. Mortality was defined as in-hospital death or discharge to hospice care. Based on prior literature, we constructed a multivariable logistic regression model to generate expected risk of death, adjusting for age; sex; self-reported race and ethnicity; body mass index; smoking history; presence of hypertension, heart failure, hyperlipidemia, coronary artery disease, diabetes, cancer, chronic kidney disease, or pulmonary disease individually as dummy variables; and admission oxygen saturation, D-dimer, C reactive protein, ferritin, and cycle threshold for RNA detection. All data were obtained from the electronic health record. We then calculated the sum of observed and expected deaths in each two-week period and multiplied each period's observed/expected (O/E) risk by the overall average crude mortality to generate biweekly adjusted rates. We calculated Poisson control limits and indicated points outside the control limits as significantly different, following statistical process control standards. The NYU institutional review board approved the study and granted a waiver of consent. Results We included 4,689 hospitalizations, of which 4,661 (99.4%) had died or been discharged. The median age, and the proportion male or with any comorbidity decreased over time; median real-time PCR cycle threshold increased (indicating relatively less concentration of virus) (Table). For instance, median age decreased from 67 years in the first two weeks to 49 in the last two. Peak hospitalizations were during the fifth and sixth study weeks, which accounted for 40% of the hospitalizations. Median length of stay for patients who died or were discharged to hospice was 8 days (interquartile range, 4-16). Unadjusted mortality dropped each period, from 30.2% in the first two weeks to 3% in the last two weeks, with the last eight weeks being lower than the 95% control limits. Risk adjustment partially attenuated the mortality decline, but adjusted mortality rates in the second-to-last two weeks remained outside the control limits (Figure, Table). The O/E risk of mortality decreased from 1.07 (0.64-1.67) in the first two weeks to 0.39 (0.08-1.12) in the last two weeks. Discussion In this 16-week study of Covid-19 mortality at a single health system, we found that changes in demographics and severity of illness at presentation account for some, but not all, of the decrease in unadjusted mortality. Even after risk adjustment for a variety of clinical and demographic factors, mortality was significantly lower towards the end of the study period. Incremental improvements in outcomes are likely a combination of increasing clinical experience, decreasing hospital volume, growing use of new pharmacologic treatments (such as corticosteroids, remdesivir and anti-cytokine treatments), non-pharmacologic treatments (such as proning), earlier intervention, community awareness, and lower viral load exposure from increasing mask wearing and social distancing. It is also possible that earlier periods had a more virulent circulating strain. In summary, data from one health system suggest that Covid-19 remains a serious disease for high risk patients, but that outcomes may be improving.
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BackgroundCOVID-19 has rapidly emerged as a pandemic infection that has caused significant mortality and economic losses. Potential therapies and means of prophylaxis against COVID-19 are urgently needed to combat this novel infection. As a result of in vitro evidence suggesting zinc sulfate may be efficacious against COVID-19, our hospitals began using zinc sulfate as add-on therapy to hydroxychloroquine and azithromycin. We performed a retrospective observational study to compare hospital outcomes among patients who received hydroxychloroquine and azithromycin plus zinc versus hydroxychloroquine and azithromycin alone. MethodsData was collected from electronic medical records for all patients being treated with admission dates ranging from March 2, 2020 through April 5, 2020. Initial clinical characteristics on presentation, medications given during the hospitalization, and hospital outcomes were recorded. Patients in the study were excluded if they were treated with other investigational medications. ResultsThe addition of zinc sulfate did not impact the length of hospitalization, duration of ventilation, or ICU duration. In univariate analyses, zinc sulfate increased the frequency of patients being discharged home, and decreased the need for ventilation, admission to the ICU, and mortality or transfer to hospice for patients who were never admitted to the ICU. After adjusting for the time at which zinc sulfate was added to our protocol, an increased frequency of being discharged home (OR 1.53, 95% CI 1.12-2.09) reduction in mortality or transfer to hospice remained significant (OR 0.449, 95% CI 0.271-0.744). ConclusionThis study provides the first in vivo evidence that zinc sulfate in combination with hydroxychloroquine may play a role in therapeutic management for COVID-19. 40-word summary: Zinc sulfate added to hydroxychloroquine and azithromycin may improve outcomes among hospitalized patients.
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BackgroundLittle is known about factors associated with hospitalization and critical illness in Covid-19 positive patients. MethodsWe conducted a cross-sectional analysis of all patients with laboratory-confirmed Covid-19 treated at an academic health system in New York City between March 1, 2020 and April 2, 2020, with follow up through April 7, 2020. Primary outcomes were hospitalization and critical illness (intensive care, mechanical ventilation, hospice and/or death). We conducted multivariable logistic regression to identify risk factors for adverse outcomes, and maximum information gain decision tree classifications to identify key splitters. ResultsAmong 4,103 Covid-19 patients, 1,999 (48.7%) were hospitalized, of whom 981/1,999 (49.1%) have been discharged, and 292/1,999 (14.6%) have died or been discharged to hospice. Of 445 patients requiring mechanical ventilation, 162/445 (36.4%) have died. Strongest hospitalization risks were age [≥]75 years (OR 66.8, 95% CI, 44.7-102.6), age 65-74 (OR 10.9, 95% CI, 8.35-14.34), BMI>40 (OR 6.2, 95% CI, 4.2-9.3), and heart failure (OR 4.3 95% CI, 1.9-11.2). Strongest critical illness risks were admission oxygen saturation <88% (OR 6.99, 95% CI 4.5-11.0), d-dimer>2500 (OR 6.9, 95% CI, 3.2-15.2), ferritin >2500 (OR 6.9, 95% CI, 3.2-15.2), and C-reactive protein (CRP) >200 (OR 5.78, 95% CI, 2.6-13.8). In the decision tree for admission, the most important features were age >65 and obesity; for critical illness, the most important was SpO2<88, followed by procalcitonin >0.5, troponin <0.1 (protective), age >64 and CRP>200. ConclusionsAge and comorbidities are powerful predictors of hospitalization; however, admission oxygen impairment and markers of inflammation are most strongly associated with critical illness.