Associations Between Gastrointestinal Symptoms and COVID-19 Severity Outcomes Based on a Propensity Score-Weighted Analysis of a Nationwide Cohort.

Background and Aims: Gastrointestinal (GI) symptoms are well-recognized manifestations of coronavirus disease 2019 (COVID-19). Our primary objective was to evaluate the association between GI symptoms and COVID-19 severity. Methods: In this nationwide cohort of US veterans, we evaluated GI symptoms (nausea/vomiting/diarrhea) reported 30 days before and including the date of positive SARS-CoV-2 testing (March 1, 2020, to February 20, 2021). All patients had ≥1 year of prior baseline data and ≥60 days follow-up relative to the test date. We used propensity score (PS)-weighting to balance covariates in patients with vs without GI symptoms. The primary composite outcome was severe COVID-19, defined as hospital admission, intensive care unit admission, mechanical ventilation, or death within 60 days of positive testing. Results: Of 218,045 SARS-CoV-2 positive patients, 29,257 (13.4%) had GI symptoms. After PS weighting, all covariates were balanced. In the PS-weighted cohort, patients with vs without GI symptoms had severe COVID-19 more often (29.0% vs 17.1%; P < .001). When restricted to hospitalized patients (14.9%; n=32,430), patients with GI symptoms had similar frequencies of intensive care unit admission and mechanical ventilation compared with patients without symptoms. There was a significant age interaction; among hospitalized patients aged ≥70 years, lower COVID-19-associated mortality was observed in patients with vs without GI symptoms, even after accounting for COVID-19-specific medical treatments. Conclusion: In the largest integrated US health care system, SARS-CoV-2-positive patients with GI symptoms experienced severe COVID-19 outcomes more often than those without symptoms. Additional research on COVID-19-associated GI symptoms may inform preventive efforts and interventions to reduce severe COVID-19.

Proton pump inhibitor use is not significantly associated with severe COVID-19 related outcomes after extensive covariate adjustment

OBJECTIVES/GOALS: Using the covariate-rich Veteran Health Administration data, estimate the association between Proton Pump Inhibitor (PPI) use and severe COVID-19, rigorously adjusting for confounding using propensity score (PS)-weighting. METHODS/STUDY POPULATION: We assembled a national retrospective cohort of United States veterans who tested positive for SARS-CoV-2, with information on 33 covariates including comorbidity diagnoses, lab values, and medications. Current outpatient PPI use was compared to non-use (two or more fills and pills on hand at admission vs no PPI prescription fill in prior year). The primary composite outcome was mechanical ventilation use or death within 60 days;the secondary composite outcome included ICU admission. PS-weighting mimicked a 1:1 matching cohort, allowing inclusion of all patients while achieving good covariate balance. The weighted cohort was analyzed using logistic regression. RESULTS/ANTICIPATED RESULTS: Our analytic cohort included 97,674 veterans with SARS-CoV-2 testing, of whom 14,958 (15.3%) tested positive (6,262 [41.9%] current PPI-users, 8,696 [58.1%] non-users). After weighting, all covariates were well-balanced with standardized mean differences less than a threshold of 0.1. Prior to PS-weighting (no covariate adjustment), we observed higher odds of the primary (9.3% vs 7.5%;OR 1.27, 95% CI 1.13-1.43) and secondary (25.8% vs 21.4%;OR 1.27, 95% CI 1.18-1.37) outcomes among PPI users vs non-users. After PS-weighting, PPI use vs non-use was not associated with the primary (8.2% vs 8.0%;OR 1.03, 95% CI 0.91-1.16) or secondary (23.4% vs 22.9%;OR 1.03, 95% CI 0.95-1.12) outcomes. DISCUSSION/SIGNIFICANCE: The associations between PPI use and severe COVID-19 outcomes that have been previously reported may be due to limitations in the covariates available for adjustment. With respect to COVID-19, our robust PS-weighted analysis provides patients and providers with further evidence for PPI safety.

APOL1 Risk Variants, Acute Kidney Injury, and Death in Participants With African Ancestry Hospitalized With COVID-19 From the Million Veteran Program.

IMPORTANCE: Coronavirus disease 2019 (COVID-19) confers significant risk of acute kidney injury (AKI). Patients with COVID-19 with AKI have high mortality rates. OBJECTIVE: Individuals with African ancestry with 2 copies of apolipoprotein L1 (APOL1) variants G1 or G2 (high-risk group) have significantly increased rates of kidney disease. We tested the hypothesis that the APOL1 high-risk group is associated with a higher-risk of COVID-19-associated AKI and death. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study included 990 participants with African ancestry enrolled in the Million Veteran Program who were hospitalized with COVID-19 between March 2020 and January 2021 with available genetic information. EXPOSURES: The primary exposure was having 2 APOL1 risk variants (RV) (APOL1 high-risk group), compared with having 1 or 0 risk variants (APOL1 low-risk group). MAIN OUTCOMES AND MEASURES: The primary outcome was AKI. The secondary outcomes were stages of AKI severity and death. Multivariable logistic regression analyses adjusted for preexisting comorbidities, medications, and inpatient AKI risk factors; 10 principal components of ancestry were performed to study these associations. We performed a subgroup analysis in individuals with normal kidney function prior to hospitalization (estimated glomerular filtration rate ≥60 mL/min/1.73 m2). RESULTS: Of the 990 participants with African ancestry, 905 (91.4%) were male with a median (IQR) age of 68 (60-73) years. Overall, 392 (39.6%) patients developed AKI, 141 (14%) developed stages 2 or 3 AKI, 28 (3%) required dialysis, and 122 (12.3%) died. One hundred twenty-five (12.6%) of the participants were in the APOL1 high-risk group. Patients categorized as APOL1 high-risk group had significantly higher odds of AKI (adjusted odds ratio [OR], 1.95; 95% CI, 1.27-3.02; P = .002), higher AKI severity stages (OR, 2.03; 95% CI, 1.37-2.99; P < .001), and death (OR, 2.15; 95% CI, 1.22-3.72; P = .007). The association with AKI persisted in the subgroup with normal kidney function (OR, 1.93; 95% CI, 1.15-3.26; P = .01). Data analysis was conducted between February 2021 and April 2021. CONCLUSIONS AND RELEVANCE: In this cohort study of veterans with African ancestry hospitalized with COVID-19 infection, APOL1 kidney risk variants were associated with higher odds of AKI, AKI severity, and death, even among individuals with prior normal kidney function.

Comparison of COVID-19 versus influenza on the incidence, features, and recovery from acute kidney injury in hospitalized United States Veterans.

Acute kidney injury is a common complication in patients hospitalized with SARSCoV-2 (COVID-19), with prior studies implicating multiple potential mechanisms of injury. Although COVID-19 is often compared to other respiratory viral illnesses, few formal comparisons of these viruses on kidney health exist. In this retrospective cohort study, we compared the incidence, features, and outcomes of acute kidney injury among Veterans hospitalized with COVID-19 or influenza and adjusted for baseline conditions using weighted comparisons. A total of 3402 hospitalizations for COVID-19 and 3680 hospitalizations for influenza admitted between October 1, 2019 and May 31, 2020 across 127 Veterans Administration hospitals nationally were studied using the electronic medical record. Acute kidney injury occurred more frequently among those with COVID-19 compared to those with influenza (40.9% versus 29.4%, weighted analysis) and was more severe. Patients with COVID-19 were more likely to require mechanical ventilation and vasopressors and experienced higher mortality. Proteinuria and hematuria were frequent in both groups but more common in COVID-19. Recovery of kidney function was less common in patients with COVID-19 and acute kidney injury but was similar among survivors. Thus, findings from this study confirm that acute kidney injury is more common and severe among patients hospitalized with COVID-19 compared to influenza, a finding that may be driven largely by illness severity. Hence, the combined impact of these two illnesses on kidney health may be significant and have important implications for resource allocation.

Early initiation of prophylactic anticoagulation for prevention of coronavirus disease 2019 mortality in patients admitted to hospital in the United States: cohort study.

OBJECTIVE: To evaluate whether early initiation of prophylactic anticoagulation compared with no anticoagulation was associated with decreased risk of death among patients admitted to hospital with coronavirus disease 2019 (covid-19) in the United States. DESIGN: Observational cohort study. SETTING: Nationwide cohort of patients receiving care in the Department of Veterans Affairs, a large integrated national healthcare system. PARTICIPANTS: All 4297 patients admitted to hospital from 1 March to 31 July 2020 with laboratory confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and without a history of anticoagulation. MAIN OUTCOME MEASURES: The main outcome was 30 day mortality. Secondary outcomes were inpatient mortality, initiating therapeutic anticoagulation (a proxy for clinical deterioration, including thromboembolic events), and bleeding that required transfusion. RESULTS: Of 4297 patients admitted to hospital with covid-19, 3627 (84.4%) received prophylactic anticoagulation within 24 hours of admission. More than 99% (n=3600) of treated patients received subcutaneous heparin or enoxaparin. 622 deaths occurred within 30 days of hospital admission, 513 among those who received prophylactic anticoagulation. Most deaths (510/622, 82%) occurred during hospital stay. Using inverse probability of treatment weighted analyses, the cumulative incidence of mortality at 30 days was 14.3% (95% confidence interval 13.1% to 15.5%) among those who received prophylactic anticoagulation and 18.7% (15.1% to 22.9%) among those who did not. Compared with patients who did not receive prophylactic anticoagulation, those who did had a 27% decreased risk for 30 day mortality (hazard ratio 0.73, 95% confidence interval 0.66 to 0.81). Similar associations were found for inpatient mortality and initiation of therapeutic anticoagulation. Receipt of prophylactic anticoagulation was not associated with increased risk of bleeding that required transfusion (hazard ratio 0.87, 0.71 to 1.05). Quantitative bias analysis showed that results were robust to unmeasured confounding (e-value lower 95% confidence interval 1.77 for 30 day mortality). Results persisted in several sensitivity analyses. CONCLUSIONS: Early initiation of prophylactic anticoagulation compared with no anticoagulation among patients admitted to hospital with covid-19 was associated with a decreased risk of 30 day mortality and no increased risk of serious bleeding events. These findings provide strong real world evidence to support guidelines recommending the use of prophylactic anticoagulation as initial treatment for patients with covid-19 on hospital admission.