322. Risk Factors for COVID-19 Disease Severity Using Electronic-Health Records in a Real-World Cohort in the United States

Abstract Background Over 32 million cases of COVID-19 have been reported in the US. Outcomes range from mild upper respiratory infection to hospitalization, acute respiratory failure, and death. We assessed risk factors associated with severe disease, defined as hospitalization within 21 days of diagnosis or death, using US electronic health records (EHR). Methods Patients in the Optum de-identified COVID-19 EHR database who were diagnosed with COVID-19 in 2020 were included in the analysis. Regularized multivariable logistic regression was used to identify risk factors for severe disease. Covariates included demographics, comorbidities, history of influenza vaccination, and calendar time. Results Of the 193,454 eligible patients, 36,043 (18.6%) were hospitalized within 21 days of COVID-19 diagnosis, and 6,397 (3.3%) died. Calendar time followed an inverse J-shaped relationship where severe disease rates rapidly declined in the first 25 weeks of the pandemic. BMI followed an asymmetric V-shaped relationship with highest rates of disease severity observed at the extremes. In the multivariable model, older age had the strongest association with disease severity (odds ratios and 95% confidence intervals of significant associations in Figure). Other risk factors were male sex, uninsured status, underweight and obese BMI, higher Charlson Comorbidity Index, and individual comorbidities including hypertension. Asthma and overweight BMI were not associated with disease severity. Blacks, Hispanics, and Asians experienced higher odds of disease severity compared to Whites. Figure. Significant associations (odds ratio and 95% confidence intervals) with COVID-19 severity (hospitalization or death), adjusted for geographical division. Reference and abbreviation categories: Charlson comorbidity index (CCI) = 0; Age = 18-30; Sex = Female; Race/Ethnicity = White; Insurance = Commercial; Body mass index (BMI) = 18.5-25; Calendar time = 0-25 weeks; Chronic obstructive pulmonary disease (COPD). Conclusion Odds of hospitalization or death have decreased since the start of the pandemic, with the steepest decline observed up to mid-August, possibly reflecting changes in both testing and treatment. Older age is the most important predictor of severe COVID-19. Obese and underweight, but not overweight, BMI were associated with increased odds of disease severity when compared to normal weight. Hypertension, despite not being included in many guidelines for vaccine prioritization, is a significant risk factor. Pronounced health disparities remain across race and ethnicity after accounting for comorbidities, with minorities experiencing higher disease severity. Disclosures Shemra Rizzo, PhD, F. Hoffmann-La Roche Ltd. (Shareholder)Genentech, Inc. (Employee) Ryan Gan, PhD, F. Hoffmann-La Roche Ltd (Shareholder)Genentech, Inc. (Employee) Devika Chawla, PhD MSPH, F. Hoffmann-La Roche Ltd. (Shareholder)Genentech, Inc. (Employee) Kelly Zalocusky, PhD, F. Hoffmann-La Roche Ltd. (Shareholder)Genentech, Inc. (Employee) Xin Chen, PhD, F. Hoffmann-La Roche Ltd. (Shareholder)Genentech, Inc. (Employee) Yifeng Chia, PhD, F. Hoffmann-La Roche Ltd (Shareholder)Genentech, Inc. (Employee)

Figure 2. Bar chart showing different percentages of the cohort who received the different COVID-19 treatment illustrated Conclusion. This first case series of hospitalized COVID-19 patients in PLWH illustrate important demographic and socioeconomic trends with an imbalance towards African Americans. The group mortality rate appear to be higher compared to the overall mortality rate of COVID-19 reported in the general population or other published HIV-COVID-19 coinfection case series. This is not surprising given the fact that only 64% of the cohort had undetected viral load and only 60% had CD4 counts > 200 despite reported 88% ART use. Correlations between lymphopenia and serum ferritin on one hand and serum creatinine on the other hand should be further explored in a larger case series or prospective study. Since COVID-19 mortality is related to HIV severity, improving socioeconomic status and ART compliance could play a big role in positively improving outcome of hospitalized HIV-COVID 19 patients.
Disclosures. Background. Over 32 million cases of COVID-19 have been reported in the US. Outcomes range from mild upper respiratory infection to hospitalization, acute respiratory failure, and death. We assessed risk factors associated with severe disease, defined as hospitalization within 21 days of diagnosis or death, using US electronic health records (EHR).
Methods. Patients in the Optum de-identified COVID-19 EHR database who were diagnosed with COVID-19 in 2020 were included in the analysis. Regularized multivariable logistic regression was used to identify risk factors for severe disease. Covariates included demographics, comorbidities, history of influenza vaccination, and calendar time.
Results. Of the 193,454 eligible patients, 36,043 (18.6%) were hospitalized within 21 days of COVID-19 diagnosis, and 6,397 (3.3%) died. Calendar time followed an inverse J-shaped relationship where severe disease rates rapidly declined in the first 25 weeks of the pandemic. BMI followed an asymmetric V-shaped relationship with highest rates of disease severity observed at the extremes. In the multivariable model, older age had the strongest association with disease severity (odds ratios and 95% confidence intervals of significant associations in Figure). Other risk factors were male sex, uninsured status, underweight and obese BMI, higher Charlson Comorbidity Index, and individual comorbidities including hypertension. Asthma and overweight BMI were not associated with disease severity. Blacks, Hispanics, and Asians experienced higher odds of disease severity compared to Whites.
Conclusion. Odds of hospitalization or death have decreased since the start of the pandemic, with the steepest decline observed up to mid-August, possibly reflecting changes in both testing and treatment. Older age is the most important predictor of severe COVID-19. Obese and underweight, but not overweight, BMI were associated with increased odds of disease severity when compared to normal weight. Hypertension, despite not being included in many guidelines for vaccine prioritization, is a significant risk factor. Pronounced health disparities remain across race and ethnicity after accounting for comorbidities, with minorities experiencing higher disease severity.
Disclosures. Shemra Rizzo, PhD, F. Hoffmann-La Roche Ltd. This also raises the question whether there is some feature of COVID-19 that predisposes to development of specific co-infections. To begin answering that question, we sought to review the distribution of microorganisms identified in bacterial and respiratory cultures in patients admitted with COVID-19.
Methods. In a retrospective review of all patients admitted with COVID-19 in the year 2020 at a single academic tertiary medical facility, all positive blood and respiratory cultures were reviewed. Common contaminants were removed. Duplicate growth of the same organism within the same patient was not counted as a separate event.
Conclusion. This suggests that the distribution of pathogens implicated in coinfections in this patient population may not be substantially different from what might be expected in patients admitted for reasons outside of COVID-19. Further investigation with a larger patient population would provide more generalizable data, including patients admitted for reasons outside of COVID-19. Methods. This retrospective observational study was conducted at multiple VA hospitals across southern California and Arizona. CAPA cases were identified in inpatients with laboratory-confirmed COVID-19 based on microbiologic or serologic evidence of aspergillosis and pulmonary abnormalities on imaging, and were classified according to ECMM/ISHAM consensus definitions. Characteristics of interest included immunosuppressive/modulatory agents used prior to onset of CAPA, COVID-19 disease course, length of hospitalization, and mortality.

COVID-19-Associated Pulmonary Aspergillosis (CAPA) at Veterans Affairs (VA) Hospitals in Southern California and Arizona
Results. Seventeen patients with probable (18%) or possible (82%) CAPA were identified from April 2020 to March 2021. Values below reported as medians. All patients were male and 13 (76%) were white, with age 74 years and BMI 26 kg/m 2 . Baseline comorbidities included diabetes mellitus (47%), cardiovascular disease (65%), and pulmonary disease (71%). Evidence of aspergillosis was mostly based on respiratory culture, with mainly A. fumigatus (75%). Systemic corticosteroids were used in 14 patients, with a total dose of 400 mg prednisone equivalents starting 10 days prior to Aspergillus detection. Patients also received tocilizumab (18%), leflunomide (6%), tacrolimus (6%), mycophenolate (6%), and investigational agent LSALT or placebo (6%); 2 patients (12%) did not receive any immunosuppression/modulation. Length of hospitalization for COVID-19 was 22 days. Death occurred in 12 patients (71%), including all patients with probable CAPA, at 34 days after COVID-19 diagnosis and 16 days after CAPA diagnosis. Eight patients (47%) were treated for aspergillosis; mortality did not appear to differ with treatment (75% vs. 67%). Conclusion. This case series reports high mortality among patients with CAPA; the primary contributor to this outcome is unclear. Frequency of lower respiratory tract sampling in patients with COVID-19 may have limited diagnosis of CAPA. Interestingly, inpatient respiratory cultures with Aspergillus spp. increased compared to previous years. Future work will attempt to identify risk factors for CAPA and attributable mortality via comparison to inpatients with COVID-19 without CAPA.