Description of the study cohort
Patients
During the study period, 650 patients with COVID-19 were admitted; 13 (2.0%) patients were excluded for subsequent readmissions and 17 (2.7%) were excluded for continued hospitalization at the end of the data collection period. Among the 620 patients included in our analysis, the mean age was 63.5 (SD 15.7) years, 430 (69.4%) were male, 267 (43.1%) were white and 181 (29.2%) were Hispanic or Latinx (Table 1). Temporal trends in patient characteristics are reported in Table 1. The median BMI was 28.2 kg/m2 (IQR 24.3-33.1) and 31 (5.0%) described themselves as current users of tobacco. A total of 303 (48.9%) patients described themselves as married and the mean household median annual adjusted gross income in the patient’s home zip code was $68,943 (SD $18,019).
By past medical history or problem list entry, 195 (31.5%) patients had hypertension, 174 (28.1%) had diabetes and 71 (11.5%) had chronic kidney disease of any stage; 277 (44.7%) had no medical comorbidities. The mean initial 24-hour SOFA score was 4.0 (SD 3.0). Additional patient details are summarized by two-week cohort in Table 1.
Treatments
321 (51.8%) received hydroxychloroquine but the percentage was not evenly distributed across the two-week cohorts (P < 0.01), with 127 (75.6%) of patients receiving hydroxychloroquine in the second two-week cohort in March 2020 and only 4 (11.8%) in the final cohort in May 2020. 109 (17.6%) patients received remdesivir with significant difference across the two-week cohorts (P = 0.03), with 4 (11.4%) receiving redesivir in the first two-week cohort and 6 (17.6%) in the final two-week cohort.
507 (81.8%) patients were on room air at some point in their hospitalization and 529 (85.3%) patients received nasal cannula at some point and neither therapy differed significantly by two-week cohort (P = 0.3 for both). 371 (59.8%) patients underwent invasive mechanical ventilation, with 23 (65.7%) patients during the first two-week cohort and significantly decreasing to 14 (41.2%) by the final 2-week cohort (P < 0.01 for the trend). Additionally, 296 (47.7%) patients received high-flow nasal cannula. There was a significant increase in the use of high-flow oxygen from the first two-week cohort (10 patients, 28.6%) to the final cohort (18 patients, 52.9%; P < 0.01). Additional treatment details are found in Table 2.
Outcomes
Overall, 403 (65.0%) patients were discharged alive, increasing from 60.0% during the first two weeks of the study period to 67.6% in the last two weeks (Figure 1a). Of the 217 patients who died during their hospitalization, 176 (81.1% of deaths) occurred in the ICU. Of those patients treated with invasive mechanical ventilation, median (IQR) time on the ventilator was 9.1 (4.7-14.4) days, with a noted temporal decrease across the two-week cohorts (P = 0.02). Median time in the ICU and hospital was 6.2 (2.7-12.5) days and 12.7 (7.5-21.8) days, respectively, and both varied significantly by two-week cohort (P < 0.01 and P = 0.01, respectively). Additional outcomes are shown in Table 2.
Trend and predictors of survival to hospital discharge
Univariate analysis
As shown in Table 3, the odds of being discharged alive increased over time, not adjusting for other covariates (bi-weekly change, OR 1.14, 95% CI 1.00 to 1.28, P = 0.04). Year of age (OR 0.94, 95%CI 0.93-0.95, P < 0.01) and smoking status (OR 0.51, 95%CI 0.35-0.74, P < 0.01) were both associated with decreased odds of survival to hospital discharge. Asian (OR 1.98, 95%CI 1.03-3.83, P = 0.04) and Hispanic/Lantix (OR 1.63, 95%CI 1.09-2.43, P = 0.02) race/ethnicity were associated with greater odds of survival to hospital discharge than White/Caucasian. Household median income based on home ZIP code was associated with increased survival to hospital discharge ($1000 change, OR 1.02, 95% CI 1.01 to 1.03, P < 0.01). Hospital occupancy was inversely associated with survival to hospital discharge (OR 0.98, 95% CI 0.97 to 0.99, P < 0.01). COVID positive/PUI percent hospital capacity was also inversely associated with survival to hospital discharge (OR 0.94, 95% CI 0.92 to 0.97, P < 0.01).
Multivariable analysis
In the final multivariable logistic regression model, the odds of being discharged alive increased over time throughout the study period, after adjusting for age, gender, BMI, race, income, smoking status, marital status, hypertension, diabetes, chronic kidney disease, coronary artery disease, congestive heart failure, COPD, asthma, and SOFA scores (bi-weekly change, aOR 1.22, 95%CI 1.04-1.420, P = 0.02, Table 3). On average, the risk-adjusted patient survival increased from 60.8% (first two weeks) to 69.5% (last two weeks) over the study period (Figure 1B). This finding held true after accounting for hospital-level random effects (bi-weekly change, aOR 1.18, 95% CI 1.00 to 1.38, P = 0.049). Other significant predictors of survival to hospital discharge include greater household median income ($1,000 change, aOR 1.02, 95% CI 1.01 to 1.04, P < 0.01), age (yearly change, aOR 0.92, 95% CI 0.90 to 0.94, P < 0.01) and BMI (one-unit change, aOR 0.93, 95% CI 0.90 to 0.96, P < 0.01).
To estimate the mean causal mediation effects on trends in patient survival to discharge, we further applied the causal mediation effects method with Quasi-Bayesian Monte Carlo approximation using statistical R package Mediation at both patient-level and hospital-level, accounting for hospital clustering effects to estimate the mean causal mediation effects of invasive mechanical ventilation on trends in patient survival to discharge.[18–20] The same set of covariates was adjusted in both mediator and outcome models.
In our a priori defined explanatory models, greater hospital occupancy and higher COVID positive/PUI percent hospital capacity were each inversely associated with survival to hospital discharge (aOR 0.98, 95% CI 0.97 to 1.00, P = 0.04 and aOR 0.94, 95% CI 0.92 to 0.97, P < 0.01, respectively). After adjusting for both hospital occupancy and COVID positive/PUI percent hospital capacity, and the same set of covariates as in the primary model, the temporal trend in risk-adjusted patient survival to hospital discharge remained the same (bi-weekly change, aOR 1.18, 95% CI 1.00 to 1.38, P = 0.04). In this model, hospital occupancy was not independently associated with survival to hospital discharge (P = 0.3); however, COVID positive/PUI percent hospital capacity remained significantly inversely associated with survival to hospital discharge (1% increase, aOR 0.95, 95% CI 0.92 to 0.98, P < 0.01).