The impact of timing of initiating invasive mechanical ventilation in COVID-19-related respiratory failure.

PURPOSE: Optimal timing of initiating invasive mechanical ventilation (IMV) in coronavirus disease 2019 (COVID-19)-related respiratory failure is unclear. We hypothesized that a strategy of IMV as opposed to continuing high flow oxygen or non-invasive mechanical ventilation each day after reaching a high FiO2 threshold would be associated with worse in-hospital mortality. METHODS: Using data from Kaiser Permanente Northern/Southern California's 36 medical centers, we identified patients with COVID-19-related acute respiratory failure who reached ≥80% FiO2 on high flow nasal cannula or non-invasive ventilation. Exposure was IMV initiation each day after reaching high FiO2 threshold (T0). We developed propensity scores with overlap weighting for receipt of IMV each day adjusting for confounders. We reported relative risk of inpatient death with 95% Confidence Interval. RESULTS: Of 28,035 hospitalizations representing 21,175 patient-days, 5758 patients were included (2793 received and 2965 did not receive IMV). Patients receiving IMV had higher unadjusted mortality (63.6% versus 18.2%, P < 0.0001). On each day after reaching T0 through day >10, the adjusted relative risk was higher for those receiving IMV compared to those not receiving IMV (Relative Risk>1). CONCLUSIONS: Initiation of IMV on each day after patients reach high FiO2 threshold was associated with higher inpatient mortality after adjusting for time-varying confounders. Remaining on high flow nasal cannula or non-invasive ventilation does not appear to be harmful compared to IMV. Prospective evaluation is needed.

Anakinra or high-dose corticosteroids in COVID-19 pneumonia patients who deteriorate on low-dose dexamethasone: An observational study of comparative effectiveness.

OBJECTIVE: To assess whether escalating to high-dose corticosteroids or anakinra compared to continuing low-dose corticosteroids reduced mortality in patients with severe coronavirus disease 2019 (COVID-19) whose respiratory function deteriorated while receiving dexamethasone 6mg daily (DEXA6). METHODS: We conducted a retrospective cohort study between 3/1-12/31/2020 of hospitalized patients with confirmed COVID-19 pneumonia. In-hospital death was analyzed using logistic regression with inverse probability of treatment weighting of receiving anakinra, high-dose corticosteroid (dexamethasone >10mg daily) or remaining on low-dose corticosteroids on the day of first respiratory deterioration. RESULTS: We analyzed 6,671 patients whose respiratory status deteriorated while receiving DEXA6 for COVID-19 pneumonia, of whom 6265 stayed on low-dose corticosteroids, 232 were escalated to high-dose corticosteroids and 174 to anakinra in addition to corticosteroids. The propensity score-adjusted odds of death were higher in the anakinra (odds ratio [OR]=1.76, 95% CI=1.13-2.72) and high-dose corticosteroid groups (OR=1.53, 95% CI=1.14-2.07) compared with those who continued low-dose corticosteroids on the day of respiratory deterioration. The odds of hospital-acquired infections were also higher in the anakinra (OR=2.00, 95% CI=1.28-3.11) and high-dose corticosteroid groups (OR=1.43, 95% CI=1.00-2.04) compared with low-dose corticosteroid group. CONCLUSION: Our findings do not support escalating patients with COVID-19 pneumonia who deteriorate on low-dose corticosteroids to high-dose corticosteroids or anakinra.

The intensity of anticoagulant dosing in hospitalized patients with COVID-19: An observational, comparative effectiveness study.

BACKGROUND: The question of anticoagulant dosing in hospitalized patients with coronavirus disease-2019 (COVID-19) is unresolved, with randomized trials showing mixed results and heterogeneity of treatment effects for in-hospital death. OBJECTIVE: To examine the association between the intensity of anticoagulation and clinical outcomes in hospitalized patients with COVID-19. DESIGN, SETTING AND PARTICIPANTS: Retrospective cohort study of patients with COVID-19 and respiratory impairment who were hospitalized between 3/1/2020-12/31/2020 in two Kaiser Permanente regions. EXPOSURE AND MAIN OUTCOME: We fit propensity score models using categorical regression to estimate the probability of receiving standard prophylactic, intermediate, or full-dose anticoagulation beginning on the day of admission or on the day of first respiratory deterioration. Exposure was defined by the highest dose on the day of admission or within 24 hours after deterioration. The primary outcome was in-hospital death. RESULTS: We included 17,130 patients in the day of admission analysis and 4,924 patients who experienced respiratory deterioration. There were no differences in propensity score-adjusted odds of in-hospital death for patients who received either intermediate (odds ratio [OR]: 1.00, 95% confidence intervals [CI] 0.89-1.12) or full anticoagulation (OR: 1.00, 95% CI: 0.85-1.17) compared with standard prophylaxis beginning on the day of admission. Similarly, there were no differences in in-hospital death for either intermediate (OR: 1.22, 95% CI: 0.82-1.82) or full anticoagulation (OR: 1.50, 95% CI: 0.90-2.51) compared with standard prophylaxis on the day of deterioration. CONCLUSION: Results of this real-world, comparative effectiveness study showed no differences in in-hospital death among newly admitted or deteriorating patients with COVID-19 who received intermediate-dose or full anticoagulation compared with standard prophylaxis.

High-dose corticosteroids in patients hospitalized for COVID-19 pneumonia: an observational study of comparative effectiveness.

OBJECTIVES: To assess whether high- compared with low-dose corticosteroids started upon hospitalization reduce mortality in patients with severe COVID-19 pneumonia or in subgroups stratified by severity of respiratory impairment on admission. METHODS: We conducted a retrospective cohort study of patients with confirmed SARS-CoV-2 infection who required oxygen supplementation upon hospitalization between March 1 and December 31, 2020. In-hospital death was analyzed using logistic regression with inverse probability of treatment weighting of receiving low- or high-dose corticosteroid (dexamethasone 6-10 mg daily or >10-20 mg daily or other corticosteroid equivalents). RESULTS: We analyzed 13,366 patients who received low-dose and 948 who received high-dose corticosteroids, of whom 31.3% and 40.4% had severe respiratory impairment (>15 l/min of oxygen or mechanical ventilation) upon admission, respectively. There were no differences in the propensity score-adjusted odds of death (odds ratio 1.17, 95% CI 0.72-1.90) or infections (odds ratio 0.70, 95% CI 0.44-1.11) for patients who received high-dose compared with low-dose corticosteroids, beginning on the day of admission. No significant differences in subgroups stratified by severity of respiratory impairment were found. CONCLUSION: Initiating high-dose compared with low-dose corticosteroids among newly hospitalized patients with COVID-19 pneumonia did not improve survival. However, benefit of high-dose corticosteroids in specific subgroups cannot be excluded.

Acute myocarditis following a third dose of COVID-19 mRNA vaccination in adults.

INTRODUCTION: Myocarditis has been reported following the second dose of COVID-19 mRNA vaccination. Whether administration of additional doses of COVID-19 vaccines further increases the risk of myocarditis is unknown. METHODS: We included individuals who received one to three doses of BNT162b2 or mRNA-1273 mRNA vaccine between 12/14/2020 and 2/18/2022. Myocarditis within 21 days of vaccine administration was identified using electronic medical records. Incidence rate ratios were calculated by comparing the observed incidence with the expected incidence from the same population during a 365-day baseline period. RESULTS: Of 3,076,660 KPSC members who received at least one dose of COVID-19 mRNA vaccines, 2,916,739 (94.5%) received at least two doses, and 1,146,254 (47.0%) received three doses. The incidence rate ratio for myocarditis was 0.86 (95% CI 0.31-1.93) for the first dose, 4.22 (95% CI 2.63-6.53) for the second dose, and 2.61 (1.13-5.29) for the third dose. Most myocarditis cases following the second and third dose occurred within seven days of vaccination. CONCLUSION: Myocarditis was a rare event observed after the second or third dose of vaccination. Most cases presented within seven days of vaccination. The incidence of myocarditis following the third dose was not significantly higher than that observed after the second dose.

Factors associated with weight gain during the COVID-19 pandemic.

BACKGROUND: To limit transmission of COVID-19, state governments issued shelter-in-place orders. These orders coincided with a decrease in daily step count and an increase in overeating. We evaluated factors associated with weight gain of ≥ 15 pounds during the pandemic within an integrated health care system. METHODS: We included adults ages 18 and above with at least one weight measurement before the pandemic (March 19, 2019-March 19, 2020) and another measurement after COVID-19 vaccines became available, more than 9 months into the pandemic (December 14, 2020-December 14, 2021). Logistic regression was used to identify factors associated with weight gain of 15 pounds or more. RESULTS: Of 524,451 adults included in the study, median age was 61 years, 43.2% were men, 36.2% self identified as White, 8.6% Black, 35.7% Hispanic, and 16.2% Asian. During the pandemic, 38,213 (7.3%) adults gained ≥ 15 pounds. A higher proportion of young adults gained weight (16.2% age 18-39, 7.6% age 40-64, 4.7% age 65-79%, and 3.1% age ≥ 80). No significant difference was observed between men and women (7.2% men and 7.4% women). Weight gain was more prevalent among adults from low-income neighborhoods (8.9% low-income neighborhoods, 8.0% intermediate-income neighborhoods, and 6.5% high-income neighborhoods). Multivariable logistic regression demonstrated that compared to adults ages 65-79 years, young adults ages 18-39 years had the highest risk of gaining ≥ 15 pounds (adjusted OR 5.19, 95% CI 5.01-5.38). Black race was associated with weight gain in an unadjusted analysis (OR 1.25, 95% CI 1.21-1.30). However, this association was significantly attenuated after adjusting for other risk factors including neighborhood income levels (adjusted OR 1.06, 95% CI 1.02-1.10). Having a diagnosis of depression pre-pandemic was also associated with weight gain during the pandemic (adjusted OR 1.54, 95% CI 1.50-1.58). CONCLUSION: In this racially and ethnically diverse population in southern California, significant weight gain of 15 pounds or more was observed in 7.3% of the adult population during the COVID-19 pandemic. Young adults, individuals who resided in low-income neighborhoods, and patients with depression were disproportionally affected.

Patterns of incident dementia codes during the COVID-19 pandemic at an integrated healthcare system.

BACKGROUND: The COVID-19 pandemic delayed diagnosis and care for some acute conditions and reduced monitoring for some chronic conditions. It is unclear whether new diagnoses of chronic conditions such as dementia were also affected. We compared the pattern of incident Alzheimer's disease and related dementia (ADRD) diagnosis codes from 2017 to 2019 through 2020, the first pandemic year. METHODS: Retrospective cohort design, leveraging 2015-2020 data on all members 65 years and older with no prior ADRD diagnosis, enrolled in a large integrated healthcare system for at least 2 years. Incident ADRD was defined as the first ICD-10 code at any encounter, including outpatient (face-to-face, video, or phone), hospital (emergency department, observation, or inpatient), or continuing care (home, skilled nursing facility, and long-term care). We also examined incident ADRD codes and use of telehealth by age, sex, race/ethnicity, and spoken language. RESULTS: Compared to overall annual incidence rates for ADRD codes in 2017-2019, 2020 incidence was slightly lower (1.30% vs. 1.40%), partially compensating later in the year for reduced rates during the early months of the pandemic. No racial or ethnic group differences were identified. Telehealth ADRD codes increased fourfold, making up for a 39% drop from face-to-face outpatient encounters. Older age (85+) was associated with higher odds of receiving telecare versus face-to-face care in 2020 (OR:1.50, 95%CI: 1.25-1.80) and a slightly lower incidence of new codes; no racial/ethnic, sex, or language differences were identified in the mode of care. CONCLUSIONS: Rates of incident ADRD codes dropped early in the first pandemic year but rose again to near pre-pandemic rates for the year as a whole, as clinicians rapidly pivoted to telehealth. With refinement of protocols for remote dementia detection and diagnosis, health systems could improve access to equitable detection and diagnosis of ADRD going forward.