ABSTRACT
Introduction: There are conflicting data on COVID-19 outcomes in pregnant women. Using the AHA COVID-19 CVD Registry we evaluated COVID-19 outcomes in pregnant vs non-pregnant women with COVID-19. Method(s): Women 18-40 years old hospitalized from March 2020 to December 2021 with symptomatic COVID-19 were included (n=2,068), with 110 (5.3%) pregnant at admission. Women with unknown pregnancy status were excluded. Vaccine data were limited (2.8% of participants), therefore omitted from analysis. Baseline demographics and symptoms at presentation were compared between pregnant and non-pregnant women (Table). Rates of death, mechanical ventilation, ICU admission, hospital stay >=5 days, myocardial infarction, stroke, DVT, PE, and a composite of all outcomes were determined. Multivariable Cox regression analyses were performed, adjusting for comorbidities and prior CVD. Result(s): Pregnant women hospitalized with COVID-19 had fewer comorbidities than non-pregnant women (Table). There were no deaths in the pregnant group and 44 (2.3%) in the non-pregnant group. Fewer pregnant women were hospitalized >=5 days (29.1% vs 41.2% non-pregnant);this difference was not statistically significant after multivariable adjustment [adjusted HR (95% CI), 0.67 (0.43-1.02)]. There were no significant differences between the groups in the composite outcome [adjusted HR (95% CI), 0.72 (0.48-1.07)] or its components (Table). Conclusion(s): Pregnant women hospitalized with symptomatic COVID-19 had fewer comorbidities compared with non-pregnant women. There were fewer deaths and lower rates of hospitalization >=5 days in pregnant vs non-pregnant women which was no longer statistically significant after multivariable adjustment. The potential for residual confounding due to healthier pregnant women presenting with milder COVID-19 illness or being admitted for non-COVID-19 indications compared to non-pregnant women must be considered when interpreting these findings.
ABSTRACT
Background. Our group performed an in-silico screen to identify FDA approved drugs that inhibit SARS-C0V-2 main protease (Mpro), followed by in vitro viral replication assays, and in vivo pharmacokinetic studies in mice. These studies identified atovaquone as a promising candidate for inhibiting viral replication. Methods. Enrolled patients were randomized in a 2:1 fashion to atovaquone 1500 mg twice daily versus matched placebo. Patients received standard of care treatment including remdesivir, dexamethasone, or convalescent plasma as deemed necessary by the treating team. Patients agreed to allow collection of saliva at baseline and twice a day while hospitalized or up to 10 days. Saliva was collected and RNA extracted for viral load (VL) measurement by Real-time PCR. Our primary outcome was to examine the between group differences in log transformed VL(copies/mL) using generalized linear mixed-effect models of repeated measures from all samples. Additional analysis of Atovquone plasma concentrations were examined and correlated with viral load and body mass index (BMI). Results. Of the 61 patients enrolled;41 were received atovaquone and 19 placebo. Overall the population was predominately male Hispanic with a mean age of 51 years. The two groups were balanced (Table 1) with regard to age, gender, race, co-morbidities, days from onset of symptoms, baseline oxygen requirements, and receipt of COVID-19 specific standard of care treatment. A higher proportion with diabetes was noted in the Atovaquone arm. The log10 VL was 5.25 copies/mL vs. 4.79 copies/mL at baseline in the atovaquone vs. placebo group. Although there was a decrease in VL over time, there was no differences between the atovaquone plus standard of care arm versus the standard of care arm (Figure 1). Additional analysis of atovaquone plasma concentration demonstrated a wide variation in atovaquone levels, inverse association between atovaquone levels and BMI (rho -0.44, p=0.03), and Day 5 concentrations and VL (rho -0.54, p=0.005). Conclusion. Although atovaquone showed promising in vitro antiviral properties for COVID-19, in this pilot study we did not detect a change in VL in patients who received atovaquone compared to placebo, possibly due to failure of patients achieve adequate drug levels.
ABSTRACT
Introduction: The pathobiology of inflammation, thrombosis, and myocardial injury associated with SARS-CoV2 may be assessed by circulating biomarkers. However, their relative prognostic importance has been incompletely described. Methods: We analyzed data from pts hospitalized with COVID-19 in Jan to Nov, 2020 at 107 US hospitals in the AHA COVID-19 Cardiovascular (CV) Disease Registry who had biomarker data for D-Dimer, CRP, ferritin, natriuretic peptides [NP], or cTn at admission. We assessed the association between each biomarker by quintile [Q] and odds of in-hospital death and a composite of CV death, myocarditis, AMI, HF, or ischemic stroke. cTn quintiles were indexed to the assay-specific 99 %ile ref limits. Multivariable logistic regression determined the relative prognostic performance of each biomarker. Results: 17,829 (83% of total) had admission values reported for at least 1 of the 5 key biomarkers (n= 2422 with values for all). Each biomarker revealed a gradient of mortality risk from Q1 to Q5: Ddimer 17-35%, CRP 11-30%, ferritin 11-29%, cTn 13-42%, and NPs 7-35% (p for each <0.001;Panel A). After adjustment for all biomarkers, the highest values (Q5) of NP, CRP, and cTn independently identified pts at greater odds of death (Panel B) and the highest values of NP, CRP, cTn and D-dimer identified greater odds of the CV composite. After further adjustment for clinical variables, Q5 values for NPs (OR:4.07, 95% CI: 2.40 to 6.92) and CRP (OR: 2.43, 95% CI:1.62 to 3.66) retained the strongest prognostic value for death;NP (OR:6.79, 95% CI: 3.56 to 12.94) and cTn (OR:4.44, 95% CI:2.75 to 7.18) were associated with the greatest odds of the CV composite. Conclusions: Among pts hospitalized with COVID-19, high levels of NPs, CRP and hsTn at the time of admission were associated with the greatest risk of death, independent of other biomarkers and clinical variables, whereas D-dimer and ferritin did not offer independent prognostic information for mortality.