Introduction Despite considerable scientific debate, there have been no prospective clinical studies on the effects of angiotensin II receptor blockers (ARBs) on the course of COVID-19 infection. Losartan is the ARB that was chosen to be tested in this study. Methods Patients with COVID-19 and mild hypoxia (receipt of ≤ 3 L/min O₂ by nasal cannula) admitted to three hospitals were randomized in a 1:1 ratio within 72 h of SARS-CoV-2 nucleic acid testing confirmation to prospectively receive standard of care (SOC) alone or SOC plus losartan 12.5 mg orally every 12 h for 10 days or until hospital discharge, with the option to titrate upward dependent on blood pressure tolerability. Primary composite endpoint was receipt of mechanical ventilation or death before receiving ventilation. Subjects were followed until discharge to home or until an endpoint was met in the hospital. Results Sixteen subjects received an ARB plus SOC and 15 subjects received SOC alone. The median age was 53 years for both groups. Median time from hospital admission to study enrollment was 2 days (range 1–6) for the ARB group and 2 days (range 1–4) for the SOC group. Mean Charlson comorbidity index was 2 for both groups. One subject in each group achieved the composite endpoint. Conclusion This small prospective randomized open-label study showed no clinically significant impacts of ARB therapy in mildly hypoxemic patients hospitalized with COVID-19 early in the pandemic. A larger prospective randomized placebo-controlled trial would be needed to confirm these findings or capture less pronounced effects and probably should focus on outpatients earlier in disease course. Trial Registration clinicaltrials.gov; March 27, 2020; NCT04340557.

Background: Interventions mitigating progression to mechanical ventilation in COVID-19 would markedly improve outcome and reduce healthcare utilization. We hypothesized that immunomodulation with IVIG would improve oxygenation and reduce length of hospital stay and progression to mechanical ventilation in COVID-19 pneumonia. Methods: Patients with COVID-19 were randomized 1:1 to prospectively receive standard of care (SOC) plus IVIG 0.5 g/kg/day × 3 days with methylprednisolone 40 mg 30 minutes before infusion versus SOC alone. Results: 16 subjects received IVIG plus SOC and 17 SOC alone. The median age was 51 years for SOC and 58 years for IVIG. APACHE II scores and Charlson comorbidity indices were similar for IVIG and SOC (median 7.5 vs 7 and 2 for both, respectively). Seven SOC versus 2 IVIG subjects required mechanical ventilation (p=0.12, Fisher exact test). Among subjects with A-a gradient of >200 mm Hg at enrollment, the IVIG group showed i) a lower rate of progression to requiring mechanical ventilation (2/14 vs 7/12, p=0.038 Fisher exact test), ii) shorter median hospital length of stay (11 vs 19 days, p=0.01 Mann Whitney U), iii) shorter median ICU stay (2.5 vs 12.5 days, p=0.006 Mann Whitey U), and iv) greater improvement in PaO ₂ /FiO ₂ at 7 days (median [range] change from time of enrollment +131 [+35 to +330] vs +44·5 [-115 to +157], p=0.01, Mann Whitney-U test) than SOC. Conclusion: This pilot prospective randomized study comprising largely of Latino patients showed that IVIG significantly improved hypoxia and reduced hospital length of stay and progression to mechanical ventilation in COVID-19 patients with A-a gradient >200 mm Hg.

A 5-question telephone survey was administered to compare satisfaction between patients receiving vancomycin vs daptomycin outpatient parenteral antimicrobial therapy (OPAT). Twenty-seven patients completed the survey (40%). Vancomycin had higher daily interference score than daptomycin (P = .03). All patients receiving daptomycin reported a satisfaction score ≥8/10, as compared to 67% of patients who received vancomycin (P < .03). OPAT antibiotics with less cumbersome administration regimens may translate into higher patient satisfaction and quicker return to life normalcy.

Rare disease Despite unprecedented speed in the execution of the COVID-19 vaccine and therapeutic clinical trials, pregnant patients have been largely excluded from initial studies. In addition, pregnant patients who are unvaccinated against SARS-CoV-2 have greater morbidity risk with severe COVID-19 disease as compared to patients of similar age and comorbidity status. Intravenous immunoglobulin (IVIG) has been deemed safe in pregnancy in other diseases. Prior data demonstrate the possible benefit of utilizing IVIG for the treatment in hospitalized patients with severe respiratory symptoms associated with COVID-19 active infections when administered within 14 days of COVID symptom onset. We administered IVIG (Privigen^®, CSL Behring) 0.5 g/kg daily for 3 consecutive days to 4 pregnant patients (ages 24-34 years of age) who were hospitalized with moderate-to-severe COVID-19 and not vaccinated against SARS-CoV-2. All patients received concomitant glucocorticoid therapy. Gestational ages were 26, 17, 35, and 35 weeks. All patients were discharged home breathing room air after a mean hospital stay of 15 days. Two patients had uncomplicated cesarean section at 35 weeks during the hospitalization. The pre-term pregnancies at 17 and 26 weeks were intact at hospital discharge and resulted in normal vaginal deliveries at term. All 4 patients consented to participate in this case series report. IVIG may be a safe treatment consideration in pregnant women with severe COVID-19 to avoid pregnancy complications. Its use warrants further study in pregnancy acute respiratory distress syndrome (ARDS) due to SARS-CoV-2, influenza, and other respiratory viruses to which pregnant patients are vulnerable.

Background: Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers (ARBs) have been hypothesized to benefit patients with COVID-19 via the inhibition of viral entry and other mechanisms. We conducted an individual participant data (IPD) meta-analysis assessing the effect of starting the ARB losartan in recently hospitalized COVID-19 patients. Methods: We searched ClinicalTrials.gov in January 2021 for U.S./Canada-based trials where an angiotensin-converting enzyme inhibitors/ARB was a treatment arm, targeted outcomes could be extrapolated, and data sharing was allowed. Our primary outcome was a 7-point COVID-19 ordinal score measured 13 to 16 days post-enrollment. We analyzed data by fitting multilevel Bayesian ordinal regression models and standardizing the resulting predictions. Results: 325 participants (156 losartan vs 169 control) from 4 studies contributed IPD. Three were randomized trials; one used non-randomized concurrent and historical controls. Baseline covariates were reasonably balanced for the randomized trials. All studies evaluated losartan. We found equivocal evidence of a difference in ordinal scores 13-16 days post-enrollment (model-standardized odds ratio [OR] 1.10, 95% credible interval [CrI] 0.76–1.71; adjusted OR 1.15, 95% CrI 0.15–3.59) and no compelling evidence of treatment effect heterogeneity among prespecified subgroups. Losartan had worse effects for those taking corticosteroids at baseline after adjusting for covariates (ratio of adjusted ORs 0.29, 95% CrI 0.08–0.99). Hypotension serious adverse event rates were numerically higher with losartan. Conclusions: In this IPD meta-analysis of hospitalized COVID-19 patients, we found no convincing evidence for the benefit of losartan versus control treatment, but a higher rate of hypotension adverse events with losartan.