An epidemiological survey of COVID-19 serology and its association with clinical infection among older adults – Does antibody titer matter? (preprint)

Background: Older adults are at increased risk of severe COVID19 infection. In this study we assessed the response to COVID19 vaccination and infection rates among nursing homes (NH) and assisted-living care home (ALCH) residents. Methods: The study was conducted between August 2021 and January 2022, after widespread population vaccination with the third dose of Pfizer-BioNtech mRNA COVID-19 vaccine in Israel. Three groups were addressed: hospitalized older patients; NH and ALCH residents. Demographic data, COVID19 serology (anti-spike IgG antibodies) and PCR test results were obtained to assess the dynamics of antibody titers and its correlation to infection rates. Results: Two-hundred eighty-five individuals were evaluated; 92 hospitalized patients; 100 ALCH residents and 93 NH residents. In the latter two groups two serology surveys were conducted three months apart. Hospitalized patients were younger than ALCH and NH residents (mean age 80.4±8 versus 82.6±8  and 83.6±5, respectively, p=0.01), and had more comorbidities (p=0.003). The degree of decline in the antibody level overtime was similar in ALCH and NH residents. Infection rates were higher among NH residents than ALCH residents [35/90 (39%) versus 11/100 (11%), p<0.001]. Antibody level was lower among those infected [2113 (1271-3512) Au/ml versus 4113 (3364-5029) Au/ml, p<0.001]. Adjusted analysis showed that NH residence, but not antibody levels, were significantly associated with infection. Conclusion: Among older adults, infection rates inversely correlated with antibody level. However, only nursing home residence was significantly associated with infection, suggesting that other factors such as crowding considerably contribute to the risk of infection.

Effect of Opaganib on Supplemental Oxygen and Mortality in Patients with Severe SARS-CoV-2 Pneumonia (preprint)

Rationale There are few treatment options for severe COVID-19 pneumonia. Opaganib is an oral treatment under investigation. Objective Evaluate opaganib treatment in hospitalized patients with severe COVID-19 pneumonia. Methods A randomized, placebo-controlled, double-blind phase 2/3 trial was conducted in 60 sites worldwide from August 2020 to July 2021. Patients received either opaganib (n=230; 500mg twice daily) or matching placebo (n=233) for 14 days. Main Outcome Measurements Primary outcome was the proportion of patients no longer requiring supplemental oxygen by day 14. Secondary outcomes included changes in the World Health Organization Ordinal Scale for Clinical Improvement, viral clearance, intubation, and mortality at 28- and 42-days. Main Results Pre-specified primary and secondary outcome analyses did not demonstrate statistically significant benefit (except for time to viral clearance). Post-hoc analysis revealed the fraction of inspired oxygen (FiO2) at baseline was prognostic for opaganib treatment responsiveness and corresponded to disease severity markers. Patients with FiO2 levels at or below the median value ([≤]60%) had better outcomes after opaganib treatment (n=117) compared to placebo (n=134). The proportion of patients with [≤]60% FIO2 at baseline that no longer required supplemental oxygen (at least 24 hours) by day 14 of opaganib treatment increased (76.9% vs 63.4%: p-value =0.033). There was a 62.6% reduction in intubation/mechanical ventilation (6.84% vs 17.91%; p-value=0.012) and a clinically meaningful 62% reduction in mortality (5.98% vs 16.7%; p-value=0.019) by day 42. No new safety concerns observed. Conclusions Post-hoc analysis supports opaganib benefit in COVID-19 severe pneumonia patients that require lower supplemental oxygen ([≤]60% FiO2). Further studies are warranted.

Compassionate Use of Opaganib For Patients with Severe COVID-19 (preprint)

BackgroundOpaganib is a selective sphingosine-kinase (SK)-2 inhibitor with anti-inflammatory and anti-viral properties. MethodsWe provided opaganib on a compassionate-use basis to patients with severe COVID-19. Patients who required oxygen support via high-flow nasal cannula (HFNC) were offered the treatment. For comparison, we used a control group with same-sex, same-severity patients. ResultsSeven patients received at least one dose of opaganib since April 2, 2020. One patient, who received both hydroxychloroquine and azithromycin, developed diarrhea and all his medications were stopped. This was the only adverse effect possibly related to opaganib. A second patient was weaned of oxygen and discharged after receiving two doses of opaganib. Therefore, five patients were included in this analysis. Baseline characteristics were not significantly different between cases and controls. Patients treated with opaganib had significantly faster increase in lymphocyte count. All other clinical outcomes had a non-statistically significant trend in favor of the treatment group: median time to weaning from HFNC was 10 and 15 days in cases vs. controls (HR= 0.3, 95% CI: 0.07-1.7, p=0.2), time to ambient air was 13 vs.14.5 days (HR=0.4, 95% CI: 0.15-1.5), none of the cases required mechanical ventilation compared with 33% of controls. ConclusionIn this small cohort of severe COVID-19 patients, opaganib was safe and well tolerated with improvement in both clinical and laboratory parameters in all treated patients. The efficacy of opaganib for COVID-19 infection should be further tested in randomized placebo-controlled trials.