Real-world effectiveness of early remdesivir and sotrovimab in the highest-risk COVID-19 outpatients during the Omicron surge.

BACKGROUND: Remdesivir and sotrovimab both have clinical trial data in the outpatient setting demonstrating reduction in the risk of hospitalizations and emergency department (ED) visits related to COVID-19. OBJECTIVES: To evaluate the effectiveness of remdesivir in comparison with sotrovimab and matched high-risk control patients in preventing COVID-19-related hospitalizations and ED visits during the Omicron B.1.1.529 surge. PATIENTS AND METHODS: This retrospective cohort study included outpatients positive for SARS-CoV-2, with non-severe symptoms for ≤7 days and deemed high-risk for severe COVID-19 by an internal scoring matrix. Patients who received remdesivir or sotrovimab from 27/12/2021 to 04/02/2022 were included (n = 82 and n = 88, respectively). These were compared with a control cohort of high-risk COVID-19 outpatients who did not receive therapy (n = 90). The primary outcome was a composite of 29 day COVID-19-related hospitalizations and/or ED visits. Pre-specified secondary outcomes included components of the primary endpoint, 29 day all-cause mortality and serious adverse drug events. RESULTS: Patients treated with remdesivir were significantly less likely to be hospitalized or visit the ED within 29 days from symptom onset (11% versus 23.3%; OR = 0.41, 95% CI = 0.17-0.95). Patients receiving sotrovimab were also less likely to be hospitalized or visit the ED (8% versus 23.3%; OR = 0.28, 95% CI = 0.11-0.71). There was no difference in the incidence of hospitalizations/ED visits between sotrovimab and remdesivir. CONCLUSIONS: Our highest-risk outpatients with Omicron-related COVID-19 who received early sotrovimab or remdesivir had significantly lower likelihoods of a hospitalization and/or ED visit.

Control of tumor-associated macrophage alternative activation by macrophage migration inhibitory factor.

Tumor stromal alternatively activated macrophages are important determinants of antitumor T lymphocyte responses, intratumoral neovascularization, and metastatic dissemination. Our recent efforts to investigate the mechanism of macrophage migration inhibitory factor (MIF) in antagonizing antimelanoma immune responses reveal that macrophage-derived MIF participates in macrophage alternative activation in melanoma-bearing mice. Both peripheral and tumor-associated macrophages (TAMs) isolated from melanoma bearing MIF-deficient mice display elevated proinflammatory cytokine expression and reduced anti-inflammatory, immunosuppressive, and proangiogenic gene products compared with macrophages from tumor-bearing MIF wild-type mice. Moreover, TAMs and myeloid-derived suppressor cells from MIF-deficient mice exhibit reduced T lymphocyte immunosuppressive activities compared with those from their wild-type littermates. Corresponding with reduced tumor immunosuppression and neo-angiogenic potential by TAMs, MIF deficiency confers protection against transplantable s.c. melanoma outgrowth and melanoma lung metastatic colonization. Finally, we report for the first time, to our knowledge, that our previously discovered MIF small molecule antagonist, 4-iodo-6-phenylpyrimidine, recapitulates MIF deficiency in vitro and in vivo, and attenuates tumor-polarized macrophage alternative activation, immunosuppression, neoangiogenesis, and melanoma tumor outgrowth. These studies describe an important functional contribution by MIF to TAM alternative activation and provide justification for immunotherapeutic targeting of MIF in melanoma patients.