Outpatient anti-spike monoclonal antibody administration is associated with decreased morbidity and mortality among patients with cancer and COVID-19

Abstract

Patients with cancer have many comorbidities that increase their risk of death from Coronavirus disease 2019 (COVID-19). Anti-spike monoclonal antibodies (mAbs) reduce the risk of hospitalization or death from COVID-19 in the general population. To our knowledge, no studies have focused on the clinical efficacy of mAbs compared to no outpatient treatment exclusively among patients with solid tumors and hematologic malignancies, who are often excluded from clinical trials. We studied patients with cancer who had COVID-19 between 11.9.2020 and 7.21.2022 and received mAbs in an outpatient setting. We compared hospitalization and mortality rates to those of patients with cancer concurrently diagnosed with COVID-19, who were eligible for mAbs, but did not receive any outpatient treatment. 63 patients received mAbs and 89 no outpatient treatment. Administration of mAbs was associated with lower 90-day hospitalization (20.6% vs. 60.7%, p <0.001), all-cause (6.3% vs. 19.1%, p 0.025) and COVID-19-attributed (3.2% vs. 14.6%, p 0.019) mortality rates, and lower peak O 2 requirements (ordinal Odds Ratio [OR] = 0.33, 95% Confidence Intervals [CI] = 0.20–0.53). Administration of mAbs (aHR 0.21, p <0.001), age (≥ 60 years, adjusted Hazard Ratio [aHR] 1.86, p =0.033), and metastases (aHR 0.41, p 0.007) were independently associated with hospitalization. mAb treatment remained significantly associated with all-cause (aHR 0.27, p 0.019) and COVID-19-attributed (aHR 0.19, p 0.031) mortality, after adjustment for other factors. mAb administration was associated with improved clinical outcomes among vulnerable patients with cancer and COVID-19. With no mAbs approved currently for treatment against the prevalent circulating variants, the development of new mAbs should be a research priority.

Oral antivirals for COVID-19 among patients with cancer

“…Our institutional database included all patients with active or historical malignancies diagnosed with COVID-19 between April 1, 2020, and August 1, 2023. Patients were excluded from the study if they met any of the following criteria: (1) they received anti-spike monoclonal antibodies (mAbs), the e cacy of which was shown in our previous study [19], (2) they had elevated oxygen requirements due to COVID-19 compared to their baseline needs, (3) they had COVID-19 before EUAs for molnupiravir or nirmatrelvir/ritonavir were issued (December 22, 2021), or (4) they were treated with both oral antivirals (Fig. 1).…”

ACE2 decoy Fc-fusions and bi-specific killer engager (BiKEs) require Fc engagement forin vivoefficacy against SARS-CoV-2

“…We hypothesized that CD64 and CD16 would have a positive effect, while the inhibitory Fc receptor, CD32b, would lead to antibody-dependent enhancement, leading to a negative effect on viremia. A benefit of these BiKEs is the ability to target activating Fc g receptors only, whereas antibodies, like human IgG1 that is current used in most antibodies used to treat SARS-CoV-2 , bind both activating and inhibitory Fc g receptors 11,12 . We found that a BiKE that both neutralized and targeted activating Fc g receptors (neutralizing aSpike-aCD16 or neutralizing aSpike-aCD64) decreased weight loss and viremia.…”

“…However, there is still an urgent need for therapeutics for people who cannot generate effective antibody levels, or who may have an adverse reaction to vaccine components. These individuals include immunocompromised patients, like leukemia patients, that had decreased morbidity and death with anti-SARS-CoV-2 mAb therapy 11,12 . Antiviral drugs partially address this issue, however, effective monoclonal antibody therapies that can withstand viral evolution would significantly benefit these patient populations.…”

Monovalent Omicron COVID-19 vaccine triggers superior neutralizing antibody responses against Omicron subvariants than Delta and Omicron bivalent vaccine

“…Neutralizing monoclonal antibodies have been increasingly used as passive antiviral reagents in prophylactic and therapeutic interventions and to guide the design of viral vaccines, including COVID-19 vaccines. 22–25 However, Omicron sublineages, particularly BA.4/BA.5, BQ.1.1, and XBB, exhibited a high level of immune evasion for the currently authorized therapeutic rabbit monoclonal antibodies (RmAbs). 5 Therefore, it is critical to develop potent monoclonal antibodies (mAbs) against the broad-spectrum Omicron subvariants.…”