Neutralizing Antibody Cocktail Against SARS-CoV-2

Ms. Alvarez is a 68-year-old woman with hypertension, type 2 diabetes, and obesity. She presents to clinic with symptoms of cough, shortness of breath, and fever to 100.4°F for the last 2 days. She was recently exposed to a family member who tested positive for SARS-CoV-2, and her SARS-CoV-2 nasopharyngeal PCR test is positive. She has a current temperature of 99.9°F, heart rate of 95 beats per minute, respiratory rate of 22 breaths per minutes, and oxygen saturation of 95% on room air. She asks about the availability and benefit of receiving a monoclonal antibody treatment for Covid-19.

Symptoms of Covid-19 can range from few or no symptoms to serious infection requiring hospitalization and supplemental oxygen. Recent data have shown high SARS-CoV-2 viral titers in hospitalized patients, suggesting that the high titers are at least partially responsible for hypoxemia.

In a study recently published in NEJM, investigators evaluated the efficacy of an antibody cocktail (REGN-COV2) containing two SARS-CoV-2-neutralizing antibodies in nonhospitalized symptomatic patients with Covid-19. Patients were randomly assigned to receive placebo, 2.4 g of REGN-COV2, or 8.0 g of REGN-COV2. An assay for anti–SARS-CoV-2 antibodies was performed in all patients at baseline. In an interim analysis, the REGN-COV2 antibody cocktail reduced viral load, with a greater effect in patients whose immune response had not yet been initiated or who had a high viral load at baseline. 

The data from this study indicate that REGN-COV2 enhanced clearance of virus, especially in patients who were serum antibody-negative or who had a high viral load at baseline. However,  due to the small numbers of clinical events in this study, it is uncertain whether REGN-COV2 offers meaningful clinical benefit. Ms. Alvarez might benefit from monoclonal antibody infusion. Further studies are ongoing to confirm these results.

The following NEJM Journal Watch summary provides more details of the study.

Rajesh T. Gandhi, MD reviewing Weinreich DM et al. N Engl J Med 2020 Dec 17

Neutralizing antibodies directed against the SARS-CoV-2 spike protein are being evaluated as a treatment for COVID-19. In an industry-sponsored trial, researchers assessed outcomes after an intravenous infusion of a cocktail of two antibodies (REGN-COV2) in 275 symptomatic outpatients testing positive for SARS-CoV-2 within 3 days of enrollment. Participants were randomized to receive placebo, 2.4 gm REGN-COV2, or 8.0 gm REGN-COV2.

Among the 41% of participants who were seronegative for endogenous SARS-CoV-2 antibodies at baseline, the time-weighted average change in viral load through day 7 was greater in the combined groups receiving either dose of REGN-COV2 than in the placebo group (difference, −0.56 log₁₀ copies/mL). Among all patients, medically attended visits (i.e., telehealth, in-person with physician, emergency department, or hospitalization) occurred in 6 of 93 (6%) placebo recipients and 6 of 182 (3%) REGN-COV2 recipients. Among those who were SARS-CoV-2 antibody negative at baseline, 5 of 33 (15%) placebo recipients and 5 of 80 (6%) antibody recipients had a medically attended visit.

Comment: Based in part on this interim analysis, an emergency use authorization (EUA) was issued for use of REGN-COV2 (the two antibodies are now called casirivimab and imdevimab) in outpatients at high risk for severe COVID-19. A similar EUA was also issued for bamlanivimab, another SARS-CoV-2–neutralizing antibody. The reduction in SARS-CoV-2 levels after infusion of REGN-COV2 is convincing, but only in those patients who had not developed their own antibody responses. Because of the small numbers of clinical events, it remains uncertain whether REGN-COV2 confers meaningful benefit. Even as we struggle with the logistics of administering this cocktail to high-risk outpatients with COVID-19, the ongoing trials must be completed to determine the clinical benefit of antibody therapy — and if such benefit is confirmed, which patients are most likely to be helped.

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Jehan is a 2020-2021 NEJM Editorial Fellow and an Infectious Disease physician. She completed her Infectious Disease fellowship at Tufts Medical Center.