Real-World Evidence of Neutralizing Monoclonal Antibodies for Preventing Hospitalization and Mortality in COVID-19 Outpatients

Abstract

Background: Neutralizing monoclonal antibodies (mAbs) were authorized for the treatment of COVID-19 outpatients based on clinical trials completed early in the pandemic, which were underpowered for mortality and subgroup analyses. Real-world data studies are promising for further assessing rapidly deployed therapeutics.

Research question: Did mAb treatment prevent progression to severe disease and death across pandemic phases and based on risk factors, including prior vaccination status?

Study design and methods: This observational cohort study included nonhospitalized adult patients with SARS-CoV-2 infection from November 2020 to October 2021 using electronic health records from a statewide health system plus state-level vaccine and mortality data. Using propensity matching, we selected approximately 2.5 patients not receiving mAbs for each patient who received mAb treatment under emergency use authorization. The primary outcome was 28-day hospitalization; secondary outcomes included mortality and hospitalization severity.

Results: Of 36,077 patients with SARS-CoV-2 infection, 2,675 receiving mAbs were matched to 6,677 patients not receiving mAbs. Compared with mAb-untreated patients, mAb-treated patients had lower all-cause hospitalization (4.0% vs 7.7%; adjusted OR, 0.48; 95% CI, 0.38-0.60) and all-cause mortality (0.1% vs 0.9%; adjusted OR, 0.11; 95% CI, 0.03-0.29) to day 28; differences persisted to day 90. Among hospitalized patients, mAb-treated patients had shorter hospital length of stay (5.8 vs 8.5 days) and lower risk of mechanical ventilation (4.6% vs 16.6%). Results were similar for preventing hospitalizations during the Delta variant phase (adjusted OR, 0.35; 95% CI, 0.25-0.50) and across subgroups. Number-needed-to-treat (NNT) to prevent hospitalization was lower for subgroups with higher baseline risk of hospitalization; for example, multiple comorbidities (NNT = 17) and not fully vaccinated (NNT = 24) vs no comorbidities (NNT = 88) and fully vaccinated (NNT = 81).

Interpretation: Real-world data revealed a strong association between receipt of mAbs and reduced hospitalization and deaths among COVID-19 outpatients across pandemic phases. Real-world data studies should be used to guide practice and policy decisions, including allocation of scarce resources.

Keywords: COVID-19; Delta variant; hospitalization; mechanical ventilation; monoclonal antibody; outpatient.

Graphical abstract

Figure 1

Cumulative incidence plots for all-cause hospitalization (A) and mortality (B) to day 28 according to mAb treatment status. mAb = monoclonal antibody.

Figure 2

Maximum respiratory support according to mAb treatment status among patients hospitalized within 28 days. Comparing severity of hospitalizations for 108 mAb-treated and 511 mAb-untreated patients, the maximum level of respiratory support was lower for mAb-treated patients (adjusted proportional OR, 0.25; 95% CI, 0.16-0.38). HFNC = high-flow nasal cannula; IMV = invasive mechanical ventilation; mAb, monoclonal antibody; NIV = noninvasive ventilation.

Figure 3

Subgroup analysis of mAb effect on 28-day hospitalization. For each subgroup, we calculated unadjusted rates of hospitalization, NNT to prevent one hospitalization (based on absolute risk reduction in unadjusted hospitalization rates), and adjusted relative odds of hospitalization. Each adjusted OR represents a separate model. All regression models adjusted for age, sex, race/ethnicity, BMI, immunocompromised status, number of comorbidities, insurance status, pandemic phase, and vaccination status. Results were not adjusted for multiple comparisons. mAb = monoclonal antibody; NNT = number-needed-to-treat.