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Monoclonal antibodies (MAbs) bind to the SARS-CoV-2 spike glycoprotein, blocking its attachment to the human angiotensin converting enzyme 2 (ACE-2) receptor. MAbs show promise as a for early COVID-19, particularly in ambulatory patients at highest risk for progression to severe COVID-19. Phase II/III clinical trials suggest that early administration of the MAbs (LY-CoV555) and of (REGEN-COV) can reduce risk of hospital admission. However, the real-word data needed to guide clinical decision-making are lacking, according to researchers.

Results from analyses of data from a pre-/post-implementation study of high-risk ambulatory adults with early COVID-19 show that MAbs were "well-tolerated and likely effective at preventing the need for subsequent emergency department [ED] or hospital care," Brandon J. Webb, MD, of Intermountain Medical Center in Murray, Utah, and colleagues concluded in their study in

In late 2020, the FDA granted emergency use authorization (EUA) for and for for the treatment of mild/moderate symptomatic COVID-19 in ambulatory patients at higher risk for hospitalization. In April 2021, the FDA for bamlanivimab monotherapy and issued an (LY-CoV016) for the same indications.

Webb and colleagues found a significant decrease in the risk of a visit to the ED or of hospitalization in patients treated with MAbs within 7 days of symptom onset compared with controls (odds ratio 0.69). Sensitivity analysis showed that the odds of 14-day hospital admission were also significantly decreased in MAbs-treated patients (OR 0.43). There was one death in the MAbs group compared with 71 and 57 in the pre- and post-implementation control groups, respectively.

"These results lend additional support to the concept that passive immune therapies are effective when administered early after symptom onset when is highest and in patients who fail to mount a robust early ," the authors wrote. "Additional investigation is needed to elucidate the impact on mortality or symptomatic improvement, the incidence of rare adverse events and the comparative effectiveness of different MAb products against emerging variant strains."

The study showed that the estimated number needed to treat was 7.6, an effect size comparable to data from subgroup analyses of higher-risk patients in . "It appears likely that focusing MAb treatment on patients both at greater risk for poor outcomes and earlier in the symptom course than specified by the EUA criteria, may enhance the expected effectiveness of the therapy," Webb and colleagues emphasized. Widespread use of MAb therapy in geographic areas with high transmission/low vaccination rates, "could play a greater role in preventing clinical deterioration and need for hospitalizations or oxygen therapy," they noted.

In this interview, Webb, who is also with the division of infectious diseases and geographic medicine at Stanford University in California, discussed the findings in greater detail.

What is your takeaway for physicians about your findings?

Webb: When used in the right patients, MAbs are both safe and effective at preventing hospitalization and likely mortality. These real-world observations argue for finding ways to break down the logistical barriers to more widespread use, but also argue for optimizing use of resources by carefully selecting patients most likely to benefit.

What adverse events (AEs) were experienced by patients treated with MAbs?

Webb: Serious events were rare and no anaphylactic-type events were observed. However, data from larger populations will be necessary to accurately characterize the incidence of rare events. A total of seven patients experienced infusion-associated AEs. Two events were considered severe: one patient with known coronary disease developed chest pain during infusion and another had a syncopal episode but both patients were managed in the ED with good outcomes.

You noted that at the time of EUA approval, transmission rates "far exceeded infusion capacity" and a simple, validated prediction score for severe COVID-19 was adopted in Utah for MAb allocation. How helpful are risk prediction tools in selecting patients for MAbs therapy?

Webb: The 'bang for the buck' of MAbs is directly proportional to the patient population targeted. In most places, the EUA criteria identify far more patients than health systems have the capacity to treat. By using to select the patients who have high probability of poor outcome, the same number of hospitalizations can be prevented than by treating a much larger group of patients who may be at lower risk. Similar methods of risk-stratification have been used by teams at [the University of California] and the Cleveland Clinic, among others.

As the pandemic continues, have your criteria for patient selection changed in any way?

Webb: Our patient selection criteria have worked well during a resource-limited pandemic phase, allowing us to optimize the benefit of this very promising therapy with dynamic supply-demand matching of infusion capacity. In the spring, when community transmission was low, we were able to offer treatment to patients at lower risk of hospitalization who may benefit in other ways.

In your expert opinion, were any of these hospitalizations in patients who received MAb therapy potentially avoidable?

Webb: MAbs work best when given as early in the symptom course as possible. This makes sense mechanistically. There is a window for neutralizing the virus early before it triggers a cascade of hyperinflammatory and organ-damaging consequences. Most of the patients who were ultimately admitted to the hospital despite receiving MAbs seemed to be further along in their disease progression despite still qualifying [for the study]. We didn't have the sample size to tease this out but an important follow-up question will be to determine whether these MAb-treated admissions still had better outcomes.

Could MAb therapies potentially prove useful in the treatment of fully vaccinated patients infected with the Delta variant?

Webb: We are studying this now. The same risk factors associated with poor outcomes such as hospitalization and death still appear to apply to vaccinated patients who suffer breakthrough infection. We're currently analyzing a larger sample of patients to get a better sense of the impact of MAbs on mortality, and to explore the relative effectiveness of MAbs in fully-vaccinated breakthrough infection. We're also launching a real-world study to evaluate whether MAbs may decrease the risk of long-term post-COVID symptoms.

Any other comments?

Webb: The use of casirivimab-imdevimab for post-exposure prophylaxis [PEP] was . If the goal is to prevent hospitalization, the number needed to treat actively infected patients is much lower than for PEP. In situations where infusion capacity may be limited, focusing on treatment of COVID-19-positive patients will be more resource-efficient.

You can read the study abstract here.