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COVID-19 Monoclonal Antibodies
Don’t Abandon Hope! Monoclonal Antibodies for Prophylaxis or Treatment of COVID-19 in Patients With Immune Compromise

Released: May 10, 2023

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Key Takeaways
  • People with immune compromise may benefit from monoclonal antibody prophylaxis and/or treatment, especially if they do not or are presumed to not exhibit an immunologic response to COVID-19 vaccination.
  • New data in European patients suggest certain monoclonal antibodies may retain some activity against currently circulating variants.

During the earlier phases of the COVID-19 pandemic, monoclonal antibodies (mAbs) had a role in prophylaxis and treatment of acute COVID-19 infections, especially when administered during the viral phase of the infection. The mAbs that were tailored to target specific viral variants and administered before SARS-CoV-2 exposure or within the first 5-7 days of COVID-19 symptom onset were proven effective both as a prophylactic measure in people with immune compromise and in preventing hospitalization in those at risk of severe disease from COVID-19.

The problem now is that, because mAbs are variant specific, they can rapidly lose their activity as SARS-CoV-2 variants evolve. For this reason, mAb use is no longer recommended by many COVID-19 guidelines, including the National Institutes of Health COVID-19 guidelines in the United States. In Europe, however, the situation is different, and some mAbs still are being used. Data show that the mAb sotrovimab (SOT) retains weak activity against the currently circulating variant BQ.1.1. At the 2023 European Congress of Clinical Microbiology and Infectious Diseases (ECCMID 2023), a few studies on mAbs as prophylaxis and early or in-hospital treatment were presented and provide updated guidance on the practical use of these agents.

COVID-19 Pre-exposure Prophylaxis With mAbs
Studies of mAbs for COVID-19 pre-exposure prophylaxis typically have included people with immune compromise who were poor vaccine responders.

One descriptive analysis presented at ECCMID 2023 was conducted in Israel and showed that, 9 months after mAbs were made available as pre-exposure prophylactic agents, fewer than 15% of eligible people with immune compromise received pre-exposure prophylaxis with the mAb combination tixagevimab (TIX) + cilgavimab (CIL). In addition, of those who received TIX + CIL, most were lung transplant recipients.

To evaluate the efficacy of TIX + CIL as a preventive strategy, another study compared TIX + CIL prophylaxis vs no prophylaxis in 110 lung transplant recipients. Breakthrough COVID-19 infections were diagnosed in 6% of the people who received TIX + CIL prophylaxis vs 29% of those who did not receive prophylaxis (P <.001). However, it is important to consider that patients were studied in June 2022. The SARS-CoV-2 variants have continued to evolve since then, rendering many mAbs ineffective for pre-exposure prophylaxis.

COVID-19 Treatment With mAbs
The MONET trial, which was conducted during the BQ.1.1 wave, evaluated the safety and efficacy of IV SOT compared with IM TIX + CIL compared with oral nirmatrelvir (NMV) + ritonavir (RTV) in ambulatory people with acute COVID-19 infections who were at high risk of progression to severe disease, including people with any immunocompromising condition. A study like this is especially important in patients with COVID-19 who cannot receive NMV + RTV, such as people with immune compromise receiving medications that could cause serious drug‒drug interactions.

A key finding was the secondary endpoint of SARS-CoV-2 viral load (VL) change from baseline to 7 days after randomization, collected via nasal swab. At baseline, VL in all 3 groups was similar, but by Day 7 it was significantly lower in patients who received NMV + RTV compared with those who received an mAb. This difference in VL likely was explained by the influence of SARS-CoV-2 variants, which affects the efficacy of mAbs but not antivirals such as NMV + RTV. The authors concluded that VL variation may be a surrogate marker of therapeutic efficacy that could be used to improve clinical trial design and evaluate mAb efficacy as the SARS-CoV-2 variants continue to evolve. In vitro data like these will be important to continue to evaluate in order to better inform COVID prevention and treatment guidelines and cost-effectiveness analyses.

The final study that I wish to discuss was conducted in Spain between May 10, 2022, and October 31, 2022, when the circulating SARS-CoV-2 variants were BA.4 and BA.5. This single-center cohort study included patients with acute COVID-19 who had immune compromise. These patients were largely vaccinated with 3 or more doses of COVID-19 vaccine (91%) but were determined to be COVID-19 vaccine nonresponders; only 58.3% had antispike immunoglobulin G >1000 BAU/mL.

The aim of the study was to compare monotherapy with either remdesivir, NMV + RTV, or SOT with combination therapy with SOT plus remdesivir or SOT plus NMV + RTV, and the results showed that COVID-19‒related hospitalizations and/or deaths occurred in 4% of those who received monotherapy vs none of the patients who received combination therapy. This suggested a trend toward therapeutic benefit with combination therapy in these high-risk patients, but the difference between groups was not statistically significant, likely because of the small sample size.

Of importance, a subanalysis of this study showed that combination therapy was specifically effective in patients with a relatively low serum titer of antispike immunoglobulin G (<1000 BAU/mL) and in patients who had received treatment with anti-CD20 antibodies. This benefit of mAb use in combination therapy occurred even though the circulating variants should have rendered SOT less effective.

Implications for Practice
Because the viral phase of a SARS-CoV-2 infection in people with immune compromise may be prolonged compared with those without immunocompromise, antiviral monotherapy may be insufficient if a person with immune compromise develops a severe COVID-19 pneumonia. It is important for us to consider other therapeutic agents in this vulnerable patient population.

Moreover, although it has been shown that NMV + RTV has more potent antiviral activity across all SARS-CoV-2 variants, it has several prescribing limitations because of serious drug‒drug interactions.

On the basis of the evidence presented at ECCMID 2023 and described herein, I believe further investigation into the use of mAbs as prophylaxis or treatment for patients with immunocompromise is warranted.

Your Thoughts?
Are you currently using mAbs as COVID-19 pre-exposure prophylaxis or treatment in your patients with immune compromise? Join the conversation by posting a comment below.