Anti-SARS-CoV-2 monoclonal antibodies for the treatment of active COVID-19 in multiple sclerosis: An observational study

Dear Editor,

In their short report “Anti-SARS-CoV-2 monoclonal antibodies for the treatment of active COVID-19 in multiple sclerosis: An observational study,”¹ Dr. Manzano et al. reported an overall safe and likely helpful profile of neutralizing anti-Spike protein monoclonal-antibody (mAbs) treatment in people with multiple sclerosis (pwMS) with acute coronavirus disease 2019 (COVID-19).

We found similar results in a cohort of 16 pwMS followed at the MS center of University of Genoa IRCCS Policlinico San Martino, who developed COVID-19 between April 2021 and February 2022.

Most of our patients (13/16) were treated before December 2021 using a combination of monoclonal antibodies (casivirimab + imdevimab and bamlanivimab + etesevimab) because the predominant variant of concern (VOC) in our region was delta. The remaining three patients were treated with sotrovimab because the predominant VOC was Omicron.² Delta was more than twice as contagious as previous variants and caused more COVID19-hospitalization, especially in people who were not fully vaccinated.³ With new less virulent VOC (such as Omicron), higher vaccination coverage and higher viral circulation, neutralizing mAbs treatment was prioritized for patients with multiple underlying conditions.

The mean interval time between first positive test and mAbs infusion was 3.5 days (range 1–7), with most patients (11; 69%) treated within 5 days of positivity. Overall, 11 (69%) patients were fully vaccinated according to current recommendations (two doses) at the time of COVID-19. Of note, five vaccinated patients (45%) were under treatment with anti-CD20 agents at the time of vaccination; therefore, it is possible that their humoral response to SARS-CoV-2 vaccines was reduced.⁴ The median interval time between the first positive and first negative swab was 12 days (range 5–30), being 10 days (range 5–20) when considering patients treated with mAbs before day 5 from symptoms onset 20 days (range 12–30) for patients treated between Day 5 and Day 10.

In our cohort, 14/16 (87%) patients did not experience COVID-19 progression. Two patients developed dyspnea after mAbs administration which required oxygen support. One of them had also chronic lymphocytic leukemia (CLL), for which she was under treatment with bendamustine and rituximab. On hospital admission, she was neutropenic, had fever, and modest reduction of saturation in ambient air (92%). She received empirical antibiotic treatment for febrile neutropenia, 1 day of oxygen therapy, no specific anti-SARS-CoV-2 antivirals was needed, and she was discharged after 7 days and resolution of neutropenia. The other patient was 84 years old and suffered from arterial hypertension; she refused hospital admission and was successfully treated at home with low-level oxygen support and steroid treatment. No patient was admitted to the intensive care unit (ICU) or died.

Overall, treatment with mAbs was well tolerated. No serious adverse events (SAEs) or infusion-related reactions occurred. Two patients reported temporary clinical worsening of neurological symptoms (without evidence of relapses or magnetic resonance imaging (MRI) activity) after the infusion, with a spontaneous return to normal functioning within 3 days. A causal correlation between the reported symptomatology and mAbs infusion could not be established.

In line with previous findings,^1,5 our limited experience highlights the negative effect of advanced age, high disability, and comorbidities. Our results confirm and strengthen those of Manzano et al.,¹ showing potential clinical benefit of early testing for SARS-CoV-2 infection coupled with prompt intervention with neutralizing mAbs, which led to a low incidence of COVID-19-related hospitalization or death and appeared to be safe and well tolerated in pwMS who develop symptomatic COVID-19.