Successful Clearance of 300 Day SARS-CoV-2 Infection in a Subject with B-Cell Depletion Associated Prolonged (B-DEAP) COVID by REGEN-COV Anti-Spike Monoclonal Antibody Cocktail

Abstract

A 59-year-old male with follicular lymphoma treated by anti-CD20-mediated B-cell depletion and ablative chemotherapy was hospitalized with a COVID-19 infection. Although the patient did not develop specific humoral immunity, he had a mild clinical course overall. The failure of all therapeutic options allowed infection to persist nearly 300 days with active accumulation of SARS-CoV-2 virus mutations. As a rescue therapy, an infusion of REGEN-COV (10933 and 10987) anti-spike monoclonal antibodies was performed 270 days from initial diagnosis. Due to partial clearance after the first dose (2.4 g), a consolidation dose (8 g) was infused six weeks later. Complete virus clearance could then be observed over the following month, after he was vaccinated with the Pfizer-BioNTech anti-COVID-19 vaccination. The successful management of this patient required prolonged enhanced quarantine, monitoring of virus mutations, pioneering clinical decisions based upon close consultation, and the coordination of multidisciplinary experts in virology, immunology, pharmacology, input from REGN, the FDA, the IRB, the health care team, the patient, and the patient’s family. Current decisions to take revolve around patient’s follicular lymphoma management, and monitoring for virus clearance persistence beyond disappearance of REGEN-COV monoclonal antibodies after anti-SARS-CoV-2 vaccination. Overall, specific guidelines for similar cases should be established.

Early Administration of Anti–SARS-CoV-2 Monoclonal Antibodies Prevents Severe COVID-19 in Kidney Transplant Patients

“…In our study, patients in the MoAb group were mostly exposed to B.1.1.7 variant considered as more pathogenic than ancestor Wuhan strain still dominant when control patients were infected, because the period of enrollment differed between the two groups ( 17 , 18 ). While MoAb could be more broadly used as preventive therapy in non-responder to vaccination or in prolonged Covid-19 ( 19 , 20 ), it is important to keep in mind that effectiveness of these treatment must regularly be updated ( 21 ) and therapeutic strategies potentially refined taking account the geographic distribution of different SARS-CoV-2 strains. The last illustration is the recent propagation of Omicron variant that escapes to casirivimab and imdevimab.…”

Coronavirus disease 2019 in patients with inborn errors of immunity: lessons learned

“…Monoclonal antibodies that neutralize SARS-CoV-2, such as the combination of casirivimab and imdevimab (Regen-Cov) or sotrovimab, have also proven effective as primary or secondary prevention of COVID-19 [ 106 , 107 ]. Therefore, passive immunotherapy with these antibodies could potentially be used early in patients with IEIs at high risk for severe disease as a strategy to prevent the development of COVID-19-related complications or as aids in clearing the infection in patients with prolonged shedding of SARS-CoV-2 [ 108 ]. Finally, some patients with IEI are able to mount a humoral and/or cellular immunity against the virus in a natural infection setting or in a vaccination setting [ 67 , 109 , 110 ].…”

Successful use of casirivimab/imdevimab anti-spike monoclonal antibodies to enhance neutralizing antibodies in a woman on anti-CD20 treatment with refractory COVID-19

“…COVID-19 convalescent plasma, remdesivir, and corticosteroids are sometimes used to treat refractory cases [ 4 ]; however, there is no established treatment for refractory COVID-19. One case report demonstrated the effectiveness of casirivimab/imdevimab in patients with COVID-19 with B-cell depletion [ 10 ], but to the best of our knowledge, this is the first case in which viral culture confirmed persistent infection and in which an increase in neutralizing antibody titer was documented after the administration of casirivimab/imdevimab. Considering the pharmacological mechanism of the drug, monoclonal antibody therapy of casirivimab/imdevimab is likely to be effective in situations where the viral load is high and antibody production is low, and may be less effective in patients with strong inflammatory responses.…”