Casirivimab/Imdevimab for Active COVID-19 Pneumonia Which Persisted for Nine Months in a Patient with Follicular Lymphoma during Anti-CD20 Therapy

Abstract

Immunocompromised patients are more likely to develop severe COVID-19, and exhibit high mortality. It is also hypothesized that chronic infection in these patients can be a risk factor for developing new variants. We describe a patient with prolonged active infection of COVID-19 who became infected during treatment with an anti-CD20 antibody (obinutuzumab) for follicular lymphoma. This patient had persistent RT-PCR positivity and live virus isolation for nine months despite treatment with remdesivir and other potential antiviral therapies. The computed tomography image of the chest showed that the viral pneumonia repeatedly appeared and disappeared in different lobes, as if a new infection had occurred continuously. The patient's SARS-CoV-2 antibody titer was negative throughout the illness, even after two doses of the BNT162b2 mRNA vaccine were administered in the seventh month of infection. A combination of monoclonal antibody therapy against COVID-19 (casirivimab and imdevimab) and antivirals resulted in negative RT-PCR results, and the virus was no longer isolated. The patient was clinically cured. During the 9-month active infection period, no fixed mutations in the spike (S) protein were detected, and the in vitro susceptibility to remdesivir was retained. Therapeutic administration of anti-SARS-CoV-2 monoclonal antibodies is essential in immunocompromised patients. Therefore, measures to prevent resistance against these key drugs are urgently needed.

Combination treatment of persistent COVID-19 in immunocompromised patients with remdesivir, nirmaltrevir/ritonavir and tixegavimab/cilgavimab

“…In a study evaluating the outcomes of various treatments in 31 cases of persistent COVID-19, mostly after BCDT, a combination of remdesivir and either CPT or casirivimab/imdevimab was associated with better chances of symptomatic improvement and viral clearance than remdesivir only [15]. In a few reports, monoclonal antibodies were curative after a very prolonged infection, sometimes unresponsive to recurrent treatments with remdesivir and steroids [16][17][18][19][20][21].…”

Radiologic Abnormalities in Prolonged SARS-CoV-2 Infection: A Systematic Review

“…Additional methodological details are provided in Figure 1 and in the Supplementary Methods and Supplementary Tables 1, 2 . This review included 19 studies that reported on a total of 24 patients (median age, 54.5 years [interquartile range (IQR) 44–64 years]; 15 male) [ 7 8 9 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 ].…”

“…In some patients, polymerase chain reaction (PCR) tests for SARS-CoV-2 can yield positive results for approximately 80–300 days from the initial positivity [ 5 6 7 ]. Prolonged SARS-CoV-2 infection poses a public health threat as it may lead to a higher number of viral mutations, potentially resulting in the emergence of drug-resistant variants and variants with increased infectivity [ 8 9 ].…”

Increased Risk of Invasive Aspergillosis in Immunocompromised Patients With Persistent SARS-CoV-2 Viral Shedding >8 Weeks, Retrospective Case-control Study

“…Finally, persistent viral shedding in this group of patients raised major therapeutic concerns because antiviral drugs could not eradicate the virus and were responsible for the emergence of mutations, resistance, and new variants [ 13 , 18–20 ]. Several risk factors for persistent viral shedding had been identified, among which are B-cell dysfunction (malignant lymphoma, multiple myeloma, anti-CD20 and anti-CD19 therapies), lymphocytopenia, serum elevation of type 1 interferon, immature neutrophils, delayed antiviral therapy, and D-dimer elevation [ 15 , 16 , 21–23 ]. Persistent viral shedding was associated with a spike protein mutation and an increased risk of bacterial infections and death [ 15 , 16 , 21–23 ].…”

“…Several risk factors for persistent viral shedding had been identified, among which are B-cell dysfunction (malignant lymphoma, multiple myeloma, anti-CD20 and anti-CD19 therapies), lymphocytopenia, serum elevation of type 1 interferon, immature neutrophils, delayed antiviral therapy, and D-dimer elevation [ 15 , 16 , 21–23 ]. Persistent viral shedding was associated with a spike protein mutation and an increased risk of bacterial infections and death [ 15 , 16 , 21–23 ]. However, the absence of a standardized definition of the duration of “persistence” makes it difficult to interpret and extrapolate previous reports [ 16 ].…”