key: cord-0999431-vzsdavba authors: Gelibter, Stefano; Orrico, Mario; Filippi, Massimo; Moiola, Lucia title: COVID-19 with no antibody response in a multiple sclerosis patient treated with cladribine: implication for vaccination program? date: 2021-01-19 journal: Mult Scler Relat Disord DOI: 10.1016/j.msard.2021.102775 sha: 51b49fd5c174eb6e60201bbdcd28ce5e0c84bcff doc_id: 999431 cord_uid: vzsdavba nan Dear editor, Immunomodulatory and immunosuppressant disease-modifying drugs (DMD) may increase the infectious risk in people with multiple sclerosis (MS) (1) . A growing bulk of evidence, however, does not suggest an increased severity of COVID-19 disease in DMD-treated patients (2) . Along with the forthcoming anti-COVID-19 vaccination program, questions are increasing concerning the possibility of mounting an immune response to SARS-CoV-2 in DMD-exposed people. In a recent paper, Zabalza et al. observed a decreased serological response to SARS-CoV-2 in MS patients treated with anti-CD20 therapies or alemtuzumab (2) . In this cohort, however, no data were available regarding antibody response to COVID-19 after cladribine treatment. Cladribine is a highly effective oral DMD exerting its action through a sustained but transient lymphocyte depletion, with negligible effects on innate immunity (3) . Few papers reported favorable COVID-19 outcomes in MS patients treated with cladribine (3-7). Here, we report the case of COVID-19 occurring in a 32-years-old female MS patient. (8)). Blood test performed the same day showed a lymphocyte count of 730/µL (Fig. 1 ). The reported patient had a self-limiting COVID-19 disease with a favorable outcome. This is in line with previous observations by other authors (3) (4) (5) (6) (7) . COVID-19 has been reported in 52 patients treated with cladribine. Among those, SARS-CoV-2 infection was confirmed by a laboratory test (i.e., nasopharyngeal swab and/or serological test) in only 23 patients (3) (4) (5) (6) (7) . In the remaining 39 patients, COVID-19 was suspected according to clinical symptoms and laboratory tests were not performed or tested negative (4, 6) In all the reports, cladribine-treated patients had favorable outcomes, even in the presence of severe lymphopenia (3, 7) , with no deaths nor need for mechanical ventilation. Serological data were available for eight patients. Of those, only one patient did not develop antibody response following infection (6) . In this report, however, a nasal swab was not performed (6) . Considering the available literature, COVID-19 disease developed only in five patients between two treatment weeks of the same year (3-6). As in our report, the second week of treatment was postponed until the recovery from COVID-19. In all cases, no severe COVID-19 disease was observed. In this subgroup, serological data were available only for two patients (5, 6) . While Celius reported a normal antibody response (5), another paper described a patient who tested negative for SARS-CoV-2 antibodies three months after the suspected infection (6) . Accordingly, also in our case, we found no antibody response two months after the infection. In the present case, COVID-19 occurred during the expected nadir of B cells count in cladribine-treated patients (9) . This may explain the lack of anti-SARS-CoV-2 antibodies response. However, the rapid decay of antibodies observed in patients with mild COVID-19 symptoms in the first 90 days after infection may have contributed to our findings (10). Our report confirms the safety of cladribine during the COVID-19 pandemic, even when infection occurs in the weeks following treatment. The finding of no antibody response, however, may hint at a reduced immunization in recently-treated patients. Should this be the case, cladribine treatment may have an impact on vaccination efficacy. The nature of our observation, however, limits its generalizability and we only considered antibody response. Data regarding the efficacy of vaccinations in patients treated with cladribine are still lacking (11) . Studies are needed to test the response to vaccines at different timepoints after cladribine administration. These studies should take into account also cell-mediated immune response that is not routinely tested and may be preserved in these patients (11) . Current guidelines do not provide indications regarding the timing of inactivated vaccines administration in DMD-treated patients (11) . Considering lymphocyte-depleting DMD, however, a blunted antibody response to vaccination has been observed in the first six months after alemtuzumab treatment (12) . Against this background, it is possible to speculate that waiting until the recovery of lymphocyte count after cladribine treatment may lead to an optimized response to vaccines against SARS-CoV-2. The patient provided her consent for this report. This research received no specific grant from any funding agency in the public, commercial, or notfor-profit sectors. The risk of infection in patients with multiple sclerosis treated with disease-modifying therapies: A Delphi consensus statement COVID-19 in MS patients: susceptibility, severity risk factors and serological response COVID-19 pneumonia in a multiple sclerosis patient with severe lymphopenia due to recent cladribine treatment Favorable outcomes after COVID-19 infection in multiple sclerosis patients treated with cladribine tablets. Multiple Sclerosis and Related Disorders Normal antibody response after COVID-19 during treatment with cladribine. 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