In addition, it would be important to compare results with RMD patients treated with anti-CD20 antibody in a dedicated study, since this cohort was under-represented in our study. Anti-TNF drugs neutralize a major component of the cytokine response that is part of the damaging excess inflammatory phase of COVID-19. This study provides a whole picture of the humoral and cellular immune responses in RMD patients by reassuring the use of DMARD treatments during COVID-19. The study points to TNF- inhibitors as those DMARDs permitting elicitation of functional antibodies to SARS-CoV-2 and adaptive effector populations available to counteract possible re-infections. Keywords: COVID-19, DMARD, immune responses, rheumatic musculoskeletal diseases, inflammatory arthritis Introduction The COVID-19 pandemic represents a challenge for health systems worldwide. SARS-CoV-2 infection has proven to be particularly dangerous, in terms of both morbidity and mortality, for patients presenting with pre-existing pathologies (1, 2). Patients at risk include those affected by rheumatic musculoskeletal disease (RMD), in which the ability to mount a productive immune response Luliconazole to SARS-CoV-2 infection could be challenged by two intrinsic aspects. First, RMDs are immune-mediated diseases, with a compromised immune system that may cause an altered inflammation status and increased complications upon infection (3, 4). Second, RMD patients are treated with immunosuppressive agents that can blunt immune responses and make them more susceptible to infections, causing a more severe course of infection compared to the general population (3, 5). These patients are generally treated with disease-modifying anti-rheumatic drugs (DMARDs) aimed at slowing disease progression. DMARDs comprise different drugs and mode of actions, but can be categorized as conventional synthetic (cs) DMARDs or biologic and targeted Luliconazole synthetic (b/ts) DMARDs. Some DMARD treatments, such as hydroxychloroquine, anti-TNF, and IL-6 inhibitors, have been employed during the COVID-19 pandemic Luliconazole to reduce the systemic inflammation associated with severe disease and are being studied for the prevention and/or treatment of COVID-19 and its complications (6C9). To date, a limited number of studies investigated the risk of infection or COVID-19 severity in RMD patients, associating seroprevalence of anti-SARS-CoV-2 antibodies. These studies are reassuring about the low impact of RMDs and immunomodulatory therapies on the risk and clinical course of COVID-19 (10C12). However, at present, the insight into the immune response to SARS-CoV-2 in RMD patients has been limited to seroprevalence analyses, while a global picture of the immune response relevant for protective immunity against SARS-CoV-2 reinfection is still missing. In this frame, our work aimed at describing the immune response following SARS-CoV-2 exposure raised in RMD patients treated with different classes of DMARDs. We show that RMD individuals under most DMARD treatments mount a sustained antibody response to the virus and effector T and B lymphocytes. In particular, these patients are able to elicit neutralizing antibodies titers comparable to non-RMD COVID-19 patients, potentially able to counteract SARS-CoV-2 infection. Among b-DMARDs, our study highlights anti-TNF treatments as more propitious drugs to mount a humoral and cellular immune response as compared to CTLA4-Ig and anti-IL6R antibodies. Materials and Methods Patient Recruitment The study involved two patient recruitments, the first in MayCJune 2020 (T1) and the second in SeptemberCOctober 2020 (T2). Recruitments occurred at the ASST Gaetano Pini-CTO Institute in Milan (Italy) and IRCCS Ca Granda Ospedale Maggiore Policlinico Foundation, and were under ethical approval by the Ethics Committee Milano Area Rabbit Polyclonal to p55CDC 2 (MAINSTREAM protocol: approval number 407; END-COVID: approval number 331). All patients signed informed consent. The study population at T1 was recruited 78.8 days (median, range 24C111) after the presentation of COVID-19 symptoms, including 358 RMD patients with a diagnosis of rheumatoid arthritis (RA, = 200, 56%) or other diseases [ankylosing spondylitis, spondyloarthritis (SpA), = 158, 44%] receiving treatments with DMARD ( Supplementary Table?1 ). These comprised conventional-synthetic (cs)-DMARDs (metotrexate, leflunomide, sulfasalazine, hydroxychloroquine, cyclosporins, and mesalazine), biological (b)-DMARDs Luliconazole (anti-TNF-.