key: cord-0706447-nhvd32ia authors: Mahmoudi, Hamidreza; Tavakolpour, Soheil; Nili, Ali; Salehi Farid, Ali; Daneshpazhooh, Maryam; Rashidian, Mohammad title: Treatment of pemphigus patients in the COVID‐19 era: a specific focus on rituximab date: 2020-08-14 journal: Dermatol Ther DOI: 10.1111/dth.14188 sha: 1361ed4697c731740bcb93dbdbfb427092a8adb3 doc_id: 706447 cord_uid: nhvd32ia nan To the Editor, The COVID-19 outbreak poses a remarkable challenge for pemphigus treatment. High-dose corticosteroids and rituximab are recommended as first-line treatments for moderate-to-severe pemphigus. High-dose corticosteroids impair both cell-mediated and humoral immunity and may increase the complications of COVID-19. There is paucity of evidence on the impact of corticosteroids on COVID-19 course. Meanwhile, there are controversial reports about either negative or positive effect of corticosteroids on COVID-19 [1] [2] [3] . During COVID-19 pandemic, the safety of rituximab is unclear. To reach a hypothesis, focus on the role of B cells and antibodies in the pathogenesis of COVID-19 can be helpful. Lymphopenia has been frequently reported in patients with severe COVID-19 [4] . In contrast to T cell, B cell count was not found to be a prognostic factor for the clinical outcome in COVID-19 [4] . Moreover, in a multicenter cohort study in multiple sclerosis (MS) patients, using diseasemodifying therapies, such as rituximab, was associated with a lower risk of severe COVID-19 [5] . A retrospective study on 712 MS patients found that suspected COVID-19 cases experienced mild to moderate disease course, although using B-cell depleting treatment increased the susceptibility to contracting the infection [6] . Also, Patients with agammaglobulinemia infected with SARS-CoV-2 had a mild and short course of COVID-19 [7] . Focusing on antibodies, several studies showed that high titers of anti-SARS-CoV-2 antibodies or higher numbers of antibody-secreting cells were associated with disease severity [8] . These findings suggest that anti-virus antibodies may not necessarily be needed for a successful immune response against This article is protected by copyright. All rights reserved. SARS-CoV-2. On the other hand, anti-virus antibodies could facilitate the entry of the virus into the phagocytic cells; a phenomenon called antibody-dependent enhancement (ADE). Although ADE has not been proved in COVID-19, it may lead to cytokine storm and COVID-19 worsening [9] . In sum, these results suggest that B cells may not necessarily be required for the recovery of COVID-19 patients; however, most likely, they can effectively protect patients against SARS-CoV-2 reinfection. For new and relapsing pemphigus cases, who are not infected with SARS-CoV-2, avoiding highdose corticosteroids is recommended. At the same time, it seems that low-dose corticosteroids seem to be relatively safe [1] . Intravenous immunoglobulin (IVIg) is a safe option in severe pemphigus cases, although it is costly and mostly not available. According to a previous recommendation for rituximab, it could be better to postpone rituximab treatment due to the critical role of B cells in the late-phase immune response against viral infections [10] . Based on the few aforementioned reports on the possibly non-essential role of B cells and antibodies in the recovery from COVID-19, rituximab may still be considered for the management of moderateto-severe pemphigus during the COVID-19 pandemic. In COVID-19 patients with active pemphigus, a minimal increase in the predniso(lo)ne dose concomitant with the use of IVIg may be an efficient strategy. Although the use of high-dose systemic corticosteroids in COVID-19 patients [10] was discouraged in the first few months of the pandemics, there is strong evidence that intravenous dexamethasone decreased mortality in severe COVID-19 patients. [1] . IVIg also appears to be a rational option for COVID-19 patients. This article is protected by copyright. All rights reserved. Notably, in pemphigus patients infected with SARS-CoV-2, rituximab is recommended to be delayed until recovery from COVID-19. To conclude, for the treatment of severe pemphigus patients during COVID-19 outbreak, although there is still a lack of strong evidence, we suggest that rituximab could still be considered as a treatment option for moderate-to-severe cases. More studies are required to gain a better insight into how B-cell depletion may affect the response to SARS-CoV-2 in pemphigus patients. This article is protected by copyright. All rights reserved. Impact of corticosteroid therapy on outcomes of persons with SARS-CoV-2, SARS-CoV, or MERS-CoV infection: a systematic review and meta-analysis Remdesivir: A beacon of hope from Ebola virus disease to COVID-19 Dexamethasone in Hospitalized Patients with Covid-19 -Preliminary Report Lymphocyte subset (CD4+, CD8+) counts reflect the severity of infection and predict the clinical outcomes in patients with COVID-19 Clinical Characteristics and Outcomes in Patients With Coronavirus Disease 2019 and Multiple Sclerosis B-cell depleting therapies may affect susceptibility to acute respiratory illness among patients with multiple sclerosis during the early COVID-19 epidemic in Iran Two X-linked agammaglobulinemia patients develop pneumonia as COVID-19 manifestation but recover Critically ill SARS-CoV-2 patients display lupus-like hallmarks of extrafollicular B cell activation. medRxiv The potential danger of suboptimal antibody responses in COVID-19 Treatment considerations for patients with pemphigus during the COVID-19 pandemic