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Vulnerability of patients on immunosuppressive therapy to SARS-CoV-2 reinfection
  1. Yashdeep Singh Pathania
  1. Department of Dermatology, Venereology and Leprology, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India
  1. Correspondence to Dr Yashdeep Singh Pathania, Department of Dermatology, Venereology and Leprology, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India; yashdeepsinghpathania{at}

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To the Editor,

The catastrophe by the novel COVID-19 has still not come to a halt in the world. There is an upsurge of COVID-19 cases and also SARS-CoV-2 reinfections or reactivations. Protective immunity following SARS-CoV-2 infection is uncertain. There are incidences of SARS-CoV-2 reinfection in patients who were on immunosuppressive therapy for other diseases. Immunosuppression in COVID-19 is a double-edged sword. It may be detrimental in the initial course of COVID-19, but may be life-saving with regard to alleviating the cytokine storm in the later course of the disease. However, it has resulted in a surge of cases of SARS-CoV-2 reinfection throughout the world.

Few viral infections provide lifelong immunity after the first infection, but seasonal coronaviruses provide short-lived protective immunity. Reinfections are expected to occur once antibody titres decrease. Gulati et al1 have reported SARS-CoV-2 reinfection in a patient with antineutrophil cytoplasmic antibody-associated vasculitis after immunosuppressive therapy. It has been demonstrated in a study by Gudbjartsson et al2 that antibodies to SARS-CoV-2 did not decrease within 4 months after infection. However, recurrences of COVID-19 have been documented in the literature. A systematic review of 1350 patients found COVID-19 reinfection after a mean of 34.5 days from first positive real-time PCR sample.3 Immune suppression either reduces the clearance of SARS-CoV-2 or reduces the development of protective antibodies. COVID-19 reinfection should be differentiated from secondary complications such as superinfection. There may be persistence of viral RNA in the respiratory samples up to 6 weeks in a clinically cured patient and therefore it should be differentiated from reinfection. Immunosuppressive agents such as long-term corticosteroids, methotrexate, azathioprine, mycophenolate mofetil and biological agents (rituximab, adalimumab, infliximab) used in patients for other disease indications within 2–3 weeks of SARS-CoV-2 infection may be responsible for blunting the immune response and the inadequate production of protective antibodies. Among the immunosuppressive agents, rituximab, a monoclonal anti-CD20 antibody, is responsible for long-lasting B cell depletion. It may be highly responsible for blunting protective antibody production and thus SARS-CoV-2 reactivation. There are mixed recommendations for use of rituximab during the pandemic. However, a cohort study by Avouac et al4 found patients with inflammatory rheumatic and musculoskeletal diseases had more severe COVID-19 outcomes after rituximab therapy. Therefore, intravenous immunoglobulin (IVIG) may be a potential alternative in the treatment of autoimmune diseases during the present scenario of COVID-19. There are reports of patients with severe COVID-19 who improved satisfactorily with high-dose IVIG.5 It may prove to be beneficial in both autoimmune diseases and COVID-19.

The current evidence of short-lived acquired protective immunity needs to be elucidated with large studies. Patients may be reinfected by SARS-CoV-2 due to long-term effects of immunosuppressive drugs or a long-lasting virus carriage, and this needs to be validated by studies in the future to curb the menace of COVID-19 resurgence. Various guidelines have been formulated for the use of immunosuppressive agents during COVID-19, but these are derived from case reports and case series with low level of evidence. Although there is a high degree of suspicion for SARS-CoV-2 reactivation or reinfection in patients on immunosuppressive agents, indispensable or short-term use of these agents should be judiciously undertaken and priority for safer alternatives should be preferred.

Ethics statements



  • Contributors YSP prepared and finalised the manuscript.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; internally peer reviewed.