Cellular immunity in COVID-19 and other infections in Common variable immunodeficiency

Abstract

COVID-19 has shed light on the role of cellular immunity in the absence of humoral response in different patient groups. Common variable immunodeficiency (CVID) is characterized by impaired humoral immunity but also an underlying T-cell dysregulation. The impact of T-cell dysregulation on cellular immunity in CVID is not clear, and this review summarizes available literature on cellular immunity in CVID with a particular focus on COVID-19. Overall mortality of COVID-19 in CVID is difficult to assess, but seems not significantly elevated, and risk factors for severe disease mirrors that of the general population, including lymphopenia. Most CVID patients have a significant T-cell response to COVID-19 disease with possible cross-reactivity to endemic coronaviruses. Several studies find a significant but impaired cellular response to basal COVID-19 mRNA vaccination that is independent of an antibody response. CVID patients with infection only have better cellular responses to vaccine in one study, but there is no clear association to T-cell dysregulation. Cellular response wane over time but responds to a third booster dose of vaccine. Opportunistic infection as a sign of impaired cellular immunity in CVID is rare but is related to the definition of the disease. CVID patients have a cellular response to influenza vaccine that in most studies is comparable to healthy controls, and annual vaccination against seasonal influenza should be recommended. More research is required to clarify the effect of vaccines in CVID with the most immediate issue being when to booster the COVID-19 vaccine.

The Scope and Impact of Viral Infections in Common Variable Immunodeficiency (CVID) and CVID-like Disorders: A Literature Review

“…This finding is supported by a study into CD8+ cell responses to the SARS-CoV-2 vaccine in patients with CVID and XLA compared to healthy controls, which showed a greater CD8+ and functional CTL response in XLA compared to controls, but a worse response in CVID compared to controls [ 91 ]. This is further supported by studies showing positive specific CD4+ T-cell responses to SARS-CoV-2 proteins in CVID patients, highlighting the role of cellular immunity in their immune response to COVID-19 [ 92 ]. Interestingly, this same group demonstrated absent T-cell response in those with severe COVID-19, indicating how dysregulated cellular immunity within the heterogenous CVID cohort may predispose individuals to severe viral infections [ 92 ].…”

“…This is further supported by studies showing positive specific CD4+ T-cell responses to SARS-CoV-2 proteins in CVID patients, highlighting the role of cellular immunity in their immune response to COVID-19 [ 92 ]. Interestingly, this same group demonstrated absent T-cell response in those with severe COVID-19, indicating how dysregulated cellular immunity within the heterogenous CVID cohort may predispose individuals to severe viral infections [ 92 ]. A patient with NFKB2 LOF mutation was reported with severe COVID-19, requiring ventilation, though T-cell studies were mostly unremarkable and he did eventually survive [ 93 ].…”