Autoimmunity and Immunodeficiency in Severe SARS-CoV-2 Infection and Prolonged COVID-19

Abstract

SARS-CoV-2 causes the complex and heterogeneous illness known as COVID-19. The disease primarily affects the respiratory system but can quickly become systemic, harming multiple organs and leading to long-lasting sequelae in some patients. Most infected individuals are asymptomatic or present mild symptoms. Antibodies, complement, and immune cells can efficiently eliminate the virus. However, 20% of individuals develop severe respiratory illness and multiple organ failure. Virus replication has been described in several organs in patients who died from COVID-19, suggesting a compromised immune response. Immunodeficiency and autoimmunity are responsible for this impairment and facilitate viral escape. Mutations in IFN signal transduction and T cell activation are responsible for the inadequate response in young individuals. Autoantibodies are accountable for secondary immunodeficiency in patients with severe infection or prolonged COVID-19. Antibodies against cytokines (interferons α, γ and ω, IL1β, IL6, IL10, IL-17, IL21), chemokines, complement, nuclear proteins and DNA, anticardiolipin, and several extracellular proteins have been reported. The type and titer of autoantibodies depend on age and gender. Organ-specific autoantibodies have been described in prolonged COVID-19. Their role in the disease is under study. Autoimmunity and immunodeficiency should be screened as risk factors for severe or prolonged COVID-19.

Keywords: COVID-19; SARS-CoV-2; autoantibodies; autoimmunity; primary immune; prolonged COVID-19; secondary immunodeficiency.

Figure 1

SARS-CoV-2 cell infection and primary cell response. The figure represents the different processes related to viral infection and cell response. The primary receptor is the ACE2 (1) receptor, along with the protein TMPRSS2 (2); heparan sulfate or heparin (3) is another receptor, especially in cells not expressing the ACE2 receptor; sintenin-1 and PALS1 proteins that interact with E protein are represented by number (4). The other type of receptors are CD26, CD147 and neuropilin 1 (5). The virus can also enter by transcytosis, binding to different proteins depending on the cell type (6). The complex virus antibodies are endocytosed through the Fc receptors, highly expressed in phagocytic cells (7). The virus can induce cellular mRNA degradation by miRNA. Viral proteins block IFN signal transduction, the transcription factor NFkB, which is crucial for the transcription of proinflammatory cytokines. Viral proteins can be presented as antigens alone or in conjunction with heat shock or other cellular proteins. Viral proteins can also be secreted into the media. Ion channels are essential for inflammasome activation but are also crucial in cell homeostasis.

Figure 2

Involvement of autoimmunity and immunodeficiency in COVID-19. Autoimmunity, unlike genetic mutations related to immunodeficiency, is frequent in severe and prolonged COVID-19. The yellow segment corresponds to antibodies against essential proteins within the immune response against COVID-19. The red area represents the ratio of autoantibodies causing immunodeficiencies (antibodies against cytokines, for example). The green area corresponds to genetic mutations related to an inadequate response against the virus. The purple segment represents the relationship between autoimmunity and immunodeficiency independent of COVID-19.