Selective IgA Deficiency May Be an Underrecognized Risk Factor for Severe COVID-19.

SARS-CoV-2, the agent responsible for COVID-19, has wreaked havoc around the globe. Hundreds of millions of individuals have been infected and well over six million have died from COVID-19. Many COVID-19 survivors have ongoing physical and psychiatric morbidity, which will remain for the rest of their lives. Early in the pandemic, it became apparent that older individuals and those with comorbidities including obesity, diabetes mellitus, coronary artery disease, hypertension, and renal and pulmonary disease were at increased risk of adverse outcomes. It is also clear that some immunodeficient patients, such as those with innate or T cell-immune defects, are at greater risk from COVID-19. Selective IgA deficiency (sIgAD) is generally regarded as a mild disorder in which most patients are asymptomatic because of redundancy in protective immune mechanisms. Recent data indicate that patients with sIgAD may be at high risk of severe COVID-19. SARS-CoV-2 gains entry primarily through the upper respiratory tract mucosa, where IgA has a critical protective role. This may underlie the vulnerability of sIgAD patients to adverse outcomes from COVID-19. This perspective highlights the need for ongoing research into mucosal immunity to improve COVID-19 treatments for patients with sIgAD.

Selective IgA deficiency may be an under-recognized risk factor for severe COVID-19

SARS-CoV-2, the agent responsible for COVID-19, has caused havoc around the globe. Hundreds of millions of individuals have been infected and well over six million have died from COVID-19. Many COVID-19 survivors have ongoing physical and psychiatric morbidity, which will remain for the rest of their lives. Early in the pandemic, it became apparent older individuals and those with comorbidities including obesity, diabetes mellitus, coronary artery disease, hypertension, renal and pulmonary disease were at increased risk of adverse outcomes. It is also clear that some immunodeficient patients, such as those with innate or T cell immune defects are at greater risk from COVID-19. Selective IgA deficiency (sIgAD) is generally regarded as a mild disorder, where the majority of patients are asymptomatic because of redundancy in protective immune mechanisms. Recent data indicates patients with sIgAD may be at high risk of severe COVID-19. SARS-CoV-2 gains entry primarily through the upper respiratory tract mucosa, where IgA plays a critical protective role. This may underlie the vulnerability of sIgAD patients for adverse outcomes from COVID-19. This perspective highlights the need for ongoing research into mucosal immunity and improving COVID-19 treatments for patients with sIgAD.

The (apparent) antibody paradox in COVID-19.

INTRODUCTION: The immunological response to COVID-19 is only partly understood. It is increasingly clear that the virus triggers an inappropriate host inflammatory reaction in patients experiencing severe disease. AREAS COVERED: The role of antibodies in COVID-19 remains to be fully defined. There is evidence for both protection and harm in different clinical syndromes triggered by SARS-CoV-2. Many patients dying from COVID-19 had both high titers of antibodies to SARS-CoV-2 and elevated viral loads. The uncertain protective role of humoral immunity is mirrored by the lack of benefit of therapeutic convalescent plasma infusions in COVID-19. In contrast, there is increasing evidence that a vigorous T-cell response is protective. Delayed or low avidity T cell reactions were seen in patients suffering severe COVID-19. EXPERT OPINION: These observations suggest T cell responses to SARS-CoV-2 are the dominant long-term protective mechanism following either infection or vaccination. The magnitude and quality of the antibody response is likely to reflect underlying T cell immunity to SARS-CoV-2. Much of what has been learned about COVID-19 will need to be revised following the recent rapid emergence and dominance of the omicron variant of SARS-CoV-2.