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2 peer-reviewed reports of 2 agammaglobulinemic COVID-19 patients each; such individuals lack B cells and therefore can’t make their own antibodies.
Report 1. Quinti, Isabella, et al. Journal of Allergy and Clinical Immunology (2020). A possible role for B cells in COVID-19? Lesson from patients with agammaglobulinemia
“2 had agammaglobulinemia (1 with X-linked agammaglobulinemia and 1 with autosomal recessive agammaglobulinemia)…
In patients with agammaglobulinemia, the COVID-19 course was characterized by mild symptoms, short duration, and no need for treatment with an immune-modulating drug blocking IL-6, and it had a favorable outcome.”
Report 2. Soresina, Annarosa, et al. Pediatric Allergy and Immunology (2020). Two X‐linked agammaglobulinemia patients develop pneumonia as COVID‐19 manifestation but recover
“We describe two patients with X-linked agammaglobulinemia (XLA) of 34 and 26 years of age with complete absence of B cells from peripheral blood who developed COVID-19, as diagnosed by SARS-Cov-2 detection by nasopharyngeal swab, while receiving immunoglobulin infusions. Both patients developed interstitial pneumonia characterized by fever, cough and anorexia and associated with elevation of CRP and ferritin, but have never required oxygen ventilation or intensive care.
Conclusion: Our report suggests that XLA patients might present high risk to develop pneumonia after SARS-Cov2 infection, but can recover from infection, suggesting that B cell response might be important, but not strictly required to overcome the disease.”
Relevance: These results proffer at least two intriguing possibilities about immunity against SARS-CoV-2.
- That antibodies may not be needed to control this virus, at least not in a primary immune response. This isn’t surprising since patients with such primary antibody deficiencies are typically highly susceptible to bacterial infections while they’re able to ward off most viral infections though they remain particularly susceptible to enteric viruses, especially those that target the CNS (central nervous system) such as polio.
- Would patients with such immunodeficiencies overcome secondary SARS-CoV-2 infections without overt symptoms as would be expected of their immunosufficient counterparts as a result of immunological memory remains an open question.
- That the antibody bolus, Immunoglobulin therapy – Wikipedia, that these immunodeficient patients receive periodically as part of their lifelong treatment might contain cross-reactive antibodies generated against other targets such as related coronaviruses at titers sufficient to help protect them against SARS-CoV-2.
Context: Antibodies are no doubt important in the immunity toolkit but it’s a rich, varied and multi-layered one with plenty of redundancy built in as a result of intense selection pressures manifested over evolutionary time. This is why a combination of innate and T cell immunity typically suffices to protect even individuals with antibody defects from many if not most infectious agents.
Cheap, quick, straightforward, circulating antibodies figure prominently in immunoassays because of such practical advantages rather than intrinsic value as surrogates of immunity that are both necessary and sufficient to control a particular infection.
- Antibodies circulate abundantly in the blood and are therefore relatively easy to collect and measure.
- Ease of access and relatively standardized approaches to measure them make antibodies an attractive focus as a biomarker of immunity, especially during a novel virus pandemic. On the other hand, cellular assays such as for T cells remain unstandardized.
No surprise then that serology tests to assess presence/absence of antibodies against SARS-CoV-2 virus are attractive tools to indirectly estimate levels of population-wide exposure to this new virus. Useful, practical.
However, if those without their own antibodies are consistently found to easily control SARS-CoV-2, antibodies as relevant surrogates of effective immunity against this virus would be in question.