Immune complexes as culprits of immunopathology in severe COVID-19

Abstract

Infection with the pandemic human coronavirus SARS-CoV-2 elicits a respiratory tract disease, termed Coronavirus disease 2019 (COVID-19). While a variable degree of disease-associated symptoms may emerge, severe COVID-19 is commonly associated with respiratory complications such as acute respiratory distress syndrome (ARDS), the necessity for mechanical ventilation or even extracorporeal membrane oxygenation (ECMO). Amongst others, disease outcome depends on age and pre-existing conditions like cardiovascular diseases, metabolic disorders but also age and biological sex. Intriguingly, increasing experimental and clinical evidence suggests that an exacerbated inflammatory response and in particular IgG immune complexes (ICs), significantly contribute to severe and prolonged COVID-19 disease progression. Vast amounts of deposited, unresolved ICs in tissue are capable to initiate an exaggerated Fc gamma receptor (FcγR) mediated signalling cascade which eventually results in common IC-associated organ diseases such as vasculitis, glomerulonephritis and arthritis, comorbidities that have been frequently reported for COVID-19. Moreover and independent of deposited ICs, very recent work identified soluble ICs (sIC) to be also present in the circulation of a majority of severely ill patients, where their systemic abundance correlated with disease severity. Thus, detection of circulating sICs in patients represents a potential marker for critical COVID-19 disease progression. Their detection early after clinical deterioration might become an indicator for the requirement of prompt anti-inflammatory treatment. Here, we review the role of ICs in COVID-19 progression, their possible origins and potential intervention strategies. Graphical abstract

Coronavirus disease 2019 (COVID-19) pandemic and autoimmune rheumatic diseases: Outcomes and prospects

“…Однако данные, касающиеся генетических дефектов системы комплемента при COVID-19, пока отсутствуют. В то же время отмечена корреляция между формированием NЕTs (комплекс миелопероксидаза -ДНК), активацией комплемента и маркерами гиперкоагуляции при COVID-19 [216], а также с образованием циркулирующих иммунных комплексов (ЦИК) [217][218][219]. ЦИК, вызывающие FcγRIIIA/ CD16A активацию моноцитов, выявлены в сыворотках 80% пациентов с тяжелым COVID-19, а их уровень сопоставим с таковым при СКВ.…”

Are the Comorbidities Constitute an Intrinsic Factor for Long COVID?

“…Therefore, detecting circulating sICs in patients may be a potential marker for critical COVID-19 disease progression. Early detection of sICs after clinical deterioration may indicate the need for prompt anti-inflammatory treatment [44]. Immunological and autoantibody response is presented in Figure 1.…”

Contemporaneous SARS-CoV-2-Neutralizing Antibodies Mediated by N-glycan Shields

“…These non-NAbs can be categorized as Fc-antibody-dependent infection enhancement antibodies produced by the previous vaccination, and the induction of such non-NAbs results in immune complex (IC) deposition and complement activation. These IC deposits have been linked to COVID-19 disease severity and many of the long-term consequences of SARS-CoV-2 infection such as arthritis and vasculitis [ 27 ]. This viral persistence based on the enhanced interference of non-NAbs has also been noted in HIV.…”