Is COVID-19 an Immune Complex Disease and are Billions Vaccinated Concomitantly Dosed with an Immunomodulatory Effector-Checkpoint Viral Mimetic Fc Receptor ?

COVID-19 has often been presented as a hundred diseases of diverse systems and organs needing many specialist experts to study and treat each aspect of this vast scope of pathological complexity in isolation. Alternatively, over the preceding decades, the Merck Manual, numerous publications, and certain patents have described systemic antigen-antibody immune complex diseases caused by viral and other infections with diverse symptoms similar to those of COVID-19. COVID-19 and systemic immune complex disease also selectively impact the same risk groups. Although, immune complex has been identified at sites of COVID-19 pathology in several publications, a recent study reported the unexpected finding that circulating immune complex (CIC) is not elevated in sera or a good biomarker for COVID-19 pathology.

A case of nephrotic syndrome secondary to HIV immune complex kidney disease

HIV immune complex disease of the kidney (HIVICK) is a rare but increasingly well-recognised cause of renal dysfunction and proteinuria in HIV-positive patients. A 56-year-old man with known HIV, diabetes mellitus type 2, liver cirrhosis and previous Hepatitis C virus (HCV) presented with a labile estimated glomerular filtration rate and significant proteinuria. Electron microscopy from a renal biopsy identified capillary wall deposition for IgG, IgM, Kappa, Lambda and focal C1q consistent with membranoproliferative glomerulonephritis (MPGN) and associated immune complex disease. A second opinion of the images confirmed the diagnosis of HIVICK. The increased recognition of HIVICK in HIV patients should prompt further research into the causes and treatment options available.

Immunogenicity and Immune Complex Disease in Preclinical Safety Studies

This article summarizes a continuing education presentation on immunogenicity that was part of a continuing education course entitled, “Clinical Pathology of Biotherapeutics.” Immunogenicity of a biotherapeutic can have diverse impacts including altered systemic exposure and pharmacologic responses and, in a fraction of the cases, safety concerns including cross-reactive neutralization of endogenous proteins or sequela related to immune complex disease (ICD). In most cases, immune complexes are readily cleared from circulation; however, based on physiochemical properties, insoluble complexes form, activate complement, and deposit in tissues. Using published information and personal experience, a set of repeat-dose monkey toxicity studies with manifestations suggestive of ICD was reviewed to summarize the spectrum of clinical and pathology findings. The most common live-phase observation linked to ICD was an acute postdosing reaction following multiple dose administrations characterized by generalized collapse and attributed to acute complement activation. Less common live-phase observations were related to syndromes such as a consumptive coagulopathy or a protein losing nephropathy. The most common histologic change attributed to ICD was multi-organ vascular/perivascular inflammation followed by glomerulonephritis. The presentation concluded with a description of the challenges in assessing the relevance of immunogenicity-related reaction in monkey to human clinical use.

Hypersensitivity diseases

Hypersensitivity reactions are aberrant immune responses that are provoked by innocuous extrinsic or self-antigens, are mediated by B-cells or T-cells, and may result in tissue or organ damage. Coombs and Gell classified hypersensitivity reactions into four types, based on the different immune responses: type I, or immediate hypersensitivity; type II, or antibody-mediated (humoral) cytotoxicity; type III, or immune-complex disease; and type IV, or delayed hypersensitivity. This chapter reviews the clinical features, diagnosis, and management of hypersensitivity reactions.

Renal Complications

Renal disease in persons with HIV has been a major cause of morbidity and mortality since the onset of the epidemic. HIV nephropathy (HIVAN) was the most common form of kidney disease initially seen, but in the post-antiretroviral therapy (ART) era it is much less common. Other renal conditions associated with HIV infection include immune complex disease and classic focal segmental glomerulosclerosis. The pathologic spectrum of renal disease in patients with HIV is extensive. Some conditions, including HIVAN, improve following treatment of the virus with ART. Acute kidney injury is much more common in HIV-infected patients and is associated with a sixfold increase in mortality. Patients with HIV are also much more likely to require renal replacement therapy, including dialysis and renal transplantation. ART may also contribute to renal disease in patients with HIV.