COVID-19 News: German Study Alarmingly Finds That Post-COVID Individuals Have A 42.6 Percent Higher Likelihood Of Acquiring Autoimmune Diseases!
: A news German study has found that people who have been exposed to the SARS-CoV-2 virus have a 42.6 percent higher likelihood of acquiring autoimmunity and various autoimmune diseases!
While different respiratory, cardiovascular, neurological and mental diseases as well as various symptoms in the context of long/post-COVID have been studied with routine health care data, the group of autoimmune diseases has not been studied in detail although autoantibodies could be found in patients after SARS-CoV-2 infection, e.g., anti-type I IFNs, anti-IFN-α and anti-nuclear antibodies (ANAs).
To date, there is very few cases reports and studies on newly manifested autoimmune diseases after a COVID-19.
With COVID-19 itself sharing some similarities with systemic autoimmune rheumatic diseases, it provides a challenge for diagnostics!
The German study team aimed to investigate whether the risk of developing an incident autoimmune disease is increased in patients with previous COVID-19 disease compared to individuals without COVID-19.
A study cohort was selected from German routine health care data covering 38.9 million individuals. Based on documented diagnoses, the study team identified individuals with polymerase chain reaction (PCR)-confirmed COVID-19 through December 31, 2020.
Patients were matched 1:3 to control patients without COVID-19. Both groups were followed up until June 30, 2021. The study team used the four quarters preceding the index date until the end of follow-up to analyze the onset of autoimmune diseases during the post-acute period. Incidence rates (IR) per 1000 person-years were calculated for each outcome and patient group. Poisson models were deployed to estimate the incidence rate ratios (IRRs) of developing an autoimmune disease conditional on a preceding diagnosis of COVID-19.
A total of 641,704 patients with COVID-19 were included.
The study team shockingly found a 42.63% higher likelihood of acquiring autoimmunity for patients who had suffered from COVID-19 when comparing the incidence rates in the COVID-19 (IR=15.05, 95% CI: 14.69-15.42) and matched control groups (IR=10.55, 95% CI: 10.25-10.86)!
Worryingly, this estimate was similar for common autoimmune diseases, such as Hashimoto thyroiditis, rheumatoid arthritis, or Sjögren syndrome.
The highest IRR was observed for autoimmune disease of
the vasculitis group.
Furthermore, patients with a more severe course of COVID-19 were at a greater risk for incident autoimmune diseases.
The study findings clearly showed that SARS-CoV-2 infection is associated with an increased risk of developing new-onset autoimmune diseases after the acute phase of infection.
The study findings were published on a preprint server and are currently being peer reviewed.
The study team comprised of researchers from University Hospital and Faculty of Medicine Carl Gustav Carus-Dresden, InGef - Institute for Applied Health Research-Berlin, BARMER Institut für Gesundheitssystemforschung (bifg)-Berlin, Vandage GmbH-Bielefeld, Bielefeld University, Techniker Krankenkasse,-Hamburg, 6 IKK classic-Dresden, 7AOK PLUS-Dresden, 8DAK-Gesundheit-Hamburg and Robert Koch Institut-Berlin.
In our past COVID-19 News
coverages, we had already highlighted that up to 41 percent of post-COVID individuals still have autoantibodies up to a year after contracting COVID-19 and also other studies supporting the same!
To date, this is the largest cohort studies to investigate the association between SARS-CoV-2 infection and the subsequent development of autoimmune diseases.
Some of the findings were worrisome:
-excess risk for any newly diagnosed autoimmune disease was 4.50 per 1000 person-years in this study. T
-highest IRRs were found for rather uncommon autoimmune diseases of the vasculitis group.
-for the more common autoimmune diseases, the highest risks were found for rheumatoid arthritis, Sjögren disease, Graves' disease and Hashimoto thyroiditis, with an increase of approximately 40% compared to a matched cohort without SARS-CoV-2 infection.
-those without a prior autoimmune disease and COVID-19 had a 43% higher likelihood of developing an incident autoimmune disease than controls, while those with any preexisting autoimmune disease and COVID-19 had a 23% higher likelihood of being diagnosed with another autoimmune disease.
-absolute incidence rates of any autoimmune disease were higher among women compared to men, among older compared to younger individuals and among those without preexisting autoimmune disease.
-comparing persons with and without COVID-19, the IRR increased with the severity of COVID-19 as indicated by hospitalization and particularly by ICU/ventilation treatment versus COVID-19 patients in the outpatient sector.
-a higher IRR for a new-onset autoimmune disease was observed in children and adolescents than in adults with/without COVID-19.
-differences between age groups did not reach statistical significance.
According to current knowledge, autoimmunity following viral infection may be triggered by mechanisms such as epitope spreading, bystander activation, molecular mimicry, and cryptic epitopes.
SARS-CoV-2 shares characteristics of other viruses associated with the development of autoimmunity.
A previous study claimed these hypotheses as causes for of autoimmunity:
-Superantigen activity: The S protein of SARS-CoV-2 contains sequence and structure motifs similar to those of a bacterial superantigen and can bind directly to the T-cell receptor.
-Molecular mimicry: Accumulating evidence demonstrates that the virus has structural similarity to host-derived components. 3
-Neutrophil extracellular trap (NET) formation.
-Type I interferon (IFN) response.
-“Overt immunity” which describes the appearance of multiple autoantibodies and diverse autoimmune diseases that are significantly associated with SARS-CoV-2.
All these possible mechanisms are in line with several serological studies demonstrating the onset of IgG autoantibodies or emergence of self-reactive B cells as a response to SARS-CoV-2.
Interestingly, autoantibodies generated during infection are negatively correlated with SARS-CoV-2 antibodies but positively correlated with hyperinflammation markers during acute illness as well as biomarkers for certain post-acute conditions.
These study findings highlight a potential link between autoreactivity, severity of COVID-19 and susceptibility to post-acute sequelae. Indeed, serological studies have found persisting patterns of autoreactivity in severe COVID-19 cases even after most autoimmunological markers have subsided after the acute phase. https://pubmed.ncbi.nlm.nih.gov/34521836/
Hence, this suggests latent autoimmunity acquired by some patients, which may lead to de novo autoimmune diseases in the long run.
Some early clinical case studies reported few cases of onset autoimmune diseases following COVID-19. There is growing consensus regarding the relevance of long-term studies on this matter.
Importantly, two recently conducted systematic reviews and meta-analyses for example show the association between diabetes mellitus and SARS-CoV-2 infection and conclude that the excess risk of type 1 diabetes is small but relevant from a public health perspective although the underlying mechanisms remain to be elucidated in order to prove a causal relationship.
Findings from the present German study regarding the excess risk of newly diagnosed type 1 diabetes in relation to documented SARS-CoV-2 infection are in line with these previous findings.
The present study findings also found the overall excess risk for a first autoimmune disease to be 4.50 per 1000 person-years, which is much smaller than previously proposed for other potential chronic sequelae of COVID-19. For cardiovascular diseases, the excess risk was 45.29; for mental diseases, it was 36.48; and for neurologic disorders, it was estimated to be 70.69 per 1000 people.
It was noted that one reason for this could be that autoimmune diseases are less frequent and the detection time is much longer than that for other diseases. The much larger IRR for hospitalized patients and patients with ICU/ventilation was also reported elsewhere.
In conclusion, this large matched cohort study found that COVID-19 was associated with an increased risk of being newly diagnosed with autoimmune disease 3-15 months after SARS-CoV-2 infection. The strength of the association with SARS-CoV-2 infection was most pronounced for autoimmune diseases in the vasculitis group. A more severe course of COVID-19 was associated with a higher likelihood of being newly diagnosed with autoimmune disease. Incident autoimmune diseases were significantly more common in the post-COVID-19 period in all age and sex groups. The autoimmunity hypothesis is supported by a body of evidence linking viral infections to the pathogenesis of autoimmune diseases as well as results from recent clinical and basic research demonstrating persisting autoantibodies and serological autoreactivity following SARS-CoV-2 infection in a subset of patients. Further epidemiologic, clinical and basic science research is warranted to determine whether SARS-CoV-2 infection triggers the onset of autoimmune disease, to identify the underlying mechanisms and persons at risk, and to investigate effective means of prevention or early treatment.
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