Study: Longitudinal analysis reveals elevation then sustained higher expression of autoantibodies for six months after SARS-CoV-2 infection. Image Credit:  Corona Borealis Studio/Shutterstock

High and sustained autoantibodies after COVID-19

A recent study published on medRxiv* The preprint server demonstrated that autoantibody levels increase after acute infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and remain elevated for approximately six months.

Study: Longitudinal analysis reveals an elevation and then a sustained higher expression of autoantibodies for six months after SARS-CoV-2 infection. Image Credit: Corona Borealis Studio/Shutterstock

Background

Existing reports suggest that people hospitalized with SARS-CoV-2 infection had elevated concentrations of autoantibodies reactive to self-epitopes such as interferons and phospholipids with possible functional significance. Previous studies have documented links between autoantibody levels and SARS-CoV-2 severity.

However, the temporal patterns and amounts of these autoantibodies months after CoV disease 2019 (COVID-19) remain unknown. Indeed, it is unclear whether the composite autoantibody profiles of recovered SARS-CoV-2 infected individuals are similar to those with confirmed autoimmune disorders.

About the study

The present study aimed to learn more about the relationships between SARS-CoV-2 infection and autoimmunity. Scientists assessed the circulatory concentrations of 17 autoantibodies correlated with autoimmune connective tissue disorders in hospitalized and outpatient COVID-19 patients. They also analyzed these autoantibody levels in people with systemic lupus erythematosus (SLE), uninfected pre-pandemic controls, and scleroderma (SSc).

Outpatient and hospitalized subjects infected with SARS-CoV-2 represented those with mild and severe COVID-19, respectively. Researchers compared autoantibody concentrations from late and early timestamps (≥90 or ≤30 days after symptom onset) of hospitalized and outpatient COVID-19 patients with two cohorts of autoimmune participants (SSc and SLE ) and uninfected pre-pandemic controls. They performed multivariate analyzes to assess the mechanism by which COVID-19 correlated with autoantibody positivity given comorbidities and participant demographics.

Additionally, the researchers examined the longitudinal trajectory of autoantibodies months after the onset of COVID-19 symptoms. For this, the team assessed various trends of change in personal autoantibody concentrations in all subjects infected with SARS-CoV-2 over time (two to five timestamps per individual, spanning approximately six month). They also used partial least squares discriminant analysis (PLS-DA) to examine individual autoantibody expression fingerprints of COVID-19 patients months after recovery compared to those with autoantibody disorders. immune and uninfected controls.

Results

The study results demonstrated that seven of 17 autoantibodies tested were elevated in hospitalized or outpatients with SARS-CoV-2 nearly six months after symptom onset than in controls. The seven autoantibodies were anti-alanyl-transfer ribonucleic acid (tRNA) synthetase (PL-12), Ku, anti-topoisomerase (Scl-70), β-2-glycoprotein, proteinase 3, ribonucleoprotein (RNP)/anti-Smith (Sm) and sjögren’s syndrome type B (SSB/La). Additionally, multivariate analyzes revealed associations between COVID-19 and positivity for SSB/La, Sm, myeloperoxidase, proteinase 3, histidyl-tRNA synthetase 1 (Jo-1), and reactive immunoglobulin Ku Gs (IgG) six months after the onset of symptoms.

COVID-19 patients’ autoantibody levels were tracked for approximately six months from the onset of symptoms, and various temporal patterns of autoantibodies were identified. Subjects infected with SARS-CoV-2 had a higher level of autoantibodies than controls not exposed to convalescent and acute timestamps. The autoantibody expression profiles of each participant showed similarities between the recovered and pre-pandemic SARS-CoV-2 infected groups, which were unique among SLE and SSc subjects. These findings suggest that COVID-19 convalescents experience random and disorganized generation of autoantibodies, reinforcing proposed processes, such as lymphopenia-induced loss of tolerance, different from epitope spreading or molecular mimicry.

In 18% of outpatients and 53% of inpatient participants, a pattern of negative then positive expression of at least one autoantibody was found, showing long-term induction and expression of self-reactive immune responses after COVID-19, especially in severe acute cases. sickness. Furthermore, positivity of a major autoantibody temporal expression profile in outpatient and hospitalized COVID-19 patients at all timestamps indicated extremely early generation of autoantibodies or its pre-existence prior to exposure. viral.

conclusion

According to the study results, autoantibodies linked to autoimmune connective tissue pathologies were found in COVID-19 patients months after recovery than in pre-pandemic controls. Furthermore, the investigation showed temporal pathways indicating the onset of new autoimmune responses after SARS-CoV-2 infection.

The study results suggest that SARS-CoV-2 leaves a significant autoimmune imprint at least within the first six months of infection. Unlike participant samples collected before the COVID-19 pandemic, autoantibodies in convalescent subjects infected with SARS-CoV-2 were significantly higher. Even when SARS-CoV-2 infection occurred approximately six months earlier, COVID-19 history showed significant correlations with the presence of many autoantibodies after controlling for medical conditions and data participant demographics.

The authors mentioned that because autoantibody positivity can occur years before autoimmune disease onset, the idea that SARS-CoV-2-related autoantibodies represent a precursor to future autoimmune diseases immune warrants further investigation. Additionally, understanding the interplay between variables, such as immune memory and pre-existing infections, new immune responses, acute viral infection and inflammation, and lymphopenia, was essential to address morbidity and disease. death related to SARS-CoV-2.

*Important Notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be considered conclusive, guide clinical practice/health-related behaviors, or treated as established information.

Journal reference:

  • Nahid Bhadelia, Alex Olson, Erika Smith, Katherine Reifler, Jacob Cabrejas, Maria Jose Ayuso, Katherine Clarke, Rachel Ruby Yuen, Nina Lin, Zach Manickas-Hill, Ian Rifkin, Andreea Monica Bujor, Manish Sagar, Anna Belkina, Jennifer Snyder- capped. (2022). Longitudinal analysis reveals an elevation and then a sustained higher expression of autoantibodies for six months after SARS-CoV-2 infection. medRxiv. do I: https://doi.org/10.1101/2022.05.04.22274681 https://www.medrxiv.org/content/10.1101/2022.05.04.22274681v1

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