Autoimmunity Contributes to the Severe Progression of COVID-19

Although elderliness and chronic comorbidities such as hypertension, diabetes, cardiovascular diseases and respiratory diseases, are known risk factors for severe progression of COVID-19, it still remains puzzling on why younger patients without any comorbidity advance to severity and even more rapidly, the underlying mechanisms for severe progression of COVID-19 still needs to be elucidated. Based on current picturing of the COVID-19, similar to SARS, besides direct viral toxicity, immune-mediated attack derived from either the release of pro-inflammatory cytokine perpetual cascade, or secondary pathogen-induced autoimmunity response may also play important roles on disease progression and partly account for the multi-system injuries related with COVID-19. Virus infection has been implicated in the initiation of autoimmunity, which can attack multiple systems. With the knowledge of characteristics of SARS, high level of autoimmune activity was shown to make severe injuries to lungs or other organs, leading to poor outcome including multi-system failure9. COVID-19 may also get autoimmunity involved which is of obviously younger and female population predominance during the pathogenesis, no matter pre-existing or secondary to viral infection. Particularly strong immune response to SARS-CoV-2 infection might not be protective, but perhaps, be harmful to the host, contributing to disease severe progression.

Study Overview

• Status: Completed
• Conditions: Coronavirus Disease 2019
• Intervention / Treatment: Behavioral: autoimmunity

• Study Type: Observational
• Enrollment (Actual): 162

Contacts and Locations

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China, 430000
      • Zhongnan Hospital of Wuhan University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The retrospective study includes two groups of adult inpatients from two centers, Zhongnan Hospital of Wuhan University and Thunder God Mountain Hospital, Wuhan, China. All patients who were diagnosed as COVID-19 with real-time PCR (RT-PCR) assay of pharyngeal swab specimens18 confirmed results were screened, and those tested with autoimmunological detections including either ANA+ENA (Antinuclear antibody + Anti-extractable nuclear antigen antibody), Anti-cardiolipin antibody (ACA), Rheumatoid factor (RF), or Anti-streptolysin O antibody (ASO) detection, were enrolled in our study from Jan 22, 2020 to Jun 24, 2020.

Description

Inclusion Criteria:

1. Adult inpatients from two centers, Zhongnan Hospital of Wuhan University and Thunder God Mountain Hospital, Wuhan, China.
2. Experimental confirmed COVID-19 patients.
3. Patients tested with autoimmunological detections including either ANA+ENA (Antinuclear antibody + Anti-extractable nuclear antigen antibody), Anti-cardiolipin antibody (ACA), Rheumatoid factor (RF), or Anti-streptolysin O antibody (ASO) detection.

Exclusion Criteria:

1. Minors.
2. Experimental un-confirmed COVID-19 patients.
3. Patients without autoimmunological detections.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Group "Severe"; Each enrolled patient was allocated into control group "Non-severe" or case group "Severe" as per the disease severity which was defined according to the Chinese novel coronavirus pneumonia prevention and control guideline (version 6.0), "severe" and "critical" types were grouped into case group as "Severe".	Behavioral: autoimmunity; autoimmunity is characterized as self attacking from self immune system, which may involve in the severe progression of COVID-19.
Group "Non-severe"; Each enrolled patient was allocated into control group "Non-severe" or case group "Severe" as per the disease severity which was defined according to the Chinese novel coronavirus pneumonia prevention and control guideline (version 6.0), "mild" and "moderate" types were grouped into control group as "Non-severe".

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Presence of Antinuclear autoantibodies detected by ANA+ENA test	Antinuclear antibodies are closely related with many autoimmune diseases, and involved in the pathogenesis of many kinds of viruses.ANA+ENA was subjected to test from the admission till the discharge of patients' hospitalization. Both positive and negative results were reported, and detailed specific autoantibodies were also reported if positive.	baseline
Presence of Antinuclear autoantibodies detected by ANA+ENA test	Antinuclear antibodies are closely related with many autoimmune diseases, and involved in the pathogenesis of many kinds of viruses.ANA+ENA was subjected to test from the admission till the discharge of patients' hospitalization. Both positive and negative results were reported, and detailed specific autoantibodies were also reported if positive.	from the admission till the discharge of patients' hospitalization, up to 100 days.
Presence of Anti-streptolysin O (ASO)	Anti-streptolysin O (ASO or ASLO) is the antibody made against streptolysin O, an immunogenic, oxygen-labile hemolytic toxin produced by most strains of group A and many strains of groups C and G streptococci.ASO was subjected to test from the admission till the discharge of patients' hospitalization. Both positive and negative results were reported, and detailed specific immune globulin types were also reported if positive.	baseline
Presence of Anti-streptolysin O (ASO)	Anti-streptolysin O (ASO or ASLO) is the antibody made against streptolysin O, an immunogenic, oxygen-labile hemolytic toxin produced by most strains of group A and many strains of groups C and G streptococci.ASO was subjected to test from the admission till the discharge of patients' hospitalization. Both positive and negative results were reported, and detailed specific immune globulin types were also reported if positive.	from the admission till the discharge of patients' hospitalization, up to 100 days.
Presence of Rheumatoid Factors (RF)	factors used for the diagnosis of the rheumatoid arthritis (RA).RF was subjected to test from the admission till the discharge of patients' hospitalization. Both positive and negative results were reported, and detailed specific immune globulin types were also reported if positive.	baseline
Presence of Rheumatoid Factors (RF)	factors used for the diagnosis of the rheumatoid arthritis (RA).RF was subjected to test from the admission till the discharge of patients' hospitalization. Both positive and negative results were reported, and detailed specific immune globulin types were also reported if positive.	From the admission till the discharge of patients' hospitalization, up to 100 days.
Presence of Anticardiolipin antibody (ACA)	Anti- cardiolipin antibody (ACA) targets against anionic phospholipids and inhibits the effect of the prothrombin-activator complex to cause arterial and/or venous thrombosis, transiently appears positive around times of acute infections and acute thrombosis.ACA was subjected to test from the admission till the discharge of patients' hospitalization. Both positive and negative results were reported, and detailed specific immune globulin types were also reported if positive.	baseline
Presence of Anticardiolipin antibody (ACA)	Anti- cardiolipin antibody (ACA) targets against anionic phospholipids and inhibits the effect of the prothrombin-activator complex to cause arterial and/or venous thrombosis, transiently appears positive around times of acute infections and acute thrombosis.ACA was subjected to test from the admission till the discharge of patients' hospitalization. Both positive and negative results were reported, and detailed specific immune globulin types were also reported if positive.	From the admission till the discharge of patients' hospitalization, up to 100 days.

Collaborators and Investigators

• Sponsor: Zhongnan Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 10, 2020
• Primary Completion (Actual): May 27, 2021
• Study Completion (Actual): May 27, 2021

Study Registration Dates

• First Submitted: July 13, 2021
• First Submitted That Met QC Criteria: July 16, 2021
• First Posted (Actual): July 20, 2021

Study Record Updates

• Last Update Posted (Actual): July 20, 2021
• Last Update Submitted That Met QC Criteria: July 16, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: AUTO001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: With the permission of the corresponding author, we can provide participant data without names and identifiers, but not the study protocol, statistical analysis plan, or informed consent form. Data can be provided after the article is published. Once the data can be made public, the research team will provide an email address for communication. The corresponding authors have the right to decide whether to share the data or not based on the research objectives and plan provided.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No