Augmentation of anti-MDA5 antibody implies severe disease in COVID-19 patients

Abstract

Recent studies have provided insights into the autoinflammation triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection, which is associated with high mortality of coronavirus disease 2019 (COVID-19). Striking similarities has been noted between COVID-19 and anti-melanoma differentiation-associated gene 5 (MDA5) antibody (Ab)-related dermatomyositis (DM), implying a shared autoinflammatory aberrance. However, it is unclear whether anti-MDA5 Ab is present in COVID-19 and correlates with the severity and adverse outcome of COVID-19 patients. Here, we found that the positive rate of anti-MDA5 Ab in patients with COVID-19 was 48.2% and the anti-MDA5 Ab positive patients tended to develop severe disease (88.6% vs 66.9%, P<0.0001). In particular, the titer of anti-MDA5 Ab was increased in the non-survivals (5.95±5.16 vs 8.22±6.64, P=0.030) and the positive rate was also higher than that in the survivals (23.5% vs 12.0%, P=0.012). Regarding to severe COVID-19 patients, we found that high titer of anti-MDA5 Ab (≥10.0 U/mL) was more prevalent in the non-survivals (31.2% vs 14.0%, P=0.006). Moreover, early profiling of anti-MDA5 Ab could distinguish severe patients from those with non-severe ones. Overall, our data reveal that anti-MDA5 Ab is prevalent in the COVID-19 patients and high titer of this antibody is correlated with severe disease and unfavorable outcomes.

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

We thank Dr. Jinmin Peng and Jingjing Bai for providing assistance with statistical analysis and preparing samples of anti-MDA5 Ab-related DM. We are grateful to clinicians of Wuhan Jinyintan Hospital for sample collection and Dr. colleagues of Hubei Provincial Center for Disease Control and Prevention for sample transportation. This study was supported by National Key R&D Program of China (2020YFA0707600) and CAMS Innovation Fund for Medical Sciences (2018-I2M-1-003, 2019-I2M-1-006, 2019-I2M-2-008), National Science Grant for Distinguished Young Scholars (81425001/H0104), The Beijing Science and Technology Project (D151100002115004)

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The study was approved by the Research Ethics Committee of the participating hospitals and the ethical board of the Institute of Pathogen Biology, Chinese Academy of Medical Sciences. The requirement for informed consent was waived by the Ethics Commission of the designated hospitals for emerging infectious diseases as described previously.

All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.

Yes

Data Availability

In this retrospective study of adult inpatients in three hospitals in China, we identified anti-MDA5 Ab in 48.2% of patients with COVID-19. The anti-MDA5 Ab positive patients tended to represent with severe disease (88.6% vs 66.9%, P<0.0001), and the titer of anti-MDA5 Ab was significantly elevated in the non-survivals (P=0.030) than that in the survivals. We also demonstrated that early profiling of anti-MDA5 Ab could distinguish severe patients from those with non-severe ones. Overall, our data suggest that early screening and serially monitoring of anti-MDA5 Ab might help identify severe COVID-19 patients with poor outcomes, or those who would probably benefit from anti-inflammation and immunosuppressive therapy. The findings are yet to be validated in a larger population of different ethnicities in future.

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