Analysis of the correlation between anti-MDA5 antibody and the severity of COVID-19: a retrospective study

Abstract

OBJECTIVE

To identify the anti-melanoma differentiation-associated gene 5 (MDA5) antibody (Ab) in coronavirus disease 2019 (COVID-19) and its relationship with the severity and clinical outcomes of COVID-19.

DESIGN

Retrospective cohort study.

SETTING

Three hospitals in China.

PARTICIPANTS

274 adult inpatients diagnosed with COVID-19 according to the Protocol for Prevention and Control of COVID-19 (Edition 7) of China and confirmed by severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) RNA testing, were included from three hospitals from Wuhan, Harbin and Beijing, China from 1 December 2019 to 19 April 2020. The Biobank of Myositis Registry Department of Rheumatology, Peking Union Medical College Hospital, provided the plasma of five patients with anti-MDA5 Ab-related dermatomyositis as positive control group. Demographic, clinical and laboratory data were collected from medical records. The anti-MDA5 Ab was determined by an ELISA assay and was verified by immunoblotting analysis.

MAIN OUTCOME MEASURES

In hospital death of all cause.

RESULTS

The positive rate of anti-MDA5 Ab in patients with COVID-19 was 48.2% (132/274) and the anti-MDA5 Ab positive patients tended to represent with severe disease (88.6% vs 66.9%, P <0.0001). The titer of anti-MDA5 Ab was significantly elevated 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.

CONCLUSION

Anti-MDA5 Ab was prevalent in the COVID-19 patients and high titer of this antibody is correlated with severe disease and unfavorable outcomes. Early screening and serially monitoring of anti-MDA5 Ab titer have the potential to predict the disease progression of COVID-19.

SciScore for 10.1101/2020.07.29.20164780: (What is this?)

Please note, not all rigor criteria are appropriate for all manuscripts.

Table 1: Rigor

Institutional Review Board Statement	IRB: All of the 5 DM patients were diagnosed based on the criteria of Bohan and Peter.24,25 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. Consent: The requirement for informed consent was waived by the Ethics Commission of the designated hospitals for emerging infectious diseases as described previously12.
Randomization	not detected.
Blinding	not detected.
Power Analysis	not detected.
Sex as a biological variable	not detected.
Cell Line Authentication	Authentication: This cell line was tested 1 month before the experiment by methods of morphology check by microscopy, growth curve analysis, and mycoplasma detection according to the ATCC cell line verification test recommendations. Contamination: This cell line was tested 1 month before the experiment by methods of morphology check by microscopy, growth curve analysis, and mycoplasma detection according to the ATCC cell line verification test recommendations.

Table 2: Resources

Antibodies
Sentences	Resources
The antibodies used included those against Flag and MDA5 were purchased from Sigma-Aldrich Co.	MDA5 suggested: None
and the antibody against β-actin were obtained from Abcam Co.	β-actin suggested: None
Experimental Models: Cell Lines
Sentences	Resources
Western Blots: 293T cell line was obtained from the American Type Culture Collection (ATCC) and grown in DMEM with 10% FBS (Hyclone) at 37°C in 5% CO2 cell culture incubator.	293T suggested: None
The antibodies used included those against Flag and MDA5 were purchased from Sigma-Aldrich Co.	MDA5 suggested: None
Software and Algorithms
Sentences	Resources
All statistical analyses were performed using SPSS 16.0 software (SPSS Inc., Chicago, IL, USA).	SPSS suggested: (SPSS, RRID:SCR_002865)

Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:

There are several limitations in our study. Firstly, since MDA5 is validated as a general sensor for diverse RNA viruses, no evidence has addressed whether anti-MDA5 Ab is present in the infection of other RNA viruses, for instance, influenza virus, enterovirus, and other coronaviruses. Therefore, the specificity of anti-MDA5 Ab in COVID-19 need to be further investigated. Secondly, due to limited sample size and endpoint events, we were not able to further evaluate whether anti-MDA5 Ab is an independent predictive factor for the death in COVID-19 or could be included in a risk stratification model. Thirdly, all patients were from China and it is not clear whether patients with other genetic backgrounds would have same results. Our findings are to be validated in a larger population of different ethnicities in future.

Results from TrialIdentifier: No clinical trial numbers were referenced.

Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

Results from JetFighter: We did not find any issues relating to colormaps.

Results from rtransparent:

Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
No protocol registration statement was detected.

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