Dr. Kitajima et al reply.

We thank Mutoh et al1 for their interest in our study on antimelanoma differentiation-associated gene 5 antibody-positive interstitial lung disease (anti-MDA5-ILD) after vaccination with coronavirus disease 2019 (COVID-19) mRNA vaccines2 and for sharing their clinical experience. Mutoh et al1 reported a case of anti-MDA5-ILD that developed 8 weeks after COVID-19 mRNA vaccination in Japan.

Antimelanoma Differentiation-Associated Gene 5 Antibody-Positive Interstitial Lung Disease After Vaccination With COVID-19 mRNA Vaccines.

OBJECTIVE: Melanoma differentiation-associated gene 5 (MDA5) is a viral RNA sensor induced by SARS-CoV-2. Similarities have been reported between the clinical presentations of coronavirus disease 2019 (COVID-19) pneumonia and anti-MDA5 antibody-positive interstitial lung disease (anti-MDA5-ILD). However, it is unknown whether COVID-19 mRNA vaccines are associated with anti-MDA5-ILD. METHODS: We retrospectively reviewed consecutive patients with anti-MDA5-ILD admitted to our hospital between April 2017 and March 2022. In addition, we investigated the clinical presentations of patients who developed anti-MDA5-ILD after vaccination with COVID-19 mRNA vaccines. We also examined the annual number of anti-MDA5-ILD cases before and after the COVID-19 vaccination campaign. RESULTS: Nine patients with anti-MDA5-ILD were seen during the study period, of whom 4 developed anti-MDA5-ILD between August and October 2021, approximately 6 to 12 weeks after vaccination with a COVID-19 mRNA vaccine and a few months after the rapid mRNA COVID-19 vaccination campaign in Japan. None of the 4 patients had evidence of SARS-CoV-2 infection. The difference in the annual number of anti-MDA5-ILD cases before vs after the COVID-19 vaccination campaign (1.25 ± 0.96 cases/yr vs 4.0 cases/yr) was not statistically significant (P = 0.08). CONCLUSION: We encountered 4 cases of anti-MDA5-ILD after COVID-19 vaccination. Further large population studies are needed to clarify the relationship between anti-MDA5-ILD and vaccination with COVID-19 mRNA vaccines.

SARS-CoV-2-related Progressive Brain White Matter Lesion Associated with an Increased Cerebrospinal Fluid Level of IL-6.

We herein report a 49-year-old man with a fever, diagnosed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. After two weeks of hospitalization, he suddenly mentioned visual field impairment. Computed tomography and magnetic resonance imaging revealed white matter damage and vasogenic edema. Cerebrospinal fluid showed increased levels of interleukin (IL)-6. His symptoms and white matter lesion deteriorated. After treatment with intravenous methylprednisolone therapy and plasmapheresis, his symptoms and white matter lesion improved gradually. We suspect that our patient was affected by a secondary hyperinflammatory syndrome related to cytokines, alone or in combination with direct viral injury through endothelial cell damage. The IL-6 levels were elevated only in the cerebrospinal fluid, suggesting focal central nervous system inflammation.