Is COVID-19 the Culprit? A Case of Anti-MDA5 Antibody Positivity in a Rapidly Progressive Organizing Pneumonia

Abstract

Introduction: Organizing pneumonia is a histologic subsect of interstitial lung disease (ILD). While a non-specific reaction to lung injury, it can be associated with infection, autoimmunity, or medication toxicity, or be characterized as idiopathic. Association with COVID-19 infection remains under active investigation. Beyond the initial viremia seen in COVID-19, the subsequent phase, characterized by an over-active host immune response, is less well understood. Anti-melanoma differentiation-associated gene 5 (MDA5) antibodies have been implicated in autoimmune pathology, including dermatomyositis and rapidly progressive ILD, and found to be positive in some patients with COVID-19. We describe a case of rapidly progressive organizing pneumonia with anti-MDA5 positivity, perhaps precipitated by earlier COVID-19 infection. Case: A 70-year-old gentleman with history of COVID-19 infection several months earlier presented with subacute dyspnea. He had not required hospitalization for COVID-19 infection, but subsequently developed slowly progressive dyspnea, wheezing, and inflammatory, migratory polyarthritis. Outpatient management with oral methylprednisolone 32mg daily, improved his arthritis, however, his respiratory symptoms did not improve despite additional inhaled corticosteroids and beta agonists. Admission imaging showed new bilateral upper lobe predominant ground glass opacities, reticulation of peripheral interstitium and bronchiectasis (Figure 1). Infectious workup, including SARS-CoV-2 testing, was negative. Rheumatologic workup revealed positive rheumatoid factor, anti-nuclear antibody (1:160, diffuse pattern) and anti-MDA5 antibody. The patient received broad spectrum antimicrobials and diuresis, but developed worsening acute hypoxemic/hypercarbic respiratory failure, requiring intubation and mechanical ventilation, proning, and neuromuscular blockade. Pulse dose steroids with intravenous methylprednisolone 250mg every six hours, were trialed for several days without improvements. Video assisted thorascopic surgery was performed and biopsy revealed bronchiolitis obliterans and organizing pneumonia with areas of fibrosis, without hyaline membrane formation or visible micro-organisms. The patient was not a candidate for extracorporeal membrane oxygenation and by the time the aforementioned biopsy resulted, he transitioned to comfort focused care, and died. Post-mortem examination revealed progression to diffuse alveolar damage with hyaline membrane formation, foci of early fibroplasia and squamous metaplasia and organizing parenchymal scars. Discussion: Anti-MDA5 antibody positivity has been implicated in rapidly progressive ILD often refractory to conventional treatments like steroids. While this patient's pathology showed organizing pneumonia, there was unfortunately no improvement with steroids. This case, of a patient with prior COVID-19 infection, who subsequently presented with rapidly progressive ILD in the setting of anti-MDA5 antibody, raises concern for viral-mediated autoimmune ILD. This highlights the urgency to understand SARS-CoV-2's interaction with the host immune response and subsequent autoantibody development.