Lung Histopathology in COVID-19 as Compared to SARS and H1N1 Influenza: A Systematic Review

Hariri, Lida P.; North, Crystal M.; Shih, Angela R.; Israel, Rebecca A.; Maley, Jason H.; Villalba, Jullian A.; Vinarsky, Vladimir; Rubin, Jonah; Okin, Daniel A.; Sclafani, Alyssa; Alladina, Jehan W.; Griffith, Jason W.; Gillette, Michael A.; Raz, Yuval; Richards, Christopher J.; Wong, Alexandra K.; Ly, Amy; Hung, Yin P.; Chivukula, Raghu R.; Petri, Camille R.; Calhoun, Tiara F.; Brenner, Laura N.; Hibbert, Kathryn A.; Medoff, Benjamin D.; Hardin, C. Corey; Stone, James R.; Mino-Kenudson, Mari

Background Patients with severe Coronavirus Disease 2019 (COVID-19) have respiratory failure with hypoxemia and acute bilateral pulmonary infiltrates, consistent with acute respiratory distress syndrome (ARDS). It has been suggested that respiratory failure in COVID-19 represents a novel pathologic entity. Research Question How does the lung histopathology described in COVID-19 compare to the lung histopathology described in SARS and H1N1 influenza? Study Design and Methods: We conducted a systematic review to characterize the lung histopathologic features of COVID-19 and compare them against findings of other recent viral pandemics, H1N1 influenza and SARS. We systematically searched MEDLINE and PubMed for studies published up to June 24, 2020 using search terms for COVID-19, H1N1 influenza and SARS with keywords for pathology, biopsy, and autopsy. Using PRISMA-IPD guidelines, our systematic review analysis included 26 articles representing 171 COVID-19 patients; 20 articles representing 287 H1N1 patients; and eight articles representing 64 SARS patients. Results In COVID-19, acute phase diffuse alveolar damage (DAD) was reported in 88% of patients, which was similar to the proportion of cases with DAD in both H1N1 (90%) and SARS (98%). Pulmonary microthrombi were reported in 57% of COVID-19 and 58% of SARS patients, as compared to 24% of H1N1 influenza patients. Interpretation DAD, the histologic correlate of ARDS, is the predominant histopathologic pattern identified in lung pathology from patients with COVID-19, H1N1 influenza and SARS. Microthrombi were reported more frequently in both patients with COVID-19 and SARS as compared to H1N1 influenza. Future work is needed to validate this histopathologic finding and, if confirmed, elucidate the mechanistic underpinnings and characterize any associations with clinically important outcomes.