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Background Patients with severe coronavirus disease 2019 (COVID-19) have respiratory failure with hypoxemia and acute bilateral pulmonary infiltrates, consistent with ARDS. Respiratory failure in COVID-19 might represent a novel pathologic entity. Research Question How does the lung histopathology described in COVID-19 compare with 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-Individual Participant Data 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 with 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 with 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.

Criteria used to define the respective roles of pulmonary mechanics and cardiovascular disease in limiting exercise performance are usually obtained at peak exercise, but are dependent on maximal patient effort. To differentiate heart from lung disease during a less effort-dependent domain of exercise, the predictive value of the breathing reserve index (BRI=minute ventilation [VE]/maximal voluntary ventilation [MVV]) at the lactate threshold (LT) was evaluated.Thirty-two patients with COPD and a pulmonary mechanical limit (PML) to exercise defined by classic criteria at maximum oxygen uptake (VO2max) were compared with 29 patients with a cardiovascular limit (CVL) and 12 normal control subjects. Expired gases and VE were measured breath by breath using a commercially available metabolic cart (Model 2001; MedGraphics Corp; St. Paul, Minn). Arterial blood gases, pH, and lactate were sampled each minute during exercise, and cardiac output (Q) was measured by first-pass radionuclide ventriculography (System 77; Baird Corp; Bedford, Mass) at rest and peak exercise.For all patients, the BRI at lactate threshold (BRILT) correlated with the BRI at VO2max (BRIMAX) (r=0.85, p0.0001). The BRILT was higher for PML (0.73+/-0.03, mean+/-SEM) vs CVL (0.27+/-0.02, p0.0001), and vs control subjects (0.24+/-0.03, p0.0001). A BRILTor = 0.42 predicted a PML at maximum exercise, with a sensitivity of 96.9%, a specificity of 95.1%, a positive predictive value of 93.9%, and a negative predictive value of 97.5%.The BRILT, a variable measured during the submaximal realm of exercise, can distinguish a PML from CVL.