Highlights d 11,394 proteins are quantified in autopsy samples from 7 organs in 19 COVID-19 patients d Elevated expression of cathepsin L1 is detected in the COVID-19 lung tissue d Dysregulation of angiogenesis, coagulation, and fibrosis is detected in multiple organs d Systemic metabolic dysregulation is detected in multiple organs

The molecular pathology of multi-organ injuries in COVID-19 patients remains unclear, preventing effective therapeutics development. Here, we report an in-depth multi-organ proteomic landscape of COVID-19 patient autopsy samples. By integrative analysis of proteomes of seven organs, namely lung, spleen, liver, heart, kidney, thyroid and testis, we characterized 11,394 proteins, in which 5336 were perturbed in COVID-19 patients compared to controls. Our data showed that CTSL, rather than ACE2, was significantly upregulated in the lung from COVID-19 patients. Dysregulation of protein translation, glucose metabolism, fatty acid metabolism was detected in multiple organs. Our data suggested upon SARS-CoV-2 infection, hyperinflammation might be triggered which in turn induces damage of gas exchange barrier in the lung, leading to hypoxia, angiogenesis, coagulation and fibrosis in the lung, kidney, spleen, liver, heart and thyroid. Evidence for testicular injuries included reduced Leydig cells, suppressed cholesterol biosynthesis and sperm mobility. In summary, this study depicts the multi-organ proteomic landscape of COVID-19 autopsies, and uncovered dysregulated proteins and biological processes, offering novel therapeutic clues.

Aims: Coronavirus Disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection has been deemed as a global pandemic by World Health Organization. While diffuse alveolar damage (DAD) is recognized to be the primary manifestation COVID-19 pneumonia, there has been little emphasis on the progression to the fibrosing phase of DAD. This topic is of great interest due to growing concerns regarding the potential long-term complications in prolonged survivors. Methods: Here we report a detailed histopathologic study of thirty autopsy cases with COVID-19 virus infection, based on minimally invasive autopsies performed between February to March, 2020. Results: The mean age was 69 years, with twenty (67%) males and 10 (33%) females and frequent (70.0%) underlying comorbidities. The duration of illness ranged from 16 to 82 (median=42) days. Histologically, the most common manifestation was diffuse alveolar damage (DAD) in 28 (93.3%) cases which showed predominantly acute (32%), organizing (25%), and/or fibrosing (43%) patterns. Patients with fibrosing DAD were one decade younger (p=0.034) and they had a longer duration of illness (p=0.033), hospitalization (p=0.037) and mechanical ventilation (p=0.014) compared to those with acute DAD. Patients with organizing DAD had a longer duration of illness (p=0.032) and hospitalization (p=0.023) compared to those with acute DAD. Conclusions: COVID-19 pneumonia patients who develop DAD can progress to the fibrosing pattern. While we observed fibrosing DAD in fatal cases, whether surviving patients are at risk for developing pulmonary fibrosis and the frequency of this complication will require further clinical and radiologic follow-up studies.

The lung tissue microbiota features of 20 deceased patients with COVID-19 To the EditorWe read with great interest the article by Yanan Chu and colleagues, accepted for publication in the Journal of Infection. 1 Secondary infection and sepsis are common complications in critically ill patients with COVID-19, 2 , 3 but the underlying pathogen is not clear. We investigated the microbiota characteristics of lung tissue from 20 deceased COVID-19 patients. All cases met the COVID-19 clinical diagnostic criteria provided by the