Enhanced eosinophil-mediated inflammation associated with antibody and complement-dependent pneumonic insults in critical COVID-19.

Despite the worldwide effect of the coronavirus disease 2019 (COVID-19) pandemic, the underlying mechanisms of fatal viral pneumonia remain elusive. Here, we show that critical COVID-19 is associated with enhanced eosinophil-mediated inflammation when compared to non-critical cases. In addition, we confirm increased T helper (Th)2-biased adaptive immune responses, accompanying overt complement activation, in the critical group. Moreover, enhanced antibody responses and complement activation are associated with disease pathogenesis as evidenced by formation of immune complexes and membrane attack complexes in airways and vasculature of lung biopsies from six fatal cases, as well as by enhanced hallmark gene set signatures of Fcγ receptor (FcγR) signaling and complement activation in myeloid cells of respiratory specimens from critical COVID-19 patients. These results suggest that SARS-CoV-2 infection may drive specific innate immune responses, including eosinophil-mediated inflammation, and subsequent pulmonary pathogenesis via enhanced Th2-biased immune responses, which might be crucial drivers of critical disease in COVID-19 patients.

Enhanced eosinophilic inflammation associated with antibody and complement-mediated pneumonic insults in severe COVID-19 (preprint)

Despite the worldwide effect of the Coronavirus disease 2019 (COVID-19) pandemic, the underlying mechanisms of fatal viral pneumonia remain elusive. Here, we conducted kinetic profiling of respiratory leukocytes and associated inflammatory mediators to show that severe COVID-19 is associated with delayed but enhanced eosinophilic inflammation when compared to mild cases. In addition, we confirmed increased Th2-biased adaptive immune responses, accompanying overt complement activation, in the severe group. Moreover, enhanced antibody responses and complement activation was associated with disease pathogenesis as evidenced by formation of immune complexes and membrane attack complexes in airways and vasculature of lung biopsies from a fatal case, as well as by enhanced hallmark gene set signatures of FcgR signaling and complement activation in myeloid cells of respiratory specimens from severe COVID-19 patients. We also observed expression of viral antigen in lung epithelial and endothelial cells without producing viruses during late stage of COVID-19, indicating abortive viral infection which may further fuel antibody responses and aggravate immune-complex-mediated inflammation. These results suggest that SARS-CoV-2 infection may drive scripted specific innate immune responses, including eosinophilic inflammation, and subsequent pulmonary pathogenesis via enhanced Th2-biased immune responses, which might be crucial drivers of severe pneumonia in COVID-19 patients.

Acute eosinophilic pneumonia associated with elevated NKT cell response in COVID-19 patients (preprint)

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)1 and often results in fatal pneumonia.2,3 Despite the worldwide effect of the COVID-19 pandemic, the underlying mechanisms of the fatal viral pneumonia remain elusive. Here, we investigated respiratory specimens, including broncholoalveolar lavage fluids (BALFs) and bloods collected from three confirmed cases of COVID-19 patients with varying degrees of disease severity. Surprisingly, over 35% of cells from BALFs obtained from two pneumonic patients was comprised of eosinophils, while 20% was comprised of lymphocytes. Cytological analysis of sputa and tracheal aspirates from all three patients also revealed that more than 90% of total cells were eosinophils. Infiltration of CD16+/CD24+ polymorphonuclear cells into lungs, together with elevated NKT cells in BALFs and peripheral blood samples, in patients with severe pneumonia was confirmed by flow cytometry. Moreover, rapid and profound IgE responses against the N protein of SARS-CoV-2 was only detected in plasma from a patient suffering from more severe and prolonged pneumonia. A significant reduction in oxygen demand with improved chest imaging was observed in two severe COVID-19 patients after treatment with a steroid, methylprednisolone. The present study provides evidence that acute eosinophilic pneumonia4 is associated with COVID-19. 

Treatment for breast cancer patients during the special period of novel coronavirus pneumonia outbreak (preprint)

Purpose: The outbreak of novel coronavirus pneumonia occurred worldwide. 2019 novel coronavirus disease (COVID-19) can be transmitted from human to human, cause hospital infection, and seriously threatens surgical staffs and inpatients. The treatment of patients with breast cancer may be affected in this special period. Methods: From 24th January to 8th March 2020, patients diagnosed with breast cancer were enrolled from 16 hospitals in Jiangsu Province, and patients, who were candidates for surgery after neoadjuvant chemotherapy, were also enrolled. Patients from 24th January to 8th March 2019 were included as control with the same criteria. Results: In 2019, 520 patients were diagnosed with breast cancer in these 16 hospital; however, only 229 patients (decreased by 56%) were diagnosed with breast cancer in the same period of 2020. The clinical characteristics were similar between the two groups, and core biopsy was performed to more patients in 2020 than that in 2019 (4.1 days ±3.2 vs 3.2 days ±2.6, P < 0.001), and more patients underwent mastectomy and axillary lymph node dissection in 2020. After neoadjuvant chemotherapy, the mean interval between last time of neoadjuvant chemotherapy and surgery in 2020 was significantly longer than that in 2019 (29.2 days ±11.1 vs 17.7 days ±8.2, P < 0.001). After examinations to rule out COVID-19, no COVID-19 was found in any patient. Conclusions: In the special period of novel coronavirus pneumonia outbreak, the treatment of patients with breast cancer was delayed, but the treatment was safe after strict exclusions of COVID-19.