Pulmonary stromal expansion and intra-alveolar coagulation are primary causes of Covid-19 death

Most Covid-19 victims are old and die from unrelated causes. Here we present twelve complete autopsies, including two rapid autopsies of young patients where the cause of death was Covid-19 ARDS. The main virus induced pathology was in the lung parenchyma and not in the airways. Most coagulation events occurred in the intra-alveolar and not in the intra-vascular space and the few thrombi were mainly composed of aggregated thrombocytes. The dominant inflammatory response was the massive accumulation of CD163+ macrophages and the disappearance of T killer, NK and B-cells. The virus was replicating in the pneumocytes and macrophages but not in bronchial epithelium, endothel, pericytes or stromal cells. The lung consolidations were produced by a massive regenerative response, stromal and epithelial proliferation and neovascularization. We suggest that thrombocyte aggregation inhibition, angiogenesis inhibition and general proliferation inhibition may have a roll in the treatment of advanced Covid-19 ARDS.

Efficacy and tolerability of bevacizumab in patients with severe Covid -19

On the basis of Covid-19-induced pulmonary pathological and vascular changes, we hypothesized that the anti-VEGF drug bevacizumab might be beneficial for treating Covid-19 patients. We recruited 26 patients from 2-centers (China and Italy) with confirmed severe Covid-19, with respiratory rate [≥] 30 times/min, oxygen saturation [≤] 93% with ambient air, or partial arterial oxygen pressure to fraction of inspiration O2 ratio (PaO2/FiO2) >100mmHg and [≤] 300 mmHg, and diffuse pneumonia confirmed by chest radiological imaging. This trial was conducted from Feb 15 to April 5, 2020, and followed up for 28 days. Relative to comparable control patients with severe Covid-19 admitted in the same centers, bevacizumab showed clinical efficacy by improving oxygenation and shortening oxygen-support duration. Among 26 hospitalized patients with severe Covid-19 (median age, 62 years, 20 [77%] males), bevacizumab plus standard care markedly improved the PaO2/FiO2 ratios at days 1 and 7 (elevated values, day 1, 50.5 [4.0,119.0], p<0.001; day 7, 111.0 [85.0,165.0], p<0.001). By day 28, 24 (92%) patients showed improvement in oxygen-support status, 17 (65%) patients were discharged, and none showed worsen oxygen-support status nor died. Significant reduction of lesion areas and ratios were shown in chest CT or X-ray analysis within 7 days. Of 14 patients with fever, body temperature normalized within 72 hours in 13 (93%) patients. Lymphocyte counts in peripheral blood were significantly increased and CRP levels were markedly decreased as shown in available data. Our findings suggested bevacizumab plus standard care was highly beneficial for treating patients with severe Covid-19. Clinical efficacy of bevacizumab warrants double blind, randomized, placebo-controlled trials. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04275414, URL: https://clinicaltrials.gov/ct2/show/NCT04275414.

A group of monoclonal antibodies reactive with the human thymocyte differentiation antigens-Production and specificity analysis / 中国免疫学杂志

In a fusion of BABL/C murine spleen cells immunizated with human fetal thymocytes and P_3X_(3)Ag_(,3), myeloma cells, six monoclonal antibodies(McAb) were produced. They were termed HIT_1. HIT_2. HIT_3. HIT_4.HIT_(6-1) and HIT_(6-2), respectively. The specificity of these McAbs were analysed by indirect immunofluorescence technique and FACS.Results showed that they reacted with 80～90%thymocytes,but hardly with peripheral blood mononuclear cells and spleen cells in adults,and nonreactive with red blood cells, granulocytes and platelets, According to their reaction with the tonsil cells, we can divide these six McAbs into three groups: Groupl including HIT_1, HIT_2, and HIT_(?) McAbs reacted approximately with 1/3 tonsil cells; basically GroupⅡ including HIT_(6-1) and HIT_(6-2) McAbs gave negative reaction with tonsil cells; GroupⅢ McAb HIT_4 reacted with 15% tonsil cells, which suggested these were a heterogeneous group McAbs with different specificities. In comparision with OKT series of McAbs in thymus, peripheral blood and tonsil, HIT_(1-3) are similar to OKT_(10) and,HTT6-l and HIT_(6-2) are just like OKT_6,but HIT_4 seems to be a new McAb different frOm HIT_(1-3) and HIT_(6-1) HII_(6-2). The competitive binding assay showed that HIT_(6-1) and HIT_(6-2) labeled with FITC can be inhibited by unlabeled HIT_(6-1) and HIT_(6-2) each other and can also be blocked by OKT_6, suggesting further these antibodies recognized a same epitope on thymocytes. Cross reaction were also demonstrated on HIT_1, and HIT_2 but not on HIT_3, suggesting HIT_1 and HIT_2 recognized the same determinant and HIT_3 recognized another. So six antibodies are McAbs against T cell differentiation antigens.They are useful for research the differentiation of T cells and the classification of malignant lymphadenosis diseases.