Severe covid-19 pneumonia: pathogenesis and clinical management

Attaway, Amy; Scheraga, Rachel G.; Bhimraj, Adarsh; Biehl, Michelle; Hatipoğlu, Umur

doi:10.1136/bmj.n436

Cited by 276 publications

(205 citation statements)

References 222 publications

(369 reference statements)

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“…Virus-specific treatment is also essential. Treatments targeting viral replication, which includes antiviral therapies like remdesivir, passive antibody therapies like monoclonal antibodies, and antibodies elicited from previous infection or vaccination (82)(83)(84), are effective in the disease process and could be more effective in the initial stage of the disease (85,86). In addition, given the complexity and heterogeneity of immune response among individuals, though it is conceptionally reasonable, it may be practically challenging to use the immune modulator without a clear picture of the basal level and response among individuals.…”

Section: Discussionmentioning

confidence: 99%

Cellular Immune Response to COVID-19 and Potential Immune Modulators

Zhou

2021

Front. Immunol.

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Coronavirus disease 2019 (COVID-19) is a respiratory infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Droplets and contacts serve as the main route of transmission of SARS-CoV-2. The characteristic of the disease is rather heterogeneous, ranging from no symptoms to critical illness. The factors associated with the outcome of COVID-19 have not been completely characterized to date. Inspired by previous studies on the relevance of infectious diseases, viral and host factors related to clinical outcomes have been identified. The severity of COVID-19 is mainly related to host factors, especially cellular immune responses in patients. Patients with mild COVID-19 and improved patients with severe COVID-19 exhibit a normal immune response to effectively eliminate the virus. The immune response in patients with fatal severe COVID-19 includes three stages: normal or hypofunction, hyperactivation, and anergy. Eventually, the patients were unable to resist viral infection and died. Based on our understanding of the kinetics of immune responses during COVID-19, we suggest that type I interferon (IFN) could be administered to patients with severe COVID-19 in the hypofunctional stage, intravenous immunoglobulin (IVIG) and glucocorticoid therapy could be administered in the immune hyperactivation stage. In addition, low molecular weight heparin (LMWH) anticoagulation therapy and anti-infective therapy with antibiotics are recommended in the hyperactivation stage.

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Section: Discussionmentioning

confidence: 99%

Cellular Immune Response to COVID-19 and Potential Immune Modulators

Zhou

2021

Front. Immunol.

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“…Three zoonotic coronaviruses (CoV) that belong to the genus Batacoronavirus within Coronaviridae have caused deadly pneumonia in humans since 2003: severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome (MERS) coronavirus, and SARS-CoV-2 [ 1 ]. The latter is associated with the ongoing global outbreak of COVID-19 pneumonia [ 2 , 3 ]. The pandemic caused by SARS-CoV-2 has inspired renewed interest in understanding the fundamental pathological changes observed in acute respiratory distress syndrome (ARDS) because fatal COVID-19 cases are most commonly linked to respiratory failure with the clinical and pathologic features of ARDS [ 4 , 5 ].…”

Section: Introductionmentioning

confidence: 99%

Cell-Type Apoptosis in Lung during SARS-CoV-2 Infection

et al. 2021

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The SARS-CoV-2 pandemic has inspired renewed interest in understanding the fundamental pathology of acute respiratory distress syndrome (ARDS) following infection. However, the pathogenesis of ARDS following SRAS-CoV-2 infection remains largely unknown. In the present study, we examined apoptosis in postmortem lung sections from COVID-19 patients and in lung tissues from a non-human primate model of SARS-CoV-2 infection, in a cell-type manner, including type 1 and 2 alveolar cells and vascular endothelial cells (ECs), macrophages, and T cells. Multiple-target immunofluorescence assays and Western blotting suggest both intrinsic and extrinsic apoptotic pathways are activated during SARS-CoV-2 infection. Furthermore, we observed that SARS-CoV-2 fails to induce apoptosis in human bronchial epithelial cells (i.e., BEAS2B cells) and primary human umbilical vein endothelial cells (HUVECs), which are refractory to SARS-CoV-2 infection. However, infection of co-cultured Vero cells and HUVECs or Vero cells and BEAS2B cells with SARS-CoV-2 induced apoptosis in both Vero cells and HUVECs/BEAS2B cells but did not alter the permissiveness of HUVECs or BEAS2B cells to the virus. Post-exposure treatment of the co-culture of Vero cells and HUVECs with a novel non-cyclic nucleotide small molecule EPAC1-specific activator reduced apoptosis in HUVECs. These findings may help to delineate a novel insight into the pathogenesis of ARDS following SARS-CoV-2 infection.

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“…Besides significant mortality benefit, tocilizumab was found with improved clinical outcome in severe COVID-19 pneumonia in several studies on different Ethnic groups worldwide 2 , 3 but, the use of this costly medicine in patients with severe COVID-19 becomes a huge treatment cost-burden specially for the people of low and middle-income countries. 5 Moreover, recent data suggest that inhibition of IL-6 is not the only way to down-regulate cytokine storm effectively in COVID-19, and there may be other potential pathways to substantially progress hyper-inflammatory responses in COVID-19 positive host body.…”

mentioning

confidence: 99%