Lung Injury In COVID-19 Research Articles

Necroptosis in alveolar epithelial cells drives lung inflammation and injury caused by SARS-CoV-2 infection

COVID-19, caused by SARS-CoV-2 infection, results in irreversible or fatal lung injury. We assumed that necroptosis of virus-infected alveolar epithelial cells (AEC) could promote local inflammation and further lung injury in COVID-19. Since CD8+ lymphocytes induced AEC cell death via cytotoxic molecules such as FAS ligands, we examined the involvement of FAS-mediated cell death in COVID-19 patients and murine COVID-19 model. We identified the occurrence of necroptosis and subsequent release of HMGB1 in the admitted patients with COVID-19. In the mouse model of COVID-19, lung inflammation and injury were attenuated in Fas-deficient mice compared to Fas-intact mice. The infection enhanced Type I interferon-inducible genes in both groups, while inflammasome-associated genes were specifically upregulated in Fas-intact mice. The treatment with necroptosis inhibitor, Nec1s, improved survival rate, lung injury, and systemic inflammation. SARS-CoV-2 induced necroptosis causes cytokine induction and lung damage, and its inhibition could be a novel therapeutic strategy for COVID-19.

An in-depth investigation of serum Krebs von den Lungen-6 and other biomarkers in COVID-19 severity and mortality.

Krebs von den Lungen-6 (KL-6) is a glycoprotein mainly expressed by type II pneumocytes and recently known as a lung injury biomarker. However, the number of studies is still limited, especially in Indonesian COVID-19 populations. Therefore, we aim to provide correlation, sensitivity, and specificity analyses of KL-6 and other biomarkers in Indonesian COVID-19 severity and mortality. We conducted a cross-sectional study involving adult COVID-19 patients at Universitas Airlangga Hospital, Surabaya, East Java, Indonesia, between March 26, 2021, and August 25, 2021. KL-6 and other biomarker levels were compared according to severity (severe versus non-severe) and mortality (non-survivor versus survivor). We also included the receiver operating characteristic analysis to define the optimal cut-off, sensitivity, and specificity of KL-6 to determine COVID-19 severity and mortality. We enrolled 78 COVID- 19 patients (23 non-survivors), including 39 non-severe and 39 severe patients. There was no significant difference in serum KL-6 levels, neither in severity nor mortality groups. KL-6 had the strongest positive correlations with ferritin in severe patients (r=0.313) and non-survivors (r=0.467). We observed that the best sensitivity was KL-6 combined with platelet-to- lymphocyte ratio (PLR) (0.818) in severe patients and with neutrophil-to-lymphocyte ratio (NLR)/PLR/ferritin/C-reactive protein (0.867) in non-survivors. In contrast, the best specificity was found when KL-6 was combined with NLR/D-dimer (0.750) in severe patients and with D-dimer (0.889) in non-survivors. Serum KL-6 is a useful auxiliary laboratory evaluation index for COVID-19 lung injury to depict its severity and mortality.

Nebulized Recombinant Tissue Plasminogen Activator (rt-PA) for Acute COVID-19-Induced Respiratory Failure: An Exploratory Proof-of-Concept Trial.

Acute lung injury in COVID-19 results in diffuse alveolar damage with disruption of the alveolar-capillary barrier, coagulation activation, alveolar fibrin deposition and pulmonary capillary thrombi. Nebulized recombinant tissue plasminogen activator (rt-PA) has the potential to facilitate localized thrombolysis in the alveolar compartment and improve oxygenation. In this proof-of-concept safety study, adults with COVID-19-induced respiratory failure and a <300 mmHg PaO2/FiO2 (P/F) ratio requiring invasive mechanical ventilation (IMV) or non-invasive respiratory support (NIRS) received nebulized rt-PA in two cohorts (C1 and C2), alongside standard of care, between 23 April-30 July 2020 and 21 January-19 February 2021, respectively. Matched historical controls (MHC; n = 18) were used in C1 to explore efficacy. Safety co-primary endpoints were treatment-related bleeds and <1.0-1.5 g/L fibrinogen reduction. A variable dosing strategy with clinical efficacy endpoint and minimal safety concerns was determined in C1 for use in C2; patients were stratified by ventilation type to receive 40-60 mg rt-PA daily for ≤14 days. Nine patients in C1 (IMV, 6/9; NIRS, 3/9) and 26 in C2 (IMV, 12/26; NIRS, 14/26) received nebulized rt-PA for a mean (SD) of 6.7 (4.6) and 9.1(4.6) days, respectively. Four bleeds (one severe, three mild) in three patients were considered treatment related. There were no significant fibrinogen reductions. Greater improvements in mean P/F ratio from baseline to study end were observed in C1 compared with MHC (C1; 154 to 299 vs. MHC; 154 to 212). In C2, there was no difference in the baseline P/F ratio of NIRS and IMV patients. However, a larger improvement in the P/F ratio occurred in NIRS patients (NIRS; 126 to 240 vs. IMV; 120 to 188) and fewer treatment days were required (NIRS; 7.86 vs. IMV; 10.5). Nebulized rt-PA appears to be well-tolerated, with a trend towards improved oxygenation, particularly in the NIRS group. Randomized clinical trials are required to demonstrate the clinical effect significance and magnitude.

Endothelial Permeability and the Angiopoietin/Tie2 System Following Mild and Severe COVID-19

Endotheliopathy plays a role in the development of acute kidney and lung injury in COVID-19, probably due to inflammation, endothelial permeability, vascular leakage and edema formation. This study examined alterations in the circulation of patients with mild and severe COVID-19 on in vitro endothelial permeability and its relation to the endothelial angiopoietin/Tie2 system, which is involved in the regulation of endothelial permeability. Plasma was obtained from COVID-19 patients admitted to the ward (n = 14) or ICU (n = 20) at admission and after 1 and 2 weeks and healthy controls (n = 5). Human kidney and lung endothelial cells were exposed to patient plasma and treated with recombinant angiopoietin-1. In vitro endothelial barrier function was assessed using electric cell-substrate impedance sensing. Circulating markers of the angiopoietin/Tie2 system, endothelial dysfunction and glycocalyx degradation were measured by ELISA. Plasma from COVID-19 patients reduced endothelial resistance compared to healthy controls, but COVID-19 plasma-induced drop in endothelial resistance did not differ between ward and ICU patients. Circulating angiopoietin-2, soluble Tie2 and soluble Tie1 levels increased over time in ICU patients, whereas levels remained stable in ward patients. The increase in angiopoietin-2 was able to predict 90-day mortality (AUC = 0.914, p < 0.001). Treatment with recombinant angiopoietin-1 did not restore COVID-19 plasma-induced hyperpermeability. In conclusion, these results suggest that indirect effects of the virus represented in the circulation of COVID-19 patients induced endothelial hyperpermeability irrespective of disease severity and changes in the endothelial angiopoietin/Tie2 system. Nonetheless, angiopoietin-2 might be of interest in the context of organ injury and patient outcome in COVID-19.

Podoplanin and CLEC-2 levels in patients with COVID-19

BackgroundPodoplanin (PDPN gene) and CLEC-2 are involved in inflammatory hemostasis and have also been related with the pathogenesis of thrombosis. Emerging evidence also suggests that podoplanin can exert protective effects in sepsis and acute lung injury. In the lungs, podoplanin is coexpressed with angiotensin-converting enzyme 2, which is the main entry receptor for SARS-CoV-2. ObjectivesTo explore the role of podoplanin and CLEC-2 in COVID-19. MethodsCirculating levels of podoplanin and CLEC-2 were measured in 30 consecutive patients with COVID-19 admitted due to hypoxia and in 30 age- and sex-matched healthy individuals. Podoplanin expression in lungs from patients who died of COVID-19 was obtained from 2 independent public databases of single-cell RNA sequencing, from which data from control lungs were also available. ResultsCirculating podoplanin levels were lower in patients with COVID-19, whereas no difference was observed in CLEC-2 levels. Podoplanin levels were significantly inversely correlated with markers of coagulation, fibrinolysis, and innate immunity. Single-cell RNA sequencing data confirmed that PDPN is coexpressed with angiotensin-converting enzyme 2 in pneumocytes and showed that PDPN expression is lower in this cell compartment in the lungs of patients with COVID-19. ConclusionCirculating levels of podoplanin are lower in patients with COVID-19, and the magnitude of this reduction is correlated with hemostasis activation. We also demonstrate the downregulation of PDPN at the transcription level in pneumocytes. Together, our exploratory study questions whether an acquired podoplanin deficiency could be involved in the pathogenesis of acute lung injury in COVID-19 and warrants additional studies to confirm and refine these findings.

Timing of Lung Transplant Referral in Patients with Severe COVID-19 Lung Injury Supported by ECMO.

Severe respiratory failure caused by COVID-19 often requires mechanical ventilation, including extracorporeal membrane oxygenation (ECMO). In rare cases, lung transplantation (LTx) may be considered as a last resort. However, uncertainties remain about patient selection and optimal timing for referral and listing. This retrospective study analyzed patients with severe COVID-19 who were supported by veno-venous ECMO and listed for LTx between July 2020 and June 2022. Out of the 20 patients in the study population, four who underwent LTx were excluded. The clinical characteristics of the remaining 16 patients were compared, including nine who recovered and seven who died while awaiting LTx. The median duration from hospitalization to listing was 85.5 days, and the median duration on the waitlist was 25.5 days. Younger age was significantly associated with a higher likelihood of recovery without LTx after a median of 59 days on ECMO, compared to those who died at a median of 99 days. In patients with severe COVID-19-induced lung damage supported by ECMO, referral to LTx should be delayed for 8-10 weeks after ECMO initiation, particularly for younger patients who have a higher probability of spontaneous recovery and may not require LTx.

Is Interstitial Macrophage Mainly Responsible for Lung Injury in SARS-CoV-2 Infection?

The course of the COVID-19 pandemic has led to high mortality rates worldwide, which justifies the development of various research studies aimed at elucidating the physiopathological mechanisms involved in the development of lung injury associated with this disease. The angiotensin-converting enzyme 2 (ACE2) receptor plays a leading role as the viral anchoring point necessary for viral replication to begin, so a thorough understanding of the regulatory mechanisms of this receptor is vital. Similarly, the distribution of ACE2 will justify the injury caused by SARS-CoV-2. Macrophages play a more significant role in lung injury since they allow the SARS-CoV-2 virus to reach tissues lacking ACE2 receptors and cause significant tissue damage. Therefore, all factors that influence macrophage migration and mobilization will be considered risk factors for the development of severe lung injury in COVID-19.

Association of Ang/Tie2 pathway mediators with endothelial barrier integrity and disease severity in COVID-19.

Endothelial barrier (EB) disruption contributes to acute lung injury in COVID-19, and levels of both VEGF-A and Ang-2, which are mediators of EB integrity, have been associated with COVID-19 severity. Here we explored the participation of additional mediators of barrier integrity in this process, as well as the potential of serum from COVID-19 patients to induce EB disruption in cell monolayers. In a cohort from a clinical trial consisting of thirty patients with COVID-19 that required hospital admission due to hypoxia we demonstrate that i) levels of soluble Tie2 were increase, and of soluble VE-cadherin were decreased when compared to healthy individuals; ii) sera from these patients induce barrier disruption in monolayers of endothelial cells; and iii) that the magnitude of this effect is proportional to disease severity and to circulating levels of VEGF-A and Ang-2. Our study confirms and extends previous findings on the pathogenesis of acute lung injury in COVID-19, reinforcing the concept that EB is a relevant component of this disease. Our results pave the way for future studies that can refine our understanding of the pathogenesis of acute lung injury in viral respiratory disorders, and contribute to the identification of new biomarkers and therapeutic targets for these conditions.

Lung Injury in COVID-19 Has Pulmonary Edema as an Important Component and Treatment with Furosemide and Negative Fluid Balance (NEGBAL) Decreases Mortality

The SARS-CoV2 promotes dysregulation of Renin-Angiotensin-Aldosterone. The result is excessive retention of water, producing a state of noxious hypervolemia. Consequently, in COVID-19 injury lung is pulmonary edema. Our report is a case-control study, retrospective. We included 116 patients with moderate-severe COVID-19 lung injury. A total of 58 patients received standard care (Control group). A total of 58 patients received a standard treatment with a more negative fluid balance (NEGBAL group), consisting of hydric restriction and diuretics. Analyzing the mortality of the population studied, it was observed that the NEGBAL group had lower mortality than the Control group, p = 0.001. Compared with Controls, the NEGBAL group had significantly fewer days of hospital stay (p < 0.001), fewer days of ICU stay (p < 0.001), and fewer days of IMV (p < 0.001). The regressive analysis between PaO2/FiO2BAL and NEGBAL demonstrated correlation (p = 0.04). Compared with Controls, the NEGBAL group showed significant progressive improvement in PaO2/FiO2 (p < 0.001), CT score (p < 0.001). The multivariate model, the vaccination variables, and linear trends resulted in p = 0.671 and quadratic trends p = 0.723, whilst the accumulated fluid balance is p < 0.001. Although the study has limitations, the promising results encourage more research on this different therapeutic approach, since in our research it decreases mortality.

An Overview of Lung Injury in Covid-19: Evaluating the Impact of Re-Exposure and Emerging Variants

The COVID-19 pandemic, induced by the SARS-CoV-2 virus, has had a profound global impact since its inception in late 2019, bringing forth unparalleled challenges in public health and medical research. A significant concern remains the potentially severe lung injuries induced by the virus, with complications ranging from acute respiratory distress syndrome (ARDS) to persistent symptoms in «Long COVID.» This comprehensive review aims to explore the intricacies of lung injuries resulting from COVID-19 and the implications and risks of re-exposure, especially amidst the evolving landscape of SARS-CoV-2 variants. Drawing from peer-reviewed articles, case studies, and meta-analyses published from December 2019 to September 2023, the review delineates the complex dynamics between pre-existing respiratory conditions and COVID-19 outcomes. The early phases of the infection are characterized by severe afflictions to the respiratory system, including pneumonia and ARDS. A substantial fraction of patients experience persistent symptoms known as «Long COVID,» where the lungs continue to show signs of inflammation and reduced functional capacity. The central facet of this exploration hinges on understanding the implications of re-exposure to the virus, with a keen focus on the potentially exacerbated impact on previously damaged lung tissues and the influence of vaccination in modulating clinical outcomes upon re-exposure. The immune responses showcase a rich tapestry of cellular engagements, from innate to adaptive immune responses. The discussion broadens to encompass the serious repercussions of newer variants, including Delta and Omicron, on re-exposure dynamics, underscoring the necessity for an adaptive healthcare approach responsive to variant-specific clinical manifestations. Furthermore, it explores the wide range of severe complications stemming from re-exposure, emphasizing the critical role of vaccination in potentially reducing the severity of pathophysiological outcomes. The review brings to the forefront the urgent need for continuous surveillance and adaptive healthcare strategies in light of the complexity introduced by evolving variants, encouraging further research in this pivotal area of study. It seeks to offer a deep insight into lung injuries and re-exposure risks, providing a rich resource for healthcare professionals and guiding future investigative efforts in this domain.

Assessing the Severity of COVID-19 Lung Injury in Rheumatic Diseases Versus the General Population Using Deep Learning-Derived Chest Radiograph Scores.

ObjectiveCOVID‐19 patients with rheumatic disease have a higher risk of mechanical ventilation than the general population. We assessed lung involvement using a validated deep learning algorithm that extracts a quantitative measure of radiographic lung disease severity.MethodsWe performed a comparative cohort study of rheumatic disease patients with COVID‐19 and ≥1chest radiograph within ±2 weeks of COVID‐19 diagnosis and matched comparators. We used unadjusted and adjusted (for age, Charlson Comorbidity Index, and interstitial lung disease) quantile regression to compare the maximum Pulmonary X‐Ray Severity (PXS) score at the 10th‐90th percentiles between groups. We evaluated the association of severe PXS score (>9) with mechanical ventilation and death using Cox regression.ResultsWe identified 70 patients with rheumatic disease and 463 general population comparators. Maximum PXS scores were similar in the rheumatic disease patients and comparators at the 10th‐60th percentiles but significantly higher among rheumatic disease patients at the 70th‐90th percentiles (90th percentile score of 10.2 vs. 9.2, adjusted p=0.03). Rheumatic disease patients were more likely to have a PXS score >9 (20% vs. 11%, p=0.02), indicating severe pulmonary disease. Rheumatic disease patients with PXS scores >9 vs. ≤9 had higher risk of mechanical ventilation (HR 24.1 [95% CI: 6.7, 86.9]) and death (HR 8.2 [95% CI: 0.7, 90.4]).ConclusionsRheumatic disease patients with COVID‐19 had more severe radiographic lung involvement than comparators. Higher PXS scores were associated with mechanical ventilation and will be important for future studies leveraging big data to assess COVID‐19 outcomes in rheumatic disease patients.This article is protected by copyright. All rights reserved.

Abrogation of neutrophil inflammatory pathways and potential reduction of neutrophil-related factors in COVID-19 by intravenous immunoglobulin.

Pathogenesis of lung injury in COVID-19 is not completely understood, leaving gaps in understanding how current treatments modulate the course of COVID-19. Neutrophil numbers and activation state in circulation have been found to correlate with COVID-19 severity, and neutrophil extracellular traps (NETs) have been found in the lung parenchyma of patients with acute respiratory distress syndrome (ARDS) in COVID-19. Targeting the pro-inflammatory functions of neutrophils may diminish lung injury in COVID-19 and ARDS. Neutrophils were isolated from peripheral blood of healthy donors, treated ex vivo with dexamethasone, tocilizumab and intravenous immunoglobulin (IVIG) and NET formation, oxidative burst, and phagocytosis were assessed. Plasma from critically ill COVID-19 patients before and after clinical treatment with IVIG and from healthy donors was assessed for neutrophil activation-related proteins. While dexamethasone and tocilizumab did not affect PMA- and nigericin-induced NET production ex vivo, IVIG induced a dose-dependent abrogation of NET production in both activation models. IVIG also reduced PMA-elicited reactive oxygen species production, but did not alter phagocytosis. COVID-19 patients were found to have elevated levels of cell-free DNA, neutrophil elastase and IL-8 as compared to healthy controls. Levels of both cell-free DNA and neutrophil elastase were lower 5 days after 4 days of daily treatment with IVIG. The lack of impact of dexamethasone or tocilizumab on these neutrophil functions suggests that these therapeutic agents may not act through suppression of neutrophil functions, indicating that the door might still be open for the addition of a neutrophil modulator to the COVID-19 therapeutic repertoire.

Lung Injury in COVID-19 and Pneumocystis Pneumonia. Similarities and Differences

In the regions with the high prevalence of HIV infection, it is necessary to perform differential diagnosis of lung injury caused by COVID-19 and pneumocystis pneumonia.The main complaints in COVID-19 and pneumocystis pneumonia are similar and include dyspnea, weakness, cough, fever, and ground glass radiographic syndrome. However, sputum production was more common in pneumocystis pneumonia. The most important differences were frequent anosmia in COVID-19 and its absence in pneumocystis pneumonia, frequent detection of oropharyngeal candidiasis in pneumocystis pneumonia which was not seen in COVID-19.Serum hepcidin concentration has a high diagnostic potential and indicates a greater likelihood of COVID-19 than pneumocystis pneumonia at values ≤ 768.044 pg/ml (ROC AUC 0.977; p &lt; 0.001).

Exploring antiviral and anti-inflammatory effects of thiol drugs in COVID-19.

The redox status of the cysteine-rich SARS-CoV-2 spike glycoprotein (SARS-2-S) is important for the binding of SARS-2-S to angiotensin-converting enzyme 2 (ACE2), suggesting that drugs with a functional thiol group ("thiol drugs") may cleave cystines to disrupt SARS-CoV-2 cell entry. In addition, neutrophil-induced oxidative stress is a mechanism of COVID-19 lung injury, and the antioxidant and anti-inflammatory properties of thiol drugs, especially cysteamine, may limit this injury. To first explore the antiviral effects of thiol drugs in COVID-19, we used an ACE-2 binding assay and cell entry assays utilizing reporter pseudoviruses and authentic SARS-CoV-2 viruses. We found that multiple thiol drugs inhibit SARS-2-S binding to ACE2 and virus infection. The most potent drugs were effective in the low millimolar range, and IC50 values followed the order of their cystine cleavage rates and lower thiol pKa values. To determine if thiol drugs have antiviral effects in vivo and to explore any anti-inflammatory effects of thiol drugs in COVID-19, we tested the effects of cysteamine delivered intraperitoneally to hamsters infected with SARS-CoV-2. Cysteamine did not decrease lung viral infection, but it significantly decreased lung neutrophilic inflammation and alveolar hemorrhage. We speculate that the concentration of cysteamine achieved in the lungs with intraperitoneal delivery was insufficient for antiviral effects but sufficient for anti-inflammatory effects. We conclude that thiol drugs decrease SARS-CoV-2 lung inflammation and injury, and we provide rationale for future studies to test if direct (aerosol) delivery of thiol drugs to the airways might also result in antiviral effects.

Vinpocetine is the forthcoming adjuvant agent in the management of COVID-19.

Vinpocetine (VPN) is an alkaloid derivative of vincamine inhibits phosphodiesterase type 1 that increase cyclic guanosine monophosphate and cyclic adenosine monophosphate. VPN have anti-inflammatory and antioxidant effects with suppression release of pro-inflammatory cytokines. Moreover, VPN mitigates oxidative stress (OS) and inflammatory reactions through inhibition of mitogen-activated protein kinase (MAPK) signaling pathway. Therefore, VPN may decrease hyper-inflammation-induced acute lung injury in COVID-19 through modulation of NF-κB pathway. Taken together, VPN has pulmonary and extra-pulmonary protective effects against COVID-19 through mitigation of OS and hyperinflammation. In conclusion, VPN has noteworthy anti-inflammatory and anti-oxidant effects through inhibition of NF-κB/MAPK signaling pathway so, it may reduce SARS-CoV-2-induced hyper inflammatory and OS.

Targeting mucin hypersecretion in COVID-19 therapy.

Targeting mucin hypersecretion in COVID-19 therapy.

ACE2 overexpressing mesenchymal stem cells alleviates COVID-19 lung injury by inhibiting pyroptosis

SummaryMesenchymal stem cells (MSCs) have shown some efficacy in the COVID-19 treatment. We proposed that exogenous supplementation of ACE2 via MSCs (ACE2-MSCs) might have better therapeutic effects. We constructed SARS-CoV-2 spike glycoprotein stably transfected AT-II and Beas-2B cells and used SARS-CoV-2 spike pseudovirus to infect hACE2 transgenic mice. The results showed that spike glycoprotein transfection triggers the release of apoptotic bodies and formation of membrane pores in pyroptosis. Inflammatory factors and pyroptosis factors were highly upregulated by spike glycoprotein transfection. SARS-CoV-2 spike pseudovirus worsened lung injury and increased the main factors of cytokine storm and pyroptosis. Compared to using MSCs or rh-ACE2 alone, the administration of ACE2-MSCs could significantly reduce these factors better and alleviate lung injury in vivo and in vitro, which might be because of the increased activities of secretory ACE2. Our proposal is a promising therapeutic solution for preclinical or clinical research.

TITAN: An end-to-end data analysis environment for the Hyperion™ imaging system.

Imaging Mass Cytometry (IMC) is a powerful high-throughput technique enabling resolution of up to 37 markers in a single fixed tissue section while also preserving in situ spatial relationships. Currently, IMC processing and analysis necessitates the use of multiple different software, labour-intensive pipeline development, different operating systems and knowledge of bioinformatics, all of which are a barrier to many potential users. Here we present TITAN - an open-source, single environment, end-to-end pipeline that can be utilized for image visualization, segmentation, analysis and export of IMC data. TITAN is implemented as an extension within the publicly available 3D Slicer software. We demonstrate the utility, application, reliability and comparability of TITAN using publicly available IMC data from recently-published breast cancer and COVID-19 lung injury studies. Compared with current IMC analysis methods, TITAN provides a user-friendly, efficient single environment to accurately visualize, segment, and analyze IMC data for all users.

Targeting chronic COVID-19 lung injury; Tofacitinib can be used against tissue-resident memory T cells

Post-Covid pulmonary fibrosis is evident following severe COVID-19. There is an urgent need to identify the cellular and pathophysiological characteristics of chronic lung squeals of Covid-19 for the development of future preventive and/or therapeutic interventions. Tissue-resident memory T (TRM) cells can mediate local immune protection against infections and cancer. Less beneficially, lung TRM cells cause chronic airway inflammation and fibrosis by stimulating pathologic inflammation. The effects of Janus kinase (JAK), an inducer pathway of cytokine storm, inhibition on acute Covid-19 cases have been previously evaluated. Here, we propose that Tofacitinib by targeting the CD8+ TRM cells could be a potential candidate for the treatment of chronic lung diseases induced by acute SARS-CoV-2 infection.

アンジオテンシン変換酵素2(ACE2)酵素活性によるCOVID-19急性肺傷害の治療効果

アンジオテンシン変換酵素2(ACE2)酵素活性によるCOVID-19急性肺傷害の治療効果