Pulmonary Edema in COVID-19 Patients: Mechanisms and Treatment Potential

Cui, Xinyu; Chen, Wuyue; Zhou, Haoyan; Gong, Yubing; Zhu, Bowen; Lv, Xiang; Guo, Hongbo; Duan, Jin‐Ao; Zhou, Jing; Marcon, Edyta; Ma, Hongyue

doi:10.3389/fphar.2021.664349

Cited by 53 publications

(40 citation statements)

References 151 publications

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“…Furthermore, in the biomedical published literature, unfortunately, we did not find a similar approach for pulmonary edema in COVID-19. However, there are numerous reports of pulmonary edema [ 4 , 5 , 6 , 7 , 16 , 17 ] together with evidence of volume overload [ 26 , 27 , 28 , 29 ] in COVID-19. This evidence, added to the promising clinical response to NEGBAL, support this approach to pulmonary edema in COVID-19 as a biological plausibility.…”

Section: Discussionmentioning

confidence: 99%

“…The “first hit” of COVID-19 pneumonitis [ 49 ], followed by dysregulation RAAS [ 17 ] “second hit”, generating excess of intra- and extravascular fluid, causing volume overload [ 26 , 28 , 29 ] and pulmonary edema [ 4 , 5 , 6 , 7 ]. With unresolved edema, appeared a “third hit” characterized by infection, fibrosis, more inflammation, and ending in ARDS [ 47 , 50 ] (see Supplementary Materials: Figures S1–S6 ).…”

Section: Discussionmentioning

confidence: 99%

“…A posteriori, it ensues a dilatation of the superior vena cava, progressively, also the cardiac index [ 27 ] is added, and the cardiac axis is expanded, increasing the dilatation of the right ventricle [ 28 , 29 ]. This causes an increase of the hydrostatic pressure [ 25 , 30 ] and the consequent pulmonary edema [ 4 , 5 , 6 , 7 , 16 , 17 ]. Once the negative fluid balance approach was established, this harmful sequence was reverted.…”

Section: Discussionmentioning

confidence: 99%

“…In COVID-19, pulmonary edema is described [ 4 , 5 , 6 , 7 ]; however, the dominant paradigm is focused on cytokine storm [ 8 , 9 , 10 , 11 , 12 ] as responsible for lung injury and subsequent acute respiratory distress syndrome (ARDS) [ 5 , 13 ]. Not everyone agreed with this paradigm.…”

Section: Introductionmentioning

confidence: 99%

“…There are bibliographic mentions of pulmonary edema in COVID 19 [ 4 , 5 , 6 , 7 ], as well as evidence of volume overload in COVID-19: Lang et al describes frequent and pronounced vasculature in affected lung areas that may be suggestive of disordered vasoregulation [ 26 ]. Eslami et al observed increased cardiothoracic ratio [ 27 ] and it is also described as right ventricular dilatation [ 28 , 29 ].…”

Section: Introductionmentioning

confidence: 99%

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Pulmonary Edema in COVID-19 Treated with Furosemide and Negative Fluid Balance (NEGBAL): A Different and Promising Approach

Santos¹,

Zanardi²,

Alo³

et al. 2021

JCM

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In COVID-19, pulmonary edema has been attributed to “cytokine storm”. However, it is known that SARS-CoV2 promotes angiotensin-converting enzyme 2 deficit, increases angiotensin II, and this triggers volume overload. Our report is based on COVID-19 patients with tomographic evidence of pulmonary edema and volume overload to whom established a standard treatment with diuretic (furosemide) guided by objectives: Negative Fluid Balance (NEGBAL approach). Retrospective observational study. We reviewed data from medical records: demographic, clinical, laboratory, blood gas, and chest tomography (CT) before and while undergoing NEGBAL, from 20 critically ill patients. Once the NEGBAL strategy was started, no patient required mechanical ventilation. All cases reverted to respiratory failure with NEGBAL, but subsequently two patients died from sepsis and acute myocardial infarction (AMI). The regressive analysis between PaO2/FiO2BAL and NEGBAL demonstrated correlation (p < 0.032). The results comparing the Pao2Fio2 between admission to NEGBAL to NEGBAL day 4, were statistically significant (p < 0.001). We noted between admission to NEGBAL and day 4 improvement in CT score (p < 0.001), decrease in the superior vena cava diameter (p < 0.001) and the decrease of cardiac axis (p < 0.001). Though our study has several limitations, we believe the promising results encourage further investigation of this different pathophysiological approach.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Pulmonary Edema in COVID-19 Treated with Furosemide and Negative Fluid Balance (NEGBAL): A Different and Promising Approach

Santos¹,

Zanardi²,

Alo³

et al. 2021

JCM

View full text Add to dashboard Cite

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Heart failure during the COVID‐19 pandemic: clinical, diagnostic, management, and organizational dilemmas

et al. 2022

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The coronavirus 2019 (COVID-19) infection pandemic has affected the care of patients with heart failure (HF). Several consensus documents describe the appropriate diagnostic algorithm and treatment approach for patients with HF and associated COVID-19 infection. However, few questions about the mechanisms by which COVID can exacerbate HF in patients with high-risk (Stage B) or symptomatic HF (Stage C) remain unanswered. Therefore, the type of HF occurring during infection is poorly investigated. The diagnostic differentiation and management should be focused on the identification of the HF phenotype, underlying causes, and subsequent tailored therapy. In this framework, the relationship existing between COVID and onset of acute decompensated HF, isolated right HF, and cardiogenic shock is questioned, and the specific management is mainly based on local hospital organization rather than a standardized model. Similarly, some specific populations such as advanced HF, heart transplant, patients with left ventricular assist device (LVAD), or valve disease remain under investigated. In this systematic review, we examine recent advances regarding the relationships between HF and COVID-19 pandemic with respect to epidemiology, pathogenetic mechanisms, and differential diagnosis. Also, according to the recent HF guidelines definition, we highlight different clinical profile identification, pointing out the main concerns in understudied HF populations.

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Efficacy and Safety of Garadacimab in Combination with Standard of Care Treatment in Patients with Severe COVID-19

Papi

Stapleton

Shore

et al. 2023

Lung

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Background Garadacimab, a fully human IgG4 monoclonal antibody, inhibits the kallikrein–kinin pathway at a key initiator, activated coagulation factor XII (FXIIa), and may play a protective role in preventing the progression of COVID-19. This phase 2 study evaluated the efficacy and safety of garadacimab plus standard of care (SOC) versus placebo plus SOC in patients with severe COVID-19. Methods Patients hospitalised with COVID-19 were randomised (1:1) to a single intravenous dose of garadacimab (700 mg) plus SOC or placebo plus SOC. Co-primary endpoint was incidence of endotracheal intubation or death between randomisation and Day 28. All-cause mortality, safety and pharmacokinetic/pharmacodynamic parameters were assessed. Results No difference in incidence of tracheal intubation or death (p = 0.274) or all-cause mortality was observed (p = 0.382). Garadacimab was associated with a lower incidence of treatment-emergent adverse events (60.3% vs 67.8%) and fewer serious adverse events (34 vs 45 events) versus placebo. No garadacimab-related deaths or bleeding events were reported, including in the 45.9% (n = 28/61) of patients who received concomitant heparin. Prolonged activated partial thromboplastin time (aPTT), and increased coagulation factor XII (FXII) levels were observed with garadacimab versus placebo to Day 14, whilst FXIIa-mediated kallikrein activity (FXIIa-mKA) was suppressed to Day 28. Conclusion In patients with severe COVID-19, garadacimab did not confer a clinical benefit over placebo. Transient aPTT prolongation and suppressed FXIIa-mKA showed target engagement of garadacimab that was not associated with bleeding events even with concomitant anticoagulant use. The safety profile of garadacimab was consistent with previous studies in patients with hereditary angioedema. ClinicalTrials. gov Identifier NCT04409509. Date of registration: 28 May, 2020.

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Pulmonary Edema in COVID-19 Patients: Mechanisms and Treatment Potential

Cited by 53 publications

References 151 publications

Pulmonary Edema in COVID-19 Treated with Furosemide and Negative Fluid Balance (NEGBAL): A Different and Promising Approach

Pulmonary Edema in COVID-19 Treated with Furosemide and Negative Fluid Balance (NEGBAL): A Different and Promising Approach

Heart failure during the COVID‐19 pandemic: clinical, diagnostic, management, and organizational dilemmas

Efficacy and Safety of Garadacimab in Combination with Standard of Care Treatment in Patients with Severe COVID-19

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