COVID-19: The Potential Treatment of Pulmonary Fibrosis Associated with SARS-CoV-2 Infection

Lechowicz, Kacper; Drożdżal, Sylwester; Machaj, Filip; Rosik, Jakub; Szostak, Bartosz; Zegan-Barańska, Małgorzata; Biernawska, Jowita; Dąbrowski, Wojciech; Rotter, Iwona; Kotfis, Katarzyna

doi:10.3390/jcm9061917

Cited by 160 publications

(164 citation statements)

References 132 publications

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“…It is also an example of unprecedented cooperation of scientists from every country united to find a cure and vaccine against one single pathogen, but also searching for future solutions. Apart from finding efficacious treatments against COVID-19, it is necessary to accommodate the needs of patients suffering from the complications of COVID-19, including pulmonary fibrosis ( Lechowicz et al, 2020 ), central and peripheral neuropathies, delirium ( Kotfis et al, 2020a , b ), depression and many other complications. Further research towards in-depth understanding of the pathological mechanisms of SARS-CoV-2 in humans is necessary to develop novel therapeutic drugs for COVID-19.…”

Section: Concluding Remarks and Future Perspectivesmentioning

confidence: 99%

FDA approved drugs with pharmacotherapeutic potential for SARS-CoV-2 (COVID-19) therapy

Drożdżal

Rosik

Lechowicz

et al. 2020

Drug Resistance Updates

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138

131

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In December 2019, a novel SARS-CoV-2 coronavirus emerged, causing an outbreak of life-threatening pneumonia in the Hubei province, China, and has now spread worldwide, causing a pandemic. The urgent need to control the disease, combined with the lack of specific and effective treatment modalities, call for the use of FDA-approved agents that have shown efficacy against similar pathogens. Chloroquine, remdesivir, lopinavir/ritonavir or ribavirin have all been successful in inhibiting SARS-CoV-2 in vitro . The initial results of a number of clinical trials involving various protocols of administration of chloroquine or hydroxychloroquine mostly point towards their beneficial effect. However, they may not be effective in cases with persistently high viremia, while results on ivermectin (another antiparasitic agent) are not yet available. Interestingly, azithromycin, a macrolide antibiotic in combination with hydroxychloroquine, might yield clinical benefit as an adjunctive. The results of clinical trials point to the potential clinical efficacy of antivirals, especially remdesivir (GS-5734), lopinavir/ritonavir, and favipiravir. Other therapeutic options that are being explored involve meplazumab, tocilizumab, and interferon type 1. We discuss a number of other drugs that are currently in clinical trials, whose results are not yet available, and in various instances we enrich such efficacy analysis by invoking historic data on the treatment of SARS, MERS, influenza, or in vitro studies. Meanwhile, scientists worldwide are seeking to discover novel drugs that take advantage of the molecular structure of the virus, its intracellular life cycle that probably elucidates unfolded-protein response, as well as its mechanism of surface binding and cell invasion, like angiotensin converting enzymes-, HR1, and metalloproteinase inhibitors.

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Section: Concluding Remarks and Future Perspectivesmentioning

confidence: 99%

FDA approved drugs with pharmacotherapeutic potential for SARS-CoV-2 (COVID-19) therapy

Drożdżal

Rosik

Lechowicz

et al. 2020

Drug Resistance Updates

Self Cite

138

131

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“…Based on current knowledge, Covid-19 infection causes mild to moderate symptoms in the majority of patients. However, these early data also suggest that even if symptoms are just 'mild to moderate' during the acute infection, fibrotic lung damage develops in some, potentially leading to long-term complications for a subset of patients (Spagnolo et al, 2020;Leask, 2020;Lechowicz et al, 2020;George et al, 2020). It is well known that over-activated MCs play a crucial role in the development of fibrotic conditions.…”

Section: Introductionmentioning

confidence: 99%

Covid-19 hyperinflammation and post-Covid-19 illness may be rooted in mast cell activation syndrome

Afrin

Weinstock

Molderings

2020

International Journal of Infectious Diseases

264

206

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Objectives: One-fifth of Covid-19 patients suffer a severe course of Covid-19 infection; however, the specific causes remain unclear. Mast cells (MCs) are activated by SARS-CoV-2. Although only recently recognized, MC activation syndrome (MCAS), usually due to acquired MC clonality, is a chronic multisystem disorder with inflammatory and allergic themes, and an estimated prevalence of 17%. This paper describes a novel conjecture explaining how MCAS might cause a propensity for severe acute Covid-19 infection and chronic post-Covid-19 illnesses. Methods: Observations of Covid-19 illness in patients with/without MCAS were compared with extensive clinical experience with MCAS. Results: The prevalence of MCAS is similar to that of severe cases within the Covid-19-infected population. Much of Covid-19's hyperinflammation is concordant with manners of inflammation which MC activation can drive. Drugs with activity against MCs or their mediators have preliminarily been observed to be helpful in Covid-19 patients. None of the authors' treated MCAS patients with Covid-19 suffered severe infection, let alone mortality. Conclusions: Hyperinflammatory cytokine storms in many severely symptomatic Covid-19 patients may be rooted in an atypical response to SARS-CoV-2 by the dysfunctional MCs of MCAS rather than a normal response by normal MCs. If proven, this theory has significant therapeutic and prognostic implications.

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“…This has led to several proposals for consideration of antifibrotic therapies to prevent or to treat COVID -19 pneumonia. (19)(20)(21) One CT study showed imaging features of interstitial fibrosis such as interstitial thickening, air bronchograms, irregular interface, coarse reticular pattern and parenchymal bands in 44% of patients discharged after treatment for COVID-19. (17) The aim of this report is to document the evolution of DAD to the fibrosing pattern in a series of minimally invasive autopsies in thirty individuals who died from COVID-19 in Wuhan, China.…”

Section: Introductionmentioning

confidence: 99%

Progression to fibrosing diffuse alveolar damage in a series of 30 minimally invasive autopsies with COVID‐19 pneumonia in Wuhan, China

Wang

et al. 2020

Histopathology

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Aims: Coronavirus Disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection has been deemed as a global pandemic by World Health Organization. While diffuse alveolar damage (DAD) is recognized to be the primary manifestation COVID-19 pneumonia, there has been little emphasis on the progression to the fibrosing phase of DAD. This topic is of great interest due to growing concerns regarding the potential long-term complications in prolonged survivors. Methods: Here we report a detailed histopathologic study of thirty autopsy cases with COVID-19 virus infection, based on minimally invasive autopsies performed between February to March, 2020. Results: The mean age was 69 years, with twenty (67%) males and 10 (33%) females and frequent (70.0%) underlying comorbidities. The duration of illness ranged from 16 to 82 (median=42) days. Histologically, the most common manifestation was diffuse alveolar damage (DAD) in 28 (93.3%) cases which showed predominantly acute (32%), organizing (25%), and/or fibrosing (43%) patterns. Patients with fibrosing DAD were one decade younger (p=0.034) and they had a longer duration of illness (p=0.033), hospitalization (p=0.037) and mechanical ventilation (p=0.014) compared to those with acute DAD. Patients with organizing DAD had a longer duration of illness (p=0.032) and hospitalization (p=0.023) compared to those with acute DAD. Conclusions: COVID-19 pneumonia patients who develop DAD can progress to the fibrosing pattern. While we observed fibrosing DAD in fatal cases, whether surviving patients are at risk for developing pulmonary fibrosis and the frequency of this complication will require further clinical and radiologic follow-up studies.

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COVID-19: The Potential Treatment of Pulmonary Fibrosis Associated with SARS-CoV-2 Infection

Cited by 160 publications

References 132 publications

FDA approved drugs with pharmacotherapeutic potential for SARS-CoV-2 (COVID-19) therapy

FDA approved drugs with pharmacotherapeutic potential for SARS-CoV-2 (COVID-19) therapy

Covid-19 hyperinflammation and post-Covid-19 illness may be rooted in mast cell activation syndrome

Progression to fibrosing diffuse alveolar damage in a series of 30 minimally invasive autopsies with COVID‐19 pneumonia in Wuhan, China

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