[Pulmonary fibrosis in patients with COVID-19: A review].

The viral infectious disease pandemic caused by SARS-CoV-2 has affected over 500 million people and killed over 6 million. This is the official data provided by the WHO as of the end of May 2022. Among people who have recovered from COVID-19, post-COVID syndrome is quite common. Scattered epidemiological studies on post-COVID syndrome, however, indicate its high relevance. One of the manifestations of post-COVID syndrome is the development of pulmonary fibrosis (PF). This article is devoted to the analysis of literature data on epidemiology, immunomorphology, as well as X-ray morphological and functional characteristics of PF in patients with post-COVID syndrome. Attention is drawn to the various phenotypes of the post-COVID syndrome and the incidence of PF, which, as clinical practice shows, is most common in people who have had severe COVID-19. This article discusses in detail the molecular biological and immunological mechanisms of PF development. The fibrotic process of the lung parenchyma is not an early manifestation of the disease; as a rule, radiomorphological signs of this pathological process develop after four weeks from the onset of acute manifestations of a viral infection. The characteristic signs of PF include those that indicate the process of remodulation of the lung tissue: volumetric decrease in the lungs, "cellular" degeneration of the lung parenchyma, bronchiectasis and traction bronchiolectasis. The process of remodulating the lung tissue, in the process of fibrosis, is accompanied by a violation of the lung function; a particularly sensitive test of functional disorders is a decrease in the diffusion capacity of the lung tissue. Therefore, in the process of monitoring patients with post-COVID syndrome, a dynamic study of the ventilation function of the lungs is recommended. The main clinical manifestation of PF is dyspnea that occurs with minimal exertion. Shortness of breath also reflects another important aspect of fibrous remodulation of the lung parenchyma - oxygen dissociation is disturbed, which reflects a violation of the gas exchange function of the lungs. There are no generally accepted treatments for PF in post-COVID syndrome. The literature considers such approaches as the possibility of prescribing antifibrotic therapy, hyaluronidase, and medical gases: thermal helium, nitric oxide, and atomic hydrogen. The article draws attention to the unresolved issues of post-covid PF in people who have had COVID-19.

Post-COVID-19 Pulmonary Fibrosis: Facts-Challenges and Futures: A Narrative Review.

Patients with coronavirus disease 2019 (COVID-19) usually suffer from post-acute sequelae of coronavirus disease 2019 (PASC). Pulmonary fibrosis (PF) has the most significant long-term impact on patients' respiratory health, called post-COVID-19 pulmonary fibrosis (PC19-PF). PC19- PF can be caused by acute respiratory distress syndrome (ARDS) or pneumonia due to COVID-19. The risk factors of PC19-PF, such as older age, chronic comorbidities, the use of mechanical ventilation during the acute phase, and female sex, should be considered. Individuals with COVID-19 pneumonia symptoms lasting at least 12 weeks following diagnosis, including cough, dyspnea, exertional dyspnea, and poor saturation, accounted for nearly all disease occurrences. PC19-PF is characterized by persistent fibrotic tomographic sequelae associated with functional impairment throughout follow-up. Thus, clinical examination, radiology, pulmonary function tests, and pathological findings should be done to diagnose PC19-PF patients. PFT indicated persistent limitations in diffusion capacity and restrictive physiology, despite the absence of previous testing and inconsistency in the timeliness of assessments following acute illness. It has been hypothesized that PC19-PF patients may benefit from idiopathic pulmonary fibrosis treatment to prevent continued infection-related disorders, enhance the healing phase, and manage fibroproliferative processes. Immunomodulatory agents might reduce inflammation and the length of mechanical ventilation during the acute phase of COVID-19 infection, and the risk of the PC19-PF stage. Pulmonary rehabilitation, incorporating exercise training, physical education, and behavioral modifications, can improve the physical and psychological conditions of patients with PC19-PF.

Liposomal Forms of Fluoroquinolones and Antifibrotics Decorated with Mannosylated Chitosan for Inhalation Drug Delivery.

The severe course of COVID-19 leads to the long-terming pulmonary diseases, such as bacterial pneumonia and post-COVID-19 pulmonary fibrosis. Thus, the essential task of biomedicine is a design of new effective drug formulations, including those for inhalation administration. In this work, we propose an approach to the creation of lipid-polymer delivery systems for fluoroquinolones and pirfenidone based on liposomes of various compositions decorated with mucoadhesive mannosylated chitosan. A generalizing study on the physicochemical patterns of the interactions of drugs with bilayers of various compositions was carried out, and the main binding sites were identified. The role of the polymer shell in the stabilization of vesicles and the delayed release of the contents has been demonstrated. For the liquid-polymer formulation of moxifloxacin, a prolonged accumulation of the drug in lung tissues was found after a single endotracheal administration to mice, significantly exceeding the control intravenous and endotracheal administration of the drug.

Humoral Response among patients with Interstitial Lung Disease Vaccinated with the BNT162b2 SARS-Cov-2 vaccine - a prospective cohort study

Background: Patients with interstitial lung disease (ILD) are at high risk of severe COVID-19 infection. Method(s): We conducted an observational prospective cohort study to evaluate the rate of anti-spike (S-IgG) antibodies after two doses of the BNT162b2 vaccine in patients with ILD. The cohort included 40 patients with idiopathic pulmonary fibrosis (IPF) treated with anti-fibrotic therapy and 29 patients with non-IPF ILD treated with anti-inflammatory therapy. An age and sex matched control groups was created from a healthy control cohort of 107 patients. Result(s): All patients in the anti-fibrotic arm were seropositive (40/40), corresponding to the matched control group (P=1.0). The antifibrotic arm had a significantly lower median antibody titer in comparison to the matched control group (361.10 [ IQR, 207-811] AU/ml vs 820.75 [IQR, 459-1313] AU/ml;P<0.001). Only 48.3% (14/29) of patients in the anti-inflammatory arm were seropositive in comparison to 100% (29/29) in the healthy control group (P<0.001). The anti-inflammatory arm had a significantly lower median antibody titer in comparison to the healthy control group (39.6 [ IQR, 4.25-165] AU/ml vs 970.1 [IQR, 505-1926] AU/ml;P<0.001). Conclusion(s): IPF patients treated with antifibrotic therapy mount an adequate immune response after 2 doses of the BNT162b2 vaccine, maintain a 100% seropositivity rate, 4-6 months after vaccination. Among patients with non-IPF ILD, treated with anti-inflammatory therapy, 48% were seronegative 4-6 months after the second vaccine dose.

Anti-fibrotic agents could be the game-changer for post-COVID-19 pulmonary fibrosis treatment

More than 220 countries and territories are globally affected by the recent pandemic COVID-19 which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). There is possibility of third wave of this pandemic as per epidemiological and public health experts. Besides that post-COVID-19 complications are alarming matter to look upon. Post-COVID-19 complications include several symptoms like as persistent fever;cough;fatigue;headache;attention disorder;dyspnea;anosmia;ageusia;chest pain discomfort;various respiratory illness;acute respiratory distress syndrome (ARDS) etc., and here the things to worry about is the development of pulmonary fibrosis after COVID-19. In some COVID-19 patients, hyper-inflammation in the form of 'cytokine storm' along with dysregulated immune response, alveolar epithelial tissue injury and wound repair collectively cause this secondary pulmonary fibrosis. Therefore, using anti-fibrotic agents e.g. pirfenidone, nintedanib and other natural compounds could be meaningful in these circumstances although their efficacy in treating COVID-19 is subject to more detailed laboratory research works. In this review article, we have discussed the progression of pulmonary fibrosis development which is triggered by COVID-19;probable solutions with anti-fibrotic agents including anti-fibrotic drugs, some well-known natural compounds, combined anti-fibrotic therapies;and the current challenges of this field.

GALACTIC-1: Galectin-3 inhibition in idiopathic pulmonary fibrosis (IPF) - rationale, objectives and design of a 52-week, Phase IIb study of GB0139

Availability of well-tolerated novel agents that can slow or stop disease progression and improve quality of life remain an unmet medical need in IPF management. GB0139, a novel inhaled galectin-3 inhibitor, has shown good tolerability and antifibrotic potential via changes in biomarkers associated with IPF progression in an animal model (Delaine, T. et al. Chembiochem 2016;17:1759-70) and a Phase I study (Hirani, N. et al. Eur Respir J 2021;57(5):2002559) in healthy participants and IPF patients. We report the design of a Phase IIb study of GB0139 in IPF. This randomised, double-blind, placebo-controlled, parallel-group, multicentre study (NCT03832946) was initiated in April 2019. The primary endpoint is rate of decline in forced vital capacity (FVC) over 52 weeks. Key secondary endpoints are proportion of participants with an absolute decline from baseline in FVC % predicted of <=10%, change from baseline in St. George's Respiratory Questionnaire total score, time to first respiratory-related hospitalisation, and time to death (all-causes). Systemic GB0139 pharmacokinetics are included as an exploratory endpoint. Despite the COVID-19 pandemic, study recruitment has continued in ~100 centres across 15 countries, with over 400 participants randomised as of February 2022. Initially, participants treated with or without standard of care (SOC) were included. Following a protocol amendment in 2021, the current target is to randomise 141 participants who are not treated with SOC, with study completion in mid-2023.

European Respiratory Society - 32nd International Congress

The 32nd European Respiratory Society (ERS) International Congress was held again in person at the FIRA Barcelona Gran Via Conference Center in Spain, as well as online. On-site attendance was limited to 10,000 delegates, with the spaces selling out before the conference began. The program included live streamed presentations, thematic poster discussion sessions, oral presentations, mini-symposia, industry exhibitors and skills workshops to discuss major respiratory fields that included thoracic oncology, respiratory infections, interstitial lung diseases, respiratory critical care, sleep and breathing disorders and pulmonary vascular diseases. This report will cover some of the most interesting presentations related to respiratory disease treatment. Copyright © 2022 Clarivate.

A Study on drug utilization pattern of antifibrotic agents in patients with post-COVID-19 lung fibrosis

Pulmonary fibrosis after COVID-19 is a serious consequence that can result in lifelong lung damage or death. A cytokine storm induced by an abnormal immune mechanism may cause the onset and progression of pulmonary fibrosis. Early detection may assist to avoid or at least slow the progression of the disease. Anti-fibrotic agents are widely used drugs in post-COVID-19 pulmonary fibrosis. There are some well-known clinical agents including Pirfenidone and Nintedanib that can be given to COVID-19 patients to prevent further progression of fibrosis and as prophylaxis as well. This study showed the use of antifibrotic therapy in SARS-CoV-2 infection, which is very officious in minimizing and avoiding fibrotic damage induced by inflammatory immune dysfunction. Evidently, pirfenidone has shown its pleiotropic effectivity to decrease the inflammation and oxidative reactive shock associated with fibrosis. Nintedanib binds to the targeted receptors' intracellular ATP pockets, inhibiting pro-fibrotic signaling and reducing fibroblast proliferation, migration, and differentiation, as well as secretion of extracellular matrix components. Copyright © 2023, Anka Publishers. All rights reserved.

Effect of spironolactone therapy on the activity of the matrix metalloproteinase system in patients with heart failure after COVID-19

Aim. To assess the change in the activity of the matrix metalloproteinase (MMP) system after 6-month spironolactone therapy in patients with heart failure (HF) with preserved (HFpEF) and mildly reduced ejection fraction (HFmrEF) after coronavirus disease 2019 (COVID-19). Material and methods. The study included 90 patients treated at the University Clinical Hospital 4 of the I. M. Sechenov First Moscow State Medical University with a laboratory-confirmed COVID-19. There were following inclusion criteria: age of 18-85 years;the presence of HFpEF and HFmrEF. The patients were randomized into two groups: group I (n=60) - patients with 6-month spironolactone therapy (25 mg/day) in addition to the standard therapy for HF, spironolactone was taken at a dose of 25 mg/day;Group II (comparison group, n=30) - patients who received standard therapy without spironolactone. All patients were determined plasma MMP concentrations. Results. There were no significant differences in the levels of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) between the groups when included in the study. A repeated investigation revealed a significant decrease in the concentrations of MMP-9 and TIMP-1 only in group I. In patients of group II, there were no significant changes in the plasma concentrations of MMP-9 and TIMP-1. The MMP-9/TIMP-1 ratio during the initial examination of patients did not have significant differences. After 6-months therapy, a significant decrease in the ratio of MMP-9/TIMP-1 was observed only in patients taking spironolactone. Conclusion. The results obtained confirm a significant decrease in MMP system activity after 6-month spironolactone therapy in patients with HFpEF and HFmrEF after COVID-19. The described antifibrotic effects of spironolactone make it possible to recommend the use of this drug in this category of patients to reduce the negative effect of MMPs on cardiovascular system. Copyright © 2022 Vserossiiskoe Obshchestvo Kardiologov. All rights reserved.

COVID-19 and the lung: from interstitial pneumonia to pulmonary fibrosis

The novel coronavirus-induced disease led to a pandemic that poses a global threat to human health. The most common cause of hospitalisation for COVID-19 is interstitial pneumonia that may be complicated by Acute Respiratory Distress Syndrome (ARDS). The monitoring of patients who have recovered from COVID-associated pneumonia demonstrates that the significant reduction in diffuse lung capacity and associated fibrotic signs in the lung parenchyma are factors associated with a negative prognosis. Thus, the long-term consequences of COVID-19 appear crucial. Risk factors, histopathological characterization, prevalence, and management of post-COVID-19 pulmonary fibrosis are poorly understood. This review addresses underlying pathobiological mechanisms and the possible predictors which might lead to the development of fibrotic lung remodeling. Potential therapeutic modalities include anti-fibrotic drugs, prolonged use of corticosteroids, other anti-inflammatory and immunosuppressive drugs, spironolactone, azithromycine, with further multiple novel compounds under investigation. Copyright © 2022, SOLEN s.r.o.. All rights reserved.

Endogenous reparative pluripotent Muse cells with a unique immune privilege system: Hint at a new strategy for controlling acute and chronic inflammation.

Multilineage-differentiating stress enduring (Muse) cells, non-tumorigenic endogenous pluripotent stem cells, reside in the bone marrow (BM), peripheral blood, and connective tissue as pluripotent surface marker SSEA-3(+) cells. They express other pluripotent markers, including Nanog, Oct3/4, and Sox2 at moderate levels, differentiate into triploblastic lineages, self-renew at a single cell level, and exhibit anti-inflammatory effects. Cultured mesenchymal stromal cells (MSCs) and fibroblasts contain several percent of SSEA-3(+)-Muse cells. Circulating Muse cells, either endogenous or administered exogenously, selectively accumulate at the damaged site by sensing sphingosine-1-phosphate (S1P), a key mediator of inflammation, produced by damaged cells and replace apoptotic and damaged cells by spontaneously differentiating into multiple cells types that comprise the tissue and repair the tissue. Thus, intravenous injection is the main route for Muse cell treatment, and surgical operation is not necessary. Furthermore, gene introduction or cytokine induction are not required for generating pluripotent or differentiated states prior to treatment. Notably, allogenic and xenogenic Muse cells escape host immune rejection after intravenous injection and survive in the tissue as functioning cells over 6 and ∼2 months, respectively, without immunosuppressant treatment. Since Muse cells survive in the host tissue for extended periods of time, therefore their anti-inflammatory, anti-fibrotic, and trophic effects are long-lasting. These unique characteristics have led to the administration of Muse cells via intravenous drip in clinical trials for stroke, acute myocardial infarction, epidermolysis bullosa, spinal cord injury, neonatal hypoxic ischemic encephalopathy, amyotrophic lateral sclerosis, and COVID-19 acute respiratory distress syndrome without HLA-matching or immunosuppressive treatment.

Advances in colchicine treatment.

Colchicine has been used for centuries for the treatment of gout. Its mechanism of action is complex, but mainly it has anti-inflammatory and antifibrotic effects that make it potentially effective on multiple processes. In this review we update on its clinical utility, emphasizing its new indications in the cardiovascular field (pericarditis and ischemic heart disease) and its possible role for the treatment of COVID-19. Copyright © 2021 Publicaciones Permanyer. All rights reserved.

Post-COVID lung disease(s).

Post-COVID lung impairment and diseases are major public health concern in the pandemic of COVID-19. Multiple etiological factors can lead to post-COVID respiratory symptoms, with post COVID fibrosis or diffuse parenchymal lung disease being the major concern. We searched PubMed database for English literature related to post-COVID lung disease and we summarized the existing evidence on radiological, physiological, and histopathological aspects of post-COVID lung diseases. We suggest a guidance on the evaluation of these patients and highlight management considerations including general care, pulmonary rehabilitation, and lung transplantation. We also explain gaps in knowledge and awaited ongoing research results, especially in the field of drug therapies including corticosteroids and antifibrotics.

Pirfenidone and post-Covid-19 pulmonary fibrosis: invoked again for realistic goals.

Pirfenidone (PFN) is an anti-fibrotic drug with significant anti-inflammatory property used for treatment of fibrotic conditions such as idiopathic pulmonary fibrosis (IPF). In the coronavirus disease 2019 (Covid-19) era, severe acute respiratory syndrome 2 (SARS-CoV-2) could initially lead to acute lung injury (ALI) and in severe cases may cause acute respiratory distress syndrome (ARDS) which is usually resolved with normal lung function. However, some cases of ALI and ARDS are progressed to the more severe critical stage of pulmonary fibrosis commonly named post-Covid-19 pulmonary fibrosis which needs an urgent address and proper management. Therefore, the objective of the present study was to highlight the potential role of PFN in the management of post-Covid-19 pulmonary fibrosis. The precise mechanism of post-Covid-19 pulmonary fibrosis is related to the activation of transforming growth factor beta (TGF-ß1), which activates the release of extracellular proteins, fibroblast proliferation, fibroblast migration and myofibroblast conversion. PFN inhibits accumulation and recruitment of inflammatory cells, fibroblast proliferation, deposition of extracellular matrix in response to TGFß1 and other pro-inflammatory cytokines. In addition, PFN suppresses furin (TGFß1 convertase activator) a protein effector involved in the entry of SARS-CoV-2 and activation of TGFß1, and thus PFN reduces the pathogenesis of SARS-CoV-2. Besides, PFN modulates signaling pathways such as Wingless/Int (Wnt/ß-catenin), Yes-Associated Protein (YAP)/Transcription Co-Activator PDZ Binding Motif (TAZ) and Hippo Signaling Pathways that are involved in the pathogenesis of post-Covid-19 pulmonary fibrosis. In conclusion, the anti-inflammatory and anti-fibrotic properties of PFN may attenuate post-Covid-19 pulmonary fibrosis.

COVID-19 and fibrosis: Mechanisms, clinical relevance, and future perspectives.

Coronavirus 2019 (COVID-19), caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) has had significant impacts worldwide since its emergence in December, 2019. Despite a high recovery rate, there is a growing concern over its residual, long-term effects. However, because of a lack of long-term data, we are still far from establishing a consensus on post-COVID-19 complications. The deposition of excessive extracellular matrix (ECM), known as fibrosis, has been observed in numerous survivors of COVID-19. Given the exceptionally high number of individuals affected, there is an urgent need to address the emergence of fibrosis post-COVID-19. In this review, we discuss the clinical relevance of COVID-19-associated fibrosis, the current status of antifibrotic agents, novel antifibrotic targets, and challenges to its management.

Temporal changes in patient-reported outcome measures stratified by liver fibrosis severity in large-duct primary sclerosing cholangitis

Background and aims: Patient-reported outcome measures (PROMs) are increasingly used as exploratory end points in clinical trials. The aim of this studywas to evaluate the temporal relationship between health-related quality of life (HrQoL) and liver fibrosis using generic (SF-36) and disease-specific (PSC-PRO) tools. Method: Patients with large-duct PSC were invited to complete HrQoL questionnaires in an outpatient setting at baseline (V1) and follow-up (V2) visits at least 12 months apart. Transient elastography liver stiffness (LS;Echosens, France) measurementswere recorded on the same day. SF-36 and PSC-PRO health domains were scored out of a maximum of 100% and 5, respectively. Mean scores were calculated for each domain with lower SF-36 and higher PSC-PRO scores representing poorer quality of life. Advanced fibrosis (F3-6) was defined based on published cutoff of LS >9.6kPa in PSC. Results: Fifty-five patients (64% male) with median age 45 years (range: 20–77) and median PSC duration 11 years (range: 2–26) attended both study visits. The median time between visits was 417 days (range: 362–582). The mean scores were numerically lower at V2 than V1 in all the SF-36 domains but only three domains showed statistically significant difference: bodily pain (74% vs 83%, p < 0.01), energy/fatigue (47% vs 57%, p < 0.0001), and mental summary score (66% vs 71%, p < 0.001). There were no differences in any of the PSCPRO domains between the visits. When stratified by baseline LS >9.6 kPa threshold (Figure 1), SF-36 physical functioning mean score dropped in the F3-6 group but increased slightly in the F0-2 group (−9.0 ± 17% vs 0.4 ± 21%, p = 0.01). In the PSC-PRO, the emotional impact mean score increased in the F3-6 group but decreased in the F0-2 group (0.6 ± 0.7 vs −0.1 ± 0.5, p < 0.01). Therewere no significant differences in mean scores in the other domains between the visits.(Figure Presented)Conclusion: Therewasworsening of bodily pain, levels of energy and mental health even within a year in patients with large-duct PSC. Patients with advanced fibrosis reported lower physical functioning and higher emotional impact of their disease compared to those without advanced fibrosis. Changes in PROMs are related to liver fibrosis and need to be considered in future antifibrotic drug trials. These findings, however, need to be interpreted in the context of imposed restrictions during the Covid-19 pandemic which may have had a significant psycho-social impact on patients.

Rationale for evaluation of PLN-74809 treatment in participants with primary sclerosing cholangitis in Phase 2a study INTEGRIS-PSC

Background and aims: Transforming growth factor beta (TGF-beta) signalling is a key driver of liver fibrosis. In primary sclerosing cholangitis (PSC), integrins over-expressed on injured cholangiocytes (alpha-v/beta-6) and myofibroblasts (alpha-v/beta-1) regulate TGFbeta activity. PLN-74809 is an oral, once-daily, dual-selective inhibitor of integrins alpha-v/beta-6 and alpha-v/beta-1 in development for the treatment of PSC and idiopathic pulmonary fibrosis. It has shown favourable tolerability in over 280 healthy participants, reduced TGF-beta signalling and achieved high target engagement in human lungs. Pre-clinical evaluation of antifibrotic activity resulting from dual integrin inhibition was performed to support clinical evaluation. Method: PLN-74809 was administered orally for 6 weeks in BALBc. Mdr2-/- mice with established fibrosis. A tool alpha-v/beta-6 and alpha-v/beta-1 inhibitor compound, PLN-75068, was tested therapeutically in a diet-induced mouse model of biliary fibrosis using 3, 5-diethoxycarbonyl-1, 4-dihydrocollidine (DDC). Hepatic collagen was quantified by hydroxyproline (OHP) and collagen proportionate area (CPA) and TGF-beta signalling by phosphorylated SMAD3 (pSMAD3) levels. An ex vivo study evaluated the effects of 2-day treatment with PLN-74809 on the expression of profibrotic genes, COL1A1 and COL1A2, in precision-cut liver slices (PCLivS) from tissue explants of participants with biliary fibrosis (n = 2 PSC;n = 2 primary biliary cholangitis [PBC]). A review of available blinded safety data from the enrolling Phase 2a study in participants with PSC was performed (NCT04480840). Results: PLN-74809 dose-dependently reduced OHP (up to ∼30%, p < 0.05), CPA (up to ∼50%, p < 0.05) and pSMAD3 (up to ∼40%, p < 0.001) in the BALBc.Mdr2-/- mouse model, as well as COL1A1 and COL1A2 gene expression (up to ∼30%, p = 0.0789) in PCLivS from tissue explants of participants with PSC and PBC. PLN-75068 reduced OHP (up to ∼20%, p < 0.05) in DDC-injured mice in a dose-dependent manner. PLN-74809waswell tolerated in participants with PSC. Most adverse events (AEs)were mild;nonewere severe. The most common AE was mild headache. One participant experienced serious AEs at least 20 days after the last dose of study drug, deemed not related by the investigator. One participant prematurely discontinued due to COVID-19. PLN-74809 pharmacokinetics in participants with PSC were consistent with those of healthy participants. Conclusion: Pharmacological inhibition of integrins alpha-v/beta-6 and alpha-v/beta-1 demonstrated antifibrotic activity in two models of biliary fibrosis and in PCLivS from participants with PSC or PBC. Available safety findings from participants with PSC enrolled in the ongoing Phase 2a INTEGRIS-PSC study, continue to support the favourable tolerability profile of PLN-74809.

Understanding Pulmonary Fibrosis and Other Postacute Sequelae of COVID-19

Current research efforts to combat the COVID-19 virus are geared toward developing therapies to treat the infection and prevent the COVID-19 virus. Moreover, health experts are learning more each day about the long-term health consequences associated with post-COVID-19 infection, including patient populations at greater risk for these complications. The CDC indicates that post-COVID-19 infection, the most common persistent symptoms reported by patients may include fatigue, cough, dyspnea, chest tightness, trouble concentrating, arthralgia, olfactory dysfunction, and headache. While most people recover from the virus, some patients, particularly those with severe infection and chronic comorbidities, may be at risk for and/or develop pulmonary fibrosis. To date, there is no definitive therapy for managing post-COVID-19 pulmonary fibrosis, but clinical trials are underway to explore the role of antifibrotic therapies.

POST-COVID-19 PULMONARY FIBROSIS – IN SEARCHING OF ANSWERS IN FOLLOW-UP AND TREATMENT

In last 2 years the infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) resulted in infection of million people around the world. Because of the lack of definitive treatment, it is reported a huge risk of mortality. The post-Covid interstitial lung fibrosis is one of the most severe consequences of associated with COVID-19 pneumonia. The persistent respiratory complications may cause substantial population morbidity, long term disability, deterioration of quality of life and even death.

Antifibrotic Risk of Bleeding with Anticoagulation -A Case Report

Introduction: Antifibrotic drugs, including nintedanib and pirfenidone, are approved for the treatment of idiopathic pulmonary fibrosis (IPF). Pirfenidone blocks the synthesis of TGF-beta and does appear to increase the risk of CV or bleeding events. Nintedanib is a Vascular Endothelial Growth Factor Receptors (VEGFR) inhibitor and may increase the risk of bleeding. Bleeding events were reported in 10% of patients in clinical trials (despite excluding patients at risk of bleeding including those on con-current anticoagulation (AC) or antiplatelet (AP) therapy. Consequently, nintedanib is relatively contraindicated for patients with IPF on anticoagulation or antiplatelet therapy. However, results from real-life data demonstrate that 17.8% of our patients with IPF are on anticoagulation or antiplatelet therapy. The overall incident of bleeding events in those patients taking either or with nintedanib is similar to that reported for Nintedanib alone. We describe two patients with antifibrotic and anticoagulation therapy to highlight how to manage these patients. Case 1. A 67-year-old female with history of acute pulmonary embolism secondary to COVID-19 on anticoagulation therapy presents for workup of acute respiratory distress syndrome or suspected exacerbation of underlying IPF-usual interstitial pneumonia. Patient treated as IPF with pirfenidione. Case 2. A 69-year-old man with a history of atrial fibrillation on anticoagulation therapy presents for follow-up of progressive fibrosing interstitial lung disease secondary to hypersensitivity pneumonitis. Nintedanib initiated for progressive fibrosing lung disease. Discussion: Concomitant use of anticoagulation and/or antiplatelet therapy with antifibrotics doesn't increase bleeding risk. Conclusion. Anticoagulation and/or antiplatelet therapy should not be a reason to withhold antifibrotic therapy in patients with IPF.