[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.

Risk of Pulmonary Fibrosis and Persistent Symptoms Post-COVID-19 in a Cohort of Outpatient Health Workers.

BACKGROUND: Infection by SARS-CoV-2 has been associated with multiple symptoms; however, still, little is known about persistent symptoms and their probable association with the risk of developing pulmonary fibrosis in patients post-COVID-19. METHODS: A longitudinal prospective study on health workers infected by SARS-CoV-2 was conducted. In this work, signs and symptoms were recorded of 149 health workers with a positive PCR test for SARS-CoV-2 at the beginning of the diagnosis, during the active infection, and during post-COVID-19 follow-up. The McNemar chi-square test was used to compare the proportions and percentages of symptoms between the baseline and each follow-up period. RESULTS: The signs and symptoms after follow-up were cardiorespiratory, neurological, and inflammatory. Gastrointestinal symptoms were unusual at the disease onset, but unexpectedly, their frequency was higher in the post-infection stage. The multivariate analysis showed that pneumonia (HR 2.4, IC95%: 1.5-3.8, p < 0.001) and positive PCR tests still after four weeks (HR 5.3, IC95%: 2.3-12.3, p < 0.001) were factors associated with the diagnosis of post-COVID-19 pulmonary fibrosis in this study group. CONCLUSIONS: Our results showed that pneumonia and virus infection persistence were risk factors for developing pulmonary fibrosis post-COVID-19, after months of initial infection.

Recovering from a pandemic: pulmonary fibrosis after SARS-CoV-2 infection.

Acute manifestations of SARS-CoV-2 infection continue to impact the lives of many across the world. Post-acute sequelae of coronavirus disease 2019 (COVID-19) may affect 10-30% of survivors of COVID-19, and post-acute sequelae of COVID-19 (PASC)-pulmonary fibrosis is a long-term outcome associated with major morbidity. Data from prior coronavirus outbreaks (severe acute respiratory syndrome and Middle East respiratory syndrome) suggest that pulmonary fibrosis will contribute to long-term respiratory morbidity, suggesting that PASC-pulmonary fibrosis should be thoroughly screened for through pulmonary function testing and cross-sectional imaging. As data accumulates on the unique pathobiologic mechanisms underlying critical COVID-19, a focus on corollaries to the subacute and chronic profibrotic phenotype must be sought as well. Key aspects of acute COVID-19 pathobiology that may account for increased rates of pulmonary fibrosis include monocyte/macrophage-T-cell circuits, profibrotic RNA transcriptomics, protracted elevated levels of inflammatory cytokines, and duration of illness and ventilation. Mechanistic understanding of PASC-pulmonary fibrosis will be central in determining therapeutic options and will ultimately play a role in transplant considerations. Well-designed cohort studies and prospective clinical registries are needed. Clinicians, researchers and healthcare systems must actively address this complication of PASC to minimise disability, maximise quality of life and confront a post-COVID-19 global health crisis.

Increasing incidence of lung transplantation in patients with post-COVID-19 pulmonary fibrosis.

Twenty months into the COVID-19 pandemic, we are still learning about the various long-term consequences of COVID-19 infection. While many patients do recover with minimal long-term consequences, some patients develop irreversible parenchymal and interstitial lung damage leading to diffuse pulmonary fibrosis. Unfortunately, these are some of the consequences of post-SARS-CoV-2 infection which thousands more people around the world will experience and which will outlast the pandemic for a long time to come. It is now being observed at various leading medical centres around the world that lung transplantation may be the only meaningful treatment available to a select group of patients experiencing serious lung damage and non-resolving COVID-19-associated respiratory failure, resulting from the triad of coronavirus infection, a hyper-inflammatory immune response to it and the inability of the human body to repair that injury.

Lung Fibrosis Sequelae After Recovery from COVID-19 Infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus that causes coronavirus diseases 2019 (COVID-19). The SARS-CoV-2 is very contagious and nobody is known to be immune to it. The post-infected lung would leave a scar known as fibrosis, a scar tissue. A study from Wuhan, China suggested the development of fibrosis, though it was too early to label these lung changes as irreversible fibrosis in a time range of 3 weeks. The occurrence of fibrosis indicates a chronic infection which greatly contributes to the hallmark symptom of COVID-19 induced ARDS such as shortness of breath and chest pain. However, many of those studies have not yet explained the condition of the patient's lung after total recovery from the COVID-19. This report demonstrates the clinical symptoms, chest CT scan, spirometry, and blood gas analysis of patient after total recovery from the COVID-19 with appearance lung fibrosis.

Post-COVID pulmonary fibrosis: therapeutic efficacy using with mesenchymal stem cells - How the lung heals.

COVID-19 is an acute respiratory infectious disease caused by SARS-COV 2 (Severe Acute Respiratory Syndrome Coronavirus) that has become a global pandemic. COVID-19 mainly causes the respiratory complications of Acute Respiratory Distress Syndrome (ARDS), cytokine storm, and severe immune disruptions. The assays depict that though people recuperate from COVID-19, there are still symptoms that persists in the body causing discomfort, which is the consequence of the viral infection due to severe immune disruptions. Upon various difficulties of post COVID-19, the pulmonary fibrosis is the stumbling block in the lungs causing severe damage. In this review, we have shown the effectiveness and importance of the Hepatocyte Growth Factor (HGF) secreted by Mesenchymal Stem Cell (MSC) therapy on selective stoppage of the Transforming Growth Factor-Beta (TGF-ß) signalling pathway by causing immunomodulatory effects that ameliorate the pulmonary fibrosis through paracrine signalling. However, more pilot studies have to be carried out to determine the efficacy and outcomes of the re-emerging complication.

Occurrence of pulmonary residuals as one of the sequelae of COVID-19 and it's predictors among moderate and severe cases.

BACKGROUND: Moderate and severe COVID-19 patients typically present with pneumonia. In this study we aimed to detect the occurrence of pulmonary residuals as a late sequela of COVID-19 and to identify it's predictors among moderate and severe cases. METHODS: This observational prospective study involved 85 COVID-19 patients confirmed by real time polymerase chain reaction (RT-PCR) nasopharyngeal swab, patients were recruited in the period of 1 st of June to 1 st of July. Demographic and clinical data were obtained for each patient. Chest imaging was performed initially and after 3 weeks to detect post COVID pulmonary residuals. RESULTS: The study population included 74 (87.1%) moderate and 11 (12.9%) severe patients. Patients with older age, male gender, high BMI and initial chest CT of consolidation/mixed consolidation and ground glass opacities (GGOs) had more frequent post COVID-19 pulmonary residuals (P 0.003, 0.026, 0.031, 0.035) respectively. There was a statistically significant difference between patients who showed complete resolution and patients who developed pulmonary residuals regarding the lymphocyte count, serum CRP and ferritin levels (P 0.0001). After logistic regression, male gender, high BMI, initial chest CT of consolidation/mixed consolidation and GGOs, lymphocytopenia, high serum CRP and ferritin levels were the predictors of pulmonary residuals. While the age wasn't statistically significant. CONCLUSION: 38.5% of moderate and severe COVID-19 patients tend to have pulmonary residuals. Independent predictors of pulmonary residuals as a sequela of COVID-19 are male gender, high BMI, initial chest CT of consolidation and mixed consolidation/GGOs, lymphocytopenia, high serum CRP and ferritin levels.

A Potential Bioelectromagnetic Method to Slow Down the Progression and Prevent the Development of Ultimate Pulmonary Fibrosis by COVID-19.

Introduction: Right now, we are facing a global pandemic caused by the coronavirus SARS-CoV-2 that causes the highly contagious human disease COVID-19. The number of COVID-19 cases is increasing at an alarming rate, more and more people suffer from it, and the death toll is on the rise since December 2019, when COVID-19 has presumably appeared. We need an urgent solution for the prevention, treatment, and recovery of the involved patients. Methods: Modulated electro-hyperthermia (mEHT) is known as an immuno-supportive therapy in oncology. Our proposal is to apply this method to prevent the progression of the disease after its identification, to provide treatment when necessary, and deliver rehabilitation to diminish the fibrotic-often fatal-consequences of the infection. Hypothesis: The effects of mEHT, which are proven for oncological applications, could be utilized for the inactivation of the virus or for treating the fibrotic consequences. The hypothesized mEHT effects, which could have a role in the antiviral treatment, it could be applied for viral-specific immune-activation and for anti-fibrotic treatments.

Post covid 19 pulmonary fibrosis. Is it real threat?

After the COVID-19 outbreak, increasing number of patients worldwide who have survived COVID-19 continue to battle the symptoms of the illness, long after they have been clinically tested negative for the disease. As we battle through this pandemic, the challenging part is to manage COVID-19 sequelae which may vary from fatigue and body aches to lung fibrosis. This review addresses underlying mechanism, risk factors, course of disease and treatment option for post covid pulmonary fibrosis. Elderly patient who require ICU care and mechanical ventilation are at the highest risk to develop lung fibrosis. Currently, no fully proven options are available for the treatment of post inflammatory COVID 19 pulmonary fibrosis.

COVID-19 lockdown leads to changes in alcohol consumption patterns. Results from the Polish national survey.

The objective of this study was to investigate the effects of nationwide lockdown during the Novel Coronavirus Disease 2019 (COVID-19) pandemic on an average volume of alcohol consumption and drinking patterns. A survey was conducted with a random sample of 4072 people. The authors found a significant influence of the pandemic period on alcohol consumption compared to the pre-pandemic period. The vast majority of respondents reduced the frequency of consumption of all types of alcohol. However, when the population was divided into subgroups, this differentiation demonstrated that particular groups are more vulnerable to alcohol misuse. Higher frequency of alcohol consumption during the COVID-19 pandemic lockdown was most often found in the group of men, people aged 18-24 years, inhabitants of big cities, and remote workers. Besides, significant differences were observed in subpopulations concerning different types of alcohol. Results emphasized the importance of monitoring and implementation of actions aimed at reducing the potential psychosocial impact of COVID-19, including alcohol-related disorders.

Long-Term Respiratory and Neurological Sequelae of COVID-19.

Since the initial reports of coronavirus disease 2019 (COVID-19) in China in late 2019, infections from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have spread rapidly, resulting in a global pandemic that has caused millions of deaths. Initially, the large number of infected people required the direction of global healthcare resources to provide supportive care for the acutely ill population in an attempt to reduce mortality. While clinical trials for safe and effective antiviral agents are ongoing, and vaccine development programs are being accelerated, long-term sequelae of SARS-CoV-2 infection have become increasingly recognized and concerning. Although the upper and lower respiratory tracts are the main sites of entry of SARS-CoV-2 into the body, resulting in COVID-19 pneumonia as the most common presentation, acute lung damage may be followed by pulmonary fibrosis and chronic impairment of lung function, with impaired quality of life. Also, increasing reports have shown that SARS-CoV-2 infection involves the central nervous system (CNS) and the peripheral nervous system (PNS) and directly or indirectly damages neurons, leading to long-term neurological sequelae. This review aims to provide an update on the mechanisms involved in the development of the long-term sequelae of SARS-CoV-2 infection in the 3 main areas of lung injury, neuronal injury, and neurodegenerative diseases, including Alzheimer disease, Parkinson disease, and multiple sclerosis, and highlights the need for patient monitoring following the acute stage of infection with SARS-CoV-2 to provide a rationale for the prevention, diagnosis, and management of these potential long-term sequelae.

Are there pulmonary sequelae in patients recovering from COVID-19?

It has been recently hypothesized that infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may lead to fibrotic sequelae in patients recovering from coronavirus disease 2019 (COVID-19). In this observational study, hospitalized patients with COVID-19 had a HRCT of the chest performed to detect the extension of fibrotic abnormalities via Hounsfield Units (HU). At follow-up, the lung density significantly improved in both lungs and in each lobe of all patients, being in the normal range (- 950 to - 700 HU). This study provides preliminary evidence that hospitalized patients with mild-to-moderate forms of COVID-19 are not at risk of developing pulmonary fibrosis.

"A Chain Only as Strong as Its Weakest Link": An Up-to-Date Literature Review on the Bidirectional Interaction of Pulmonary Fibrosis and COVID-19.

The COVID-19 pandemic rapidly became a worldwide healthcare emergency affecting millions of people, with poor outcomes for patients with chronic conditions and enormous pressure on healthcare systems. Pulmonary fibrosis (PF) has been cited as a risk factor for a more severe evolution of COVID-19, primarily because its acute exacerbations are already associated with high mortality. We reviewed the available literature on biochemical, pathophysiological, and pharmacological mechanisms of PF and COVID-19 in an attempt to foresee the particular risk of infection and possible evolution of PF patients if infected with SARS-COV-2. We also analyzed the possible role of medication and risk factors (such as smoking) in the disease's evolution and clinical course. We found out that there is a complexity of interactions between coexisting idiopathic pulmonary fibrosis/interstitial lung disease (ILD) and COVID-19 disease. Also, patients recovering from severe COVID-19 disease are at serious risk of developing PF. Smokers seem to have, in theory, a chance for a better outcome if they develop a severe form of COVID-19 but statistically are at much higher risk of dying if they become critically ill.

SARS-CoV-2 induces transcriptional signatures in human lung epithelial cells that promote lung fibrosis.

BACKGROUND: Severe acute respiratory syndrome (SARS)-CoV-2-induced coronavirus disease-2019 (COVID-19) is a pandemic disease that affects > 2.8 million people worldwide, with numbers increasing dramatically daily. However, there is no specific treatment for COVID-19 and much remains unknown about this disease. Angiotensin-converting enzyme (ACE)2 is a cellular receptor of SARS-CoV-2. It is cleaved by type II transmembrane serine protease (TMPRSS)2 and disintegrin and metallopeptidase domain (ADAM)17 to assist viral entry into host cells. Clinically, SARS-CoV-2 infection may result in acute lung injury and lung fibrosis, but the underlying mechanisms of COVID-19 induced lung fibrosis are not fully understood. METHODS: The networks of ACE2 and its interacting molecules were identified using bioinformatic methods. Their gene and protein expressions were measured in human epithelial cells after 24 h SARS-CoV-2 infection, or in existing datasets of lung fibrosis patients. RESULTS: We confirmed the binding of SARS-CoV-2 and ACE2 by bioinformatic analysis. TMPRSS2, ADAM17, tissue inhibitor of metalloproteinase (TIMP)3, angiotensinogen (AGT), transformation growth factor beta (TGFB1), connective tissue growth factor (CTGF), vascular endothelial growth factor (VEGF) A and fibronectin (FN) were interacted with ACE2, and the mRNA and protein of these molecules were expressed in lung epithelial cells. SARS-CoV-2 infection increased ACE2, TGFB1, CTGF and FN1 mRNA that were drivers of lung fibrosis. These changes were also found in lung tissues from lung fibrosis patients. CONCLUSIONS: Therefore, SARS-CoV-2 binds with ACE2 and activates fibrosis-related genes and processes to induce lung fibrosis.

Serious adverse events with tocilizumab: Pharmacovigilance as an aid to prioritize monitoring in COVID-19.

Given its approval for the treatment of cytokine release syndrome, tocilizumab is under investigation in severe coronavirus disease-2019. To characterize serious adverse events (AEs) with tocilizumab, we queried the worldwide FDA Adverse Event Reporting System and performed disproportionality analysis, selecting only designated medical events (DMEs) where tocilizumab was reported as suspect, with a focus on hepatic reactions. The reporting odds ratios (RORs) were calculated, deemed significant by a lower limit of the 95% confidence interval (LL 95% CI) > 1. A total of 2,433 reports of DMEs were recorded with tocilizumab, mainly in rheumatic diseases. Statistically significant RORs emerged for 13 DMEs, with drug-induced liver injury (n = 91; LL 95% CI 3.07), pancreatitis (151; 1.41), and pulmonary fibrosis (222; 7.21) as unpredictable AEs. A total of 174 cases of liver-related DMEs were retrieved (proportion of deaths = 18.4%), with median onset of 27.5 days. These serious unpredictable reactions occurring in chronic real-world tocilizumab use may support patient care and monitoring of ongoing clinical trials.