Biomarkers of Fibrosis in Patients with COVID-19 One Year After Hospital Discharge: A Prospective Cohort Study.

Beyond the acute infection of coronavirus disease (COVID-19), concern has arisen about long-term effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The aim of our study was to analyze if there is any biomarker of fibrogenesis in patients with COVID-19 pneumonia capable of predicting post-COVID-19 pulmonary sequelae. We conducted a multicenter, prospective, observational cohort study of patients admitted to a hospital with bilateral COVID-19 pneumonia. We classified patients into two groups according to severity, and blood sampling to measure matrix metalloproteinase 1 (MMP-1), MMP-7, periostin, and VEGF and respiratory function tests and high-resolution computed tomography were performed at 2 and 12 months after hospital discharge. A total of 135 patients were evaluated at 12 months. Their median age was 61 (interquartile range, 19) years, and 58.5% were men. We found between-group differences in age, radiological involvement, length of hospital stay, and inflammatory laboratory parameters. Differences were found between 2 and 12 months in all functional tests, including improvements in predicted forced vital capacity (98.0% vs. 103.9%; P = 0.001) and DlCO <80% (60.9% vs. 39.7%; P = 0.001). At 12 months, 63% of patients had complete high-resolution computed tomography resolution, but fibrotic changes persisted in 29.4%. Biomarker analysis demonstrated differences at 2 months in periostin (0.8893 vs. 1.437 ng/ml; P < 0.001) and MMP-7 (8.7249 vs. 15.2181 ng/ml; P < 0.001). No differences were found at 12 months. In multivariable analysis, only 2-month periostin was associated with 12-month fibrotic changes (odds ratio, 1.0013; 95% confidence interval, 1.0006-1.00231; P = 0.003) and 12-month DlCO impairment (odds ratio, 1.0006; 95% confidence interval, 1.0000-1.0013; P = 0.047). Our data suggest that early periostin postdischarge could predict the presence of fibrotic pulmonary changes.

Living with pulmonary sequelae of COVID-19 and the implications for clinical nursing practice: A qualitative systematised review.

AIM: To synthesise qualitative research on pulmonary sequelae of COVID-19 and identify patient needs and experiences to develop nursing care strategies. BACKGROUND: Qualitative research on long COVID by subtype has not yet occurred. As pulmonary sequelae constitute a serious long COVID subtype, exploring patient experience and needs can generate knowledge to guide nursing practice. DESIGN: Systematised review methodology utilised on a purposive sample of published articles and reported using the PRISMA guidelines and checklists. Searched MEDLINE, Cumulative Index to Nursing and Allied Health, and Google Scholar, for English or French articles published from February 2020 to June 2022; qualitative research with adults recovering from COVID-19 with evidence of pulmonary sequelae. METHODS: Established principles for data extraction followed related to data reduction, data presentation, data comparison, and conclusion formulation and verification. Analysis was informed by Thorne's Interpretive Description and extended with Meleis' transitions theory, Mishel's uncertainty in illness theory and Moore et al.'s holistic theory of unpleasant symptoms. The quality of included studies was assessed Joanna Briggs Institute critical appraisal tool for qualitative research. RESULTS: Four articles with six pooled participants provided data to yield three main themes: (1) a novel health-illness transition, (2) lung injury and pulmonary fibrosis as antecedent to illness uncertainty, (3) and pulmonary symptoms that are compounded by fatigue and weakness. CONCLUSION: Pulmonary sequelae of COVID-19 confers a unique health-illness transition, uncertainties and symptoms that can be addressed by theory informed nursing practice. RELEVANCE TO CLINICAL PRACTICE: Advocacy, optimising the nurse-patient relationship, offering up-to-date information and addressing uncertainty may help patients cope with pulmonary sequelae, a complex subtype of long COVID with important considerations for clinical nursing care. Despite a lack of evidence-informed clinical pathways, nurses can support patients to understand novel treatments, support discharge planning and acknowledge the synergistic nature of pulmonary symptoms and fatigue to support health-illness transitions. NO PATIENT OR PUBLIC CONTRIBUTION: This article involved analysis of previously published works.

Exploring the pathologist's role in understanding COVID-19: from pneumonia to long-COVID lung sequelae.

The crucial role of pathologists in enhancing our understanding of SARS-CoV-2-related disease, from initial pneumonia manifestations to persistent long COVID lung symptoms, is the focus of this review. Pathological explorations have offered unprecedented insights into the early stages of severe COVID-19, shedding light on the interplay between the virus and subsequent complications, thereby shaping clinical approaches. Growing interest is directed to residual lung abnormalities of COVID-19 survivors. Although various radiological studies reported long-lasting pulmonary changes (e.g., ground glass opacities, reticulations, and bronchiectasis), the true incidence of pulmonary fibrosis and corresponding pathological findings in these patients remains largely unknown. There are a few high-impact and knowledgeable works on late complications in COVID-19 survivors, several coming from explant or autopsy cases, and rare cases from in vivo sampling. The study of biopsy samples has further deepened our knowledge of the aftermath of COVID-19 on lung tissue, uncovering alterations at the cellular level and shifts in vascular and epithelial dynamics. Despite the substantial progress made, future research is needed to devise a uniform strategy for interpreting lung biopsies, with a focus on leveraging advanced tools such as molecular and digital pathology techniques, along with artificial intelligence.

Post-COVID-19 sequelae in lungs: retrospective computed tomography analysis in selected tertiary care hospitals of Mangalore.

Purpose: The radiological features of COVID-19 during the active disease process are well established, but the radio-logical features in the convalescent and post-recovery period of the disease are still unclear. The objectives of this study are to document and assess the proportion of the residual changes in lung post COVID-19 infection and to look for evidence and the proportion of fibrosis post COVID-19 infection on high-resolution computed tomography (HRCT). Material and methods: HRCT thorax of COVID-positive cases done during the disease process and in the recovery/post recovery phase were included in the study. Sample Size: 75. Categorical data are represented in the form of frequencies and proportions. The c2 test was used as a test of significance for qualitative data. Continuous data are represented as mean and standard deviation. A p-value (probability that the result is true) of < 0.05 was considered as statistically significant after assuming all the rules of statistical tests. Results: Initial computed tomography (CT) findings mainly included ground glass opacity (GGO) (93.3%), inter-lobular septal thickening (66.7%), consolidation (52.0%), and fibrotic bands (8.0%). Ninety-two per cent of the CT scans demonstrated some pulmonary change in the follow-up CT. This was mostly in the form of GGO (58%). Approximately 17% of cases showed fibrotic changes in the follow-up CT. Conclusions: Post-COVID lung sequelae can be present in a significant number of patients. This are mostly seen in patients with severe initial disease and in older patients. Statistically significant post-COVID sequelae changes include GGO, fibrotic bands, and bronchiectasis.

Lung function and radiological findings 1 year after COVID-19: a prospective follow-up.

BACKGROUND: The coronavirus disease (COVID-19) pandemic has already affected more than 400 million people, with increasing numbers of survivors. These data indicate that a myriad of people may be affected by pulmonary sequelae of the infection. The aim of this study was to evaluate pulmonary sequelae in patients with bilateral COVID-19 pneumonia according to severity 1 year after hospital discharge. METHODS: COVID-FIBROTIC is a multicenter prospective observational cohort study for admitted patients with bilateral COVID-19 pneumonia. Pulmonary functional outcomes and chest computed tomography sequelae were analyzed 12 months after hospital discharge and we classified patients into three groups according to severity. A post hoc analysis model was designed to establish how functional test changed between groups and over time. A multivariable logistic regression model was created to study prognostic factors for lung diffusion impairment and radiological fibrotic-like changes at 12 months. RESULTS: Among 488 hospitalized patients with COVID-19 pneumonia, 284 patients had completed the entire evaluation at 12 months. Median age was 60.5 ± 11.9 and 55.3% were men. We found between-group differences in male sex, length of hospital stay, radiological involvement and inflammatory laboratory parameters. The functional evaluation of pulmonary sequelae showed that severe patients had statistically worse levels of lung diffusion at 2 months but no between group differences were found in subsequent controls. At 12-month follow up, however, we found impaired lung diffusion in 39.8% unrelated to severity. Radiological fibrotic-like changes at 12 months were reported in 22.7% of patients (102/448), only associated with radiological involvement at admission (OR: 1.55, 95% CI 1.06-2.38; p = 0.02) and LDH (OR: 0.99, 95% CI 0.98-0.99; p = 0.046). CONCLUSION: Our data suggest that a significant percentage of individuals would develop pulmonary sequelae after COVID 19 pneumonia, regardless of severity of the acute process. Trial registration clinicaltrials.gov NCT04409275 (June 1, 2020).

Impact of time to intubation on mortality and pulmonary sequelae in critically ill patients with COVID-19: a prospective cohort study.

QUESTION: We evaluated whether the time between first respiratory support and intubation of patients receiving invasive mechanical ventilation (IMV) due to COVID-19 was associated with mortality or pulmonary sequelae. MATERIALS AND METHODS: Prospective cohort of critical COVID-19 patients on IMV. Patients were classified as early intubation if they were intubated within the first 48 h from the first respiratory support or delayed intubation if they were intubated later. Surviving patients were evaluated after hospital discharge. RESULTS: We included 205 patients (140 with early IMV and 65 with delayed IMV). The median [p25;p75] age was 63 [56.0; 70.0] years, and 74.1% were male. The survival analysis showed a significant increase in the risk of mortality in the delayed group with an adjusted hazard ratio (HR) of 2.45 (95% CI 1.29-4.65). The continuous predictor time to IMV showed a nonlinear association with the risk of in-hospital mortality. A multivariate mortality model showed that delay of IMV was a factor associated with mortality (HR of 2.40; 95% CI 1.42-4.1). During follow-up, patients in the delayed group showed a worse DLCO (mean difference of - 10.77 (95% CI - 18.40 to - 3.15), with a greater number of affected lobes (+ 1.51 [95% CI 0.89-2.13]) and a greater TSS (+ 4.35 [95% CI 2.41-6.27]) in the chest CT scan. CONCLUSIONS: Among critically ill patients with COVID-19 who required IMV, the delay in intubation from the first respiratory support was associated with an increase in hospital mortality and worse pulmonary sequelae during follow-up.

Post-COVID-19 cardio-pulmonary manifestations after 1-year of SARS-CoV-2 infection among Indian population: A single centre, case-control study (OneCoV2 study).

BACKGROUND: The evolving challenge of persistent symptoms post-Coronavirus disease-2019 (COVID-19), particularly debilitating cardio-pulmonary manifestations, necessitates further exploration. Our study aimed to assess the cardio-pulmonary complications in patients a year after hospital discharge from severe COVID-19, contrasting these with findings from a non-COVID group. METHODS: The OneCoV2 study, a prospective, case-control study, was conducted at a tertiary care teaching hospital in northern India. We enrolled 43 subjects, with a mean age of 25.57 ± 7.94 years (COVID group) and 27.30 ± 8.17 years (non-COVID group). Comprehensive tests included pulmonary function tests, cardiac function tests, 6-min walk tests, and laboratory investigations. RESULTS: Significant differences were found in the pulmonary function [forced vital capacity (FVC) (p = 0.037), forced expiratory flow (FEF) 25-75 % (p = 0.013)], and cardiac function [left ventricular ejection fraction (LVEF) (p = 0.032), heart rate (HR) (p = 0.047)], along with the six-minute walk test results between the two groups. In the COVID group, Pearson's correlation showed a negative correlation between FVC and C-reactive protein (CRP) [r = -0.488, p = 0.007] and a positive correlation between the six-minute walk test [r = 0.431, p = 0.003] and HR [r = 0.503, p = 0.013]. CONCLUSIONS: Our data suggest that pulmonary abnormalities are prevalent in COVID patients even after 1-year of hospital discharge. Cardiac biomarkers also show an inclination towards the COVID group. While we found significant correlations involving some parameters like FVC, CRP, HR, and results from the six-minute walk test, we did not find any significant correlations with the other tested parameters in our study.

Persistent pulmonary abnormalities after 18 months of SARS-CoV-2 pneumonia.

OBJECTIVE: To describe persistent pulmonary abnormalities detected on HRCT after 18 months of SARS-CoV-2 pneumonia, and to determine their extension and correlation with pulmonary function. PATIENTS AND METHODS: A prospective cross-sectional study with an initial cohort of 90 patients in follow-up due to persisting lung abnormalities on imaging, functional respiratory impairment and/or respiratory symptoms. Of these, 31 (34%) were selected for analysis due to the persistence of their lung abnormalities on HRCT at 18 months after infection. A double reading was performed for each HRCT (62 observations). RESULTS: Of the 31 patients included: 20 (65%) were men; mean age was 67 years; 17 (55%) were smokers/ex-smokers. The mean hospitalisation time was 38 days. Eighteen (58%) patients were admitted to intensive care units. Five patients (16%) suffered an acute pulmonary thromboembolism and three (9.7%) had a pneumothorax. The mean time between the onset of pneumonia and the follow-up HRCT was 20.34 months. Nineteen percent of patients suffered from total lung function abnormalities; and ground-glass opacities and reticulation were present in 12% and 4.5% respectively. The findings of the 62 readings were: ground-glass opacities (100%), reticulation (83%), subpleural curvilinear lines (62%), parenchymal bands (34%), traction bronchiectasis (69%), displacement of vessels/fissures (46%) and honeycombing (4.9%). Pulmonary function 18 months after the acute episode revealed a mean FVC of 92% of predicted value, with an FVC < 80% of predicted value in 11 patients (35.4%). Mean DLCO was 71% of predicted value, with a DLCO < 80% in 22 patients (70%). We observed a statistically significant relationship between total lung function abnormalities on HRCT and FVC (P < 0.05), and a trend towards statistical significance with DLCO (P = 0.051); there was a statistically significant relationship between the presence of ground-glass opacities and FEV1/FVC (P < 0.01). The relationships between reticulation and FVC, FVC%, FEV1, FEV1% and DLCO% were also considered statistically significant (P < 0.05). CONCLUSION: Persistent interstitial lung abnormalities are seen on HRCT for a subset of patients infected with SARS-CoV-2 pneumonia. Seventy percent of these patients suffered a slight decrease in DLCO.

Pulmonary function and chest CT abnormalities 3 months after discharge from COVID-19, 2020-2021: A nation-wide multicenter prospective cohort study from the Japanese respiratory society.

BACKGROUND: No comprehensive analysis of the pulmonary sequelae of coronavirus disease 2019 (COVID-19) in Japan based on respiratory function tests and chest computed tomography (CT) has been reported. We evaluated post-COVID-19 conditions, especially focusing on pulmonary sequelae assessed by pulmonary function tests and chest CT. METHODS: For this prospective cohort study, we enrolled 1069 patients who presented pneumonia at the time of admission in 55 hospitals from February 2020 to September 2021. Disease severity was classified as moderateⅠ, moderate II, and severe, defined primarily according to the degree of respiratory failure. The data on post-COVID-19 conditions over 12 months, pulmonary function, and chest CT findings at 3 months were evaluated in this study. Additionally, the impact of COVID-19 severity on pulmonary sequelae, such as impaired diffusion capacity, restrictive pattern, and CT abnormalities, was also evaluated. RESULTS: The most frequently reported post-COVID-19 conditions at 3 months after COVID-19 were muscle weakness, dyspnea, and fatigue (48.4%, 29.0%, and 24.7%, respectively). The frequency of symptoms gradually decreased over subsequent months. In pulmonary function tests at 3 months, the incidence of impaired diffusion capacity and restrictive pattern increased depending on disease severity. There also were differences in the presence of chest CT abnormalities at the 3 months, which was markedly correlated with the severity. CONCLUSION: We reported a comprehensive analysis of post-COVID-19 condition, pulmonary function, and chest CT abnormalities in Japanese patients with COVID-19. The findings of this study will serve as valuable reference data for future post-COVID-19 condition research in Japan.

Determination of global chemical patterns in exhaled breath for the discrimination of lung damage in postCOVID patients using olfactory technology.

The objective of this work was to evaluate the use of an electronic nose and chemometric analysis to discriminate global patterns of volatile organic compounds (VOCs) in breath of postCOVID syndrome patients with pulmonary sequelae. A cross-sectional study was performed in two groups, the group 1 were subjects recovered from COVID-19 without lung damage and the group 2 were subjects recovered from COVID-19 with impaired lung function. The VOCs analysis was executed using a Cyranose 320 electronic nose with 32 sensors, applying principal component analysis (PCA), Partial Least Square-Discriminant Analysis, random forest, canonical discriminant analysis (CAP) and the diagnostic power of the test was evaluated using the ROC (Receiver Operating Characteristic) curve. A total of 228 participants were obtained, for the postCOVID group there are 157 and 71 for the control group, the chemometric analysis results indicate in the PCA an 84% explanation of the variability between the groups, the PLS-DA indicates an observable separation between the groups and 10 sensors related to this separation, by random forest, a classification error was obtained for the control group of 0.090 and for the postCOVID group of 0.088 correct classification. The CAP model showed 83.8% of correct classification and the external validation of the model showed 80.1% of correct classification. Sensitivity and specificity reached 88.9% (73.9%-96.9%) and 96.9% (83.7%-99.9%) respectively. It is considered that this technology can be used to establish the starting point in the evaluation of lung damage in postCOVID patients with pulmonary sequelae.

Pharmacological approaches to pulmonary fibrosis following COVID-19.

Background: In the past few years, COVID-19 became the leading cause of morbidity and mortality worldwide. Although the World Health Organization has declared an end to COVID-19 as a public health emergency, it can be expected, that the emerging new cases at the top of previous ones will result in an increasing number of patients with post-COVID-19 sequelae. Despite the fact that the majority of patients recover, severe acute lung tissue injury can in susceptible individuals progress to interstitial pulmonary involvement. Our goal is to provide an overview of various aspects associated with the Post-COVID-19 pulmonary fibrosis with a focus on its potential pharmacological treatment options. Areas covered: We discuss epidemiology, underlying pathobiological mechanisms, and possible risk and predictive factors that were found to be associated with the development of fibrotic lung tissue remodelling. Several pharmacotherapeutic approaches are currently being applied and include anti-fibrotic drugs, prolonged use or pulses of systemic corticosteroids and non-steroidal anti-inflammatory and immunosuppressive drugs. In addition, several repurposed or novel compounds are being investigated. Fortunately, clinical trials focused on pharmacological treatment regimens for post-COVID-19 pulmonary fibrosis have been either designed, completed or are already in progress. However, the results are contrasting so far. High quality randomised clinical trials are urgently needed with respect to the heterogeneity of disease behaviour, patient characteristics and treatable traits. Conclusion: The Post-COVID-19 pulmonary fibrosis contributes to the burden of chronic respiratory consequences among survivors. Currently available pharmacotherapeutic approaches mostly comprise repurposed drugs with a proven efficacy and safety profile, namely, corticosteroids, immunosuppressants and antifibrotics. The role of nintedanib and pirfenidone is promising in this area. However, we still need to verify conditions under which the potential to prevent, slow or stop progression of lung damage will be fulfilled.

Radiological Findings as Predictors of COVID-19 Lung Sequelae: A Systematic Review and Meta-analysis.

RATIONALE AND OBJECTIVES: This systematic review and meta-analysis aimed to investigate the radiological predictors of post-coronavirus disease 19 (COVID-19) pulmonary fibrosis and incomplete absorption of pulmonary lesions. MATERIALS AND METHODS: We systematically searched PubMed, EMBASE, and Web of Science for studies reporting the predictive value of radiological findings in patients with post-COVID-19 lung residuals published through November 11, 2022. The pooled odds ratios with a 95% confidence interval (CI) were assessed. The random-effects model was used due to the heterogeneity of the true effect sizes. RESULTS: We included 11 studies. There were 1777 COVID-19-positive patients, and 1014 (57%) were male. All studies used chest computed tomography (CT) as a radiologic tool. Moreover, chest X-ray (CXR) and lung ultrasound were used in two studies, along with a CT scan. CT severity score (CTSS), Radiographic Assessment of Lung Edema score (RALE), interstitial score, lung ultrasound score (LUS), patchy opacities, abnormal CXR, pleural traction, and subpleural abnormalities were found to be predictors of post-COVID-19 sequels. CTSS and consolidations were the most common predictors among included studies. Pooled analysis revealed that pulmonary residuals in patients with initial consolidation are about four times more likely than in patients without this finding (odds ratio: 3.830; 95% CI: 1.811-8.102, I2: 4.640). CONCLUSION: Radiological findings can predict the long-term pulmonary sequelae of COVID-19 patients. CTSS is an important predictor of lung fibrosis and COVID-19 mortality. Lung fibrosis can be diagnosed and tracked using the LUS. Changes in RALE score during hospitalization can be used as an independent predictor of mortality.

Critical Damage of Lung Parenchyma Complicated with Massive Pneumothorax in COVID-19 Pneumonia.

It is already known that Coronavirus disease 2019 (COVID-19) may lead to various degrees and forms of lung parenchyma damage, but some cases take a strikingly severe course that is difficult to manage. We report the case of a 62-year old male, non-obese, non-smoker, and non-diabetic, who presented with fever, chills, and shortness of breath. The infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was diagnosed by real-time Polymerase Chain Reaction. Although the patient had been vaccinated with 2 doses of Pfizer-BioNTech COVID-19 vaccine 7 months earlier and had no risk factors for a severe outcome, serial computed tomography (CT) scan revealed lung involvement progressively extending from an initial 30% to 40% to almost 100% 2.5 months later. The spectrum of lung lesions included at first only ground-glass opacities and some tiny emphysema bullae, but later also bronchiectasis, pulmonary fibrosis, and large emphysema bullae as post-COVID-19 pulmonary sequelae. For fear of severe evolution of superimposed bacterial infection (Clostridoides difficile enterocolits and possibly bacterial pneumonia) the administration of corticosteroids was intermittent. Massive right pneumothorax secondary to bulla rupture, possibly favored by the indispensable high flow oxygen therapy, led to respiratory failure compounded by hemodynamic instability, and ultimately to the patient's final demise. COVID-19 pneumonia may cause severe lung parenchyma damage which requires long-term supplemental oxygen therapy. Beneficial or even lifesaving as it might be, high flow oxygen therapy may nonetheless have deleterious effects too, including the development of bullae that may rupture engendering pneumothorax. Corticosteroid treatment should probably be pursued despite superimposed bacterial infection to limit the viral induced damage to lung parenchyma.

Elevated circulating monocytes and monocyte activation in COVID-19 convalescent individuals.

Background: Monocytes and macrophages play a pivotal role in inflammation during acute SARS-CoV-2 infection. However, their contribution to the development of post-acute sequelae of SARS-CoV-2 infection (PASC) are not fully elucidated. Methods: A cross-sectional study was conducted comparing plasma cytokine and monocyte levels among three groups: participants with pulmonary PASC (PPASC) with a reduced predicted diffusing capacity for carbon monoxide [DLCOc, <80%; (PG)]; fully recovered from SARS-CoV-2 with no residual symptoms (recovered group, RG); and negative for SARS-CoV-2 (negative group, NG). The expressions of cytokines were measured in plasma of study cohort by Luminex assay. The percentages and numbers of monocyte subsets (classical, intermediate, and non-classical monocytes) and monocyte activation (defined by CD169 expression) were analyzed using flow cytometry analysis of peripheral blood mononuclear cells. Results: Plasma IL-1Ra levels were elevated but FGF levels were reduced in PG compared to NG. Circulating monocytes and three subsets were significantly higher in PG and RG compared to NG. PG and RG exhibited higher levels of CD169+ monocyte counts and higher CD169 expression was detected in intermediate and non-classical monocytes from RG and PG than that found in NG. Further correlation analysis with CD169+ monocyte subsets revealed that CD169+ intermediate monocytes negatively correlated with DLCOc%, and CD169+ non-classical monocytes positively correlated with IL-1α, IL-1ß, MIP-1α, Eotaxin, and IFN-γ. Conclusion: This study present evidence that COVID convalescents exhibit monocyte alteration beyond the acute COVID-19 infection period even in convalescents with no residual symptoms. Further, the results suggest that monocyte alteration and increased activated monocyte subsets may impact pulmonary function in COVID-19 convalescents. This observation will aid in understanding the immunopathologic feature of pulmonary PASC development, resolution, and subsequent therapeutic interventions.

Single-cell RNA sequencing reveals characteristics of myeloid cells in post-acute sequelae of SARS-CoV-2 patients with persistent respiratory symptoms.

Background: Although our understanding of the immunopathology and subsequent risk and severity of COVID-19 disease is evolving, a detailed account of immune responses that contribute to the long-term consequences of pulmonary complications in COVID-19 infection remains unclear. Few studies have detailed the immune and cytokine profiles associated with post-acute sequelae of SARS-CoV-2 infection (PASC) with persistent pulmonary symptoms. The dysregulation of the immune system that drives pulmonary sequelae in COVID-19 survivors and PASC sufferers remains largely unknown. Results: To characterize the immunological features of pulmonary PASC (PPASC), we performed droplet-based single-cell RNA sequencing (scRNA-seq) to study the transcriptomic profiles of peripheral blood mononuclear cells (PBMCs) from a participant naïve to SARS-CoV-2 (Control) (n=1) and infected with SARS-CoV-2 with chronic pulmonary symptoms (PPASC) (n=2). After integrating scRNA-seq data with a naïve participant from a published dataset, 11 distinct cell populations were identified based on the expression of canonical markers. The proportion of myeloid-lineage cells ([MLCs]; CD14+/CD16+monocytes, and dendritic cells) was increased in PPASC (n=2) compared to controls (n=2). MLCs from PPASC displayed up-regulation of genes associated with pulmonary symptoms/fibrosis, while glycolysis metabolism-related genes were downregulated. Similarly, pathway analysis showed that fibrosis-related (VEGF, WNT, and SMAD) and cell death pathways were up-regulated, but immune pathways were down-regulated in PPASC. Further comparison of PPASC with scRNA-seq data with Severe COVID-19 (n=4) data demonstrated enrichment of fibrotic transcriptional signatures. In PPASC, we observed interactive VEGF ligand-receptor pairs among MLCs, and network modules in CD14+ (cluster 4) and CD16+ (Cluster 5) monocytes displayed a significant enrichment for biological pathways linked to adverse COVID-19 outcomes, fibrosis, and angiogenesis. Further analysis revealed a distinct metabolic alteration in MLCs with a down-regulation of glycolysis/gluconeogenesis in PPASC compared to SARS-CoV-2 naïve samples. Conclusion: Analysis of a small scRNA-seq dataset demonstrated alterations in the immune response and cellular landscape in PPASC. The presence of elevated MLC levels and their corresponding gene signatures associated with fibrosis, immune response suppression, and altered metabolic states suggests a potential role in PPASC development.

Organizing Pneumonia as a Pulmonary Sequela of Post-COVID-19 Syndrome in a Patient in Trinidad: A Case Report.

Cryptogenic organizing pneumonia (COP) is a form of idiopathic interstitial pneumonia that commonly presents with exertional dyspnea. The mainstay diagnostic criterion is with histopathological confirmation alongside excluding secondary causes of interstitial lung disease. The COVID-19 pandemic left many mysteries regarding the long-term sequelae of this disease. We explore a case of post-COVID-19 syndrome organizing pneumonia (PCOP) in a patient presenting with new-onset respiratory symptoms seven weeks after recovery from COVID-19 infection. Upon further review of the literature, there were no published case reports on PCOP in Trinidad and Tobago. We describe a case of PCOP presented at Apley Medical Clinic, Trinidad, and Tobago, West Indies, with the aim of increasing awareness of this condition to allow for early identification and effective management.

Corrigendum: Phenotypic alteration of low-density granulocytes in people with pulmonary post-acute sequelae of SARS-CoV-2 infection.

[This corrects the article DOI: 10.3389/fimmu.2022.1076724.].

Combined Silymarin and Cotrimoxazole Therapy Attenuates Pulmonary Fibrosis in Experimental Paracoccidioidomycosis.

Paracoccidioidomycosis (PCM), which mainly affects rural workers, is a systemic mycosis caused by the Paracoccidioides genus that induces pulmonary sequelae in most adult patients, causing serious disability and impairing their quality of life. Silymarin is herbal medicine with an effective antifibrotic activity. Considering that in PCM, antifibrotic treatment is still not available in pulmonary fibrosis, we aimed to evaluate combined silymarin and cotrimoxazole (CMX) therapy via the intratracheal route in BALB/c mice infected with P. brasiliensis yeast. After 12 weeks of treatment, the lungs were collected for the determination of fungal burden, production of OH-proline, deposition of collagen fibers, pulmonary concentrations of cytokines, and expression of fibronectin, α-SMA, MMP-2, MMP-9, and TIMP-2. Spleen cell cultures were also performed. Our results showed that infected mice treated with combined silymarin/CMX showed lower deposition of collagen fibers in the lungs and lower pulmonary concentrations of hydroxyproline than the placebo groups. Decreased levels of TGF-ß1 and fibronectin and high levels of MMP-2 and IFN-γ were also observed in this group of mice. Collectively, our findings indicate that the combination of antifungal treatment with silymarin has a potent antifibrotic effect associated with an immunomodulatory effect that potentializes the antifungal immune response.

Severe chronic cough relating to post-COVID-19 interstitial lung disease: a case report.

Cough is a common symptom occurring in patients with acute coronavirus disease 2019 (COVID-19) infection as well as during the post-COVID-19 period. The post-COVID-19 cough can improve over time and the incidence of sustained post-COVID-19 chronic cough is low. Approaching post-COVID-19 cough is challenging to clinicians including pulmonologists and allergists due to a diverse set of etiologies and the lack of published guidance on effective treatments. A 60-year-old male ex-smoker presented to the outpatient long COVID-19 clinic because of a prolonged cough for 4 months after a severe COVID-19 infection. His cough was so violent that he had suffered a spontaneous pneumothorax on 2 occasions. In addition, he also complained of exertional breathlessness. Due to concerns over ongoing systemic inflammation from COVID-19 or thromboembolism, a serum C-reactive protein and d-dimer where checked and were normal. Chest computed tomography (CT) images revealed diffuse ground glass opacities combined with scattered emphysema in the bilateral upper lobes and several small bullae located close to the pleura. His diagnosis was post-COVID-19 interstitial lung disease (ILD) and he was treated with methylprednisolone 32 mg/day. After 2 weeks of treatment, he showed improvement with near cessation of cough and a significant decline in dyspnea. The follow-up chest CT also showed improvement in the ground glass opacities. Severe chronic cough could be a manifestation of post-COVID-19 ILD. This case demonstrates the use of systemic corticosteroid to improve both post-COVID-19 ILD and its associated chronic cough.