Corrigendum: Post-COVID-19 interstitial lung disease: Insights from a machine learning radiographic model.

[This corrects the article DOI: 10.3389/fmed.2022.1083264.].

Implications of obesity and adiposopathy on respiratory infections; focus on emerging challenges.

Obesity is characterized by excessive adipose tissue accumulation, which impacts physiological, metabolic, and immune functions. Several respiratory infections, including bacterial pneumonia, influenza, and coronavirus disease 2019, appear to be linked to unfavorable results in individuals with obesity. These may be attributed to the direct mechanical/physiological effects of excess body fat on the lungs' function. Notably, adipose tissue dysfunction is associated with a low-grade chronic inflammatory status and hyperleptinemia, among other characteristics. These have all been linked to immune system dysfunction and weakened immune responses to these infections. A better understanding and clinical awareness of these risk factors are necessary for better disease outcomes.

Post-COVID-19 interstitial lung disease: Insights from a machine learning radiographic model.

Introduction: Post-acute sequelae of COVID-19 seem to be an emerging global crisis. Machine learning radiographic models have great potential for meticulous evaluation of post-COVID-19 interstitial lung disease (ILD). Methods: In this multicenter, retrospective study, we included consecutive patients that had been evaluated 3 months following severe acute respiratory syndrome coronavirus 2 infection between 01/02/2021 and 12/5/2022. High-resolution computed tomography was evaluated through Imbio Lung Texture Analysis 2.1. Results: Two hundred thirty-two (n = 232) patients were analyzed. FVC% predicted was ≥80, between 60 and 79 and <60 in 74.2% (n = 172), 21.1% (n = 49), and 4.7% (n = 11) of the cohort, respectively. DLCO% predicted was ≥80, between 60 and 79 and <60 in 69.4% (n = 161), 15.5% (n = 36), and 15.1% (n = 35), respectively. Extent of ground glass opacities was ≥30% in 4.3% of patients (n = 10), between 5 and 29% in 48.7% of patients (n = 113) and <5% in 47.0% of patients (n = 109). The extent of reticulation was ≥30%, 5-29% and <5% in 1.3% (n = 3), 24.1% (n = 56), and 74.6% (n = 173) of the cohort, respectively. Patients (n = 13, 5.6%) with fibrotic lung disease and persistent functional impairment at the 6-month follow-up received antifibrotics and presented with an absolute change of +10.3 (p = 0.01) and +14.6 (p = 0.01) in FVC% predicted at 3 and 6 months after the initiation of antifibrotic. Conclusion: Post-COVID-19-ILD represents an emerging entity. A substantial minority of patients presents with fibrotic lung disease and might experience benefit from antifibrotic initiation at the time point that fibrotic-like changes are "immature." Machine learning radiographic models could be of major significance for accurate radiographic evaluation and subsequently for the guidance of therapeutic approaches.

COVID-19 and liver injury in individuals with obesity.

Coronavirus disease 2019 is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 that manifests as a variety of clinical manifestations, including liver damage commonly detected by a hepatocellular pattern from liver function tests. Liver injury is associated with a worse prognosis overall. Conditions associated with the severity of the disease include obesity and cardiometabolic comorbidities, which are also associated with nonalcoholic fatty liver disease (NAFLD). The presence of NAFLD, similarly to obesity, is associated with an unfavourable impact on the coronavirus disease 2019 outcome. Individuals with these conditions could present with liver damage and elevated liver function tests due to direct viral cytotoxicity, systemic inflammation, ischemic or hypoxic liver damage or drug side effects. However, liver damage in the setting of NAFLD could also be attributed to a pre-existing chronic low-grade inflammation associated with surplus and dysfunctional adipose tissue in these individuals. Here we investigate the hypothesis that a pre-existing inflammatory status is exacerbated after severe acute respiratory syndrome coronavirus 2 infection, which embodies a second hit to the underestimated liver damage.

Exploring the Role of ACE2 as a Connecting Link between COVID-19 and Parkinson's Disease.

Coronavirus disease 2019 (COVID-19) is frequently accompanied by neurological manifestations such as headache, delirium, and epileptic seizures, whereas ageusia and anosmia may appear before respiratory symptoms. Among the various neurological COVID-19-related comorbidities, Parkinson's disease (PD) has gained increasing attention. Some cases of PD disease have been linked to COVID-19, and both motor and non-motor symptoms in Parkinson's disease patients frequently worsen following SARS-CoV-2 infection. Although it is still unclear whether PD increases the susceptibility to SARS-CoV-2 infection or whether COVID-19 increases the risk of or unmasks future cases of PD, emerging evidence sheds more light on the molecular mechanisms underlying the relationship between these two diseases. Among them, angiotensin-converting enzyme 2 (ACE2), a significant component of the renin-angiotensin system (RAS), seems to play a pivotal role. ACE2 is required for the entry of SARS-CoV-2 to the human host cells, and ACE2 dysregulation is implicated in the severity of COVID-19-related acute respiratory distress syndrome (ARDS). ACE2 imbalance is implicated in core shared pathophysiological mechanisms between PD and COVID-19, including aberrant inflammatory responses, oxidative stress, mitochondrial dysfunction, and immune dysregulation. ACE2 may also be implicated in alpha-synuclein-induced dopaminergic degeneration, gut-brain axis dysregulation, blood-brain axis disruption, autonomic dysfunction, depression, anxiety, and hyposmia, which are key features of PD.

Post-COVID-19 interstitial lung disease: Insights from a machine learning radiographic model

Introduction Post-acute sequelae of COVID-19 seem to be an emerging global crisis. Machine learning radiographic models have great potential for meticulous evaluation of post-COVID-19 interstitial lung disease (ILD). Methods In this multicenter, retrospective study, we included consecutive patients that had been evaluated 3 months following severe acute respiratory syndrome coronavirus 2 infection between 01/02/2021 and 12/5/2022. High-resolution computed tomography was evaluated through Imbio Lung Texture Analysis 2.1. Results Two hundred thirty-two (n = 232) patients were analyzed. FVC% predicted was ≥80, between 60 and 79 and <60 in 74.2% (n = 172), 21.1% (n = 49), and 4.7% (n = 11) of the cohort, respectively. DLCO% predicted was ≥80, between 60 and 79 and <60 in 69.4% (n = 161), 15.5% (n = 36), and 15.1% (n = 35), respectively. Extent of ground glass opacities was ≥30% in 4.3% of patients (n = 10), between 5 and 29% in 48.7% of patients (n = 113) and <5% in 47.0% of patients (n = 109). The extent of reticulation was ≥30%, 5–29% and <5% in 1.3% (n = 3), 24.1% (n = 56), and 74.6% (n = 173) of the cohort, respectively. Patients (n = 13, 5.6%) with fibrotic lung disease and persistent functional impairment at the 6-month follow-up received antifibrotics and presented with an absolute change of +10.3 (p = 0.01) and +14.6 (p = 0.01) in FVC% predicted at 3 and 6 months after the initiation of antifibrotic. Conclusion Post-COVID-19-ILD represents an emerging entity. A substantial minority of patients presents with fibrotic lung disease and might experience benefit from antifibrotic initiation at the time point that fibrotic-like changes are "immature.” Machine learning radiographic models could be of major significance for accurate radiographic evaluation and subsequently for the guidance of therapeutic approaches.

A Simple Prognostic Score for Critical COVID-19 Derived from Patients without Comorbidities Performs Well in Unselected Patients.

We aimed to search for laboratory predictors of critical COVID-19 in consecutive adults admitted in an academic center between 16 September 2020-20 December 2021. Patients were uniformly treated with low-molecular-weight heparin, and dexamethasone plus remdesivir when SpO2 < 94%. Among consecutive unvaccinated patients without underlying medical conditions (n = 241, 49 year-old median, 71% males), 22 (9.1%) developed critical disease and 2 died (0.8%). White-blood-cell counts, neutrophils, neutrophil-to-lymphocyte ratio, CRP, fibrinogen, ferritin, LDH and γ-GT at admission were each univariably associated with critical disease. ROC-defined cutoffs revealed that CRP > 61.8 mg/L, fibrinogen > 616.5 mg/dL and LDH > 380.5 U/L were each associated with critical disease development, independently of age, sex and days from symptom-onset. A score combining higher-than-cutoff CRP (0/2), LDH (0/1) and fibrinogen (0/1) predicted critical disease (AUC: 0.873, 95% CI: 0.820-0.926). This score performed well in an unselected patient cohort (n = 1228, 100% unvaccinated) predominantly infected by the alpha variant (AUC: 0.718, 95% CI: 0.683-0.753), as well as in a mixed cohort (n = 527, 65% unvaccinated) predominantly infected by the delta variant (AUC: 0.708, 95% CI: 0.656-0.760). Therefore, we propose that a combination of standard biomarkers of acute inflammatory response, cell death and hypercoagulability reflects the severity of COVID-19 per se independently of comorbidities, age and sex, being of value for risk stratification in unselected patients.

Comparison of liver function test- and inflammation-based prognostic scores for coronavirus disease 2019: a single center study.

BACKGROUND: Although several liver- and inflammation-based scores to predict the clinical course of patients with coronavirus disease 2019 (COVID-19) have been evaluated, no direct comparison regarding their predictive ability has been performed. METHODS: 1038 patients (608 males, age 63.5 ± 17 years) hospitalized with documented COVID-19 infection to the non-ICU ward, were included retrospectively. Clinical and laboratory characteristics on admission including evaluation of Fibrosis-4 (FIB-4) score and C-Reactive Protein (CRP) to albumin ratio (CAR) were recorded. RESULTS: One hundred and twenty-four patients (11.9%) died during hospitalization after 8 (3-72) days. In multivariate analysis, FIB-4 (hazard ratio, 1.11; 95% confidence interval (CI), 1.034-1.19; P = 0.004), was independently associated with mortality, with very good discriminative ability (area under the receiver operating characteristic curve curve, 0.76). The patients with FIB-4 &gt;2.67 (n = 377), compared to those with ≤2.67 (n = 661), had worse survival (log-rank 32.6; P &lt; 0.001). Twenty-four (6.8%) of 352 patients with possible nonalcoholic fatty liver disease (NAFLD) (defined as Hepatic Steatosis Index &gt;36) died during hospitalization. In multivariate analysis, CAR was an independent risk factor (1) for mortality (hazard ratio, 1.014; 95% CI, 1.002-1.025; P = 0.021), (2) the need for high-flow nasal cannula with or without intubation (hazard ratio, 1.016; 95% CI, 1.004-1.027; P = 0.007) and (3) development of acute kidney injury (hazard ratio, 1.017; 95% CI, 1.006-1.028; P = 0.002). In addition, the patients with possible NAFLD and CAR &gt;12 (n = 154), compared to those with CAR ≤12 (n = 198), had worse survival (log-rank 5.1; P = 0.024). CONCLUSIONS: FIB-4 was an independent factor for mortality with better performance compared to other liver function test- and inflammation-based scores in patients with COVID-19, while CAR was the only score independently associated with the clinical course in COVID-19 patients with possible NAFLD.

COVID-19 and Acute Pancreatitis: A Systematic Review of Case Reports and Case Series.

BACKGROUND: Coronavirus disease 2019 (COVID-19) presents mainly with mild symptoms and involvement of the respiratory system. Acute pancreatitis has also been reported during the course of COVID-19. OBJECTIVE: Our aim is to review and analyze all reported cases of COVID-19 associated acute pancreatitis, reporting the demographics, clinical characteristics, laboratory and imaging findings, comorbidities and outcomes. DATA SOURCES: We conducted a systematic search of Pubmed/MEDLINE, SciELO and Google Scholar to identify case reports and case series, reporting COVID-19 associated acute pancreatitis in adults. STUDY SELECTION: There were no ethnicity, gender or language restrictions. The following terms were searched in combination:"COVID-19" OR "SARS-CoV-2" OR "Coronavirus 19" AND "Pancreatic Inflammation" OR "Pancreatitis" OR "Pancreatic Injury" OR "Pancreatic Disease" OR "Pancreatic Damage". Case reports and case series describing COVID-19 associated acute pancreatitis in adults were included. COVID-19 infection was established with testing of nasal and throat swabs using reverse transcription polymerase chain reaction. The diagnosis of acute pancreatitis was confirmed in accordance to the revised criteria of Atlanta classification of the Acute Pancreatitis Classification Working Group. Exclusion of other causes of acute pancreatitis was also required for the selection of the cases. DATA EXTRACTION: The following data were extracted from each report: the first author, year of publication, age of the patient, gender, gastrointestinal symptoms due to acute pancreatitis, respiratory-general symptoms, COVID-19 severity, underlying diseases, laboratory findings, imaging features and outcome. DATA SYNTHESIS: Finally, we identified and analyzed 31 articles (30 case reports and 1 case series of 2 cases), which included 32 cases of COVID-19 induced acute pancreatitis. CONCLUSION: COVID-19 associated acute pancreatitis affected mostly females. The median age of the patients was 53.5 years. Concerning laboratory findings, lipase and amylase were greater than three times the ULN while WBC counts and CRP were elevated in the most of the cases. The most frequent gastrointestinal, respiratory and general symptom was abdominal pain, dyspnea and fever, respectively. The most common imaging feature was acute interstitial edematous pancreatitis and the most frequent comorbidity was arterial hypertension while several patients had no medical history. The outcome was favorable despite the fact that most of the patients experienced severe and critical illness. LIMITATIONS: Our results are limited by the quality and extent of the data in the reports. More specifically, case series and case reports are unchecked, and while they can recommend hypotheses they are not able to confirm robust associations. CONFLICT OF INTEREST: None.

Prevalence of abnormal liver biochemistry and its impact on COVID-19 patients' outcomes: a single-center Greek study.

Background: Abnormalities in aminotransferases are frequently observed in hospitalized COVID-19 patients, but their clinical impact is poorly characterized. Methods: A total of 1046 patients hospitalized to the non-intensive care unit ward with documented COVID-19 were included retrospectively. Demographic, clinical and laboratory characteristics on admission and during hospital stay, including the presence of liver injury (LI), defined as aspartate aminotransferase (AST) >200 IU/L, were recorded. Results: On admission, 363 (34.7%) and 269 (25.7%) patients had abnormal AST and ALT values (i.e., >40 IU/L), respectively, while during hospitalization 53 (5%) patients fulfilled the criteria for LI. In multivariate logistic regression analysis, AST (odds ratio [OR] 1.023, 95% confidence interval [CI] 1.016-1.029; P<0.001), and ferritin (OR 1.01, 95%CI 1.001-1.02; P<0.001) were the baseline factors independently associated with the development of LI during hospital stay. One hundred twenty-three (11.7%) patients died during hospitalization. The independent variables associated with mortality were: age (hazard ratio [HR] 1.043, 95%CI 1.029-1.056; P<0.001), ferritin (HR 1.1, 95%CI 1.05-1.2; P<0.001), platelets (HR 0.996, 95%CI 0.994-0.999; P=0.003), and administration of remdesivir (HR 0.50, 95%CI 0.30-0.85; P=0.009). The patients with abnormal baseline AST (i.e., >40 IU/L), compared to those with normal AST values, had worse outcomes (log rank test: 8.8, P=0.003). Conclusions: Elevated aminotransferases are commonly seen in COVID-19 patients. They possibly reflect disease severity and may be associated with in-hospital mortality.

Hematological Abnormalities in COVID-19 Disease: Association With Type I Interferon Pathway Activation and Disease Outcomes.

Increased expression of interferon (IFN)-stimulated genes (ISGs) in peripheral blood, has been previously reported in viral infections, as well as in autoimmune disorders, in association with reduced leukocyte and platelet counts. Though cytopenias are common in patients with COVID-19 disease and predict severe outcomes, the underlying mechanisms have not been fully elucidated. In the current study, we aimed to determine the prevalence of hematological abnormalities in the setting of active COVID-19 infection and to explore whether they associate with disease outcomes and activation of type I IFN pathway. One-hundred-twenty-three consecutive SARS-CoV2 infected patients were included in the study. Clinical and laboratory parameters were recorded for all study participants. In 114 patients, total RNA was extracted from whole peripheral blood and subjected to real time PCR. The relative expression of three interferon stimulated genes (ISGs; IFIT1, MX-1, and IFI44) was determined and a type I IFN score reflecting peripheral type I IFN activity was calculated. The rates of anemia, leukopenia, and thrombocytopenia were 28.5, 14.6, and 24.4%, respectively. Among leukocytopenias, eosinopenia, and lymphopenia were the most prominent abnormalities being found in 56.9 and 43.1%, respectively. Of interest, patients with either eosinopenia and/or thrombocytopenia but no other hematological abnormalities displayed significantly increased peripheral type I IFN scores compared to their counterparts with normal/high eosinophil and platelet counts. While eosinopenia along with lymphopenia were found to be associated with increased risk for intubation and severe/critical disease, such an association was not detected between other hematological abnormalities or increased type I IFN scores. In conclusion, hematological abnormalities are commonly detected among patients with COVID-19 infection in association with severe disease outcomes and activation of the type I IFN pathway.

Elderly adults with COVID-19 admitted to intensive care unit: A narrative review.

BACKGROUND: In the context of the Coronavirus disease 2019 (COVID-19) pandemic, it has been reported that elderly patients are particularly at risk of developing severe illness and exhibiting increased mortality. While many studies on hospitalized elderly patients with COVID-19 have been published, limited information is available on the characteristics and clinical outcomes of those elderly patients admitted to intensive care unit (ICU). AIM: To review the available evidence of the clinical data of elderly patients admitted to the ICU due to COVID-19. METHODS: We searched for published articles available in English literature to identify those studies conducted in critically ill patients admitted to the ICU due to COVID-19, either exclusively designed for the elderly or for the whole ICU population with COVID-19, provided that analyses according to the patients' age had been conducted. RESULTS: Only one study exclusively focusing on critically ill elderly patients admitted to the ICU due to COVID-19 was found. Eighteen additional studies involving 17011 ICU patients and providing information for elderly patients as a subset of the whole study population have also been included in the present review article. Among the whole patient population, included in these studies, 8310 patients were older than 65 years of age and 2630 patients were older than 70 years. Clinical manifestations were similar for all patients; however, compared to younger ones, they suffered from more comorbidities and showed a varied, albeit high mortality. CONCLUSION: In summary, at present, although elderly patients constitute a considerable proportion of critically ill patients admitted to the ICU due to severe COVID-19, studies providing specific information are limited. The evidence so far suggests that advanced age and comorbidities are associated with worse clinical outcome. Future studies exclusively designed for this vulnerable group are needed.

The Impact of Peripheral Eosinophil Counts and Eosinophil to Lymphocyte Ratio (ELR) in the Clinical Course of COVID-19 Patients: A Retrospective Study.

BACKGROUND/AIM: Eosinophils are blood cells responsible for response against parasites and allergens. Eosinophil to lymphocyte ratio (ELR) is a biomarker for inflammatory conditions. Our aim was to evaluate the role of eosinophils and ELR in COVID-19 patients. PATIENTS AND METHODS: The study included 96 patients hospitalized with COVID-19. They were classified into moderate to severe cases and critical cases. Eosinophils and ELR were determined in both groups, in patients that died or survived and were correlated to duration of hospitalization. RESULTS: There was a statistically significant decrease in eosinophils and ELR between patients that died and patients that survived (p<0.05), and in mean values of the two biomarkers (p<0.05 for eosinophils and p<0.05 for ELR) between patients hospitalized for more or less than 15 days among those with moderate to severe disease. CONCLUSION: Lower eosinophil counts and ERL could probably predict worse outcome in COVID-19 patients.