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

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

Reduced immunogenicity of the mRNA vaccine BNT162b2 in patients with idiopathic pulmonary fibrosis.

Patients with #IPF do not mount appreciable anti-spike antibody responses to two doses of #SARSCoV2 mRNA vaccine compared to the general population. National authorities should prioritise patients with IPF for booster doses. https://bit.ly/3K2KXQ0.

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.

Tocilizumab versus baricitinib in hospitalized patients with severe COVID-19: an open label, randomized controlled trial.

OBJECTIVE: Randomized controlled trials comparing tocilizumab and baricitinib in patients with coronavirus disease 2019 (COVID-19) are needed. This was an open-label, randomized controlled trial aiming to address this unmet need. METHODS: To determine whether baricitinib was non-inferior to tocilizumab, we assessed whether the upper boundary of the two-sided 95% CI of the hazard ratio (HR) did not exceed 1.50. The primary outcome was mechanical ventilation or death by day 28. Secondary outcomes included time to hospital discharge by day 28 and change in WHO progression scale at day 10. RESULTS: We assigned 251 patients with COVID-19 and a PaO2/FiO2 ratio of <200 to receive either tocilizumab (n = 126) or baricitinib (n = 125) plus standard of care. Baricitinib was non-inferior to tocilizumab for the primary composite outcome of mechanical ventilation or death by day 28 (mechanical ventilation or death for patients who received baricitinib, 39.2% [n = 49/125]; mechanical ventilation or death for patients who received tocilizumab, 44.4% [n = 56/126]; HR, 0.83; 95% CI, 0.56-1.21; p 0.001 for non-inferiority). Baricitinib was non-inferior to tocilizumab for the time to hospital discharge within 28 days (patients who received baricitinib- discharged alive: 58.4% [n = 73/125] vs. patients who received tocilizumab- discharged alive: 52.4% [n = 66/126]; HR, 0.85; 95% CI, 0.61-1.18; p < 0.001 for non-inferiority). There was no significant difference between the baricitinib and tocilizumab arms in the change in WHO scale at day 10 (0.0 [95% CI, 0.0-0.0] vs. 0.0 [95% CI, 0.0-1.0]; p 0.83). DISCUSSION: In the setting of this trial, baricitinib was non-inferior to tocilizumab with regards to the composite outcome of mechanical ventilation or death by day 28 and the time to discharge by day 28 in patients with severe COVID-19.

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.

Reduced immunogenicity of the mRNA vaccine BNT162b2 in patients with IPF

The emergence and spread of 2019 coronavirus disease (COVID-19) are causing a growing global public health crisis. Despite advances in treatment, vaccination remains the best way to contain the pandemic [1]. Vaccines are currently available by means of conditional marketing approval, full approval and emergency use authorization pathways [2]. Evidence suggest that immunocompromised individuals including solid organ transplants recipients and patients under immunosuppressive treatment may have increased mortality from SARS-CoV-2 infection despite double dose messenger RNA (mRNA) vaccine regimens [3]. This is partially attributed to blunted immune responses to vaccination since only 38–54% of kidney and liver transplant recipients developed detectable SARS-CoV-2 antibodies following the second dose of mRNA vaccines [3, 4].

Tocilizumab improves 28-day survival in hospitalized patients with severe COVID-19: an open label, prospective study.

BACKGROUND: Data on the safety and efficacy profile of tocilizumab in patients with severe COVID-19 needs to be enriched. METHODS: In this open label, prospective study, we evaluated clinical outcomes in consecutive patients with COVID-19 and PaO2/FiO2 < 200 receiving tocilizumab plus usual care versus usual care alone. Tocilizumab was administered at the time point that PaO2/FiO2 < 200 was observed. The primary outcome was 28-day mortality. Secondary outcomes included time to discharge, change in PaO2/FiO2 at day 5 and change in WHO progression scale at day 10. FINDINGS: Overall, 114 patients were included in the analysis (tocilizumab plus usual care: 56, usual care: 58). Allocation to usual care was associated with significant increase in 28-day mortality compared to tocilizumab plus usual care [Cox proportional-hazards model: HR: 3.34, (95% CI: 1.21-9.30), (p = 0.02)]. There was not a statistically significant difference with regards to hospital discharge over the 28 day period for patients receiving tocilizumab compared to usual care [11.0 days (95% CI: 9.0 to 16.0) vs 14.0 days (95% CI: 10.0-24.0), HR: 1.32 (95% CI: 0.84-2.08), p = 0.21]. ΔPaO2/FiO2 at day 5 was significantly higher in the tocilizumab group compared to the usual care group [42.0 (95% CI: 23.0-84.7) vs 15.8 (95% CI: - 19.4-50.3), p = 0.03]. ΔWHO scale at day 10 was significantly lower in the tocilizumab group compared to the usual care group (-0.5 ± 2.1 vs 0.6 ± 2.6, p = 0.005). CONCLUSION: Administration of tocilizumab, at the time point that PaO2/FiO2 < 200 was observed, improved survival and other clinical outcomes in hospitalized patients with severe COVID-19 irrespective of systemic inflammatory markers levels.

Commonalities Between ARDS, Pulmonary Fibrosis and COVID-19: The Potential of Autotaxin as a Therapeutic Target.

Severe COVID-19 is characterized by acute respiratory distress syndrome (ARDS)-like hyperinflammation and endothelial dysfunction, that can lead to respiratory and multi organ failure and death. Interstitial lung diseases (ILD) and pulmonary fibrosis confer an increased risk for severe disease, while a subset of COVID-19-related ARDS surviving patients will develop a fibroproliferative response that can persist post hospitalization. Autotaxin (ATX) is a secreted lysophospholipase D, largely responsible for the extracellular production of lysophosphatidic acid (LPA), a pleiotropic signaling lysophospholipid with multiple effects in pulmonary and immune cells. In this review, we discuss the similarities of COVID-19, ARDS and ILDs, and suggest ATX as a possible pathologic link and a potential common therapeutic target.

Epidemiological characteristics and outcomes from 187 patients with COVID-19 admitted to 6 reference centers in Greece: an observational study during the first wave of the COVID-19 pandemic.

INTRODUCTION: Epidemiological data from patients with COVID-19 has been recently published in several countries. Nationwide data of hospitalized patients with COVID-19 in Greece remain scarce. MATERIAL AND METHODS: This was an observational, retrospective study from 6 reference centers between February 26 and May 15, 2020. RESULTS: The patients were mostly males (65.7%) and never smokers (57.2%) of median age 60 (95% CI: 57.6-64) years. The majority of the subjects (98%) were treated with the standard-of-care therapeutic regimen at that time, including hydroxychlo-roquine and azithromycin. Median time of hospitalization was 10 days (95% CI: 10-12). Twenty-five (13.3%) individuals were intubated and 8 died (4.2%). The patients with high neutrophil-to-lymphocyte ratio (NLR) ( > 3.58) exhibited more severe disease as indicated by significantly increased World Health Organization (WHO) R&D ordinal scale (4; 95% CI: 4-4 vs 3; 95% CI: 3-4, p = 0.0001) and MaxFiO2% (50; 95% CI: 38.2-50 vs 29.5; 95% CI: 21-31, p < 0.0001). The patients with increased lactate dehydrogenase (LDH) levels ( > 270 IU/ml) also exhibited more advanced disease compared to the low LDH group ( < 270 IU/ml) as indicated by both WHO R&D ordinal scale (4; 95% CI: 4-4 vs 4; 95% CI: 3-4, p = 0.0001) and MaxFiO2% (50; 95% CI: 35-60 vs 28; 95% CI: 21-31, p < 0.0001). CONCLUSION: We present the first epidemiological report from a low-incidence and mortality COVID-19 country. NLR and LDH may represent reliable disease prognosticators leading to timely treatment decisions.

Reduction in Hospitalizations for Respiratory Diseases during the First COVID-19 Wave in Greece.

INTRODUCTION: During the first COVID-19 wave, a considerable decline in hospital admissions was observed worldwide. AIM: This retrospective cohort study aimed to assess if there were any changes in the number of patients hospitalized for respiratory diseases in Greece during the first CO-VID-19 wave. METHODS: In the present study, we evaluated respiratory disease hospitalization rates across 9 tertiary hospitals in Greece during the study period (March-April 2020) and the corresponding period of the 2 previous years (2018-2019) that served as the control periods. Demographic data and discharge diagnosis were documented for every patient. RESULTS: Of the 1,307 patients who were hospitalized during the study period, 444 (35.5%) were males with a mean (±SD) age of 66.1 ± 16.6 years. There was a 47 and 46% reduction in all-cause respiratory morbidity compared to the corresponding periods of 2018 and 2019, respectively. The mean incidence rate for respiratory diseases during the study period was 21.4 admissions per day, and this rate was significantly lower than the rate during the same period in 2018 (40.8 admissions per day; incidence rate ratio [IRR], 0.525; 95% confidence interval [CI], 0.491-0.562; p < 0.001) or the rate during 2019 (39.9 admissions per day; IRR, 0.537; 95% CI, 0.502-0.574; p < 0.001). The greatest reductions (%) in the number of daily admissions in 2020 were observed for sleep apnoea (87% vs. 2018 and 84% vs. 2019) followed by admissions for asthma (76% vs. 2018 and 79% vs. 2019) and chronic obstructive pulmonary disease (60% vs. 2018 and 51% vs. 2019), while the lowest reductions were detected in hospitalizations for pulmonary embolism (6% vs. 2018 and 23% vs. 2019) followed by tuberculosis (25% vs. both 2018 and 2019). DISCUSSION/CONCLUSION: The significant reduction in respiratory admissions in 2020 raises the reasonable question of whether some patients may have avoided seeking medical attention during the COVID-19 pandemic and suggests an urgent need for transformation of healthcare systems during the pandemic to offer appropriate management of respiratory diseases other than COVID-19.

Bronchoscopy during the COVID-19 pandemic: effect on current practices and strategies to reduce procedure-associated transmission.

Introduction: Bronchoscopy and related procedures have unambiguously been affected during the Corona Virus Disease 2019 (COVID-19) pandemic caused by Severe Acute Respiratory Syndrome-Corona Virus-2 (SARS COV-2). Ordinary bronchoscopy practices and lung cancer services might have changed over this pandemic and for the years to come.Areas covered: This manuscript summarizes the utility of bronchoscopy in COVID-19 patients, and the impact of the pandemic in lung cancer diagnostic services, in view of possible viral spread during these We conducted a literature review of articles published in PubMed/Medline from inception to November 5th, 2020 using relevant terms.Expert opinion: Without doubt this pandemic has changed the way bronchoscopy and related procedures are being performed. Mandatory universal personal protective equipment, pre-bronchoscopy PCR tests, dedicated protective barriers and disposable bronchoscopes might be the safest and simpler way to perform even the most complicated procedures.

Increased Red Cell Distribution Width Is Associated With Disease Severity in Hospitalized Adults With SARS-CoV-2 Infection: An Observational Multicentric Study.

Background: There is an amenable need for clinically applicable biomarkers in patients with SARS-CoV-2 infection. Red Cell Distribution Width (RDW) has been recently suggested as a prognostic biomarker for COVID-19. Methods: This was an observational study enrolling patients between February 26 and May 15 2020. We aimed to validate the association of the previously published RDW threshold of 14.5% with markers of disease progression and mortality. Results: A total number of 193 hospitalized patients with COVID-19 were enrolled and analyzed. Median age was 61 years (95% CI: 58-64). Patients with baseline RDW ≥14.5% (n = 41, 19.2%) presented with more progressive disease compared to patients with baseline RDW <14.5% (n = 156, 80.8%) as indicated by significant differences in maximum FiO2% during hospitalization (median: 100, 95% CI: 45.2-100, vs. 35, 95% CI: 31-40, p = 0.0001, respectively). Values of RDW ≥14.5% were also strongly associated with increased risk of mortality (HR: 4.1, 95% CI: 0.88-19.23), (p = 0.02). Conclusion: Our study provides evidence to support reproducibility and validity of a specified cut-off threshold of RDW as biomarker of disease severity and mortality in patients with COVID-19.

False Positive COVID-19 Antibody Test in a Case of Granulomatosis With Polyangiitis.

Collateral damage due to 2019 novel coronavirus disease (COVID-19) represents an emerging issue. Symptoms of COVID-19 are not disease-specific. Differential diagnosis is challenging and the exclusion of other life-threatening diseases has major caveats. In the era of this pandemic, diagnosis of other life-threatening diseases might delay treatment. The Food and Drug Administration has recently authorized the first antibody-based test for COVID-19; however, RT-PCR of nasopharyngeal or oropharyngeal swabs remains the recommended test for diagnosis. We present the first report of a false positive COVID-19 antibody test in a case of Granulomatosis with Polyangiitis (GPA). Specifically, the case concerns an 82-year-old female, never smoker, who was admitted to our hospital with symptoms of fever and general fatigue that had lasted 7 days. She already had a positive IgM test for COVID-19, yet multiple RT-PCR tests had returned as negative for SARS-CoV-2. In the following days, her renal function deteriorated, while hematuria and proteinuria with active urinary sediment developed. Based on high clinical suspicion for ANCA-associated vasculitis, we performed a complete immunologic profile which revealed positive c-ANCA with elevated titers of anti-PR3. Pulses of methylprednisolone along with cyclophosphamide were applied. At day 10, treatment response was noticed as indicated by respiratory and renal function improvement. This report highlights the need for meticulous patient evaluation in order to avoid misdiagnosis in the era of COVID-19.