BACKGROUND: Recovery from acute COVID-19 may be slow and incomplete: cases of Post-Acute Sequelae of COVID (PASC) are counted in millions, worldwide. We aimed to explore if and how the pre-existing Socio-economic-status (SES) influences such recovery.
METHODS: We analyzed a database of 1536 consecutive patients from the first wave of COVID-19 in Italy (February-September 2020), previously admitted to our referral hospital, and followed-up in a dedicated multidisciplinary intervention. We excluded those seen earlier than 12 weeks (the conventional limit for a possible PASC syndrome), and those reporting a serious complication from the acute phase (possibly accounting for symptoms persistence). We studied whether the exposition to disadvantaged SES (estimated through the Italian Institute of Statistics\'s model - ISTAT 2017) was affecting recovery outcomes, that is: symptoms (composite endpoint, i.e. at least one among: dyspnea, fatigue, myalgia, chest pain or palpitations); Health-Related-Quality-of-Life (HRQoL, as by SF-36 scale); post-traumatic-stress-disorder (as by IES-R scale); and lung structural damage (as by impaired CO diffusion, DLCO).
RESULTS: Eight-hundred and twenty-five patients were included in the analysis (median age 59 years; IQR: 50-69 years, 60.2% men), of which 499 (60.5%) were previously admitted to hospital and 27 (3.3%) to Intensive-Care Unit (ICU). Those still complaining of symptoms at follow-up were 337 (40.9%; 95%CI 37.5-42.2%), and 256 had a possible Post-Traumatic Stress Disorder (PTSD) (31%, 95%CI 28.7-35.1%). DLCO was reduced in 147 (19.6%, 95%CI 17.0-22.7%). In a multivariable model, disadvantaged SES was associated with a lower HRQoL, especially for items exploring physical health (Limitations in physical activities: OR = 0.65; 95%CI = 0.47 to 0.89; p = 0.008; AUC = 0.74) and Bodily pain (OR = 0.57; 95%CI = 0.40 to 0.82; p = 0.002; AUC = 0.74). We did not observe any association between SES and the other outcomes.
CONCLUSIONS: Recovery after COVID-19 appears to be independently affected by a pre-existent socio-economic disadvantage, and clinical assessment should incorporate SES and HRQoL measurements, along with symptoms. The socioeconomic determinants of SARS-CoV-2 disease are not exclusive of the acute infection: this finding deserves further research and specific interventions.

Background: Immune checkpoint blockade (ICB) has presented a breakthrough in the treatment of malignant tumors and increased the overall survival of patients with various tumor entities. ICB may also cause immune-related adverse events, such as pneumonitis or interstitial lung disease. The lung clearance index (LCI) is a multiple-breath washout technique offering information on lung pathology in addition to conventional spirometry. It measures the degree of pulmonary ventilation inhomogeneity and allows early detection of pulmonary damage, especially that to peripheral airways. Methods: This cross-sectional study compared the lung function of patients with melanoma or metastatic cutaneous squamous cell carcinoma who received programmed cell death 1 (PD-1) and cytotoxic T-Lymphocyte-associated Protein 4 (CTLA-4) antibodies, alone or in combination, to age- and sex-matched controls. Lung function was assessed using spirometry, according to American Thoracic Society and European Respiratory Society standards, the LCI, and a diffusion capacity of carbon monoxide (DLCO) measurement. Results: Sixty-one screened patients and thirty-eight screened controls led to nineteen successfully included pairs. The LCI in the ICB-treated patients was 8.41 ± 1.15 (mean ± SD), which was 0.32 higher compared to 8.07 ± 1.17 in the control group, but the difference was not significant (p = 0.452). The patients receiving their ICB therapy for under five months showed a significantly lower LCI (7.98 ± 0.77) compared to the ICB patients undergoing therapy for over five months (9.63 ± 1.22) at the point of testing (p = 0.014). Spirometric analysis revealed that the forced expiratory volume between 25 and 75% of the forced vital capacity (FEF25-75%) in the ICB-treated patients was significantly reduced (p = 0.047) compared to the control group. DLCO (%predicted and adjusted for hemoglobin) was 94.4 ± 19.7 in the ICB patients and 93.4 ± 21.7 in the control group (p = 0.734). Conclusions: The patients undergoing ICB therapy showed slightly impaired lung function compared to the controls. Longer periods of ICB treatment led to deterioration of the LCI, which may be a sign of a subclinical inflammatory process. The LCI is feasible and may be easily integrated into the clinical daily routine and could contribute to early detection of pulmonary (auto-)inflammation.

Decreased diffusion capacity for carbon monoxide (DLCO) is the most prevalent pulmonary testing abnormality among COVID-19 recoverees. We prospectively followed 51 individuals with impaired DLCO at an average of ∼3 months following COVID-19 and re-examined them at one year. At follow-up, mean DLCO increased from 68.0 % to 72.6 % (p = 0.002); while 33 % of the cohort experienced a clinically significant rise (>10 points) in DLCO, only 29 % normalized their values. While DLCO change did not correlate with symptoms, lack of improvement was more prevalent among individuals with obesity. Regardless of COVID-19 severity, a substantial proportion continued to exhibit DLCO impairment at 1-year.

Background and Objectives: Assessment of the prothrombotic, proinflammatory, and functional status of a cohort of COVID-19 patients at least two years after the acute infection to identify parameters with potential therapeutic and prognostic value. Materials and Methods: We conducted a retrospective, descriptive study that included 117 consecutive patients admitted to Iasi Pulmonary Rehabilitation Clinic for reassessment and a rehabilitation program at least two years after a COVID-19 infection. The cohort was divided into two groups based on the presence (n = 49) or absence (n = 68) of pulmonary fibrosis, documented through high-resolution computer tomography. Results: The cohort comprises 117 patients, 69.23% females, with a mean age of 65.74 ± 10.19 years and abnormal body mass index (31.42 ± 5.71 kg/m2). Patients with pulmonary fibrosis have significantly higher levels of C-reactive protein (CRP) (p < 0.05), WBC (7.45 ± 7.86/mm3 vs. 9.18 ± 17.24/mm3, p = 0.053), neutrophils (4.68 ± 7.88/mm3 vs. 9.07 ± 17.44/mm3, p < 0.05), mean platelet volume (MPV) (7.22 ± 0.93 vs. 10.25 ± 0.86 fL, p < 0.05), lactate dehydrogenase (p < 0.05), and D-dimers (p < 0.05), but not ferritin (p = 0.470), reflecting the chronic proinflammatory and prothrombotic status. Additionally, patients with associated pulmonary fibrosis had a higher mean heart rate (p < 0.05) and corrected QT interval (p < 0.05). D-dimers were strongly and negatively correlated with diffusion capacity corrected for hemoglobin (DLCO corr), and ROC analysis showed that the persistence of high D-dimers values is a predictor for low DLCO values (ROC analysis: area under the curve of 0.772, p < 0.001). The results of pulmonary function tests (spirometry, body plethysmography) and the 6-minute walk test demonstrated no significant difference between groups, without notable impairment within either group. Conclusions: Patients with COVID-19-related pulmonary fibrosis have a persistent long-term proinflammatory, prothrombotic status, despite the functional recovery. The persistence of elevated D-dimer levels could emerge as a predictive factor associated with impaired DLCO.

To determine the cardiopulmonary changes in the survivors of acute COVID-19 infection at 3-6 month and 6-12 month. We followed up 53 patients out of which 28 (52%) had mild COVID-19 and 25 (48%) had severe COVID-19. The first follow-up was between 3 month after diagnosis up to 6 month and second follow-up between 6 and 12 month from the date of diagnosis of acute COVID-19. They were monitored using vital parameters, pulmonary function tests, echocardiography and a chest computed tomography (CT) scan. We found improvement in diffusing capacity for carbon monoxide (DLCO) with a median of 52% of predicted and 80% of predicted at the first and second follow-up, respectively. There was improvement in the CTSS in severe group from 22 (18-24) to 12 (10-18; p-0.001). Multivariable logistic regression revealed increased odds of past severe disease with higher CTSS at follow-up (OR-1.7 [CI 1.14-2.77]; P = 0.01). Correlation was found between CTSS and DLCO at second follow-up (r2 = 0.36; p < 0.01). Most of patients recovered from COVID-19 but a subgroup of patients continued to have persistent radiological and pulmonary function abnormalities necessitating a structured follow-up.

The 2017 American Thoracic Society/European Respiratory Society (ATS/ERS) diffusing capacity of the lung for carbon monoxide (DLCO) standards specify a control rule for assessing biologic quality control (BioQC) but have limited guidance on how to establish expected values for control rule variables. This study aimed to determine expected values for DLCO BioQC using coefficient of variation (CV) and compare that the mean ± 2 SD control rule yields the same precision as mean ± 12% of the mean.
DLCO BioQC data were collected from a multi-center inhaled medication study. This descriptive study spanned 42 months ending in 2018. The annual DLCO CV was based upon 10 DLCO values separated by at least 5 d. The root mean square CV (RMSCV) was computed for each year and Friedman test evaluated within subject annual CV changes. Ninetieth percentile values were computed for annual control rule limits/mean DLCO.
Of 217 BioQCs, the study\'s first year had 168 subjects with fewer in subsequent years. Annual CV values from RMSCV were 5.3, 4.5, and 4.6% in years 1, 2, and 3, respectively. No change was seen in the CV for those subjects with data for all 3 years, n = 24, P = .07. The 90th percentile of measurements 2 SD/mean DLCO were 15, 12.4, and 11% in years 1, 2, and 3, respectively.
A DLCO BioQC CV ≤ 6% is achievable across multiple sites, technologists, and brands of equipment. This CV value assures that measurements for control rule variables emerge from an expected range. A control rule of mean ± 2 SD appeared to yield similar results as the mean ± 12% of the mean rule reported in the 2017 ATS/ERS DLCO standards.

Factors associated with long-term sequelae emerging after the acute phase of COVID-19 (so called \"long COVID\") are unclear. Here, we aimed to identify risk factors for the development of COVID-19 sequelae in a prospective cohort of subjects hospitalized for SARS-CoV-2 infection and followed up one year after discharge.
A total of 324 subjects underwent a comprehensive and multidisciplinary evaluation one year after hospital discharge for COVID-19. A subgroup of 247/324 who consented to donate a blood sample were tested for a panel of circulating cytokines.
In 122 patients (37.8%) there was evidence of at least one persisting physical symptom. After correcting for comorbidities and COVID-19 severity, the risk of developing long COVID was lower in the 109 subjects admitted to the hospital in the third wave of the pandemic than in the 215 admitted during the first wave, (OR 0.69, 95%CI 0.51-0.93, p=0.01). Univariable analysis revealed female sex, diffusing capacity of the lungs for carbon monoxide (DLCO) value, body mass index, anxiety and depressive symptoms to be positively associated with COVID-19 sequelae at 1 year. Following logistic regression analysis, DLCO was the only independent predictor of residual symptoms (OR 0.98 CI 95% (0.96-0.99), p=0.01). In the subgroup of subjects with normal DLCO (> 80%), for whom residual lung damage was an unlikely explanation for long COVID, the presence of anxiety and depressive symptoms was significantly associated to persistent symptoms, together with increased levels of a set of pro-inflammatory cytokines: interferon-gamma, tumor necrosis factor-alpha, interleukin (IL)-2, IL-12, IL-1β, IL-17. In logistic regression analysis, depressive symptoms (p=0.02, OR 4.57 [1.21-17.21]) and IL-12 levels (p=0.03, OR 1.06 [1.00-1.11]) 1-year after hospital discharge were independently associated with persistence of symptoms.
Long COVID appears mainly related to respiratory sequelae, prevalently observed during the first pandemic wave. Among patients with little or no residual lung damage, a cytokine pattern consistent with systemic inflammation is in place.

Background: Up to 53% of individuals who had mild COVID-19 experience symptoms for >3-month following infection (Long-CoV). Dyspnea is reported in 60% of Long-CoV cases and may be secondary to impaired exercise capacity (VO2peak) as a result of pulmonary, pulmonary vascular, or cardiac insult. This study examined whether cardiopulmonary mechanisms could explain exertional dyspnea in Long-CoV. Methods: A cross-sectional study of participants with Long-CoV (n = 28, age 40 ± 11 years, 214 ± 85 days post-infection) and age- sex- and body mass index-matched COVID-19 naïve controls (Con, n = 24, age 41 ± 12 years) and participants fully recovered from COVID-19 (ns-CoV, n = 14, age 37 ± 9 years, 198 ± 89 days post-infection) was conducted. Participants self-reported symptoms and baseline dyspnea (modified Medical Research Council, mMRC, dyspnea grade), then underwent a comprehensive pulmonary function test, cardiopulmonary exercise test, exercise pulmonary diffusing capacity measurement, and rest and exercise echocardiography. Results: VO2peak, pulmonary function and cardiac/pulmonary vascular parameters were not impaired in Long- or ns-CoV compared to normative values (VO2peak: 106 ± 25 and 107 ± 25%predicted, respectively) and cardiopulmonary responses to exercise were otherwise normal. When Long-CoV were stratified by clinical dyspnea severity (mMRC = 0 vs mMRC≥1), there were no between-group differences in VO2peak. During submaximal exercise, dyspnea and ventilation were increased in the mMRC≥1 group, despite normal operating lung volumes, arterial saturation, diffusing capacity and indicators of pulmonary vascular pressures. Interpretation: Persistent dyspnea after COVID-19 was not associated with overt cardiopulmonary impairment or exercise intolerance. Interventions focusing on dyspnea management may be appropriate for Long-CoV patients who report dyspnea without cardiopulmonary impairment.

Idiopathic pulmonary fibrosis (IPF) is a disease that primarily occurs in elderly individuals. However, it is difficult to diagnose and has a complex disease course. High-resolution computed tomography (HRCT) and lung function testing are crucial for its diagnosis and follow-up. However, the correlation of HRCT findings with lung function test results has not been extensively investigated.
This study retrospectively analysed the medical records and images of patients with IPF. Patients with evident emphysema and lung cancer were excluded. The diagnosis of all the included cases was confirmed following a discussion among specialists from multiple disciplines. The correlation of HRCT findings, including fibrotic score, HRCT lung volume, pulmonary artery trunk (PA) diameter and pulmonary vascular volume (PVV), with lung function test parameters, such as forced vital capacity (FVC) and diffusing capacity for carbon monoxide (DLCO), was analysed.
A total of 32 patients were included. Higher fibrotic and PVV scores were significantly correlated with lower DLCO (r =  - 0.59, p = 0.01; r =  - 0.43, p = 0.03, respectively) but not with FVC. Higher PVV score significantly correlated with higher fibrotic score (r = 0.59, p < 0.01) and PA diameter (r = 0.47, p = 0.006).
Our study demonstrated the structural and functional correlation of IPF. The extent of lung fibrosis (fibrotic score) and PVV score were associated with DLCO but not with FVC. The PA diameter, which reflects the pulmonary artery pressure, was found to be associated with the PVV score.

BACKGROUND: The first wave of the COVID-19 pandemic initiated officially in October 2020. Since then several observations have been made regarding the disease and its symptoms.
METHODS: We included eighty seven in our observational study. Our main aim was to investigate their long term respiratory follow-up in correlation with their initial radiological and laboratory findings and values. The nose swab PCR test for COVID-19 was used for diagnosis. Patients were monitored at 3 and 6 months after their hospital reception whereas basic parameters of health condition (smoking, PO2, SPO2, WBC, CXR, CRP, intercurrent findings, days of nursing, colchicine administration) in joint with gender and age were recorded.
RESULTS: Males seem more susceptible to the viral disease than females in a ratio 1,8:1. The parameters FEV1 and FVC (as % relative changes) were not affected, apart from the DLCO to which CRP (in loge+1 transformation) and SPO2 showed a statistically significant effect.
CONCLUSIONS: None of these patients were intubated, or admitted to the intensive care unit. The respiratory function is affected by the virus and the effect is reversed within the first three months. Males are more affected and the radiological and laboratory findings are associated with the respiratory functions.