Association between serum ferritin level and decreased diffusion capacity 3 months after the onset of COVID-19 pneumonia.

BACKGROUND: Coronavirus disease 2019 (COVID-19) pneumonia can have prolonged sequelae and lead to respiratory dysfunction, mainly because of impaired diffusion capacity for carbon monoxide (DLCO). The clinical factors associated with DLCO impairment, including blood biochemistry test parameters, remain unclear. METHODS: Patients with COVID-19 pneumonia who underwent inpatient treatment between April 2020 and August 2021 were included in this study. A pulmonary function test was performed 3 months after onset, and the sequelae symptoms were investigated. Clinical factors, including blood test parameters and abnormal chest shadows on computed tomography, of COVID-19 pneumonia associated with DLCO impairment were investigated. RESULTS: In total, 54 recovered patients participated in this study. Twenty-six patients (48%) and 12 patients (22%) had sequelae symptoms 2 and 3 months after, respectively. The main sequelae symptoms at 3 months were dyspnea and general malaise. Pulmonary function tests showed that 13 patients (24%) had both DLCO <80% predicted value (pred) and DLCO/alveolar volume (VA) <80% pred, and appeared to have DLCO impairment not attributable to an abnormal lung volume. Clinical factors associated with impaired DLCO were investigated in multivariable regression analysis. Ferritin level of >686.5 ng/mL (odds ratio: 11.08, 95% confidence interval [CI]: 1.84-66.59; p = 0.009) was most strongly associated with DLCO impairment. CONCLUSIONS: Decreased DLCO was the most common respiratory function impairment, and ferritin level was a significantly associated clinical factor. Serum ferritin level could be used as a predictor of DLCO impairment in cases of COVID-19 pneumonia.

Evolution and long­term respiratory sequelae after severe COVID-19 pneumonia: nitric oxide diffusion measurement value.

INTRODUCTION: There are no published studies assessing the evolution of combined determination of the lung diffusing capacity for both nitric oxide and carbon monoxide (DLNO and DLCO) 12 months after the discharge of patients with COVID-19 pneumonia. METHODS: Prospective cohort study which included patients who were assessed both 3 and 12 months after an episode of SARS-CoV-2 pneumonia. Their clinical status, health condition, lung function testings (LFTs) results (spirometry, DLNO-DLCO analysis, and six-minute walk test), and chest X-ray/computed tomography scan images were compared. RESULTS: 194 patients, age 62 years (P25-75, 51.5-71), 59% men, completed the study. 17% required admission to the intensive care unit. An improvement in the patients' exercise tolerance, the extent of the areas of ground-glass opacity, and the LFTs between 3 and 12 months following their hospital discharge were found, but without a decrease in their degree of dyspnea or their self-perceived health condition. DLNO was the most significantly altered parameter at 12 months (19.3%). The improvement in DLNO-DLCO mainly occurred at the expense of the recovery of alveolar units and their vascular component, with the membrane factor only improving in patients with more severe infections. CONCLUSIONS: The combined measurement of DLNO-DLCO is the most sensitive LFT for the detection of the long-term sequelae of COVID-19 pneumonia and it explain better their pathophysiology.

Effect of Altitude on Respiratory Functional Status in COVID-19 Survivors: Results from a Latin American Cohort-FIRCOV.

Laura Gochicoa-Rangel, Santiago C. Arce, Carlos Aguirre-Franco, Wilmer Madrid-Mejía, Mónica Gutiérrez-Clavería, Lorena Noriega-Aguirre, Patricia Schonffeldt-Guerrero, Agustín Acuña-Izcaray, Arturo Cortés-Telles, Luisa Martínez-Valdeavellano, Federico Isaac Hernández-Rocha, Omar Ceballos-Zúñiga, Rodrigo Del Rio Hidalgo, Sonia Sánchez, Erika Meneses-Tamayo, and Iván Chérrez-Ojeda; and on Behalf of the Respiratory Physiology Project in COVID-19 (FIRCOV). Effect of altitude on respiratory functional status in COVID-19 survivors: results from a Latin American Cohort-FIRCOV. High Alt Med Biol 24:37-48, 2023. Persistent symptoms and lung function abnormalities are common in COVID-19 survivors. Objectives: To determine the effect of altitude and other independent variables on respiratory function in COVID-19 survivors. Methods: Analytical, observational, cross-sectional cohort study done at 13 medical centers in Latin America located at different altitudes above sea level. COVID-19 survivors were invited to perform pulmonary function tests at least 3 weeks after diagnosis. Results: 1,368 participants (59% male) had mild (20%), moderate (59%), and severe (21%) disease. Restriction by spirometry was noted in 32%; diffusing capacity of the lung for carbon monoxide (DLCO) was low in 43.7%; and 22.2% walked less meters during the 6-minute walk test (6-MWT). In multiple linear regression models, higher altitude was associated with better spirometry, DLCO and 6-MWT, but lower oxygen saturation at rest and during exercise. Men were 3 times more likely to have restriction and 5.7 times more likely to have a low DLCO. Those who had required mechanical ventilation had lower DLCO and walked less during the 6-MWT. Conclusions: Men were more likely to have lower lung function than women, even after correcting for disease severity and other factors. Patients living at a higher altitude were more likely to have better spirometric patterns and walked farther but had lower DLCO and oxygen saturation.

Longitudinal follow-up of postacute COVID-19 syndrome: DLCO, quality-of-life and MRI pulmonary gas-exchange abnormalities.

129Xe MRI red blood cell to alveolar tissue plasma ratio (RBC:TP) abnormalities have been observed in ever-hospitalised and never-hospitalised people with postacute COVID-19 syndrome (PACS). But, it is not known if such abnormalities resolve when symptoms and quality-of-life scores improve. We evaluated 21 participants with PACS, 7±4 months (baseline) and 14±4 months (follow-up) postinfection. Significantly improved diffusing capacity of the lung for carbon monoxide (DLCO, Δ=14%pred ;95%CI 7 to 21, p<0.001), postexertional dyspnoea (Δ=-0.7; 95%CI=-0.2 to -1.2, p=0.019), St George's Respiratory Questionnaire-score (SGRQ Δ=-6; 95% CI=-1 to -11, p=0.044) but not RBC:TP (Δ=0.03; 95% CI=0.01 to 0.05, p=0.051) were observed at 14 months. DLCO correlated with RBC:TP (r=0.60, 95% CI=0.22 to 0.82, p=0.004) at 7 months. While DLCO and SGRQ measurements improved, these values did not normalise 14 months post-infection. ClinicalTrials.gov NCT04584671.

An assessment of post-COVID-19 infection pulmonary functions in healthcare professionals.

BACKGROUND: The medium- and long-term effects of COVID-19 infection on pulmonary function are still unknown. The present study aimed to investigate the pulmonary functions in healthcare professionals who had persistent complaints after contracting COVID-19 and returning to work. METHODS: The study included COVID-19-infected healthcare professionals from the Düzce University Medical Faculty Hospital who volunteered to participate. Medical histories, medical records, pulmonary function tests, the diffusing capacity of the lungs for carbon monoxide (DLCO) test, and the 6-minute walk test (6MWT) were used to collect data from all participants. RESULTS: The study included 53 healthcare professionals, with an average age of 38 ± 10 years (min: 24 years and max: 71 years), including 29 female (54.7%) and 24 male (45.3%) participants. Of the participants, 22.6% were smokers, 35.8% (19 individuals) had comorbidities, and 17% (9 individuals) were hospitalized. The mean length of stay was 9 ± 4 days (mean ± standard deviation). The most prevalent symptoms were weakness (88.7%), muscle aches (67.9%), inability to smell/taste (60.4%), headache (54.7%), fever (45.3%), cough (41.5%), and shortness of breath (37.7%). The mean time to return to work after a positive polymerase chain reaction (PCR) test for COVID-19 was 18 ± 13 days. The average time among post-disease pulmonary function, 6MW, and DLCO tests was 89 ± 36 days (min: 15 and max: 205). The DLCO level decreased in 39.6% (21) of the participants. Female participants had a significantly higher rate of decreased DLCO levels than male participants (25% vs. 55.2%, P = .026). DLCO levels were significantly higher in participants with long-term persistent complaints (P = .043). The later the time to return to work, the lower the DLCO value (r = -0.290 and P = .035). The 6MWT distance was positively correlated with hemoglobin and lymphocyte levels at the time of the disease onset and negatively correlated with D-dimer levels. The most prevalent symptoms during the control visits were shortness of breath/effort dyspnea (24.6%), weakness (9.5%), and muscle aches (7.6%). CONCLUSION: Significant persistent complaints (47.2%) and low DLCO levels (39.6%) were observed in healthcare professionals during control visits at a mean time of 3 months after the COVID-19 infection. Symptoms and spirometry measurements, including DLCO, may be helpful in the follow-up of healthcare professionals who contracted COVID-19. Further comprehensive studies with long-term follow-up periods are required.

Elevated plasma levels of epithelial and endothelial cell markers in COVID-19 survivors with reduced lung diffusing capacity six months after hospital discharge.

BACKGROUND: Some COVID-19 survivors present lung function abnormalities during follow-up, particularly reduced carbon monoxide lung diffusing capacity (DLCO). To investigate risk factors and underlying pathophysiology, we compared the clinical characteristics and levels of circulating pulmonary epithelial and endothelial markers in COVID-19 survivors with normal or reduced DLCO 6 months after discharge. METHODS: Prospective, observational study. Clinical characteristics during hospitalization, and spirometry, DLCO and plasma levels of epithelial (surfactant protein (SP) A (SP-A), SP-D, Club cell secretory protein-16 (CC16) and secretory leukocyte protease inhibitor (SLPI)), and endothelial (soluble intercellular adhesion molecule 1 (sICAM-1), soluble E-selectin and Angiopoietin-2) 6 months after hospital discharge were determined in 215 COVID-19 survivors. RESULTS: DLCO was < 80% ref. in 125 (58%) of patients, who were older, more frequently smokers, had hypertension, suffered more severe COVID-19 during hospitalization and refer persistent dyspnoea 6 months after discharge. Multivariate regression analysis showed that age ≥ 60 years and severity score of the acute episode ≥ 6 were independent risk factors of reduced DLCO 6 months after discharge. Levels of epithelial (SP-A, SP-D and SLPI) and endothelial (sICAM-1 and angiopoietin-2) markers were higher in patients with reduced DLCO, particularly in those with DLCO ≤ 50% ref. Circulating SP-A levels were associated with the occurrence of acute respiratory distress syndrome (ARDS), organizing pneumonia and pulmonary embolisms during hospitalization. CONCLUSIONS: Reduced DLCO is common in COVID-19 survivors 6 months after hospital discharge, especially in those older than 60 years with very severe acute disease. In these individuals, elevated levels of epithelial and endothelial markers suggest persistent lung damage.

Severity of respiratory failure and computed chest tomography in acute COVID-19 correlates with pulmonary function and respiratory symptoms after infection with SARS-CoV-2: An observational longitudinal study over 12 months.

INTRODUCTION: Prospective and longitudinal data on pulmonary injury over one year after acute coronavirus disease 2019 (COVID-19) are sparse. We aim to determine reductions in pulmonary function and respiratory related quality of life up to 12 months after acute COVID-19. METHODS: Patients with acute COVID-19 were enrolled into an ongoing single-centre, prospective observational study and prospectively examined 6 weeks, 3, 6 and 12 months after onset of COVID-19 symptoms. Chest CT-scans, pulmonary function and symptoms assessed by St. Georges Respiratory Questionnaire were used to evaluate respiratory limitations. Patients were stratified according to severity of acute COVID-19. RESULTS: Median age of all patients was 57 years, 37.8% were female. Higher age, male sex and higher BMI were associated with acute-COVID-19 severity (p < 0.0001, 0.001 and 0.004 respectively). Also, pulmonary restriction and reduced carbon monoxide diffusion capacity was associated with disease severity. In patients with restriction and impaired diffusion capacity, FVC improved over 12 months from 61.32 to 71.82, TLC from 68.92 to 76.95, DLCO from 60.18 to 68.98 and KCO from 81.28 to 87.80 (percent predicted values; p = 0.002, 0.045, 0.0002 and 0.0005). The CT-score of lung involvement in the acute phase was associated with restriction and reduction in diffusion capacity in follow-up. Respiratory symptoms improved for patients in higher severity groups during follow-up, but not for patients with initially mild disease. CONCLUSION: Severity of respiratory failure during COVID-19 correlates with the degree of pulmonary function impairment and respiratory quality of life in the year after acute infection.

Long-term sequelae are highly prevalent one year after hospitalization for severe COVID-19.

Many coronavirus disease 2019 (Covid-19) survivors show symptoms months after acute illness. The aim of this work is to describe the clinical evolution of Covid-19, one year after discharge. We performed a prospective cohort study on 238 patients previously hospitalized for Covid-19 pneumonia in 2020 who already underwent clinical follow-up 4 months post-Covid-19. 200 consented to participate to a 12-months clinical assessment, including: pulmonary function tests with diffusing lung capacity for carbon monoxide (DLCO); post-traumatic stress (PTS) symptoms evaluation by the Impact of Event Scale (IES); motor function evaluation (by Short Physical Performance Battery and 2 min walking test); chest Computed Tomography (CT). After 366 [363-369] days, 79 patients (39.5%) reported at least one symptom. A DLCO < 80% was observed in 96 patients (49.0%). Severe DLCO impairment (< 60%) was reported in 20 patients (10.2%), related to extent of CT scan abnormalities. Some degree of motor impairment was observed in 25.8% of subjects. 37/200 patients (18.5%) showed moderate-to-severe PTS symptoms. In the time elapsed from 4 to 12 months after hospital discharge, motor function improves, while respiratory function does not, being accompanied by evidence of lung structural damage. Symptoms remain highly prevalent one year after acute illness.

Clinical, radiological and functional outcomes in patients with SARS-CoV-2 pneumonia: a prospective observational study.

BACKGROUND: All over the world, SARS-CoV-2 pneumonia is causing a significant short-term morbidity and mortality, but the medium-term impact on lung function and quality of life of affected patients are still unknown. METHODS: In this prospective observational study, 39 patients with SARS-CoV-2 pneumonia were recruited from a single COVID-19 hospital in Southern Switzerland. At three months patients underwent radiological and functional follow-up through CT scan, lung function tests, and 6 min walking test. Furthermore, quality of life was assessed through self-reported questionnaires. RESULTS: Among 39 patients with SARS-CoV-2 pneumonia, 32 (82% of all participants) presented abnormalities in CT scan and 25 (64.1%) had lung function tests impairment at three months. Moreover, 31 patients (79.5%) reported a perception of poor health due to respiratory symptoms and all 39 patients showed an overall decreased quality of life. CONCLUSIONS: Medium-term follow up at three months of patients diagnosed with SARS-CoV-2 pneumonia shows the persistence of abnormalities in CT scans, a significant functional impairment assessed by lung function tests and a decreased quality of life in affected patients. Further studies evaluating the long-term impact are warranted to guarantee an appropriate follow-up to patients recovering from SARS-CoV-2 pneumonia.

Gas Exchange Impairment During COVID-19 Recovery.

BACKGROUND: Persistent impairment of pulmonary function and exercise capacity has been known to last for months or even years in the survivors who recovered from other coronavirus pneumonia. Some reports showed that subjects with coronavirus disease 2019 pneumonia after being discharged could have several sequelae, but there are few studies on gas exchange and exercise capacity complications in these subjects. AIMS: To describe residual gas exchange abnormalities during recovery from coronavirus disease 2019 pneumonia. METHODS: In an observational study, ∼90 d after onset of disease, we scheduled almost 200 subjects for an out-patient visit with pulmonary function testing and computed tomography of the lungs. Lung mechanics by using body plethysmography, gas exchange with diffusing lung capacity for carbon monoxide determined by the single-breath technique (DLCOsb) and diffusing lung capacity for nitric oxide determined by the single-breath technique (DLNOsb), and exercise ability by using the 6-min walk test (6MWT) were measured in the subjects. The results were compared between those who required invasive mechanical ventilation and those who did not. RESULTS: A total of 171 subjects were included, the majority (96%) had signs of residual pneumonia (such as an excess of high attenuation areas) on computed tomography of the lungs. The DLCOSB results were below the lower limit of the normal range in 29.2% of the subjects; during the 6MWT, 67% experienced oxygen desaturation ([Formula: see text]) > 4%; and, in 81 (47%), the dropped below 88%. Subjects who required invasive mechanical ventilation (49.7%) were more likely to have lower lung volumes, more gas exchange abnormality, less exercise capacity and more radiologic abnormality. CONCLUSIONS: Subjects who recovered from severe COVID-19 pneumonia continued to have abnormal lung function and abnormal radiologic findings.

Residual respiratory impairment after COVID-19 pneumonia.

INTRODUCTION: The novel coronavirus SARS-Cov-2 can infect the respiratory tract causing a spectrum of disease varying from mild to fatal pneumonia, and known as COVID-19. Ongoing clinical research is assessing the potential for long-term respiratory sequelae in these patients. We assessed the respiratory function in a cohort of patients after recovering from SARS-Cov-2 infection, stratified according to PaO2/FiO2 (p/F) values. METHOD: Approximately one month after hospital discharge, 86 COVID-19 patients underwent physical examination, arterial blood gas (ABG) analysis, pulmonary function tests (PFTs), and six-minute walk test (6MWT). Patients were also asked to quantify the severity of dyspnoea and cough before, during, and after hospitalization using a visual analogic scale (VAS). Seventy-six subjects with ABG during hospitalization were stratified in three groups according to their worst p/F values: above 300 (n = 38), between 200 and 300 (n = 30) and below 200 (n = 20). RESULTS: On PFTs, lung volumes were overall preserved yet, mean percent predicted residual volume was slightly reduced (74.8 ± 18.1%). Percent predicted diffusing capacity for carbon monoxide (DLCO) was also mildly reduced (77.2 ± 16.5%). Patients reported residual breathlessness at the time of the visit (VAS 19.8, p < 0.001). Patients with p/F below 200 during hospitalization had lower percent predicted forced vital capacity (p = 0.005), lower percent predicted total lung capacity (p = 0.012), lower DLCO (p < 0.001) and shorter 6MWT distance (p = 0.004) than patients with higher p/F. CONCLUSION: Approximately one month after hospital discharge, patients with COVID-19 can have residual respiratory impairment, including lower exercise tolerance. The extent of this impairment seems to correlate with the severity of respiratory failure during hospitalization.

Short-Term Consequences of SARS-CoV-2-Related Pneumonia: A Follow Up Study.

The aim of the study was to assess the short-term consequences of SARS-CoV-2-related pneumonia, also in relation to radiologic/laboratory/clinical indices of risk at baseline. This prospective follow-up cohort study included 94 patients with confirmed COVID-19 admitted to a medical ward at the Montichiari Hospital, Brescia, Italy from February 28th to April 30th, 2020. Patients had COVID-19 related pneumonia with respiratory failure. Ninety-four patients out of 193 survivors accepted to be re-evaluated after discharge, on average after 4 months. In » of the patients an evidence of pulmonary fibrosis was detected, as indicated by an altered diffusing capacity of the lung for carbon monoxide (DLCO); in 6-7% of patients the alteration was classified as of moderate/severe degree. We also evaluated quality of life thorough a structured questionnaire: 52% of the patients still lamented fatigue, 36% effort dyspnea, 10% anorexia, 14% dysgeusia or anosmia, 31% insomnia and 21% anxiety. Finally, we evaluated three prognostic indices (the Brixia radiologic score, the Charlson Comorbidity Index and the 4C mortality score) in terms of prediction of the clinical consequences of the disease. All of them significantly predicted the extent of short-term lung involvement. In conclusion, our study demonstrated that SARS-CoV-2-related pneumonia is associated to relevant short-term clinical consequences, both in terms of persistence of symptoms and in terms of impairment of DLCO (indicator of a possible development of pulmonary fibrosis); some severity indices of the disease may predict short-term clinical outcome. Further studies are needed to ascertain whether such manifestations may persist long-term.

Impaired diffusing capacity for carbon monoxide is common in critically ill Covid-19 patients at four months post-discharge.

There is limited knowledge about the long-term effects on pulmonary function of COVID-19 in patients that required intensive care treatment. Spirometry and diffusing capacity for carbon monoxide (DLCO) were measured in 60 subjects at 3-6 months post discharge. Impaired lung function was found in 52% of the subjects, with reduced DLCO as the main finding. The risk increased with age above 60 years, need for mechanical ventilation and longer ICU stay as well as lower levels of C-reactive protein at admission. This suggests the need of follow-up with pulmonary function testing in intensive-care treated patients.

Post COVID-19 Organizing Pneumonia: The Right Time to Interfere.

The COVID-19 pandemic dramatically changed medical care. Healthcare professionals are faced with new issues. Patients who survived COVID-19 have plenty of different continuing symptoms, of which the most common are fatigue and breathlessness. It is not well known how to care for patients with persistent or worsening respiratory symptoms and changes on chest X-ray following COVID-19 pneumonia. In this article, we talk about a subgroup of patients with organizing pneumonia following COVID-19 pneumonia that could be effectively treated with systemic glucocorticoids. It is important that patients with COVID-19 pneumonia be followed-up at least three weeks after diagnosis, in order to recognize early lung damage. We are providing a management algorithm for early diagnosis of lung diseases after COVID-19 pneumonia.

Radiological and functional lung sequelae of COVID-19: a systematic review and meta-analysis.

BACKGROUND: The coronavirus disease 2019 (COVID-19) causes a wide spectrum of lung manifestations ranging from mild asymptomatic disease to severe respiratory failure. We aimed to clarify the characteristics of radiological and functional lung sequelae of COVID-19 patients described in follow-up period. METHOD: PubMed and EMBASE were searched on January 20th, 2021 to investigate characteristics of lung sequelae in COVID-19 patients. Chest computed tomography (CT) and pulmonary function test (PFT) data were collected and analyzed using one-group meta-analysis. RESULTS: Our search identified 15 eligible studies with follow-up period in a range of 1-6 months. A total of 3066 discharged patients were included in these studies. Among them, 1232 and 1359 patients were evaluated by chest CT and PFT, respectively. The approximate follow-up timing on average was 90 days after either symptom onset or hospital discharge. The frequency of residual CT abnormalities after hospital discharge was 55.7% (95% confidential interval (CI) 41.2-70.1, I2 = 96.2%). The most frequent chest CT abnormality was ground glass opacity in 44.1% (95% CI 30.5-57.8, I2 = 96.2%), followed by parenchymal band or fibrous stripe in 33.9% (95% CI 18.4-49.4, I2 = 95.0%). The frequency of abnormal pulmonary function test was 44.3% (95% CI 32.2-56.4, I2 = 82.1%), and impaired diffusion capacity was the most frequently observed finding in 34.8% (95% CI 25.8-43.8, I2 = 91.5%). Restrictive and obstructive patterns were observed in 16.4% (95% CI 8.9-23.9, I2 = 89.8%) and 7.7% (95% CI 4.2-11.2, I2 = 62.0%), respectively. CONCLUSIONS: This systematic review suggested that about half of the patients with COVID-19 still had residual abnormalities on chest CT and PFT at about 3 months. Further studies with longer follow-up term are warranted.