Persistent respiratory symptoms and impaired gas exchange are common in patients recovering from COVID-19 pneumonia. The Lung Diffusing Capacity for Carbon Monoxide (DLCO) and Carbon Monoxide Transfer Coefficient (KCO) do not adequately distinguish alveolar membrane dysfunction from vascular abnormalities. This study aimed to characterize persistent diffusion impairment in post-ICU patients with prior SARS-CoV-2 pneumonia and reduced DLCO.

After hospital discharge, patients underwent spirometry, DLCO measurement, and a 6-minute walking test every six months. If DLCO remained impaired at 18-24 months, a combined Lung Diffusing Capacity for Nitric Oxide (DLNO) and DLCO assessment was performed to differentiate alveolar-capillary membrane (DmCO) and pulmonary capillary blood volume (Vc) alterations.

Among 20 patients with persistent DLCO reduction, 3 had an obstructive ventilatory pattern, 6 had restriction, and 12 had low KCO. In restrictive cases, KCO was reduced but remained within normal limits without compensation. The DLNO/DLCO ratio exceeded 113.5% predicted in all patients. DmCO was impaired in 7 patients, while Vc was reduced in 16.

Both DLCO determinants were affected, with vascular impairment predominating. Vc reduction was present in most patients, with mean values below the lower limit of normality, whereas DmCO was less affected and often normal. The elevated DLNO/DLCO ratio suggests that persistent DLCO reduction is primarily driven by prolonged pulmonary capillary circulation dysfunction rather than alveolar membrane alterations, highlighting the vascular component as the primary site of long-term impairment.

Post-COVID-19 lung disease (PCLD) is a significant concern following the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. PCLD encompasses persistent debilitating respiratory symptoms and radiological changes beyond the acute disease phase. It highlights the ongoing search to identify and manage lingering diseases. This prospective study utilizes F18-Fludeoxyglucose (FDG) PET/CT to identify residual inflammatory lung lesions in PCLD. Treatment response was assessed after anti-inflammatory and antifibrotic therapies.

Thirty patients post-severe COVID-19 pneumonia enrolled. They underwent baseline 18F-FDG PET/CT scans to unveil residual lung inflammation lesions on FDG and CT. They received antifibrotic (Pirfenidone) and anti-inflammatory (Methylprednisolone) drugs for 6-12 weeks. They were followed up for clinical, biochemical, and imaging treatment responses.

Baseline 18F-FDG PET/CT revealed ongoing lung inflammation in all PCLD (mean SUVmax: 3.8 ± 2.3 and number of segments: 8±3 ). The mean CT severity score was 17.7 ± 3.4 with moderate (n = 16) or severe (n = 14) disease involvement. Mild, moderate, and severe 18F-FDG PET/CT categories were noted in the 8, 14, and 8 patients, respectively. Following treatment, a PET scan showed a significant decrease in disease extent (segments) and severity (FDG uptake) and an improvement in disease grading on imaging (97% of patients). In PET concordance, there was a significant clinical and radiological improvement with a fall in inflammatory markers (p < 0.005). Serum Ferritin and total leukocyte counts were significantly associated with PCLD severity on 18F-FDG PET/CT(p < 0.05).

This prospective study identifies and quantifies ongoing significant residual lung inflammation in PCLD on 18F-FDG PET/CT. Anti-inflammatory and antifibrotic drug therapy led to clinical and radiological improvement. 18F-FDG PET/CT as a non-invasive biomarker helped manage and follow up PCLD patients.

Not applicable.

We aimed to characterize the fibrosis following COVID-19 pneumonia, using quantitative analysis, after three months and subsequently, after two years of patients' release from the hospital, and to identify the risk factors for pulmonary fibrosis.

We performed a retrospective, observational cohort study on 420 patients with severe forms of COVID-19. For all patients, we registered demographic, inflammatory and biochemical parameters, complete blood count and D-dimers; all patients underwent three computed tomography scans (at admittance, at 3 months and at 2 years).

We found fibrosis in 67.9% of patients at the 3-month evaluation and in 42.4% of patients at the 2-year evaluation, registering a significant decrease in the severe and moderate fibrosis cases, with a slight increase in the mild fibrosis cases. The risk of fibrosis was found to be proportional to the values of age, duration of hospital stay, inflammatory markers (ESR, fibrinogen), cytolytic markers (LDH, AST) and D-dimers. The highest correlations with lung fibrosis were registered for interstitial pulmonary involvement (for the 3-month evaluation) and total pulmonary involvement (for the 2-year evaluation).

Lung fibrosis represents a significant post-COVID-19 complication found in 42% of patients with severe forms of pneumonia at the 2-year evaluation. A significant overall decrease in the severity of lung fibrosis was registered at the 2-year evaluation compared to the 3-month evaluation. We consider that the amount of interstitial pulmonary involvement represents the optimal parameter to estimate the risk of lung fibrosis following SARS-CoV-2 pneumonia.

To investigate the test-retest reliability and construct validity of the LCADL scale applied via online form in individuals after hospitalization for COVID-19.

Methodological study. After hospitalization for COVID-19 individuals completed the LCADL via online form at two separate times. They also answered the post-COVID-19 Functional Status Scale (PCFS), dyspnea, fatigue, and health perception scales, modified Medical Research Council (MRCm), Short Form Health Survey 36 (SF-36). Hospitalization data were collected from the individual's medical record.

104 individuals participated in the study (57 men, 45.2 ± 11.9 years). The LCADL showed moderately to high test-retest reliability (ICC: 0.73-0.86; p < 0.001), there was no difference in scores between test and retest (p > 0.05), the mean difference between the applications was smaller than the standard error of measurement and the internal consistency was adequate (Cronbach's α = 0.70-0.94). In addition, it demonstrated adequate construct validity, showing correlations with PCFS, dyspnea perception, fatigue and health scales, mMRC, SF-36, and length of stay in the Intensive Care Unit (p < 0.05). The LCADL as percentage of the total score presented a significant floor effect (25%).

The LCADL applied online was reliable and valid for assessing limitations due to dyspnea in ADL in individuals after hospitalization for COVID-19.

There is a paucity of evidence on the impact of mild COVID-19 on the respiratory system, particularly in non-healthcare seeking individuals.

To investigate the effects of mild COVID-19 on respiratory function and to identify indicators of decreased lung function.

We conducted a cross-sectional study in 175 non-healthcare-seeking individuals with confirmed acute SARS-CoV-2 infection who did not require hospitalisation. Participants were divided into three groups: those who had pulmonary function tests (PFTs) within 6 months, between 6 and 12 months, and between 12 and 24 months after infection. Each participant underwent spirometry, measurement of the diffusing capacity of the lungs for carbon monoxide (DLCO ), a 6-minute walking distance test (6MWD) and plethysmography.

The mean age of the participants was 44.3 years, and the mean body mass index (BMI) 32.7 kg/m². Forty-six participants had PFTs within 6 months, 64 between 6 and 12 months, and 65 between 12 and 24 months. Lower than expected DLCO was the most commonly detected abnormality (57%). Spirometry anomalies were noted in 23%, 10% showing an obstructive impairment and 13% a restrictive impairment, confirmed by a total lung capacity <80%. An increased BMI was the only variable that was significantly and independently linearly associated with lower than predicted (<80%) forced vital capacity, forced expiratory volume in the 1st second, DLCO and 6MWD.

DLCO was low in a considerable proportion of non-healthcare-seeking individuals 2 years after mild COVID-19. A high BMI was found to be significantly and independently associated with lower than predicted PFT results and 6MWD.

What the study adds. We found that pulmonary function, particularly diffusing capacity, was lower than predicted in a significant proportion of non-healthcare-seeking individuals up to 2 years after mild COVID-19. A high body mass index (BMI) was found to be significantly and independently associated with decreased lung function.Implications of the findings. There is a paucity of evidence on the medium-term effects of mild COVID-19 on the respiratory system in non-healthcare-seeking individuals. We investigated the medium-term effects of mild COVID-19 on the respiratory system, showed lower than predicted lung function, and identified one independent predictor, BMI. Even individuals classified as having 'mild' COVID-19 could have medium-term respiratory sequelae.

Co-infection with diverse bacteria is commonly seen in patients infected with the novel coronavirus, SARS-CoV-2. This type of co-infection significantly impacts the occurrence and development of novel coronavirus infection. Bacterial co-pathogens are typically identified in the respiratory system and blood culture, which complicates the diagnosis, treatment, and prognosis of COVID-19, and even exacerbates the severity of disease symptoms and increases mortality rates. However, the status and impact of bacterial co-infections during the COVID-19 pandemic have not been properly studied. Recently, the amount of literature on the co-infection of SARS-CoV-2 and bacteria has gradually increased, enabling a comprehensive discussion on this type of co-infection. In this study, we focus on bacterial infections in the respiratory system and blood of patients with COVID-19 because these infection types significantly affect the severity and mortality of COVID-19. Furthermore, the progression of COVID-19 has markedly elevated the antimicrobial resistance among specific bacteria, such as Klebsiella pneumoniae, in clinical settings including intensive care units (ICUs). Grasping these resistance patterns is pivotal for the optimal utilization and stewardship of antibiotics, including fluoroquinolones. Our study offers insights into these aspects and serves as a fundamental basis for devising effective therapeutic strategies. We primarily sourced our articles from PubMed, ScienceDirect, Scopus, and Google Scholar. We queried these databases using specific search terms related to COVID-19 and its co-infections with bacteria or fungi, and selectively chose relevant articles for inclusion in our review.

Limited data are available on long-term respiratory disabilities in patients following acute COVID-19.

This prospective, monocentric, observational cohort study included patients admitted to our hospital with acute COVID-19 between 12 March and 24 April 2020. Clinical, functional and radiological data were collected up to 28 months after hospital discharge.

Among 715 patients hospitalised for COVID-19, 493 (69.0%) were discharged alive. We could access complete medical records for 268 out of 493 patients (54.4%); 138 out of 268 (51.5%) exhibited persistent respiratory symptoms and agreed with the data collection and follow-up. Patients were predominantly male (64.5%), with a mean±sd age of 58.9±15.3 years. At the last follow-up, the leading symptoms were asthenia (31.5%), dyspnoea (29.8%) and neuropsychological symptoms (17.7%). Lung function improved up to the last visit. Mean diffusing capacity of the lung for carbon monoxide (D LCO) was 77.8% of predicted value, total lung capacity (TLC) was 83.5% and O2 desaturation during exercise (O2 desaturation) was 2.3%. While D LCO improved over the entire period, TLC improved in the early phase and O2 desaturation in the late phase. Except for those with lung comorbidities, only one patient presented with minor functional and chest radiological alterations at 28 months.

Patients with acute COVID-19 discharged alive showed improved clinical symptoms, lung function parameters and radiological signs up to 28 months post-infection. Persistent symptoms consisted mainly of asthenia and dyspnoea, with lung function returning to normal. One patient without prior respiratory issues exhibited moderate pulmonary fibrosis.

Respiratory symptoms may persist for several weeks following the initial coronavirus disease 2019 (COVID-19) infection. The aims and objectives were to assess the clinical symptoms, pulmonary functions, and radiological changes and to assess the cardio-vascular complications in post-COVID-19 patients.

This observational study was conducted in the Department of Pulmonary Medicine in collaboration with the Department of Cardiology, SCBMCH, Cuttack, from March 2021 to August 2022 on 75 post-COVID-19 patients with respiratory symptoms from 4 weeks to 2 years after treatment for COVID-19 infection. Post-COVID patients having previous respiratory diseases were excluded from the study.

Among 75 patients, the most common age group was 18-30 years with a male-to-female ratio of 2.5:1. Based on O2 requirement, patients were divided into the mild symptomatic group and moderate to severe pneumonia group. The most common respiratory symptom was dyspnea, followed by cough with expectoration. Bilateral crepitations were found in 17% of cases. C-reactive protein (CRP) and D-dimer were increased in 38.6% and 32% of patients, respectively. 42.6% had abnormal chest X-ray, and the most common abnormal finding was reticular thickening. In spirometry, the restrictive pattern and mixed pattern were the predominant types documented in 49.3% and 13.3% of cases, respectively, which were significant in the moderate-severe group. Diffusion capacity of the lungs for carbon monoxide (DLCO) was performed in only 19 patients (mild group 13 and moderate-severe group 6). Twelve (63.2%) patients had abnormal DLCO. P- values were significant for RV (0.0482) and RV/TLC (0.0394). High-resolution computed tomography (HRCT) of the thorax was abnormal in 55.7% with the most common abnormalities as inter- and intra-lobular septal thickening. The left ventricular ejection fraction was preserved in all patients, with right atrium and right ventricle enlargement in 2.6% and pulmonary hypertension in 4.0% of participants.

All post-COVID-19 patients having respiratory symptoms after recovery from acute COVID-19 may be referred by family care physicians to a dedicated post-COVID center for further evaluation, management, and early rehabilitation to decrease the morbidity in recovered patients. Persistent increased blood parameters like TLC, N/L ratio, RBS, CRP, and D-dimer seen in recovered post-COVID-19 patients. The long-term impact of CT findings on respiratory symptoms, pulmonary functions, and quality of life is unknown. Cardiovascular abnormalities in post-COVID-19 patients are infrequent.

Understanding the prevalence of abnormal lung function and its associated factors among patients recovering from COVID-19 is crucial for enhancing post-COVID care strategies. This study primarily aimed to determine the prevalence and types of spirometry abnormalities among post-COVID-19 patients in Malaysia, with a secondary objective of identifying its associated factors. Conducted at the COVID-19 Research Clinic, Faculty of Medicine, University Technology MARA, from March 2021 to December 2022, this study included patients at least three months post-discharge from hospitals following moderate-to-critical COVID-19. Of 408 patients studied, abnormal spirometry was found in 46.8%, with 28.4% exhibiting a restrictive pattern, 17.4% showing preserved ratio impaired spirometry (PRISm), and 1.0% displaying an obstructive pattern. Factors independently associated with abnormal spirometry included consolidation on chest X-ray (OR 8.1, 95% CI 1.75-37.42, p = 0.008), underlying cardiovascular disease (OR 3.5, 95% CI 1.19-10.47, p = 0.023), ground-glass opacity on chest X-ray (OR 2.6, 95% CI 1.52-4.30, p < 0.001), and oxygen desaturation during the 6-min walk test (OR 1.9, 95% CI 1.20-3.06, p = 0.007). This study highlights that patients recovering from moderate-to-critical COVID-19 often exhibit abnormal spirometry, notably a restrictive pattern and PRISm. Routine spirometry screening for high-risk patients is recommended.

Impaired lung gas exchange is commonly seen in patients with pulmonary involvement related to SARS-CoV-2 acute infection or post-acute COVID-19 syndrome (PACS). The primary aim of our study was to assess lung gas transfer, measuring the pulmonary diffusion capacity for nitric oxide (DLNO) and carbon monoxide (DLCO) in all COVID-19 patients. Our secondary aim was to decipher the respective roles of perturbed lung membrane conductance (DM) and reduced pulmonary capillary volume (VC) in patients with impaired lung gas exchange. From May to October 2020, we measured DLNO-DLCO in 118 patients during their post-COVID-19 period (4.6 months after infection) to decipher alveolo-capillary gas transfer disturbances. DLNO-DLCO measurement was also performed in 28 healthy non-smokers as controls. Patients were classified into three groups according to the severity (mild, moderate, and severe) of acute COVID-19 infection. Patients with mild COVID-19 had normal lung volumes and airways expiratory flows but impaired pulmonary gas exchange, as shown by the significant decreases in DLNO, DLCO, DM, and VC as compared with controls. VC was significantly impaired and the DLNO/DLCO ratio was increased in patients with moderate (n = 4, 11%) and severe COVID-19 (n = 23, 49%). Abnormal membrane conductance was also seen in all three groups of post-COVID-19 patients. These findings suggest a persistent alveolo-capillary gas transfer defect, implying not only reduced membrane conductance but also abnormal pulmonary vascular capacitance in all PACS patients, even those with a milder form of COVID-19 infection.

The reduction of lung capillary blood volume (Vc) had been identified as the microvascular injury mostly underlying the respiratory Long-COVID syndrome following post-COVID-19 pneumonia. The same kind of injury have been recently also found in several individuals after milder paucisymptomatic SARS-CoV-2 infections. Though current guidelines strongly recommend vac-cination, studies aimed to investigate the in vivo protection of anti-SARS-CoV-2 vaccines on lung microvascular targets still are missing to our best knowledge.

to assess the protection of mRNA vaccines from the reduction of lung capillary blood volume (Vc) caused by pauci-symptomatic SARS.CoV-2 infections in vaccinated compared to unvaccinated individuals.

Non-smoking individuals with recent paucisymptomatic SARS-CoV-2 infection were divided into vaccinated and unvaccinated groups. Lung function parameters, including single-breath diffusing capacity and microvascular blood volume, were compared between groups.

fifty vaccinated and twenty-five unvaccinated well-matched individuals were studied. Differently than usual lung function parameters, only the single-breath simultaneous assessment of sDLCO, sDLNO/sDLCO ratio and Vc allowed to identify the occurrence of the lung microvascular injury with high sensitivity and specificity (p<0.001).

mRNA vaccines proved to exert a high protection from the loss of lung capillary blood volume (Vc) induced by SARS.CoV-2 paucisymptomatic infections (p<0.001). The availability of this non-invasive investigational model should be regarded as a very helpful tool for assessing and comparing in vivo the protective effect of mRNA vaccines on the human microvascular structures of the deep lung.

Impaired lung function has been observed in patients following COVID-19 infection, with studies reporting persistent lung volume and diffusing capacity impairments. Some studies have demonstrated significantly higher small airway resistance in COVID-19 positive cases. This retrospective study aims to examine impulse oscillometry (IOS) data of patients with persistent symptoms after COVID-19 infection, focusing on the relationship between time and symptoms.

The study analyzed data from adult patients with persistent symptoms who underwent IOS testing within and after 84 days from the diagnosis date.

The results showed that patients within 84 days and those between 31 and 84 days had higher small airway resistance values, indicating peripheral airway disease. Patients with dyspnea exhibited higher IOS values compared to those with cough symptoms, suggesting more significant impairment in the peripheral airways.

The study highlights the importance of using comprehensive diagnostic tools like IOS to assess respiratory impairments in post-COVID-19 patients, particularly in the small airways. Understanding the relationship between time and symptoms can provide valuable insights for the treatment of peripheral airway dysfunction in post-COVID-19 patients.

While coronavirus disease 2019 (COVID-19) is generally considered to exhibit a less severe clinical course in children than in adults, studies have demonstrated that respiratory symptoms can endure for more than 3 months following infection in at least one-third of pediatric cases. The present study evaluates the respiratory functions of children aged 3-15 years within 3-6 months of their recovery from COVID-19 using impulse oscillometry (IOS) and compares them with the values of healthy children.

Included in this prospective cross-sectional study were 63 patients (patient group) aged 3-15 years who contracted COVID-19 between December 2021 and May 2022, as well as 57 healthy children as a control group, matched for age and sex. The demographic, clinical, and laboratory data of the patients were recorded, and respiratory function was assessed based on airway resistance (zR5, zR20, R5-20) and reactance (zX5, zX20, reactance area [AX], resonant frequency [Fres]) using an IOS device.

There were no significant differences in the age, weight, height, and body weight z score values of the two groups (p > .05). While the zR5 and R5-20 levels of the patient group were higher (p = .008 and p < .001, respectively) than those of the controls, the zR20, AX, and Fres values did not differ significantly between the groups (p > .05). The parameters indicating the reactance, including zX5 and zX20, were significantly lower in the patient group than in the control group (p = .028 and p < .001, respectively).

Total and peripheral airway resistances were found to be elevated in children who had recovered from COVID-19 in the preceding 3-6 months.

The aim of this study was to determine the short-term consequences of coronavirus disease 2019 (COVID-19) infection on pulmonary diffusion in patients with severe (but not critical) and moderately severe COVID-19 pneumonia during three months after COVID-19 infection.

A prospective study included 81 patients with an RT-PCR-test confirmed diagnosis of COVID-19 infection treated in the COVID Department of Lung Diseases of University Clinical Hospital Mostar. Inclusion criteria were ≥18-year-old patients, COVID-19 infection confirmed using real-time RT-PCR, radiologically confirmed bilateral COVID-19 pneumonia, and diffusion capacity of the lungs for carbon monoxide (DLCO) one and three months after COVID-19 infection. The pulmonary function was tested using the MasterScreen Body Jaeger (Jaeger Corporation, Omaha, USA) and MasterScreen PFT Jaeger (Jaeger Corporation, Omaha, USA) according to American Thoracic Society guidelines one and three months after COVID-19 infection.

Forced vital capacity significantly increased three months after COVID-19 infection compared to the first-month control (p<0.0005). Also, a statistically significant increase in the FEV1 value (p<0.0005), FEV1%FVC ratio (p<0.005), DLCO/SB (p<0.0005), DLCO/VA value (p<0.0005), and total lung capacity (TLC) (p<0.0005) was observed in all patients.

Our study showed that recovery of DLCO/VA and spirometry parameters was complete after three months, while DLCO/SB was below normal values even after three months. Therefore, one month after the COVID-19 infection patients had partial recovery of lung function, while a significant recovery of lung function was observed three months after the COVID-19 infection.

As the long-term consequences of coronavirus disease 2019 (COVID-19) have not been defined, it is necessary to explore persistent symptoms, long-term respiratory impairment, and impact on quality of life over time in COVID-19 survivors. In this prospective cohort study, convalescent individuals diagnosed with COVID-19 were followed-up 2 and 3 years after discharge from hospital. Participants completed an in-person interview to assess persistent symptoms and underwent blood tests, pulmonary function tests, chest high-resolution computed tomography, and the 6-min walking test. There were 762 patients at the 2-year follow-up and 613 patients at the 3-year follow-up. The mean age was 60 years and 415 (54.5%) were men. At 3 years, 39.80% of the participants had at least one symptom; most frequently, fatigue, difficulty sleeping, joint pain, shortness of breath, muscle aches, and cough. The participants experienced different degrees of pulmonary function impairment, with decreased carbon monoxide diffusion capacity being the main feature; results remained relatively stable over the 2-3 years. Multiple logistic regression analysis demonstrated that female sex and smoking were independently associated with impaired diffusion capacity. A subgroup analysis based on disease severity was performed, indicating that there was no difference in other parameters of lung function except forced vital capacity at 3-year follow-up. Persistent radiographic abnormalities, most commonly fibrotic-like changes, were observed at both timepoints. At 3 years, patients had a significantly improved Mental Component Score compared with that at 2 years, with a lower percentage with anxiety. Our study indicated that symptoms and pulmonary abnormalities persisted in COVID-19 survivors at 3 years. Further studies are warranted to explore the long-term effects of COVID-19 and develop appropriate rehabilitation strategies.

COVID-19 has serious consequences on different body systems particularly the respiratory system with its impact on pulmonary function, exercise capacities, and physical activities. This study aimed to investigate the long-term effect of COVID-19 on pulmonary function, exercise capacities, and physical activities in patients with non-severe COVID-19.

160 individuals were selected to participate in a cross-section study. Group-I: 80 male and female patients with non-severe COVID-19 at least 3 months after the recovery time. Group-II: 80 male and female matched (non-infected with COVID-19) participants. The spirometer, six-minute walk test (6MWT), and International Physical Activity Questionnaire (IPAQ) were used to assess pulmonary function, exercise capacities, and physical activities respectively. The Kolmogorov-Smirnov test was used to test normality of data. The Mann-Whitney and independent t-tests were used to compare the significant differences between both groups.

The results show significant differences in FVC & FEV 1 of the pulmonary function, exercise capacities, and physical activities of the work & transportations between both COVID-19 and matched groups p-value = (0.001 & 0.001, 0.001 and 0.005 & 0.012) respectively.

Pulmonary function, exercise capacities, and physical activities are negatively influenced by COVID-19 as long-term consequences indicating the need for extended health care, and prescription of proper rehabilitative training programs for non- severe COVID-19 patients whatever their severity degree of infection or history of hospitalization. Outcome reflections of the current results raise awareness of physical therapists to the importance of the proper rehabilitative training programs for non-severe COVID-19 patients.

Lingering breathing difficulties are common after COVID-19. However, the underlying causes remains unclear, with spirometry often being normal. We hypothesized that small airway dysfunction (SAD) can partly explain these symptoms. We examined 48 individuals (32 women, 4 hospitalized in the acute phase) who experienced dyspnea and/or cough in the acute phase and/or aftermath of COVID-19, and 22 non-COVID-19 controls. Time since acute infection was, median (range), 65 (10-131) weeks. We assessed SAD using multiple breath washout (MBW) and impulse oscillometry (IOS) and included spirometry and diffusing-capacity test (DLCO). One-minute-sit-to-stand test estimated physical function, and breathing difficulties were defined as answering "yes" to the question "do you experience lingering breathing difficulties?" Spirometry, DLCO, and IOS were normal in almost all cases (spirometry: 90%, DLCO: 98%, IOS: 88%), while MBW identified ventilation inhomogeneity in 50%. Breathing difficulties (n = 21) was associated with increased MBW-derived Sacin . However, physical function did not correlate with SAD. Among individuals with breathing difficulties, 25% had reduced physical function, 25% had SAD, 35% had both, and 15% had normal lung function and physical function. Despite spirometry and DLCO being normal in almost all post-COVID-19 individuals, SAD was present in a high proportion and was associated with lingering breathing difficulties.

One of the most commonly observed complications after COVID-19 is persistent pulmonary impairment. The aim of this study was to evaluate the impact of individual factors during the acute phase of COVID-19 on subsequent pulmonary function test results. The study involved 46 patients who were admitted to hospital due to respiratory failure caused by SARS-CoV-2 and who were assessed during follow-up visits at 3 and 9 months after discharge. Patients were divided into two subgroups according to the severity of respiratory failure. The severe group included patients requiring mechanical ventilation or HFNOT. The results of the study showed that a severe course of the disease was associated with a lower FVC and a higher FEV1/FVC ratio 3 months after discharge (both p < 0.05). In addition, it has been revealed that the length of hospitalization is a factor that negatively impacts the FEV1, FVC and TLC values measured at follow-up after 3 months. Furthermore, the obtained results identify the presence of cough in the acute phase of the disease as a factor having a positive impact on several PFT parameters (especially the FEV1/FVC ratio) as well as the 6MWT outcome after 3 months. The FVC improved significantly (p < 0.05) between the follow-up visits. The findings may indicate that COVID-19-induced respiratory dysfunction is usually temporary and spontaneously resolves during recovery. Recovery is slower in those who required more intensive oxygenation. The results of this study may be useful in identifying patients who require more intensive and longer rehabilitation after COVID-19.

Understanding pulmonary function at various phases after coronavirus disease 2019 (COVID-19) infection is critical for determining the exact pathophysiological mechanism of COVID-19.

What is the correlation between spirometry indices and clinical indicators in COVID-19 patients over a 6-week follow-up?

1) To assess deterioration or improvement in spirometry parameters including forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and ratio FEV1/FVC in COVID-19 patients. 2) To study the correlation between FVC, FEV1, and FEV1/FVC with oxygen saturation and clinical findings.

A prospective observational study was conducted for a 6-week period among 25, COVID-19 patients who were either asymptomatic or mildly symptomatic. Each patient received a home-use-connected spirometer-SpiroPRO®, a pulse oximeter, and a thermometer from Briota Technologies Pvt Ltd. (BRIOTA). Patients and healthcare professionals were given training for performing spirometry twice a day as well as access to mobile apps was provided. Spirometry indices, patient symptoms, and vital statistics were used to calculate the VIEW™ score using machine learning algorithms.

The Bland-Altman plots showed that FEV1 reduced slightly up to 21-28 days and comes back to normal around 42 days. VIEW™ score increased up to day 21 and then decreased toward day 42. An increase in VIEW™ score increases the risk of COVID-19 complications. VIEW™ score and FEV1 showed a significant correlation.

Home-based spirometry acts as an effective tool for COVID-19 patients to predict lung complications and also promote self-monitoring thereby reducing the burden on the health system.

Coronavirus disease 2019 (COVID-19) predominantly impacts the respiratory system. Historically, numerous lung diseases have shown sex-related differences throughout their progression. This study aimed to identify sex-linked disparities in pulmonary function tests (PFTs) among individuals who have recovered from COVID-19 when subjected to a six-minute walk test (6MWT). In this observational cross-sectional study, we analyzed 61 participants, consisting of 39 (64%) males and 22 (36%) females, all of whom previously contracted COVID-19 three months or more prior. We measured vitals such as blood pressure, pulse, oxygen saturation, and PFT values before and after the 6MWT. The post-6MWT evaluation revealed notable mean differences between males and females in parameters systolic blood pressure (SBP) (p = 0.003), diastolic blood pressure (DBP) (p = 0.026), forced expiratory volume in the first second (FEV1) (p = 0.038), forced vital capacity (FVC) (p = 0.041), and maximum voluntary ventilation (MVV) index (p = 0.011). PFT outcomes indicated sex-based variations among post-COVID-19 subjects. Specifically, post-stress values for FEV1, FVC, MVV index, SBP, and DBP were more elevated in males than in females. However, females presented with higher oxygen saturation levels post-COVID-19 compared to males. Using multiple linear regression modeling, sex was not found to be a strong predictor of PFT results. However, individual regression analyses for FEV1, FVC, and MVV index consistently showcased higher values in males. In conclusion, significant PFT differences exist between males and females after recovery from COVID-19 when exposed to stress induction via the 6MWT.

Post-COVID-19 syndrome (PCS) has been increasingly recognized as an emerging problem: 50% of patients report ongoing symptoms 1 year after acute infection, with most typical manifestations (fatigue, dyspnea, psychiatric and neurological symptoms) having potentially debilitating effect. Early identification of high-risk candidates for PCS development would facilitate the optimal use of resources directed to rehabilitation of COVID-19 convalescents.

To study the in-hospital clinical characteristics of COVID-19 survivors presenting with self-reported PCS at 3 months and to identify the early predictors of its development.

221 hospitalized COVID-19 patients underwent symptoms assessment, 6-min walk test, and echocardiography pre-discharge and at 1 month; presence of PCS was assessed 3 months after discharge. Unsupervised machine learning was used to build a SANN-based binary classification model of PCS development.

PCS at 3 months has been detected in 75% patients. Higher symptoms level in the PCS group was not associated with worse physical functional recovery or significant echocardiographic changes. Despite identification of a set of pre-discharge predictors, inclusion of parameters obtained at 1 month proved necessary to obtain a high accuracy model of PCS development, with inputs list including age, sex, in-hospital levels of CRP, eGFR and need for oxygen supplementation, and level of post-exertional symptoms at 1 month after discharge (fatigue and dyspnea in 6MWT and MRC Dyspnea score).

Hospitalized COVID-19 survivors at 3 months were characterized by 75% prevalence of PCS, the development of which could be predicted with an 89% accuracy using the derived neural network-based classification model.

Detection of the physiological response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is challenging in the absence of overt clinical signs but remains necessary to understand a full subclinical disease spectrum. In this study, our objective was to use radiomics (from computed tomography images) and blood biomarkers to predict SARS-CoV-2 infection in a nonhuman primate model (NHP) with inapparent clinical disease. To accomplish this aim, we built machine-learning models to predict SARS-CoV-2 infection in a NHP model of subclinical disease using baseline-normalized radiomic and blood sample analyses data from SARS-CoV-2-exposed and control (mock-exposed) crab-eating macaques. We applied a novel adaptation of the minimum redundancy maximum relevance (mRMR) feature-selection technique, called mRMR-permute, for statistically-thresholded and unbiased feature selection. Through performance comparison of eight machine-learning models trained on 14 feature sets, we demonstrated that a logistic regression model trained on the mRMR-permute feature set can predict SARS-CoV-2 infection with very high accuracy. Eighty-nine percent of mRMR-permute selected features had strong and significant class effects. Through this work, we identified a key set of radiomic and blood biomarkers that can be used to predict infection status even in the absence of clinical signs. Furthermore, we proposed and demonstrated the utility of a novel feature-selection technique called mRMR-permute. This work lays the foundation for the prediction and classification of SARS-CoV-2 disease severity.

From the first reports of SARS-CoV-2, at the end of 2019 to the present, the global mortality associated with COVID-19 has reached 6,952,522 deaths as reported by the World Health Organization (WHO). Early intubation and mechanical ventilation can increase the survival rate of critically ill patients. This prospective study was carried out on 885 patients in the ICU of Mureș County Clinical Hospital, Romania. After applying inclusion and exclusion criteria, a total of 54 patients were included. Patients were monitored during hospitalization and at 6-month follow-up. We analyzed the relationship between invasive mechanical ventilation (IMV) and non-invasive mechanical ventilation (NIMV) and radiological changes on thoracic CT scans performed at 6-month follow-up and found no significant association. Regarding paraclinical analysis, there was a statistically significant association between patients grouped by IMV and ferritin level on day 1 of admission (p = 0.034), and between patients grouped by PaO2/FiO2 ratio with metabolic syndrome (p = 0.03) and the level of procalcitonin (p = 0.01). A significant proportion of patients with COVID-19 admitted to the ICU developed pulmonary fibrosis as observed at a 6-month evaluation. Patients with oxygen supplementation or mechanical ventilation require dynamic monitoring and radiological investigations, as there is a possibility of long-term pulmonary fibrosis that requires pharmacological interventions and finding new therapeutic alternatives.

Limitation in exercise capacity has not been described in athletes affected by SARS-CoV-2 infection. However, patients who have recovered from COVID-19 without cardiopulmonary impairment show exaggerated ventilatory response during exercise. Therefore, we aimed to evaluate the ventilatory efficiency (VEf) in competitive athletes recovered from COVID-19 and to characterize the ventilation versus carbon dioxide relationship (VE/VCO2 ) slope in this population. Thirty-seven competitive athletes with COVID-19 were recruited for this study. All participants underwent spirometry, echocardiography, and cardiopulmonary exercise testing (CPET). z-FVC values and end-title pressure of CO2 (PET CO2 ) were lower in the third tertile compared with the first tertile: -0.753 ± 0.473 vs. 0.037 ± 0.911, p = 0.05; 42.2 ± 2.7 vs. 37.1 ± 2.5 mmHg, p < 0.01. VE/VCO2 slope was significantly correlated to maximal VCO2 /VE and maximal VO2 /VE: coefficient = -0.5 R2  = 0.58, p < 0.0001 and coefficient = -0.3 R2  = 0.16, p = 0.008. Competitive athletes affected by SARS-CoV-2 infection, without cardio-respiratory disease sequel, may present ventilatory inefficiency (ViE), without exercise capacity limitation. FVC is higher in athletes with better ventilatory performance during exercise, and increased VE/VCO2 slope is inversely correlated to max VCO2 /VE and max VO2 /VE.

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has had significant impacts on pulmonary function. This study aimed to comprehensively evaluate pulmonary function and structure in patients 40 days post-SARS-CoV-2 infection, employing an array of testing methodologies including spirometry, plethysmography, forced oscillometry, and CT scanning. It also sought to establish potential correlations between these metrics and evaluate if forced oscillometry could provide additional value in post-infective lung function assessment. A 40-day post-infection follow-up observational study was conducted involving 66 patients with confirmed SARS-CoV-2 infection. The results revealed decreases in FVC and FEF25-75 with the increasing severity of COVID-19. Specifically, patients with severe symptoms exhibited statistically significant decreases in FVC (mean = 86.8) compared with those with mild symptoms (mean = 106.0; p = 0.018). The FEF25-75 showed a similar trend, with severe patients exhibiting a mean of 77.7 compared with 82.9 in the mild group (p = 0.017). Furthermore, resonant frequency (RF) increased with disease severity, with the severe group exhibiting a statistically significant increase (mean = 17.4) compared with the mild group (mean = 14.3; p = 0.042). CT scans showed an increase in ground-glass opacities with disease severity, with 81.8% of severe patients demonstrating this finding (p = 0.037). Multiple regression analysis revealed that Reactance at 4 Hz (X4), Forced Expiratory Flow 25-75% (FEF25-75), and Resonant Frequency (RF) were significantly related to COVID-19 severity. Specifically, for each unit increase in these factors, the risk of the event was estimated to increase by a factor of 3.16, 2.09, and 1.90, respectively. Conversely, Resistance at 4 Hz (R4) and Airway Resistance (RAW) were found to significantly decrease the event hazard, highlighting their potential protective role. Spirometry, plethysmography, and forced oscillometry are effective in assessing these changes. Forced oscillometry may be particularly beneficial in identifying subtle changes in lung function post-COVID-19. Further studies are warranted to validate these findings and develop strategies to manage post-infective pulmonary changes in SARS-CoV-2 patients.

Persistent pulmonary impairment post-COVID-19 has been reported, albeit variably. This single-center observational study aims to longitudinally evaluate pulmonary function in 140 COVID-19 survivors one year after recovery, assessing associations with disease severity and pre-existing lung conditions. Participants aged 18 and older, with confirmed SARS-CoV-2 infection, were evaluated using spirometry and Diffusion Capacity of Lungs for Carbon Monoxide (DLCO) tests. Pulmonary function parameters like Forced Expiratory Volume at 1 s (FEV1), Forced Vital Capacity (FVC), and Total Lung Capacity (TLC) were measured. Participants were stratified by age, gender, body mass index, smoking status, and lung damage severity via computed tomography (CT). The cohort consisted of mostly males (58.6%), with a mean age of 53.8 years and body mass index of 24.9 kg/m2. Post-COVID fibrosis was seen in 22.7%, 27.3%, and 51.9% of mild, moderate, and severe disease patients, respectively (p = 0.003). FVC significantly reduced with disease severity (p < 0.001), while FEV1, FEF25-75, and DLCO showed a non-significant downward trend. FEV1/FVC ratio increased with disease severity (p = 0.033), and TLC and RV significantly declined (p = 0.023 and p = 0.003, respectively). A one-year follow-up indicated a non-significant change in FVC, FEV1, FEV1/FVC ratio, FEF25-75, and RV compared with the 40-day measurement, but it revealed significant improvements in DLCO and TLC (p = 0.010). There were significant mean increases in FVC, FEV1, DLCO, TLC, and RV across all disease severities over one year. They were most pronounced in the patients with a history of severe COVID-19, who had a better recovery over one year, compared with the mild and moderate COVID-19 patients whose lung function almost normalized. One year after the SARS-CoV-2 infection, we observed a significant association between disease severity and post-COVID fibrotic changes. Though some lung function parameters remained stable over the year, significant improvements were noted in DLCO and TLC. Particularly, individuals with severe disease showed substantial recovery in lung function, indicating the potential reversibility of COVID-19-related pulmonary damage.

To investigate the impact of impaired pulmonary function on patient-centered outcomes after hospital discharge due to severe COVID-19 in patients without preexisting respiratory disease.

This is an ongoing prospective cohort study evaluating patients (> 18 years of age) 2-6 months after hospital discharge due to severe COVID-19. Respiratory symptoms, health-related quality of life, lung function, and the six-minute walk test were assessed. A restrictive ventilatory defect was defined as TLC below the lower limit of normal, as assessed by plethysmography. Chest CT scans performed during hospitalization were scored for the presence and extent of parenchymal abnormalities.

At a mean follow-up of 17.2 ± 5.9 weeks after the diagnosis of COVID-19, 120 patients were assessed. Of those, 23 (19.2%) reported preexisting chronic respiratory diseases and presented with worse lung function and exertional dyspnea at the follow-up visit in comparison with their counterparts. When we excluded the 23 patients with preexisting respiratory disease plus another 2 patients without lung volume measurements, a restrictive ventilatory defect was observed in 42/95 patients (44%). This subgroup of patients (52.4% of whom were male; mean age, 53.9 ± 11.3 years) showed reduced resting gas exchange efficiency (DLCO), increased daily-life dyspnea, increased exertional dyspnea and oxygen desaturation, and reduced health-related quality of life in comparison with those without reduced TLC (50.9% of whom were male; mean age, 58.4 ± 11.3 years). Intensive care need and higher chest CT scores were associated with a subsequent restrictive ventilatory defect.

The presence of a restrictive ventilatory defect approximately 4 months after severe COVID-19 in patients without prior respiratory comorbidities implies worse clinical outcomes.

As the population of patients recovering from COVID-19 grows, post COVID-19 challenges are recognizing by ongoing evidences at once. Long COVID is defined as a syndrome with a range of persistent symptoms that remain long after (beyond 12 weeks) the acute SARS-CoV-2 infection. Studies have shown that long COVID can cause multi-organ damages with a wide spectrum of manifestations. Many systems, but not limited to, including respiratory, cardiovascular, nervous, gastrointestinal, and musculoskeletal systems, are involved in long COVID. Fatigue and dyspnea are the most common symptoms of long COVID. Long COVID-19 may be driven by tissue damage caused by virus-specific pathophysiologic changes or secondary to pathological long-lasting inflammatory response because of viral persistence, immune dysregulation, and autoimmune reactions. Some risk factors like sex and age, more than five early symptoms, and specific biomarkers have been revealed as a probable long COVID predicator discussed in this review. It seems that vaccination is the only way for prevention of long COVID and it can also help patients who had already long COVID. Managing long COVID survivors recommended being in a multidisciplinary approach, and a framework for identifying those at high risk for post-acute COVID-19 must be proposed. Possible therapeutic options and useful investigation tools for follow-up are suggested in this review. In sum, as evidence and researches are regularly updated, we provide the current understanding of the epidemiology, clinical manifestation, suspected pathophysiology, associated risk factors, and treatment options of long COVID in this review.

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.

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.

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.

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.

We investigated abnormalities and recovery in respiratory function after COVID-19 infection in an unvaccinated elite athlete population.

Measurements included maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP), forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and peak expiratory flow (PEF).

The most frequent reported symptoms were fatigue with 80% and muscle/joint pain and headache with 50%, whereas only 10% reported dyspnoea and 30% cough. During follow-up, MIP was up to 13% and MEP up to 8% lower following COVID-19 infection. Likewise, FEV₁ was up to 2% and FVC up to 5% lower. While MEP and FEV₁ rapidly normalised, MIP and FVC still remained abnormal after 52 days of COVID-19 infection, thereby leading to a restrictive ventilatory pattern. PEF seemed unaffected during follow-up.

COVID-19 decreases respiratory function in unvaccinated athletes despite reporting few respiratory symptoms and having mild disease. An initiative aimed at reducing the long-term adverse effects following COVID-19 infection seems warranted, which perhaps may be avoided through vaccination.

Post-COVID-19 exercise intolerance is poorly understood. Cardiopulmonary exercise testing (CPET) can identify the underlying exercise limitations.

To evaluate the source and magnitude of exercise intolerance in post-COVID-19 subjects.

Cohort study assessing subjects with different COVID-19 illness severities and a control group selected by propensity score matching. In a selected sample with CPET prior to viral infection, before and after comparisons were performed. Level of significance was 5% in the entire analysis.

One hundred forty-four subjects with COVID-19 were assessed (median age: 43.0 years, 57% male), with different illness severities (60% mild, 21% moderate, 19% severe). CPET was performed 11.5 (7.0, 21.2) weeks after disease onset, with exercise limitations being attributed to the peripheral muscle (92%), and the pulmonary (6%), and cardiovascular (2%) systems. Lower median percent-predicted peak oxygen uptake was observed in the severe subgroup (72.2%) as compared to the controls (91.6%). Oxygen uptake differed among illness severities and controls at peak and ventilatory thresholds. Conversely, ventilatory equivalents, oxygen uptake efficiency slope, and peak oxygen pulse were similar. Subgroup analysis of 42 subjects with prior CPET revealed significant reduction in only peak treadmill speed in the mild subgroup and in oxygen uptake at peak and ventilatory thresholds in the moderate/severe subgroup. By contrast, ventilatory equivalents, oxygen uptake efficiency slope, and peak oxygen pulse did not change significantly.

Peripheral muscle fatigue was the most common exercise limitation etiology in post-COVID-19 patients regardless of the illness severity. Data suggest that treatment should emphasize comprehensive rehabilitation programs, including aerobic and muscle strengthening components.

Survivors of severe-to-critical COVID-19 may have functional impairment, radiological sequelae and persistent symptoms requiring prolonged follow-up. This pragmatic study aimed to describe their clinical follow-up and determine their respiratory recovery trajectories, and factors that could influence them and their health-related quality of life.

Adults hospitalised for severe-to-critical COVID-19 were evaluated at 3 months and up to 12 months post-hospital discharge in this prospective, multicentre, cohort study.

Among 485 enrolled participants, 293 (60%) were reassessed at 6 months and 163 (35%) at 12 months; 89 (51%) and 47 (27%) of the 173 ones initially managed with standard oxygen were reassessed at 6 and 12 months, respectively. At 3 months, 34%, 70% and 56% of the participants had a restrictive lung defect, impaired DL_CO and significant radiological sequelae, respectively. During extended follow-up, DL_CO and FVC (% of predicted value) increased by means of +4 points at 6 months, and +6 points at 12 months. Sex, body mass index, chronic respiratory disease, immunosuppression, pneumonia extent or corticosteroid use during acute COVID-19 and prolonged invasive mechanical ventilation (IMV) were associated with DL_CO at month 3, but not its trajectory thereafter. Among 475 (98%) patients with at least one chest computed-tomography scan during follow-up, 196 (41%) had significant sequelae on their last images.

Although pulmonary function and radiological abnormalities improved up to 1 year post-acute-COVID-19, high percentages of severe-to-critical disease survivors, including a notable proportion of those managed with standard oxygen, had significant lung sequelae and residual symptoms justifying prolonged follow-up.

After COVID-19 infection, persistent exercise intolerance, changes in lung function have been shown. Our aim is to investigate the correlation between impulse oscillometry (IOS) parameters and exercise capacity by using incremental and endurance shuttle walk tests (ISWT, ESWT) and investigate the factors and parameters which might have an effect on both IOS parameters and exercise capacity tests.

The patients who had a history of COVID-19 were enrolled into cross-sectional study according to inclusion criteria. The IOS parameters, ISWT, ESWT, smoking status, time since COVID-19 diagnosis, length of hospital stay, forced vital capacity (FVC), forced expiratory volume in one second (FEV1), body mass index (BMI), fat-free mass index (FFMI), dyspnea, hospital anxiety-depression and fatigue severity scores were recorded.

The study comprised 72 patients, 71% of whom were male, with a mean age of 54 ± 10 years. After COVID-19 diagnosis, the median duration was 3 (min: 1, max: 5) months and 51 (71%) of the patients were hospitalized. The FEV1 and FVC values were in normal range. The area of reactance (AX), resonance frequency (Fres), reactance at 20 Hz (X20) and the difference between resonance at 20 and 5 Hz (R5-20) correlated with both ISWT and ESWT. The FEV1 correlated with all IOS parameters (p < 0.05). Reactance correlated with FFMI (p = 024, r = 0.267), different according to hospitalization (p = 0.02).

In COVID-19 survivors, there could be correlations between IOS parameters and exercise capacity; and between these parameters and FEV and FVC. Furthermore, small airway disease with normal spirometric functions could be related to decreased exercise capacity in COVID-19 survivors regardless of concomitant diseases, BMI, smoking status and time since COVID-19 diagnosis.

Pulmonary microvascular occlusions can aggravate SARS-CoV-2 pneumonia and result in a variable decrease in capillary blood volume (Vc). Dyspnoea may persist for several weeks after hospital discharge in many patients who have "radiologically recovered" from COVID-19 pneumonia. Dyspnoea is frequently "unexplained" in these cases because abnormalities in lung vasculature are understudied. Furthermore, even when they are identified, therapeutic options are still lacking in clinical practice, with nitric oxide (NO) supplementation being used only for severe respiratory failure in the hospital setting. Nebivolol is the only selective β¹ adrenoceptor antagonist capable of inducing nitric oxide-mediated vasodilation by stimulating endothelial NO synthase via β₃ agonism. The purpose of this study was to compare the effect of nebivolol versus placebo in patients who had low Vc and complained of dyspnoea for several weeks after COVID-19 pneumonia.

Patients of both genders, aged ≥18 years, non-smokers, who had a CT scan that revealed no COVID-related parenchymal lesions but still complaining of dyspnoea 12-16 weeks after hospital discharge, were recruited. Spirometrical volumes, blood haemoglobin, SpO₂, simultaneous diffusing capacity for carbon monoxide (CO) and NO (DL_CO and DL_NO, respectively), DL_NO/DL_CO ratio, Vc and exhaled NO (eNO) were measured together with their dyspnoea score (DS), heart frequency (HF), and blood arterial pressure (BAP). Data were collected before and one week after both placebo (P) and nebivolol (N) (2.5 mg od) double-blind cross-over administered at a two-week interval. Data were statistically compared, and p<0.05 assumed as statistically significant.

Eight patients (3 males) were investigated. In baseline, their mean DS was 2.5±0.6 SD, despite the normality of lung volumes. DL_CO and DL_NO mean values were lower than predicted, while mean DL_NO/DL_CO ratio was higher. Mean Vc proved substantially reduced. Placebo did not modify any variable (all p=ns) while N improved DLco and Vc significantly (+8.5%, p<0.04 and +17.7%, p<0.003, respectively). eNO also was significantly increased (+17.6%, p<0.002). Only N lowered the dyspnoea score (-76%, p<0.001). Systolic and diastolic BAP were slightly lowered (-7.5%, p<0.02 and -5.1%, p<0.04, respectively), together with HF (-16.8%, p<0.03).

The simultaneous assessment of DL_NO, DL_CO, DL_NO/DL_CO ratio, and Vc confirmed that long-lasting dyspnoea is related to hidden abnormalities in the lung capillary vasculature. These abnormalities can persist even after the complete resolution of parenchymal lesions regardless of the normality of lung volumes. Nebivolol, but not placebo, improves DS and Vc significantly. The mechanism suggested is the NO-mediated vasodilation via the β3 adrenoceptor stimulation of endothelial NO synthase. This hypothesis is supported by the substantial increase of eNO only assessed after nebivolol. As the nebivolol tolerability in these post-COVID normotensive patients was very good, the therapeutic use of nebivolol against residual and symptomatic signs of long-COVID can be suggested in out-patients.

Beginning with the various strategies of the SARS-CoV-2 virus to invade our bodies and manifest infection, and ending with the recent long COVID, we are witnessing the evolving course of the disease in addition to the pandemic. Given the partially controlled course of the COVID-19 pandemic, the greatest challenge currently lies in managing the short- and long-term complications of COVID-19. We have assembled current knowledge of the broad spectrum of cardiovascular, pulmonary, and neuropsychiatric sequelae following SARS-CoV-2 infection to understand how these clinical manifestations collectively lead to a severe form of the disease. The ultimate goal would be to better understand these complications and find ways to prevent clinical deterioration.

Data on the long-term trajectories of lung function are scarce in COVID-19 survivors.

We re-analyzed the data from a prospective longitudinal cohort follow-up study of COVID-19 survivors over 2 years after infection. All participants were divided into scale 3, scale 4 and scale 5-6 groups according to seven-category ordinal scale. The changes of pulmonary function tests (PFTs), the Modified Medical Research Council (mMRC) Dyspnea Scale, 6-min walking test health-related quality of life (HRQoL) across the three serial follow-up visits were evaluated, and compared among three groups. We performed liner regression to determine potential factors that were associated with changes of PFTs and distance walked in 6 minutes (6MWD).

In this study, 288 participants generally presented an improvement of PFTs parameters from 6 months to 1 year after infection. The scale 5-6 group displayed a significantly higher increase of PFTs compared with scale 3 and scale 4 groups (all p<0.0167), and corticosteroids therapy was identified as a protective factor for the PFTs improvement with a correlation coefficient of 2.730 (0.215-5.246) for forced vital capacity (FVC), 2.909 (0.383-5.436) for total lung capacity (TLC), and 3.299 (0.211-6.387) for diffusion capacity for carbon monoxide (DLco), respectively. From 1-year to 2-year follow-up, the PFTs parameters generally decreased, which was not observed to be associated with changes of 6MWD and HRQoL. Dyspnea (mMRC≥1) generally decreased over time (23.3% [61/262] for 6-month, 27.9% [67/240] for 1-year, 13.4% [35/261] for 2-year), and 6MWD increased continuously (500.0 m vs 505.0 m vs 525.0 m).

Corticosteroids therapy during hospitalization was a protective factor for PFTs improvement from 6 months to 1 year. The relatively fast decline trend of PFTs from 1 year to 2 years needs to be paid attention and further validated in the future follow-up study.

This work was supported by Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (CIFMS 2021-I2M-1-048) and the National Key Research and Development Program of China (2021YFC0864700).