Impact of impaired pulmonary function on clinical outcomes in survivors of severe COVID-19 without pre-existing respiratory disease.

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

[Follow-up of patients after COVID-19 pneumonia. Pulmonary sequelae]. / Seguimiento de los pacientes después de neumonía por COVID-19. Secuelas pulmonares.

Coronavirus disease 2019 (COVID-19) is an infection caused by SARS-CoV-2 that has caused an unprecedented pandemic with a high rate of morbidity and mortality worldwide. Although most cases are mild, there are a considerable number of patients who develop pneumonia or even acute respiratory distress syndrome (ARDS). After having recovered from the initial disease, many patients continue with various symptoms (fatigue, dry cough, fever, dyspnea, anosmia, and chest pain, among others.), which has led to consider the possible existence of "post-COVID-19 syndrome". Although the definition and validity of this syndrome are not clear yet, several studies report that individuals who have recovered from COVID-19 may have persistent symptoms, radiological abnormalities, and compromised respiratory function. Current evidence suggests that there is a large number of pulmonary sequelae after COVID-19 pneumonia (interstitial thickening, ground glass opacities, crazy paving pattern, and bronchiectasis, among others.). Likewise, it seems that pulmonary function tests (spirometry, DLCO, 6MWT, and measurement of maximum respiratory pressures), in addition to high-resolution computed axial tomographies (CAT scan), are useful for the assessment of these post-COVID-19 pulmonary sequelae. This review aims to describe the possible pulmonary sequelae after COVID-19 pneumonia, as well as to suggest diagnostic procedures for their correct assessment and follow-up; thus, allowing proper management by a multidisciplinary medical team.

COVID-19 es la enfermedad causada por el virus SARS-CoV-2, la cual ha ocasionado una pandemia sin precedentes, con gran cantidad de infectados y muertos en el mundo. Aunque la mayoría de los casos son leves, existe una cantidad considerable de pacientes que desarrollan neumonía o, incluso, síndrome de distrés respiratorio agudo (SDRA). Luego de recuperarse del cuadro inicial, muchos pacientes continúan con diversos síntomas (fatiga, tos seca, fiebre, disnea, anosmia, dolor torácico, entre otras), lo que ha llevado a considerar la posible existencia del "síndrome pos-COVID-19". Aunque la definición y validez de este síndrome aún no son claras, varios estudios reportan que los individuos recuperados de la COVID-19 pueden tener persistencia de síntomas, anormalidades radiológicas y compromiso en la función respiratoria. La evidencia actual sugiere que existe gran cantidad de secuelas pulmonares despues de una neumonía por COVID-19 (engrosamiento intersticial, infiltrado en vidrio esmerilado, patrón en empedrado, bronquiectasias, entre otras.). De igual forma, parece ser que las pruebas de función pulmonar (espirometría, prueba de difusión pulmonar de monóxido de carbono, prueba de caminata de seis minutos y la medición de las presiones respiratorias máximas), además de la tomografía axial computarizada de alta resolución, son útiles para evaluar las secuelas pulmonares pos-COVID-19. En esta revisión se pretende describir las posibles secuelas a nivel pulmonar posteriores a neumonía por COVID-19, así como sugerir procedimientos diagnósticos para su correcta evaluación y seguimiento, que permitan el manejo adecuado por parte de un equipo médico multidisciplinario.

What Have We Learned About Transmission of Coronavirus Disease-2019: Implications for Pulmonary Function Testing and Pulmonary Procedures.

Because of the potential for high aerosol transmission during pulmonary function testing and pulmonary procedures, performing these tests and procedures must be considered carefully during the coronavirus disease-2019 (COVID-19) pandemic. Much has been learned about the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by aerosols and the potential for such transmission through pulmonary function tests and pulmonary procedures, and subsequently preventative practices have been enhanced and developed to reduce the risk of transmission of virus to patients and personnel. This article reviews what is known about the potential for transmission of SARS-CoV-2 during pulmonary function testing and pulmonary procedures and the recommended mitigation steps to prevent the spread of COVID-19.

Cardiopulmonary rehabilitation programme improves physical health and quality of life in post-COVID syndrome.

BACKGROUND: Many patients with previous COVID-19 infection suffer from prolonged symptoms after their recovery: cough, dyspnea, chest pain, shortness of breath, fatigue, anxiety or depression, regardless of milder or severe coronavirus infection. Review of the literature demonstrates underrepresented complex cardiopulmonary rehabilitation of patients with post-COVID syndrome. The aim of our quasi-experimental study was to evaluate the effectiveness of complex cardiopulmonary rehabilitation and to assess the quality of life, functional parameters before and after a 14-day specific cardiopulmonary rehabilitation and two months later. METHODS: Sixty-eight patients participated in rehabilitation at Semmelweis University's Department of Pulmonology. Respiratory function: forced expiratory volume in 1 second (FEV1%pred), 6-minute walk test (6MWT), chest kinematics (CK), quality of life [EuroQol-5D (EQ-5D), Post-COVID-19 Functional Status (PCFS)] and Modified Medical Research Council (mMRC) dyspnea scale were measured at the beginning and end of the programme and two months after the rehabilitation. RESULTS: The 14-day rehabilitation programme resulted in significant improvement of 6MWT {492 [interquartile range (IQR), 435-547] vs. 523 (IQR, 477-580) m; P=0.031}, mMRC [1 (IQR, 0.25-1) vs. 0 (IQR, 0-1); P=0.003], EQ-VAS score [75 (IQR, 65-80) vs. 85 (IQR, 75-90); P=0.015], and PCFS [1 (IQR, 1-2) vs. 0.5 (IQR, 0-1); P=0.032]. Respiratory function and chest kinematics also improved, FEV1(%pred) [86 (IQR, 73-103) vs. 91 (IQR, 80-99); P=0.360], chest kinematics [3.5 (IQR, 2.75-4.25) vs. 4 (IQR, 1-5.25) cm; P=0.296], and breath-holding test (BHT) [33 (IQR, 23-44) vs. 41 (IQR, 28-58) s; P=0.041]. CONCLUSIONS: Complex cardiopulmonary rehabilitation improved workload, quality of life, respiratory function, complaints and clinical status of patients with post-COVID syndrome. Personalized complex pulmonary rehabilitation can be beneficial and recommended for patients suffer from post-COVID syndrome, who have good potential for recovery and are able to participate in the two weeks complex pulmonary rehabilitation.

What can we learn from the Baduanjin rehabilitation as COVID-19 treatment?: A narrative review.

AIM: To understand Baduanjin rehabilitation therapy in mild COVID-19 patients. DESIGN: A narrative review. METHODS: A literature search for COVID-19 and Baduanjin treatments was conducted on Chinese and English electronic databases: China National Knowledge Infrastructure, Wanfang Data, Embase, PubMed, Scopus, Science Direct, Ebscohost, SPORTDiscus and ProQuest. RESULTS: Twelve studies on the Baduanjin rehabilitation for COVID-19 patients have been included. We acknowledged the considerable published research and current clinical practice using Baduanjin for COVID-19 treatment in the following areas: anxiety, depression, insomnia, lung function rehabilitation, immunity and activity endurance. CONCLUSION: The use of Baduanjin as adjuvant therapy for COVID-19 patients' rehabilitation is still limited, therefore, more clinical studies are needed to confirm its efficacy.

Effect of weight-bearing Liuzijue Qigong on cardiopulmonary function.

BACKGROUND: Since the outbreak of coronavirus disease 2019, many people have had to reduce their outdoor activities. Therefore, a convenient, simple, at-home training method to improve or maintain cardiopulmonary function is required. This study aimed to explore the therapeutic effect of weight-bearing Liuzijue Qigong on cardiopulmonary function in healthy volunteers. METHODS: This study was a longitudinal trial. The health participants completed a 4-week Liuzijue Qigong exercise with 0.25 kg sandbag wore on each wrist. Each training session took 30 minutes to complete 2 consecutive cycles, and 5 times a week. The cardiopulmonary function of participants was evaluated at baseline (T0) and the end of the intervention (T4). Outcomes measures were pulmonary function, diaphragm movement, and cardiac hemodynamic parameters. Paired t test was used to analyze differences within the group. RESULTS: After 4 weeks of weight-bearing Liuzijue Qigong exercise intervention, the differences in the forced expiratory volume in the 1st second (P = .006), forced vital capacity rate of 1 second (P = .003), maximal mid-expiratory flow curve (P = .002), forced expiratory flow at 50% of forced vital capacity (P = .003), and maximum ventilatory volume (P < .001) of the participants were statistically significant. The diaphragmatic excursion (P = .009) under the calm breathing mode and the diaphragmatic contraction speed (P = .003) under the deep breathing mode improved significantly. The cardiac output (P = .04), cardiac index (P = .035), contractility index (P = .018), early diastolic filling ratio (P = .042), systemic vascular resistance index (P = .019), systemic vascular resistance (P = .017), and estimated ejection fraction (P = .016) of participants improved significantly in the resting stage. At the end stage of fast walking, that is, the sixth minute of six-minute walk test, the stroke volume index (P = .048), heart rate (P = .019), cardiac output (P = .008), cardiac index (P = .003), and left cardiac work index (P = .028) of participants were significantly increased compared with those before training, and the systemic vascular resistance index (P = .003) and systemic vascular resistance (P = .005) were decreased. CONCLUSION: Weight-bearing Liuzijue Qigong training significantly improved cardiopulmonary function in healthy volunteers, thus representing home-based cardiopulmonary rehabilitation training.

The impact of COVID-19 on pulmonary function and airway reactivity after recovery in college-aged adults.

The purpose of this study was to determine (1) whether pulmonary function is reduced, and airway reactivity is increased after recovery from COVID-19 in individuals who did not have severe illness, and (2) whether physical activity levels had any impact on pulmonary function or airway reactivity. An exploratory aim of the study was also to assess whether number of symptoms was associated with pulmonary function outcomes. The maximal flow volume loop was used to measure pulmonary function in individuals who had previously tested positive for COVID-19 (COV; n = 20, 23.0 ± 5.4 years) and those who had not (CON; n = 20, 23.7 ± 5.5 years) before and after a hypertonic saline challenge (HSC) designed to increase airway reactivity. Self-reported symptoms and physical activity levels (MET (min/week)) were collected to examine their correlation with pulmonary outcomes. There were no significant differences in any pulmonary function outcomes between the COV and CON groups before or after the HSC. There were also no associations between physical activity and pulmonary function outcomes. However, among participants who reported greater than four symptoms, there was a larger decline in forced expiratory volume in 1 s divided by forced vital capacity following HSC (p = 0.035). Pulmonary function and airway reactivity are not impacted after recovery from COVID-19 in young individuals; however, it appears that the number of symptoms reported may be associated with increased airway reactivity even after recovery in young adults who were not hospitalized with the virus.

The Role of Pulmonary Function Testing and Lung Imaging in the Long-Term Follow-Up of Patients with COVID-19 Pneumonia Role of Pulmonary Function Tests and High-Resolution Computed Tomography in Post-COVID-19 Interstitial Lung Disease.

BACKGROUND: Post-COVID-19 Interstitial Lung Disease (PC-ILD) is characterized by fibrotic-like signs at high-resolution computed tomography (HRCT) and pulmonary function tests (PFTs) abnormalities after SARS-CoV-2 infection. It is still not clear how frequent these tests should be performed to rule out long-term consequences of COVID-19 pneumonia. OBJECTIVES: The aims of our study were to evaluate the incidence and risk factors of PC-ILD and possibly to propose a long-term follow-up program. METHOD: One-hundred patients, hospitalized in our ward for moderate to critical COVID-19, underwent two follow-up visits at three and 15 months in which PFTs and HRCT were performed. RESULTS: At the 15-month follow-up, 8% of patients showed residual radiological and functional signs consistent with PC-ILD. All but one of these patients had already demonstrated PFTs and HRCT alterations at first follow-up visit, and the last 1 patient showed worsening of lung function during follow-up. These findings highlight the negative predictive value of PFTs at 3-month follow-up for the development of PC-ILD. Aging, severity of COVID-19, and degree of pulmonary involvement during acute infection proved to be significant risk factors for developing PC-ILD. CONCLUSIONS: Our study highlights the importance of PFTs in the long-term follow-up of patients affected by moderate to critical COVID-19 pneumonia. Further studies are needed to confirm our hypothesis that HRCT should be performed only in patients with PFTs abnormalities.

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.

Interstitial lung disease following coronavirus disease 2019.

PURPOSE OF REVIEW: The aim of this review was to summarize the recent data concerning interstitial lung disease after COVID-19, a field where knowledge is evolving very quickly. RECENT FINDINGS: It has been found that a proportion of patients displayed fibrotic-like pattern on chest computed tomography shortly after COVID-19 pneumonia. Those lesions can potentially represent precursors of fibrosis, although most of them will resolve until 1 year postinfection. There was a wide range of the prevalence of post-COVID-19 interstitial lung disease detected in the literature, which can be attributed to the heterogeneous definition of lung abnormalities and the discrepancy of study design. The severity of acute COVID-19 disease has been linked to increased risk of residual imaging and functional abnormalities, while reduced DLco was the most common functional abnormality in long-term survivors. Studies indicated that pathophysiology of post-COVID interstitial lung disease shares common mechanisms with idiopathic pulmonary fibrosis. Regarding therapeutic strategies of post-COVID-19 interstitial lung disease, the role of immunosuppressive and antifibrotic treatment is currently under investigation. SUMMARY: We still need to learn about the natural history of COVID-19 disease, allowing for a better targeting of therapeutic interventions through a multidisciplinary approach.

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.

Inhaled Marijuana and the Lung.

Although vaping has recently increased as a mode of inhaling marijuana and has been associated with numerous and sometimes fatal cases of acute severe lung injury, smoking remains the most common method of inhaling marijuana and has been studied more extensively. Smoking marijuana has been shown to produce modest but significant short-term bronchodilation both in healthy subjects and in those with asthma. Long-term effects of habitual marijuana smoking include the following: (1) symptoms of chronic bronchitis (increased cough, sputum production, and wheezing); (2) modest effects on lung function in cross-sectional studies (no significant decrease in FEV1 but mild reductions in FEV1/forced vital capacity ratio, an increase in forced vital capacity and other lung volumes, reductions in specific airway conductance, and variable effects of maximal midexpiratory flow rates and diffusing capacity); and (3) variable effects on age-related decline in FEV1 in longitudinal studies. Most cohort and case-control studies have failed to show that marijuana smoking is a significant risk factor for lung cancer despite the presence of procarcinogenic components in marijuana smoke, although further study is warranted. The question whether marijuana smoking is associated with asthma is unclear and requires further investigation. Although delta-9 tetrahydrocannabinol, the principal psychoactive component of marijuana, has immunomodulatory properties that hypothetically could increase the risk of pneumonia, the few available studies in marijuana smokers have failed to find an increased risk of pneumonia in immunocompetent users, although effects in immunosuppressed individuals have been variable.

Lung function and breathing patterns in hospitalised COVID-19 survivors: a review of post-COVID-19 Clinics.

INTRODUCTION: There is relatively little published on the effects of COVID-19 on respiratory physiology, particularly breathing patterns. We sought to determine if there were lasting detrimental effect following hospital discharge and if these related to the severity of COVID-19. METHODS: We reviewed lung function and breathing patterns in COVID-19 survivors > 3 months after discharge, comparing patients who had been admitted to the intensive therapy unit (ITU) (n = 47) to those who just received ward treatments (n = 45). Lung function included spirometry and gas transfer and breathing patterns were measured with structured light plethysmography. Continuous data were compared with an independent t-test or Mann Whitney-U test (depending on distribution) and nominal data were compared using a Fisher's exact test (for 2 categories in 2 groups) or a chi-squared test (for > 2 categories in 2 groups). A p-value of < 0.05 was taken to be statistically significant. RESULTS: We found evidence of pulmonary restriction (reduced vital capacity and/or alveolar volume) in 65.4% of all patients. 36.1% of all patients has a reduced transfer factor (TLCO) but the majority of these (78.1%) had a preserved/increased transfer coefficient (KCO), suggesting an extrapulmonary cause. There were no major differences between ITU and ward lung function, although KCO alone was higher in the ITU patients (p = 0.03). This could be explained partly by obesity, respiratory muscle fatigue, localised microvascular changes, or haemosiderosis from lung damage. Abnormal breathing patterns were observed in 18.8% of subjects, although no consistent pattern of breathing pattern abnormalities was evident. CONCLUSIONS: An "extrapulmonary restrictive" like pattern appears to be a common phenomenon in previously admitted COVID-19 survivors. Whilst the cause of this is not clear, the effects seem to be similar on patients whether or not they received mechanical ventilation or had ward based respiratory support/supplemental oxygen.

Has the pandemic changed the test quality of the pulmonary function test laboratory?

Introduction: Pulmonary function tests are used in the evaluation of the respiratory system. Maneuvers during spirometry can create aerosols and spread viruses such as SARS-CoV-2. Measures due to the pandemic can negatively affect both the number and the quality of the spirometry tests. There are no comparative studies on this subject. Materials and Methods: The tests conducted in the spirometry laboratory between November 2019 and November 2021 were evaluated. Result: Four hundred forty patients were included in the study. 50.5% of the patients were male and the mean age was 61.8 ± 16.5 years. The age, gender, height, and weight of the patients were similar. 75.2% (331) of the tests were evaluated as successful. The most common errors in tests were early termination (84.1%), uncooperative patients (29%), and poor effort (22.4%). The types of errors were not different between the two periods. The median number of tests performed for each patient was six. The total number of spirometry tests performed were 262 and 178 for 2019 and 2021 (p= 0.011), but test success remained unchanged over the years (p= 0.513). There was no significant difference between the three operators and the test success (p= 0.909), which was similar for both periods. However, the number of tests performed until the successful maneuver varied significantly (p= 0.009), and fewer maneuvers were required before the pandemic. Conclusions: According to this study, the measures taken during the pandemic did not affect the quality of spirometry, but they did lead to more tests being done up until the successful maneuver was performed.

Pulmonary sequelae of SARS-CoV-2 infection and factors associated with persistent abnormal lung function at six months after infection: Prospective cohort study.

BACKGROUND: Information on the long-term pulmonary sequelae following SARS-CoV-2 infection is limited. METHODS: Prospective cohort study of hospitalized and non-hospitalized adult patients age >18 with documented SARS-CoV-2 infection by RT-PCR three months prior to enrolment between June and December 2020. Participants underwent full pulmonary function test (PFT), cardiopulmonary exercise testing at 3 months and 6 months. Primary outcome was mean differences of forced vital capacity (FVC), diffuse capacity of lung for carbon monoxide (DLCO), and oxygen consumption (VO2) at 6 vs. 3 months. Secondary outcomes were respiratory outcomes classified into 5 clinical groups-no lung disease, resolved lung disease, persistent lung disease, PFT abnormalities attributable to pre-existing lung disease or other factors, and mild PFT abnormalities of uncertain clinical significance. RESULTS: Fifty-one, 30 hospitalized and 21 non-hospitalized, participants were included. Median age was 51 years; 20 (39.2%) were female. Mean (±SD) percent predicted values of FVC, DLCO and VO2 at 3 vs 6-month-visits were 96.2 ± 15.6 vs. 97.6 ± 15.5, 73.74 ±18 vs. 78.5 ± 15.5, and 75.5 ± 18.9 vs. 76.1 ± 21.5, respectively. Nineteen (37%) patients had physiologic and/or radiographic evidence of lung disease at 3 months with eight (15.7%) continuing to have persistent disease at 6 months. History of diabetes, hypertension, ICU admission and elevated D-Dimer levels were associated with persistent lung disease at 6 months. INTERPRETATION: Persistent lung disease at 6 months post SARS-CoV-2 infection exists. Changes of lung function between 3- and 6-months are not significant. A longer follow-up is required to determine long-term prognosis.

Efficacy and safety of Treamid in the rehabilitation of patients after COVID-19 pneumonia: a phase 2, randomized, double-blind, placebo-controlled trial.

BACKGROUND: Many patients who recovered from COVID are still suffering from pulmonary dysfunction that can be persistent even for months after infection. Therefore, treatment to prevent irreversible impairment of lung function is needed. Treamid (bisamide derivative of dicarboxylic acid, BDDA) was shown to have anti-inflammatory and antifibrotic effects in animal models of pulmonary fibrosis. This study was designed to assess the safety, tolerability, and efficacy of Treamid in the rehabilitation of patients after COVID pneumonia. The aim was to establish whether Treamid could be effective in ameliorating post-COVID sequelae. METHODS: The phase 2, randomized, double-blind, placebo-controlled clinical trial was done at 8 medical centers in Russia. Patients with a diagnosis of COVID in the past medical history (with the first symptoms of COVID appear no earlier than 2 months before screening) and having fibrotic changes in the lungs, decreased lung function (percentage of predicted FVC and/or DLCO < 80%), and moderate or severe dyspnea according to mMRC scale were enrolled and randomly assigned in a 1:1 ratio (stratified by the initial degree of lung damage, age, and concomitant chronic diseases) by use of interactive responsive technology to peroral administration of Treamid 50 mg or placebo once a day for 4 weeks. The primary outcome was the proportion of patients who achieved clinically significant improvement in FVC and/or DLCO (defined as a relative increase in FVC of ≥ 10% or a relative increase in FVC in the range of ≥ 5 to < 10% plus a relative increase in DLCO of ≥ 15%) at week 4 compared with baseline. Secondary endpoints included changes from baseline in dyspnea scoring evaluated by the modified Borg and mMRC scales, pulmonary function (FEV1, FVC, FEV1/FVC ratio, DLCO, TLC, FRC), 6-min walk distance, the overall score of the KBILD questionnaire, and the proportion of patients with a reduction in the degree of lung damage assessed by CT scores. This trial was registered on ClinicalTrials.gov (Identifier: NCT04527354). The study was fully funded by PHARMENTERPRISES LLC. RESULTS: 12 out of 29 patients (41%) in Treamid group achieved clinically significant improvement in FVC and/or DLCO compared to 5 out of 30 patients (17%) in placebo group (p = 0.036). There was a significant decrease of dyspnea according to modified Borg scale observed in the Treamid group (- 0.9 ± 0.7 vs. - 0.4 ± 0.8, p = 0.018). No significant differences in the adverse events were noted. Exploratory analysis of the female population indicated superiority of Treamid over placebo by decreasing dyspnea and the extent of lung damage as well as increasing TLC. CONCLUSIONS: 4 weeks oral administration of 50 mg Treamid was associated with clinically significant improvement in the post-COVID patients, evident by an increase in FVC and/or DLCO as well as decreasing dyspnea. Treamid was well tolerated and can be safely administered to patients discharged after COVID. Treamid was more effective in women visible by superior improvement of COVID sequalae after 4 weeks treatment. Considering that female gender is a risk factor associated with the development of post-COVID symptoms, Treamid might offer a pharmacological treatment for long-term sequalae after COVID and supports further investigation in future clinical trials in post-COVID patients.

Altered lung physiology in two cohorts after COVID-19 infection as assessed by computed cardiopulmonography.

The longer-term effects of COVID-19 on lung physiology remain poorly understood. Here, a new technique, computed cardiopulmonography (CCP), was used to study two COVID-19 cohorts (MCOVID and C-MORE-LP) at both ∼6 and ∼12 mo after infection. CCP is comprised of two components. The first is collection of highly precise, highly time-resolved measurements of gas exchange with a purpose-built molecular flow sensor based around laser absorption spectroscopy. The second component is estimation of physiological parameters by fitting a cardiopulmonary model to the data set. The measurement protocol involved 7 min of breathing air followed by 5 min of breathing pure O₂. One hundred seventy-eight participants were studied, with 97 returning for a repeat assessment. One hundred twenty-six arterial blood gas samples were drawn from MCOVID participants. For participants who had required intensive care and/or invasive mechanical ventilation, there was a significant increase in anatomical dead space of ∼30 mL and a significant increase in alveolar-to-arterial Po₂ gradient of ∼0.9 kPa relative to control participants. Those who had been hospitalized had reductions in functional residual capacity of ∼15%. Irrespectively of COVID-19 severity, participants who had had COVID-19 demonstrated a modest increase in ventilation inhomogeneity, broadly equivalent to that associated with 15 yr of aging. This study illustrates the capability of CCP to study aspects of lung function not so easily addressed through standard clinical lung function tests. However, without measurements before infection, it is not possible to conclude whether the findings relate to the effects of COVID-19 or whether they constitute risk factors for more serious disease.NEW & NOTEWORTHY This study used a novel technique, computed cardiopulmonography, to study the lungs of patients who have had COVID-19. Depending on severity of infection, there were increases in anatomical dead space, reductions in absolute lung volumes, and increases in ventilation inhomogeneity broadly equivalent to those associated with 15 yr of aging. However, without measurements taken before infection, it is unclear whether the changes result from COVID-19 infection or are risk factors for more severe disease.

Post-COVID-19 respiratory problems: burden and management.

PURPOSE OF REVIEW: To describe the burden of post-COVID respiratory sequelae in posthospital and nonhospitalized COVID-19 survivors and to describe the priorities of clinical management. RECENT FINDINGS: Due to varying definitions of 'Long COVID' or 'Post-COVID', the prevalence of post-COVID sequelae or persisting symptoms is challenging to estimate but ranges from 2.3 to 51%. Risk factors for persistent post-COVID symptoms include age, female sex, deprivation, presence of comorbidities; and in posthospital COVID-19 survivors, the severity of acute infection. Common post-COVID respiratory symptoms include breathlessness, cough and chest pain and many individuals also experience exercise intolerance. The most common pulmonary function test abnormality is impaired diffusing capacity for carbon monoxide. In posthospital COVID-19 survivors, the prevalence of interstitial lung damage is 5-11%. Disordered breathing is common in all post-COVID patients and respiratory physiotherapy is helpful. SUMMARY: The vast numbers of COVID-19 infections globally implies that a large number of people will be affected by post-COVID sequelae even with conservative estimates. A significant number of people are affected for several months and up to years following acute infection. Post-COVID sequelae have a detrimental impact on quality of life and ability to work.