Post-tuberculosis lung disease: a comparison of Brazilian, Italian, and Mexican cohorts.

OBJECTIVE: To evaluate lung function in a cohort of patients with a history of pulmonary tuberculosis in Brazil, as well as to evaluate the decline in lung function over time and compare it with that observed in similar cohorts in Mexico and Italy. METHODS: The three cohorts were compared in terms of age, smoking status, pulmonary function test results, six-minute walk test results, and arterial blood gas results. In the Brazilian cohort, pulmonary function test results, six-minute walk test results, and arterial blood gas results right after the end of tuberculosis treatment were compared with those obtained at the end of the follow-up period. RESULTS: The three cohorts were very different regarding pulmonary function test results. The most common ventilatory patterns in the Brazilian, Italian, and Mexican cohorts were an obstructive pattern, a mixed pattern, and a normal pattern (in 58 patients [50.9%], in 18 patients [41.9%], and in 26 patients [44.1%], respectively). Only 2 multidrug-resistant tuberculosis cases were included in the Brazilian cohort, whereas, in the Mexican cohort, 27 cases were included (45.8%). Mean PaO2 and mean SaO2 were lower in the Mexican cohort than in the Brazilian cohort (p < 0.0001 and p < 0.002 for PaO2 and SaO2, respectively). In the Brazilian cohort, almost all functional parameters deteriorated over time. CONCLUSIONS: This study reinforces the importance of early and effective treatment of drug-susceptible tuberculosis patients, because multidrug-resistant tuberculosis increases lung damage. When patients complete their tuberculosis treatment, they should be evaluated as early as possible, and, if post-tuberculosis lung disease is diagnosed, they should be managed and offered pulmonary rehabilitation because there is evidence that it is effective in these patients.

Renin Angiotensin System Blockers and Risk of Mortality in Hypertensive Patients Hospitalized for COVID-19: An Italian Registry.

BACKGROUND: It is uncertain whether exposure to renin-angiotensin system (RAS) modifiers affects the severity of the new coronavirus disease 2019 (COVID-19) because most of the available studies are retrospective. METHODS: We tested the prognostic value of exposure to RAS modifiers (either angiotensin-converting enzyme inhibitors [ACE-Is] or angiotensin receptor blockers [ARBs]) in a prospective study of hypertensive patients with COVID-19. We analyzed data from 566 patients (mean age 75 years, 54% males, 162 ACE-Is users, and 147 ARBs users) hospitalized in five Italian hospitals. The study used systematic prospective data collection according to a pre-specified protocol. All-cause mortality during hospitalization was the primary outcome. RESULTS: Sixty-six patients died during hospitalization. Exposure to RAS modifiers was associated with a significant reduction in the risk of in-hospital mortality when compared to other BP-lowering strategies (odds ratio [OR]: 0.54, 95% confidence interval [CI]: 0.32 to 0.90, p = 0.019). Exposure to ACE-Is was not significantly associated with a reduced risk of in-hospital mortality when compared with patients not treated with RAS modifiers (OR: 0.66, 95% CI: 0.36 to 1.20, p = 0.172). Conversely, ARBs users showed a 59% lower risk of death (OR: 0.41, 95% CI: 0.20 to 0.84, p = 0.016) even after allowance for several prognostic markers, including age, oxygen saturation, occurrence of severe hypotension during hospitalization, and lymphocyte count (adjusted OR: 0.37, 95% CI: 0.17 to 0.80, p = 0.012). The discontinuation of RAS modifiers during hospitalization did not exert a significant effect (p = 0.515). CONCLUSIONS: This prospective study indicates that exposure to ARBs reduces mortality in hospitalized patients with COVID-19.

Cardiac and pulmonary sequelae after COVID-19 pneumonia: a case series

Aims Although the new coronavirus (SARS-CoV-2) may cause an acute multiorgan syndrome (COVID-19), data are emerging on mid- and long-term sequelae of COVID-19 pneumonia. Since no study has hitherto investigated the role of both cardiac and pulmonary ultrasound techniques in detecting such sequelae, this study aimed at evaluating these simple diagnostic tools to appraise the cardiopulmonary involvement occurring after COVID-19 pneumonia. Methods and results Twenty-nine patients fully recovered from COVID-19 pneumonia were considered at our centre. On admission, all patients underwent 12-lead electrocardiogram (ECG) and transthoracic echocardiography (TTE) evaluation. Compression ultrasound (CUS) and lung ultrasound (LUS) were also performed. Finally, in each patient, pathological findings detected on LUS were correlated with the pulmonary involvement occurring after COVID-19 pneumonia as assessed on thoracic computed tomography (CT). Out of 29 patients (mean age 70 ± 10 years old;M 69%), prior cardiovascular and pulmonary comorbidities were recorded in 22 (76%). Twenty-seven patients (93%) were in sinus rhythm and two (7%) in atrial fibrillation. ECG repolarization abnormalities were extremely common (93%) and reflected the high prevalence of pericardial involvement on TTE (86%). Likewise, pleural abnormalities were frequently observed (66%). TTE signs of left and right ventricular dysfunction were reported in two patients only, but values of systolic pulmonary artery pressure were abnormal in 16 (55%) despite absence of prior comorbidities in 44% of them. Regarding LUS evaluation, most patients displayed abnormal values of diaphragmatic thickness and excursion (93%) which well correlated with the high prevalence (76%) of on pathological findings on CT scan. CUS ruled out deep vein thrombosis in all patients. Conclusions Data on cardiopulmonary sequelae after COVID-19 pneumonia are scarce. In our study, simple diagnostic tools (TTE and LUS) proved clinically useful for detection of cardiopulmonary involvement after COVID-19 pneumonia.

Combined Use of Electrocardiography and Ultrasound to Detect Cardiac and Pulmonary Involvement after Recovery from COVID-19 Pneumonia: A Case Series.

BACKGROUND: Although severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) may cause an acute multiorgan syndrome (coronavirus disease 2019 (COVID-19)), data are emerging on mid- and long-term sequelae of COVID-19 pneumonia. Since no study has hitherto investigated the role of both cardiac and pulmonary ultrasound techniques in detecting such sequelae, this study aimed at evaluating these simple diagnostic tools to appraise the cardiopulmonary involvement after COVID-19 pneumonia. METHODS: Twenty-nine patients fully recovered from COVID-19 pneumonia were considered at our centre. On admission, all patients underwent 12-lead electrocardiogram (ECG) and transthoracic echocardiography (TTE) evaluation. Compression ultrasound (CUS) and lung ultrasound (LUS) were also performed. Finally, in each patient, pathological findings detected on LUS were correlated with the pulmonary involvement occurring after COVID-19 pneumonia, as assessed on thoracic computed tomography (CT). RESULTS: Out of 29 patients (mean age 70 ± 10 years; males 69%), prior cardiovascular and pulmonary comorbidities were recorded in 22 (76%). Twenty-seven patients (93%) were in sinus rhythm and two (7%) in atrial fibrillation. Persistence of ECG abnormalities from the acute phase was common, and nonspecific repolarisation abnormalities (93%) reflected the high prevalence of pericardial involvement on TTE (86%). Likewise, pleural abnormalities were frequently observed (66%). TTE signs of left and right ventricular dysfunction were reported in two patients, and values of systolic pulmonary artery pressure were abnormal in 16 (55%, despite the absence of prior comorbidities in 44% of them). Regarding LUS evaluation, most patients displayed abnormal values of diaphragmatic thickness and excursion (93%), which correlated well with the high prevalence (76%) of pathological findings on CT scan. CUS ruled out deep vein thrombosis in all patients. CONCLUSIONS: Data on cardiopulmonary involvement after COVID-19 pneumonia are scarce. In our study, simple diagnostic tools (TTE and LUS) proved clinically useful for the detection of cardiopulmonary complications after COVID-19 pneumonia.

Time course of exercise capacity in patients recovering from COVID-19-associated pneumonia.

OBJECTIVE: High prevalences of muscle weakness and impaired physical performance in hospitalized patients recovering from COVID-19-associated pneumonia have been reported. Our objective was to determine whether the level of exercise capacity after discharge would affect long-term functional outcomes in these patients. METHODS: From three to five weeks after discharge from acute care hospitals (T0), patients underwent a six-minute walk test (6MWT) and were divided into two groups according to the distance walked in percentage of predicted values: <75% group and ≥75% group. At T0 and three months later (T1), patients completed the Short Physical Performance Battery and the Euro Quality of Life Visual Analogue Scale, and pulmonary function and respiratory muscle function were assessed. In addition, a repeat 6MWT was also performed at T1. RESULTS: At T0, 6MWD values and Short Physical Performance Battery scores were lower in the <75% group than in the ≥75% group. No differences were found in the Euro Quality of Life Visual Analogue Scale scores, pulmonary function variables, respiratory muscle function variables, length of hospital stay, or previous treatment. At T1, both groups improved their exercise capacity, but only the subjects in the <75% group showed significant improvements in dyspnea and lower extremity function. Exercise capacity and functional status values returned to predicted values in all of the patients in both groups. CONCLUSIONS: Four weeks after discharge, COVID-19 survivors with exercise limitation showed no significant differences in physiological or clinical characteristics or in perceived health status when compared with patients without exercise limitation. Three months later, those patients recovered their exercise capacity.

SARS-CoV-2 vaccines: Lights and shadows.

Vaccines to prevent acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection elicit an immune neutralizing response. Some concerns have been raised regarding the safety of SARS-CoV-2 vaccines, largely based on case-reports of serious thromboembolic events after vaccination. Some mechanisms have been suggested which might explain the adverse cardiovascular reactions to SARS-CoV-2 vaccines. Different vaccine platforms are currently available which include live attenuated vaccines, inactivated vaccines, recombinant protein vaccines, vector vaccines, DNA vaccines and RNA vaccines. Vaccines increase the endogenous synthesis of SARS-CoV-2 Spike proteins from a variety of cells. Once synthetized, the Spike proteins assembled in the cytoplasma migrate to the cell surface and protrude with a native-like conformation. These proteins are recognized by the immune system which rapidly develops an immune response. Such response appears to be quite vigorous in the presence of DNA vaccines which encode viral vectors, as well as in subjects who are immunized because of previous exposure to SARS-CoV-2. The resulting pathological features may resemble those of active coronavirus disease. The free-floating Spike proteins synthetized by cells targeted by vaccine and destroyed by the immune response circulate in the blood and systematically interact with angiotensin converting enzyme 2 (ACE2) receptors expressed by a variety of cells including platelets, thereby promoting ACE2 internalization and degradation. These reactions may ultimately lead to platelet aggregation, thrombosis and inflammation mediated by several mechanisms including platelet ACE2 receptors. Whereas Phase III vaccine trials generally excluded participants with previous immunization, vaccination of huge populations in the real life will inevitably include individuals with preexisting immunity. This might lead to excessively enhanced inflammatory and thrombotic reactions in occasional subjects. Further research is urgently needed in this area.

Joint effect of heart failure and coronary artery disease on the risk of death during hospitalization for COVID-19.

AIMS: heart failure (HF) and coronary artery disease (CAD) are independent predictors of death in patients with COVID-19. The adverse prognostic impact of the combination of HF and CAD in these patients is unclear. METHODS AND RESULTS: we analysed data from 954 consecutive patients hospitalized for SARS-CoV-2 in five Italian Hospitals from February 23 to May 22, 2020. The study was a systematic prospective data collection according to a pre-specified protocol. All-cause mortality during hospitalization was the outcome measure. Mean duration of hospitalization was 33 days. Mortality was 11% in the total population and 7.4% in the group without evidence of HF or CAD (reference group). Mortality was 11.6% in the group with CAD and without HF (odds ratio [OR]: 1.6, p = 0.120), 15.5% in the group with HF and without CAD (OR: 2.3, p = 0.032), and 35.6% in the group with CAD and HF (OR: 6.9, p<0.0001). The risk of mortality in patients with CAD and HF combined was consistently higher than the sum of risks related to either disorder, resulting in a significant synergistic effect (p<0.0001) of the two conditions. Age-adjusted attributable proportion due to interaction was 64%. Adjusting for the simultaneous effects of age, hypotension, and lymphocyte count did not significantly lower attributable proportion which persisted statistically significant (p = 0.0360). CONCLUSION: The combination of HF and CAD exerts a marked detrimental impact on the risk of mortality in hospitalized patients with COVID-19, which is independent on other adverse prognostic markers.

Coronavirus Disease-19: An Interim Evidence Synthesis of the World Association for Infectious Diseases and Immunological Disorders (Waidid).

Coronavirus disease 2019 (COVID-19) is a rapidly evolving, highly transmissible, and potentially lethal pandemic caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). As of June 11 2020, more than 7,000,000 COVID-19 cases have been reported worldwide, and more than 400,000 patients have died, affecting at least 188 countries. While literature on the disease is rapidly accumulating, an integrated, multinational perspective on clinical manifestations, immunological effects, diagnosis, prevention, and treatment of COVID-19 can be of global benefit. We aimed to synthesize the most relevant literature and experiences in different parts of the world through our global consortium of experts to provide a consensus-based document at this early stage of the pandemic.

Current developments and future directions in COPD.

The European Respiratory Society journals publish respiratory research and policy documents of the highest quality, offering a platform for the exchange and promotion of scientific knowledge. In this article, focusing on COPD, the third leading cause of death globally, we summarise novel research highlights focusing on the disease's underlying mechanisms, epidemiology and management, with the aim to inform and inspire respiratory clinicians and researchers.

Pulmonary Rehabilitation in Patients Recovering from COVID-19.

BACKGROUND: In hospitalized patients recovering from the SARS-coronavirus-2 disease 19 (COVID-19), high prevalence of muscle weakness and physical performance impairment has been observed. OBJECTIVES: The aim of this study was to evaluate the effectiveness of pulmonary rehabilitation in these subjects in a real-life setting. METHODS: Retrospective data analysis of patients recovering from COVID-19, including those requiring assisted ventilation or oxygen therapy, consecutively admitted to an in-patient pulmonary rehabilitation program between April 1 and August 15, 2020. Short Physical Performance Battery (SPPB: primary outcome), Barthel Index (BI), and six-min walking distance were assessed as outcome measures. RESULTS: Data of 140 patients were analyzed. After rehabilitation, patients showed improvements in SPPB {from: (median [IQR]) 0.5 (0-7) to 7 (4-10), p < 0.001} and BI (from 55 [30-90] to 95 [65-100], p < 0.001), as well as in other assessed outcome measures. The proportion of patients unable at admission to stand, rise from a chair and walk was significantly reduced (p < 0.00). CONCLUSIONS: Pulmonary rehabilitation is possible and effective in patients recovering from COVID-19. Our findings may be useful to guide clinicians taking care of patients surviving COVID-19 infection.

Tuberculosis, COVID-19 and hospital admission: Consensus on pros and cons based on a review of the evidence.

The scientific debate on the criteria guiding hospitalization of tuberculosis (TB) and COVID-19 patients is ongoing. The aim of this review is to present the available evidence on admission for TB and TB/COVID-19 patients and discuss the criteria guiding hospitalization. Furthermore, recommendations are made as derived from recently published World Health Organization documents, based on Global Tuberculosis Network (GTN) expert opinion. The core published documents and guidelines on the topic have been reviewed. The proportion of new TB cases admitted to hospital ranges between 50% and 100% while for multidrug-resistant (MDR) TB patients it ranges between 85 and 100% globally. For TB patients with COVID-19 the proportion of cases admitted is 58%, probably reflecting different scenarios related to the diagnosis of COVID-19 before, after or at the same time of the active TB episode. The hospital length of stay for drug-susceptible TB ranges from 20 to 60 days in most of countries, ranging from a mean of 10 days (USA) to around 90 days in the Russian Federation. Hospitalization is longer for MDR-TB (50-180 days). The most frequently stated reasons for recommending hospital admission include: severe TB, infection control concerns, co-morbidities and drug adverse events which cannot be managed at out-patient level. The review also provides suggestions on hospital requirements for safe admissions as well as patient discharge criteria, while underlining the relevance of patient-centred care through community/home-based care.

Epidemic and pandemic viral infections: impact on tuberculosis and the lung: A consensus by the World Association for Infectious Diseases and Immunological Disorders (WAidid), Global Tuberculosis Network (GTN), and members of the European Society of Clinical Microbiology and Infectious Diseases Study Group for Mycobacterial Infections (ESGMYC).

Major epidemics, including some that qualify as pandemics, such as severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), HIV, influenza A (H1N1)pdm/09 and most recently COVID-19, affect the lung. Tuberculosis (TB) remains the top infectious disease killer, but apart from syndemic TB/HIV little is known regarding the interaction of viral epidemics and pandemics with TB. The aim of this consensus-based document is to describe the effects of viral infections resulting in epidemics and pandemics that affect the lung (MERS, SARS, HIV, influenza A (H1N1)pdm/09 and COVID-19) and their interactions with TB. A search of the scientific literature was performed. A writing committee of international experts including the European Centre for Disease Prevention and Control Public Health Emergency (ECDC PHE) team, the World Association for Infectious Diseases and Immunological Disorders (WAidid), the Global Tuberculosis Network (GTN), and members of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Mycobacterial Infections (ESGMYC) was established. Consensus was achieved after multiple rounds of revisions between the writing committee and a larger expert group. A Delphi process involving the core group of authors (excluding the ECDC PHE team) identified the areas requiring review/consensus, followed by a second round to refine the definitive consensus elements. The epidemiology and immunology of these viral infections and their interactions with TB are discussed with implications for diagnosis, treatment and prevention of airborne infections (infection control, viral containment and workplace safety). This consensus document represents a rapid and comprehensive summary on what is known on the topic.

Electrocardiographic features of patients with COVID-19 pneumonia.

BACKGROUND: . The electrocardiographic (ECG) changes which may occur during hospitalization for COVID-19 have not yet been comprehensively assessed. PATIENTS AND METHODS: . We examined 50 patients admitted to hospital with proven COVID-19 pneumonia. At entry, all patients underwent a detailed clinical examination, 12-lead ECG, laboratory tests and arterial blood gas test. ECG was also recorded at discharge and in case of worsening clinical conditions. RESULTS: . Mean age of patients was 64 years and 72% were men. At baseline, 30% of patients had ST-T abnormalities, and 33% had left ventricular hypertrophy. During hospitalization, 26% of patients developed new ECG abnormalities which included atrial fibrillation, ST-T changes, tachy-brady syndrome, and changes consistent with acute pericarditis. One patient was transferred to intensive care unit for massive pulmonary embolism with right bundle branch block, and another for non-ST segment elevation myocardial infarction. Patients free of ECG changes during hospitalization were more likely to be treated with antiretrovirals (68% vs 15%, p = 0.001) and hydroxychloroquine (89% vs 62%, p = 0.026) versus those who developed ECG abnormalities after admission. Most measurable ECG features at discharge did not show significant changes from baseline (all p>0.05) except for a slightly decrease in Cornell voltages (13±6 vs 11±5 mm; p = 0.0001) and a modest increase in the PR interval. The majority (54%) of patients with ECG abnormalities had 2 prior consecutive negative nasopharyngeal swabs. ECG abnormalities were first detected after an average of about 30 days from symptoms' onset (range 12-51 days). CONCLUSIONS: . ECG abnormalities during hospitalization for COVID-19 pneumonia reflect a wide spectrum of cardiovascular complications, exhibit a late onset, do not progress in parallel with pulmonary abnormalities and may occur after negative nasopharyngeal swabs.