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BACKGROUND: TB is a leading infectious cause of death worldwide. The COVID-19 pandemic raised concerns that the burden of TB disease and death would increase due to the synergy between the two conditions. METHODS: We used individual-level data submitted to the WHO Global Clinical Platform for COVID-19 on hospitalised patients to explore associations of TB with mortality using multivariable logistic regression. RESULTS: Data were available from 453,233 persons with COVID-19 and known TB status and mortality outcomes from 62 countries (96% SARS-CoV-2 test-positive). Of these, 48% were male, and the median age was 53 years (IQR 38-67). There were 8,214 cases with current TB reported by 46 countries, mainly from Africa. Of people with current TB, 31.4% were admitted with severe illness, and 24.5% died. Current TB was independently associated with higher mortality when adjusted for age, sex, HIV status, illness severity at hospital admission, and underlying conditions (adjusted RR 1.47, 95% CI 1.35-1.61). CONCLUSION: Current or past TB were independent risk factors for in-hospital mortality regardless of illness severity at admission. Caveats for interpretation include changes during the data collection period (viral variation, vaccination coverage) and opportunistic sampling. However, the platform exemplifies how timely, coordinated global reporting can inform our understanding of health emergencies and the vulnerable populations affected.

CONTEXTE: La TB est l'une des principales causes infectieuses de décès dans le monde. La pandémie de COVID-19 a fait craindre que le fardeau de la TB et des décès n'augmente en raison de la synergie entre les deux maladies. MÉTHODES: Nous avons utilisé les données individuelles soumises à la Plateforme clinique mondiale de l'OMS pour la COVID-19 sur les patients hospitalisés pour explorer les associations entre la TB et la mortalité à l'aide d'une régression logistique multivariée. RÉSULTATS: Des données étaient disponibles sur 453 233 personnes atteintes de COVID-19 et connues pour le statut de TB et les résultats de mortalité dans 62 pays (96% de tests positifs au SRAS-CoV-2). Parmi eux, 48% étaient des hommes et l'âge médian était de 53 ans (IQR 38­67). Un total de 8 214 cas de TB ont été signalés par 46 pays, principalement en Afrique. Parmi les personnes atteintes de TB actuelle, 31,4% ont été admises avec une maladie grave et 24,5% sont décédées. La TB actuelle était indépendamment associée à une mortalité plus élevée lorsqu'elle était ajustée en fonction de l'âge, du sexe, du statut VIH, de la gravité de la maladie à l'admission à l'hôpital et des affections sous-jacentes (RR ajusté 1,47 ; IC à 95% 1,35­1,61). CONCLUSION: La TB actuelle ou passée était un facteur de risque indépendant de mortalité à l'hôpital, quelle que soit la gravité de la maladie à l'admission. Les mises en garde concernant l'interprétation comprennent les changements au cours de la période de collecte des données (variation virale, couverture vaccinale) et l'échantillonnage opportuniste. Cependant, la plateforme illustre comment des rapports mondiaux opportuns et coordonnés peuvent éclairer notre compréhension des urgences sanitaires et des populations vulnérables touchées.

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BACKGROUND: Post-TB lung disease (PTLD) is an important but under-recognised chronic respiratory disease in high TB burden settings such as Tanzania.METHODS: This was a cross-sectional survey of adults within 2 years of completion of TB treatment in Kilimanjaro, Tanzania. Data were collected using questionnaires (symptoms and exposures), spirometry and chest radiographs to assess outcome measures, which were correlated with daily life exposures, including environment and diet.RESULTS: Of the 219 participants enrolled (mean age: 45 years ± 10; 193 88% males), 98 (45%) reported chronic respiratory symptoms; 46 (22%) had received treatment for TB two or more times; and HIV prevalence was 35 (16%). Spirometric abnormalities were observed in 146 (67%). Chest X-ray abnormalities occurred in 177 (86%). A diagnosis of PTLD was made in 200 (91%), and half had clinically relevant PTLD. The prevalence of mMRC ≥Grade 3 chronic bronchitis and dyspnoea was respectively 11% and 26%. Older age, multiple episodes of TB and poverty indicators were linked with clinically relevant PTLD.CONCLUSIONS: We found a substantial burden of PTLD in adults who had recently completed TB treatment in Tanzania. There is a pressing need to identify effective approaches for both the prevention and management of this disease.

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BACKGROUND: Persistent respiratory symptoms and lung function deficits are common after patients with TB. We aimed to define the burden of post-TB lung disease (PTLD) and assess associations between symptoms and impairment in two high TB incidence communities.METHODS: This was a cross-sectional survey of adults in Cape Town, South Africa who completed TB treatment 1-5 years previously. Questionnaires, spirometry and 6-minute walking distance (6MWD) were used to assess relationships between outcome measures and associated factors.RESULTS: Of the 145 participants recruited (mean age: 42 years, range: 18-75; 55 [38%] women), 55 (38%) had airflow obstruction and 84 (58%) had low forced vital capacity (FVC); the mean 6MWD was 463 m (range: 240-723). Respiratory symptoms were common: chronic cough (n = 27, 19%), wheeze (n = 61, 42%) and dyspnoea (modified MRC dyspnoea score 3 or 4: n = 36, 25%). There was poor correlation between FVC or obstruction and 6MWD. Only low body mass index showed consistent association with outcomes on multivariable analyses. Only 19 (13%) participants had a diagnosis of respiratory disease, and 16 (11%) currently received inhalers.CONCLUSION: There was substantial burden of symptoms and physiological impairment in this "cured" population, but poor correlation between objective outcome measures, highlighting deficits in our understanding of PTLD.

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Although the COVID-19 pandemic has left no country untouched there has been limited research to understand clinical and immunological responses in African populations. Here we comprehensively characterise patients hospitalised with suspected or confirmed COVID-19, and healthy community controls. PCR-confirmed COVID-19 participants were more likely to receive dexamethasone and a beta-lactam antibiotic, and survive to hospital discharge than PCR-/IgG+ and PCR-/IgG-participants. PCR-/IgG+ participants exhibited a nasal and systemic cytokine signature analogous to PCR-confirmed COVID-19 participants, but increased propensity for Staphylococcus aureus and Streptococcus pneumoniae colonisation. We did not find evidence that HIV co-infection in COVID-19 participants was associated with mortality or altered cytokine responses. The nasal immune signature in PCR-/IgG+ and PCR-confirmed COVID-19 participants was distinct and predominated by chemokines and neutrophils. In addition, PCR-/IgG+ individuals with high COVID-19 clinical suspicion had inflammatory profiles analogous to PCR-confirmed disease and potentially represent a target population for COVID-19 treatment strategies.

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BACKGROUND: Pulmonary rehabilitation (PR) is a highly effective non-pharmacological treatment for patients with chronic respiratory diseases.OBJECTIVE: To synthesise the evidence for PR practice and efficacy in sub-Saharan Africa.METHODS: We searched in PubMed and Scopus for relevant studies and scanned reference lists of relevant studies from these databases for additional studies. Articles meeting the inclusion criteria were included. Pre-determined data were extracted independently by two reviewers. A narrative synthesis approach was used in the interpretation of findings.RESULTS: Six studies were included, totalling 275 participants. Indications for PR were chronic obstructive pulmonary disease, asthma, pulmonary tuberculosis and post-tuberculosis lung disease. Programmes ran for 6-12 weeks, universally incorporated exercise, and variously used home-based and hospital-based delivery models. All were interventional studies, of which two were randomised controlled trials, and primarily reported pulmonary function and exercise tolerance endpoints. Evidence for individualising the exercise regimen was available in three studies.CONCLUSIONS: There is limited evidence on PR design and efficacy in sub-Saharan Africa, but available data support its use in a variety of chronic respiratory conditions. Future studies should report core outcome sets and their individualised exercise and education regimens.

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OBJECTIVE: To refine and validate a neutrophil function assay with clinical relevance for patients with community-acquired pneumonia (CAP). DESIGN: Two phase cross-sectional study to standardise and refine the assay in blood from healthy volunteers and test neutrophil phagocytic function in hospital patients with CAP. PARTICIPANTS: Phase one: Healthy adult volunteers (n = 30). Phase two: Critical care patients with severe CAP (n = 16), ward-level patients with moderate CAP (n = 15) and respiratory outpatients (no acute disease, n = 15). RESULTS: Our full standard operating procedure for the assay is provided. Patients with severe CAP had significantly decreased neutrophil function compared to moderate severity disease (median phagocytic index 2.8 vs. 18.0, p = 0.014). Moderate severity pneumonia neutrophil function was significantly higher than control samples (median 18.0 vs. 1.6, p = 0.015). There was no significant difference between critical care and control neutrophil function (median 2.8 vs. 1.6, p = 0.752). CONCLUSIONS: Our whole blood neutrophil assay is simple, reproducible and clinically relevant. Changes in neutrophil function measured in this pneumonia cohort is in agreement with previous studies. The assay has potential to be used to identify individuals for clinical trials of immunomodulatory therapies, to risk-stratify patients with pneumonia, and to refine our understanding of 'normal' neutrophil function in infection.

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OBJECTIVE: To examine the prevalence and magnitude of chronic lung disease (CLD) and its association with empiric anti-tuberculosis treatment (due to lack of bacteriologic confirmation) among recurrent tuberculosis (TB) survivors in a human immunodeficiency virus (HIV) prevalent setting. METHODS: Prospective cohort study of retreatment TB survivors in Harare, Zimbabwe. At median follow-up of 2 years post-treatment initiation, we characterized mortality, respiratory impairment, and mental health. RESULTS: Among 175 retreatment TB survivors, 65% of whom were HIV-positive and 21% had been empirically treated, multiparameter CLD was noted at follow-up among 14% of patients (95%CI 9.0-19.7), with a six-fold increase in age-adjusted death in the first year following treatment completion. Empirically treated TB (relative risk [RR] 3.4, 95%CI 1.4-8.3) was associated with CLD, as was the number of previous anti-tuberculosis treatment courses in dose-dependent fashion (three vs. one, RR 6.2, 95%CI 1.7-22.1). Among retreatment TB survivors, 33% (95%CI 26.0-40.1) had persistent respiratory symptoms (Chronic Obstructive Pulmonary Disease Assessment Test score 10); 26% (95%CI 19.8-33.0) significant deficits in exercise capacity (median incremental shuttle walk test distance, 550 m; Q1-Q3 440-730 m); 83% (95%CI 75.7-89.7) residual radiographic abnormalities on chest X-ray; 12% (95%CI 6.6-16.1%) moderate-to-severe obstruction on spirometry; and 13% (95%CI 7.6-17.5%) major depression. CONCLUSIONS: Despite successful treatment, retreatment TB survivors retain a substantial risk of morbidity and mortality.

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BACKGROUND: A proportion of children with sickle-cell disease (SCD) demonstrate clinical findings consistent with the diagnosis of asthma. These children are at increased risk of complications, including acute chest syndrome. OBJECTIVE: To assess lung function and symptoms of asthma in children with SCD in Blantyre, Malawi. DESIGN: Twenty-five children aged 7-16 years with electrophoretically confirmed SCD were recruited to undergo spirometry and questionnaire screening of asthma symptoms. Forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC) and FEV1/FVC ratio were compared with local and international reference ranges. Symptoms were assessed using the International Study of Asthma and Allergies in Childhood questionnaire. RESULTS: Mean spirometric indices, represented as Z-scores derived from international reference ranges, were low: FEV1 -1.64 (95%CI -2.04 to -1.23), FVC -1.49 (95%CI -1.90 to -1.09), FEV1/FVC -0.39 (95%CI -0.76 to -0.03). Comparison with local reference ranges, represented as percentage of predicted value, revealed similar impairments: FEV1 86.9 (95%CI 81.1 to 92.7), FVC 89.0 (95%CI 83.5 to 94.4), FEV1/FVC ratio 97.7 (95%CI 95.4 to 99.9). The prevalence of wheeze was 16.7%. CONCLUSION: We present spirometric abnormalities suggestive of restrictive lung disease with no evidence of obstructive defects or increased prevalence of wheeze.

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