Convalescent Plasma for Preventing Critical Illness in COVID-19: a Phase 2 Trial and Immune Profile.

The COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an unprecedented event requiring frequent adaptation to changing clinical circumstances. Convalescent immune plasma (CIP) is a promising treatment that can be mobilized rapidly in a pandemic setting. We tested whether administration of SARS-CoV-2 CIP at hospital admission could reduce the rate of ICU transfer or 28-day mortality or alter levels of specific antibody responses before and after CIP infusion. In a single-arm phase II study, patients >18 years-old with respiratory symptoms with confirmed COVID-19 infection who were admitted to a non-ICU bed were administered two units of CIP within 72 h of admission. Levels of SARS-CoV-2 detected by PCR in the respiratory tract and circulating anti-SARS-CoV-2 antibody titers were sequentially measured before and after CIP transfusion. Twenty-nine patients were transfused high titer CIP and 48 contemporaneous comparable controls were identified. All classes of antibodies to the three SARS-CoV-2 target proteins were significantly increased at days 7 and 14 post-transfusion compared with baseline (P < 0.01). Anti-nucleocapsid IgA levels were reduced at day 28, suggesting that the initial rise may have been due to the contribution of CIP. The groups were well-balanced, without statistically significant differences in demographics or co-morbidities or use of remdesivir or dexamethasone. In participants transfused with CIP, the rate of ICU transfer was 13.8% compared to 27.1% for controls with a hazard ratio 0.506 (95% CI 0.165-1.554), and 28-day mortality was 6.9% compared to 10.4% for controls, hazard ratio 0.640 (95% CI 0.124-3.298). IMPORTANCE Transfusion of high-titer CIP to non-critically ill patients early after admission with COVID-19 respiratory disease was associated with significantly increased anti-SARS-CoV-2 specific antibodies (compared to baseline) and a non-significant reduction in ICU transfer and death (compared to controls). This prospective phase II trial provides a suggestion that the antiviral effects of CIP from early in the COVID-19 pandemic may delay progression to critical illness and death in specific patient populations. This study informs the optimal timing and potential population of use for CIP in COVID-19, particularly in settings without access to other interventions, or in planning for future coronavirus pandemics.

Differentiating transient from persistent diabetic range hyperglycemia in a cohort of people completing tuberculosis treatment in Dhaka, Bangladesh.

BACKGROUND: In recent non-pandemic periods, tuberculosis (TB) has been the leading killer worldwide from a single infectious disease. Patients with DM are three times more likely to develop active TB and poor treatment outcomes. Single glycemic measurements at TB diagnosis may inaccurately diagnose or mischaracterize DM severity. Data are limited regarding glycemic dynamics from TB diagnosis through treatment. METHODS: Prospective study of glycemia dynamics in response to TB treatment measured glycosylated haemoglobin (HbA1c) in patients presenting to TB screening centres in Bangladesh to determine the prevalence and risk factors of hyperglycemia before and at TB treatment completion. RESULTS: 429 adults with active TB disease were enrolled and divided into groups based on history of DM and initial HbA1c range: normoglycemia, prediabetes, and DM. DM was diagnosed in 37%. At treatment completion,14(6%) patients from the normoglycemia and prediabetes groups had HbA1c>6.5%, thus increasing the prevalence of DM to 39%. The number needed to screen to diagnose one new case of DM at TB diagnosis was 5.7 and 16 at treatment completion in the groups without DM. Weight gain>5% at treatment completion significantly increased the risk of hyperglycemia in the groups without DM at TB diagnosis (95% CI 1.23-26.04, p<0.05). CONCLUSION: HbA1c testing prior to and at TB treatment completion found a high prevalence of prediabetes and DM, including a proportion found at treatment completion and commonly in people with a higher percentage of weight gain. Further longitudinal research is needed to understand the effects of TB disease and treatment on insulin resistance and DM complications.

Convalescent plasma for preventing critical illness in COVID-19: A phase 2 trial and immune profile.

RATIONALE: The COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an unprecedented event requiring rapid adaptation to changing clinical circumstances. Convalescent immune plasma (CIP) is a promising treatment that can be mobilized rapidly in a pandemic setting. OBJECTIVES: We tested whether administration of SARS-CoV-2 CIP at hospital admission could reduce the rate of ICU transfer or 28 day mortality. METHODS: In a single-arm phase II study, patients >18 years-old with respiratory symptoms documented with COVID-19 infection who were admitted to a non-ICU bed were administered two units of CIP within 72 hours of admission. Detection of respiratory tract SARS-CoV-2 by polymerase chain reaction and circulating anti-SARS-CoV-2 antibody titers were measured before and at time points after CIP transfusion. MEASUREMENTS AND MAIN RESULTS: Twenty-nine patients were transfused CIP and forty-eight contemporaneous controls were identified with comparable baseline characteristics. Levels of anti-SARS-CoV-2 IgG, IgM, and IgA anti-spike, anti-receptor-binding domain, and anti-nucleocapsid significantly increased from baseline to post-transfusion for all proteins tested. In patients transfused with CIP, the rate of ICU transfer was 13.8% compared to 27.1% for controls with a hazard ratio 0.506 (95% CI 0.165-1.554), and 28-day mortality was 6.9% compared to 10.4% for controls, hazard ratio 0.640 (95% CI 0.124-3.298). CONCLUSIONS: Transfusion of high-titer CIP to patients early after admission with COVID-19 respiratory disease was associated with reduced ICU transfer and 28-day mortality but was not statistically significant. Follow up randomized trials may inform the use of CIP for COVID-19 or future coronavirus pandemics.

A public-private model to scale up diabetes mellitus screening among people accessing tuberculosis diagnostics in Dhaka, Bangladesh.

BACKGROUND: Data are scarce regarding the prevalence of diabetes mellitus (DM) among tuberculosis (TB) patients in Bangladesh. This study was undertaken to estimate the number needed to screen (NNS) to identify a case of DM among those with TB symptoms and those with confirmed TB disease, and to identify factors predicting treatment outcomes of TB patients with and without DM. METHODS: Persons attending public-private model screening centres in urban Dhaka for the evaluation of TB were offered free blood glucose testing in addition to computer-aided chest X-ray and sputum Xpert MTB/RIF. RESULTS: Among 7647 people evaluated for both TB and DM, the NNS was 35 (95% confidence interval (CI) 31-40) to diagnose one new case of DM; among those diagnosed with TB, the NNS was 21 (95% CI 17-29). Among those with diagnosed TB, patients with DM were more likely to have cavitation on chest X-ray compared to those without DM (31% vs 22%). Treatment failure (odds ratio (OR) 18.9, 95% CI 5.43-65.9) and death (OR 2.08, 95% CI 1.11-3.90) were more common among TB patients with DM than among TB patients without DM. DM was the most important predictor of a poor treatment outcome in the classification analysis for TB patients aged 39 years and above. CONCLUSIONS: A considerable burden of DM was found among patients accessing TB diagnostics through a public-private model in urban Bangladesh, and DM was associated with advanced TB disease and a high rate of poor treatment outcome.

Performance of computed tomography versus chest radiography in patients with pulmonary tuberculosis with and without diabetes at a tertiary hospital in Riyadh, Saudi Arabia.

BACKGROUND: Prior research suggests that diabetes mellitus (DM) is associated with increasing risk for developing cavitary lung disease in patients with pulmonary tuberculosis (TB). Additionally, chest computed tomography (CT) scan may be more sensitive than chest X-ray in detecting cavitary disease in such patients. The aim of this study was to compare the performance of chest CT to chest X-ray in detecting cavitary lung disease and to compare the frequency of cavities between TB patients with DM and without DM. PATIENTS AND METHODS: We conducted a retrospective cohort study at King Fahad Medical City, Riyadh, Saudi Arabia, from January 2004 to December 2015. We included patients aged 18 years and older with a positive sputum culture for Mycobacterium tuberculosis, and their medical charts were reviewed from admission to discharge. RESULTS: Of the 133 patients who met the inclusion criteria, 38 (28.6%) patients were known to have DM and were compared with 95 (71.4%) patients without DM. DM patients with glycated hemoglobin (HbA1c) >6.5% had significantly more cavitary lesions when compared to all patients (with or without DM) with HbA1c <6.4% and/or random blood sugar <200 mg/dL. Furthermore, CT was able to detect lung cavities in 58.8% of the patients who had negative chest X-ray findings for cavities. CONCLUSION: The presence of lung cavities was significantly associated with the presence of DM and levels of HbA1c in patients with pulmonary TB. CT scan in those with normal radiography increased the detection of cavities.

Diabetes-related tuberculosis in the Middle East: an urgent need for regional research.

OBJECTIVES: Diabetes mellitus (DM) triples the risk of tuberculosis (TB) disease, complicates TB treatment, and increases the risk of a poor TB outcome. As DM prevalence is increasing across the Middle East, this review was performed to identify regional gaps in knowledge and research priorities for DM/TB. METHODS: Online databases were searched for studies published from Middle East countries on DM and TB and the studies summarized based on topic and major findings. Studies included had a principle hypothesis related to both diseases, or described TB patients with individual data on DM. RESULTS: Fifty-nine studies from 10 countries met search criteria. No published studies were found from Lebanon, Bahrain, Syria, Jordan, Cyprus, or the United Arab Emirates. DM prevalence among TB patients was high, but varied considerably across studies. The vast majority of studies were not specifically designed to compare DM/TB and non-DM/TB patients, but many suggested worse treatment outcomes for DM/TB, in accordance with reports from other regions. CONCLUSIONS: Opportunity exists for the regional study of bidirectional screening, management strategies for both DM and TB diseases, and whether such efforts could take place through the integration of services.