Convalescent plasma in the treatment of moderate to severe COVID-19 pneumonia: a randomized controlled trial (PROTECT-Patient Trial).

There is a need for effective therapy for COVID-19 pneumonia. Convalescent plasma has antiviral activity and early observational studies suggested benefit in reducing COVID-19 severity. We investigated the safety and efficacy of convalescent plasma in hospitalized patients with COVID-19 in a population with a high HIV prevalence and where few therapeutic options were available. We performed a double-blinded, multicenter, randomized controlled trial in one private and three public sector hospitals in South Africa. Adult participants with COVID-19 pneumonia requiring non-invasive oxygen were randomized 1:1 to receive a single transfusion of 200 mL of either convalescent plasma or 0.9% saline solution. The primary outcome measure was hospital discharge and/or improvement of ≥ 2 points on the World Health Organisation Blueprint Ordinal Scale for Clinical Improvement by day 28 of enrolment. The trial was stopped early for futility by the Data and Safety Monitoring Board. 103 participants, including 21 HIV positive individuals, were randomized at the time of premature trial termination: 52 in the convalescent plasma and 51 in the placebo group. The primary outcome occurred in 31 participants in the convalescent plasma group and and 32 participants in the placebo group (relative risk 1.03 (95% CI 0.77 to 1.38). Two grade 1 transfusion-related adverse events occurred. Participants who improved clinically received convalescent plasma with a higher median anti-SARS-CoV-2 neutralizing antibody titre compared with those who did not (298 versus 205 AU/mL). Our study contributes additional evidence for recommendations against the use of convalescent plasma for COVID-19 pneumonia. Safety and feasibility in this population supports future investigation for other indications.

Multiple microbiologic tests for tuberculosis improve diagnostic yield of bronchoscopy in medically complex patients.

Background: Bronchoalveolar lavage (BAL) is indicated for medical evaluation of complex cases of lung disease.  There is limited data on the performance of tuberculosis (TB) microbiologic tests on BAL in such patients, particularly in human immunodeficiency virus (HIV) and TB endemic areas. Methods: We evaluated the performance of Mycobacterium tuberculosis (Mtb) culture and up to two simultaneous Xpert MTB/RIF tests on BAL fluid against a consensus clinical diagnosis in 98 medically complex patients undergoing bronchoscopy over a two-year period in Durban, South Africa. Results: TB was the most frequently diagnosed lung disease, found in 19 of 98 participants (19%) and was microbiologically proven in 14 of these (74%); 9 (47%) were culture positive and 5 were positive on at least one Xpert MTB/RIF assay. Immunosuppression prevalence was high (26% HIV-infected, 29% on immunosuppressive therapy and 4% on chemotherapy). Xpert MTB/RIF had low sensitivity (45%) and high specificity (99%) when assessed against the consensus clinical diagnosis. Compared to TB culture, a single Xpert MTB/RIF increased the diagnostic yield by 11% and a second Xpert MTB/RIF by a further 16%. Conclusion: Although Xpert MTB/RIF had a low sensitivity, sending two tests improved the microbiologically-proven diagnostic yield of bronchoscopy from 47% to 74% compared to culture alone.

TRAV1-2+ CD8+ T-cells including oligoconal expansions of MAIT cells are enriched in the airways in human tuberculosis.

Mucosal-associated invariant T (MAIT) cells typically express a TRAV1-2+ semi-invariant TCRα that enables recognition of bacterial, mycobacterial, and fungal riboflavin metabolites presented by MR1. MAIT cells are associated with immune control of bacterial and mycobacterial infections in murine models. Here, we report that a population of pro-inflammatory TRAV1-2+ CD8+ T cells are present in the airways and lungs of healthy individuals and are enriched in bronchoalveolar fluid of patients with active pulmonary tuberculosis (TB). High-throughput T cell receptor analysis reveals oligoclonal expansions of canonical and donor-unique TRAV1-2+ MAIT-consistent TCRα sequences within this population. Some of these cells demonstrate MR1-restricted mycobacterial reactivity and phenotypes suggestive of MAIT cell identity. These findings demonstrate enrichment of TRAV1-2+ CD8+ T cells with MAIT or MAIT-like features in the airways during active TB and suggest a role for these cells in the human pulmonary immune response to Mycobacterium tuberculosis.