Anti-SARS-CoV-2 antibody-containing plasma improves outcome in patients with hematologic or solid cancer and severe COVID-19: a randomized clinical trial.

Patients with cancer are at high risk of severe coronavirus disease 2019 (COVID-19), with high morbidity and mortality. Furthermore, impaired humoral response renders severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines less effective and treatment options are scarce. Randomized trials using convalescent plasma are missing for high-risk patients. Here, we performed a randomized, open-label, multicenter trial ( https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-001632-10/DE ) in hospitalized patients with severe COVID-19 (n = 134) within four risk groups ((1) cancer (n = 56); (2) immunosuppression (n = 16); (3) laboratory-based risk factors (n = 36); and (4) advanced age (n = 26)) randomized to standard of care (control arm) or standard of care plus convalescent/vaccinated anti-SARS-CoV-2 plasma (plasma arm). No serious adverse events were observed related to the plasma treatment. Clinical improvement as the primary outcome was assessed using a seven-point ordinal scale. Secondary outcomes were time to discharge and overall survival. For the four groups combined, those receiving plasma did not improve clinically compared with those in the control arm (hazard ratio (HR) = 1.29; P = 0.205). However, patients with cancer experienced a shortened median time to improvement (HR = 2.50; P = 0.003) and superior survival with plasma treatment versus the control arm (HR = 0.28; P = 0.042). Neutralizing antibody activity increased in the plasma cohort but not in the control cohort of patients with cancer (P = 0.001). Taken together, convalescent/vaccinated plasma may improve COVID-19 outcomes in patients with cancer who are unable to intrinsically generate an adequate immune response.

Accuracy and ease-of-use of seven point-of-care SARS-CoV-2 antigen-detecting tests: A multi-centre clinical evaluation.

BACKGROUND: Antigen-detecting rapid diagnostic tests (Ag-RDTs) for SARS-CoV-2 are important diagnostic tools. We assessed clinical performance and ease-of-use of seven Ag-RDTs in a prospective, manufacturer-independent, multi-centre cross-sectional diagnostic accuracy study to inform global decision makers. METHODS: Unvaccinated participants suspected of a first SARS-CoV-2 infection were recruited at six sites (Germany, Brazil). Ag-RDTs were evaluated sequentially, with collection of paired swabs for routine reverse transcription polymerase chain reaction (RT-PCR) testing and Ag-RDT testing. Performance was compared to RT-PCR overall and in sub-group analyses (viral load, symptoms, symptoms duration). To understandusability a System Usability Scale (SUS) questionnaire and ease-of-use (EoU) assessment were performed. FINDINGS: 7471 participants were included in the analysis. Sensitivities across Ag-RDTs ranged from 70·4%-90·1%, specificities were above 97·2% for all Ag-RDTs but one (93·1%).Ag-RDTs, Mologic, Bionote, Standard Q, showed diagnostic accuracy in line with WHO targets (> 80% sensitivity, > 97% specificity). All tests showed high sensitivity in the first three days after symptom onset (≥87·1%) and in individuals with viral loads≥ 6 log10SARS-CoV2 RNA copies/mL (≥ 88·7%). Usability varied, with Rapigen, Bionote and Standard Q reaching very good scores; 90, 88 and 84/100, respectively. INTERPRETATION: Variability in test performance is partially explained by variable viral loads in population evaluated over the course of the pandemic. All Ag-RDTs reach high sensitivity early in the disease and in individuals with high viral loads, supporting their role in identifying transmission relevant infections. For easy-to-use tests, performance shown will likely be maintained in routine implementation. FUNDING: Ministry of Science, Research and Arts, State of Baden-Wuerttemberg, Germany, internal funds from Heidelberg University Hospital, University Hospital Charité - Universitätsmedizin Berlin, UK Department of International Development, WHO, Unitaid.

Advances in Molecular Diagnosis of Tuberculosis.

Molecular tests for tuberculosis (TB) have the potential to help reach the three million people with TB who are undiagnosed or not reported each year and to improve the quality of care TB patients receive by providing accurate, quick results, including rapid drug-susceptibility testing. The World Health Organization (WHO) has recommended the use of molecular nucleic acid amplification tests (NAATs) tests for TB detection instead of smear microscopy, as they are able to detect TB more accurately, particularly in patients with paucibacillary disease and in people living with HIV. Importantly, some of these WHO-endorsed tests can detect mycobacterial gene mutations associated with anti-TB drug resistance, allowing clinicians to tailor effective TB treatment. Currently, a wide array of molecular tests for TB detection is being developed and evaluated, and while some tests are intended for reference laboratory use, others are being aimed at the point-of-care and peripheral health care settings. Notably, there is an emergence of molecular tests designed, manufactured, and rolled out in countries with high TB burden, of which some are explicitly aimed for near-patient placement. These developments should increase access to molecular TB testing for larger patient populations. With respect to drug susceptibility testing, NAATs and next-generation sequencing can provide results substantially faster than traditional phenotypic culture. Here, we review recent advances and developments in molecular tests for detecting TB as well as anti-TB drug resistance.

Point-of-Care Ultrasound for Extrapulmonary Tuberculosis in India: A Prospective Cohort Study in HIV-Positive and HIV-Negative Presumptive Tuberculosis Patients.

Diagnosing extrapulmonary tuberculosis (EPTB) is challenging. Point-of-care ultrasound (POCUS) for human immunodeficiency virus (HIV)-associated EPTB is applied in sub-Saharan Africa. This study aimed at evaluating the applicability of POCUS for diagnosing EPTB in HIV-positive and HIV-negative presumptive tuberculosis (TB) patients in India, a country of moderate relative TB and HIV burden. Presumptive TB patients at Kasturba Hospital, Manipal, India, prospectively underwent POCUS evaluating for pericardial, pleural and ascitic effusion, abdominal lymphadenopathy, and hepatic and splenic microabscesses. Findings were correlated with TB category (confirmed TB, clinical TB, unlikely TB), HIV status, and discharge diagnoses. A total of 425 patients underwent POCUS; 81 (20%) were HIV-positive. POCUS findings were more common in HIV/TB coinfected patients than in HIV-positive patients with unlikely TB (24/40 (60%) versus 9/41 (22%), P < 0.001). Abdominal lymphadenopathy and splenic microabscesses were strongly associated with TB in HIV-positive patients (P = 0.002 and P = 0.001). POCUS findings did not correlate with TB in HIV-negative patients; a third of HIV-negative patients with unlikely TB and POCUS findings had cancer, another third other infectious diseases. Sonographic findings were common in HIV-positive and HIV-negative presumptive TB patients. POCUS was a useful bedside test for the detection of HIV-associated EPTB. In HIV-negative patients, POCUS detected features associated with EPTB but also of malignancy and other infectious diseases.