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.

Recommendations for lung cancer screening in Southern Africa.

Lung cancer remains the leading cause of cancer-related deaths in southern Africa. Early trials of chest radiograph-based screening in males at high risk for lung cancer found no mortality benefit of a radiograph alone, or a radiograph plus sputum cytology screening strategy. Large prospective studies, including the National Lung Screening Trial, have shown an all-cause mortality benefit when low-dose computed tomography (LDCT) was used as a screening modality in patients that are at high risk of developing lung cancer. The South African Thoracic Society, based on these findings, and those from several international guidelines, recommend that annual LDCT should be offered to patients between 55-74 years of age who are current or former smokers (having quit within the preceding 15 years), with at least a 30-pack year smoking history and with no history of lung cancer. Patients should be in general good health, fit for surgery, and willing to undergo further investigations if deemed necessary. Given the high local prevalence of tuberculosis (TB) infection and post-TB lung disease, which can radiographically mimic lung cancer, a conservative threshold (nodule size ≥6 mm) should be used to determine whether the baseline LDCT screen is positive (thus nodules <6 mm require no action until the next annual screen). If a non-calcified, solid or partly solid nodule is ≥6 mm, but <10 mm with no malignant features (e.g., distinct spiculated margins), the LDCT should be repeated in 6 months. If a solid nodule or the largest component of a non-solid nodule is ≥10 or ≥6 mm and enlarging or with additional malignant features present, definitive action to exclude lung cancer is warranted. Patients should be screened annually until 15 years have elapsed from date of smoking cessation, they turn 80, become unfit for a curative operation or significant changes are observed.