Double-blinded, randomised, placebo-controlled trial of convalescent plasma for COVID-19: analyses by neutralising antibodies homologous to recipients' variants.

INTRODUCTION: Convalescent plasma (CP) emerged as potential treatment for COVID-19 early in the pandemic. While efficacy in hospitalised patients has been lacklustre, CP may be beneficial at the first stages of disease. Despite multiple new variants emerging, no trials have involved analyses on variant-specific antibody titres of CP. METHODS: We recruited hospitalised COVID-19 patients within 10 days of symptom onset and, employing a double-blinded approach, randomised them to receive 200 ml convalescent plasma with high (HCP) or low (LCP) neutralising antibody (NAb) titre against the ancestral strain (Wuhan-like variant) or placebo in 1:1:1 ratio. Primary endpoints comprised intubation, corticosteroids for symptom aggravation, and safety assessed as serious adverse events. For a preplanned ad hoc analysis, the patients were regrouped by infused CP's NAb titers to variants infecting the recipients i.e. by titres of homologous HCP (hHCP) or LCP (hLCP). RESULTS: Of the 57 patients, 18 received HCP, 19 LCP and 20 placebo, all groups smaller than planned. No significant differences were found for primary endpoints. In ad hoc analysis, hHCPrecipients needed significantly less respiratory support, and appeared to be given corticosteroids less frequently (1/14; 7.1%) than those receiving hLCP (9/23; 39.1%) or placebo (8/20; 40%), (p = 0.077). DISCUSSION: Our double-blinded, placebo-controlled CP therapy trial remained underpowered and does not allow any firm conclusions for early-stage hospitalised COVID-19 patients. Interestingly, however, regrouping by homologous - recipients' variant-specific - CP titres suggested benefits for hHCP. We encourage similar re-analysis of ongoing/previous larger CP studies. TRIAL REGISTRATION: ClinTrials.gov identifier: NCT0473040.

Association of CT findings with invasive subtypes and the new grading system of lung adenocarcinoma.

AIM: To predict the differentiation between invasive growth patterns and new grades of lung adenocarcinoma (LAC) using computed tomography (CT). MATERIALS AND METHODS: The CT features of 180 surgically treated LAC patients were compared retrospectively to pathological invasive subtypes and tumour grades as defined by the new grading system published in 2021 by the World Health Organization. Two radiologists reviewed the images semi-quantitatively and independently. Univariable and multivariable regression models were built from the statistical means of their assessments to predict invasive subtypes and grades. The area under the curve (AUC) calculation was used to select the best models. The Youden index was applied to determine the cut-off values for radiological parameters. RESULTS: The acinar/papillary patterns were associated with ill-defined margins, lower consolidation/tumour ratio and air bronchogram. The solid growth pattern was associated with a well-defined margin and hypodensity, and the micropapillary (MP) subtype with spiculation. From Grades 1 to 3, the amount of air bronchogram decreased and the consolidation/tumour ratio increased. In the sub-analyses, the best model for differentiating Grade 2 from Grade 1 had the following CT features: solid/subsolid type, consolidation/tumour ratio, well-defined margin, and air bronchogram (AUC = 0.783) and Grade 3 from Grade 2: size of the consolidation part/whole tumour ratio, size of the consolidation part, and well-defined margin (AUC = 0.759). The interobserver agreements between the two radiologists varied between 0.67 and 0.98. CONCLUSIONS: Air bronchogram, consolidation/tumour ratio, and well-defined margin are among the best imaging findings to discriminate between both invasive subtypes and the new grades in LAC.

Isolation precautions cause minor delays in diagnostics and treatment of non-COVID patients.

BACKGROUND: Isolation precautions are essential prevent spread of COVID-19 infection but may have a negative impact on inpatient care. The impact of these measures on non-COVID-19 patients remains largely unexplored. AIM: This study aimed to investigate diagnostic and treatment delays related to isolation precautions, the associated patient outcome, and the predisposing risk factors for delays. METHODS: This observational study was conducted in seven Helsinki region hospitals during the first wave of the COVID-19 pandemic in Finland. The study used data on all non-COVID-19 inpatients, who were initially isolated due to suspected COVID-19, to estimate whether isolation precautions resulted in diagnostic or treatment delays. RESULTS: Out of 683 non-COVID-19 patients, 33 (4.8%) had delays related to isolation precautions. Clinical condition deteriorated non-fatally in seven (1.0%) patients. The following events were associated with an increased risk of treatment or a diagnostic delay: more than three ward transfers (P = 0.025); referral to an incorrect speciality in the emergency department (P = 0.004); more than three SARS-CoV-2 RT-PCR tests performed (P = 0.022); and where cancer was the final diagnosis (P = 0.018). In contrast, lower respiratory tract symptoms (P = 0.013) decreased the risk. CONCLUSIONS: The use of isolation precautions for patients who did not have COVID-19 had minor negative effects on patient outcomes. The present study underlines the importance of targeting diagnostic efforts to patients with unspecified symptoms and to those with a negative SARS-CoV-2 test result. Thorough investigations to achieve an accurate diagnosis improves the prognosis of patients and facilitates appropriate targeting of hospital resources.