ABSTRACT
Background: Convalescent plasma could be an inexpensive and widely available drug for COVID-19 patients. Reports on its effectiveness are inconclusive. We collected convalescent plasma with high titers of neutralizing anti-SARS-CoV-2 antibodies effectively blocking SARS-CoV-2 infection and assessed their clinical and viro-immunological responses in COVID-19 patients with severe disease. Methods: In a multicentre open-label randomized clinical trial in 14 secondary and academic hospitals in the Netherlands, included patients were admitted for COVID-19 with SARS-CoV-2 detected by PCR and not on mechanical ventilation for >96hours. Convalescent plasma donors were selected based on SARS-CoV-2 plaque reduction neutralization test (PRNT50) result of ≥1:80. Primary outcome was day 60 mortality. Secondary outcomes were disease severity, inflammatory and virological markers. Results: Included patients were 72% male, median 63 years (IQR 56-74) and with median 10 days of symptoms (IQR 6-15) at inclusion when they were randomized to convalescent plasma or standard of care. We found no significant difference in mortality at day 60 by using 300mL of convalescent plasma (median PRNT50 1:640) between the arms after adjustment (OR: 0.95, 95%CI: 0.20-4.67). Improvements in WHO COVID-19 disease severity scores at day 15 (OR: 1.30, 95%CI 0.52-3.32) and time to discharge (HR: 0.88, 95%CI: 0.49-1.60) were also comparable. The vast majority of patients already had potent neutralizing anti-SARS-CoV-2 antibodies at hospital admission and at comparable titers as the carefully selected plasma donors. No effect of convalescent plasma on viral clearance in the respiratory tract, anti- SARS-CoV-2 antibody development or changes in serum pro-inflammatory cytokine levels were observed. After the inclusion of 86 patients and per DSMB recommendation, we decided to interrupt the study for futility. Conclusion: Convalescent plasma treatment in this patient group did not improve survival or disease course, nor did it alter relevant virological and immunological parameters. Together, these data indicate that the variable effectivity observed in trials on convalescent plasma for COVID-19 may be explained by the timing of treatment and varying levels of preexisting anti-SARS-CoV-2 immunity in patients. It also substantiates that convalescent plasma should be studied as early as possible in the disease course or at least preceding the start of an autologous humoral response. (Clinicaltrials.gov: NCT04342182).
ABSTRACT
Background: After SARS-CoV-2 reached the Netherlands in February 2020, rapid interventions were taken to mitigate viral spread and optimise care for COVID-19 patients. Lockdowns and downscaling of regular healthcare practices were necessary to scale up COVID-19-related care. The effect of these interventions on HIV care are uncertain. We assessed the impact of the nationwide lockdown in March and May during the first COVID-19 wave on HIV diagnosis and linkage to care. Methods: An observational study was conducted at the Erasmus MC, a regional reference tertiary hospital in the Netherlands. All patients ≥ 18 years presenting with HIV indicator conditions (ICs) were identified in electronic patient records, using an automated identification system for ICD-10 and health insurance codes. Primary outcomes measured were the number of HIV tests performed, number of HIV ICs and corresponding HIV testing rates, and new HIV diagnoses before, during and after lockdown. Results: From January to April, all newly registered diagnoses decreased by 35%, and in patients referred for HIV ICs by 69% (figure 1). The proportion of patients presenting with HIV ICs that were adequately tested for HIV remained relatively stable, especially where HIV testing is standardised, even during lockdown in March, April and May when a cumulative 328 proven or suspected COVID-19 patients were admitted. The absolute number of HIV tests performed during the first half year of 2020 was 13% lower than the same period in 2019, and new HIV patient referrals dropped 67%. The number of HIV IC, HIV testing rates and HIV referrals showed recovery after the lockdown. Conclusion: The first two pillars of the HIV care continuum were affected by the lockdown during the COVID-19 pandemic. Standardisation of HIV testing could prevent diagnostic delays to a certain extent. With an eye on subsequent COVID-19 waves, these data indicate that maintaining focus on adequate identification and testing of patients with undiagnosed HIV is essential to prevent unwanted declines affecting the 95-95-95 goals.