Safety and efficacy of convalescent plasma for severe COVID-19: a randomized, single blinded, parallel, controlled clinical study.

BACKGROUND: Convalescent plasma (CP) has been widely used to treat COVID-19 and is under study. However, the variability in the current clinical trials has averted its wide use in the current pandemic. We aimed to evaluate the safety and efficacy of CP in severe coronavirus disease 2019 (COVID-19) in the early stages of the disease. METHODS: A randomized controlled clinical study was conducted on 101 patients admitted to the hospital with confirmed severe COVID-19. Most participants had less than 14 days from symptoms onset and less than seven days from hospitalization. Fifty patients were assigned to receive CP plus standard therapy (ST), and 51 were assigned to receive ST alone. Participants in the CP arm received two doses of 250 mL each, transfused 24 h apart. All transfused plasma was obtained from "super donors" that fulfilled the following criteria: titers of anti-SARS-CoV-2 S1 IgG ≥ 1:3200 and IgA ≥ 1:800 antibodies. The effect of transfused anti-IFN antibodies and the SARS-CoV-2 variants at the entry of the study on the overall CP efficacy was evaluated. The primary outcomes were the reduction in viral load and the increase in IgG and IgA antibodies at 28 days of follow-up. The per-protocol analysis included 91 patients. RESULTS: An early but transient increase in IgG anti-S1-SARS-CoV-2 antibody levels at day 4 post-transfusion was observed (Estimated difference [ED], - 1.36; 95% CI, - 2.33 to - 0.39; P = 0.04). However, CP was not associated with viral load reduction in any of the points evaluated. Analysis of secondary outcomes revealed that those patients in the CP arm disclosed a shorter time to discharge (ED adjusted for mortality, 3.1 days; 95% CI, 0.20 to 5.94; P = 0.0361) or a reduction of 2 points on the WHO scale when compared with the ST group (HR adjusted for mortality, 1.6; 95% CI, 1.03 to 2.5; P = 0.0376). There were no benefits from CP on the rates of intensive care unit admission (HR, 0.82; 95% CI, 0.35 to 1.9; P = 0.6399), mechanical ventilation (HR, 0.66; 95% CI, 0.25 to 1.7; P = 0.4039), or mortality (HR, 3.2; 95% CI, 0.64 to 16; P = 0.1584). Anti-IFN antibodies and SARS-CoV-2 variants did not influence these results. CONCLUSION: CP was not associated with viral load reduction, despite the early increase in IgG anti-SARS-CoV-2 antibodies. However, CP is safe and could be a therapeutic option to reduce the hospital length of stay. Trial registration NCT04332835.

Spatial and Temporal Distribution of Norovirus and E. coli in Sydney Rock Oysters Following a Sewage Overflow into an Estuary.

This paper reports a study of norovirus (NoV) GII distribution and persistence in Sydney rock oysters (SRO) (Saccostrea glomerata) located in an estuary after a pump station sewage overflow. SRO were strategically placed at six sites spanning the length of the estuary from the pump station to the sea. The spatial and temporal distribution of NoV, hepatitis A virus (HAV) and Escherichia coli (E. coli) in oysters was mapped after the contamination event. NoV GI and GII, HAV and E. coli were quantified for up to 48 days in oysters placed at six sites ranging from 0.05 to 8.20 km from the sewage overflow. NoV GII was detected up to 5.29 km downstream and persisted in oysters for 42 days at the site closest to the overflow. NoV GII concentrations decreased significantly over time; a reduction rate of 8.5% per day was observed in oysters (p < 0.001). NoV GII concentrations decreased significantly as a function of distance at a rate of 5.8% per km (p < 0.001) and the decline in E. coli concentration with distance was 20.1% per km (p < 0.001). HAV and NoV GI were not detected. A comparison of NoV GII reduction rates from oysters over time, as observed in this study and other published research, collectively suggest that GII reduction rates from oysters may be broadly similar, regardless of environmental conditions, oyster species and genotype.

An outbreak of norovirus genogroup II associated with New South Wales oysters.

INTRODUCTION: Currently available antigen tests for norovirus (NoV) have excellent specificity but negative results do not always rule out infection. Real-time reverse transcription polymerase chain reaction (RT-PCR) is a useful method for detecting and genotyping NoV in humans and oysters. An outbreak of NoV associated with oyster consumption in northern New South Wales confirmed the value of real-time RT-PCR where immunochromatography (ICT) tests were negative. METHODS: Eight cases of gastrointestinal illness in northern NSW, clinically suggestive of NoV infection, were associated with consumption of oysters. A joint environmental investigation was conducted by the New South Wales Food Authority and local council. One human sample was collected and tested for NoV using ICT and real-time RT-PCR. Oyster samples were tested for NoV utilising real-time RT-PCR. RESULTS: The patient with a stool sample had NoV genogroup II (GII) confirmed by real-time RT-PCR after testing negative by ICT. Illness in all cases was consistent with NoV with median incubation and duration of 36 and 50.5 hours respectively. All cases consumed oysters that were harvested from the same area. Three oyster samples from the harvest area were also positive for NoV GII. A nearby leaking sewer line was identified as the likely source of the contamination with hydrological studies confirming its potential to contaminate implicated oyster leases. CONCLUSION: This investigation confirmed the value of real-time RT-PCR testing of human specimens where ICT tests are negative and clinical illness is suggestive of NoV infection. NoV real-time RT-PCR and epidemiological evidence effectively linked human infection with oyster contamination to motivate a thorough environmental investigation and appropriate action to mitigate further public health risk.