SummaryBackgroundInfluenza causes significant morbidity and mortality despite currently available treatments. Anecdotal reports suggest plasma with high antibody titers towards influenza may be of benefit in the treatment of severe influenza.MethodsWe conducted a randomized, open-label, multicenter phase 2 trial at 29 academic medical centers in the United States to assess the safety and efficacy of anti-influenza plasma with hemagglutination inhibition (HAI) antibody titers of ≥ 1:80 to the infecting strain. Hospitalized children and adults (including pregnant women) with severe influenza A or B (defined as hypoxia or tachypnea) were randomly assigned to receive either 2 units (or pediatric equivalent) of anti-influenza plasma plus standard care (P+S), versus standard care alone (S), and were followed for 28 days. The primary endpoint was time to normalization of patients’ respiratory status (respiratory rate of ≤ 20 for adults or age defined thresholds of 20–38 for children), and a room air saturation of oxygen ≥ 93%. ClinicalTrials.gov Identifier: NCT01052480FindingsBetween January 13, 2011 and March 2, 2015, 113 participants were screened, and 98 were randomized. Of the participants with confirmed influenza, 28 of 42 (67%) of P+S participants normalized their respiratory status by Day 28, as compared to 24 of 45 (53%) of S participants (p=0·069). The estimated hazard ratio comparing P+S to S was 1·71 (95% CI: 0·96 to 3·06). Six participants died, 1 (2%) and 5 (10%) from the P+S and S arms respectively (p=0·093). P+S participants had non-significant reductions in days in hospital (median 6 vs. 11 days, p=0·13) and days on mechanical ventilation (median 0 vs. 3 days, p=0·14), and significantly improved clinical status at Day 7 (p=0·020). Fewer P+S participants experienced SAEs compared to S recipients (20% vs. 38%, p= 0·041), the most frequent of which were acute respiratory distress syndrome (1 [2%] vs 2 [4%]) and stroke (1 [2%] vs 2 [4%]).InterpretationResults from this Phase II randomized trial of immune plasma for the treatment of severe influenza provides support for a possible benefit of immunotherapy across the primary and secondary endpoints. A Phase III randomized trial is now underway to further evaluate this intervention.

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Objective: We hypothesized healthcare workers (HCW) with high-risk exposures outside the healthcare system would have less asymptomatic coronavirus 2019 (COVID-19) disease and more symptoms than those without such exposures. Design: A longitudinal point prevalence study during August 17- September 4 2020 and December 2nd - 23rd. Setting: Community based teaching health system Participants: All HCS were invited to participate. Among HCW who acquired COVID-19, logistic regression models were used to evaluate the adjusted odds of asymptomatic disease using high-risk exposure outside the healthcare system as the explanatory variable. The number of symptoms between exposure groups was evaluated with the Wilcoxon rank-sum test. The risk of seropositivity among all HCS by work exposure was evaluated during both periods. Interventions: Survey and serological testing Result: Seroprevalence increased from 1.9% (95% CI 1.2% - 2.6%) to 13.7% (95% CI 11.9% - 15.5%) during the study. Only during Period 2 did HCW with the highest work exposure (versus low exposure) have an increased risk of seropositivity (RD 7% [95% CI 1% -13%]). Participants who had a high-risk exposure outside of work (compared to those without) had a decreased probability of asymptomatic disease (OR 0.38 [95% CI 0.16 – 0.86]) and demonstrated more symptoms (median of 3 [IQR 5] vs 1 [IQR 2]; P = 0.001). Conclusions Health care acquired COVID-19 increases the probability of asymptomatic or mild COVID-19 disease compared to community acquired disease. This suggests infection prevention strategies (including masks and eye protection) may be mitigating inoculum and supports the variolation theory in COVID-19.

CRRT may have beneficial effects in patients with RIH. Given the high mortality rate and poor neurological outcome associated with RIH, further research may be warranted.