Widespread Exposure to Mosquitoborne California Serogroup Viruses in Caribou, Arctic Fox, Red Fox, and Polar Bears, Canada.

Northern Canada is warming at 3 times the global rate. Thus, changing diversity and distribution of vectors and pathogens is an increasing health concern. California serogroup (CSG) viruses are mosquitoborne arboviruses; wildlife reservoirs in northern ecosystems have not been identified. We detected CSG virus antibodies in 63% (95% CI 58%-67%) of caribou (n = 517), 4% (95% CI 2%-7%) of Arctic foxes (n = 297), 12% (95% CI 6%-21%) of red foxes (n = 77), and 28% (95% CI 24%-33%) of polar bears (n = 377). Sex, age, and summer temperatures were positively associated with polar bear exposure; location, year, and ecotype were associated with caribou exposure. Exposure was highest in boreal caribou and increased from baseline in polar bears after warmer summers. CSG virus exposure of wildlife is linked to climate change in northern Canada and sustained surveillance could be used to measure human health risks.

Effect of Ivermectin 600 mcg/kg for 6 days vs Placebo on Time to Sustained Recovery in Outpatients with Mild to Moderate COVID-19: A Randomized Clinical Trial (preprint)

Background: Whether ivermectin, with a maximum targeted dose of 600 mcg/kg, shortens symptom duration or prevents hospitalization among outpatients with mild to moderate coronavirus disease 2019 (COVID-19) remains unknown. Our objective was to evaluate the effectiveness of ivermectin, dosed at 600 mcg/kg, daily for 6 days compared with placebo for the treatment of early mild to moderate COVID-19. Methods: ACTIV-6, an ongoing, decentralized, randomized, double-blind, placebo-controlled, platform trial, was designed to evaluate repurposed therapies in outpatients with mild to moderate COVID-19. A total of 1206 participants age >=30 years with confirmed COVID-19, experiencing >=2 symptoms of acute infection for <=7 days, were enrolled from February 16, 2022, through July 22, 2022, with follow-up data through November 10, 2022, at 93 sites in the US. Participants were randomized to ivermectin, with a maximum targeted dose of 600 mcg/kg (n=602), daily vs. placebo daily (n=604) for 6 days. The primary outcome was time to sustained recovery, defined as at least 3 consecutive days without symptoms. The 7 secondary outcomes included a composite of hospitalization, death, or urgent/emergent care utilization by day 28. Results: Among 1206 randomized participants who received study medication or placebo, median (interquartile range) age was 48 (38-58) years; 713 (59%) were women; and 1008 (84%) reported 2 or more SARS-CoV-2 vaccine doses. Median time to recovery was 11 (11-12) days in the ivermectin group and 11 (11-12) days in the placebo group. The hazard ratio (HR) (95% credible interval [CrI], posterior probability of benefit) for improvement in time to recovery was 1.02 (0.92-1.13; P[HR>1]=0.68). In those receiving ivermectin, 34 (5.7%) were hospitalized, died, or had urgent or emergency care visits compared with 36 (6.0%) receiving placebo (HR 1.0, 0.6-1.5; P[HR<1]=0.53). In the ivermectin group, 1 participant died and 4 were hospitalized (0.8%); 2 participants (0.3%) were hospitalized in the placebo group and there were no deaths. Adverse events were uncommon in both groups. Conclusions: Among outpatients with mild to moderate COVID-19, treatment with ivermectin, with a maximum targeted dose of 600 mcg/kg daily for 6 days, compared with placebo did not improve time to recovery. These findings do not support the use of ivermectin in patients with mild to moderate COVID-19. Trial registration: ClinicalTrials.gov Identifier: NCT04885530 .

Hydroxychloroquine for pre-exposure prophylaxis of COVID-19 in health care workers: a randomized, multicenter, placebo-controlled trial (HERO-HCQ) (preprint)

ABSTRACT Objective To determine whether hydroxychloroquine (HCQ) is safe and effective at preventing COVID-19 infections among health care workers (HCW). Design Multicenter, 1:1 randomized, placebo-controlled, double-blind, parallel-group, superiority trial. Setting 34 clinical centers in the United States. Participants 1360 HCW at risk for COVID-19 infection enrolled between April and November 2020. Interventions A loading dose of HCQ 600 mg twice on Day 1 followed by 400 mg daily for 29 days or matching placebo taken orally. Main Outcome Measure Composite of confirmed or suspected COVID-19 clinical infection by Day 30 defined as new onset fever, cough, or dyspnea and either a positive SARS-CoV-2 PCR test (confirmed) or a lack of confirmatory testing due to local restrictions (suspected). Results Enrollment for the study was closed before full accrual due to difficulties recruiting additional participants. The primary composite endpoint occurred in 41 (6.0%) participants receiving HCQ and 53 (7.8%) participants receiving placebo. No statistically significant difference in the proportion of participants experiencing clinical infection (estimated difference of -1.8%, 95% confidence interval -4.6% to 0.9%, p=0.20). We identified no significant safety issues. Conclusion Oral HCQ taken as prescribed appeared to be safe in a group of HCW. No significant clinical benefits were observed. The study was underpowered to rule out a small but potentially important reduction in COVID-19 infections. Trial Registration NCT04334148

Prognostic value of Neutrophil-to-lymphocyte ratio in COVID-19 patients: A systematic review and meta-analysis (preprint)

Background: Neutrophil-to-lymphocyte ratio (NLR) is an accessible and widely used biomarker. NLR may be used as an early marker of poor prognosis in patients with COVID-19. Methods: We conducted a systematic review and meta-analysis. Observational studies that reported the association between baseline NLR values (i.e. at hospital admission) and severity or all-cause mortality in COVID-19 patients were included. The quality of the studies was assessed using the Newcastle-Ottawa scale (NOS). Random effects models and inverse variance method were used for meta-analyses. The effects were expressed as odds ratios (OR) and their 95% confidence intervals (CI). Small study effects were assessed with the Egger’s test. Results: Twenty studies, 19 cohorts and one case-control were included. An increase of one unit of NLR was associated with a higher odds of COVID-19 severity (OR 6.6, 95% CI: 4.71 - 7.19; p<0.001) and higher odds of all-cause mortality (OR 12.7, 95% CI: 1.32, 123.36; p=0.025). No differences were found in subgroup analyses by study design. The subgroup analysis of the studies, by country of origin, showed that the strength of the association between NLR and mortality was greater in Chinese studies (OR 31.1; 95%CI 19.57 to 49.3; p<0.0001) with moderate heterogeneity (I2 =43%). In our sensitivity analysis, we found that 7 studies with low risk of bias maintained strong association between both outcomes and the NLR values (severity: OR 4.7; 95% CI 3.5 to 6.34; p < 0.001 vs mortality: OR 31.1; 95% CI 19.57 to 49.3; p <0.0001), with low (I2 = 37%) and moderate (I2 = 43%) heterogeneity for severity and mortality outcomes, respectively. No publication bias was found for studies that evaluated effects for the severity of disease. Conclusions: Higher values of NLR were associated with severity and all-cause mortality in hospitalized COVID-19 patients.

Healthcare Worker Exposure Response and Outcomes of Hydroxychloroquine