Doxycycline as a potential partner of COVID-19 therapies

Coronavirus disease 2019 (COVID-19) is a major public health challenge, and the current antiviral arsenal for treatment is limited, with questionable efficacy. Major efforts are under way for discovery of new effective agents, but the validation of new potential treatments for COVID-19 may take a long time. Therefore, the repurposing of existing drugs for new indications is needed. In this article, we argue for the potential benefits of using doxycycline with either hydroxycholoroquine or other putative agents for COVID-19 treatment, as doxycycline has antiviral and anti-inflammatory activities by dampening the cytokine storm and to prevent lung damage

Characterization of a West Nile Virus Isolate from a Human on the Gulf Coast of Texas

Genetic characterization of a human cerebrospinal fluid West Nile virus isolate from Beaumont, Texas, revealed several nucleotide changes and amino acid substitutions that differentiated it from all other North American strains isolated to date, suggesting that isolates from the Texas Gulf Coast may form a unique genetic group among North American strains

Correlation between Circulating Fungal Biomarkers and Clinical Outcome in Invasive Aspergillosis

Objective means are needed to predict and assess clinical response in patients treated for invasive aspergillosis (IA). We examined whether early changes in serum galactomannan (GM) and/or β-D-glucan (BDG) can predict clinical outcomes. Patients with proven or probable IA were prospectively enrolled, and serial GM and BDG levels and GM optical density indices (GMI) were calculated twice weekly for 6 weeks following initiation of standard-of-care antifungal therapy. Changes in these biomarkers during the first 2 and 6 weeks of treatment were analyzed for associations with clinical response and survival at weeks 6 and 12. Among 47 patients with IA, 53.2% (25/47) and 65.9% (27/41) had clinical response by weeks 6 and 12, respectively. Changes in biomarkers during the first 2 weeks were associated with clinical response at 6 weeks (GMI, P = 0.03) and 12 weeks (GM+BDG composite, P = 0.05; GM, P = 0.04; GMI, P = 0.02). Changes in biomarkers during the first 6 weeks were also associated with clinical response at 6 weeks (GM, P = 0.05; GMI, P = 0.03) and 12 weeks (BDG+GM, P = 0.02; GM, P = 0.02; GMI, P = 0.01). Overall survival rates at 6 weeks and 12 weeks were 87.2% (41/47) and 79.1% (34/43), respectively. Decreasing biomarkers in the first 2 weeks were associated with survival at 6 weeks (BDG+GM, P = 0.03; BDG, P = 0.01; GM, P = 0.03) and at 12 weeks (BDG+GM, P = 0.01; BDG, P = 0.03; GM, P = 0.01; GMI, P = 0.007). Similar correlations occurred for biomarkers measured over 6 weeks. Patients with negative baseline GMI and/or persistently negative GMI during the first 2 weeks were more likely to have CR and survival. These results suggest that changes of biomarkers may be informative to predict and/or assess response to therapy and survival in patients treated for IA

Correlation between Circulating Fungal Biomarkers and Clinical Outcome in Invasive Aspergillosis

Objective means are needed to predict and assess clinical response in patients treated for invasive aspergillosis (IA). We examined whether early changes in serum galactomannan (GM) and/or β-D-glucan (BDG) can predict clinical outcomes. Patients with proven or probable IA were prospectively enrolled, and serial GM and BDG levels and GM optical density indices (GMI) were calculated twice weekly for 6 weeks following initiation of standard-of-care antifungal therapy. Changes in these biomarkers during the first 2 and 6 weeks of treatment were analyzed for associations with clinical response and survival at weeks 6 and 12. Among 47 patients with IA, 53.2% (25/47) and 65.9% (27/41) had clinical response by weeks 6 and 12, respectively. Changes in biomarkers during the first 2 weeks were associated with clinical response at 6 weeks (GMI, P = 0.03) and 12 weeks (GM+BDG composite, P = 0.05; GM, P = 0.04; GMI, P = 0.02). Changes in biomarkers during the first 6 weeks were also associated with clinical response at 6 weeks (GM, P = 0.05; GMI, P = 0.03) and 12 weeks (BDG+GM, P = 0.02; GM, P = 0.02; GMI, P = 0.01). Overall survival rates at 6 weeks and 12 weeks were 87.2% (41/47) and 79.1% (34/43), respectively. Decreasing biomarkers in the first 2 weeks were associated with survival at 6 weeks (BDG+GM, P = 0.03; BDG, P = 0.01; GM, P = 0.03) and at 12 weeks (BDG+GM, P = 0.01; BDG, P = 0.03; GM, P = 0.01; GMI, P = 0.007). Similar correlations occurred for biomarkers measured over 6 weeks. Patients with negative baseline GMI and/or persistently negative GMI during the first 2 weeks were more likely to have CR and survival. These results suggest that changes of biomarkers may be informative to predict and/or assess response to therapy and survival in patients treated for IA.status: publishe

(a) Mean Z-scores for the time-weighted averages of galactomannan and beta-D-glucan composite values, and (b) time-weighted averages for beta-D-glucan values, galactomannan values, and galactomannan optical density index, in responders vs non-responders at week 6 and week 12.

<p>GM: Galactomannan, BDG: Beta-D-Glucan, GMI: Galactomannan Optical Density Index, W: Week, R: Responder, NR: Non-responder, N: Number, CI: Confidence Interval.</p><p>^<b>a</b> Some patients did not have data available for both biomarkers throughout the study; therefore, the numbers of patients with BDG, GM and/or GMI at weeks 2 and 6 differ from the total number of patients in the BDG and GM column.</p><p>(a) Mean Z-scores for the time-weighted averages of galactomannan and beta-D-glucan composite values, and (b) time-weighted averages for beta-D-glucan values, galactomannan values, and galactomannan optical density index, in responders vs non-responders at week 6 and week 12.</p

Association of galactomannan assay optical density index (GMI) as a dichotomous variable (positive [GMI ≥ 0.5] vs negative) between baseline and week 2 of treatment with clinical response and survival at 6 and 12 weeks.

<p>GMI: Galactomannan Optical Density Index, OR: Odds Ratio, CI: Confidence Interval</p><p>^a Clinical response: complete or partial response, as described in Methods [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0129022#pone.0129022.ref005" target="_blank">5</a>].</p><p>^b Only one patient had positive GMI at baseline and negative GMI by week 2, so this category (+/-) was not included in the analysis.</p><p>^c Due to low number of observations, there was lack of model convergence and no results were generated.</p><p>Association of galactomannan assay optical density index (GMI) as a dichotomous variable (positive [GMI ≥ 0.5] vs negative) between baseline and week 2 of treatment with clinical response and survival at 6 and 12 weeks.</p