Real-world response of COVID-19 patients in Mexico

Currently in Mexico, the available clinical guidelines published for COVID-19 treatment recommend symptom treatment and home isolation for mild forms; and other medications for severe and acute forms. The effectiveness of how real-world treatment patterns impact mortality and recovery is still unknown. In this retrospective observational study, we investigated 5,575 medicated patients with COVID-19 treated at two Mexican states seen in the largest healthcare system in Mexico. A survival analysis was performed using death and discharge as primary and secondary outcomes (respectively). Machine learning models were built to predict mortality and discharge. The higher prevalence of obesity, diabetes, and heart disease comorbidities is consistent with Mexico's epidemiological profile. Mortality occurs around 15-20 days from the start of symptoms. Antivirals in combination with antibiotics present lower survival rates, with patients undertaking neuraminidase inhibitors (NAIs) being the most affected. Our findings recommend against using specific treatment combinations with NAIs, and should help improve the country's clinical guidelines.

Broadly-neutralizing antibodies that bind to the influenza hemagglutinin stalk domain enhance the effectiveness of neuraminidase inhibitors via Fc-mediated effector functions

The conserved hemagglutinin stalk domain is an attractive target for broadly effective antibody-based therapeutics and next generation universal influenza vaccines. Protection provided by hemagglutinin stalk binding antibodies is principally mediated through activation of immune effector cells. Titers of stalk-binding antibodies are highly variable on an individual level, and tend to increase with age as a result of increasing exposures to influenza virus. In our study, we show that stalk-binding antibodies cooperate with neuraminidase inhibitors to protect against influenza virus infection in an Fc-dependent manner. These data suggest that the effectiveness of neuraminidase inhibitors is likely influenced by an individual's titers of stalk-binding antibodies, and that neuraminidase inhibitors may enhance the effectiveness of future stalk-binding monoclonal antibody-based treatments.

Characterization of Natural and Synthetic Sialoglycans Targeting the Hemagglutinin-Neuraminidase of Mumps Virus

The inhibition of surface viral glycoproteins offers great potential to hamper the attachment of viruses to the host cells surface and the spreading of viral infection. Mumps virus (MuV) is the etiological agent of the mumps infectious disease and causes a wide spectrum of mild to severe symptoms due to the inflammation of the salivary glands. Here we focus our attention on the hemagglutinin-neuraminidase (HN) isolated from MuV SBL-1 strain. We describe the molecular features of host sialoglycans recognition by HN protein by means of NMR, fluorescence assays and computational studies. Furthermore, we also describe the synthesis of a N-acetylneuraminic acid-derived thiotrisaccharide targeting the viral protein, and the corresponding 3D-complex. Our results provide the basis to improve the design and synthesis of potent viral hemagglutinin-neuraminidase inhibitors.

Neuraminidase Inhibitors During Pregnancy and Adverse Birth Outcomes: A Meta-Analysis

Neuraminidase inhibitors (NAIs) are commonly used to treat influenza and are also considered the potential treatment for COVID-19. The association of using NAIs during pregnancy with the risk of adverse birth defects has been investigated repeatedly by epidemiological studies; however, results are largely inconsistent. We herein performed this meta-analysis to investigate the true association of NAIs with adverse birth defects, including preterm birth (PTB), low birth weight (LBW), and small for gestational age (SGA). A systematic search was performed through PubMed, Scopus, and Embase to indentify all pertinent studies; The ORs with their corresponding 95% CIs were extracted or calculated. Heterogeneity was assessed using the Cochran Q test and the I2 statistic. A random-effect model was used for this meta-analysis due to existing heterogeneity. Overall, eight studies were included in our analysis, meta-analysis using a random-effect model showed that NAIs during pregnancy reduced the risk of LBW (OR=0.78, 95% CI=0.66–0.91) and SGA (OR=0.76, 95% CI=0.67–0.86) but is not associated with PTB (OR=1.01, 95% CI=0.87–1.16). Results of the present study suggested that NAIs during pregnancy are safe and may reduce the risk of LBW and SGA. However, further studies from different ethnic populations are warranted to confirm our results.

Evaluation of Neuraminidase Inhibitory Activity of Compounds and Extracts from Traditional Medicines by HPLC-FLD

A simple and effective method was established and validated to determine 4-methylumbelliferone (4-MU) for screening the natural neuraminidase inhibitors (NAIs) from traditional medicines (TMs) by high performance liquid chromatography combined with fluorescence detection (HPLC-FLD). 4-MU and TMs compounds were separated on a Hedera TM ODS column (5 μm, 4.6 × 250 mm) using an isocratic elution of 55% methanol at 35°C. The flow rate was 1 mL min−1. The excitation and emission wavelength were performed at 320 nm and 480 nm. Some extracts of TMs and compounds were selected as examples to demonstrate the feasibility of the new HPLC-FLD method. It was found that the results of most compounds except for the auto fluorescence substances determined by HPLC-FLD were in good agreement with NA enzyme-based inhibitory assays. Comparing to traditional NA enzyme-based inhibitory assays, the HPLC-FLD method could prevent interference from fluorescence pigments of compounds. It was considered a simple, effective, and economical technique for the screening the natural neuraminidase inhibitors from traditional medicines.

Characterization of influenza A(H1N1)pdm09 viruses in Germany in season 2019-2020 – co-circulation of an antigenic drift variant

Background Influenza A(H1N1)pdm09 virus entered the human population in 2009 and evolved within this population for more than ten years. Despite genetic evolution no remarkable changes in the antigenic reactive pattern of these viruses were observed so far. Methods Primary respiratory samples of the German influenza virological sentinel were investigated by qPCR. Influenza virus-positive samples were characterized genetically and antigenetically. Results In December 2019, a antigenic drift variant characterized by an N156K substitution in the hemagglutinin of influenza A(H1N1)pdm09 virus emerged in Germany, which exhibited a reactivity to ferret antiserum that was an average 6 log2 lower than the vaccine virus A/Brisbane/02/2018 and the other A(H1N1)pdm09 viruses circulating in the influenza season 2019-2020. These viruses accounted for 20% of all A(H1N1)pdm09 viruses characterized in the German influenza sentinel. Patients infected with these viruses had a shorter median time period of medical consultation after onset of symptoms and were more frequently treated with neuraminidase inhibitors in comparison to patients infected with other A(H1N1)pdm09 viruses. Conclusions This parallel circulation of two antigenic variants of A(H1N1)pdm09 viruses which differ remarkably in their antigenic reactive pattern contributes to a greater variability in circulating influenza viruses and challenges vaccination.