Association of the Interleukin 1B-31*C Proinflammatory Allele with the Severity of COVID-19 Patients: A Preliminary Report.

Individuals with no known comorbidities or risk factors may develop severe coronavirus disease 2019 (COVID-19). The present study assessed the effect of certain host polymorphisms and viral lineage on the severity of COVID-19 among hospitalized patients with no known comorbidities in Mexico. The analysis included 117 unrelated hospitalized patients with COVID-19. Patients were stratified by whether they required intensive care unit (ICU) admission: the ICU group (n = 40) and non-ICU group (n = 77). COVID-19 was diagnosed on the basis of a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcription-polymerase chain reaction (RT-PCR) assay and clinical and radiographic criteria. The presence of the IL1B-31 (T/C) polymorphism was determined for all patients using PCR and nucleotide sequencing. Genotyping of the IL-4 (-590, T/C) and IL-8 (-251, T/A) polymorphisms was performed by the amplification refractory mutation system-PCR method. Genotyping of IL1-RN was performed using PCR. Viral genome sequencing was performed using the ARTIC Network amplicon sequencing protocol using a MinION. Logistic regression analysis identified the carriage of IL-1 B*-31 *C as an independent potential risk factor (odds ratio [OR] = 3.1736, 95% confidence interval [CI] = 1.0748-9.3705, p = 0.0366) for ICU admission and the presence of IL-RN*2 as a protective factor (OR = 0.4371, 95% CI = 0.1935-0.9871, p = 0.0465) against ICU admission. Under the codominant model, the CC genotype of IL1B-31 significantly increased the risk of ICU admission (OR: 6.38, 95% CI: 11.57-25.86, p < 0.024). The IL1B-31 *C-IL-4-590 *T haplotype increased the risk of ICU admission (OR = 2.53, 95% CI = 1.02-6.25, p = 0.047). The 42 SARS-CoV-2 genomes sequenced belonged to four clades, 20A-20D. No association was detected between SARS-CoV-2 clades and ICU admission or death. Thus, in patients with no known comorbidities or risk factors, the IL1B-31*C proinflammatory allele was observed to be associated with the risk of ICU admission owing to COVID-19.

Unraveling the Molecular Mechanisms Involved in HCV-Induced Carcinogenesis.

Cancer induced by a viral infection is among the leading causes of cancer. Hepatitis C Virus (HCV) is a hepatotropic oncogenic positive-sense RNA virus that leads to chronic infection, exposing the liver to a continuous process of damage and regeneration and promoting hepatocarcinogenesis. The virus promotes the development of carcinogenesis through indirect and direct molecular mechanisms such as chronic inflammation, oxidative stress, steatosis, genetic alterations, epithelial-mesenchymal transition, proliferation, and apoptosis, among others. Recently, direct-acting antivirals (DAAs) showed sustained virologic response in 95% of cases. Nevertheless, patients treated with DAAs have reported an unexpected increase in the early incidence of Hepatocellular carcinoma (HCC). Studies suggest that HCV induces epigenetic regulation through non-coding RNAs, DNA methylation, and chromatin remodeling, which modify gene expressions and induce genomic instability related to HCC development that persists with the infection's clearance. The need for a better understanding of the molecular mechanisms associated with the development of carcinogenesis is evident. The aim of this review was to unravel the molecular pathways involved in the development of carcinogenesis before, during, and after the viral infection's resolution, and how these pathways were regulated by the virus, to find control points that can be used as potential therapeutic targets.

Development of a Rapid Gold Nanoparticle-Based Lateral Flow Immunoassay for the Detection of Dengue Virus.

Flavivirus detection in humans and mosquito reservoirs has been an important issue since it can cause a variety of illnesses and could represent a health problem in geographical zones where the vector is endemic. In this work, we designed and characterized a biosensor based on gold nanoparticles (AuNPs) and antibody 4G2 for the detection of dengue virus (DENV) in vitro, obtaining different conjugates (with different antibody concentrations). The AuNP-4G2 conjugates at concentrations of 1, 3, and 6 µg/mL presented an increase in the average hydrodynamic diameter compared to the naked AuNPs. Also, as part of the characterization, differences in the UV-Vis absorbance spectrum and electrophoretic migration were observed between the conjugated AuNPs (with BSA or antibody) and naked AuNPs. Additionally, we used this biosensor (AuNP-4G2 conjugate with 3 µg/mL antibody) in the assembly of a competitive lateral flow assay (LFA) for the development of an alternative test to detect the flavivirus envelope protein in isolated DENV samples as a future tool for dengue detection (and other flaviviruses) in the mosquito vector (Aedesaegypti) for the identification of epidemic risk regions. Functionality tests were performed using Dengue virus 2 isolated solution (TCID50/mL = 4.58 × 103) as a positive sample and PBS buffer as a negative control. The results showed that it is possible to detect Dengue virus in vitro with this gold nanoparticle-based lateral flow assay with an estimated detection limit of 5.12 × 102 PFU. We suggest that this biosensor could be used as an additional detection tool by coupling it to different point-of-care tests (POCT) for the easy detection of other flaviviruses.

Prevalence of SARS-CoV-2 Variants of Concern and Variants of Interest in COVID-19 Breakthrough Infections in a Hospital in Monterrey, Mexico.

SARS-CoV-2 variants of concern (VOCs) or of interest (VOIs) causing vaccine breakthrough infections pose an increased risk to worldwide public health. An observational case-control study was performed of SARS-CoV-2 vaccine breakthrough infections in hospitalized or ambulatory patients in Monterrey, Mexico, from April through August 2021. Vaccination breakthrough was defined as a SARS-CoV-2 infection that occurred any time after 7 days of inoculation with partial (e.g., first dose of two-dose vaccines) or complete immunization (e.g., second dose of two-dose vaccines or single-dose vaccine, accordingly). Case group patients (n = 53) had partial or complete vaccination schemes with CanSino (45%), Sinovac (19%), Pfizer/BioNTech (15%), and AstraZeneca/Oxford (15%). CanSino was administered most frequently in ambulatory patients (p < 0.01). The control group (n = 19) received no COVID-19 vaccines. Among SARS-CoV-2 variants detected by whole-genome sequencing, VOC Delta B.1.617.2 predominated in vaccinated ambulatory patients (p < 0.01) and AY.4 in hospitalized patients (p = 0.04); VOI Mu B.1.621 was detected in four (7.55%) vaccinated patients. SARS-CoV-2 breakthrough infections in our hospital occurred mostly in patients vaccinated with CanSino due to the higher prevalence of CanSino vaccine administration in our population. These patients developed mild COVID-19 symptoms not requiring hospitalization. The significance of this study lies on the detection of SARS-CoV-2 variants compromising the efficacy of local immunization therapies in Monterrey, Mexico.

Determinants of COVID-19 Vaccine Hesitancy: A Cross-Sectional Study on a Mexican Population Using an Online Questionnaire (COV-AHQ).

Mexico has become one of the most highly affected countries by coronavirus disease 2019 (COVID-19) pandemic in Latin America. Therefore, efficient vaccination programs are needed to address COVID-19 pandemic. Although recent advances around the world have made it possible to develop vaccines in record time, there has been increasing fear and misinformation around the vaccines. Hence, understanding vaccine hesitancy is imperative for modeling successful vaccination strategies. In this study, we analyzed the attitude and perceptions toward COVID-19 vaccination, in a Mexican population (n = 1,512), using the proposed COVID-19 Vaccine Acceptance and Hesitancy Questionnaire (COV-AHQ) (Cronbach's alpha > 0.8), which evaluates a mild perception of danger and contamination with respect to COVID-19, a moderate perception of xenophobia generated throughout COVID-19 quarantine, fear of adverse effects of COVID-19 vaccination, and hesitancy of parent toward vaccination of children; furthermore, a section including sociodemographic variables was included. According to the results of this study, the statistical correlation analysis of the general vaccination posture seems to correlate significantly (p < 0.05) with a mild perception of danger and contamination with respect to COVID-19, a moderate perception of xenophobia generated throughout COVID-19 quarantine, hesitancy of parent toward vaccination of children, willingness to get COVID-19 vaccine, previous influenza vaccination, perception of the vaccine that could help the economy of country, occupation, gender, age, and participants actively researching COVID-19 vaccine information. An in-depth analysis assisted by binary logistic regression concluded that the young adult population around ages 18-34 years are the most likely to get vaccinated. This posture seems to be highly influenced by a mild perception of danger and contamination with respect to COVID-19, a moderate perception of xenophobia generated throughout COVID-19 quarantine, fear of adverse effects of COVID-19 vaccination, and hesitancy of parents toward vaccination of children. While their own personal religious beliefs and economic status, the level of education does not seem to have an effect on the willingness to get vaccinated neither did having a previous COVID-19 diagnosis or even knowing someone with a positive COVID-19 diagnosis. Health authorities and policymakers could use the results of this study to aid in modeling vaccination programs and strategies and identify population groups with high vaccine hesitancy prevalence and assess significant public health issues.

Seroprevalence of Anti-SARS-CoV-2 Antibodies in Blood Donors from Nuevo Leon State, Mexico, during 2020: A Retrospective Cross-Sectional Evaluation.

The progression and distribution of the SARS-CoV-2 pandemic are continuously changing over time and can be traced by blood donors' serological survey. Here, we investigated the seroprevalence of anti-SARS-CoV-2 antibodies in blood donors in Nuevo Leon, Mexico during 2020 as a strategy for the rapid evaluation of the spread of SARS-CoV-2 and asymptomatic case detection. We collected residual plasma samples from blood donors who attended two regional donation centers from January to December of 2020 to identify changes in anti-SARS-CoV-2 IgG prevalence. Plasma samples were analyzed on the Abbott Architect instrument using the commercial Abbott SARS-CoV-2 IgG chemiluminescent assay. We found a total of 99 reactive samples from 2068 analyzed plasma samples, resulting in a raw prevalence of 4.87%. Donors aged 18-49 years were more likely to be seropositive compared to those aged >50 years (p < 0.001). Weekly seroprevalence increased from 1.8% during the early pandemic stage to 27.59% by the end of the year. Prevalence was 1.46-fold higher in females compared to males. Case geographical mapping showed that Monterrey city recorded the majority of SARS-CoV-2 cases. These results show that there is a growing trend of seroprevalence over time associated with asymptomatic infection that is unnoticed under the current epidemiological surveillance protocols.

Inflammatory effect on the gastrointestinal system associated with COVID-19.

The severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) that causes coronavirus disease-2019 (COVID-19) has provoked a global pandemic, mainly affecting the respiratory tract; however, a percentage of infected individuals can develop gastrointestinal (GI) symptoms. Some studies describe the development of GI symptoms and how they affect the progression of COVID-19. In this review, we summarize the main mechanisms associated with gut damage during infection by SARS-CoV-2 as well as other organs such as the liver and pancreas. Not only are host factors associated with severe COVID-19 but intestinal microbiota dysbiosis is also observed in patients with severe disease.

Teaching Anxiety, Stress and Resilience During the COVID-19 Pandemic: Evaluating the Vulnerability of Academic Professionals in Mexico Through the Adapted COVID-19 Stress Scales.

To mitigate the COVID-19 infection, many world governments endorsed the cessation of non-essential activities, such as the school attendance, forcing a shift of the teaching model to the virtual classroom. From this shift, several changes in the teaching paradigm derived, in addition to the COVID-19 pandemic, which could have an impact in academic professional's mental health. In the present work we show the application of a modified version of the adapted COVID-19 stress scales (ACSS) which also included teaching anxiety and preparedness, and resilience for academic professionals in Mexico. These scales were applied during the unprecedented transformation of the education system undergone in the COVID-19 quarantine. Most of the studied variables: gender, age, academic degree, household occupants, having a disease, teaching level, teaching mode, work hours, resilience, teaching anxiety and preparedness, and fear of being an asymptomatic patient (FOBAP), showed significant statistical correlation between each other (p < 0.050) and to the 6 areas of the ACSS (danger, contamination, social economical, xenophobia, traumatic stress, and compulsive checking). Our results further showed that the perceived stress and anxiety fell into the category of Absent to Mild, with only the danger section of the ACSS falling into the Moderate category. Finally, the resilience generated throughout the quarantine was very high, which seems to be a predictor of adaptation the academic professional has undergone to cope with stress.

Decline in influenza cases in Mexico after the implementation of public health measures for COVID-19.

Mexico took swift action and has strictly followed mitigation measures to prevent the spread of coronavirus disease, COVID-19. In this study we compared influenza activity indicators in our country after the implementation of public health measures for COVID-19. We compared indicators of influenza activity in 2020 before and after public health measures were taken to reduce COVID-19 with the corresponding indicators from three preceding years and the immediate one, and the potential decrease in seasonal influenza cases/deaths. Nationwide surveillance data revealed a drastic decline in influenza diagnosis in outpatient clinics and public hospitals, influenza positivity rates of clinical specimens, and confirmed severe cases during the following 10 weeks of 2020 as lockdown activities and control measures were established compared with the same period of 2019. Our results suggest that the measures taken for COVID-19 were effective in reducing the spread of other viral respiratory diseases as influenza in our country.

SARS-CoV-2 in Mexico: Beyond Detection Methods, Scope and Limitations.

The new coronavirus that was first identified in December 2019 in Wuhan China, now called SARS-CoV-2, which causes the disease called COVID-19, has spread from China to the entire world in a few months. Due to its contagious potential (R0: 5.7) and because there is still no effective treatment to stop the infection, and a vaccine for prevention it is not yet available to the general population, COVID-19 is currently considered a global health problem. The need to implement sensitive methods for the identification of individuals with COVID-19 has led to the development of different molecular and immunological tests. The importance of a timely and accurate diagnosis is essential to determine the course of the pandemic. The interpretation of the results obtained by each test as well as the factors that affect these results have not been fully described. In this review, we describe and analyze the different SARS-CoV-2 detection methods that have been performed in Mexico and are available worldwide, outlining their strengths and weaknesses. Further, a broader perspective of the correct use and interpretation of the results obtained with these diagnostic tools is proposed to improve the containment strategy and identify the true impact of the pandemic.

Parent's Perspective towards Child COVID-19 Vaccination: An Online Cross-Sectional Study in Mexico.

COVID-19 vaccination programs continue in child populations. Thus, parents' attitude towards COVID-19 vaccination of their children is crucial for these strategies to succeed. The present study derives from the application of an online COVID-19 Vaccine Acceptance & Hesitancy Questionnaire (COV-AHQ) in which we measure parent's hesitancy towards children's vaccination (section 4 of the COV-AHQ) and other significant factors. A logistic regression analysis with backward stepwise method was used to quantify the associations between factors and parent's hesitancy. According to the correlation analysis, the most representative factors predicting vaccine hesitancy/acceptance were positive attitude towards vaccination, parents believing that the COVID-19 vaccine will enhance the economic situation of the country, parents actively researching information, having the willingness to obtain the COVID-19 vaccine themselves, and the possibility of their children developing adverse effects. Our findings also showed that parents are highly interested in having their children vaccinated. Nonetheless, parents expressed high levels of concern involving their children in developing adverse effects from the vaccine. In addition, obtaining influenza immunization prompted interest in obtaining the COVID-19 vaccine, and younger-aged parents are much more concerned with having their children vaccinated. Therefore, in order to ensure successful vaccination programs, policymakers and health authorities should design strategies to gain confidence and provide security amongst the population, including giving continuous information about the benefits of vaccination and presenting the frequency of side effects to bring parents on board with vaccinating their children.

SARS-CoV-2 another kind of liver aggressor, how does it do that?

Clinical manifestations of SARS-CoV-2 infection include more frequently fever and cough, but complications (such as pneumonia, respiratory distress syndrome, and multiorgan failure) can occur in persons with additional comorbidities. Liver dysfunction is one of the most striking affections among patients suggesting that SARS-CoV-2 may represent a new king of liver aggressor. However, the molecular process underlying this phenomenon is still unclear. In this work, we overview the most recent findings between the molecular biology of the virus, pathogenic mechanisms, and its relationship to liver disease observed in patients.

The anti­dengue virus properties of statins may be associated with alterations in the cellular antiviral profile expression.

Dengue virus (DENV) susceptibility to cholesterol depleting treatments has been previously reported. There are numerous questions regarding how DENV seizes cellular machinery and cholesterol to improve viral production and the effect of cholesterol sequestering agents on the cellular antiviral response. The aim of the present study was to evaluate the mechanisms involved in the negative regulation of DENV replication induced by agents that diminish intracellular cholesterol levels. Cholesterol synthesis was pharmacologically (fluvastatin, atorvastatin, lovastatin, pravastatin and simvastatin treatment) and genetically (HMGCR­RNAi) inhibited, in uninfected and DENV2­infected hepatoma Huh­7 cells. The cholesterol levels, DENV titer and cellular antiviral expression profile were evaluated. A reduction in the DENV titer, measured as plaque forming units, was observed in DENV­infected cells following 48 h treatment with 10 µM fluvastatin, 10 µM atorvastatin, 20 µM lovastatin and 20 µM simvastatin, which achieved 70, 70, 65 and 55% DENV2 inhibition, respectively, compared with the untreated cells. In addition, the cytopathic effect was reduced in the statin­treated DENV­infected cells. Statins simultaneously reduced cholesterol levels at 48 h, with the exception of DENV2 infected cells. Genetic inhibition of cholesterol synthesis was performed using RNA interference for 3­hydroxy­3­methylglutaryl­CoA reductase (HMGCR­siRNA), which indicated a slight reduction in DENV2 titer at 48 h post­infection, however, with no significant reduction in cholesterol levels. In addition, DENV2 infection was observed to augment the intracellular cholesterol levels in all experimental conditions. Comparison between the cellular antiviral response triggered by DENV2 infection, statin treatment and HMGCR­siRNA in infected, uninfected, treated and untreated Huh7 cells, showed different expression profiles for the antiviral genes evaluated. All downregulating cholesterol agents evaluated reduced the expression of genes associated with cellular immune and pro­inflammatory responses. These results indicate that statin-mediated downregulation of DENV2 infectious particles number is independent of cholesterol levels and it is partially mediated by the modulation of the cellular antiviral profile.