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Background Coronavirus disease 2019 (COVID-19) has created the need to evaluate drugs such as favipiravir (FPV), an antiviral inhibitor of RNA-dependent RNA-polymerase (RdRp), and Maraviroc (MVC), an antiretroviral that antagonizes the chemokine receptor CCR5, which could affect the modulation of inflammation and viral replication in the treatment of COVID-19. We sought to evaluate the effect of MVC and/or FPV plus systemic steroid (SS) vs. SS alone on the viral load and progression to critical disease. Methods Sixteen patients with severe COVID-19 were evaluated in three treatment arms: 1) SS only (n=6), 2) SS plus one test drug MVC or FPV (n=5), and 3) SS plus both test drugs (MVC and FPV, n=5). The viral load was determined for N, E, and RdRp viral genes. Results A significant decrease in viral load was observed in the three treatment groups, with a larger effect size in the group that combined SS with both test drugs. The E, N, and RdRp genes with Cohen’s d were 120%, 123%, and 50%, respectively. Conclusions The largest effect on viral load reduction, as measured by effect size, was observed in the combination treatment group; however, no statistical significance was found, and it did not prevent progression to critical illness.

Background Coronavirus disease 2019 (COVID-19) has created the need to evaluate drugs such as favipiravir (FPV), an antiviral inhibitor of RNA-dependent RNA-polymerase (RdRp), and Maraviroc (MVC), an antiretroviral that antagonizes the chemokine receptor CCR5, which could affect the modulation of inflammation and viral replication in the treatment of COVID-19. We sought to evaluate the effect of MVC and/or FPV plus systemic steroid (SS) vs. SS alone on the viral load and progression to critical disease. Methods Sixteen patients with severe COVID-19 were evaluated in three treatment arms: 1) SS only (n=6), 2) SS plus one test drug MVC or FPV (n=5), and 3) SS plus both test drugs (MVC and FPV, n=5). The viral load was determined for N, E, and RdRp viral genes. Results A significant decrease in viral load was observed in the three treatment groups, with a larger effect size in the group that combined SS with both test drugs. The E, N, and RdRp genes with Cohen’s d were 120%, 123%, and 50%, respectively. Conclusions The largest effect on viral load reduction, as measured by effect size, was observed in the combination treatment group; however, no statistical significance was found, and it did not prevent progression to critical illness.

Abstract Background COVID-19 was initially described as a severe acute respiratory disease that could drive to pneumonia, compromising the life of the patients in the worst scenario. However, even though in most of the cases the respiratory symptoms are still the most common manifestations of the disease, nowadays it is considered as a complex multisystem illness, affecting a variety of organs and tissues. Asymptomatic and atypic cases have also been described, where symptoms are not related to those first described, as is the case of this report. Case presentation On November 23, 2020, a 53-year-old woman goes to the emergency room due to gastrointestinal symptoms. The admission diagnosis was inflammatory bowel disease and a mild event of idiopathic chronic ulcerative colitis, and the initial treatment was focused on the metabolic acidosis, and the reestablishment the hydroelectrolytic and hemodynamic balance. Then, she was transferred to the Gastroenterology Unit where she was treated for one week. During her hospitalization, she showed a refractory shock caused by progressive organ deterioration (renal and neurological), requiring a double-vasopressor support, oxygenation, and ventilation. Considering the laboratory tests results and computed tomography scans, a COVID-19 test was carried out, obtaining a positive result with a high viral load. The S gene of the virus was amplified and sequenced, finding an uncommon mutation rarely reported worldwide. After considerable systemic deterioration, the patient presented cardiorespiratory arrest, with no response and died on December 1, after 8 days of hospitalization. Conclusions In this report we describe the pathogenesis, clinical manifestations, and outcome of a patient with atypical COVID-19 symptoms (mainly gastrointestinal), rapidly evolving and with lethal consequences. Therefore, it is important to emphasize the need to strengthen patient surveillance in health centers, including those who do not present typical symptoms of COVID-19. In addition, it will be important to track the identified mutation (H1058Y) in the S viral gene and assess whether it could be associated with a different clinical manifestation of the disease or if it was just an isolated event.

Background: Phase III clinical trials have documented the efficacy of the SARS-CoV-2 vaccines in preventing symptomatic COVID-19. Nonetheless, it is imperative to continue analyzing the clinical response to different vaccines in real-life studies. Our objective was to evaluate the effectiveness of five different vaccines in hospitalized patients with COVID-19 during the third COVID-19 outbreak in Mexico dominated by the Delta variant. Methods: A test-negative case–control study was performed in nine tertiary-care hospitals for COVID-19. We estimated odds ratios (OR) adjusted by variables related a priori with the likelihood of SARS-CoV-2 infection and its severity. Results: We studied 761 subjects, 371 cases, and 390 controls with a mean age of 53 years (SD, 17 years). Overall, 51% had a complete vaccination scheme, and an incomplete scheme (one dose from a scheme of two), 14%. After adjustment for age, gender, obesity, and diabetes mellitus, we found that the effectiveness of avoiding a SARS-CoV-2 infection when hospitalized with at least one vaccination dose was 71% (OR 0.29, 95% CI 0.19–0.45), that of an incomplete vaccination scheme, 67% (OR 0.33, 95% CI 0.18–0.62), and that of any complete vaccination scheme, 73% (OR 0.27, 95% CI 0.17–0.43). Conclusions: The SARS-CoV-2 vaccination program showed effectiveness in preventing SARS-CoV-2 infection in hospitalized patients during a Delta variant outbreak.

Influenza has been a stationary disease in Mexico since 2009, and this causes a high cost for the national public health system, including its detection using RT-qPCR tests, treatments, and absenteeism in the workplace. Despite influenza’s relevance, the main clinical features to detect the disease defined by international institutions like the World Health Organization (WHO) and the United States Centers for Disease Control and Prevention (CDC) do not follow the same pattern in all populations. The aim of this work is to find a machine learning method to facilitate decision making in the clinical differentiation between positive and negative influenza patients, based on their symptoms and demographic features. The research sample consisted of 15480 records, including clinical and demographic data of patients with a positive/negative RT-qPCR influenza tests, from 2010 to 2020 in the public healthcare institutions of Mexico City. The performance of the methods for classifying influenza cases were evaluated with indices like accuracy, specificity, sensitivity, precision, the f1-measure and the area under the curve (AUC). Results indicate that random forest and bagging classifiers were the best supervised methods; they showed promise in supporting clinical diagnosis, especially in places where performing molecular tests might be challenging or not feasible.

The cyclin-dependent kinase inhibitor 3 (CDKN3) gene, involved in mitosis, is upregulated in cervical cancer (CC). We investigated CDKN3 mRNA as a survival biomarker and potential therapeutic target for CC. CDKN3 mRNA was measured in 134 CC and 25 controls by quantitative PCR. A 5-year survival study was conducted in 121 of these CC patients. Furthermore, CDKN3-specific siRNAs were used to investigate whether CDKN3 is involved in proliferation, migration, and invasion in CC-derived cell lines (SiHa, CaSki, HeLa). CDKN3 mRNA was on average 6.4-fold higher in tumors than in controls (p = 8 x 10-6, Mann-Whitney). A total of 68.2% of CC patients over expressing CDKN3 gene (fold change ≥ 17) died within two years of diagnosis, independent of the clinical stage and HPV type (Hazard Ratio = 5.0, 95% CI: 2.5-10, p = 3.3 x 10-6, Cox proportional-hazards regression). In contrast, only 19.2% of the patients with lower CDKN3 expression died in the same period. In vitro inactivation of CDKN3 decreased cell proliferation on average 67%, although it had no effect on cell migration and invasion. CDKN3 mRNA may be a good survival biomarker and potential therapeutic target in CC.

We investigated the role of tumor copy number (CN)-altered genome (CN-AG) in the carcinogenesis of cervical cancer (CC), especially its effect on gene expression, biological processes, and patient survival. Fifty-nine human papillomavirus 16 (HPV16)-positive CCs were investigated with microarrays-31 for mapping CN-AG and 55 for global gene expression, with 27 CCs in common. Five-year survival was investigated in 55 patients. Deletions and amplifications >2.5 Mb were defined as CN alterations. The %CN-AG varied from 0 to 32.2% (mean = 8.1±8.9). Tumors were classified as low (mean = 0.5±0.6, n = 11), medium (mean = 5.4±2.4, n = 10), or high (mean = 19.2±6.6, n = 10) CN. The highest %CN-AG was found in 3q, which contributed an average of 55% of all CN alterations. Genome-wide, only 5.3% of CN-altered genes were deregulated directly by gene dosage. In contrast, the rate in fully duplicated 3q was twice as high. Amplification of 3q explained 23.2% of deregulated genes in whole tumors (r2 = 0.232, p = 0.006; analysis of variance), including genes located in 3q and other chromosomes. A total of 862 genes were deregulated exclusively in high-CN tumors, but only 22.9% were CN altered. This suggests that the remaining genes are not deregulated directly by gene dosage, but by mechanisms induced in trans by CN-altered genes. Anaphase-promoting complex/cyclosome (APC/C)-dependent proteasome proteolysis, glycolysis, and apoptosis were upregulated, whereas cell adhesion and angiogenesis were downregulated exclusively in high-CN tumors. The high %CN-AG and upregulated gene expression profile of APC/C-dependent proteasome proteolysis were associated with poor patient survival (p0.38, p

Several copy number-altered regions (CNAs) have been identified in the genome of cervical cancer, notably, amplifications of 3q and 5p. However, the contribution of copy-number alterations to cervical carcinogenesis is unresolved because genome-wide there exists a lack of correlation between copy-number alterations and gene expression. In this study, we investigated whether CNAs in the cell lines CaLo, CaSki, HeLa, and SiHa were associated with changes in gene expression. On average, 19.2% of the cell-line genomes had CNAs. However, only 2.4% comprised minimal recurrent regions (MRRs) common to all the cell lines. Whereas 3q had limited common gains (13%), 5p was entirely duplicated recurrently. Genome-wide, only 15.6% of genes located in CNAs changed gene expression; in contrast, the rate in MRRs was up to 3 times this. Chr 5p was confirmed entirely amplified by FISH; however, maximum 33.5% of the explored genes in 5p were deregulated. In 3q, this rate was 13.4%. Even in 3q26, which had 5 MRRs and 38.7% recurrently gained SNPs, the rate was only 15.1%. Interestingly, up to 19% of deregulated genes in 5p and 73% in 3q26 were downregulated, suggesting additional factors were involved in gene repression. The deregulated genes in 3q and 5p occurred in clusters, suggesting local chromatin factors may also influence gene expression. In regions amplified discontinuously, downregulated genes increased steadily as the number of amplified SNPs increased (p

Throughout the early stages of the COVID-19 pandemic in Mexico (August—December 2020), we closely followed a cohort of n = 100 healthcare workers. These workers were initially seronegative for Immunoglobulin G (IgG) antibodies against SARS-CoV-2, the virus that causes COVID-19, and maintained close contact with patients afflicted by the disease. We explored the database of demographic, physiological and laboratory parameters of the cohort recorded at baseline to identify potential risk factors for infection with SARS-CoV-2 at a follow-up evaluation six months later. Given that susceptibility to infection may be a systemic rather than a local property, we hypothesized that a multivariate statistical analysis, such as MANOVA, may be an appropriate statistical approach. Our results indicate that susceptibility to infection with SARS-CoV-2 is modulated by sex. For men, different physiological states appear to exist that predispose to or protect against infection, whereas for women, we did not find evidence for divergent physiological states. Intriguingly, male participants who remained uninfected throughout the six-month observation period, had values for mean arterial pressure and waist-to-hip ratio that exceeded the normative reference range. We hypothesize that certain risk factors that worsen the outcome of COVID-19 disease, such as being overweight or having high blood pressure, may instead offer some protection against infection with SARS-CoV-2. [ABSTRACT FROM AUTHOR]

Background: Phase III clinical trials have documented the efficacy of the SARS-CoV-2 vaccines in preventing symptomatic COVID-19. Nonetheless, it is imperative to continue analyzing the clinical response to different vaccines in real-life studies. Our objective was to evaluate the effectiveness of five different vaccines in hospitalized patients with COVID-19 during the third COVID-19 outbreak in Mexico dominated by the Delta variant. Methods: A test-negative case–control study was performed in nine tertiary-care hospitals for COVID-19. We estimated odds ratios (OR) adjusted by variables related a priori with the likelihood of SARS-CoV-2 infection and its severity. Results: We studied 761 subjects, 371 cases, and 390 controls with a mean age of 53 years (SD, 17 years). Overall, 51% had a complete vaccination scheme, and an incomplete scheme (one dose from a scheme of two), 14%. After adjustment for age, gender, obesity, and diabetes mellitus, we found that the effectiveness of avoiding a SARS-CoV-2 infection when hospitalized with at least one vaccination dose was 71% (OR 0.29, 95% CI 0.19–0.45), that of an incomplete vaccination scheme, 67% (OR 0.33, 95% CI 0.18–0.62), and that of any complete vaccination scheme, 73% (OR 0.27, 95% CI 0.17–0.43). Conclusions: The SARS-CoV-2 vaccination program showed effectiveness in preventing SARS-CoV-2 infection in hospitalized patients during a Delta variant outbreak. [ABSTRACT FROM AUTHOR]

Influenza has been a stationary disease in Mexico since 2009, and this causes a high cost for the national public health system, including its detection using RT-qPCR tests, treatments, and absenteeism in the workplace. Despite influenza's relevance, the main clinical features to detect the disease defined by international institutions like the World Health Organization (WHO) and the United States Centers for Disease Control and Prevention (CDC) do not follow the same pattern in all populations. The aim of this work is to find a machine learning method to facilitate decision making in the clinical differentiation between positive and negative influenza patients, based on their symptoms and demographic features. The research sample consisted of 15480 records, including clinical and demographic data of patients with a positive/negative RT-qPCR influenza tests, from 2010 to 2020 in the public healthcare institutions of Mexico City. The performance of the methods for classifying influenza cases were evaluated with indices like accuracy, specificity, sensitivity, precision, the f1-measure and the area under the curve (AUC). Results indicate that random forest and bagging classifiers were the best supervised methods; they showed promise in supporting clinical diagnosis, especially in places where performing molecular tests might be challenging or not feasible. [ABSTRACT FROM AUTHOR]

Introduction: Patients with cervical cancer (CC) may experience local recurrence very often after treatment; when only clinical parameters are used, most cases are diagnosed in late stages, which decreases the chance of recovery. Molecular markers can improve the prediction of clinical outcome. Glycolysis is altered in 70% of CCs, so molecular markers of this pathway associated with the aggressiveness of CC can be identified. Methods: The expression of 14 glycolytic genes was analyzed in 97 CC and 29 healthy cervical tissue (HCT) with microarray; only LDHA and PFKP were validated at the mRNA and protein levels in 36 of those CC samples and in 109 new CC samples, and 31 HCT samples by qRT–PCR, Western blotting, or immunohistochemistry. A replica analysis was performed on 295 CC from The Cancer Genome Atlas (TCGA) database. Results: The protein expression of LDHA and PFKP was associated with poor overall survival [OS: LDHA HR = 4.0 (95% CI = 1.4–11.1); p = 8.0 × 10−3; PFKP HR = 3.3 (95% CI = 1.1–10.5); p = 4.0 × 10−2] and disease‐free survival [DFS: LDHA HR = 4.5 (95% CI = 1.9–10.8); p = 1.0 × 10−3; PFKP HR = 3.2 (95% CI = 1.2–8.2); p = 1.8 × 10−2] independent of FIGO clinical stage, and the results for mRNA expression were similar. The risk of death was greater in patients with overexpression of both biomarkers than in patients with advanced FIGO stage [HR = 8.1 (95% CI = 2.6–26.1; p = 4.3 × 10−4) versus HR = 7 (95% CI 1.6–31.1, p = 1.0 × 10−2)] and increased exponentially as the expression of LDHA and PFKP increased. Conclusions: LDHA and PFKP overexpression at the mRNA and protein levels was associated with poor OS and DFS and increased risk of death in CC patients regardless of FIGO stage. The measurement of these two markers could be very useful for evaluating clinical evolution and the risk of death from CC and could facilitate better treatment decision making. [ABSTRACT FROM AUTHOR]

Background: COVID-19 was initially described as a severe acute respiratory disease that could drive to pneumonia, compromising the life of the patients in the worst scenario. However, even though in most of the cases the respiratory symptoms are still the most common manifestations of the disease, nowadays it is considered as a complex multisystem illness, affecting a variety of organs and tissues. Asymptomatic and atypic cases have also been described, where symptoms are not related to those first described, as is the case of this report. Case presentation: On November 23, 2020, a 53-year-old woman goes to the emergency room due to gastrointestinal symptoms. The admission diagnosis was inflammatory bowel disease and a mild event of idiopathic chronic ulcerative colitis, and the initial treatment was focused on the metabolic acidosis, and the reestablishment the hydroelectrolytic and hemodynamic balance. Then, she was transferred to the Gastroenterology Unit where she was treated for one week. During her hospitalization, she showed a refractory shock caused by progressive organ deterioration (renal and neurological), requiring a double-vasopressor support, oxygenation, and ventilation. Considering the laboratory tests results and computed tomography scans, a COVID-19 test was carried out, obtaining a positive result with a high viral load. The S gene of the virus was amplified and sequenced, finding an uncommon mutation rarely reported worldwide. After considerable systemic deterioration, the patient presented cardiorespiratory arrest, with no response and died on December 1, after 8 days of hospitalization. Conclusions: In this report we describe the pathogenesis, clinical manifestations, and outcome of a patient with atypical COVID-19 symptoms (mainly gastrointestinal), rapidly evolving and with lethal consequences. Therefore, it is important to emphasize the need to strengthen patient surveillance in health centers, including those who do not present typical symptoms of COVID-19. In addition, it will be important to track the identified mutation (H1058Y) in the S viral gene and assess whether it could be associated with a different clinical manifestation of the disease or if it was just an isolated event. [ABSTRACT FROM AUTHOR]

Throughout the entire coronavirus disease 19 (COVID-19) pandemic, there were disruptions in the supply chain of test materials around the world, primarily in poor- and middle-income countries. The use of 3D prints is an alternative to address swab supply shortages. In this study, the feasibility of the clinical use of 3D-printed swabs for oropharyngeal and nasopharyngeal sampling for the detection of SARS-CoV-2 infection was evaluated. For that purpose, paired samples with the 3D printed and the control swabs were taken from 42 adult patients and 10 pediatric patients, and the results obtained in the detection of SARS-CoV-2 by reverse transcription and quantitative polymerase chain reaction (RT-qPCR) were compared. Additionally, in those cases where the result was positive for SARS-CoV-2, the viral load was calculated by means of a mathematical algorithm proposed by us. For both adults and children, satisfactory results were obtained in the detection of SARS-CoV-2 by RT-qPCR; no significant differences were found in the quantification cycle values between the 3D-printed swab samples and the control samples. Furthermore, we corroborated that the 3D-printed swabs caused less discomfort and pain at the time of sampling. In conclusion, this study shows the feasibility of routinely using 3D-printed swabs for both adults and children. In this way, it is possible to maintain local and cheaper consumption along with fewer distribution difficulties. [ABSTRACT FROM AUTHOR]

Health care workers (HCW) are at high risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The incidence of SARS-CoV-2 infection in HCW has been examined in cross-sectional studies by quantitative polymerase chain reaction (qPCR) tests, which may lead to underestimating exact incidence rates. We thus investigated the incidence of SARS-CoV-2 infection in a group of HCW at a dedicated coronavirus disease 2019 (COVID-19) hospital in a six-month follow-up period. We conducted a prospective cohort study on 109 participants of both sexes working in areas of high, moderate, and low SARS-CoV-2 exposure. qPCR tests in nasopharyngeal swabs and anti-SARS-CoV-2 IgG serum antibodies were assessed at the beginning and six months later. Demographic, clinical, and laboratory parameters were analyzed according to IgG seropositivity by paired Student's T-test or the chi-square test. The incidence rate of SARS-CoV-2 infection was considerably high in our cohort of HCW (58%), among whom 67% were asymptomatic carriers. No baseline risk factors contributed to the infection rate, including the workplace. It is still necessary to increase hospital safety procedures to prevent virus transmissibility from HCW to relatives and non-COVID-19 patients during the upcoming waves of contagion. [ABSTRACT FROM AUTHOR]