Neutralizing antibody responses to the Delta variant of SARS-CoV-2 following vaccination with Ad5-nCoV (CanSino) in the Mexican population.

During the COVID-19 pandemic, the Ad5-nCoV vaccine was applied to the Mexican population before the WHO approved it. In a transversal study, we compare the CanSino vaccine efficacy and a natural SARS-CoV-2 infection in eliciting neutralizing antibodies against the SARS-CoV-2 Delta variant in Guadalajara, Mexico. Participants between 30-60 years were included in the study and classified into three groups: 1) Natural immunity (unvaccinated), 2) Vaccine-induced immunity (vaccinated individuals without a COVID-19 history), and 3) Natural immunity + vaccine-induced immunity. These groups were matched by age and gender. We assessed the ability of individuals' serum to neutralize the Delta variant and compared the results of the different groups using a neutralization test followed by plaque-forming units. Results showed that 39% of individuals' serum with a history of COVID-19 (natural immunity, Group 1) could not neutralize the Delta variant, compared to 33% in vaccinated individuals without COVID-19 (vaccine immunity, Group 2). In contrast, only 7% of vaccinated individuals with a history of COVID-19 (natural + vaccine immunities) could not neutralize the Delta variant. We concluded that the effectiveness of the Ad5-nCoV vaccine to induce neutralizing antibodies against the Delta variant is comparable to that of natural infection (61% vs. 67%). However, in individuals with both forms of immunity (Group 3), it increased to 93%. Based on these results, despite the Ad5-nCoV vaccine originally being designed as a single-dose regimen, it could be recommended that even those who have recovered from COVID-19 should consider vaccination to boost their immunity against this variant.

Seroprevalence of IgM/IgG and Neutralizing Antibodies against SARS-CoV-2 in Unvaccinated Young Adults from Mexico Who Reported Not Having Had a Previous COVID-19 Infection.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus that causes coronavirus disease 2019 (COVID-19). It is estimated that more than half of new infections are transmitted by asymptomatic people; therefore, the isolation of symptomatic people is not enough to control the spread of the disease. Methods: A total of 171 unvaccinated young adults (18-35 years) from Sonora, Mexico, who underwent a structured survey to identify prior COVID-19 infections, were included in this study. A qualitative determination of anti-SARS-CoV-2 antibodies in serum was performed by lateral flow immunoassay (Certum IgG/IgM Rapid Test™ cassette kit) and neutralizing antibodies were also determined (GenScript cPass assay). Results: A total of 36 people reported a history of COVID-19 infection, and 135 reported no history of COVID-19. In contrast, 49.6% (67/135) of individuals who had not reported a previous SARS-CoV-2 infection were seropositive to the rapid anti-SARS-CoV-2 antibody test, and 48.1% (65/135) of them had neutralizing antibodies. Conclusions: These results suggest that in young adults, SARS-CoV-2 infections could be asymptomatic in a high percentage of individuals, which could contribute in part to the slow control of the current pandemic due to the large number of asymptomatic cases that are contagious and that could be a silent spread of the virus.

Aberrant B-cell activation and B-cell subpopulations in rheumatoid arthritis: analysis by clinical activity, autoantibody seropositivity, and treatment.

Few studies analyze the role of B-cell subpopulations in rheumatoid arthritis (RA) pathophysiology. Therefore, this study aimed to analyze the differences in B-cell subpopulations and B-cell activation according to disease activity, RA subtype, and absence of disease-modifying antirheumatic drugs (DMARDs) therapy. These subgroups were compared with control subjects (CS). One hundred and thirty-nine subjects were included, of which 114 were RA patients, and 25 were controls. Patients were divided into 99 with seropositive RA, 6 with seronegative RA, and 9 without DMARDs. The patients with seropositive RA were subclassified based on the DAS28 index. A seven-color multicolor flow cytometry panel was used to identify B-cell immunophenotypes and cell activation markers. There were no changes in total B-cell frequencies between RA patients and controls. However, a lower frequency of memory B cells and pre-plasmablasts was observed in seropositive RA compared to controls (P < 0.0001; P = 0.0043, respectively). In contrast, a higher frequency of mature B cells was observed in RA than in controls (P = 0.0002). Among patients with RA, those with moderate activity had a higher percentage of B cells (P = 0.0021). The CD69+ marker was increased (P < 0.0001) in RA compared to controls, while the CD40+ frequency was decreased in patients (P < 0.0001). Transitional, naïve, and double-negative B-cell subpopulations were higher in seronegative RA than in seropositive (P < 0.01). In conclusion, in seropositive and seronegative RA patients, there are alterations in B-cell activation and B-cell subpopulations, independently of clinical activity and DMARDs therapy.

Transcriptional upregulation of galectin-3 in multiple sclerosis.

Multiple sclerosis (MS) is an autoimmune, demyelinating disorder of the central nervous system (CNS) affecting approximately 2.5 million people worldwide. The mechanisms underlying the pathogenesis of MS are still only partially elucidated. Galectins are a family of ß-galactoside-binding lectins that are involved in the regulation of immune and inflammatory responses and have been shown to exert a role in the maintenance of central nervous system (CNS) homeostasis. There has been an increasing interest in the role of galectin-3 in neuroinflammation and neurodegeneration. In the current study, we have evaluated the expression levels of galectin-3 in different cellular populations involved in the etiopathogenesis of MS. We have observed dramatically higher transcriptomic levels of galectin-3 in encephalitogenic CD4+ T cells in a preclinical model of MS, the MOG-induced experimental allergic encephalomyelitis (EAE). Also, significantly higher levels of galectin-3 were found in microglial cells, astrocytes, and oligodendrocytes isolated from the spinal cord of EAE mice, as well as in human MS-related white matter lesions. Modular co-expression analysis revealed that galectin-3 is co-expressed with genes involved in the regulation of microglia, cytokine production, and chemotaxis. This is the first comprehensive analysis of the expression of galectin-3 in MS, further strengthening its potential pathogenetic role in the etiopathogenesis of this CNS autoimmune disorder.

BNT162b2 Vaccination after SARS-CoV-2 Infection Changes the Dynamics of Total and Neutralizing Antibodies against SARS-CoV-2: A 6-Month Prospective Cohort Study.

This study aimed to analyze the dynamics, duration, and production of total and neutralizing antibodies induced by the BNT162b2 vaccine and the possible effect of gender and prior SARS-CoV-2 infection on the generation of these antibodies. Total antibodies were quantified via chemiluminescent microparticle immunoassay (CMIA), and neutralizing antibodies were quantified using the cPass SARS-CoV-2 kit. Individuals with a history of COVID-19 produced twice as many antibodies than vaccinated individuals without prior SARS-CoV-2 infection, with an exponential increase observed in just six days. In those without a COVID-19 history, similar antibody production was reached 45 days after vaccination. Although total antibodies decline considerably in the first two months, the neutralizing antibodies and their inhibitory capacity (>96%) persist up to 6 months after the first dose. There was a tendency for higher total antibodies in women than men, but not at the inhibition capacity level. We suggest that the decline in total antibodies should not be considered as an indicator of loss of protective immunity because most antibodies decay two months after the second dose, but neutralizing antibodies remain constant for at least six months. Therefore, these latter antibodies could be better indicators for estimating the time-dependent vaccine efficacy.

Prevalence of symptoms, comorbidities, and reinfections in individuals infected with Wild-Type SARS-CoV-2, Delta, or Omicron variants: a comparative study in western Mexico.

Introduction: The variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been classified into variants of interest (VOIs) or concern (VOCs) to prioritize global monitoring and research on variants with potential risks to public health. The SARS-CoV-2 high-rate mutation can directly impact the clinical disease progression, epidemiological behavior, immune evasion, vaccine efficacy, and transmission rates. Therefore, epidemiological surveillance is crucial for controlling the COVID-19 pandemic. In the present study, we aimed to describe the prevalence of wild-type (WT) SARS-CoV-2 and Delta and Omicron variants in Jalisco State, Mexico, from 2021 to 2022, and evaluate the possible association of these variants with clinical manifestations of COVID-19. Methods: Four thousand and ninety-eight patients diagnosed with COVID-19 by real-time PCR (COVIFLU, Genes2Life, Mexico) from nasopharyngeal samples from January 2021 to January 2022 were included. Variant identification was performed by the RT-qPCR Master Mut Kit (Genes2Life, Mexico). A study population follow-up was performed to identify patients who had experienced reinfection after being vaccinated. Results and Discussion: Samples were grouped into variants according to the identified mutations: 46.3% were Omicron, 27.9% were Delta, and 25.8% were WT. The proportions of dry cough, fatigue, headache, muscle pain, conjunctivitis, fast breathing, diarrhea, anosmia, and dysgeusia were significantly different among the abovementioned groups (p < 0.001). Anosmia and dysgeusia were mainly found in WT-infected patients, while rhinorrhea and sore throat were more prevalent in patients infected with the Omicron variant. For the reinfection follow-up, 836 patients answered, from which 85 cases of reinfection were identified (9.6%); Omicron was the VOC that caused all reported reinfection cases. In this study, we demonstrate that the Omicron variant caused the biggest outbreak in Jalisco during the pandemic from late December 2021 to mid-February 2022 but with a less severe form than the one demonstrated by Delta and WT. The co-analysis of mutations and clinical outcomes is a public health strategy with the potential to infer mutations or variants that could increase disease severity and even be an indicator of long-term sequelae of COVID-19.

Vitamin D in Depression: A Potential Bioactive Agent to Reduce Suicide and Suicide Attempt Risk.

Suicide is one of the leading causes of death worldwide. According to the World Health Organization (WHO), every year, more than 700 thousand people die from this cause. Therefore, suicide is a public health issue. The complex interaction between different factors causes suicide; however, depression is one of the most frequent factors in people who have attempted suicide. Several studies have reported that vitamin D deficiency may be a relevant risk factor for depression, and vitamin D supplementation has shown promising effects in the adjunctive treatment of this mood disorder. Among the beneficial mechanisms of vitamin D, it has been proposed that it may enhance serotonin synthesis and modulate proinflammatory cytokines since low serotonin levels and systemic inflammation have been associated with depression and suicide. The present narrative review shows the potential pathogenic role of vitamin D deficiency in depression and suicide and the potential benefits of vitamin D supplementation to reduce their risk.

A Novel Approach to Obtain Vaccine Effectiveness Continuous Profiles. Example Case: COVID-19 in Elderly Mexicans.

Population-wide vaccination is the most promising long-term COVID-19 disease management strategy. However, the protection offered by the currently available COVID-19 vaccines wanes over time, requiring boosters to be periodically given, which represents an unattainable challenge, especially if it is necessary to apply several doses per year. Therefore, it is essential to design strategies that contribute to maximizing the control of the pandemic with the available vaccines. Achieving this objective requires knowing, as precisely and accurately as possible, the changes in vaccine effectiveness over time in each population group, considering the eventual dependence on age, sex, etc. Thus, the present work proposes a novel approach to calculating realistic effectiveness profiles against symptomatic disease. In addition, this strategy can be adapted to estimate realistic effectiveness profiles against hospitalizations or deaths. All such time-dependent profiles allow the design of improved vaccination schedules, where each dose can be administrated to the population groups so that the fulfillment of the containment objectives is maximized. As a practical example for this analysis, vaccination against COVID-19 in Mexico was considered. However, this methodology can be applied to other countries' data or to characterize future vaccines with time-dependent effectiveness values. Since this strategy uses aggregated observational data collected from massive databases, assumptions about the data validity and the course of the studied epidemic could eventually be necessary.

Severe COVID-19: Drugs and Clinical Trials.

By January of 2023, the COVID-19 pandemic had led to a reported total of 6,700,883 deaths and 662,631,114 cases worldwide. To date, there have been no effective therapies or standardized treatment schemes for this disease; therefore, the search for effective prophylactic and therapeutic strategies is a primary goal that must be addressed. This review aims to provide an analysis of the most efficient and promising therapies and drugs for the prevention and treatment of severe COVID-19, comparing their degree of success, scope, and limitations, with the aim of providing support to health professionals in choosing the best pharmacological approach. An investigation of the most promising and effective treatments against COVID-19 that are currently available was carried out by employing search terms including "Convalescent plasma therapy in COVID-19" or "Viral polymerase inhibitors" and "COVID-19" in the Clinicaltrials.gov and PubMed databases. From the current perspective and with the information available from the various clinical trials assessing the efficacy of different therapeutic options, we conclude that it is necessary to standardize certain variables-such as the viral clearance time, biomarkers associated with severity, hospital stay, requirement of invasive mechanical ventilation, and mortality rate-in order to facilitate verification of the efficacy of such treatments and to better assess the repeatability of the most effective and promising results.

TGFB1 mRNA expression and frequency of the + 869T>C and + 915G>C genetic variants: impact on risk for systemic sclerosis.

Systemic Sclerosis (SSc) is a chronic autoimmune disease characterized by immune disorder, microvascular damage, and fibrosis. TGFB1 gene encodes for the transforming growth factor isoform 1 (TGF-ß1), one of the most important pro-fibrotic cytokines. Therefore, variants in TGFB1 and changes in its expression could be associated with the pathogenesis of SSc. We aimed to evaluate the association of TGFB1 variants (+ 869T>C [rs1982073] and + 915G > C [rs1800471]) with the TGFB1 mRNA expression and SSc risk in the Southern Mexican population. We included 56 SSc patients and 112 control subjects (CS). The genetic variants were determined by the PCR-RFLP method. The TGFB1 mRNA expression was determined by qPCR. For the + 869T>C variant, the C allele was associated with SSc risk (OR = 1.733; CI = 1.087-2.762; p = 0.020). The C allele for the + 915G>C variant was also associated with SSc risk (OR = 11.168; CI = 1.289-96.754; p = 0.023). The relative expression of TGFB1 mRNA was 1.77-fold lower in SSc patients than in CS. Carriers of polymorphic alleles (TC or CC genotypes) for the + 869T>C variant showed 3.7-fold lower mRNA expression than the TT genotype in patients and 4.81-fold lower in CS. For the + 915G>C variant, patients with GA genotype had 1.78-fold lower mRNA expression than GG genotype carriers. In conclusion, the present study showed that + 869T>C and + 915G>C variants could be SSc risk factors for patients from Southern Mexico, and these genetic variants could induce lower mRNA expression of TGFB1.

Transforming growth factor beta isoforms and TGF-ßR1 and TGF-ßR2 expression in systemic sclerosis patients.

Systemic sclerosis (SSc) is characterized by chronic inflammation and fibrosis, two processes associated with transforming growth factor ß (TGF-ß) functions. In the present study, we investigated the expression of TGF-ß isoforms in serum and the skin distribution of TGF-ß and two receptors (TGF-ßR1 and TGF-ßR2) and their relationship with some clinical, inflammatory, autoimmune (autoantibodies), and vascular (platelets) biomarkers in SSc patients. A total of 56 SSc patients and 120 control subjects (CS) were included. The serum levels of TGF-ß isoforms were quantified by immunoassay with magnetic microspheres, and the skin biopsies were processed by immunohistochemistry. The soluble levels of the three active TGF-ß isoforms were lower in SSc patients than in CS (p < 0.0001). However, sTGF-ß1 and sTGF-ß3 levels were positively correlated with C-reactive protein levels in SSc patients. Additionally, sTGF-ß2 and sTGF-ß3 levels were positively correlated with the number of platelets in SSc patients. In skin biopsies, TGF-ß1, TGF-ßR1, and TGF-ßR2 expression levels were higher in SSc patients than CS. In conclusion, this is the first study showing a joint decrease of the 3 active TGF-ß isoforms in SSc patients. However, TGF-ß1, TGF-ßR1, and TGF-ßR2 are possibly increased in clinically involved skin. Therefore, it is likely that a distinct role is played by TGF-ß at the local (skin lesions) and systemic levels in SSc patients.

Comparison of three different COVID-19 vaccine platforms (CoronaVac, BTN162b2, and Ad5-nCoV) in individuals with and without prior COVID-19: Reactogenicity and neutralizing antibodies.

Neutralizing antibodies (NAbs) can be indicators of collective immunity, vaccine efficacy, and the longevity of the humoral response. This study aimed to compare reactogenicity and NAbs generated by three different COVID-19 vaccine platforms in individuals with and without prior COVID-19. 336 individuals vaccinated (112 with CoronaVac [inactivated virus], 112 with BNT162b2 [messenger RNA], and 112 with Ad5-nCoV [non-replicating viral vector]) were included. NAbs were quantified with the cPass SARS-CoV-2 kit. Individuals immunized with the Ad5-nCoV showed higher reactogenicity than those immunized with the other vaccines (p < 0.001). The BTN162b2 vaccine-induced NAbs with higher inhibition capacity than the other platforms in the first dose. In individuals without prior COVID-19, the Ad5-nCoV vaccine generated lower NAbs against SARS-CoV-2 than those induced by two doses of the BTN162b2 (Ad5-nCoV 72.10 [55.6-93.4] vs. BTN162b2 98.41 [98.16-98.56], p < 0.0001). One individual did not generate NAbs (0.89%) after a complete immunization with CoronaVac; in BTN162b2, all generated these antibodies, and in the Ad5-nCoV group, four individuals (3.57%) did not generate NAbs. Comorbidities, gender, age, and reactogenicity did not significantly influence the generation of NAbs (p > 0.05); however, a history of COVID-19 before vaccination was associated with antibodies with greater neutralizing capacity after the first dose (p < 0.01). In conclusion, the mRNA vaccine (BTN162b2) had a remarkable better ability to produce NAbs and lower reactogenicity than the other platforms, whereas the Ad5-nCov vaccine induced the lowest NAbs response in individuals without a history of COVID-19; therefore, we suggest that a booster could benefit these individuals.

PADI4 Haplotypes Contribute to mRNA Expression, the Enzymatic Activity of Peptidyl Arginine Deaminase and Rheumatoid Arthritis Risk in Patients from Western Mexico.

Citrullination is catalyzed by the peptidyl arginine deiminase 4 (PAD4) enzyme, encoded by the PADI4 gene. Increased PAD4 activity promotes the onset and progression of rheumatoid arthritis (RA). This study aimed to evaluate the association of PADI4 haplotypes with RA risk, mRNA expression, and the PAD4 activity in patients with RA from Mexico. Methodology: 100 RA patients and 100 control subjects (CS) were included. Genotyping was performed by PCR-RFLP method, PADI4 mRNA expression was quantified by real-time PCR, the contribution of PADI4 alleles (PADI4_89 G>A, PADI4_90 T>C, and PADI4_92 G>C) to mRNA expression by the ASTQ method, and PAD4 activity by HPLC. Also, the anti-CCP and anti-PADI4 antibodies were quantified by ELISA. Results: The three PADI4 polymorphisms were associated with RA susceptibility (OR = 1.72, p = 0.005; OR = 1.62; p = 0.014; OR = 1.69; p = 0.009; respectively). The 89G, 90T, and 92G alleles have a higher relative contribution to PADI4 mRNA expression from RA patients than 89A, 90C, and 92C alleles in RA patients. Moreover, the GTG/GTG haplotype was associated with RA susceptibility (OR = 2.86; p = 0.024). The GTG haplotype was associated with higher PADI4 mRNA expression (p = 0.04) and higher PAD4 enzymatic activity (p = 0.007) in RA patients. Conclusions: The evaluated polymorphisms contribute to PADI4 mRNA expression and the enzymatic activity of PAD4 in leukocytes. Therefore, the GTG haplotype is a genetic risk factor for RA in western Mexico, and is associated with increased PADI4 mRNA expression and higher PAD4 activity in these patients.

Differences in B-Cell Immunophenotypes and Neutralizing Antibodies Against SARS-CoV-2 After Administration of BNT162b2 (Pfizer-BioNTech) Vaccine in Individuals with and without Prior COVID-19 - A Prospective Cohort Study.

Purpose: Understanding the humoral immune response dynamics carried out by B cells in COVID-19 vaccination is little explored; therefore, we analyze the changes induced in the different cellular subpopulations of B cells after vaccination with BNT162b2 (Pfizer-BioNTech). Methods: This prospective cohort study evaluated thirty-nine immunized health workers (22 with prior COVID-19 and 17 without prior COVID-19) and ten subjects not vaccinated against SARS-CoV-2 (control group). B cell subpopulations (transitional, mature, naïve, memory, plasmablasts, early plasmablast, and double-negative B cells) and neutralizing antibody levels were analyzed and quantified by flow cytometry and ELISA, respectively. Results: The dynamics of the B cells subpopulations after vaccination showed the following pattern: the percentage of transitional B cells was higher in the prior COVID-19 group (p < 0.05), whereas virgin B cells were more prevalent in the group without prior COVID-19 (p < 0.05), mature B cells predominated in both vaccinated groups (p < 0.01), and memory B cells, plasmablasts, early plasmablasts, and double-negative B cells were higher in the not vaccinated group (p < 0.05). Conclusion: BNT162b2 vaccine induces changes in B cell subpopulations, especially generating plasma cells and producing neutralizing antibodies against SARS-CoV-2. However, the previous infection with SARS-CoV-2 does not significantly alter the dynamics of these subpopulations but induces more rapid and optimal antibody production.

Specific T-Cell Immune Response to SARS-CoV-2 Spike Protein over Time in Naïve and SARS-CoV-2 Previously Infected Subjects Vaccinated with BTN162b2.

Due to the COVID-19 pandemic, the rapid development of vaccines against SARS-CoV-2 has been promoted. BNT162b2 is a lipid-nanoparticle mRNA vaccine with 95% efficacy and is the most administered vaccine globally. Nevertheless, little is known about the cellular immune response triggered by vaccination and the immune behavior over time. Therefore, we evaluated the T-cell immune response against the SARS-CoV-2 spike protein and neutralization antibodies (nAbs) in naïve and SARS-CoV-2 previously infected subjects vaccinated with BTN162b2. Methods: Forty-six BTN162b2 vaccinated subjects were included (twenty-six naïve and twenty SARS-CoV-2 previously infected subjects vaccinated with BTN162b2). Blood samples were obtained at basal (before vaccination), 15 days after the first dose, and 15 days after the second dose, to evaluate cellular immune response upon PBMC's stimulation and cytokine levels. The nAbs were determined one and six months after the second dose. Results: SARS-CoV-2 previously infected subjects vaccinated with BTN162b2 showed the highest proportion of nAbs compared to naïve individuals one month after the second dose. However, women were more prone to lose nAbs percentages over time significantly. Furthermore, a diminished CD154+ IFN-γ+ CD4+ T-cell response was observed after the second BTN162b2 dose in those with previous SARS-CoV-2 infection. In contrast, naïve participants showed an overall increased CD8+ IFN-γ+ TNF-α+ T-cell response to the peptide stimulus. Moreover, a significant reduction in IP-10, IFN-λI, and IL-10 cytokine levels was found in both studied groups. Additionally, the median fluorescence intensity (MFI) levels of IL-6, IFNλ-2/3, IFN-𝛽, and GM-CSF (p < 0.05) were significantly reduced over time in the naïve participants. Conclusion: We demonstrate that a previous SARS-CoV-2 infection can also impact cellular T-cell response, nAbs production, and serum cytokine concentration. Therefore, the study of T-cell immune response is essential for vaccination scheme recommendations; future vaccine boost should be carefully addressed as continued stimulation by vaccination might impact the T-cell response.

ICOS Gene Polymorphisms (IVS1 + 173 T/C and c. 1624 C/T) in Primary Sjögren's Syndrome Patients: Analysis of ICOS Expression.

Background: Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease, which affects exocrine glands. T cell activation is a trigger mechanism in the immune response. Hyperreactivity of T cells and antibody production are features in pSS. ICOS can be critical in the pathogenesis of pSS. Methods: A total of 134 pSS patients and 134 control subjects (CS) were included. Genotyping was performed by PCR-RFLP. ICOS mRNA expression was quantified by real-time PCR, and CD4+ ICOS+ T cells were determined by flow cytometry. Results: The ICOS IVS1 + 173 T>C polymorphisms were not associated with susceptibility to pSS (p = 0.393, CI = 0.503−1.311). However, the c.1624 C>T polymorphism was associated with a reduction in the risk of development of pSS (p = 0.015, CI = 0.294−0.884). An increase in ICOS mRNA expression in patients was observed (3.7-fold). Furthermore, pSS patients showed an increase in membranal-ICOS expression (mICOS). High expression of mICOS (MFI) was associated with lymphocytic infiltration. Conclusions: The IVS1 + 173 polymorphism is not a genetic marker for the development of pSS, while c.1624 T allele was associated with a low risk. However, elevated mICOS expression in pSS patients with high lymphocytic infiltration was found. ICOS may have an important role in the immunopathogenesis of pSS and should be analyzed in T cell subsets in pSS patients as a possible disease marker.

An Upgrade on the Surveillance System of SARS-CoV-2: Deployment of New Methods for Genetic Inspection.

SARS-CoV-2 variants surveillance is a worldwide task that has been approached with techniques such as Next Generation Sequencing (NGS); however, this technology is not widely available in developing countries because of the lack of equipment and limited funding in science. An option is to deploy a RT-qPCR screening test which aids in the analysis of a higher number of samples, in a shorter time and at a lower cost. In this study, variants present in samples positive for SARS-CoV-2 were identified with a RT-qPCR mutation screening kit and were later confirmed by NGS. A sample with an abnormal result was found with the screening test, suggesting the simultaneous presence of two viral populations with different mutations. The DRAGEN Lineage analysis identified the Delta variant, but there was no information about the other three mutations previously detected. When the sequenced data was deeply analyzed, there were reads with differential mutation patterns, that could be identified and classified in terms of relative abundance, whereas only the dominant population was reported by DRAGEN software. Since most of the software developed to analyze SARS-CoV-2 sequences was aimed at obtaining the consensus sequence quickly, the information about viral populations within a sample is scarce. Here, we present a faster and deeper SARS-CoV-2 surveillance method, from RT-qPCR screening to NGS analysis.

Efficacy and Safety of Heterologous Booster Vaccination after Ad5-nCoV (CanSino Biologics) Vaccine: A Preliminary Descriptive Study.

Several studies have reported the benefits and safety of heterologous vaccination among different approved vaccines; however, there are no specific reports on the effects of vaccination with the Ad5-nCoV and other vaccines of the same or different technologies. In the present study, we evaluated the neutralizing antibodies percentage against SARS-CoV-2 in Mexican patients immunized with the Ad5-nCoV vaccine six months after its application. Moreover, the effect of the heterologous vaccination with the Ad5-nCoV vaccine and a booster dose of ChAdOx1-S-Nov-19, Ad26.COV2.S, BNT162b2, or mRNA-127 were determined. Our results suggest that a heterologous regimen of one dose with Ad5-nCoV vaccine followed by a booster dose of a different vaccine is safe and induces a stronger humoral immune response.

The PI3K/Akt/mTOR pathway: A potential pharmacological target in COVID-19.

Coronavirus disease 2019 (COVID-19) has emerged as a serious threat to global health. The disregulation of the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) cell signaling pathway observed in patients with COVID-19 has attracted attention for the possible use of specific inhibitors of this pathway for the treatment of the disease. Here, we review emerging data on the involvement of the PI3K/Akt/mTOR pathway in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the clinical studies investigating its tailored inhibition in COVID-19. Current in silico, in vitro, and in vivo data convergently support a role for the PI3K/Akt/mTOR pathway in COVID-19 and suggest the use of specific inhibitors of this pathway that, by a combined mechanism entailing downregulation of excessive inflammatory reactions, cell protection, and antiviral effects, could ameliorate the course of COVID-19.