Towards the development of an epitope-focused vaccine for SARS-CoV-2.

The rapid spread of COVID-19 on all continents and the mortality induced by SARS-CoV-2 virus, the cause of the pandemic coronavirus disease 2019 (COVID-19) has motivated an unprecedented effort for vaccine development. Inactivated viruses as well as vaccines focused on the partial or total sequence of the Spike protein using different novel platforms such us RNA, DNA, proteins, and non-replicating viral vectors have been developed. The high global need for vaccines, now and in the future, and the emergence of new variants of concern still requires development of accessible vaccines that can be adapted according to the most prevalent variants in the respective regions. Here, we describe the immunogenic properties of a group of theoretically predicted RBD peptides to be used as the first step towards the development of an effective, safe and low-cost epitope-focused vaccine. One of the tested peptides named P5, proved to be safe and immunogenic. Subcutaneous administration of the peptide, formulated with alumina, induced high levels of specific IgG antibodies in mice and hamsters, as well as an increase of IFN-γ expression by CD8+ T cells in C57 and BALB/c mice upon in vitro stimulation with P5. Neutralizing titers of anti-P5 antibodies, however, were disappointingly low, a deficiency that we will attempt to resolve by the inclusion of additional immunogenic epitopes to P5. The safety and immunogenicity data reported in this study support the use of this peptide as a starting point for the design of an epitope restricted vaccine.

A Comprehensive Meta-Analysis of COVID-19 in Latin America

Background: Latin America has become the epicenter of the coronavirus disease 2019 (COVID-19) pandemic. We aim to perform a systematic comparative review of the clinical characteristics that are associated with this disease in Latin American countries. Methods: We conducted a systematic review of published articles, journal and/or epidemiological reports of confirmed COVID-19 cases in Latin America. Data were obtained either through publicly available information from Ministries of Health, published journal reports and/or unpublished datasets. We analyzed data from SARS-CoV-2 positive patients evaluated at healthcare centers and hospitals of 8 countries including Brazil, Peru, Mexico, Argentina, Colombia, Venezuela, Ecuador, and Bolivia, between March 1st and July 30th, 2020. These countries consist of a total population that exceeds 519 million. Demographics, comorbidities, and clinical symptoms were collected. Statistical descriptive analysis and correlation analyses of symptoms, comorbidities and mortality were performed. Results: A total of 728,282 COVID-19 patients were included in this study. Of these, 52.6% were female. The average age was 48.4 years. Peru had the oldest cohort with 56.8 years and highest rate of females (56.8%) while Chile had the youngest cohort (39 years old). Venezuela had the highest male prevalence (56.7%). Most common symptoms were cough with 60.1% (Bolivia had the highest rate 78%), fatigue/tiredness with 52.0%, sore throat with 50.3%, and fever with 44.2%. Bolivian patients had fever as the top symptom (83.3%). GI symptoms included diarrhea which was highest in Mexico with 22.9%. Hypertension was among the top (12.1%) comorbidities, followed by diabetes with 8.3% and obesity at 4.5%. In multivariate analyses, the leading and significant comorbidities were hypertension (r = 0.83, p = 0.02), diabetes (r = 0.91, p = 0.01), and obesity (r = 0.86, p = 0.03). Mortality was highest in Mexico (16.6%) and lowest in Venezuela (0.9%) among the analyzed cohorts. Conclusion: Overall, COVID-19 patients in Latin America display cough, fatigue, and fever as main symptoms. Up to 53% of patients with COVID-19 have GI manifestations. Different clinical symptoms were associated with COVID-19 in Latin American countries. Metabolic syndrome components were the main comorbidities associated with poor outcome. Country-specific management and prevention plans are needed and can be established from this meta-analysis.

COVID-19 in Latin America and the caribbean region: Symptoms and morbidities in the epidemiology of infection.

The COVID-19 pandemic has widespread economic and social effects on Latin America (LA) and the Caribbean (CA). This region, which has a high prevalence of chronic diseases, has been one of the most affected during the pandemic. Multiple symptoms and comorbidities are related to distinct COVID-19 outcomes. However, there has been no explanation as to why different patients present with different arrays of clinical presentations. Studies report that similar to comorbidities, each country in LA and the CA has its own particular health issues. Moreover, economic and social features have yet to be studied in detail to obtain a complete perspective of the disease in the region. Herein, the impact of demographic and economic characteristics in LA and the CA on COVID-19 are presented in combination with symptoms and comorbidities related to the disease as important aspects that can influence management and treatment.

An RBD-Based Diagnostic Method Useful for the Surveillance of Protective Immunity against SARS-CoV-2 in the Population.

After more than two years, the COVID-19 pandemic is still ongoing and evolving all over the world; human herd immunity against SARS-CoV-2 increases either by infection or by unprecedented mass vaccination. A substantial change in population immunity is expected to contribute to the control of transmission. It is essential to monitor the extension and duration of the population's immunity to support the decisions of health authorities in each region and country, directed to chart the progressive return to normality. For this purpose, the availability of simple and cheap methods to monitor the levels of relevant antibodies in the population is a widespread necessity. Here, we describe the development of an RBD-based ELISA for the detection of specific antibodies in large numbers of samples. The recombinant expression of an RBD-poly-His fragment was carried out using either bacterial or eukaryotic cells in in vitro culture. After affinity chromatography purification, the performance of both recombinant products was compared by ELISA in similar trials. Our results showed that eukaryotic RBD increased the sensitivity of the assay. Interestingly, our results also support a correlation of the eukaryotic RBD-based ELISA with other assays aimed to test for neutralizing antibodies, which suggests that it provides an indication of protective immunity against SARS-CoV-2.

Scavenger Receptors in the Pathogenesis of Viral Infections.

Scavenger receptors (SR) are not only pattern recognition receptors involved in the immune response against pathogens but are also important receptors exploited by different virus to enter host cells, and thus represent targets for antiviral therapy. The high mutation rates of viruses, as well as their small genomes are partly responsible for the high rates of virus resistance and effective treatments remain a challenge. Most currently approved formulations target viral-encoded factors. Nevertheless, host proteins may function as additional targets. Thus, there is a need to explore and develop new strategies aiming at cellular factors involved in virus replication and host cell entry. SR-virus interactions have implications in the pathogenesis of several viral diseases and in adenovirus-based vaccination and gene transfer technologies, and may function as markers of severe progression. Inhibition of SR could reduce adenoviral uptake and improve gene therapy and vaccination, as well as reduce pathogenesis. In this review, we will examine the crucial role of SR play in cell entry of different types of human virus, which will allow us to further understand their role in protection and pathogenesis and its potential as antiviral molecules. The recent discovery of SR-B1 as co-factor of SARS-Cov-2 (severe acute respiratory syndrome coronavirus 2) entry is also discussed. Further fundamental research is essential to understand molecular interactions in the dynamic virus-host cell interplay through SR for rational design of therapeutic strategies.

Intranasal dexamethasone: a new clinical trial for the control of inflammation and neuroinflammation in COVID-19 patients.

BACKGROUND: By end December of 2021, COVID-19 has infected around 276 million individuals and caused over 5 million deaths worldwide. Infection results in dysregulated systemic inflammation, multi-organ dysfunction, and critical illness. Cells of the central nervous system are also affected, triggering an uncontrolled neuroinflammatory response. Low doses of glucocorticoids, administered orally or intravenously, reduce mortality among moderate and severe COVID-19 patients. However, low doses administered by these routes do not reach therapeutic levels in the CNS. In contrast, intranasally administered dexamethasone can result in therapeutic doses in the CNS even at low doses. METHODS: This is an approved open-label, multicenter, randomized controlled trial to compare the effectiveness of intranasal versus intravenous dexamethasone administered in low doses to moderate and severe COVID-19 adult patients. The protocol is conducted in five health institutions in Mexico City. A total of 120 patients will be randomized into two groups (intravenous vs. intranasal) at a 1:1 ratio. Both groups will be treated with the corresponding dexamethasone scheme for 10 days. The primary outcome of the study will be clinical improvement, defined as a statistically significant reduction in the NEWS-2 score of patients with intranasal versus intravenous dexamethasone administration. The secondary outcome will be the reduction in mortality during hospitalization. CONCLUSIONS: This protocol is currently in progress to improve the efficacy of the standard therapeutic dexamethasone regimen for moderate and severe COVID-19 patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT04513184 . Registered November 12, 2020. Approved by La Comisión Federal para la Protección contra Riesgos Sanitarios (COFEPRIS) with identification number DI/20/407/04/36. People are currently being recruited.

COVID-19 and gastrointestinal symptoms in Mexico, a systematic review: does location matter?

BACKGROUND: Covid-19 in Mexico is on the rise in different parts of the country. We aimed to study the symptoms and comorbidities that associate with this pandemic in 3 different regions of Mexico. METHODS: We analyzed data from SARS-CoV-2 positive patients evaluated at healthcare centers and hospitals of Mexico (n = 1607) including Northwest Mexico (Sinaloa state), Southeast Mexico (Veracruz state) and West Mexico (Jalisco state) between March 1 and July 30, 2020. Mexico consists of a total population that exceeds 128 million. Demographics, comorbidities and clinical symptoms were collected. Statistical descriptive analysis and correlation analyses of symptoms, comorbidities and mortality were performed. RESULTS: A total of 1607 hospitalized patients positive for COVID-19 across all 3 regions of Mexico were included. The average age was 54.6 years and 60.4% were male. A mortality rate of 33.1% was observed. The most common comorbidities were hypertension (43.2%), obesity (30.3%) and diabetes (31.4%). Hypertension was more frequent in West (45%), followed by Northwest (37%) and Southeast Mexico (29%). Obesity was around 30% in Northwest and West whereas an 18% was reported in Southeast. Diabetes was most common in West (34%) followed by Northwest (22%) and Southeast (13%). This might be related to the highest mortality rate in Northwest (31%) and West (37%) when compared to Southeast. Most common symptoms in our overall cohort were fever (80.8%), cough (79.8%), headache (66%), dyspnea (71.1%), myalgia (53.8%), joints pain (50.8%) and odynophagia (34.8%). Diarrhea was the main gastrointestinal (GI) symptom (21.3%), followed by abdominal pain (18%), and nausea/ vomiting (4.5%). Diarrhea and abdominal pain were more common in West (23.1 and 21%), followed by Southeast (17.8, and 9.8%) and Northwest (11.4 and 3.1%). CONCLUSION: Our study showed a high mortality rate likely related to high frequencies of comorbidities (hypertension, obesity and diabetes). Mortality was different across regions. These discrepancies might be related to the differences in the frequencies of comorbidities, and partially attributed to differences in socio-economic conditions and quality of care. Thus, our findings stress the need for improved strategies to get better outcomes in our population.

COVID-19 and the liver: What do we know after six months of the pandemic?

Despite liver injury in patients infected with severe acute respiratory syndrome (SARS) coronavirus (CoV)-2 (SARS-CoV-2) is associated with prolonged hospitalization, and liver dysfunction is mainly described in patients with severe viral disease. How liver abnormalities may affect virus infection is still unknown. Improved understanding of host genetics, lifestyle, underlying comorbidities and adequate follow-up of patients with liver damage are critical in the new scenario of the pandemic virus.