Elevated Levels of Cytotoxicity, Cytokines, and Anti-SARS-CoV-2 Antibodies in Mild Cases of COVID-19.

Current evidence shows higher production of cytokines and antibodies against severe acute respiratory coronavirus 2 (SARS-CoV-2) in severe and critical cases of Coronavirus Disease 2019 (COVID-19) in comparison with patients with moderate or mild disease. A recent hypothesis proposes an important role of genotoxicity and cytotoxicity in the induction of the cytokine storm observed in some patients at later stages of the disease. Interestingly, in this study, we report significantly higher levels of interleukin (IL)-1ß, IL-6, MCP-1, and IL-4 cytokines in mild COVID-19 patients versus severe cases, as well as a high frequency of karyorrhexis (median [Me] = 364 vs. 20 cells) and karyolysis (Me = 266 vs. 52 cells) in the mucosal epithelial cells of both groups of patients compared with uninfected individuals. Although we observed higher levels of anti-SARS-CoV-2 IgM and IgG antibodies in COVID-19 patients, IgM antibodies were significantly higher only in mild cases, for the N and the S viral antigens. High levels of IgG antibodies were observed in both mild and severe cases. Our results showed elevated concentrations of proinflammatory and anti-inflammatory cytokines in mild cases, which may reflect an active innate immune response and could be related to the higher IgM and IgG antibody levels found in those patients. In addition, we found that SARS-CoV-2 infection induces cytotoxic damage in the oral mucosa, highlighting the importance of studying the genotoxic and cytotoxic events induced by infection and its role in the pathophysiology of COVID-19.

Seroconversion dynamic and SARS-CoV-2 seropositivity in unvaccinated population during the first and second outbreaks in Mexico.

Serosurveillance helps establish reopening guidelines and determine the immunity levels in different populations to reach herd immunity. Then, there is an urgent need to estimate seroprevalence population wide. In Mexico, information about COVID-19 cases and related deaths is scarce. Also, there is no official serosurveillance, limiting our knowledge of the impact of the SARS-CoV-2 pandemic. Here, we report the prevalence of anti-SARS-CoV-2 antibodies in 522,690 unvaccinated people from July 5th to December 31st, 2020. The overall seroprevalence was 32.8% and highest in adults aged 30-39 years (38.5%) than people under 20 years (33.0%) or older (28.9%). Moreover, in a cohort of 1655 individuals confirmed COVID-19 by PCR, we found that symptomatic people (HR = 2.56) increased seroconversion than presymptomatic. Also, we identified that the most discriminative symptoms for COVID-19 that could predict seroconversion were anosmia and ageusia (HR = 1.70), fever, myalgia/arthralgia, and cough (HR = 1.75). Finally, we found that obese people had lower seroconversion (HR = 0.53) than healthy people, but the opposite happens in diabetic people (HR = 1.39). These findings reveal that around one-third of Mexican outpatients had anti-SARS-CoV-2 antibodies before vaccination. Also, some symptoms improve empirically COVID-19 diagnosis and seroconversion. This information could help fine-tune vaccination schemes and the reopening and back-to-work algorithms.

The Evolutionary Landscape of SARS-CoV-2 Variant B.1.1.519 and Its Clinical Impact in Mexico City.

The SARS-CoV-2 pandemic is one of the most concerning health problems around the globe. We reported the emergence of SARS-CoV-2 variant B.1.1.519 in Mexico City. We reported the effective reproduction number (Rt) of B.1.1.519 and presented evidence of its geographical origin based on phylogenetic analysis. We also studied its evolution via haplotype analysis and identified the most recurrent haplotypes. Finally, we studied the clinical impact of B.1.1.519. The B.1.1.519 variant was predominant between November 2020 and May 2021, reaching 90% of all cases sequenced in February 2021. It is characterized by three amino acid changes in the spike protein: T478K, P681H, and T732A. Its Rt varies between 0.5 and 2.9. Its geographical origin remain to be investigated. Patients infected with variant B.1.1.519 showed a highly significant adjusted odds ratio (aOR) increase of 1.85 over non-B.1.1.519 patients for developing a severe/critical outcome (p = 0.000296, 1.33-2.6 95% CI) and a 2.35-fold increase for hospitalization (p = 0.005, 1.32-4.34 95% CI). The continuous monitoring of this and other variants will be required to control the ongoing pandemic as it evolves.

Control and Prevention of SARS-CoV-2 Outbreaks among Healthcare Workers from 129 Healthcare Facilities in Mexico.

Few reports have shared the workflows to reduce SARS-CoV-2 infections among risk groups, including healthcare workers (HCWs). This study describes an occupational health program implemented to reduce the incidence of COVID-19 and establishes a back-to-work algorithm in HCWs of 129 Salud Digna outpatient care clinics in Mexico. This program was composed of training plans, screening SARS-CoV-2 infections, the containment of infections, follow-up COVID-19 cases, and continuing supervision in addition to the steady supply and training for the correct use of PPE. From 16 April 2020 to 15 April 2021, 7376 individuals were enrolled, of which 423 were excluded because they did not meet the inclusion criteria or refused the follow-up. In the cohort studied, we found a COVID-19 incidence of 35.4% (2610 individuals), lower hospitalization (0.11%), ICU (0.04%) and lethality rate (0.04%). Additionally, 85.9% of COVID-19 cases tested negative for SARS-CoV-2 after 14 days of the first positive test with an average isolation time of 26-33 days. Finally, 99% of people received personal protective equipment and adequate training to use it. Our results show that the program implemented reduced the hospitalization ICU admission and lethality in HCWs; we consider this workflow to help other workplaces offer safe conditions for HCWs and patients.

Epidemiology of COVID-19 in Mexico: Symptomatic profiles and presymptomatic people.

OBJECTIVES: The COVID-19 diagnosis is difficult and ambiguous due to nonspecific symptoms. Further, data from Mexico arehospitable population-based without signs and symptoms information. Thus, this work aims to provide epidemiology information about the burden of COVID-19 in Mexican outpatients and to identify symptomatic COVID-19 profiles that could help in the early diagnosis of the disease. METHODS: From June to September, epidemiological, clinical, and demographic data of 482,413 individuals diagnosed by RT-PCR test for SARS-CoV-2 in Salud Digna clinics were collected. RESULTS: We observed a 41% incidence of SARS-CoV-2 infections with a mean age of 36 years and with young adults (20-40 years) being the most affected. Among occupations, delivery persons (OR 1.38) or informal traders (OR 1.33) had a higher risk of COVID-19. Moreover, 13% of SARS-CoV-2 infections were in presymptomatic patients. Finally, we identified three different symptomatic profiles (common, respiratory, and gastrointestinal) associated with COVID-19. CONCLUSION: The incidence of SARS-CoV-2 was high among outpatients with a significant proportion of presymptomatic carriers, and thus it is necessary to increase testing and continue SARS-CoV-2 surveillance with a better description of signs and symptoms; in this regard, we identified three symptomatic profiles that could help in the diagnosis of COVID-19.

lincRNA-RP11400K9.4 Regulates Cell Survival and Migration of Breast Cancer Cells.

BACKGROUND/AIM: Several works in the past decades pointed out the key role of long intergenic non-coding RNA (lincRNA) in breast cancer development. Here in we report for first time the importance of deregulation of lincRNA RP11-400K9.4 in breast cancer cells which played a role in cell survival and migration. MATERIALS AND METHODS: After RP11-400K9.4 silencing by short hairpin RNAs or overexpression by GeneBlocks, real-time quantitative polymerase chain reaction (RT-PCR), microarray, migration, proliferation and viability assay were performed. RESULTS: RP11-400K9.4 expression was mainly in the cytoplasmic fraction in 2D culture. Overexpression of RP11-400K9.4 led to a reduction of migration by MCF-7 and MDA-MB-368 cells and an increase in cellular survival after UV-C radiation. Bioinformatic analyses highlighted irradiation-induced DNA damage, DNA repair and cell-cycle pathways as the mainly affected by RP11-400K9.4. Furthermore RT-PCR assay demonstrated the overexpression of baculoviral IAP repeat containing 3 (BIRC3) a known oncogene that promotes radiotherapy resistance through the nuclear factor kappa B (NFĸB) pathway. CONCLUSION: RP11-400K9.4 participates in the modulation of migration and survival processes probably via the BIRC3/NFĸB pathway.

Outer membrane vesicles of Pasteurella multocida contain virulence factors.

Pasteurella multocida (Pm) is a gram-negative bacterium able to infect different animal species, including human beings. This bacterium causes economic losses to the livestock industry because of its high morbidity and mortality in animals. In this work, we report the characterization of outer membrane vesicles (OMVs) released into the culture medium by different Pm serogroups. Purified OMVs in the range of 50-300 nm were observed by electron microscopy. Serum obtained from chickens infected with Pm recognized several proteins from Pm OMVs. Additionally, rabbit antiserum directed against a secreted protease from Actinobacillus pleuropneumoniae recognized a similar protein in the Pm OVMs, suggesting that OMVs from these bacterial species contain common immunogenic proteins. OmpA, a multifunctional protein, was identified in OMVs from different Pm serogroups, and its concentration was twofold higher in OMVs from Pm serogroups B and D than in OMVs from other serogroups. Three outer membrane proteins were also identified: OmpH, OmpW, and transferrin-binding protein. Three bands of 65, 110, and 250 kDa with proteolytic activity were detected in Pm OMVs of serogroups A and E. Additionally, ß-lactamase activity was detected only in OMVs from Pm 12945 Amp(r) (serogroup A). Pm OMVs may be involved in different aspects of disease pathogenesis.