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Molecular and Cellular Biomarkers of COVID-19 Prognosis: Protocol for the Prospective Cohort TARGET Study
No full textBackground: Since the beginning of the COVID-19 pandemic, the world's attention has been focused on better understanding the relation between the human host and the SARS-CoV-2 virus, as its action has led to hundreds of thousands of deaths.
Objective: In this context, we decided to study certain consequences of the abundant cytokine release over the innate and adaptive immune systems, inflammation, and hemostasis, comparing mild and severe forms of COVID-19.
Methods: To accomplish these aims, we will analyze demographic characteristics, biochemical tests, immune biomarkers, leukocyte phenotyping, immunoglobulin profile, hormonal release (cortisol and prolactin), gene expression, thromboelastometry, neutralizing antibodies, metabolic profile, and neutrophil function (reactive oxygen species production, neutrophil extracellular trap production, phagocytosis, migration, gene expression, and proteomics). A total of 200 reverse transcription polymerase chain reaction-confirmed patients will be enrolled and divided into two groups: mild/moderate or severe/critical forms of COVID-19. Blood samples will be collected at different times: at inclusion and after 9 and 18 days, with an additional 3-day sample for severe patients. We believe that this information will provide more knowledge for future studies that will provide more robust and useful clinical information that may allow for better decisions at the front lines of health care.
Results: The recruitment began in June 2020 and is still in progress. It is expected to continue until February 2021. Data analysis is scheduled to start after all data have been collected. The coagulation study branch is complete and is already in the analysis phase.
Conclusions: This study is original in terms of the different parameters analyzed in the same sample of patients with COVID-19. The project, which is currently in the data collection phase, was approved by the Brazilian Committee of Ethics in Human Research (CAAE 30846920.7.0000.0008)
Evaluation of ELISA-Based Multiplex Peptides for the Detection of Human Serum Antibodies Induced by Zika Virus Infection across Various Countries
No full textJ. Craig Venter Institute, La Jolla, CA 92137, USA; [email protected] (M.d.P.M.V.);
[email protected] (G.S.T.)
2 J. Craig Venter Institute, Rockville, MD 20850, USA; [email protected]
3 Department of Microbiology and Molecular Biology, Brigham Young University, Provo, UT 84602, USA;
[email protected]
4 Instituto de Investigacion en Microbiologia, Universidad Nacional Autónoma de Honduras,
Tegucigalpa, Honduras; [email protected] (K.G.); [email protected] (I.F.);
[email protected] (L.P.); [email protected] (I.L.)
5 Institute Goncalo Moniz, Fiocruz Bahia, Salvador 40296-710, Brazil; [email protected] (L.d.M.);
[email protected] (L.N.G.); [email protected] (V.B.)
6 Departmento de Enfermedades Infecciosas e Inmunología Pediátrica, Escuela de Medicina, Pontificia
Universidad Católica de Chile, Santiago H955+8Q, Chile; [email protected] (T.G.-S.); [email protected] (C.P.);
[email protected] (R.A.M.)
7 Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology,
La Jolla, CA 92037, USA; [email protected] (D.W.); [email protected] (A.S.); [email protected] (A.D.D.S.)
8 Department of Medicine, Infectious Diseases Division, University of California San Diego,
La Jolla, CA 92037, USA
9 Hospital Universitário-Universidade Federal do Maranhão, São Luís 65000-000, Brazil;
[email protected]
10 Faculdade de Medicina da Bahia-Universidade Federal da Bahia, Salvador 40000-000, Brazil;
[email protected] (K.M.A.); [email protected] (R.K.)
11 Instituto Nacional de Nutricion, Universidad Nacional Autonoma de Mexico, Mexico City 04510, Mexico;
[email protected]
12 Department of Medicine, University of California San Diego, La Jolla, CA 92037, USA
13 Genetech Research Institute, Colombo 00800, Sri Lanka
14 Department of Paraclinical Sciences, Faculty of Medicine, General Sir John Kotelawala Defence University,
Ratmalana 10390, Sri Lanka
15 Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
16 Department of Pediatrics, Section of Infectious Diseases, University of Colorado School of Medicine,
Aurora, CO 80045, USA; [email protected] Institutes of Health (contract
75N9301900065 to D.W. and A.S.). The recruitment and study set-up used in Chile based on influenza
virus studies were established in part with the support from the FONDECYT 1161971 and PIA
ACT 1408 grants from the Agencia Nacional de Investigación y Desarrollo (ANID) of Chile and the
FLUOMICS Consortium from the U.S. National Institute of Allergies and Infectious Disease (NIAID)
(grant U19AI135972 to R.A.M.). The recruitment and study set-up used in Brazil for this study
was financed in part by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq,
439967/2016-3). The Guatemalan study was funded by the U.S. National Institutes of Health NIAID
(grant 1K23AI143967 to D.O.). We also gratefully acknowledge funding by the United States Agency
for International Development (USAID) under the Combating Zika and Future Threats, A Grand
Challenge for Development initiative (award ID-OAA-F-17-00084 to B.E.P.).Zika virus (ZIKV) is a mosquito-borne Flavivirus with a positive-sense RNA genome, which
are generally transmitted through the bite of an infected Aedes mosquito. ZIKV infections could be
associated with neurological sequelae that, and otherwise produces similar clinical symptoms as other
co-circulating pathogens. Past infection with one member of the Flavivirus genus often induces crossreactive
antibodies against other flaviruses. These attributes complicate the ability to differentially
diagnose ZIKV infection from other endemic mosquito-borne viruses, making it both a public health
issue as well as a diagnostic challenge. We report the results from serological analyses using arbovirusspecific
peptides on 339 samples that were previously collected from 6 countries. Overall, we found
that our multiplexed peptide-based ELISA was highly efficient for identifying ZIKV antibodies as
early as 2 weeks post infection, and that it correlates with microneutralization, plaque reduction
neutralization tests (PRNTs) and commercial tests for ZIKV in previously characterized samples. We
observed that seropositivity varied by patient cohort, reflecting the sampling period in relation to the 2015–2016 ZIKV outbreak. This work evaluates the accuracy, specificity, and sensitivity of our
peptide-based ELISA method for detecting ZIKV antibodies from geographically diverse regions.
These findings can contribute to ongoing serological methods development and can be adapted for
use in future studies
Does Work after Retirement Matter? Sleep Features among Workers in the Brazilian Longitudinal Study of Adult Health
No full textA growing number of people keep working after retirement, a phenomenon known as
bridge employment. Sleep features, which are related to morbidity and mortality outcomes, are
expected to be influenced by bridge employment or permanent retirement. The objective of this study
was to analyze sleep duration and quality of bridge employees and permanent retirees compared to
nonretired, i.e., active workers, from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).
Participants (second wave of ELSA-Brasil, 2012–2014) comprised permanently retired (n = 2348),
career bridge workers (n = 694), bridge workers in a different place (n = 760), and active workers
(n = 6271). The associations of all studied retirement schemes and self-reported sleep quality and
duration were estimated through logistic and linear regression analysis. Workers from all studied
retirement schemes showed better sleep patterns than active workers. In comparison to active
workers, bridge workers who had changed workplace also showed a reduced chance of difficulty
falling asleep and too-early awakenings, which were not found among career bridge workers. Bridge
employment and permanent retirement were associated with a reduced chance of reporting sleep
deficit. Bridge work at a different place rather than staying at the same workplace seems to be
favorable for sleep. Further study is needed to explain mechanisms
The Inflammatory Cytokine Profile Associated with Liver Damage is Broader and Stronger in Chronic Hepatitis B Patients Compared to Acute Hepatitis B Patients
No full textLiver damage in hepatitis B is immune driven and correlates with inflammatory markers in patient
serum. There is no comparison of these markers to determine if inflammatory profiles are distinct to
different types of liver damage across patients at different stages of disease. We measured 25
inflammatory markers in acute hepatitis B, chronic hepatitis B patients with HBeAg seroconversion
and chronic patients stopping nucleoside analogue therapy. Myeloid markers dominated the
inflammatory profile in all stages of hepatitis B. More inflammatory markers were detectable in
chronic patients, including elevated concentrations of cytotoxic effectors Fas ligand, TRAIL and TNF-a.202
Personalized nutrition for depression: impact on the unholy trinity
No full textMajor depressive disorder (MDD) is a chronic affective disorder that has a strong neuroinflammatory component underpinning its etiology. Recent studies indicate that MDD is also associated with changes in the gut microbiota and that the latter is mainly modulated by diet. Microbiota-based personalized nutrition aims to provide an individual-specific diet that will yield the maximum benefit from a given diet since the gut microbiota is accounted for the variations that individuals present in response to a given food. In this review, we present and discuss 5 possible outcomes of using microbiota-based personalized nutrition. Harnessing this approach is essential to design more accurate therapies to prevent and treat MDD or to even help in drug metabolism, especially in the case of antidepressants.2030-12-3
Perinatal Outcome of Selective Intrauterine Growth Restriction in Monochorionic Twins: Evaluation of a Retrospective Cohort in a Developing Country
No full textSelective intrauterine growth restriction (sIUGR) in monochorionic twin pregnancies is associated with greater morbidity and mortality for both fetuses when compared to singleton and dichorionic pregnancies. This retrospective cohort study aimed to assess the perinatal outcomes of monochorionic twin pregnancies affected by this disorder and conducted expectantly, by analyzing the results according to the end-diastolic flow in the umbilical artery Doppler of the smaller twin (type I: persistently forward/type II: persistently absent or reversed/type III: intermittently absent or reversed). Seventy-five monochorionic diamniotic twin pregnancies with sIUGR were included in this study. sIUGR was defined by estimated fetal weight below the 3rd centile for gestational age, or below the 10th centile, when associated with at least one of the following three criteria: abdominal circumference below the 10th percentile, umbilical artery pulsatility index of the smaller twin above the 95th percentile, or estimated fetal weight discordance of 25% or more. Perinatal outcomes were analyzed from the prenatal period to hospital discharge and included perinatal death, neurological injury, retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), and sepsis. The mortality rate was 1.33% in this cohort. The overall morbidity rate was lower in type I twin pregnancies. In conclusion, this study shows that sIUGR type I has lower morbidity than types II and III in expectant management
Impairment of CD4+ T and Memory B Cell Responses but Normal Memory CD8+T-Cell Activation on Crohn’s Disease after COVID-19 Vaccination: A Twin Case
No full textVaccines to prevent the impact of SARS-CoV-2 are now available, including for patients with autoimmune diseases. However, there is no information about how inflammatory bowel disease (IBD) treatment could impact the cellular and humoral immune responses. This study evaluated SARS-CoV-2-specific humoral and cellular responses after vaccination with a two-dose schedule in a Crohn’s disease patient treated with Infliximab (10 mg/kg); we included comparisons with a monozygotic twin. The results showed that the Crohn’s disease’s twin (twin 2) had no antibody detection and reduced activation of CD4+ T cell responses, unlike the twin without the autoimmune disease (twin 1). Twin 2 developed antigen-specific central memory CD8+ T-cells and IFN production after the second dose of COVID-19 vaccination, similar to twin 1. These findings elucidated the role of T-cell immunity after COVID-19 immunization on IBD patients despite the lack of antibody production. Finally, our observation supports the consensus recommendation for IBD patients to receive COVID-19 vaccines
Influence of Environmental Factors on the Presence and Severity of Molar Incisor Hypomineralization
No full textObjective: To assess the association between environmental factors during pregnancy and early childhood
with the presence and severity of Molar Incisor Hipomineralization (MIH). Material and Methods: This
cross-sectional study was conducted with 120 patients between 7 and 14 years of age. MIH was evaluated
according to EAPD criteria. Data collected included the child’s medical history and the mother’s health.
Chi-square and logistic regression were performed to determine any statistical evidence of the
environmental factors, with the significance level set at 5%. Results: The participants were divided into
groups with MIH (n=60) and without MIH (n=60), with average ages of 9.9 (±1.9) and 9.7 (±1.7) years,
respectively. There was a statistically significant difference between intercurrences during pregnancy
(OR=3.55; IC95%=1.35-10.57) and medication taken by the child (OR=3.01; IC95%=1.74-8.42) and the
presence of MIH. In addition, other variables were also associated with the MIH (p≤0.05). However, there
was no association with variables and degree of MIH severity (p>0.05). Conclusion: The use of medications
in childhood and complications during pregnancy can be association to the presence of MIH. However,
these factors do not interaction to MIH severity
Rapamycin Improves the Response of Effector and Memory CD8 + T Cells Induced by Immunization With ASP2 of Trypanosoma cruzi
No full textDeficiency in memory formation and increased immunosenescence are pivotal features of Trypanosoma cruzi infection proposed to play a role in parasite persistence and disease development. The vaccination protocol that consists in a prime with plasmid DNA followed by the boost with a deficient recombinant human adenovirus type 5, both carrying the ASP2 gene of T. cruzi, is a powerful strategy to elicit effector memory CD8+ T-cells against this parasite. In virus infections, the inhibition of mTOR, a kinase involved in several biological processes, improves the response of memory CD8+ T-cells. Therefore, our aim was to assess the role of rapamycin, the pharmacological inhibitor of mTOR, in CD8+ T response against T. cruzi induced by heterologous prime-boost vaccine. For this purpose, C57BL/6 or A/Sn mice were immunized and daily treated with rapamycin for 34 days. CD8+ T-cells response was evaluated by immunophenotyping, intracellular staining, ELISpot assay and in vivo cytotoxicity. In comparison with vehicle-injection, rapamycin administration during immunization enhanced the frequency of ASP2-specific CD8+ T-cells and the percentage of the polyfunctional population, which degranulated (CD107a+) and secreted both interferon gamma (IFNγ) and tumor necrosis factor (TNF). The beneficial effects were long-lasting and could be detected 95 days after priming. Moreover, the effects were detected in mice immunized with ten-fold lower doses of plasmid/adenovirus. Additionally, the highly susceptible to T. cruzi infection A/Sn mice, when immunized with low vaccine doses, treated with rapamycin, and challenged with trypomastigote forms of the Y strain showed a survival rate of 100%, compared with 42% in vehicle-injected group. Trying to shed light on the biological mechanisms involved in these beneficial effects on CD8+ T-cells by mTOR inhibition after immunization, we showed that in vivo proliferation was higher after rapamycin treatment compared with vehicle-injected group. Taken together, our data provide a new approach to vaccine development against intracellular parasites, placing the mTOR inhibitor rapamycin as an adjuvant to improve effective CD8+ T-cell response
Should COVID-19 be branded to Viral Thrombotic Fever?
No full textCoronaviruses can cause a diverse array of clinical manifestations, from fever with symptoms of the common cold to highly lethal Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS). SARS-CoV-2, the coronavirus discovered in Hubei province, China, at the end of 2019, became known worldwide for causing COVID-19. Over one time-period, the scientific community has produced a large bulk of knowledge about this disease and countless reports about its immune-pathological aspects. This knowledge, including data obtained in postmortem studies, points unequivocally to a hypercoagulability state. However, the name COVID 19 tells us very little about the true meaning of the disease. Our proposal is more comprehensive; it intends to frame COVID-19 in more clinical terminology, making an analogy to Viral Hemorrhagic Fever (VHF). Thus, we found irrefutable evidence in the current literature that COVID-19 is the first viral disease that can be branded as a Viral Thrombotic Fever. This manuscript points out that SARS CoV-2 goes far beyond pneumonia or SARS. COVID-19 infections promote remarkable interactions among the endothelium, coagulation, and immune response, building up a background capable of promoting a “thrombotic storm,” much more than a “cytokine storm.” The importance of a viral protease called main protease (Mpro) is highlighted as a key component for SARS-CoV-2 replication in the host cell. A deeper analysis of this protease and its importance on the coagulation system is also discussed for the first time, mainly because of its similarity with the thrombin and factor Xa molecules, as recently pointed out by structural comparison of crystallographic structures