Azamor, T. | bioRxiv Science

bioRxiv2023

Immunometabolic rewiring in long COVID patients with chronic headache

Almost 20% of patients with COVID-19 experience long-term effects, known as post-COVID condition or long COVID. Among many lingering neurologic symptoms, chronic headache is the most common. Despite this health concern, the etiology of long COVID headache is still not well characterized. Here, we present a longitudinal multi-omics analysis of blood leukocyte transcriptomics, plasma proteomics and metabolomics of long COVID patients with chronic headache. Long COVID patients experienced a state of hyper-inflammation prior to chronic headache onset and maintained persistent inflammatory activation throughout the progression of chronic headache. Metabolomic analysis also revealed augmented arginine and lipid metabolisms, skewing towards a nitric oxide-based pro-inflammation. Furthermore, metabolisms of neurotransmitters including serotonin, dopamine, glutamate, and GABA were markedly dysregulated during the progression of long COVID headache. Overall, these findings illustrate the immuno-metabolomics landscape of long COVID patients with chronic headache, which may provide insights to potential therapeutic interventions.

microbiology↗

bioRxiv2020

In Vitro Inhibition of SARS-CoV-2 Infection by Bovine Lactoferrin

Since its emergence in late 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been posing a serious threat to public health worldwide as the causative agent of coronavirus disease 2019 (COVID-19). Now distributed in a pandemic pattern, this disease still lacks an effective drug treatment with low toxicity, leading pharmaceutical companies and research labs to work against time to find a candidate molecule to efficiently treat the affected patients. Due to the well-known broad-spectrum antimicrobial activity of the lactoferrin protein, we sought to verify whether its bovine form (bLf) would also be effective in vitro against SARS-CoV-2. Using an antiviral assay based on quantitative reverse transcription-polymerase chain reaction (qRT-PCR), we found that bLf reduced progeny virus yield by up to [~]84,6% in African green monkey kidney epithelial cells (Vero E6) and [~]68,6% in adenocarcinomic human alveolar basal epithelial cells (A549) at 1 mg/mL, a concentration previously shown to have low cytotoxicity. Therefore, our preliminary data suggest that bLf has the potential to constitute a biochemical approach to fight the new coronavirus pandemic.

microbiology↗

bioRxiv2019

Congenital Zika Syndrome is associated with maternal genetic background

BackgroundHost factors that influence Congenital Zika Syndrome (CZS) outcome remain elusive. Interferons have been reported as the main antiviral factor in Zika and other flavivirus infections. MethodsWe accessed samples from Zika pregnancies, conducted a case-control study to verify whether interferon alfa receptor 1 (IFNAR1) and interferon lambda 2 and 4 (IFNL2/4) single nucleotide polymorphisms (SNPs) contribute to CZS newborn outcome and we characterized placenta gene expression profile at term. FindingsNewborns carrying CG/CC genotypes of rs2257167 in IFNAR1 presented higher risk of developing CZS (OR=3.73; IC=1.36-10.21; Pcorrected=0.02646). No association between IFNL SNPs and CZS was observed. Placenta from CZS cases displayed lower levels of IFNL2 and ISG15 along with higher IFIT5. The rs2257167 CG/CC placentas also demonstrated high levels of IFIT5 and inflammation-related genes. InterpretationWe found CZS to be related with exacerbated type I IFN and insufficient type III IFN in placenta at term, forming an unbalanced response modulated by the IFNAR1 rs2257167 genotype. These findings shed light on the host-pathogen interaction focusing on the genetically regulated type I / type III IFN axis that could lead to better management of Zika and other TORCH (Toxoplasma, Others, Rubella, Cytomegalovirus, Herpes) congenital infections. FundingThis work was supported by the Instituto Oswaldo Cruz (Rio de Janeiro, Brazil) and by the Instituto de Tecnologia em Imunobiologicos (Rio de Janeiro, Brazil). Research in contextO_ST_ABSEvidence before this studyC_ST_ABSLevels of type I and type III interferons are genetically controlled and decisively regulate outcome of spontaneous viral infections or response to antiviral treatment. Hepatitis C virus, Yellow Fever and Zika virus belong to the Flaviviridae family and elicit similar host immune responses. Congenital Zika Syndrome presents well-known risk factors, mainly the first trimester of pregnancy as well as social and nutritional factors, however, these do not entirely explain abnormal outcomes. Added value of this studyWe conducted a case-control study to evaluate SNPs in type I and III interferon genes using samples from newborns and mothers who had zika infection during pregnancy. We have shown that newborn interferon type I background contributes to the development of abnormal CSZ. This specific genetic makeup regulates placental immunological responses and prevents an exacerbated type I, and lack of type III, interferon response in syndromic cases. Implications of all the available evidenceOur study suggests an important factor regulating the host-pathogen interaction during Zika virus (ZIKV) infections in humans. During pregnancy, genetic variations play a role in balancing tissue-specific type I and III interferons during ZIKV congenital infection influencing fetal neurological damage. Custom pharmacological interventions could be used to modulate immunity and inflammation towards protective responses. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=104 SRC="FIGDIR/small/715862v3_ufig1.gif" ALT="Figure 1"> View larger version (24K): org.highwire.dtl.DTLVardef@ee554forg.highwire.dtl.DTLVardef@122c773org.highwire.dtl.DTLVardef@547695org.highwire.dtl.DTLVardef@13543db_HPS_FORMAT_FIGEXP M_FIG C_FIG

genetics↗