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2.
Frontiers in immunology ; 13, 2022.
Article in English | EuropePMC | ID: covidwho-1823023

ABSTRACT

To gain access to the brain, a so-called immune-privileged organ due to its physical separation from the blood stream, pathogens and particularly viruses have been selected throughout evolution for their use of specific mechanisms. They can enter the central nervous system through direct infection of nerves or cerebral barriers or through cell-mediated transport. Indeed, peripheral lymphoid and myeloid immune cells can interact with the blood–brain and the blood–cerebrospinal fluid barriers and allow viral brain access using the “Trojan horse” mechanism. Among immune cells, at the frontier between innate and adaptive immune responses, dendritic cells (DCs) can be pathogen carriers, regulate or exacerbate antiviral responses and neuroinflammation, and therefore be involved in viral transmission and spread. In this review, we highlight an important contribution of DCs in the development and the consequences of viral brain infections.

3.
Diagnostics (Basel) ; 12(3)2022 Mar 02.
Article in English | MEDLINE | ID: covidwho-1760429

ABSTRACT

Hepatitis B (HBV) infection is a major public health concern. Perinatal transmission of HBV from mother to child represents the main mode of transmission. Despite the existence of effective immunoprophylaxis, the preventive strategy is inefficient in neonates born to mothers with HBV viral loads above 2 × 105 IU/mL. To prevent mother-to-child transmission, it is important to identify highly viremic pregnant women and initiate antiviral therapy to decrease their viral load. We developed a simple innovative molecular approach avoiding the use of automatic devices to screen highly viremic pregnant women. This method includes rapid DNA extraction coupled with an isothermal recombinase polymerase amplification (RPA) combined with direct visual detection on a lateral flow assay (LFA). We applied our RPA-LFA approach to HBV DNA-positive plasma samples with various loads and genotypes. We designed a triage test by adapting the analytical sensitivity to the recommended therapeutic decision threshold of 2 × 105 IU/mL. The sensitivity and specificity were 98.6% (95% CI: 92.7-99.9%) and 88.2% (95% CI: 73.4-95.3%), respectively. This assay performed excellently, with an area under the ROC curve value of 0.99 (95% CI: 0.99-1.00, p < 0.001). This simple method will open new perspectives in the development of point-of-care testing to prevent HBV perinatal transmission.

5.
J Infect Dis ; 2022 Mar 01.
Article in English | MEDLINE | ID: covidwho-1713677

ABSTRACT

BACKGROUND: SARS-CoV-2 nucleocapsid antigen (N-Ag) can be detected in the blood of patients with Covid-19. We used a highly sensitive and specific assay to explore the presence of N-Ag in urine during the course of Covid-19, and explore its relationship with the severity of the disease. METHODS: We studied urine and blood N-Ag using highly sensitive immunoassay in 82 patients with a SARS-CoV-2 infection proven by PCR. RESULTS: In the first and second weeks of Covid-19, hospitalized patients tested positive for urinary N-Ag (81.25% and 71.79%, respectively), and blood N-Ag (93.75% and 94.87%, respectively). High urinary N-Ag levels were associated with the absence of SARS-CoV-2 nucleocapsid antibodies, admission in intensive care units, high C-reactive protein levels, lymphopenia, eosinopenia, and high lactate dehydrogenase. A higher accuracy was observed for urine N-Ag as a predictor of severe Covid-19 compared to blood N-Ag. CONCLUSIONS: Our study demonstrate that N-Ag is present in the urine of patients hospitalized in the early phase of Covid-19. As a direct marker of SARS-CoV-2, urinary N-Ag reflects the dissemination of viral compounds in the body. Urine N-Ag may be a useful marker for disease severity of SARS-CoV-2 infections.

6.
Front Immunol ; 12: 697329, 2021.
Article in English | MEDLINE | ID: covidwho-1357529

ABSTRACT

Various neurological symptoms have been associated to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection including headache, fever, anosmia, ageusia, but also, encephalitis, Guillain-Barre syndrome and ischemic stroke. Responsible for the current coronavirus disease (COVID-19) pandemic, SARS-CoV-2 may access and affect the central nervous system (CNS) by several pathways such as axonal retrograde transport or through interaction with the blood-brain barrier (BBB) or blood-cerebrospinal fluid (CSF) barrier. Here, we explored the molecular and cellular effects of direct SARS-CoV-2 infection of human BBB cells. We observed low replication of SARS-CoV-2 that was accompanied by very moderate inflammatory response. Using a human in vitro BBB model, we also described low replication levels without strong inflammatory response or modulation of endothelium integrity. Finally, using serum samples from COVID-19 patients, we highlighted strong concentrations of pro-inflammatory factors that did not perturb BBB integrity after short term exposure. Altogether, our results show that the main mechanism of brain access following SARS-CoV-2 infection does not seem to be directed by brain infection through endothelial cells.


Subject(s)
Blood-Brain Barrier/virology , Brain/virology , Endothelial Cells/virology , SARS-CoV-2/growth & development , Virus Replication/physiology , Animals , COVID-19/pathology , Cell Line, Tumor , Chlorocebus aethiops , Humans , Vero Cells
7.
Breastfeed Med ; 16(1): 29-38, 2021 01.
Article in English | MEDLINE | ID: covidwho-1228415

ABSTRACT

In addition to providing life-giving nutrients and other substances to the breastfed infant, human milk can also represent a vehicle of pathogen transfer. As such, when an infectious disease outbreak, epidemic, or pandemic occurs-particularly when it is associated with a novel pathogen-the question will naturally arise as to whether the pathogen can be transmitted through breastfeeding. Until high-quality data are generated to answer this question, abandonment of breastfeeding due to uncertainty can result. The COVID-19 pandemic, which was in full swing at the time this document was written, is an excellent example of this scenario. During these times of uncertainty, it is critical for investigators conducting research to assess the possible transmission of pathogens through milk, whether by transfer through the mammary gland or contamination from respiratory droplets, skin, breast pumps, and milk containers, and/or close contact between mother and infant. To promote the most rigorous science, it is critical to outline optimal methods for milk collection, handling, storage, and analysis in these situations, and investigators should openly share their methods in published materials. Otherwise, the risks of inconsistent test results from preanalytical and analytical variation, false positives, and false negatives are unacceptably high and the ability to provide public health guidance poor. In this study, we provide "best practices" for collecting human milk samples for COVID-19 research with the intention that this will also be a useful guide for future pandemics.


Subject(s)
Benchmarking , Breast Feeding/methods , COVID-19/prevention & control , Infection Control/methods , Infectious Disease Transmission, Vertical/prevention & control , COVID-19/transmission , Female , Humans , Infant, Newborn , Intention , Milk, Human/virology , Mothers/psychology , SARS-CoV-2
8.
J Med Virol ; 93(5): 3069-3076, 2021 05.
Article in English | MEDLINE | ID: covidwho-1196539

ABSTRACT

The implementation of rapid diagnostic tests (RDTs) may enhance the efficiency of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing, as RDTs are widely accessible and easy to use. The aim of this study was to evaluate the performance of a diagnosis strategy based on a combination of antigen and immunoglobulin M (IgM) or immunoglobulin G (IgG) serological RDTs. Plasma and nasopharyngeal samples were collected between 14 March and 11 April 2020 at hospital admission from 45 patients with reverse transcription polymerase chain reaction (RT-PCR) confirmed COVID-19 and 20 negative controls. SARS-CoV-2 antigen (Ag) was assessed in nasopharyngeal swabs using the Coris Respi-Strip. For IgM/IgG detection, SureScreen Diagnostics and Szybio Biotech RDTs were used in addition to laboratory assays (Abbott Alinity i SARS-CoV-2 IgG and Theradiag COVID-19 IgM enzyme-linked immunosorbent assay). Using the Ag RDT, 13 out of 45 (29.0%) specimens tested positive, the sensitivity was 87.0% for cycle threshold (Ct ) values ≤25% and 0% for Ct values greater than 25. IgG detection was associated with high Ct values and the amount of time after the onset of symptoms. The profile of isolated IgM on RDTs was more frequently observed during the first and second week after the onset of symptoms. The combination of Ag and IgM/IgG RDTs enabled the detection of up to 84.0% of COVID-19 confirmed cases at hospital admission. Antigen and antibody-based RDTs showed suboptimal performances when used alone. However when used in combination, they are able to identify most COVID-19 patients admitted in an emergency department.


Subject(s)
Antibodies, Viral/blood , Antigens, Viral/blood , COVID-19 Serological Testing/methods , COVID-19/diagnosis , SARS-CoV-2/isolation & purification , Adult , Aged , Aged, 80 and over , COVID-19/virology , Enzyme-Linked Immunosorbent Assay , Female , Hospitalization , Humans , Immunoglobulin G/blood , Immunoglobulin M/blood , Male , Middle Aged , Nasopharynx/virology , Reverse Transcriptase Polymerase Chain Reaction/methods , Serologic Tests/methods
9.
Contemp Clin Trials ; 105: 106402, 2021 06.
Article in English | MEDLINE | ID: covidwho-1188374

ABSTRACT

Post-natal HIV infection through breastfeeding remains a challenge in many low and middle-income countries, particularly due to non-availability of alternative infant feeding options and the suboptimal Prevention of Mother to Child Transmission of HIV-1 (PMTCT) cascade implementation and monitoring. The PROMISE-EPI study aims to address the latter by identifying HIV infected mothers during an almost never-missed visit for their infant, the second extended program on immunization visit at 6-8 weeks of age (EPI-2). The study is divided into 3 components inclusive of an open-label randomized controlled trial aiming to assess the efficacy of a responsive preventive intervention compared to routine intervention based on the national PMTCT guidelines for HIV-1 uninfected exposed breastfeeding infants. The preventive intervention includes: a) Point of care testing for early infant HIV diagnosis and maternal viral load; b) infant, single-drug Pre-Exposure Prophylaxis (PrEP) (lamivudine) if mothers are virally unsuppressed. The primary outcome is HIV-transmission rate from EPI-2 to 12 months. The study targets to screen 37,000 mother/infant pairs in Zambia and Burkina Faso to identify 2000 mother/infant pairs for the clinical trial. The study design and challenges faced during study implementation are described, including the COVID-19 pandemic and the amended HIV guidelines in Zambia in 2020 (triple-drug PrEP in HIV exposed infants guided by quarterly maternal viral load). The changes in the Zambian guidelines raised several questions including the equipoise of PrEP options, the standard of care-triple-drug (control arm in Zambia) versus the study-single-drug (intervention arm). Trial registration number (www.clinicaltrials.gov): NCT03869944. Submission category: Study Design, Statistical Design, Study Protocols.


Subject(s)
Anti-HIV Agents/therapeutic use , Breast Feeding , HIV Infections/drug therapy , HIV Infections/transmission , Infectious Disease Transmission, Vertical/prevention & control , Lamivudine/therapeutic use , Adolescent , Adult , Anti-HIV Agents/administration & dosage , Anti-HIV Agents/adverse effects , Burkina Faso , COVID-19/epidemiology , Cross-Sectional Studies , Female , HIV Infections/diagnosis , Humans , Infant , Lamivudine/administration & dosage , Lamivudine/adverse effects , Pandemics , Pre-Exposure Prophylaxis/methods , Research Design , SARS-CoV-2 , Viral Load , Young Adult , Zambia
10.
Lancet Glob Health ; 9(4): e552-e557, 2021 04.
Article in English | MEDLINE | ID: covidwho-1104369

ABSTRACT

The COVID-19 pandemic has raised concern about the possibility and effects of mother-infant transmission of SARS-CoV-2 through breastfeeding and close contact. The insufficient available evidence has resulted in differing recommendations by health professional associations and national health authorities. We present an approach for deciding public health policy on infant feeding and mother-infant contact in the context of COVID-19, or for future emerging viruses, that balances the risks that are associated with viral infection against child survival, lifelong health, and development, and also maternal health. Using the Lives Saved Tool, we used available data to show how different public health approaches might affect infant mortality. Based on existing evidence, including population and survival estimates, the number of infant deaths in low-income and middle-income countries due to COVID-19 (2020-21) might range between 1800 and 2800. By contrast, if mothers with confirmed SARS-CoV-2 infection are recommended to separate from their newborn babies and avoid or stop breastfeeding, additional deaths among infants would range between 188 000 and 273 000.


Subject(s)
COVID-19 , Mother-Child Relations , Policy Making , Public Health , Female , Global Health , Humans , Infant
11.
J Infect Dis ; 223(4): 562-567, 2021 02 24.
Article in English | MEDLINE | ID: covidwho-1101848

ABSTRACT

We assessed the expression of CD169, a type I interferon-inducible receptor, on monocytes (monocyte CD169 [mCD169]) in 53 adult patients admitted to the hospital during the coronavirus disease 2019 (COVID-19) outbreak for a suspicion of severe acute respiratory syndrome coronavirus 2 infection. Monocyte CD169 was strongly overexpressed in 30 of 32 (93.7%) confirmed COVID-19 cases, compared with 3 of 21 (14.3%) patients in whom the diagnosis of COVID-19 was finally ruled out. Monocyte CD169 was associated with the plasma interferon-alpha level and thrombocytopenia. Monocyte CD169 testing may be helpful for the rapid triage of suspected COVID-19 patients during an outbreak.


Subject(s)
COVID-19/diagnosis , Monocytes/metabolism , Sialic Acid Binding Ig-like Lectin 1/metabolism , Aged , Biomarkers/metabolism , COVID-19/metabolism , Early Diagnosis , Female , Flow Cytometry , Humans , Male , Middle Aged , Monocytes/virology , ROC Curve
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