Mucosal Immune Responses Predict Clinical Outcomes during Influenza Infection Independently of Age and Viral Load

AbstractTo examine innate immune responses in early SARS-CoV-2 infection that may change clinical outcomes, we compared nasopharyngeal swab data from 20 virus-positive and 20 virus-negative individuals. Multiple innate immune-related and ACE-2 transcripts increased with infection and were strongly associated with increasing viral load. We found widespread discrepancies between transcription and translation. Interferon proteins were unchanged or decreased in infected samples suggesting virally-induced shut-off of host anti-viral protein responses. However, IP-10 and several interferon-stimulated gene proteins increased with viral load. Older age was associated with modifications of some effects. Our findings may characterize the disrupted immune landscape of early disease.

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Distinct systemic and mucosal immune responses during acute SARS-CoV-2 infection

Nature Immunology ◽

10.1038/s41590-021-01028-7 ◽

2021 ◽

Author(s):

Nikaïa Smith ◽

Pedro Goncalves ◽

Bruno Charbit ◽

Ludivine Grzelak ◽

Maxime Beretta ◽

...

Keyword(s):

Viral Load ◽

Immune Responses ◽

Clinical Outcomes ◽

Neutralizing Antibodies ◽

Respiratory Infections ◽

Acute Infection ◽

Mucosal Inflammation ◽

Integrated Analysis ◽

Humoral Responses ◽

Interferon Responses

AbstractCoordinated local mucosal and systemic immune responses following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection either protect against coronavirus disease 2019 (COVID-19) pathologies or fail, leading to severe clinical outcomes. To understand this process, we performed an integrated analysis of SARS-CoV-2 spike-specific antibodies, cytokines, viral load and bacterial communities in paired nasopharyngeal swabs and plasma samples from a cohort of clinically distinct patients with COVID-19 during acute infection. Plasma viral load was associated with systemic inflammatory cytokines that were elevated in severe COVID-19, and also with spike-specific neutralizing antibodies. By contrast, nasopharyngeal viral load correlated with SARS-CoV-2 humoral responses but inversely with interferon responses, the latter associating with protective microbial communities. Potential pathogenic microorganisms, often implicated in secondary respiratory infections, were associated with mucosal inflammation and elevated in severe COVID-19. Our results demonstrate distinct tissue compartmentalization of SARS-CoV-2 immune responses and highlight a role for the nasopharyngeal microbiome in regulating local and systemic immunity that determines COVID-19 clinical outcomes.

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Early amplified respiratory bioactive lipid response is associated with worse outcomes in pediatric influenza-related respiratory failure

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa122 ◽

2020 ◽

Author(s):

Veronica G Anania ◽

Adrienne G Randolph ◽

Xiaoying Yang ◽

Allen Nguyen ◽

Margaret M Newhams ◽

...

Keyword(s):

Viral Load ◽

Respiratory Failure ◽

Clinical Outcomes ◽

Influenza Infection ◽

Bioactive Lipids ◽

Ventilator Support ◽

Lipid Response ◽

Cytokine Levels ◽

Patients At Risk ◽

Anti Inflammatory

Abstract Background Biomarkers are needed for early identification of patients at risk of severe complications from influenza infection, including prolonged respiratory failure and death. Eicosanoids are bioactive lipid mediators with pro- and anti-inflammatory properties produced in response to infection. This study assessed the relationships between the host bioactive lipid response, influenza viral load, and clinical outcomes. Methods Influenza positive, intubated children <18 years old were enrolled across 26 U.S. PICUs. Mass spectrometry was used to measure >100 lipid metabolites in endotracheal and nasopharyngeal samples. Influenza viral load was measured by quantitative PCR. Results Age and bacterial co-infection were associated with multiple bioactive lipids (p<0.05). Influenza viral load was lower in patients with bacterial co-infection compared to those without, and pro-inflammatory bioactive lipids positively correlated with viral load in bacterially co-infected children (p<0.05). Lipids associated with disease resolution correlated with viral load in patients without bacterial co-infection (p<0.01). After adjusting for age and bacterial co-infection status, elevated pro- and anti-inflammatory lipids measured early in the ICU course were associated with higher mortality, whereas influenza viral load and endotracheal cytokine levels were not associated with clinical outcomes. Prostaglandin E2, arachidonic acid, docosahexaenoic acid, and 12-hydroxyeicosatetraenoic acid measured within 72 hours of PICU admission predicted death or prolonged (≥28 days) mechanical ventilator support (AUC 0.72-0.79, p<0.02), not explained by admission illness severity. Conclusions Children with influenza-related complications have early bioactive lipid responses that may reflect lung disease severity. Respiratory bioactive lipids are candidate prognostic biomarkers to identify children with the most severe clinical outcomes.

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Distinct systemic and mucosal immune responses to SARS-CoV-2

10.1101/2021.03.01.21251633 ◽

2021 ◽

Author(s):

Nikaïa Smith ◽

Pedro Goncalves ◽

Bruno Charbit ◽

Ludivine Grzelak ◽

Maxime Beretta ◽

...

Keyword(s):

Viral Load ◽

Immune Responses ◽

Clinical Outcomes ◽

Neutralizing Antibodies ◽

Respiratory Infections ◽

Acute Infection ◽

Mucosal Inflammation ◽

Integrated Analysis ◽

Humoral Responses ◽

Interferon Responses

SummaryCoordinated local mucosal and systemic immune responses following SARS-CoV-2 infection protect against COVID-19 pathologies or fail leading to severe clinical outcomes. To understand this process, we performed an integrated analysis of SARS-CoV-2 spike-specific antibodies, cytokines, viral load and 16S bacterial communities in paired nasopharyngeal swabs and plasma samples from a cohort of clinically distinct COVID-19 patients during acute infection. Plasma viral load was associated with systemic inflammatory cytokines that were elevated in severe COVID-19, and also with spike-specific neutralizing antibodies. In contrast, nasopharyngeal viral load correlated with SARS-CoV-2 humoral responses but inversely with interferon responses, the latter associating with protective microbial communities. Potential pathogenic microrganisms, often implicated in secondary respiratory infections, were associated with mucosal inflammation and elevated in severe COVID-19. Our results demonstrate distinct tissue compartmentalization of SARS-CoV-2 immune responses and highlight a role for the nasopharyngeal microbiome in regulating local and systemic immunity that determines COVID-19 clinical outcomes.

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CEA (Carcinoembryonic antigen) shows identity to gp189 and can modulate mucosal immune responses

Gastroenterology ◽

10.1016/s0016-5085(01)80295-x ◽

2001 ◽

Vol 120 (5) ◽

pp. A60-A60

Author(s):

M PARK ◽

K BECKER ◽

L MAYER

Keyword(s):

Immune Responses ◽

Carcinoembryonic Antigen ◽

Mucosal Immune Responses

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Faculty Opinions recommendation of Fasting-Refeeding Impacts Immune Cell Dynamics and Mucosal Immune Responses.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.736470900.793564498 ◽

2019 ◽

Author(s):

Daniel Mucida

Keyword(s):

Immune Responses ◽

Immune Cell ◽

Cell Dynamics ◽

Mucosal Immune Responses

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Couples-focused intervention to improve engagement in HIV care: protocol for a randomised controlled trial

BMJ Open ◽

10.1136/bmjopen-2020-037468 ◽

2021 ◽

Vol 11 (3) ◽

pp. e037468

Author(s):

Alyssa Paige Tabrisky ◽

Lara S Coffin ◽

David P Olem ◽

Torsten B Neilands ◽

Mallory O'Neill Johnson

Keyword(s):

Viral Load ◽

Medication Adherence ◽

Clinical Outcomes ◽

Virological Suppression ◽

Hiv Care ◽

Randomised Control Trial ◽

Engagement In Care ◽

Engagement In Hiv Care ◽

Living With Hiv ◽

Counselling Intervention

Introduction Advances in HIV treatment have proven to be effective in increasing virological suppression, thereby decreasing morbidity, and increasing survival. Medication adherence is an important factor in reducing viral load among people living with HIV (PLWH) and in the elimination of transmission of HIV to uninfected partners. Achieving optimal medication adherence involves individuals taking their medications every day or as prescribed by their provider. However, not all PLWH in the USA are engaged in care, and only a minority have achieved suppressed viral load (viral load that is lower than the detectable limit of the assay). Sexual and gender minorities (SGM; those who do not identify as heterosexual or those who do not identify as the sex they were assigned at birth) represent a high-risk population for poor clinical outcomes and increased risk of HIV transmission, as they face barriers that can prevent optimal engagement in HIV care. Research in dyadic support, specifically within primary romantic partnerships, offers a promising avenue to improving engagement in care and treatment outcomes among SGM couples. Dyadic interventions, especially focused on primary romantic partnerships, have the potential to have a sustained impact after the structured intervention ends. Methods and analysis This paper describes the protocol for a randomised control trial of a theory-grounded, piloted intervention (DuoPACT) that cultivates and leverages the inherent sources of support within primary romantic relationships to improve engagement in HIV care and thus clinical outcomes among persons who are living with HIV and who identify as SGM (or their partners). Eligible participants must report being in a primary romantic relationship for at least 3 months, speak English, at least one partner must identify as a sexual or gender minority and at least one partner must be HIV+ with suboptimal engagement in HIV care, defined as less than excellent medication adherence, having not seen a provider in at least the past 8 months, having a detectable or unknown viral load or not currently on antiretroviral therapy. Eligible consenting couples are allocated equally to the two study arms: a structured six-session couples counselling intervention (DuoPACT) or a three-session individually-delivered HIV adherence counselling intervention (LifeSteps). The primary aim is to evaluate the efficacy of DuoPACT on virological suppression among HIV+ members of SGM couples with suboptimal engagement in care. The DuoPACT study began its target enrolment of 150 couples (300 individuals) in August 2017, and will continue to enrol until June 2021. Ethics and dissemination All procedures are approved by the Institutional Review Board at the University of California, San Francisco. Written informed consent is obtained from all participants at enrolment, and study progress is reviewed twice yearly by an external Safety Monitoring Committee. Dissemination activities will include formal publications and report back sessions with the community. Trial registration number NCT02925949; Pre-results.

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Observational study of the populations accessing rapid point-of-care HIV testing in Winnipeg, Manitoba, Canada, through a retrospective chart review of site records

Sexually Transmitted Infections ◽

10.1136/sextrans-2017-053195 ◽

2017 ◽

Vol 94 (3) ◽

pp. 194-199 ◽

Cited By ~ 4

Author(s):

James Blain Johnston ◽

Joss N Reimer ◽

John L Wylie ◽

Jared Bullard

Keyword(s):

Viral Load ◽

Hiv Testing ◽

Clinical Outcomes ◽

Point Of Care ◽

Age Groups ◽

Linkage To Care ◽

Hiv Positive ◽

Hiv Status ◽

Viral Load Suppression ◽

Hiv Test

ObjectivesHIV point-of-care testing (POCT) has been available in Manitoba since 2008. This study evaluated the effectiveness of POCT at identifying individuals with previously unknown HIV status, its effects on clinical outcomes and the characteristics of the populations reached.MethodsA retrospective database review was conducted for individuals who received HIV POCT from 2011 to 2014. Time to linkage to care and viral load suppression were compared between individuals who tested positive for HIV using POCT and controls identified as positive through standard screening. Testing outcomes for labouring women with undocumented HIV status accessing POCT during labour were also assessed.Results3204 individuals received POCT (1055 females (32.9%) and 2149 males (67.1%)), being the first recorded HIV test for 2205 (68.8%). Males were more likely to be targeted with POCT as their first recorded HIV test (adjusted OR (AOR) 1.40). Between the two main test sites (Main Street Project (MSP) and Nine Circles Community Health Centre), MSP tested relatively fewer males (AOR 0.79) but a higher proportion of members of all age groups over 30 years old (AOR 1.83, 2.51 and 3.64 for age groups 30–39, 40–49 and >50, respectively). There was no difference in time to linkage to care (p=0.345) or viral load suppression (p=0.405) between the POCT and standard screening cohorts. Of 215 women presenting in labour with unknown HIV status, one was identified as HIV positive.ConclusionsPOCT in Manitoba has been successful at identifying individuals with previously unknown HIV-positive status. Demographic differences between the two main testing sites support that this intervention is reaching unique populations. Given that we observed no significant difference in time to clinical outcomes, it is reasonable to continue using POCT as a targeted intervention.MeSH termsHIV infection; rapid HIV testing; vertical infectious disease transmission; community outreach; service delivery; marginalised populations.

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