Two distinct immunopathological profiles in autopsy lungs of COVID-19

Abstract Coronavirus Disease 19 (COVID-19) is a respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has grown to a worldwide pandemic with substantial mortality. Immune mediated damage has been proposed as a pathogenic factor, but immune responses in lungs of COVID-19 patients remain poorly characterized. Here we show transcriptomic, histologic and cellular profiles of post mortem COVID-19 (n = 34 tissues from 16 patients) and normal lung tissues (n = 9 tissues from 6 patients). Two distinct immunopathological reaction patterns of lethal COVID-19 are identified. One pattern shows high local expression of interferon stimulated genes (ISGhigh) and cytokines, high viral loads and limited pulmonary damage, the other pattern shows severely damaged lungs, low ISGs (ISGlow), low viral loads and abundant infiltrating activated CD8+ T cells and macrophages. ISGhigh patients die significantly earlier after hospitalization than ISGlow patients. Our study may point to distinct stages of progression of COVID-19 lung disease and highlights the need for peripheral blood biomarkers that inform about patient lung status and guide treatment.

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Two distinct immunopathological profiles in lungs of lethal COVID-19

10.21203/rs.3.rs-37729/v1 ◽

2020 ◽

Author(s):

Ronny Nienhold ◽

Yari Ciani ◽

Viktor Koelzer ◽

Alexandar Tzankov ◽

Jasmin Haslbauer ◽

...

Keyword(s):

Immune Responses ◽

The Other ◽

High Expression ◽

Normal Lung ◽

Post Mortem ◽

Viral Loads ◽

Interferon Stimulated Genes ◽

Hospitalization Time ◽

Pulmonary Damage ◽

Reaction Patterns

Abstract Immune responses in lungs of Coronavirus Disease 2019 (COVID-19) are poorly characterized. We conducted transcriptomic, histologic and cellular profiling of post mortem COVID-19 and normal lung tissues. Two distinct immunopathological reaction patterns were identified. One pattern showed high expression of interferon stimulated genes (ISGs) and cytokines, high viral loads and limited pulmonary damage, the other pattern showed severely damaged lungs, low ISGs, low viral loads and abundant immune infiltrates. Distinct patterns of pulmonary COVID-19 immune responses correlated to hospitalization time and may guide treatment and vaccination approaches.

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Two distinct immunopathological profiles in lungs of lethal COVID-19

10.1101/2020.06.17.20133637 ◽

2020 ◽

Cited By ~ 3

Author(s):

Ronny Nienhold ◽

Yari Ciani ◽

Viktor H. Koelzer ◽

Alexandar Tzankov ◽

Jasmin D. Haslbauer ◽

...

Keyword(s):

Immune Responses ◽

The Other ◽

High Expression ◽

Normal Lung ◽

Post Mortem ◽

Viral Loads ◽

Interferon Stimulated Genes ◽

Hospitalization Time ◽

Pulmonary Damage ◽

Reaction Patterns

AbstractImmune responses in lungs of Coronavirus Disease 2019 (COVID-19) are poorly characterized. We conducted transcriptomic, histologic and cellular profiling of post mortem COVID-19 and normal lung tissues. Two distinct immunopathological reaction patterns were identified. One pattern showed high expression of interferon stimulated genes (ISGs) and cytokines, high viral loads and limited pulmonary damage, the other pattern showed severely damaged lungs, low ISGs, low viral loads and abundant immune infiltrates. Distinct patterns of pulmonary COVID-19 immune responses correlated to hospitalization time and may guide treatment and vaccination approaches.

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Modelling upper respiratory viral load dynamics of SARS-CoV-2

BMC Medicine ◽

10.1186/s12916-021-02220-0 ◽

2022 ◽

Vol 20 (1) ◽

Author(s):

Joseph D. Challenger ◽

Cher Y. Foo ◽

Yue Wu ◽

Ada W. C. Yan ◽

Mahdi Moradi Marjaneh ◽

...

Keyword(s):

Viral Load ◽

Immune Responses ◽

Mechanistic Model ◽

Severity Of Illness ◽

Upper Respiratory Tract ◽

Neutralising Antibodies ◽

Immune Mediated ◽

Peak Viral Load ◽

Upper Respiratory ◽

Serial Measurements

AbstractRelationships between viral load, severity of illness, and transmissibility of virus are fundamental to understanding pathogenesis and devising better therapeutic and prevention strategies for COVID-19. Here we present within-host modelling of viral load dynamics observed in the upper respiratory tract (URT), drawing upon 2172 serial measurements from 605 subjects, collected from 17 different studies. We developed a mechanistic model to describe viral load dynamics and host response and contrast this with simpler mixed-effects regression analysis of peak viral load and its subsequent decline. We observed wide variation in URT viral load between individuals, over 5 orders of magnitude, at any given point in time since symptom onset. This variation was not explained by age, sex, or severity of illness, and these variables were not associated with the modelled early or late phases of immune-mediated control of viral load. We explored the application of the mechanistic model to identify measured immune responses associated with the control of the viral load. Neutralising antibodies correlated strongly with modelled immune-mediated control of viral load amongst subjects who produced neutralising antibodies. Our models can be used to identify host and viral factors which control URT viral load dynamics, informing future treatment and transmission blocking interventions.

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The Mycobacterium tuberculosis PE_PGRS Protein Family Acts as an Immunological Decoy to Subvert Host Immune Response

International Journal of Molecular Sciences ◽

10.3390/ijms23010525 ◽

2022 ◽

Vol 23 (1) ◽

pp. 525

Author(s):

Tarina Sharma ◽

Anwar Alam ◽

Aquib Ehtram ◽

Anshu Rani ◽

Sonam Grover ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

Immune Responses ◽

Current Knowledge ◽

Immune Effector ◽

Host Immune Responses ◽

Intrinsically Disordered ◽

Multiple Strategies ◽

Latent Stage ◽

Immune Mediated ◽

Critical Edge

Mycobacterium tuberculosis (M.tb) is a successful pathogen that can reside within the alveolar macrophages of the host and can survive in a latent stage. The pathogen has evolved and developed multiple strategies to resist the host immune responses. M.tb escapes from host macrophage through evasion or subversion of immune effector functions. M.tb genome codes for PE/PPE/PE_PGRS proteins, which are intrinsically disordered, redundant and antigenic in nature. These proteins perform multiple functions that intensify the virulence competence of M.tb majorly by modulating immune responses, thereby affecting immune mediated clearance of the pathogen. The highly repetitive, redundant and antigenic nature of PE/PPE/PE_PGRS proteins provide a critical edge over other M.tb proteins in terms of imparting a higher level of virulence and also as a decoy molecule that masks the effect of effector molecules, thereby modulating immuno-surveillance. An understanding of how these proteins subvert the host immunological machinery may add to the current knowledge about M.tb virulence and pathogenesis. This can help in redirecting our strategies for tackling M.tb infections.

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In depth characterization of vaccine breakthrough infections with SARS-CoV-2 among healthcare workers of a Dutch academic medical center

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab553 ◽

2021 ◽

Author(s):

Lidewij W Rümke ◽

Femke C Groenveld ◽

Yvonne M G van Os ◽

Patrique Praest ◽

Anniek A N Tanja ◽

...

Keyword(s):

Immune Responses ◽

Healthcare Workers ◽

Medical Center ◽

Academic Medical Center ◽

Risk Exposure ◽

Live Virus ◽

Viral Loads ◽

Academic Medical ◽

T Cell Immune Responses

Abstract SARS-CoV-2 infection after COVID-19 vaccination raises concerns about the emergence of vaccine escape variants. Here we characterize 14 breakthrough infections among 5860 fully vaccinated Dutch healthcare workers ≥14 days post final dose of vaccination with either BNT162b2, mRNA-1273 or Ad26.COV2.S. These breakthrough infections presented with regular B.1.1.7 (Alpha) and B.1.617.2 (Delta) variants and high viral loads, despite normal vaccine induced B- and T-cell immune responses detected by live virus neutralization assays and ELISpot. High-risk exposure settings, such as in households, indicate a potential risk of viral transmission despite full vaccination.

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Human Cystic Echinococcosis: Old Problems and New Perspectives

Interdisciplinary Perspectives on Infectious Diseases ◽

10.1155/2009/474368 ◽

2009 ◽

Vol 2009 ◽

pp. 1-7 ◽

Cited By ~ 35

Author(s):

Alessandra Siracusano ◽

Antonella Teggi ◽

Elena Ortona

Keyword(s):

Molecular Biology ◽

Inflammatory Response ◽

Immune Responses ◽

Cystic Echinococcosis ◽

Clinical Management ◽

Host Immune Responses ◽

New Concepts ◽

Immune Mediated ◽

Parasite Survival ◽

Human Cystic Echinococcosis

Cystic echinococcosis (CE) is a widespread chronic endemic helminthic disease caused by infection with metacestodes of the tapewormEchinococcus granulosus. CE affects humans and has a worldwide prevalence of approximately six million. In this review, we discuss current findings in diagnosis and clinical management of CE and new concepts relating toE. granulosusmolecules that directly modulate the host immune responses favouring a strong anti-inflammatory response and perpetuating parasite survival in the host. New insights into the molecular biology ofE. granulosuswill improve considerably our knowledge of the disease and will provide new potential therapeutic applications to treat or prevent inflammatory immune-mediated disease.

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Immunogenicity and protective efficacy of orally administered recombinant Lactococcus lactis expressing surface-bound HIV Env

Blood ◽

10.1182/blood-2003-01-0110 ◽

2003 ◽

Vol 102 (1) ◽

pp. 223-228 ◽

Cited By ~ 94

Author(s):

Ke-Qin Xin ◽

Yuka Hoshino ◽

Yoshihiko Toda ◽

Shizunobu Igimi ◽

Yoshitsugu Kojima ◽

...

Keyword(s):

Immune Responses ◽

Lactococcus Lactis ◽

Potential Role ◽

Protective Efficacy ◽

Oral Immunization ◽

Vaccine Strategy ◽

Regional Lymph Nodes ◽

Viral Loads ◽

Recombinant Lactococcus Lactis ◽

Further Development

Abstract This study investigates whether genetically modified orally administered Lactococcus lactis (L lactis) could be used as an HIV vaccine. L lactis is immunogenic and extremely safe when delivered orally. We created a recombinant L lactis vector expressing the envelope protein of HIV on its cell surface. Oral immunization with this vector induced high levels of HIV-specific serum IgG and fecal IgA antibodies. Cell-mediated immune responses also were generated in both the regional lymph nodes and the spleen. Dendritic cells are readily infected by L lactis and appear to play a potential role in mediating the development of these immune responses. The protective efficacy of this vaccine strategy was demonstrated by challenging mice intraperitoneally with an HIV Env–expressing vaccinia virus. Their viral loads were 350-fold lower than those of control mice. These findings support the further development of L lactis–based HIV vaccines. (Blood. 2003; 102:223-228)

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Innate immune-mediated antiviral response to SARS-CoV-2 and convalescent sera a potential prophylactic and therapeutic agent to tackle COVID-19

Antibody Therapeutics ◽

10.1093/abt/tbaa019 ◽

2020 ◽

Vol 3 (3) ◽

pp. 212-220

Author(s):

Abdullah ◽

Shah Faisal ◽

Komal Aman ◽

Anees ur Rahman

Keyword(s):

Immune Responses ◽

Viral Replication ◽

Neutralizing Antibodies ◽

Passive Immunization ◽

Nuclear Factor Κb ◽

Innate Immune ◽

Alveolar Cells ◽

Experimental Drugs ◽

Immune Mediated

ABSTRACT The whole world is confronting the pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Unfortunately, there is no vaccine to prevent novel coronavirus infection. Besides several experimental drugs, the strong immune responses and convalescent sera are the current two potential options to tackle coronavirus disease 2019 (COVID-19) infection. Innate immune-mediated antiviral responses are initiated by the recognition of viral invasion through pathogen-associated molecular patterns (PAMPs). In coronavirus, the PAMPs are recognized by Toll-like receptors 3 and 7, endosomal ribonucleic acid receptors, RNA in cytosol, and by pattern recognition receptor (RIG-1) in the alveolar cells and site of invasion. Nuclear factor-κB and interferon regulatory transcription factor (IRF3) are activated in response to the above recognition episode and translocate to nucleus. These transcription factors in the nucleus initiate the expression of interferon type 1 and pro-inflammatory cytokine storm, which leads to first line of defense at the site of viral entrance. The effectiveness of innate immune system is greatly relies on type 1 interferons and its cascade, because of their role in the inhibition of viral replication and initiation of adaptive immune responses. The successful interferon type 1 response put down the viral replication and transmission at prompt point. Passive immunization is the administering of antibodies into infected patients, which is taken from recovered individuals. The convalescent sera of the recovered COVID-19 patients are containing antiviral neutralizing antibodies and are used therapeutically for infected individuals by SARS-CoV-2 and for the purpose of prophylaxis in exposed individuals. The convalescent sera is found effective when administered early at the onset of symptoms.

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ncRNAs in Type-2 Immunity

Non-Coding RNA ◽

10.3390/ncrna6010010 ◽

2020 ◽

Vol 6 (1) ◽

pp. 10 ◽

Cited By ~ 2

Author(s):

Riccardo Guidi ◽

Christopher J. Wedeles ◽

Mark S. Wilson

Keyword(s):

Immune Responses ◽

Immune Cell ◽

Allergic Diseases ◽

Parasitic Helminths ◽

Medical Needs ◽

Type 2 Immunity ◽

Non Coding Rna ◽

Immune Mediated ◽

Immunological Diseases

Immunological diseases, including asthma, autoimmunity and immunodeficiencies, affect a growing percentage of the population with significant unmet medical needs. As we slowly untangle and better appreciate these complex genetic and environment-influenced diseases, new therapeutically targetable pathways are emerging. Non-coding RNA species, which regulate epigenetic, transcriptional and translational responses are critical regulators of immune cell development, differentiation and effector function, and may represent one such new class of therapeutic targets. In this review we focus on type-2 immune responses, orchestrated by TH2 cell-derived cytokines, IL-4, IL-5 and IL-13, which stimulate a variety of immune and tissue responses- commonly referred to as type-2 immunity. Evolved to protect us from parasitic helminths, type-2 immune responses are observed in individuals with allergic diseases, including Asthma, atopic dermatitis and food allergy. A growing number of studies have identified the involvement of various RNA species, including microRNAs (miRNA) and long non-coding (lncRNA), in type-2 immune responses and in both clinical and pre-clinical disease settings. We highlight these recent findings, identify gaps in our understanding and provide a perspective on how our current understanding can be harnessed for novel treat opportunities to treat type-2 immune-mediated diseases.

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Interplay between Intrinsic and Innate Immunity during HIV Infection

Cells ◽

10.3390/cells8080922 ◽

2019 ◽

Vol 8 (8) ◽

pp. 922 ◽

Cited By ~ 9

Author(s):

Louis Bergantz ◽

Frédéric Subra ◽

Eric Deprez ◽

Olivier Delelis ◽

Clémence Richetta

Keyword(s):

Innate Immunity ◽

Immune Responses ◽

Hiv Infection ◽

Type I ◽

Restriction Factors ◽

Intrinsic Immunity ◽

First Line ◽

Hiv Replication ◽

Interferon Stimulated Genes ◽

Immunodeficiency Virus

Restriction factors are antiviral components of intrinsic immunity which constitute a first line of defense by blocking different steps of the human immunodeficiency virus (HIV) replication cycle. In immune cells, HIV infection is also sensed by several pattern recognition receptors (PRRs), leading to type I interferon (IFN-I) and inflammatory cytokines production that upregulate antiviral interferon-stimulated genes (ISGs). Several studies suggest a link between these two types of immunity. Indeed, restriction factors, that are generally interferon-inducible, are able to modulate immune responses. This review highlights recent knowledge of the interplay between restriction factors and immunity inducing antiviral defenses. Counteraction of this intrinsic and innate immunity by HIV viral proteins will also be discussed.

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