scholarly journals The COVID-19 immune landscape is dynamically and reversibly correlated with disease severity

2020 ◽  
Author(s):  
Hamid Bolouri ◽  
Cate Speake ◽  
David Skibinski ◽  
S. Alice Long ◽  
Anne M. Hocking ◽  
...  
Keyword(s):  
Immune Response ◽  
Disease Severity ◽  
Severe Disease ◽  
Disease Trajectory ◽  
Adaptive Immune ◽  
Immune Correlates ◽  
Moderate Disease ◽  
Immune Alterations ◽  
Blood Specimens ◽  
Selection Of

AbstractDespite a rapidly growing body of literature on COVID-19, our understanding of the immune correlates of disease severity, course and outcome remains poor. Using mass cytometry, we assessed the immune landscape in longitudinal whole blood specimens from 59 patients presenting with acute COVID-19, and classified based on maximal disease severity. Hospitalized patients negative for SARS-CoV-2 were used as controls. We found that the immune landscape in COVID-19 forms three dominant clusters, which correlate with disease severity. Longitudinal analysis identified a pattern of productive innate and adaptive immune responses in individuals who have a moderate disease course, whereas those with severe disease have features suggestive of a protracted and dysregulated immune response. Further, we identified coordinate immune alterations accompanying clinical improvement and decline that were also seen in patients who received IL-6 pathway blockade. The hospitalized COVID-19 negative cohort allowed us to identify immune alterations that were shared between severe COVID-19 and other critically ill patients. Collectively, our findings indicate that selection of immune interventions should be based in part on disease presentation and early disease trajectory due to the profound differences in the immune response in those with mild to moderate disease and those with the most severe disease.

scholarly journals Stochastic Model of the Adaptive Immune Response Predicts Disease Severity and Captures Enhanced Cross-Reactivity in Natural Dengue Infections

2021 ◽  
Vol 12 ◽  
Author(s):  
Hung D. Nguyen ◽  
Sidhartha Chaudhury ◽  
Adam T. Waickman ◽  
Heather Friberg ◽  
Jeffrey R. Currier ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Stochastic Model ◽  
Disease Severity ◽  
Secondary Infection ◽  
Severe Disease ◽  
Adaptive Immune Response ◽  
Cross Reactivity ◽  
Adaptive Immune ◽  
Severe Manifestation

The dengue virus circulates as four distinct serotypes, where a single serotype infection is typically asymptomatic and leads to acquired immunity against that serotype. However, the developed immunity to one serotype is thought to underlie the severe manifestation of the disease observed in subsequent infections from a different serotype. We developed a stochastic model of the adaptive immune response to dengue infections. We first delineated the mechanisms initiating and sustaining adaptive immune responses during primary infections. We then contrasted these immune responses during secondary infections of either a homotypic or heterotypic serotype to understand the role of pre-existing and reactivated immune pathways on disease severity. Comparison of non-symptomatic and severe cases from heterotypic infections demonstrated that overproduction of specific antibodies during primary infection induces an enhanced population of cross-reactive antibodies during secondary infection, ultimately leading to severe disease manifestations. In addition, the level of disease severity was found to correlate with immune response kinetics, which was dependent on beginning lymphocyte levels. Our results detail the contribution of specific lymphocytes and antibodies to immunity and memory recall that lead to either protective or pathological outcomes, allowing for the understanding and determination of mechanisms of protective immunity.

scholarly journals Pattern Recognition Proteins: First Line of Defense Against Coronaviruses

2021 ◽  
Vol 12 ◽  
Author(s):  
Carlos A. Labarrere ◽  
Ghassan S. Kassab
Keyword(s):  
Immune Response ◽  
Pattern Recognition ◽  
Global Economy ◽  
Rna Viruses ◽  
Severe Disease ◽  
Adaptive Immune Response ◽  
Adaptive Immune ◽  
Recognition Protein ◽  
Pattern Recognition Protein

The rapid outbreak of COVID-19 caused by the novel coronavirus SARS-CoV-2 in Wuhan, China, has become a worldwide pandemic affecting almost 204 million people and causing more than 4.3 million deaths as of August 11 2021. This pandemic has placed a substantial burden on the global healthcare system and the global economy. Availability of novel prophylactic and therapeutic approaches are crucially needed to prevent development of severe disease leading to major complications both acutely and chronically. The success in fighting this virus results from three main achievements: (a) Direct killing of the SARS-CoV-2 virus; (b) Development of a specific vaccine, and (c) Enhancement of the host’s immune system. A fundamental necessity to win the battle against the virus involves a better understanding of the host’s innate and adaptive immune response to the virus. Although the role of the adaptive immune response is directly involved in the generation of a vaccine, the role of innate immunity on RNA viruses in general, and coronaviruses in particular, is mostly unknown. In this review, we will consider the structure of RNA viruses, mainly coronaviruses, and their capacity to affect the lungs and the cardiovascular system. We will also consider the effects of the pattern recognition protein (PRP) trident composed by (a) Surfactant proteins A and D, mannose-binding lectin (MBL) and complement component 1q (C1q), (b) C-reactive protein, and (c) Innate and adaptive IgM antibodies, upon clearance of viral particles and apoptotic cells in lungs and atherosclerotic lesions. We emphasize on the role of pattern recognition protein immune therapies as a combination treatment to prevent development of severe respiratory syndrome and to reduce pulmonary and cardiovascular complications in patients with SARS-CoV-2 and summarize the need of a combined therapeutic approach that takes into account all aspects of immunity against SARS-CoV-2 virus and COVID-19 disease to allow mankind to beat this pandemic killer.

scholarly journals ANTIBODY RESPONSE TO COVID-19 INFECTION- CLINICAL VARIABLES AT PLAY

2020 ◽  
Author(s):  
Anuj Parkash ◽  
Parul Singla ◽  
Meenu Bhatia
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Disease Severity ◽  
Statistical Significance ◽  
Severe Disease ◽  
Initial Symptom ◽  
Igg Antibody ◽  
Duration Of Symptoms ◽  
Clinical Variables ◽  
Significant Difference

ABSTRACTBackgroundThe current COVID19 pandemic began in December 2019 and rapidly expanded to become a global pandemic. The COVID 19 presents multitude of clinical disorders, ranges from asymptomatic infection to severe disease, which can accompanied by multisystem failure leading to death. The immune response to SARS CoV 2 is understood to involve all the components of the system that together causes viral elimination and recovery from the infection. However, such immune responses implicated in the disease has varied presentation ranging from mild to a severe form, which appears to hinge on the loss of the immune regulation between protective and altered responses. In this study, we want to unravel this association of immune responses to various clinical variables, which might have a major role to play, while generating the immune response. The objective was to test this hypothesis in our settings and comparing the results of serologic tests from a group of COVID 19 patients and will analyzed the disease severity in comparison.MethodsTesting for SARS COV2 IgG Antibody was done with chemiluminescent assay on the Ortho Clinical Diagnostic’s (OCD) Vitros 5600 platform.ResultsA total of 106 COVID 19 patients were included in this study, of whom 61 were male and 45 were female. Their mean age was 43.7 years (range 17–83) and the median interval between initial symptom onset and sample collection was 12.33 days. Eighty patients (82%) had mild or moderate symptoms and twenty-six patients (18%) had severe symptoms. The antibody titers were positive in 99 patients (93%) and were found negative in 7 patients (7%). When comparing patients with mild/moderate symptoms and patients with severe/critical diseases, no statistically significant difference was observed between their gender ratios (P = 0.373) and age composition (P = 0.224).ConclusionsThe data presented in this research study did not find any statistical significance between SARS CoV 2 IgG antibody levels with COVID 19 disease severity, duration of symptoms, age, gender, and length of convalescence.

scholarly journals Some Clinical and Immunological Features of Imported COVID-19 Cases in Mongolia

2021 ◽  
Author(s):  
Tsogtsaikhan Sandag ◽  
Enkhsaikhan Lkhagvasuren ◽  
Munkhundrakh Batmunkh ◽  
Oyungerel Ravjir
Keyword(s):  
Immune Response ◽  
Severe Disease ◽  
Lower Percentage ◽  
Enzyme Linked Immunosorbent Assay ◽  
P Value ◽  
Mild Disease ◽  
Pulmonary Infiltrates ◽  
Cytokines And Chemokines ◽  
Moderate Disease ◽  
Serum Crp

SARS-CoV-2 disturbs the normal immune responses causing an uncontrolled inflammatory response in patients with severe COVID-19. The pattern of the immune response to the SARS-CoV-2 in individuals may fluctuate. Some have a virus-dependent protective immune response resulting in asymptomatic or mild disease with elimination of the virus within 7-10 days after onset of infection. Others develop virus non-dependent uncontrolled hyper-inflammation in the later period, leading to severe disease with cytokine storm, acute respiratory distress syndrome, disseminated intravascular coagulation and multi-organ failure. Methods: The serum of 72 patients was investigated for titers of 15 cytokines and chemokines using Enzyme-linked immunosorbent assay (ELISA) kits in the serum of peripheral blood samples. The means of groups were compared using ANOVA followed by Tukey multiple post hoc comparisons if the ANOVA p-value was <0.05. Results: Patients with pulmonary infiltrates on CT demonstrated a lower percentage of eosinophils (1.38±1.46%) and elevated level of serum CRP (8.57±19.10 mg/dL) compared to patients without pulmonary infiltrates (2.52±1.47% and 1.96±3.02 mg/dL respectively; p<0.05). ROC analysis for patients aged ≥35 years showed patients with mild disease (n=3) had a significantly higher titer of IL-1α and MCP-1 (AUC, 0.958 and 0.917 respectively, p<0.05) compared to patients with moderate disease (n=7).

scholarly journals Higher Circulating Concentration of Interleukin-38 in Patients with Knee Osteoarthritis: Its Association with Disease Severity

2021 ◽  
Author(s):  
Mitra Abassifard ◽  
Hossein Khorramdelazad ◽  
Shayan Rezaee ◽  
Abdollah Jafarzadeh
Keyword(s):  
Inflammatory Responses ◽  
Severe Disease ◽  
Serum Levels ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Adaptive Immune ◽  
Valuable Marker ◽  
Vas Scores ◽  
Blood Specimens ◽  
Group Serum

Evidence showed that chronic inflammatory and immunopathological responses play a pivotal role in the development of osteoarthritis (OA). Interleukin-38 (IL-38) as a novel antiinflammatory cytokine with influential modulatory properties on both innate and adaptive immune responses can be involved in the pathogenesis of OA. Therefore, this study aimed to measure the serum level of IL-38 in OA patients to clarify the positive or negative association with disease and its severity. Blood specimens were collected from two groups including 23 newly-diagnosed OA patients and 22 healthy sex and age-matched subjects as a control group. Serum IL-38 quantities were measured using enzyme-linked immunosorbent assay (ELISA). Significantly higher IL-38 levels were detected in OA patients in comparison with the healthy group (265.78±41.27 pg/mL vs 44.23±6.04 pg/mL, p=0.0001). The IL-38 concentration in OA patients with Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores>40 and in OA patients with visual analog scale (VAS) scores>5 were higher than those with WOMAC scores<40, and VAS scores<5 (p=0.026 and p=0.035, respectively). The IL-38 levels in OA patients with body mass index (BMI)<25 were also significantly higher than in patients with BMI>25 (p=0.05). According to our findings, WOMAC, VAS, and BMI indices may influence the IL-38 serum levels in OA patients and it may be elevated in OA patients to modulate inflammatory responses in a compensatory manner. The patients with OA, especially those with more severe disease express higher serum amounts of IL-38. Accordingly, IL-38 may be considered as a valuable marker for OA.

scholarly journals Steroid harms if given early in COVID-19 viraemia

2021 ◽  
Vol 14 (2) ◽  
pp. e241105
Author(s):  
Kanupriya Arora ◽  
Prasan Kumar Panda
Keyword(s):  
Immune Response ◽  
Immune Regulation ◽  
Severe Disease ◽  
Preventive Measure ◽  
Disease Course ◽  
Supportive Treatment ◽  
Cytokine Storm ◽  
Adaptive Immune ◽  
The One ◽  
Anti Inflammation

COVID-19 is a biphasic illness with an initial viraemia phase and later effective adaptive immune phase, except in a minority of people who develop severe disease. Immune regulation is the key target to treat COVID illness. In anticipation, an elderly man self-medicated himself with dexamethasone on the day of symptom onset of a flu-like illness, took other symptomatic measures and was tested positive for SARS-CoV-2. His condition deteriorated with each passing day resulting in hospitalisation. He demanded oxygen and declared as severe COVID. With supportive treatment, he recovered after the 20th day of illness. Immunosuppression and anti-inflammation are likely to benefit when the immune response is dysregulated and turning into a cytokine storm. A medication that has saved many could be the one predisposing to severity if taken as a preventive measure, too early in the disease course, especially the viraemia phase.

scholarly journals Evidence of Long-Lasting Humoral and Cellular Immunity against SARS-CoV-2 Even in Elderly COVID-19 Convalescents Showing a Mild to Moderate Disease Progression

Life ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 805
Author(s):  
Bastian Fischer ◽  
Christopher Lindenkamp ◽  
Christoph Lichtenberg ◽  
Ingvild Birschmann ◽  
Cornelius Knabbe ◽  
...  
Keyword(s):  
Immune Response ◽  
Cellular Immune Response ◽  
Nucleocapsid Protein ◽  
Interferon Γ ◽  
Special Equipment ◽  
Humoral And Cellular Immunity ◽  
Moderate Disease ◽  
Ifn Γ ◽  
Blood Specimens ◽  
Cellular Immune

We here evaluate the humoral and cellular immune response against SARS-CoV-2 in 41 COVID-19 convalescents. As previous studies mostly included younger individuals, one advantage of our study is the comparatively high mean age of the convalescents included in the cohort considered (54 ± 8.4 years). While anti-SARS-CoV-2 antibodies were still detectable in 95% of convalescents up to 8 months post infection, an antibody-decay over time was generally observed in most donors. Using a multiplex assay, our data additionally reveal that most convalescents exhibit a broad humoral immunity against different viral epitopes. We demonstrate by flow cytometry that convalescent donors show a significantly elevated number of natural killer cells when compared to healthy controls, while no differences were found concerning other leucocyte subpopulations. We detected a specific long-lasting cellular immune response in convalescents by stimulating immune cells with SARS-CoV-2-specific peptides, covering domains of the viral spike, membrane and nucleocapsid protein, and measuring interferon-γ (IFN-γ) release thereafter. We modified a commercially available ELISA assay for IFN-γ determination in whole-blood specimens of COVID-19 convalescents. One advantage of this assay is that it does not require special equipment and can, thus, be performed in any standard laboratory. In conclusion, our study adds knowledge regarding the persistence of immunity of convalescents suffering from mild to moderate COVID-19. Moreover, our study provides a set of simple methods to characterize and confirm experienced COVID-19.

scholarly journals Coronavirus Disease (COVID-19) Outbreak and Adaptive Immune System of the Body: A Review

2020 ◽  
Author(s):  
Amar Deep ◽  
Suchit Swaroop ◽  
Ajay Kumar ◽  
Sumit Rungta
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Viral Infection ◽  
Severe Disease ◽  
The Body ◽  
World Health ◽  
Cochrane Library ◽  
Research Database ◽  
First Line ◽  
Adaptive Immune

In December 2019, a severe disease with an unknown aetiology has appeared in a Wuhan City, Hubei province, China. Immediately, it was identified as novel Coronavirus Disease (COVID-19) that has spread globally and also called Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), and was characterised in China. As we know the presence of viruses with new genetic diversity in nature, it is unclear from where this virus has evolved and transmitted to humans at the first place. As the outbreak of COVID-19 progresses, epidemiological data is essential to guide situational awareness, and intervention strategies and also immune response in COVID-19. That’s why treatments dealing with the immune-pathology of SARS-CoV-2 infection is a major issue for focus now-a-days, while a rapid and well-coordinated immune response represent the first line of defence against the viral infection. Presently, limited data and information is available on the host innate and adaptive immune status of SARS-CoV-2 infected patients. Here, authors described that how the immune system plays the first line of defence against viral infection, and attempt to compile, accumulate and disseminate the immune response information on COVID-19 from the World Health Organisation (WHO), MEDLINE, Embase, Cochrane Library, Centers for Disease Control and Prevention COVID-19 Research Database and trials registries for the recognition in progress and finished studies, cohort, and from Randomised Controlled Trials (RCTs).

SARS-CoV-2 elicits robust adaptive immune responses regardless of disease severity

2020 ◽  
Author(s):  
Stine SF Nielsen ◽  
Line K Vibholm ◽  
Ida Monrad ◽  
Rikke Olesen ◽  
Giacomo S Frattari ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Immune Responses ◽  
Disease Severity ◽  
Adaptive Immune Response ◽  
T Cell Responses ◽  
Adaptive Immune Responses ◽  
Cell Responses ◽  
Adaptive Immune ◽  
Robust Adaptive

AbstractThe SARS-CoV-2 pandemic currently prevails worldwide. To understand the immunological signature of SARS-CoV-2 infections and aid the search for treatments and vaccines, comprehensive characterization of adaptive immune responses towards SARS-CoV-2 is needed. We investigated the breadth and potency of antibody-, and T-cell immune responses, in 203 recovered SARS-CoV-2 infected patients who presented with asymptomatic to severe infections. We report very broad serological profiles with cross-reactivity to other human coronaviruses. Further, >99% had SARS-CoV-2 epitope specific antibodies, with SARS-CoV-2 neutralization and spike-ACE2 receptor interaction blocking observed in 95% of individuals. A significant positive correlation between spike-ACE2 blocking antibody titers and neutralization potency was observed. SARS-CoV-2 specific CD8+ T-cell responses were clear and quantifiable in 90% of HLA-A2+ individuals. The viral surface spike protein was identified as the dominant target for both neutralizing antibodies and CD8+ T cell responses. Overall, the majority of patients had robust adaptive immune responses, regardless of disease severity.Author summarySARS-CoV-2 can cause severe and deadly infections. However, the immunological understanding of this viral infection is limited. Currently, several vaccines are being developed to help limit transmission and prevent the current pandemic. However, basic understanding of the adaptive immune response developed during SARS-CoV-2 infections is needed to inform further vaccine development and to understand the protective properties of the developed immune response. We investigated, the adaptive immune response developed during SARS-CoV-2 infections in recovered patients experiencing a full spectrum of disease severity, from asymptomatic infections to severe cases requiring hospitalization. We used a novel multiplex serological platform, cell-based neutralization assays and dextramer flow cytometry assays to characterize a broad and robust humoral and cellular immune response towards SARS-CoV-2. We found that the vast majority of recovered individuals have clear detectable and functional SARS-CoV-2 spike specific adaptive immune responses, despite diverse disease severities. The detection of both a humoral and cellular functional spike specific immune response in the vast majority of the individuals, irrespective of asymptomatic manifestations, supports vaccine designs currently underway, and encourages further exploration of whether primary infections provide protection to reinfection.

scholarly journals Age, Disease Severity and Ethnicity Influence Humoral Responses in a Multi-Ethnic COVID-19 Cohort

Viruses ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 786
Author(s):  
Muneerah Smith ◽  
Houari B. Abdesselem ◽  
Michelle Mullins ◽  
Ti-Myen Tan ◽  
Andrew J. M. Nel ◽  
...  
Keyword(s):  
Immune Response ◽  
Disease Severity ◽  
Humoral Immune Response ◽  
Nucleocapsid Protein ◽  
Natural Infection ◽  
Severe Disease ◽  
Humoral Response ◽  
Humoral Immune ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions

The COVID-19 pandemic has affected all individuals across the globe in some way. Despite large numbers of reported seroprevalence studies, there remains a limited understanding of how the magnitude and epitope utilization of the humoral immune response to SARS-CoV-2 viral anti-gens varies within populations following natural infection. Here, we designed a quantitative, multi-epitope protein microarray comprising various nucleocapsid protein structural motifs, including two structural domains and three intrinsically disordered regions. Quantitative data from the microarray provided complete differentiation between cases and pre-pandemic controls (100% sensitivity and specificity) in a case-control cohort (n = 100). We then assessed the influence of disease severity, age, and ethnicity on the strength and breadth of the humoral response in a multi-ethnic cohort (n = 138). As expected, patients with severe disease showed significantly higher antibody titers and interestingly also had significantly broader epitope coverage. A significant increase in antibody titer and epitope coverage was observed with increasing age, in both mild and severe disease, which is promising for vaccine efficacy in older individuals. Additionally, we observed significant differences in the breadth and strength of the humoral immune response in relation to ethnicity, which may reflect differences in genetic and lifestyle factors. Furthermore, our data enabled localization of the immuno-dominant epitope to the C-terminal structural domain of the viral nucleocapsid protein in two independent cohorts. Overall, we have designed, validated, and tested an advanced serological assay that enables accurate quantitation of the humoral response post natural infection and that has revealed unexpected differences in the magnitude and epitope utilization within a population.

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