scholarly journals 519. Immune responses and COVID-19 severity

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S325-S325
Author(s):  
mirella salvatore ◽  
Charles K Vorkas ◽  
Harjot Sing ◽  
Ayana Morales ◽  
Rosemary Soave ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Disease Severity ◽  
Severe Disease ◽  
Laboratory Data ◽  
Disease Onset ◽  
Disease Evolution ◽  
Igm Antibody ◽  
Immune Correlates ◽  
Over Time

Abstract Background The coronavirus-19-disease (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread to >200 countries and surpassed 7 million cases. There is a broad range of COVID-19 illness, ranging from milder disease to a rapidly progressive respiratory disease and ARDS. The causes of this different clinical course and the drivers for severe disease are currently unknown. A fulminant increase of pro-inflammatory cytokines is thought to play a role in causing a rapid disease evolution, however the immune correlates of severe COVID-19 remain unclear. Methods To gain insight into relationship between immune responses and disease severity we built a longitudinal cohort of 40 adult patients with known COVID-19. Samples were collected at diagnosis and every 7 days until hospital discharge or death. As controls we also included a group of convalescent patients, and subjects who tested negative for COVID-19 by PCR. Clinical and laboratory data and were also collected. Multicolor flow cytometry was used to determine the presence and phenotype of B, T and natural killer (NK) cells. We also identified specific sub-populations (Tfh, activated/cytotoxic CD8 and NK) and assessed lymphoid exhaustion of different cell types such as naïve, memory T cells, or NK over time. Anti-Sars-CoV2 IgG and IgM antibody were detected using lateral flow method. Results We found that the absolute number of lymphocytes and monocytes was decreased starting at diagnosis and correlated with disease severity. Disease severity correlated with decreased NK and T cell. In severe COVID-19 cases, NK cell populations were strongly decreased over time in intubated patients while they recovered in patients who improved and were discharged. CD8+ were also decreased at disease onset and seemed to correlate with disease severity. A high percentage of CD4+ and CD8+ T cells showed an exhausted phenotype. All patients tested at admission had IgM antibody responses irrespective of the course of the disease. Further analyses are ongoing. Conclusion The characterization and role of the immune responses in COVID-19 evolution is still under investigation. Further characterization of viral and immune factors will help in identifying subjects at high risk of severe disease and targets for intervention. Disclosures All Authors: No reported disclosures

scholarly journals Longitudinal analyses reveal age-specific immune correlates of COVID-19 severity

2021 ◽  
Author(s):  
Sloan A. Lewis ◽  
Suhas Sureshchandra ◽  
Michael Z. Zulu ◽  
Brianna Doratt ◽  
Amanda Pinski ◽  
...  
Keyword(s):  
T Cells ◽  
Disease Severity ◽  
Severe Disease ◽  
Myeloid Cells ◽  
Type I ◽  
Older Individuals ◽  
Aged Patients ◽  
Immune Correlates ◽  
The Impact ◽  
Over Time

ABSTRACTSevere COVID-19 disproportionately impacts older individuals and those with comorbidities. It is estimated that approximately 80% of COVID-19 deaths are observed among individuals >65 years of age. However, the immunological underpinnings of severe COVID-19 in the aged have yet to be defined. This study captures the longitudinal immune response to SARS-CoV-2 infection in a cohort of young and aged patients with varying disease severity. Phenotypic transcriptional and functional examination of the peripheral mononuclear cells revealed age-, time, and disease severity-specific adaptations. Gene expression signatures within memory B cells suggest qualitative differences in the antibody responses in aged patients with severe disease. Examination of T cells showed profound lymphopenia, that worsened over time and correlated with lower levels of plasma cytokines important for T cell survival in aged patients with severe disease. Single cell RNA sequencing revealed augmented signatures of activation, exhaustion, cytotoxicity, and type-I interferon signaling in memory T cells and NK cells. Although hallmarks of a cytokine storm were evident in both groups, older individuals exhibited elevated levels of chemokines that mobilize inflammatory myeloid cells, notably in those who succumbed to disease. Correspondingly, we observed a re-distribution of DC and monocytes with severe disease that was accompanied by a rewiring towards a more regulatory phenotype. Several of these critical changes, such as the reduction of surface HLA-DR on myeloid cells, were reversed in young but not aged patients over time. In summary, the data presented here provide novel insights into the impact of aging on the host response to SARS-CoV2 infection.

scholarly journals Baseline T cell immune phenotypes predict virologic and disease control upon SARS-CoV infection

2020 ◽  
Author(s):  
Jessica B. Graham ◽  
Jessica L. Swarts ◽  
Sarah R. Leist ◽  
Alexandra Schäfer ◽  
Vineet D. Menachery ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Clinical Outcomes ◽  
Severe Disease ◽  
Collaborative Cross ◽  
Viral Control ◽  
Major Barrier ◽  
Mild Disease ◽  
Immune Correlates ◽  
Wide Range

AbstractThe COVID-19 pandemic has revealed that infection with SARS-CoV-2 can result in a wide range of clinical outcomes in humans, from asymptomatic or mild disease to severe disease that can require mechanical ventilation. An incomplete understanding of immune correlates of protection represents a major barrier to the design of vaccines and therapeutic approaches to prevent infection or limit disease. This deficit is largely due to the lack of prospectively collected, pre-infection samples from indiviuals that go on to become infected with SARS-CoV-2. Here, we utilized data from a screen of genetically diverse mice from the Collaborative Cross (CC) infected with SARS-CoV to determine whether circulating baseline T cell signatures are associated with a lack of viral control and severe disease upon infection. SARS-CoV infection of CC mice results in a variety of viral load trajectories and disease outcomes. Further, early control of virus in the lung correlates with an increased abundance of activated CD4 and CD8 T cells and regulatory T cells prior to infections across strains. A basal propensity of T cells to express IFNg and IL17 over TNFa also correlated with early viral control. Overall, a dysregulated, pro-inflammatory signature of circulating T cells at baseline was associated with severe disease upon infection. While future studies of human samples prior to infection with SARS-CoV-2 are required, our studies in mice with SARS-CoV serve as proof of concept that circulating T cell signatures at baseline can predict clinical and virologic outcomes upon SARS-CoV infection. Identification of basal immune predictors in humans could allow for identification of individuals at highest risk of severe clinical and virologic outcomes upon infection, who may thus most benefit from available clinical interventions to restrict infection and disease.SummaryWe used a screen of genetically diverse mice from the Collaborative Cross infected with mouse-adapted SARS-CoV in combination with comprehensive pre-infection immunophenotyping to identify baseline circulating immune correlates of severe virologic and clinical outcomes upon SARS-CoV infection.

scholarly journals Comparison of the Immunogenicities and Cross-Lineage Efficacies of Live Attenuated Peste des Petits Ruminants Virus Vaccines PPRV/Nigeria/75/1 and PPRV/Sungri/96

2018 ◽  
Vol 92 (24) ◽  
Author(s):  
Sophia Hodgson ◽  
Katy Moffat ◽  
Holly Hill ◽  
John T. Flannery ◽  
Simon P. Graham ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Immune Responses ◽  
Severe Disease ◽  
Small Ruminants ◽  
Virus Antigen ◽  
Enzyme Linked Immunosorbent Assay ◽  
Peste Des Petits Ruminants ◽  
Systematic Analysis ◽  
Genetic Lineages

ABSTRACTPeste des petits ruminants (PPR) is a severe disease of goats and sheep that is widespread in Africa, the Middle East, and Asia. Several effective vaccines exist for the disease, based on attenuated strains of the virus (PPRV) that causes PPR. While the efficacy of these vaccines has been established by use in the field, the nature of the protective immune response has not been determined. In addition, while the vaccine derived from PPRV/Nigeria/75/1 (N75) is used in many countries, those developed in India have never been tested for their efficacy outside that country. We have studied the immune response in goats to vaccination with either N75 or the main Indian vaccine, which is based on isolate PPRV/India/Sungri/96 (S96). In addition, we compared the ability of these two vaccines, in parallel, to protect animals against challenge with pathogenic viruses from the four known genetic lineages of PPRV, representing viruses from different parts of Africa, as well as Asia. These studies showed that, while N75 elicited a stronger antibody response than S96, as measured by both enzyme-linked immunosorbent assay and virus neutralization, S96 resulted in more pronounced cellular immune responses, as measured by virus antigen-induced proliferation and interferon gamma production. While both vaccines induced comparable numbers of PPRV-specific CD8+T cells, S96 induced a higher number of CD4+T cells specifically responding to virus. Despite these quantitative and qualitative differences in the immune responses following vaccination, both vaccines gave complete clinical protection against challenge with all four lineages of PPRV.IMPORTANCEDespite the widespread use of live attenuated PPRV vaccines, this is the first systematic analysis of the immune response elicited in small ruminants. These data will help in the establishment of the immunological determinants of protection, an important step in the development of new vaccines, especially DIVA vaccines using alternative vaccination vectors. This study is also the first controlled test of the ability of the two major vaccines used against virulent PPRV strains from all genetic lineages of the virus, showing conclusively the complete cross-protective ability of these vaccines.

scholarly journals Granzyme B skews CD4+ T cell differentiation resulting in increased intestinal pathogenicity

2020 ◽  
Author(s):  
Kristen L. Hoek ◽  
Michael J. Greer ◽  
Kathleen G. McClanahan ◽  
Ali Nazmi ◽  
M. Blanca Piazuelo ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Differentiation ◽  
T Cell ◽  
Immune Responses ◽  
Cell Biology ◽  
Intestinal Inflammation ◽  
Granzyme B ◽  
Disease Onset ◽  
T Cell Differentiation ◽  
Transfer Model

AbstractCD4+ T cell activation and differentiation are important events that set the stage for proper immune responses. Many factors are involved in the activation and differentiation of T cells, and these events are tightly controlled to prevent unwanted and/or exacerbated immune responses that may harm the host. It has been well documented that granzyme B, a potent serine protease involved in cell-mediated cytotoxicity, is readily expressed by certain CD4+ T cells, such as regulatory T cells and CD4+CD8aa+ intestinal intraepithelial lymphocytes, both of which display cytotoxicity associated with granzyme B. However, because not all CD4+ T cells expressing granzyme B are cytotoxic, additional roles for this protease in CD4+ T cell biology remain unknown. Here, using a combination of in vivo and in vitro approaches, we report that granzyme B-deficient CD4+ T cells display increased IL-17 production. In the adoptive transfer model of intestinal inflammation, granzyme B-deficient CD4+ T cells triggered a more rapid disease onset than their WT counterparts, and presented a differential transcription profile. Similar results were also observed in granzyme B-deficient mice infected with Citrobacter rodentium. Our results suggest that granzyme B modulates CD4+ T cell differentiation, providing a new perspective into the biology of this enzyme.

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 Severity of Maternal SARS-CoV-2 Infection in Pregnancy Predicts Neonatal Outcomes

2021 ◽  
Author(s):  
Beril Yasa ◽  
Seyma Memur ◽  
Dilek Yavuzcan Ozturk ◽  
Onur Bagci ◽  
Sait Ilker Uslu ◽  
...  
Keyword(s):  
Hospital Stay ◽  
Disease Severity ◽  
Severe Disease ◽  
Laboratory Data ◽  
Ventilatory Support ◽  
Neonatal Outcomes ◽  
Prolonged Hospital Stay ◽  
Key Points ◽  
Prolonged Hospital ◽  
Maternal Disease

Objective The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak had an enormous global impact. Pregnant women with SARS-CoV-2 appear to have higher morbidity and mortality. This study aimed to evaluate the effect of the severity of maternal SARS-CoV-2 infection on neonatal outcomes. Study Design The clinical and laboratory data of 40 women and neonates evaluated retrospectively. Results This retrospective study showed that SARS-CoV-2 infection had an adverse impact on neonatal outcomes proportionally with the maternal disease severity including increased prematurity rates, postnatal resuscitation need, prolonged hospital stay and longer ventilatory support requirement in infants born to mothers with moderate or severe disease. Conclusion Maternal disease severity had adverse effects on neonatal outcomes. The severity of maternal disease was found to be associated with increased rates of prematurity, requirement of postnatal resuscitation, prolonged hospital stay, and longer ventilatory support. Key Points

scholarly journals Shigella -Specific Immune Profiles Induced after Parenteral Immunization or Oral Challenge with Either Shigella flexneri 2a or Shigella sonnei

mSphere ◽  
2021 ◽  
Author(s):  
Kristen A. Clarkson ◽  
Chad K. Porter ◽  
Kawsar R. Talaat ◽  
Robert W. Frenck ◽  
Cristina Alaimo ◽  
...  
Keyword(s):  
Immune Responses ◽  
Protective Immunity ◽  
Shigella Flexneri ◽  
Severe Disease ◽  
Oral Challenge ◽  
Immune Markers ◽  
Correlates Of Protection ◽  
Immune Correlates ◽  
Shigella Flexneri 2A ◽  
Parenteral Immunization

Although immune correlates of protection have yet to be defined for shigellosis, prior studies have demonstrated that Shigella infection provides protection against reinfection in a serotype-specific manner. Therefore, it is likely that subjects with moderate to severe disease post-oral challenge would be protected from a homologous rechallenge, and investigating immune responses in these subjects may help identify immune markers associated with the development of protective immunity.

scholarly journals Neutralizing antibody responses over time in demographically and clinically diverse individuals recovered from SARS-CoV-2 infection in the United States and Peru: A cohort study

PLoS Medicine ◽  
2021 ◽  
Vol 18 (12) ◽  
pp. e1003868
Author(s):  
Shelly Karuna ◽  
Shuying Sue Li ◽  
Shannon Grant ◽  
Stephen R. Walsh ◽  
Ian Frank ◽  
...  
Keyword(s):  
United States ◽  
Disease Severity ◽  
Disease Onset ◽  
Clinical Manifestations ◽  
The United States ◽  
Immune Defense ◽  
Severe Illness ◽  
Pseudotyped Virus ◽  
Wide Range ◽  
Over Time

Background People infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) experience a wide range of clinical manifestations, from asymptomatic and mild illness to severe illness and death, influenced by age and a variety of comorbidities. Neutralizing antibodies (nAbs) are thought to be a primary immune defense against the virus. Large, diverse, well-characterized cohorts of convalescent individuals provide standardized values to benchmark nAb responses to past SARS-CoV-2 infection and define potentially protective levels of immunity. Methods and findings This analysis comprises an observational cohort of 329 HIV–seronegative adults in the United States (n = 167) and Peru (n = 162) convalescing from SARS-CoV-2 infection from May through October 2020. The mean age was 48 years (range 18 to 86), 54% of the cohort overall was Hispanic, and 34% identified as White. nAb titers were measured in serum by SARS-CoV-2.D614G Spike-pseudotyped virus infection of 293T/ACE2 cells. Multiple linear regression was applied to define associations between nAb titers and demographic variables, disease severity and time from infection or disease onset, and comorbidities within and across US and Peruvian cohorts over time. nAb titers peaked 28 to 42 days post-diagnosis and were higher in participants with a history of severe Coronavirus Disease 2019 (COVID-19) illness (p < 0.001). Diabetes, age >55 years, male sex assigned at birth, and, in some cases, body mass index were also independently associated with higher nAb titers, whereas hypertension was independently associated with lower nAb titers. nAb titers did not differ by race, underlying pulmonary disease or smoking. Two months post-enrollment, nAb ID50 (ID80) titers declined 3.5 (2.8)-fold overall. Study limitations in this observational, convalescent cohort include survivorship bias and missing early viral loads and acute immune responses to correlate with the convalescent responses we observed. Conclusions In summary, in our cohort, nAb titers after SARS-CoV-2 infection peaked approximately 1 month post-diagnosis and varied by age, sex assigned at birth, disease severity, and underlying comorbidities. Our data show great heterogeneity in nAb responses among people with recent COVID-19, highlighting the challenges of interpreting natural history studies and gauging responses to vaccines and therapeutics among people with recent infection. Our observations illuminate potential correlations of demographic and clinical characteristics with nAb responses, a key element for protection from COVID-19, thus informing development and implementation of preventative and therapeutic strategies globally. Trial registration ClinicalTrials.gov NCT04403880.

scholarly journals Analysis of respiratory and systemic immune responses in COVID-19 reveals mechanisms of disease pathogenesis

2020 ◽  
Author(s):  
Peter A. Szabo ◽  
Pranay Dogra ◽  
Joshua I. Gray ◽  
Steven B. Wells ◽  
Thomas J. Connors ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Severe Disease ◽  
Specific Treatment ◽  
High Level Expression ◽  
Disease Pathogenesis ◽  
Treatment And Prevention ◽  
Human Immunity ◽  
High Level ◽  
And Function

SUMMARYImmune responses to respiratory viruses like SARS-CoV-2 originate and function in the lung, yet assessments of human immunity are often limited to blood. Here, we conducted longitudinal, high-dimensional profiling of paired airway and blood samples from patients with severe COVID-19, revealing immune processes in the respiratory tract linked to disease pathogenesis. Survival from severe disease was associated with increased CD4+T cells and decreased monocyte/macrophage frequencies in the airway, but not in blood. Airway T cells and macrophages exhibited tissue-resident phenotypes and activation signatures, including high level expression and secretion of monocyte chemoattractants CCL2 and CCL3 by airway macrophages. By contrast, monocytes in blood expressed the CCL2-receptor CCR2 and aberrant CD163+ and immature phenotypes. Extensive accumulation of CD163+monocyte/macrophages within alveolar spaces in COVID-19 lung autopsies suggested recruitment from circulation. Our findings provide evidence that COVID-19 pathogenesis is driven by respiratory immunity, and rationale for site-specific treatment and prevention strategies.

Adaptive Immune Responses in Humans During Nipah Virus Acute and Convalescent Phases of Infection

2019 ◽  
Vol 69 (10) ◽  
pp. 1752-1756 ◽  
Author(s):  
Govindakarnavar Arunkumar ◽  
Santhosha Devadiga ◽  
Anita K McElroy ◽  
Suresh Prabhu ◽  
Shahin Sheik ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Responses ◽  
Cd8 T Cells ◽  
B Lymphocyte ◽  
Nipah Virus ◽  
Disease Onset ◽  
Immunoglobulin M ◽  
Enzyme Linked Immunosorbent Assay ◽  
Humoral Immune

Abstract Background Nipah virus (NiV) is 1 of 10 potential causes of imminent public health emergencies of international concern. We investigated the NiV outbreak that occurred in May 2018 in Kerala, India. Here we describe the longitudinal characteristics of cell-mediated and humoral immune responses to NiV infection during the acute and convalescent phases in 2 human survivors. Methods Serial blood samples were obtained from the only 2 survivors of the NiV outbreak in Kerala. We used flow cytometry to determine the absolute T-lymphocyte and B-lymphocyte counts and the phenotypes of both T and B cells. We also detected and quantitated the humoral immune response to NiV by virus-specific immunoglobulin M (IgM) and immunoglobulin G (IgG) enzyme-linked immunosorbent assay. Results Absolute numbers of T lymphocytes remained within normal limits throughout the period of illness studied in both survivors. However, a marked elevation of activated CD8 T cells was observed in both cases. More than 30% of total CD8 T cells expressed Ki67, indicating active proliferation. Proliferating (Ki-67+) CD8 T cells expressed high levels of granzyme B and PD-1, consistent with the profile of acute effector cells. Total B-lymphocyte, activated B-cell, and plasmablast counts were also elevated in NiV survivors. These individuals developed detectable NiV-specific IgM and IgG antibodies within a week of disease onset. Clearance of NiV RNA from blood preceded the appearance of virus-specific IgG and coincided with the peak of activated CD8 T cells. Conclusions We describe for the first time longitudinal kinetic data on the activation status of human B- and T-cell populations during acute NiV infection. While marked CD8 T-cell activation was observed with effector characteristics, activated CD4 T cells were less prominent.

Sign in / Sign up

Export Citation Format

Share Document