scholarly journals Early and High SARS-CoV-2 Neutralizing Antibodies Are Associated with Severity in COVID-19 Patients from India

2021 ◽  
Author(s):  
Shubham Shrivastava ◽  
Sonali Palkar ◽  
Jignesh Shah ◽  
Prajakta Rane ◽  
Sanjay Lalwani ◽  
...  
Keyword(s):  
Disease Severity ◽  
Neutralizing Antibodies ◽  
Wide Spectrum ◽  
Severe Disease ◽  
Fatal Outcome ◽  
Asymptomatic Infection ◽  
Live Virus ◽  
Immune Correlates ◽  
Asymptomatic Individuals ◽  
Time Of Presentation

Patients with SARS-CoV-2 infection have a wide spectrum of clinical presentations, from asymptomatic infection, to mild illness, to severe disease with recovery or fatal outcome. Immune correlates of protection are not yet clear. To understand the association between presence and titers of neutralizing antibodies (NAb) with recovery, we screened 82 COVID-19 patients classified in mild (n = 56) and severe (n = 26) disease groups on different days post onset of disease and 27 viral RNA–positive asymptomatic contacts examined within 1 week of the identification of index cases. Of 26 patients with severe disease, six died and 20 recovered. Anti-SARS-CoV-2 NAb levels in plasma and serum were measured using a plaque reduction neutralization test with live virus. The proportion of asymptomatic and symptomatic infections was 1:7.8 in males and 1:1 in females, with males predominating the severe disease group (21/26, 80.7%). At the time of presentation, NAb positivity and titers were comparable among groups with asymptomatic and mild infections. Notably, patients with severe disease exhibited higher NAb seropositivity and titers (25 of 26, 96.2%; 866 ± 188) than those in the mild category (39 of 56, 69.6%; 199 ± 50, P < 0.0001) and asymptomatic individuals (21 of 27, 77.8%; 124 ± 28, P = 0.0002). Within first 2 weeks of onset, NAb titers were significantly higher among patients with severe disease than those with mild presentation. Our data suggest that irrespective of fatal outcome, progression to disease severity was associated with induction of early and high levels of NAb. In our patient series, clinical disease, severity and fatality were predominantly seen in males. The role of NAbs in immunopathogenesis or protection needs to be defined.

scholarly journals Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio and Their Role as Predictors of Disease Severity of Coronavirus Disease 2019 (COVID-19)

2021 ◽  
Author(s):  
Rohit Jain ◽  
Arun Gopal ◽  
Basant Kumar Pathak ◽  
Sourya Sourabh Mohakuda ◽  
TVSVGK Tilak ◽  
...  
Keyword(s):  
Disease Severity ◽  
Complete Blood Count ◽  
Wide Spectrum ◽  
Statistical Significance ◽  
Severe Disease ◽  
Neutrophil To Lymphocyte Ratio ◽  
Screening Tools ◽  
Platelet To Lymphocyte Ratio ◽  
Lymphocyte Ratio ◽  
Time Of Admission

Abstract Context Due to the wide spectrum of clinical illness in coronavirus disease 2019 (COVID-19) patients, it is important to stratify patients into severe and nonsevere categories. Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been evaluated rapidly by a few studies worldwide for its association with severe disease, but practically none have been conducted in the Indian population. This study was undertaken to examine the role of NLR and PLR in predicting severe disease in Indian patients. Objectives The objective was to study the association of NLR and PLR observed at the time of admission with maximum disease severity during hospitalization and to study their role in predicting disease severity. Material and Methods A total of 229 COVID-19 patients were admitted at the center during the study period. After applying inclusion and exclusion criteria, 191 patients were included in the study. The demographic, clinical, and laboratory (complete blood count, NLR, and PLR) data of all patients were obtained at the time of admission. Maximum disease severity of all patients was assessed during hospitalization. Statistical Analysis Chi-square and Mann–Whitney U tests were used to assess statistical significance. Receiver operating characteristic curve (ROC) was plotted for NLR and PLR to estimate the cutoff values and sensitivity and specificity using Youden’s index for predicting severe disease. Logistic regression analysis was used to estimate the odds ratios (OR) and 95% confidence intervals. Results Mean NLR and PLR were significantly higher in severe patients (NLR = 7.41; PLR = 204) compared with nonsevere patients (NLR = 3.30; PLR = 121). ROC analysis showed that NLR, in comparison to PLR, had a higher area under the curve (AUC) of 0.779, with a larger OR of 1.237 and cutoff of 4.1, and showed 69% sensitivity and 78% specificity in predicting severe disease. Cut off for PLR was 115.3, which showed 79% sensitivity and 62% specificity in predicting severe disease. Conclusion NLR and PLR, both showing acceptable AUCs, can be used as screening tools to predict disease severity. However, NLR was a better predictor of disease severity.

scholarly journals Titers of Neutralizing Antibodies against SARS-CoV-2 Are Independent of Symptoms of Non-Severe COVID-19 in Young Adults

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 284
Author(s):  
Hulda R. Jonsdottir ◽  
Michel Bielecki ◽  
Denise Siegrist ◽  
Thomas W. Buehrer ◽  
Roland Züst ◽  
...  
Keyword(s):  
Young Adults ◽  
Neutralizing Antibodies ◽  
Severe Disease ◽  
Humoral Response ◽  
Neutralizing Antibody ◽  
Neutralization Assay ◽  
Asymptomatic Infection ◽  
Homogeneous Population ◽  
Humoral Immune ◽  
Antibody Titers

Neutralizing antibodies are an important part of the humoral immune response to SARS-CoV-2. It is currently unclear to what extent such antibodies are produced after non-severe disease or asymptomatic infection. We studied a cluster of SARS-CoV-2 infections among a homogeneous population of 332 predominantly male Swiss soldiers and determined the neutralizing antibody response with a serum neutralization assay using a recombinant SARS-CoV-2-GFP. All patients with non-severe COVID-19 showed a swift humoral response within two weeks after the onset of symptoms, which remained stable for the duration of the study. One month after the outbreak, titers in COVID-19 convalescents did not differ from the titers of asymptomatically infected individuals. Furthermore, symptoms of COVID-19 did not correlate with neutralizing antibody titers. Therefore, we conclude that asymptomatic infection can induce the same humoral immunity as non-severe COVID-19 in young adults.

The Basics of Microbiology

2021 ◽  
Author(s):  
Werner Solbach
Keyword(s):  
Infectious Diseases ◽  
Defense Mechanisms ◽  
Wide Spectrum ◽  
Severe Disease ◽  
Laboratory Diagnosis ◽  
Asymptomatic Infection ◽  
The Body ◽  
Sufficient Evidence ◽  
Effective Measure ◽  
Hygiene Measures

Microorganisms constitute 70 percent of the biomass on Planet Earth. Comparatively few species are adapted to colonize human surfaces and form a complex Meta-Organism with manyfold mutual benefits. Occasionally, microorganisms may overcome the barriers of the skin and mucosal surfaces and may multiply locally or in multiple sites inside the body. This process is called infection. Infections can be caused by bacteria, viruses, parasites, helminths, and fungi. Immediately after infection, numerous defense mechanisms of the immune system are activated to combat replication of the microbes. There is a balance between microorganism and human defense mechanisms, which may lead to either asymptomatic infection or result in a wide spectrum of symptoms from mild to severe disease and even death. The most important factors in the diagnosis of infectious diseases are a careful history, physical examination and the appropriate collection of body fluids and tissues. Laboratory diagnosis requires between 2 and 72 hours. Wherever possible, antibiotics should only be used when sufficient evidence of efficacy is available. Then, however, they should be used as early as possible and in high doses. In addition to everyday hygiene measures, vaccination is the most effective measure to prevent infectious diseases.

scholarly journals TNFA and IL10 Polymorphisms and IL-6 and IL-10 Levels Influence Disease Severity in Influenza A(H1N1)pdm09 Virus Infected Patients

Genes ◽  
2021 ◽  
Vol 12 (12) ◽  
pp. 1914
Author(s):  
Kalichamy Alagarasu ◽  
Himanshu Kaushal ◽  
Pooja Shinde ◽  
Mahadeo Kakade ◽  
Urmila Chaudhary ◽  
...  
Keyword(s):  
Disease Severity ◽  
Influenza A ◽  
Severe Disease ◽  
Fatal Outcome ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Mild Disease ◽  
Pdm09 Virus ◽  
Potential Biomarker ◽  
Influenza A H1n1

Cytokines are key modulators of immune response, and dysregulated production of proinflammatory and anti-inflammatory cytokines contributes to the pathogenesis of influenza A(H1N1)pdm09 virus infection. Cytokine production is impacted by single nucleotide polymorphisms (SNPs) in the genes coding for them. In the present study, SNPs in the IL6, TNFA, IFNG, IL17A, IL10, and TGFB were investigated for their association with disease severity and fatality in influenza A(H1N1)pdm09-affected patients with mild disease (n = 293) and severe disease (n = 86). Among those with severe disease, 41 patients had fatal outcomes. In a subset of the patients, levels of IL-2, IL-4, IL-6, IL-10, TNF, IFN-γ, and IL-17 were assayed in the plasma for their association with severe disease. The frequency of TNFA rs1800629 G/A allele was significantly higher in severe cases and survived severe cases group compared to that of those with mild infection (OR with 95% for mild vs. severe cases 2.95 (1.52–5.73); mild vs. survived severe cases 4.02 (1.84–8.82)). IL10 rs1800896-rs1800872 G-C haplotype was significantly lower (OR with 95% 0.34 (0.12–0.95)), while IL10 rs1800896-rs1800872 G-A haplotype was significantly higher (OR with 95% 12.11 (2.23–76.96)) in fatal cases group compared to that of the mild group. IL-6 and IL-10 levels were significantly higher in fatal cases compared to that of survived severe cases. IL-6 levels had greater discriminatory power than IL-10 to predict progression to fatal outcome in influenza A(H1N1)pdm09 virus-infected patients. To conclude, the present study reports the association of TNFA and IL10 SNPs with severe disease in Influenza A(H1N1)pdm09 virus-infected subjects. Furthermore, IL-6 levels can be a potential biomarker for predicting fatal outcomes in Influenza A(H1N1)pdm09 virus infected subjects.

scholarly journals Serological Analysis Reveals an Imbalanced IgG Subclass Composition Associated with COVID-19 Disease Severity

2020 ◽  
Author(s):  
Jennifer L. Yates ◽  
Dylan J. Ehrbar ◽  
Danielle T. Hunt ◽  
Roxanne C. Girardin ◽  
Alan Dupuis ◽  
...  
Keyword(s):  
Disease Severity ◽  
Wide Spectrum ◽  
Severe Disease ◽  
Neutralizing Antibody ◽  
Igg Subclass ◽  
Serological Analysis ◽  
Serum Samples ◽  
Plasma Therapy ◽  
Igg3 Subclass ◽  
Antibody Levels

SummaryCOVID-19 is associated with a wide spectrum of disease severity, ranging from asymptomatic to acute respiratory distress syndrome (ARDS). Paradoxically, a direct relationship has been suggested between COVID-19 disease severity, and the levels of circulating SARS-CoV-2-specific antibodies, including virus neutralizing titers. Through a serological analysis of serum samples from 536 convalescent healthcare workers, we found that SARS-CoV-2-specific and virus-neutralizing antibody levels were indeed elevated in individuals that experienced severe disease. The severity-associated increase in SARS-CoV-2-specific antibody was dominated by IgG, with an IgG subclass ratio skewed towards elevated receptor binding domain (RBD)- and S1-specific IgG3. However, RBD- and S1-specific IgG1, rather than IgG3 were best correlated with virus-neutralizing titers. We propose that Spike-specific IgG3 subclass utilization contributes to COVID-19 disease severity through potent Fc-mediated effector functions. These results have significant implications for SARS-CoV-2 vaccine design, and convalescent plasma therapy.

scholarly journals Diverse Functional Autoantibodies in Patients with COVID-19

2020 ◽  
Author(s):  
Eric Y. Wang ◽  
Tianyang Mao ◽  
Jon Klein ◽  
Yile Dai ◽  
John D. Huck ◽  
...  
Keyword(s):  
Disease Severity ◽  
Healthcare Workers ◽  
Immune Cell ◽  
Wide Spectrum ◽  
Severe Disease ◽  
Surface Proteins ◽  
Complement Components ◽  
Host Immune Responses ◽  
High Prevalence ◽  
The Impact

COVID-19 manifests with a wide spectrum of clinical phenotypes that are characterized by exaggerated and misdirected host immune responses1–8. While pathological innate immune activation is well documented in severe disease1, the impact of autoantibodies on disease progression is less defined. Here, we used a high-throughput autoantibody discovery technique called Rapid Extracellular Antigen Profiling (REAP) to screen a cohort of 194 SARS-CoV-2 infected COVID-19 patients and healthcare workers for autoantibodies against 2,770 extracellular and secreted proteins (the “exoproteome”). We found that COVID-19 patients exhibit dramatic increases in autoantibody reactivities compared to uninfected controls, with a high prevalence of autoantibodies against immunomodulatory proteins including cytokines, chemokines, complement components, and cell surface proteins. We established that these autoantibodies perturb immune function and impair virological control by inhibiting immunoreceptor signaling and by altering peripheral immune cell composition, and found that murine surrogates of these autoantibodies exacerbate disease severity in a mouse model of SARS-CoV-2 infection. Analysis of autoantibodies against tissue-associated antigens revealed associations with specific clinical characteristics and disease severity. In summary, these findings implicate a pathological role for exoproteome-directed autoantibodies in COVID-19 with diverse impacts on immune functionality and associations with clinical outcomes.

scholarly journals Preserved recognition of Omicron Spike following COVID-19 mRNA vaccination in pregnancy

2022 ◽  
Author(s):  
Yannic C Bartsch ◽  
Caroline Atyeo ◽  
Jaewon Kang ◽  
Kathryn J Gray ◽  
Andrea G. Edlow ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Disease Severity ◽  
Receptor Binding ◽  
Neutralizing Antibodies ◽  
Severe Disease ◽  
Fc Receptor ◽  
Binding Domain ◽  
Vaccine Uptake ◽  
Receptor Binding Domain ◽  
In Pregnancy

Summary Background SARS-CoV-2 infection is associated with enhanced disease severity in pregnant women. Despite the potential of COVID-19 vaccines to reduce severe disease, vaccine uptake remained relatively low among pregnant women. Just as coordinated messaging from the CDC and leading obstetrics organizations began to increase vaccine confidence in this vulnerable group, the evolution of SARS-CoV-2 variants of concerns (VOC) including the Omicron VOC raised new concerns about vaccine efficacy, given their ability to escape vaccine-induced neutralizing antibodies. Early data point to a milder disease course following omicron VOC infection in vaccinated individuals. Thus, these data suggest that alternate vaccine induced immunity, beyond neutralization, may continue to attenuate omicron disease, such as antibody-Fc-mediated activity. However, whether vaccine induced antibodies raised in pregnancy continue to bind and leverage Fc-receptors remains unclear. Methods VOC including Omicron receptor binding domain (RBD) or full Spike specific antibody isotype binding titers and FcγR binding were analyzed in pregnant women after the full dose regimen of either Pfizer/BioNtech BNT62b2 (n=10) or Moderna mRNA-1273 (n=10) vaccination using a multiplexing Luminex assay. Findings Comparable, albeit reduced, isotype recognition was observed to the Omicron Spike and receptor binding domain (RBD) following both vaccines. Yet, despite the near complete loss of Fc-receptor binding to the Omicron RBD, Fc-receptor binding was largely preserved to the Omicron Spike. Interpretation Reduced binding titer to the Omicron RBD aligns with observed loss of neutralizing activity. Despite the loss of neutralization, preserved Omicron Spike recognition and Fc-receptor binding potentially continues to attenuate disease severity in pregnant women. Funding NIH and the Bill and Melinda Gates Foundation

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 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 Durability of SARS-CoV-2-specific T cell responses at 12-months post-infection

2021 ◽  
Author(s):  
Zhongyan Lu ◽  
Eric D Laing ◽  
Jarina Pena-Damata ◽  
Katherine Pohida ◽  
Marana S Tso ◽  
...  
Keyword(s):  
T Cells ◽  
Disease Severity ◽  
Post Infection ◽  
Cellular Response ◽  
Wide Spectrum ◽  
Natural Infection ◽  
Severe Disease ◽  
Intracellular Cytokine Staining ◽  
Therapeutic Interventions ◽  
Specific Antibodies

Background. Characterizing the longevity and quality of cellular immune responses to SARS-CoV-2 is critical to understanding immunologic approaches to protection against COVID-19. Prior studies suggest SARS-CoV-2-specific T cells are present in peripheral blood 10 months after infection. Further analysis of the function, durability, and diversity of the cellular response long after natural infection, over a wider range of ages and disease phenotypes, is needed to further identify preventative and therapeutic interventions. Methods. We identified participants in our multi-site longitudinal, prospective cohort study 12-months post SARS-CoV-2 infection representing a range of disease severity. We investigated the function, phenotypes, and frequency of T cells specific for SARS-CoV-2 using intracellular cytokine staining and spectral flow cytometry. In parallel, the magnitude of SARS-CoV-2-specific antibodies was compared. Results. SARS-CoV-2-specific antibodies and T cells were detected at 12-months post-infection. Severity of acute illness was associated with higher frequencies of SARS-CoV-2-specific CD4 T cells and antibodies at 12-months. In contrast, polyfunctional and cytotoxic T cells responsive to SARS-CoV-2 were identified in participants over a wide spectrum of disease severity. Conclusions. Our data show that SARS-CoV-2 infection induces polyfunctional memory T cells detectable at 12-months post-infection, with higher frequency noted in those who originally experienced severe disease.

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