scholarly journals SARS-CoV-2 Infection, COVID-19, and long covid: Saga of erratic immune response, waning immunity, and immune system failure

2021 ◽  
Vol 5 (1) ◽  
pp. 077-086
Author(s):  
Nikhra Vinod
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Disease Transmission ◽  
Neutralizing Antibodies ◽  
Evolutionary Dynamics ◽  
Immune Escape ◽  
Clinical Manifestations ◽  
System Failure ◽  
S Protein ◽  
Adaptive Mutations

Introduction - evolution of SARS-CoV-2 variants: With the unrestrained pandemic for over last one-and-half year, SARS-CoV-2 seems to have adapted to its habitat, the human host, through mutations that facilitate its replication and transmission. The G variant incorporating D614G mutation, potently more transmissible than the ancestral virus arose during January 2020 and spread widely. Since then, various SARS-CoV-2 variants of concern (VOCs) and variants of interest (VOIs) with higher infectivity or virulence or both, have evolved on the background of G variant, and spread widely. SARS-CoV-2 infection and the immunodynamics: As the virus becomes more transmissible, its lethality may drop. Apart from the humoral immunity, T-cell recognition from a previous SARS-CoV-2 infection or vaccination may modify the disease transmission correlates and its clinical manifestations. On the other hand, the immunity generated may reduce probability of re-infection as well as limit evolution of adaptive mutations, and emergence of highly infectious and immune-escape variants. There are complex issues related to the SARS-CoV-2 evolutionary dynamics and host’s immunodynamics. Trending etiopathoimmunological correlates: The evolution potential of SARS-CoV-2 is limited because of proofreading function of nsp14. The S protein mutations affect transmissibility, virulence, and vaccine efficacy. The D614G mutation in G variant with higher infectivity has turned the Chinese epidemic into a pandemic. Other SARS-CoV-2 variants, such as Alpha, Beta, Gamma, and Delta seem to have evolved as result of adaptation to selective pressures during periods of prolonged infections and subsequent transmission. Further, there is issue of convergent association of mutations. Basics of immunity and immune system failure: The nature of the immune response after natural SARS-CoV-2 infection is variable and diverse. There are pre-existing neutralizing antibodies and sensitized T cells elicited during previous infection with seasonal CoVs influencing the disease susceptibility and course. The virus has evolved adaptive mechanisms to reduce its exposure to IFN-I and there are issues related to erratic and overactive immune response. The altered neutralizing epitopes in the S protein in SARS-CoV-2 variants modify the immune landscapes and clinical manifestations. Conclusion: current scenarios and prospects: Presently, the SARS-CoV-2 infection is widespread with multiple evolving infectious variants. There is probability of its transition from epidemic to endemic phase in due course manifesting as a mild disease especially in the younger population. Conversely, the pandemic may continue with enhanced disease severity due to evolving variants, expanded infection pool, and changing immunity landscape. There is need to plan for the transition and continued circulation of the virus during the endemic phase or continuing pandemic for indefinite period.

scholarly journals The Emergence and Spread of Novel SARS-CoV-2 Variants

2021 ◽  
Vol 9 ◽  
Author(s):  
Huaimin Yi ◽  
Jin Wang ◽  
Jiong Wang ◽  
Yuying Lu ◽  
Yali Zhang ◽  
...  
Keyword(s):  
Immune Response ◽  
Severe Acute Respiratory Syndrome ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Neutralizing Antibodies ◽  
Whole Genome ◽  
Distribution Characteristics ◽  
S Protein ◽  
The World ◽  
Viral Genes

Since severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) began to spread in late 2019, laboratories around the world have widely used whole genome sequencing (WGS) to continuously monitor the changes in the viral genes and discovered multiple subtypes or branches evolved from SARS-CoV-2. Recently, several novel SARS-CoV-2 variants have been found to be more transmissible. They may affect the immune response caused by vaccines and natural infections and reduce the sensitivity to neutralizing antibodies. We analyze the distribution characteristics of prevalent SARS-CoV-2 variants and the frequency of mutant sites based on the data available from GISAID and PANGO by R 4.0.2 and ArcGIS 10.2. Our analysis suggests that B.1.1.7, B.1.351, and P.1 are more easily spreading than other variants, and the key mutations of S protein, including N501Y, E484K, and K417N/T, have high mutant frequencies, which may have become the main genotypes for the spread of SARS-CoV-2.

scholarly journals Glycans of SARS-CoV-2 Spike Protein in Virus Infection and Antibody Production

2021 ◽  
Vol 8 ◽  
Author(s):  
Xiaohui Zhao ◽  
Huan Chen ◽  
Hongliang Wang
Keyword(s):  
Immune Response ◽  
Antibody Production ◽  
Viral Entry ◽  
Neutralizing Antibodies ◽  
Vaccine Development ◽  
Protein Glycosylation ◽  
The Other ◽  
Defense System ◽  
S Protein ◽  
Receptor Interactions

Viral protein glycosylation represents a successful strategy employed by the parasite to take advantage of host–cell machinery for modification of its own proteins. The resulting glycans have unneglectable roles in viral infection and immune response. The spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which presents on the surface of matured virion and mediates viral entry into the host, also undergoes extensive glycosylation to shield it from the human defense system. It is believed that the ongoing COVID-19 pandemic with more than 90,000,000 infections and 1,900,000 deaths is partly due to its successful glycosylation strategy. On the other hand, while glycan patches on S protein have been reported to shield the host immune response by masking “nonself” viral peptides with “self-glycans,” the epitopes are also important in eliciting neutralizing antibodies. In this review, we will summarize the roles of S protein glycans in mediating virus–receptor interactions, and in antibody production, as well as indications for vaccine development.

scholarly journals Neutralizing antibody responses to SARS-CoV-2 in a COVID-19 recovered patient cohort and their implications

2020 ◽  
Author(s):  
Fan Wu ◽  
Aojie Wang ◽  
Mei Liu ◽  
Qimin Wang ◽  
Jun Chen ◽  
...  
Keyword(s):  
Immune Response ◽  
Neutralizing Antibodies ◽  
Time Course ◽  
Lentiviral Vector ◽  
Young Patients ◽  
Clinical Manifestations ◽  
Humoral Response ◽  
Neutralizing Antibody ◽  
Effective Vaccine ◽  
Global Public Health

BackgroundThe COVID-19 pandemic caused by SARS-CoV-2 coronavirus threatens global public health. Currently, neutralizing antibodies (NAbs) versus this virus are expected to correlate with recovery and protection of this disease. However, the characteristics of these antibodies have not been well studied in association with the clinical manifestations in patients.MethodsPlasma collected from 175 COVID-19 recovered patients with mild symptoms were screened using a safe and sensitive pseudotyped-lentiviral-vector-based neutralization assay. Spike-binding antibody in plasma were determined by ELISA using RBD, S1, and S2 proteins of SARS-CoV-2. The levels and the time course of SARS-CoV-2-specific NAbs and the spike-binding antibodies were monitored at the same time.FindingsSARS-CoV-2 NAbs were unable to cross-reactive with SARS-CoV virus. SARS-CoV-2-specific NAbs were detected in patients from day 10-15 after the onset of the disease and remained thereafter. The titers of NAb among these patients correlated with the spike-binding antibodies targeting S1, RBD, and S2 regions. The titers of NAbs were variable in different patients. Elderly and middle-age patients had significantly higher plasma NAb titers (P<0.0001) and spike-binding antibodies (P=0.0003) than young patients. Notably, among these patients, there were ten patients whose NAb titers were under the detectable level of our assay (ID50: < 40); while in contrast, two patients, showed very high titers of NAb, with ID50 :15989 and 21567 respectively. The NAb titers were positive correlated with plasma CRP levels but negative correlated with the lymphocyte counts of patients at the time of admission, indicating an association between humoral response and cellular immune response.InterpretationThe variations of SARS-CoV-2 specific NAbs in recovered COVID-19 patients may raise the concern about the role of NAbs on disease progression. The correlation of NAb titers with age, lymphocyte counts, and blood CRP levels suggested that the interplay between virus and host immune response in coronavirus infections should be further explored for the development of effective vaccine against SARS-CoV-2 virus. Furthermore, titration of NAb is helpful prior to the use of convalescent plasma for prevention or treatment.FundingMinistry of Science and Technology of China, National Natural Science Foundation of China, Shanghai Municipal Health Commission, and Chinese Academy of Medical Sciences

scholarly journals SARS-CoV-2 and interferon blockade

2020 ◽  
Vol 26 (1) ◽  
Author(s):  
Betty Diamond ◽  
Bruce T. Volpe ◽  
Sonya VanPatten ◽  
Yousef Al Abed
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Innate Immune System ◽  
Neutralizing Antibodies ◽  
Cytotoxic T Cells ◽  
Adaptive Immune Response ◽  
Innate Immune ◽  
Interferon Production ◽  
Therapeutic Implications ◽  
Adaptive Immune

Abstract The response to viral infection generally includes an activation of the adaptive immune response to produce cytotoxic T cells and neutralizing antibodies. We propose that SARS-CoV-2 activates the innate immune system through the renin-angiotensin and kallikrein-bradykinin pathways, blocks interferon production and reduces an effective adaptive immune response. This model has therapeutic implications.

scholarly journals Unique Resistance of I/LnJ Mice to a Retrovirus Is Due to Sustained Interferon γ–dependent Production of Virus-neutralizing Antibodies

2003 ◽  
Vol 197 (2) ◽  
pp. 233-243 ◽  
Author(s):  
Alexandra Purdy ◽  
Laure Case ◽  
Melody Duvall ◽  
Max Overstrom-Coleman ◽  
Nilah Monnier ◽  
...  
Keyword(s):  
Immune System ◽  
Neutralizing Antibodies ◽  
Immune Escape ◽  
Interferon Γ ◽  
Retroviral Infection ◽  
Targeted Deletion ◽  
Humoral Immune ◽  
Tumor Virus ◽  
Ifn Γ ◽  
Retroviral Infections

Selection of immune escape variants impairs the ability of the immune system to sustain an efficient antiviral response and to control retroviral infections. Like other retroviruses, mouse mammary tumor virus (MMTV) is not efficiently eliminated by the immune system of susceptible mice. In contrast, MMTV-infected I/LnJ mice are capable of producing IgG2a virus-neutralizing antibodies, sustain this response throughout their life, and secrete antibody-coated virions into the milk, thereby preventing infection of their progeny. Antibodies were produced in response to several MMTV variants and were cross-reactive to them. Resistance to MMTV infection was recessive and was dependent on interferon (IFN)-γ production, because I/LnJ mice with targeted deletion of the INF-γ gene failed to produce any virus-neutralizing antibodies. These findings reveal a novel mechanism of resistance to retroviral infection that is based on a robust and sustained IFN-γ–dependent humoral immune response.

scholarly journals Idiosyncratic Drug-Induced Liver Injury: Mechanistic and Clinical Challenges

2021 ◽  
Vol 22 (6) ◽  
pp. 2954
Author(s):  
Alison Jee ◽  
Samantha Christine Sernoskie ◽  
Jack Uetrecht
Keyword(s):  
Immune Response ◽  
Immune System ◽  
T Cell ◽  
Liver Injury ◽  
Clinical Manifestations ◽  
Adaptive Immune System ◽  
Human Leukocyte ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
Adaptive Immune

Idiosyncratic drug-induced liver injury (IDILI) remains a significant problem for patients and drug development. The idiosyncratic nature of IDILI makes mechanistic studies difficult, and little is known of its pathogenesis for certain. Circumstantial evidence suggests that most, but not all, IDILI is caused by reactive metabolites of drugs that are bioactivated by cytochromes P450 and other enzymes in the liver. Additionally, there is overwhelming evidence that most IDILI is mediated by the adaptive immune system; one example being the association of IDILI caused by specific drugs with specific human leukocyte antigen (HLA) haplotypes, and this may in part explain the idiosyncratic nature of these reactions. The T cell receptor repertoire likely also contributes to the idiosyncratic nature. Although most of the liver injury is likely mediated by the adaptive immune system, specifically cytotoxic CD8+ T cells, adaptive immune activation first requires an innate immune response to activate antigen presenting cells and produce cytokines required for T cell proliferation. This innate response is likely caused by either a reactive metabolite or some form of cell stress that is clinically silent but not idiosyncratic. If this is true it would make it possible to study the early steps in the immune response that in some patients can lead to IDILI. Other hypotheses have been proposed, such as mitochondrial injury, inhibition of the bile salt export pump, unfolded protein response, and oxidative stress although, in most cases, it is likely that they are also involved in the initiation of an immune response rather than representing a completely separate mechanism. Using the clinical manifestations of liver injury from a number of examples of IDILI-associated drugs, this review aims to summarize and illustrate these mechanistic hypotheses.

scholarly journals Immune Response to the Pathogenesis of COVID-19 Infection: Possible Mechanism of Nutrition (Vitamins, Supplement) and Exercise

2021 ◽  
Author(s):  
Abdullahi Alausa ◽  
Rofiat Adeyemi ◽  
Barakat Olaleke ◽  
Aminat Ismail ◽  
Faith Sunday Oyelere
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Immune Cell ◽  
Clinical Manifestations ◽  
Immune Dysfunction ◽  
Nutritional Intake ◽  
Moderate Exercise ◽  
The World ◽  
Positive Results

COVID-19 infection, a ravaging disease attributed to a SARS-CoV-like illness, has brought the world to its knee, causing a pandemic, with human-human transmission as a major source of the spread of this ailment. Alarmingly, this infection based on clinical manifestations is diagnosed as virus-induced pneumonia, with over 5 million cases with a mortality rate of about 7% (based on the recently published global report). However, most deaths have been associated with patients with underlying immune dysfunction or a compromised immunesystem. As no specific therapeutics and vaccines have been reported, the strengthening of the immune system through nutritional intake and exercise is essential. Also, previous studies have documented the immune-activating capabilities of Vitamin A and D, along with supplementary induction, yielding positive results in combating previous viral challenges. Typically, the gradual upsurge of T-lymphocytes and immune cell activities has been implemented by moderate exercise activities. This review examines the role of nutrition and exercise in immune system enhancement and proposes the possible mechanism of nutrition and exercise in combating COVID-19 infection.

scholarly journals THE MECHANISMS OF IMMUNE ESCAPE BY HEPATITIS B VIRUS

2017 ◽  
Vol 72 (6) ◽  
pp. 408-419 ◽  
Author(s):  
M. V. Sokolova ◽  
M. V. Konopleva ◽  
Т. A. Semenenko ◽  
V. G. Akimkin ◽  
A. V. Tutelyan ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Immune Escape ◽  
Adaptive Immune Response ◽  
Host Cells ◽  
Cell Functions ◽  
Adaptive Immune ◽  
B Virus

The high prevalence of the hepatitis B virus (HBV) in population occurs mainly due to numerous mechanisms formed in the process of the virus evolution, contributing to its survival under immunological pressure. The review presents the most complete systematization and classification of various HBV protective mechanisms basing on their influence on different parts of congenital and adaptive immune response. The analysis of literature data allows for the conclusion that two basic principles underlie the mechanisms: the strategy of the «stealth virus» (virus’s escape from recognition by the immune system) and strategy of immunosuppression. The stealth virus strategy is performed as follows: special strategy of the HBV replication which prevents the recognition by the receptors of congenital immune system; occurrence of the vaccine escape mutants; isolation of the virus in host cells and tissues providing its inaccessibility to T-cells along with hyperproduction of subviral particles as traps for specific antibodies. The core principle of the immunosuppression implemented in hepatitis B therapy is based on the phenomenon of the viral apoptotic mimicry. The result of this interaction strategy is dysfunction of NK and NKT-cells, inactivation of dendritic cell functions, and suppression of the adaptive immune response. The review demonstrates that interaction between HBV and the immune system of the macro organism is in some kind of «dynamic equilibrium» depending on numerous factors. Specific molecular targets of the viral impact are described. We propose to expand the research on the influence of the host’s genetic factors on the development of congenital and adaptive immune response against HBV, especially during the real infectious process which results in the improvement of approaches to the therapy by developing personalized treatment methods.

scholarly journals Multiantibody Strategies for HIV

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Andrew Hiatt ◽  
Larry Zeitlin ◽  
Kevin J. Whaley
Keyword(s):  
Immune Response ◽  
Monoclonal Antibodies ◽  
Immune System ◽  
Immune Evasion ◽  
Neutralizing Antibodies ◽  
Active Immunization ◽  
Robust Immune Response ◽  
Viral Immune Evasion ◽  
Vaccination Strategies ◽  
Appropriate Responsiveness

Vaccination strategies depend entirely on the appropriate responsiveness of our immune system against particular antigens. For this active immunization to be truly effective, neutralizing antibodies (nAbs) need to efficiently counter the infectivity or propagation of the pathogen. Some viruses, including HIV, are able to take advantage of this immune response in order to evade nAbs. This review focuses on viral immune evasion strategies that result directly from a robust immune response to infection or vaccination. A rationale for multi-Ab therapy to circumvent this phenomenon is discussed. Progress in the formulation, production, and regulatory approval of monoclonal antibodies (mAbs) is presented.

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