A Novel Hypothesis for Original Antigenic Sin in the Severe Disease of SARS-CoV-2 Infection

Köhler, Heinz; Nara, Peter L.

doi:10.1089/mab.2020.0029

Cited by 19 publications

(12 citation statements)

References 38 publications

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“…Therefore, combining IgM and IgG serology testing may not provide much diagnostic value during the later stages of the disease, questioning the rationale for measuring IgM antibodies. In addition, the early appearance of anti-SARS-CoV-2 IgG antibodies is interesting to note as similar studies have reported detectable responses as early as 3-5 days post-infection [32,50,51]. Usually, early detection of specific IgG antibodies is expected in secondary immune responses when there is a memory to cross-reactive antigens from a previous infection with a coronavirus [52,53].…”

Section: Discussionmentioning

confidence: 87%

“…Usually, early detection of specific IgG antibodies is expected in secondary immune responses when there is a memory to cross-reactive antigens from a previous infection with a coronavirus [52,53]. A phenomenon known as the "original antigenic syndrome" has been suggested to explain the underlying immune response in SARS-CoV-2, where previous infections influence the response to future virus encounters [50]. The early IgG response is possibly a memory response from earlier coronavirus infection, producing cross-reactive antibodies that do not have neutralizing potency [52].…”

Section: Discussionmentioning

confidence: 99%

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Evaluation of Antibody Response in Symptomatic and Asymptomatic COVID-19 Patients and Diagnostic Assessment of New IgM/IgG ELISA Kits

et al. 2021

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This study aims to study the immune response and evaluate the performances of four new IgM and five IgG enzyme-linked immunosorbent assay (ELISA) kits for detecting anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies against different antigens in symptomatic and asymptomatic coronavirus disease 2019 (COVID-19) patients. A total of 291 samples collected from symptomatic and asymptomatic RT–PCR-confirmed patients were used to evaluate the ELISA kits’ performance (EDI, AnshLabs, DiaPro, NovaLisa, and Lionex). The sensitivity was measured at three different time-intervals post symptoms onset or positive SARS-CoV-2 RT–PCR test (≤14, 14–30, >30 days). The specificity was investigated using 119 pre-pandemic serum samples. The sensitivity of all IgM kits gradually decreased with time, ranging from 48.7% (EDI)–66.4% (Lionex) at ≤14 days, 29.1% (NovaLisa)–61.8% (Lionex) at 14–30 days, and 6.0% (AnshLabs)–47.9% (Lionex) at >30 days. The sensitivity of IgG kits increased with time, peaking in the latest interval (>30 days) at 96.6% (Lionex). Specificity of IgM ranged from 88.2% (Lionex)–99.2% (EDI), while IgG ranged from 75.6% (DiaPro)–98.3% (Lionex). Among all RT–PCR-positive patients, 23 samples (7.9%) were seronegative by all IgG kits, of which only seven samples (30.4%) had detectable IgM antibodies. IgM assays have variable and low sensitivity, thus considered a poor marker for COVID-19 diagnosis. IgG assays can miss at least 8% of RT–PCR-positive cases.

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Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Evaluation of Antibody Response in Symptomatic and Asymptomatic COVID-19 Patients and Diagnostic Assessment of New IgM/IgG ELISA Kits

et al. 2021

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“…This is particularly essential in novel viral infections, such as SARS-CoV-2 in which a pre-existing immunity is not possible ( Pichlmair and Reis e Sousa, 2007 ; Ayegbusi et al, 2018 ; Costela-Ruiz et al, 2020 ). The acute nature of the infection may also account for the possibility of severe re-infection due to its deceptive imprinting ( Kohler and Nara, 2020 ; Westerhuis et al, 2020 ). Deceptive imprinting refers to immune evasion mechanisms by certain viruses in which antibodies are mounted against immunodominant epitopes, thereby inducing strain-specific immunity, which offers little or no neutralization activity between serotypes and subtypes.…”

Section: Pathogenesis Of Sars-cov-2 Infectionmentioning

confidence: 99%

Microglial Implications in SARS-CoV-2 Infection and COVID-19: Lessons From Viral RNA Neurotropism and Possible Relevance to Parkinson’s Disease

Awogbindin

Ben-Azu

Olusola

et al. 2021

Front. Cell. Neurosci.

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Since December 2019, humankind has been experiencing a ravaging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak, the second coronavirus pandemic in a decade after the Middle East respiratory syndrome coronavirus (MERS-CoV) disease in 2012. Infection with SARS-CoV-2 results in Coronavirus disease 2019 (COVID-19), which is responsible for over 3.1 million deaths worldwide. With the emergence of a second and a third wave of infection across the globe, and the rising record of multiple reinfections and relapses, SARS-CoV-2 infection shows no sign of abating. In addition, it is now evident that SARS-CoV-2 infection presents with neurological symptoms that include early hyposmia, ischemic stroke, meningitis, delirium and falls, even after viral clearance. This may suggest chronic or permanent changes to the neurons, glial cells, and/or brain vasculature in response to SARS-CoV-2 infection or COVID-19. Within the central nervous system (CNS), microglia act as the central housekeepers against altered homeostatic states, including during viral neurotropic infections. In this review, we highlight microglial responses to viral neuroinfections, especially those with a similar genetic composition and route of entry as SARS-CoV-2. As the primary sensor of viral infection in the CNS, we describe the pathogenic and neuroinvasive mechanisms of RNA viruses and SARS-CoV-2 vis-à-vis the microglial means of viral recognition. Responses of microglia which may culminate in viral clearance or immunopathology are also covered. Lastly, we further discuss the implication of SARS-CoV-2 CNS invasion on microglial plasticity and associated long-term neurodegeneration. As such, this review provides insight into some of the mechanisms by which microglia could contribute to the pathophysiology of post-COVID-19 neurological sequelae and disorders, including Parkinson’s disease, which could be pervasive in the coming years given the growing numbers of infected and re-infected individuals globally.

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“…(1,2) The finding that common cold cross-reacting antibodies are not neutralizing SARS-CoV-2 (3) have been discussed earlier with respect to the symmetrical network hypothesis. (4) A variety of therapeutic strategies have been used with limited effectiveness. (5) Thus, it is imperative to better understand the pathology and to find new medicines and improve currently used therapeutics.…”

Section: Introductionmentioning

confidence: 99%

How IvIg Can Mitigate Covid-19 Disease: A Symmetrical Immune Network Model

Köhler

Kaveri

2021

Monoclonal Antibodies in Immunodiagnosis and Immunotherapy

Self Cite

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In this report we provide a hypothesis of how intravenous immunoglobulin (IvIg) (pooled therapeutic normal IgG) mitigates the severe disease after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. The disease is caused by an overreaction of the innate immune system producing a cytokine storm and inflicting multiple organ damage. Our interpretation of IvIg therapy hinges on a recent analysis of the immune dysregulation in Covid-19 infection. Previous infections with common cold coronavirus induce suppressor memory B cells that inhibit an immune response to Covid-19. The repertoire of natural antibodies (IvIg) contains suppressing antibodies in a symmetrically balanced network structure. When this repertoire interacts with the imbalanced network in the infected patient, it can neutralize the suppression of an antibody response against Covid-19. The described scenario for IvIg in Covid-19 infection may also apply in the therapy of autoimmune diseases.

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A Novel Hypothesis for Original Antigenic Sin in the Severe Disease of SARS-CoV-2 Infection

Cited by 19 publications

References 38 publications

Evaluation of Antibody Response in Symptomatic and Asymptomatic COVID-19 Patients and Diagnostic Assessment of New IgM/IgG ELISA Kits

Evaluation of Antibody Response in Symptomatic and Asymptomatic COVID-19 Patients and Diagnostic Assessment of New IgM/IgG ELISA Kits

Microglial Implications in SARS-CoV-2 Infection and COVID-19: Lessons From Viral RNA Neurotropism and Possible Relevance to Parkinson’s Disease

How IvIg Can Mitigate Covid-19 Disease: A Symmetrical Immune Network Model

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