Anti-nucleocapsid antibodies enhance the production of IL-6 induced by SARS-CoV-2 N protein

Nakayama, Emi E.; Kubota‐Koketsu, Ritsuko; Sasaki, Tadahiro; Suzuki, Komei; Uno, Kazuko; Shimizu, Jun; Okamoto, Tomoyoshi; Matsumoto, Hisatake; Mizunuma, Hiroshi; Hirano, Shoji; Tanaka, Toshio; Harada, Hiromasa; Tomita, Mitsuhiro; Kaneko, Mitsunori; Yoshizaki, Kazuyuki; Shioda, Tatsuo

doi:10.1038/s41598-022-12252-y

Cited by 21 publications

(24 citation statements)

References 70 publications

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“…Therefore, the comparison of correlation between cytokines and antibody response in the infected group and the vaccinated group can imply the future role of cytokine supplements on vaccine development. In another study, increased IL‐6 in COVID‐19 patients with severe diseases has been reported to be associated with SARS‐CoV‐2 N protein 41 . It may be correlated with the stronger immune response in the infected individuals.…”

Section: Discussionmentioning

confidence: 89%

“…[29][30][31] Clinical factors were also verified to influence antibody levels in with severe diseases has been reported to be associated with SARS-CoV-2 N protein. 41 It may be correlated with the stronger immune response in the infected individuals. Accordingly, the influence of cytokines on vaccine outcomes should be considered in the future of vaccine development.…”

Section: Different Expression Of Cytokines Between Previously Infecte...mentioning

confidence: 99%

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Distinct immune responses in the early phase to natural SARS‐CoV‐2 infection or vaccination

Peng¹,

Deng²,

Li³

et al. 2022

Journal of Medical Virology

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Immune responses elicited by viral infection or vaccination play key roles in the viral elimination and the prevention of reinfection, as well as the protection of healthy persons. As one of the most widely used Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines, there have been increasing concerns about the necessity of additional doses of inactivated vaccines, due to the waning immune response several months after vaccination. To further optimize inactivated SARS-CoV-2 vaccines, we compared immune responses to SARS-CoV-2 elicited by natural infection and immunization with inactivated vaccines in the early phase. We observed the lower antibody levels against SARS-CoV-2 spike (S) and nucleocapsid (N) proteins in the early phase of postvaccination with a slow increase, compared to the acute phase of SARS-CoV-2 natural infection. Specifically, IgA antibodies have the most significant differences. Moreover, we further analyzed cytokine expression between these two groups. A wide variety of cytokines presented high expression in the infected individuals, while a few cytokines were elicited by inactivated vaccines. The differences in antibody responses and cytokine levels between natural SARS-CoV-2 infection and vaccination with the inactivated vaccines may provide implications for the optimization of inactivated SARS-CoV-2 vaccines and the additional application of serological tests.

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Section: Discussionmentioning

confidence: 89%

Section: Different Expression Of Cytokines Between Previously Infecte...mentioning

confidence: 99%

Distinct immune responses in the early phase to natural SARS‐CoV‐2 infection or vaccination

Peng¹,

Deng²,

Li³

et al. 2022

Journal of Medical Virology

View full text Add to dashboard Cite

show abstract

“… 41 – 43 The repercussion(s) of the lack of anti-N antibodies is unclear, but has recently been suggested to be important for IL6 production and possibly cytokine storm induction. 44 Investigating these possibilities was beyond the scope of our current study but warrants further investigation. Since antibodies against N protein are often used to confirm past infection, our current finding has important implications on the utility of existing serological diagnostic and surveillance for SARS-CoV-2 prevalence in breakthrough infections.…”

Section: Discussionmentioning

confidence: 89%

Absence of antibody responses to SARS-CoV-2 N protein in COVID-19 vaccine breakthrough cases

Wallace

Phan

et al. 2022

Exp Biol Med (Maywood)

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Understanding the risk factors for breakthrough coronavirus disease 2019 (COVID-19) (BC19) is critical to inform policy. Herein, we assessed Delta (Lineage B.1.617.2) variant-specific effectiveness of the BNT162b2 (Pfizer) vaccine and characterized Delta-driven BC19 cases (fully vaccinated individuals who get infected) with known-time-since-vaccination. In this longitudinal prospective study (January 21–October 30, 2021), 90 naïve and 15 convalescent individuals were enrolled at the initiation of vaccination. Samples from 27 unvaccinated individuals with previous laboratory-confirmed COVID-19 diagnosis were collected at a single time point. Longitudinal serology profile (antibodies against severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] S and N proteins) and live-virus-based neutralization capacities were assessed while controlling for age. Sex, age, history of reactions to the COVID-19 vaccine, and viral neutralization capacities were identified as significant risk factors for breakthrough COVID-19. At 8 months postvaccination, male sex, individuals ⩾65 years of age, and individuals who experienced noticeable side effects with the COVID-19 vaccine were at 5.47 ( p-value = 0.0102), 4.33 ( p-value = 0.0236), and 4.95 ( p-value = 0.0159) fold greater risk of BC19 as compared to their peers, respectively. Importantly, every five-fold increase in viral neutralization capacities (by live-virus-based assays) was significantly associated with ~4-fold reduction in the risk occurrence of breakthrough COVID-19 ( p-value = 0.045). Vaccine boosting remarkably increased these viral neutralization capacities by 16.22-fold ( p- value = 0.0005), supporting the importance of the BNT162b2 booster in efforts to control the incursion of future variants into the population at large. Strikingly, BC19 cases exhibited a delayed/absent antibody response to the N protein, suggesting limited exposure to the virus. Since antibodies against N protein are widely used to evaluate the extent of virus spread in communities, our finding has important implications on the utility of existing serological diagnostic and surveillance for COVID-19.

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“…Additionally, there is substantial evidence that anti-S antibodies are crucial in the recovery from COVID-19 [ 23 , 25 , 26 , 28 ]. There is even evidence that anti-N antibodies might contribute to the pathogenesis of the cytokine storm in COVID-19 [ 33 ]. Therefore, we focused on anti-S antibody response and utilised just the test to assess the presence of anti-S antibodies.…”

Section: Discussionmentioning

confidence: 99%

Anti-SARS-CoV-2 Antibody Status at the Time of Hospital Admission and the Prognosis of Patients with COVID-19: A Prospective Observational Study

Jurenka

Nagyová

Dababseh

et al. 2022

Infectious Disease Reports

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The association between COVID-19 severity and antibody response has not been clearly determined. We aimed to assess the effects of antibody response to SARS-CoV-2 S protein at the time of hospital admission on in-hospital and longitudinal survival. Methods: A prospective observational study in naive hospitalised COVID-19 patients. The presence of anti-S SARS-CoV-2 IgM and IgG was evaluated using a lateral flow assay at the time of admission. The patients were followed up for 8–30 months to assess survival. We recruited 554 patients (330 men and 224 women). Overall, 63.0% of the patients had positive IgG or IgM anti-S SARS-CoV-2 antibodies at the time of hospital admission. In the univariate analysis, the patients with negative anti-S SARS-CoV-2 IgM and IgG antibodies were referred to the hospital sooner, had lower CRP and D-dimer concentrations, and were hospitalised longer. They were also more likely to be admitted to an intensive care unit and more often received baricitinib treatment. During their hospital stay, 8.5% of the antibody-positive and 22.3% of the antibody-negative patients died (p = 0.0001). The median duration of the follow-up was 21 months. During the follow-up after hospital discharge, 3.6% of antibody-positive and 9.1% of antibody-negative patients died (p = 0.027). In the multivariate analysis, the negative anti-S SARS-CoV-2 antibodies were associated with a higher risk of in-hospital death (OR 3.800; 95% CI 1.844–7.829; p = 0.0001) and with a higher risk of death during follow-up (OR 2.863; 95% CI 1.110–7.386; p = 0.030). These associations were independent of age, the time from symptom onset to hospital admission, CRP, D-Dimer, the number of comorbidities, disease severity at the time of hospital admission, and baricitinib therapy. Our study concludes that negative anti-S SARS-CoV-2 IgM and IgG at the time of admission are associated with higher in-hospital mortality and cause a higher risk of all-cause death during follow-up after discharge.

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Anti-nucleocapsid antibodies enhance the production of IL-6 induced by SARS-CoV-2 N protein

Cited by 21 publications

References 70 publications

Distinct immune responses in the early phase to natural SARS‐CoV‐2 infection or vaccination

Distinct immune responses in the early phase to natural SARS‐CoV‐2 infection or vaccination

Absence of antibody responses to SARS-CoV-2 N protein in COVID-19 vaccine breakthrough cases

Anti-SARS-CoV-2 Antibody Status at the Time of Hospital Admission and the Prognosis of Patients with COVID-19: A Prospective Observational Study

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