Lasting antibody and T cell responses to SARS-CoV-2 in COVID-19 patients three months after infection

Jiang, Xiao Lin; Wang, Guo Lin; Zhao, Xiang; Yan, Fei; Ye, Lilin; Kou, Zeng Qiang; Ji, Sheng Xiang; Zhang, Xiao Li; Li, Cun Bao; Duan, Li Jun; Li, Yan; Zhang, Yu Wen; Duan, Qing; Wang, Tie Cheng; Li, En Tao; Wei, Xin; Wang, Qing Yang; Wang, Xue Feng; Sun, Wei; Gao, Yu; Kang, Dianming; Zhang, Ji Yan; Ma, Mai‐Juan

doi:10.1038/s41467-021-21155-x

Cited by 81 publications

(68 citation statements)

References 46 publications

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“…To answer the intriguing question whether mild SARS-CoV-2 infections could trigger long-term autoimmune events that can be detected during convalescent phase, our prospective study demonstrates that indeed in former SARS-CoV-2 infected individuals that suffered mild symptoms elevated autoantibody levels and rare diagnostic patterns on HEp 2 cells (ANA) actually persist months later. This long-lasting effects appear similar to those persistent antibody and T-cell responses observed in acute COVID-19 patients [ 34 ]. The induction of autoimmune events has been frequently monitored as a common event during acute viral infections and anti-viral antibodies have been shown to react against tissue antigens [ 35 ].…”

Section: Discussionsupporting

confidence: 77%

Unique autoantibody prevalence in long-term recovered SARS-CoV-2-infected individuals

Lingel

Meltendorf

Billing

et al. 2021

Journal of Autoimmunity

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The variability in resolution of SARS-CoV-2-infections between individuals neither is comprehended, nor are the long-term immunological consequences. To assess the long-term impact of a SARS-CoV-2-infection on the immune system, we conducted a prospective study of 80 acute and former SARS-CoV-2 infected individuals and 39 unexposed donors to evaluate autoantibody responses and immune composition. Autoantibody levels against cyclic citrullinated peptide (CCP), a specific predictor for rheumatoid arthritis (RA), were significantly (p = 0.035) elevated in convalescents only, whereas both acute COVID-19 patients and long-term convalescents showed critically increased levels of anti-tissue transglutaminase (TG), a specific predictor of celiac disease (CD) (p = 0.002). Both, anti-CCP and anti-TG antibody levels were still detectable after 4–8 months post infection. Anti-TG antibodies occurred predominantly in aged patients in a context of a post-SARS-CoV-2-specific immune composition (R 2 = 0.31; p = 0.044). This study shows that increased anti-CCP and anti-TG autoantibody levels can remain long-term after recovering even from mildly experienced COVID-19. The inter-relationship of the lung as viral entry side and RA- and CD-associated autoimmunity indicates that a SARS-CoV-2-infection could be a relevant environmental factor in their pathogenesis.

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Section: Discussionsupporting

confidence: 77%

Unique autoantibody prevalence in long-term recovered SARS-CoV-2-infected individuals

Lingel

Meltendorf

Billing

et al. 2021

Journal of Autoimmunity

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“…One potential limitation of our study is that the median number of days from clinical onset to sampling was different between the groups of patients due to the confinement decreed by the Spanish Government, which prevented the patients with mild COVID-19 to participate in the study until the confinement ended. However, the adaptive immune response is expected to be fully active within 3 weeks after the infection and SARS-CoV-2-specific CD4+ or CD8+ T cell responses, as well as high levels of neutralizing antibodies, are still detectable after 3–4 months post-infection ( 54 ). Due to the vast majority of our patients were recruited within this range of 3 weeks to 4 months post-infection, the immune response data should be comparable between groups.…”

Section: Discussionmentioning

confidence: 99%

Impaired Cytotoxic Response in PBMCs From Patients With COVID-19 Admitted to the ICU: Biomarkers to Predict Disease Severity

et al. 2021

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Infection by novel coronavirus SARS-CoV-2 causes different presentations of COVID-19 and some patients may progress to a critical, fatal form of the disease that requires their admission to ICU and invasive mechanical ventilation. In order to predict in advance which patients could be more susceptible to develop a critical form of COVID-19, it is essential to define the most adequate biomarkers. In this study, we analyzed several parameters related to the cellular immune response in blood samples from 109 patients with different presentations of COVID-19 who were recruited in Hospitals and Primary Healthcare Centers in Madrid, Spain, during the first pandemic peak between April and June 2020. Hospitalized patients with the most severe forms of COVID-19 showed a potent inflammatory response that was not translated into an efficient immune response. Despite the high levels of effector cytotoxic cell populations such as NK, NKT and CD8+ T cells, they displayed immune exhaustion markers and poor cytotoxic functionality against target cells infected with pseudotyped SARS-CoV-2 or cells lacking MHC class I molecules. Moreover, patients with critical COVID-19 showed low levels of the highly cytotoxic TCRγδ+ CD8+ T cell subpopulation. Conversely, CD4 count was greatly reduced in association to high levels of Tregs, low plasma IL-2 and impaired Th1 differentiation. The relative importance of these immunological parameters to predict COVID-19 severity was analyzed by Random Forest algorithm and we concluded that the most important features were related to an efficient cytotoxic response. Therefore, efforts to fight against SARS-CoV-2 infection should be focused not only to decrease the disproportionate inflammatory response, but also to elicit an efficient cytotoxic response against the infected cells and to reduce viral replication.

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“…As efforts are underway to curtail further spread of COVID-19 worldwide, it is critical to understand the longevity and potency of immune response to SARS□CoV□2. Antibody production represents a significant component of the immune response to SARS-CoV-2, and serologic assays to detect circulating antibody levels are a readily available tool in clinical laboratory settings for tracking immune responses over time [1, 2].…”

Section: Introductionmentioning

confidence: 99%

Anti-SARS-CoV-2 Serology persistence over time in COVID-19 Convalescent Plasma Donors

Giorgi

West

Henning

et al. 2021

Preprint

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Background: Characterizing the kinetics of the antibody response to SARS-CoV-2 is of critical importance to developing strategies that may mitigate the public health burden of COVID-19. We sought to determine how circulating antibody levels change over time following natural infection. Methods/Materials: We conducted a prospective, longitudinal analysis of COVID-19 convalescent plasma (CCP) donors at multiple time points over a 9-month period. At each study visit, subjects either donated plasma or only had study samples drawn. In all cases, anti-SARS-CoV-2 donor testing was performed using semi-quantitative chemiluminescent immunoassays (ChLIA) targeting subunit 1 (S1) of the SARS-CoV-2 spike (S) protein, and an in-house fluorescence reduction neutralization assay (FRNA). Results: From April to November 2020 we enrolled 202 donors, mean age 47.3 +/- 14.7 years, 55% female, 75% Caucasian. Most donors reported a mild clinical course (91%, n=171) without hospitalization. One hundred and five (105) (52%) donors presented for repeat visits with a median 42 (12 -163) days between visits. The final visit occurred at a median 160 (53-273) days post-symptom resolution. Total anti-SARS-CoV-2 antibodies (Ab), SARS-CoV-2 specific IgG and neutralizing antibodies were detected in 97.5%, 91.1%, and 74% of donors respectively at initial presentation. Neutralizing Ab titers based on FRNA50 were positively associated with mean IgG levels (p = <0.0001). Mean IgG levels and neutralizing titers were positively associated with COVID-19 severity, increased donor age and BMI (p=0.0006 and p=0.0028, p=0.0083 and p=0.0363, (p=0.0008 and p=0.0018, respectively). Over the course of repeat visits, IgG decreased in 74.1% of donors; FRNA50 decreased in 44.4% and remained unchanged in 33.3% of repeat donors. A weak negative correlation was observed between total Ab levels and number of days post-symptom recovery (r = 0.09). Conclusion: Anti-SARS-CoV-2 antibodies were identified in 97% of convalescent donors at initial presentation. In a cohort that largely did not require hospitalization. IgG and neutralizing antibodies were positively correlated with age, BMI and clinical severity, and persisted for up to 9 months post-recovery from natural infection. On repeat presentation, IgG anti-SARS-CoV-2 levels decreased in 56% of repeat donors. Overall, these data suggest that CP donors possess a wide range of IgG and neutralizing antibody levels that are proportionally distributed across demographics, with the exception of age, BMI and clinical severity.

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Lasting antibody and T cell responses to SARS-CoV-2 in COVID-19 patients three months after infection

Cited by 81 publications

References 46 publications

Unique autoantibody prevalence in long-term recovered SARS-CoV-2-infected individuals

Unique autoantibody prevalence in long-term recovered SARS-CoV-2-infected individuals

Impaired Cytotoxic Response in PBMCs From Patients With COVID-19 Admitted to the ICU: Biomarkers to Predict Disease Severity

Anti-SARS-CoV-2 Serology persistence over time in COVID-19 Convalescent Plasma Donors

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