New-onset IgG autoantibodies in hospitalized patients with COVID-19

Chang, Sarah; Feng, Allan; Meng, Wenzhao; Apostolidis, Sokratis A.; Mack, Elisabeth; Artandi, Maja; Barman, Linda; Bennett, Kate; Chakraborty, Saborni; Chang, Iris; Cheung, Peggie; Chinthrajah, Sharon; Dhingra, Shaurya; Do, Evan; Finck, Amanda; Gaano, Andrew; Geßner, Reinhard; Giannini, H.M.; González, Joyce; Greib, Sarah; Gündisch, Margrit; Hsu, Alexander; Kuo, Alex; Manohar, Monali; Mao, Rong; Neeli, Indira; Neubauer, Andreas; Oniyide, Oluwatosin; Chen, Alex; Puri, Rajan; Renz, Harald; Schapiro, Jeffrey M.; Weidenbacher, Payton A.; Wittman, Richard; Ahuja, Neera; Chung, Ho‐Ryun; Jagannathan, Prasanna; James, Judith A.; Kim, Peter; Meyer, Nuala J.; Nadeau, Kari; Radic, Marko; Robinson, William H.; Singh, Upinder; Wang, Taia T.; Wherry, E. John; Skevaki, Chrysanthi; Prak, Eline T. Luning; Utz, Paul J.

doi:10.1038/s41467-021-25509-3

Cited by 371 publications

(435 citation statements)

References 61 publications

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“…In the observation with the context of severe COVID-19, numerous antibody secreting cells are produced as a result of upregulation of extrafollicular B cells, including clonotypes that are autoreactive ( Woodruff et al, 2020 ). Considering these data in cellular structuring, ANA was detected in 18% of COVID-19 patients in our study, but this was lower than the data in the literature (21.3%–64%) ( Pascolini et al, 2021 ; Gazzaruso et al, 2020 ; Lerma et al, 2020 ; Sacchi et al, 2020 ; Chang et al, 2021b ; Chang et al, 2021a ; Trahtemberg et al, 2021 ). The relationship between disease severity or the time of sampling and antibody titers were not significant, but the majority of ANAs were strongly positive at a titer of 3+.…”

Section: Discussioncontrasting

confidence: 89%

“…Although various ANA patterns have been detected in the initiation of COVID-19, the presence of patterns directed mainly against nuclear antigens has been reported ( Lerma et al, 2020 ; Chang et al, 2021b ; Chang et al, 2021a ). In agreement with the literature, mainly nucleolar patterns were detected in our study.…”

Section: Discussionmentioning

confidence: 99%

“…There are only a limited number of studies showing vasculitis associated autoantibodies in COVID-19 patients ( Gazzaruso et al, 2020 ; Sacchi et al, 2020 ; Vlachoyiannopoulos et al, 2020 ; Chang et al, 2021a ). In ANCA associated vasculitis, the most common ANCAs target MPO and PR3 which are closely related with small vessel vasculitis ( Sundqvist et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

“…Nuclear antigens are usually the target of autoantibodies and anti-nuclear antibodies (ANA) can be detected in many autoimmune diseases such as systemic lupus erythematosus (SLE), but also in many viral infections ( Sener et al, 2014 ). Although there are several studies in the literature, autoantibodies are commonly seen in COVID-19 patients (21.3%–64%), but larger studies are needed to investigate their association with disease prognosis ( Pascolini et al, 2021 ; Gazzaruso et al, 2020 ; Lerma et al, 2020 ; Sacchi et al, 2020 ; Chang et al, 2021b ; Chang et al, 2021a ; Trahtemberg et al, 2021 ). However, because ANA is also positive in the healthy population (with a weak titer and prevalence ranging from 8% to 15%) and in other clinical conditions, positive results must be interpreted with clinical data ( Kaklıkkaya et al, 2020 ; Yurttutan Uyar et al, 2017 ; Damoiseaux et al, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

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Antinuclear antibodies (ANAs) detected by indirect immunofluorescence (IIF) method in acute COVID-19 infection; future roadmap for laboratory diagnosis

Peker

Şener

Aydoğmuş

2021

Journal of Immunological Methods

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Section: Discussioncontrasting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Antinuclear antibodies (ANAs) detected by indirect immunofluorescence (IIF) method in acute COVID-19 infection; future roadmap for laboratory diagnosis

Peker

Şener

Aydoğmuş

2021

Journal of Immunological Methods

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“…Recent studies have demonstrated the significant breadth of emerging autoreactivity in severe SARS-CoV-2 infection [1][2][3] . More specifically, we have identified a relaxation of peripheral tolerance within early antibody secreting cells that emerge in patients with COVID-19 as important drivers of those responses 2 .…”

Section: Main Textmentioning

confidence: 99%

Inflammation and autoreactivity define a discrete subset of patients with post-acute sequelae of COVID-19, or long-COVID

Woodruff

Walker

Truong

et al. 2021

Preprint

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Recent studies have demonstrated the significant breadth of emerging autoreactivity in severe SARS-CoV-2 infection. Importantly, we have identified a relaxation of peripheral tolerance within early antibody secreting cells that emerge in patients with COVID-19 as important drivers of those responses. While often viral-specific, these extrafollicular-derived cells also display cross reactivity to autoantigens present in the inflammatory lung environment, and despite resolution of most autoreactivity within 6 months, they persisted in some patients. These results raise questions regarding autoreactive antibodies that arise during acute SARS-CoV-2 infection and their persistence in patients with symptoms in Post-Acute Sequelae of SARS-CoV-2 infection (PASC). Through clinical autoreactive antibody screening of 95 patients with PASC and no history of autoimmune disease, we identify significant autoreactive profiles in patients with ongoing symptoms post-recovery, with 80% of patients returning positive tests for at least one autoantigen, and 40% showing breaks in tolerance to 2 or more. Anti-nuclear antigen positivity was most common, displaying positivity in 63% of patients, however, positive tests were broad and included reactivities against carbamylated protein responses, RNA polymerase III, and phospholipids. We also identify patients with reactivity against dsDNA in the PASC cohort -- a reactivity not observed in acute infection even in the critically ill. These results demonstrate evidence of serum autoantibodies in patients who present to PASC clinics with persistent symptoms up 14 months following SARS-CoV-2 infection, and further confirm the growing linkage between COVID-19 and observed clinical autoreactivity -- even into the recovery phase of disease.

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COVID-19 as a Risk Factor For Autoimmune Skin Disease

Arkin,

Barbieri,

Cowen

2024

JAMA Dermatol

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The COVID-19 pandemic is officially endemic, with more than 775 million cases now reported by the World Health Organization. Thanks to the effectiveness of vaccination combined with natural immunity, SARS-CoV-2 infection is no longer the novel and life-threatening virus it was in the early days of the pandemic, although it still carries risk to some.Conversely, 4 years of experience with COVID-19 has led to numerous reports of long-term sequelae, including various autoimmune disorders. Most literature regarding autoimmune skin disease has been limited to case reports and small case series with limited long-term follow-up. 1,2 In this issue of JAMA Dermatology, Heo et al 3 characterize the long-term risk of autoimmune and autoinflammatory disorders following confirmed SARS-CoV-2 infection. Investigators used data from the National Health Insurance Service Cohort in Korea, which encompasses more than 99% of the Korean population. Approximately 3 million individuals with polymerase chain reaction-confirmed SARS-CoV-2 infection were compared to nearly 4 million individuals without polymerase chain reaction-confirmed infection. Individuals were followed up for at least 180 days (October 2020-December 2022), a substantially longer follow-up than in previous studies. The study 3 found a significantly increased risk of many autoimmune and autoinflammatory diseases in individuals with confirmed COVID-19, including alopecia areata, alopecia totalis, vitiligo, bullous pemphigoid, and systemic lupus erythematosus, among others. Those with severe infection harbored greater risk of autoimmunity, whereas those who were vaccinated (with presumed greater protection from severe infection) had significantly decreased risk. Although genotyping was unavailable, data were analyzed based on time periods dominated by the Omicron and Delta variants. Infection during the peak period of the Delta variant, which was widely reported to cause increased risk of severe infection, 4 lower respiratory tract involvement, and hospital admission, was associated with greater risk for autoimmunity relative to infection during the peak Omicron variant.This well-executed study by Heo et al 3 provides compelling evidence to support an association between COVID-19 infection and the development of subsequent autoimmune and auto-inflammatory skin diseases. The study had several strengths, including the high-quality data available in this cohort and the extended follow-up period. In addition, the use of a negative control group helped mitigate the likelihood that these findings were reflective of ascertainment bias. Although there is a risk of misclassification bias (ie, control population was also exposed to COVID-19), this would be expected

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New-onset IgG autoantibodies in hospitalized patients with COVID-19

Cited by 371 publications

References 61 publications

Antinuclear antibodies (ANAs) detected by indirect immunofluorescence (IIF) method in acute COVID-19 infection; future roadmap for laboratory diagnosis

Antinuclear antibodies (ANAs) detected by indirect immunofluorescence (IIF) method in acute COVID-19 infection; future roadmap for laboratory diagnosis

Inflammation and autoreactivity define a discrete subset of patients with post-acute sequelae of COVID-19, or long-COVID

COVID-19 as a Risk Factor For Autoimmune Skin Disease

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