Interferon autoantibodies not implicated in long-COVID

In a recent study published in The Journal of Infectious Diseases, researchers assess the proportion of interferon (IFN) autoantibodies in long-coronavirus disease (COVID) patients.

Study: Low Prevalence of Interferon α Autoantibodies in People Experiencing Symptoms of Post–Coronavirus Disease 2019 (COVID-19) Conditions, or Long COVID. Image Credit: WIROJE PATHI /

Study: Low Prevalence of Interferon α Autoantibodies in People Experiencing Symptoms of Post–Coronavirus Disease 2019 (COVID-19) Conditions, or Long COVID. Image Credit: WIROJE PATHI /

COVID-19 and IFN

IFNs play a crucial function in innate antiviral immune reactions. It has been demonstrated that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection inhibits type I and III IFN responses. In addition, the existence of IFN-specific autoantibodies has been suggested as a possible cause of post-acute sequelae of COVID-19 (PASC), particularly long-COVID.

Recently, a provocative investigation established a correlation between IFN-ɑ2-specific autoantibodies and pulmonary symptoms during acute COVID-19, as well as two to three months after initial SARS-CoV-2 infection presentation.

About the study

In the present study, researchers obtained samples as well as demographic, clinical, and symptom data from the Long-term Impact of Infection with Novel Coronavirus (LIINC) research participants who had nucleic acid-confirmed COVID-19, many of whom developed post-COVID-19 conditions like long-COVID.

Patients with a history of COVID-19 verified by nucleic acid amplification tests were recruited. Whole-blood samples containing ethylenediaminetetraacetic acid were centrifuged to obtain plasma.

Samples were obtained between April 21, 2020, and June 29, 2021. These specimens accounted for all cohort members who were enrolled prior to receiving the SARS-CoV-2 vaccination.

During each visit, long-COVID was diagnosed using cross-sectional analysis. Long COVID was defined in as the presence of COVID-19-attributable symptoms observed at a visit 60 days or more after the onset of initial SARS-CoV-2 symptoms. An immunoprecipitation technique was employed to quantify anti-IFN-ɑ2 antibodies.


Biospecimens were collected at 394-time points between 0.5 and 14.7 months after the onset of symptoms from 215 unique subjects. Ninety-nine participants were women, and 48 were hospitalized due to acute COVID-19. Out of the hospitalized patients, 16 were in the intensive care unit, while six needed mechanical ventilation.

A total of 272 of the 394-time points that represented 185 unique participants occurred 60 days after the onset of COVID-19 symptoms, which facilitated the detection of long-COVID during the visit.

Long COVID criteria were met by 121 unique subjects over 182 distinct time periods. The cohort suffering from long-COVID was extremely symptomatic.

The median number of long COVID symptoms at any time point among individuals who reported long COVID symptoms was five. Approximately 64 unique subjects at 91-time points reported five or more symptoms, while 22 unique subjects at 29-time points reported over ten symptoms.

Autoantibodies specific to IFN-ɑ2 were found in only two of 215 subjects across all time points. Anti-IFN antibodies were identified in the first participant 87 and 115 days after acute COVID-19 infection.

Ten days after COVID-19 symptom onset, this patient originally presented in the spring of 2020 with pulseless electrical activity arrest necessitating resuscitation and artificial respiration. Following hospitalization, he reported intermittent neuropathic pain condition and persistent anosmia for 18 months or more, and occasional viral shedding confirmed with clinical nucleic acid amplification tests for almost six months.

The second individual exhibited measurable anti-IFN antibodies approximately 41 and 90 days after acute COVID-19 and required supplementary oxygen when hospitalized in early 2021. Thereafter, he was diagnosed with long-COVID, characterized by fatigue, headache, shortness of breath, alterations in vision, peripheral neuropathy, and concentration difficulties that were persistent for at least 12 months.

In both patients, chronic symptoms were accounted for by long-COVID, despite the fact that both patients had complex hospital courses that could have led to post-hospitalization disorders. In contrast to these two patients with IFN-ɑ2-specific autoantibodies, most of the study group exhibited no levels of detectable anti-IFN antibodies at any time period.

Autoantibodies specific to IFN-ɑ2 were not detected in any of the outpatients treated for COVID-19. In addition to the two people described here, IFN-ɑ2-specific autoantibodies were not detected in any additional individuals who developed moderate-to-severe COVID symptoms lasting up to two years.


Anti-IFN-ɑ2 antibodies, which serve as a contributing factor to severe acute COVID-19 and play a potential role in long-COVID symptoms, were uncommon in the post-acute COVID-19 sample that included long-COVID patients.

Given the heterogeneous nature of long COVID and the various terminology used to describe the syndrome, understanding the causes of long COVID presents a number of obstacles. This further underscores the necessity for clear and larger mechanistic research in clinical cohorts.

Journal reference:
  • Peluso, M. J., Mitchell, A., Wang, C. Y., et al. (2023). Low Prevalence of Interferon α Autoantibodies in People Experiencing Symptoms of Post–Coronavirus Disease 2019 (COVID-19) Conditions, or Long COVID. The Journal of Infectious Diseases 227(2); 246-250. doi:10.1093/infdis/jiac372
Bhavana Kunkalikar

Written by

Bhavana Kunkalikar

Bhavana Kunkalikar is a medical writer based in Goa, India. Her academic background is in Pharmaceutical sciences and she holds a Bachelor's degree in Pharmacy. Her educational background allowed her to foster an interest in anatomical and physiological sciences. Her college project work based on ‘The manifestations and causes of sickle cell anemia’ formed the stepping stone to a life-long fascination with human pathophysiology.


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