Nasal Swab Test Can Predict COVID-19 Severity Through Autoantibody Analysis

New research published in Science Translational Medicine demonstrates a protective role for nasal anti-interferon-α (anti–IFN-α) autoantibodies in blood in the immunopathology of COVID-19, which could provide a more precise prediction of disease severity to inform personalized treatment protocol in patients.^1,2

Determining disease severity through nasal swab diagnostic testing could be a major breakthrough in treating patients with COVID-19. | Image Credit: © BASILICOSTUDIO STOCK | stock.adobe.com

Severe COVID-19 can be life-threatening for patients who develop it. The mechanisms behind severe infection have been thoroughly investigated since the COVID-19 pandemic began, but some aspects are still unknown. For example, previous research from this group of investigators found that severe COVID-19 is associated with an uncontrolled hyperinflammatory response in the airways, rather than an uncontrolled viral load. However, it remains unknown what immune-mediated mechanisms restrict viral replication in the airways in patients with severe disease.^1,3

IFNs, due to their protective antiviral properties when produced early at the onset of disease, have been extensively studied. It has been determined that patients with preexisting defects in IFN-α are more likely to experience life-threatening COVID-19 when infected. In the current study, the investigators utilized a newly developed flow cytometry-based bead assay (FlowBEAT) to reveal the contributions of anti–IFN-α autoantibodies in the airway, infection site, and matching blood of patients with severe COVID-19 disease.¹

After applying the FlowBEAT assay to longitudinal COVID-19 patient samples from the airway and blood, results indicated that additional antibody isotypes and specificities against SARS-CoV-2 host IFNS were observed as disease moved from mild to severe. The assay was able to distinguish “the full breadth of anti-body response against SARS-CoV-2” across disease states, according to the investigators.¹

In over 70% of mild and moderate COVID-19 cases, nasal IgA1 anti–IFN-α autoantibodies were induced after infection onset and were associated with robust immunity, fewer symptoms associated with COVID-19, and more efficient recovery.^1,2

Interestingly, nasal anti–IFN-α autoantibodies quickly waned with disease recovery. In contrast to this observation, systematic IgG1 and anti–IFN-α autoantibodies were detected later, only in a subset of patients that had worsening symptoms of severe disease and elevated systemic inflammation.¹

Eliver Ghosn, a senior author of the trial, explained how autoantibodies are generally associated with a negative prognosis, but that according to these findings, the mechanism is opposite with COVID-19.²

“The nasal autoantibodies showed up soon after infection, targeting an important inflammatory molecule produced by the patient's cells,” Ghosn said. “These autoantibodies latched on to the molecule, likely to prevent excessive inflammation, and faded as people recovered, suggesting the body uses them to keep things in balance."²

Overall, these findings suggest that autoantibody presence in the nose can play a protective role in regulating the immune system to both prevent excessive inflammation and more effectively fight the virus. Additionally, and perhaps most critically, the presence of these autoantibodies in the nasal cavity could allow for a more precise diagnosis of the severity of COVID-19 that a patient has. This would allow for more personalized treatments and faster treatment initiation, leading to better health outcomes.^1,2

When advancements in diagnostic testing stemming from this research come to pass, pharmacists will have a huge role to play. Already, pharmacists are relied on to be the individuals providing COVID-19 diagnostic testing for those who feel sick or have been exposed. Oftentimes, though, patient counseling can be vague, since the potential disease course is unknown to both the patient and pharmacist.

Personalized treatment, including thorough guidance on whether to initiate available COVID-19 antiviral treatments, can be determined based on the results of this potential new test, better guiding pharmacists when counseling their patients and allowing them to play a direct role in enhancing patient outcomes.

"If this nasal autoantibody response turns out to be a common mechanism to protect us against other viral infections, it can be a paradigm shift in how we study protective immunity," Ghosn concluded, noting that this research could hopefully inspire new, more effective therapeutic options for common respiratory infections such as COVID-19.²

REFERENCES

1. Babcock BR, Kosters A, Eddins DJ, et al. Transient anti-interferon autoantibodies in the airways are associated with recovery from COVID-19. Science Translational Medicine. 2024;16(772). doi:10.1126/scitranslmed.adq1789

2. Emory Health Sciences. Nasal swab test predicts COVID-19 disease severity, study finds. ScienceDaily. News Release. Released November 6, 2024. Accessed November 18, 2024. https://www.sciencedaily.com/releases/2024/11/241106142611.htm

3. Eddins DJ, Yang J, Kosters A, et al. Transcriptional reprogramming of infiltrating neutrophils drives lung pathology in severe COVID-19 despite low viral load. Blood Adv. 2023;7(5):778-799. doi:10.1182/bloodadvances.2022008834