Epithelial Antimicrobial Peptide/Protein and Cytokine Expression Profiles Obtained from Nasopharyngeal Swabs of SARS-CoV-2-Infected and Non-Infected Subjects.
Gambichler. Thilo T; Goesmann. Silke S; Skrygan. Marina M; Susok. Laura L; Schütte. Christian C; Hamdani. Nahza N; Schmidt. Wolfgang W
Key Findings
- LL‑37, hBD‑1, and trappin‑2 mRNA are increased in the nasopharynx of COVID‑19 patients
- Higher TNF‑α mRNA levels early in infection predict a lower risk of pneumonia
- Low IFN‑γ and IL‑6 mRNA levels are associated with more severe outcomes
Practical Outcomes
- For biohackers, the data support the idea that boosting innate immunity—e.g., through vitamin D or other LL‑37‑inducing strategies—might help early viral defense, but no specific dosage or protocol is proven. Monitoring or aiming to increase LL‑37 and TNF‑α activity could be a potential preventive angle, though further trials are needed.
Summary
The study found that people with early COVID‑19 infection have higher levels of the antimicrobial peptide LL‑37 and other immune proteins in their nose swabs, and that higher TNF‑α gene activity was linked to a lower chance of developing pneumonia. This suggests LL‑37 and certain cytokines are part of the body’s first line of defense against the virus, but the research does not test any treatments.
Abstract
Immune responses of the epithelia of the upper respiratory tract are likely crucial in early inhibition of the viral replication and finally clearance of SARS-CoV-2. We aimed to compare the expression profiles of antimicrobial peptides/proteins (AMPs) and related cytokines observed in the nasopharynx of SARS-CoV-2-infected patients and non-infected controls and to assess the associations between these parameters and COVID-19 patients' outcomes. We included 45 subjects who had tested positive for SARS-CoV-2 and 22 control subjects who had tested negative for SARS-CoV-2. Biomaterial for SARS-CoV-2 detection, as well as gene and protein expression studies, was obtained from all subjects using nasopharyngeal swabs which were performed a maximum of 7 days before inclusion in the study. Univariable and multivariable statistics were performed. When compared to the controls, the mRNA expression levels of human β-defensin 1 (hBD-1), LL-37, and trappin-2 were significantly higher in specimens of nasopharyngeal swabs from COVID-19 patients. Protein expression of hBD-1 was also increased in the COVID-19 group. mRNA expression levels of interferon-ɣ (IFN-ɣ), tumor necrosis factor- ɑ (TNF-ɑ), and interleukin-6 (IL-6) measured in SARS-CoV-2-infected patients were significantly higher than those observed in the controls, which could also be confirmed in the protein levels of IFN-ɣ and IL-6. A significant correlation between mRNA and protein levels could be observed only for IL-6. Univariable analysis revealed that low IFN-ɣ mRNA levels were associated with severe/fatal outcomes. The occurrence of COVID-19 pneumonia was significantly associated with lower expression levels of IL-6 mRNA, IFN-ɣ mRNA, and TNF-ɑ mRNA. Concerning the severe/fatal outcomes, the multivariable logistic regression model revealed that none of the aforementioned parameters remained significant in the model. However, the logistic regression model revealed that higher TNF-ɑ mRNA expression was a significant independent predictor of absence of pneumonia [odds ratio: 0.35 (95% CI 0.14 to 0.88, <i>p</i> = 0.024)]. In conclusion, nasopharyngeal expression of AMPs (hBD-1, LL-37, and trappin-2) and cytokines (IL-6, IFN-ɣ, and TNF-ɑ) is upregulated in response to early SARS-CoV-2 infection, indicating that these AMPs and cytokines play a role in the local host defense against the virus. Upregulated nasopharyngeal TNF-ɑ mRNA expression during the early phase of SARS-CoV-2 infection was a significant independent predictor of the absence of COVID-19 pneumonia. Hence, high TNF-ɑ mRNA expression in the nasopharynx appears to be a protective factor for lung complications in COVID-19 patients.
Study Information
pubmed
2024
2024-09-15T00:00:00.000Z
10.3390/v16091471
53