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Article

Low Systemic IFN Response and High Viral Load Are Associated with COVID-19 Disease Severity in Unvaccinated Patients in Kenya, 2022–2023

by
Rebeccah M. Ayako
1,2,*,
Kirtika Patel
1,
Isaac Ndede
1,
Simeon K. Mining
1,
Jonas Klingström
2,
Johan Nordgren
2 and
Marie Larsson
2,*
1
Department of Pathology, School of Medicine, Moi University, Eldoret 4606-20100, Kenya
2
Department of Biomedical and Clinical Sciences, Division of Molecular Medicine and Virology, Linköping University, SE-581 83 Linköping, Sweden
*
Authors to whom correspondence should be addressed.
COVID 2026, 6(3), 51; https://doi.org/10.3390/covid6030051
Submission received: 19 February 2026 / Revised: 9 March 2026 / Accepted: 13 March 2026 / Published: 17 March 2026
(This article belongs to the Section COVID Clinical Manifestations and Management)
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Abstract

The clinical severity of COVID-19 is influenced by cellular and humoral immune responses, as well as the dynamics of viral replication. In line with this, the current study examined systemic and mucosal immunity responses alongside viral load in unvaccinated SARS-CoV-2-infected individuals during the period of Omicron predominance. Between 2022 and 2023, when Omicron prevalence was at its peak, 48 SARS-CoV-2-positive cases with varied severity were recruited using positive PCR testing, and 48 negative controls were recruited using negative PCR testing at Moi Teaching and Referral Hospital, Kenya. Severe patients showed higher viral loads and systemic anti-spike IgG levels compared to moderate and asymptomatic individuals. Asymptomatic individuals had higher mucosal anti-spike IgG and receptor-binding domain (RBD) levels compared to severe patients. Systemic IFN-α mRNA transcripts were higher in asymptomatic individuals compared to patients with severe COVID-19 and healthy individuals. Severe patients had significantly lower expression of IFN-γ mRNA transcript levels in both blood and mucosa, as well as significantly lower systemic IFI-16 mRNA transcript levels. These findings reflect associations observed in a cross-sectional design and should not be interpreted as causal mechanisms. Suppressed interferon responses, both mucosal and systemic, were associated with severe disease. In conclusion, high systemic IgG and viral loads and low interferon responses were closely linked to severe COVID-19 outcomes.
Keywords: COVID-19 severity; IgG; viral load; interferon; mucosal; systemic COVID-19 severity; IgG; viral load; interferon; mucosal; systemic

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MDPI and ACS Style

Ayako, R.M.; Patel, K.; Ndede, I.; Mining, S.K.; Klingström, J.; Nordgren, J.; Larsson, M. Low Systemic IFN Response and High Viral Load Are Associated with COVID-19 Disease Severity in Unvaccinated Patients in Kenya, 2022–2023. COVID 2026, 6, 51. https://doi.org/10.3390/covid6030051

AMA Style

Ayako RM, Patel K, Ndede I, Mining SK, Klingström J, Nordgren J, Larsson M. Low Systemic IFN Response and High Viral Load Are Associated with COVID-19 Disease Severity in Unvaccinated Patients in Kenya, 2022–2023. COVID. 2026; 6(3):51. https://doi.org/10.3390/covid6030051

Chicago/Turabian Style

Ayako, Rebeccah M., Kirtika Patel, Isaac Ndede, Simeon K. Mining, Jonas Klingström, Johan Nordgren, and Marie Larsson. 2026. "Low Systemic IFN Response and High Viral Load Are Associated with COVID-19 Disease Severity in Unvaccinated Patients in Kenya, 2022–2023" COVID 6, no. 3: 51. https://doi.org/10.3390/covid6030051

APA Style

Ayako, R. M., Patel, K., Ndede, I., Mining, S. K., Klingström, J., Nordgren, J., & Larsson, M. (2026). Low Systemic IFN Response and High Viral Load Are Associated with COVID-19 Disease Severity in Unvaccinated Patients in Kenya, 2022–2023. COVID, 6(3), 51. https://doi.org/10.3390/covid6030051

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