Induction of interferon response by high viral loads at early stage infection may protect against severe outcomes in COVID-19 patients

Abstract Key elements for viral pathogenesis include viral strains, viral load, co-infection, and host responses. Several studies analyzing these factors in the function of disease severity of have been published; however, no studies have shown how all of these factors interplay within a defined coh...

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Autores principales:	Eric C. Rouchka, Julia H. Chariker, Brian Alejandro, Robert S. Adcock, Richa Singhal, Julio Ramirez, Kenneth E. Palmer, Amanda B. Lasnik, Ruth Carrico, Forest W. Arnold, Stephen Furmanek, Mei Zhang, Leslie A. Wolf, Sabine Waigel, Wolfgang Zacharias, Jose Bordon, Donghoon Chung
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9a3bddb7b2b24ac1b6dc3b294cd6fd10
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spelling	oai:doaj.org-article:9a3bddb7b2b24ac1b6dc3b294cd6fd102021-12-02T17:06:31ZInduction of interferon response by high viral loads at early stage infection may protect against severe outcomes in COVID-19 patients10.1038/s41598-021-95197-y2045-2322https://doaj.org/article/9a3bddb7b2b24ac1b6dc3b294cd6fd102021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-95197-yhttps://doaj.org/toc/2045-2322Abstract Key elements for viral pathogenesis include viral strains, viral load, co-infection, and host responses. Several studies analyzing these factors in the function of disease severity of have been published; however, no studies have shown how all of these factors interplay within a defined cohort. To address this important question, we sought to understand how these four key components interplay in a cohort of COVID-19 patients. We determined the viral loads and gene expression using high throughput sequencing and various virological methods. We found that viral loads in the upper respiratory tract in COVID-19 patients at an early phase of infection vary widely. While the majority of nasopharyngeal (NP) samples have a viral load lower than the limit of detection of infectious viruses, there are samples with an extraordinary amount of SARS-CoV-2 RNA and a high viral titer. No specific viral factors were identified that are associated with high viral loads. Host gene expression analysis showed that viral loads were strongly correlated with cellular antiviral responses. Interestingly, however, COVID-19 patients who experience mild symptoms have a higher viral load than those with severe complications, indicating that naso-pharyngeal viral load may not be a key factor of the clinical outcomes of COVID-19. The metagenomics analysis revealed that the microflora in the upper respiratory tract of COVID-19 patients with high viral loads were dominated by SARS-CoV-2, with a high degree of dysbiosis. Finally, we found a strong inverse correlation between upregulation of interferon responses and disease severity. Overall our study suggests that a high viral load in the upper respiratory tract may not be a critical factor for severe symptoms; rather, dampened antiviral responses may be a critical factor for a severe outcome from the infection.Eric C. RouchkaJulia H. CharikerBrian AlejandroRobert S. AdcockRicha SinghalJulio RamirezKenneth E. PalmerAmanda B. LasnikRuth CarricoForest W. ArnoldStephen FurmanekMei ZhangLeslie A. WolfSabine WaigelWolfgang ZachariasJose BordonDonghoon ChungNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Eric C. Rouchka Julia H. Chariker Brian Alejandro Robert S. Adcock Richa Singhal Julio Ramirez Kenneth E. Palmer Amanda B. Lasnik Ruth Carrico Forest W. Arnold Stephen Furmanek Mei Zhang Leslie A. Wolf Sabine Waigel Wolfgang Zacharias Jose Bordon Donghoon Chung Induction of interferon response by high viral loads at early stage infection may protect against severe outcomes in COVID-19 patients
description	Abstract Key elements for viral pathogenesis include viral strains, viral load, co-infection, and host responses. Several studies analyzing these factors in the function of disease severity of have been published; however, no studies have shown how all of these factors interplay within a defined cohort. To address this important question, we sought to understand how these four key components interplay in a cohort of COVID-19 patients. We determined the viral loads and gene expression using high throughput sequencing and various virological methods. We found that viral loads in the upper respiratory tract in COVID-19 patients at an early phase of infection vary widely. While the majority of nasopharyngeal (NP) samples have a viral load lower than the limit of detection of infectious viruses, there are samples with an extraordinary amount of SARS-CoV-2 RNA and a high viral titer. No specific viral factors were identified that are associated with high viral loads. Host gene expression analysis showed that viral loads were strongly correlated with cellular antiviral responses. Interestingly, however, COVID-19 patients who experience mild symptoms have a higher viral load than those with severe complications, indicating that naso-pharyngeal viral load may not be a key factor of the clinical outcomes of COVID-19. The metagenomics analysis revealed that the microflora in the upper respiratory tract of COVID-19 patients with high viral loads were dominated by SARS-CoV-2, with a high degree of dysbiosis. Finally, we found a strong inverse correlation between upregulation of interferon responses and disease severity. Overall our study suggests that a high viral load in the upper respiratory tract may not be a critical factor for severe symptoms; rather, dampened antiviral responses may be a critical factor for a severe outcome from the infection.
format	article
author	Eric C. Rouchka Julia H. Chariker Brian Alejandro Robert S. Adcock Richa Singhal Julio Ramirez Kenneth E. Palmer Amanda B. Lasnik Ruth Carrico Forest W. Arnold Stephen Furmanek Mei Zhang Leslie A. Wolf Sabine Waigel Wolfgang Zacharias Jose Bordon Donghoon Chung
author_facet	Eric C. Rouchka Julia H. Chariker Brian Alejandro Robert S. Adcock Richa Singhal Julio Ramirez Kenneth E. Palmer Amanda B. Lasnik Ruth Carrico Forest W. Arnold Stephen Furmanek Mei Zhang Leslie A. Wolf Sabine Waigel Wolfgang Zacharias Jose Bordon Donghoon Chung
author_sort	Eric C. Rouchka
title	Induction of interferon response by high viral loads at early stage infection may protect against severe outcomes in COVID-19 patients
title_short	Induction of interferon response by high viral loads at early stage infection may protect against severe outcomes in COVID-19 patients
title_full	Induction of interferon response by high viral loads at early stage infection may protect against severe outcomes in COVID-19 patients
title_fullStr	Induction of interferon response by high viral loads at early stage infection may protect against severe outcomes in COVID-19 patients
title_full_unstemmed	Induction of interferon response by high viral loads at early stage infection may protect against severe outcomes in COVID-19 patients
title_sort	induction of interferon response by high viral loads at early stage infection may protect against severe outcomes in covid-19 patients
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/9a3bddb7b2b24ac1b6dc3b294cd6fd10
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Induction of interferon response by high viral loads at early stage infection may protect against severe outcomes in COVID-19 patients

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