“LONG COVID”—A hypothesis for understanding the biological basis and pharmacological treatment strategy
Abstract Infection of humans with SARS‐CoV‐2 virus causes a disease known colloquially as “COVID‐19” with symptoms ranging from asymptomatic to severe pneumonia. Initial pathology is due to the virus binding to the ACE‐2 protein on endothelial cells lining blood vessels and entering these cells in o...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2022-02-01
|
| Series: | Pharmacology Research & Perspectives |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/prp2.911 |
| _version_ | 1828892015136342016 |
|---|---|
| author | Bevyn Jarrott Richard Head Kirsty G. Pringle Eugenie R. Lumbers Jennifer H. Martin |
| author_facet | Bevyn Jarrott Richard Head Kirsty G. Pringle Eugenie R. Lumbers Jennifer H. Martin |
| author_sort | Bevyn Jarrott |
| collection | DOAJ |
| description | Abstract Infection of humans with SARS‐CoV‐2 virus causes a disease known colloquially as “COVID‐19” with symptoms ranging from asymptomatic to severe pneumonia. Initial pathology is due to the virus binding to the ACE‐2 protein on endothelial cells lining blood vessels and entering these cells in order to replicate. Viral replication causes oxidative stress due to elevated levels of reactive oxygen species. Many (~60%) of the infected people appear to have eliminated the virus from their body after 28 days and resume normal activity. However, a significant proportion (~40%) experience a variety of symptoms (loss of smell and/or taste, fatigue, cough, aching pain, “brain fog,” insomnia, shortness of breath, and tachycardia) after 12 weeks and are diagnosed with a syndrome named “LONG COVID.” Longitudinal clinical studies in a group of subjects who were infected with SARS‐CoV‐2 have been compared to a non‐infected matched group of subjects. A cohort of infected subjects can be identified by a battery of cytokine markers to have persistent, low level grade of inflammation and often self‐report two or more troubling symptoms. There is no drug that will relieve their symptoms effectively. It is hypothesized that drugs that activate the intracellular transcription factor, nuclear factor erythroid‐derived 2‐like 2 (NRF2) may increase the expression of enzymes to synthesize the intracellular antioxidant, glutathione that will quench free radicals causing oxidative stress. The hormone melatonin has been identified as an activator of NRF2 and a relatively safe chemical for most people to ingest chronically. Thus, it is an option for consideration of re‐purposing studies in “LONG COVID” subjects experiencing insomnia, depression, fatigue, and “brain fog” but not tachycardia. Appropriately designed clinical trials are required to evaluate melatonin. |
| first_indexed | 2024-12-13T13:28:12Z |
| format | Article |
| id | doaj.art-114570a35c2f498f8a50f59daeaf5591 |
| institution | Directory Open Access Journal |
| issn | 2052-1707 |
| language | English |
| last_indexed | 2024-12-13T13:28:12Z |
| publishDate | 2022-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Pharmacology Research & Perspectives |
| spelling | doaj.art-114570a35c2f498f8a50f59daeaf55912022-12-21T23:44:14ZengWileyPharmacology Research & Perspectives2052-17072022-02-01101n/an/a10.1002/prp2.911“LONG COVID”—A hypothesis for understanding the biological basis and pharmacological treatment strategyBevyn Jarrott0Richard Head1Kirsty G. Pringle2Eugenie R. Lumbers3Jennifer H. Martin4Florey Institute of Neuroscience & Mental Health University of Melbourne Parkville Victoria AustraliaUniversity of South Australia Adelaide South Australia AustraliaSchool of Biomedical Sciences and Pharmacy Faculty of Health and Medicine University of Newcastle Newcastle New South Wales AustraliaSchool of Biomedical Sciences and Pharmacy Faculty of Health and Medicine University of Newcastle Newcastle New South Wales AustraliaCentre for Drug Repurposing and Medicines Research Clinical Pharmacology University of Newcastle New Lambton New South Wales AustraliaAbstract Infection of humans with SARS‐CoV‐2 virus causes a disease known colloquially as “COVID‐19” with symptoms ranging from asymptomatic to severe pneumonia. Initial pathology is due to the virus binding to the ACE‐2 protein on endothelial cells lining blood vessels and entering these cells in order to replicate. Viral replication causes oxidative stress due to elevated levels of reactive oxygen species. Many (~60%) of the infected people appear to have eliminated the virus from their body after 28 days and resume normal activity. However, a significant proportion (~40%) experience a variety of symptoms (loss of smell and/or taste, fatigue, cough, aching pain, “brain fog,” insomnia, shortness of breath, and tachycardia) after 12 weeks and are diagnosed with a syndrome named “LONG COVID.” Longitudinal clinical studies in a group of subjects who were infected with SARS‐CoV‐2 have been compared to a non‐infected matched group of subjects. A cohort of infected subjects can be identified by a battery of cytokine markers to have persistent, low level grade of inflammation and often self‐report two or more troubling symptoms. There is no drug that will relieve their symptoms effectively. It is hypothesized that drugs that activate the intracellular transcription factor, nuclear factor erythroid‐derived 2‐like 2 (NRF2) may increase the expression of enzymes to synthesize the intracellular antioxidant, glutathione that will quench free radicals causing oxidative stress. The hormone melatonin has been identified as an activator of NRF2 and a relatively safe chemical for most people to ingest chronically. Thus, it is an option for consideration of re‐purposing studies in “LONG COVID” subjects experiencing insomnia, depression, fatigue, and “brain fog” but not tachycardia. Appropriately designed clinical trials are required to evaluate melatonin.https://doi.org/10.1002/prp2.911“LONG COVID”COVID‐19endotheliummelatoninNRF2oxidative stress |
| spellingShingle | Bevyn Jarrott Richard Head Kirsty G. Pringle Eugenie R. Lumbers Jennifer H. Martin “LONG COVID”—A hypothesis for understanding the biological basis and pharmacological treatment strategy Pharmacology Research & Perspectives “LONG COVID” COVID‐19 endothelium melatonin NRF2 oxidative stress |
| title | “LONG COVID”—A hypothesis for understanding the biological basis and pharmacological treatment strategy |
| title_full | “LONG COVID”—A hypothesis for understanding the biological basis and pharmacological treatment strategy |
| title_fullStr | “LONG COVID”—A hypothesis for understanding the biological basis and pharmacological treatment strategy |
| title_full_unstemmed | “LONG COVID”—A hypothesis for understanding the biological basis and pharmacological treatment strategy |
| title_short | “LONG COVID”—A hypothesis for understanding the biological basis and pharmacological treatment strategy |
| title_sort | long covid a hypothesis for understanding the biological basis and pharmacological treatment strategy |
| topic | “LONG COVID” COVID‐19 endothelium melatonin NRF2 oxidative stress |
| url | https://doi.org/10.1002/prp2.911 |
| work_keys_str_mv | AT bevynjarrott longcovidahypothesisforunderstandingthebiologicalbasisandpharmacologicaltreatmentstrategy AT richardhead longcovidahypothesisforunderstandingthebiologicalbasisandpharmacologicaltreatmentstrategy AT kirstygpringle longcovidahypothesisforunderstandingthebiologicalbasisandpharmacologicaltreatmentstrategy AT eugenierlumbers longcovidahypothesisforunderstandingthebiologicalbasisandpharmacologicaltreatmentstrategy AT jenniferhmartin longcovidahypothesisforunderstandingthebiologicalbasisandpharmacologicaltreatmentstrategy |