Dear Editor,
Long COVID-19 (also termed post-acute sequelae of COVID-19 or long COVID) is a multi-organ disease with high global prevalence and causes serious repercussions, including suicide [1,2]. The clinical spectrum of long COVID is associated with more than 200 symptoms and multiple organ dysfunctions, ranging from lung which cardiovascular disorders to nervous and gastrointestinal disorders [3]. In the long-term, the effects of long COVID might be devasting, especially in the low- and middle-income regions due to their lower healthcare capacity. In India, about 27.9 million people were affected due to long COVID in 2021 which is approximately 2.3-fold more than in 2020 [4]. A study on the Indian population found that 60.8% of inpatients who have received treatment for COVID-19 presented with long COVID symptoms six weeks after their hospital discharge [5].
Considering the scale of the burden, it is quintessential to investigate the critical risk factors for long COVID. According to a recent report, India has been grappling with an alarming increase in death due to Non-Communicable Diseases (NCDs) from 37.9% in 1990 to 61.8% in 2016—possibly even more now [6]. It is accentuated that an unhealthy diet is one of the four major risk factors (others include physical inactivity and use of tobacco and alcohol) for NCDs. In this context, a first-of-its-kind study in India showed that about 60% of the Used Cooking Oil (UCO) is being diverted back into the food stream, which makes the diet unhealthy and poses serious public health repercussions [7]. Repeatedly heated UCO (RH-UCO) generates umpteen oxidative compounds like hydroperoxide, aldehydes, polycyclic aromatic hydrocarbons, acrylamide, etc. These thermally-activated complex and heterogeneous compounds are known as dietary advanced glycation end products (AGEs) or glycotoxins [8]. Regular consumption of diet containing such noxious products and their intermediates (in the form of RH-UCO) has been associated with an array of diseases, including cancers, cardiovascular diseases, gastrointestinal diseases, and multi-organ damage [[8], [9], [10]].
The binding of glycotoxins with the receptor for advanced glycation end-product (RAGE) causes aberrant activation of oxidative/nitrosative stress, inflammation, and adaptive immune response pathways. Besides, these glycotoxins crosstalk with proteins and lipids to form irreversible protein complexes and altered lipid profiles, thereby leading to metabolic dysfunctions [8,11]. Notably, the generation of AGEs and activation of their receptor (RAGE; receptor for advanced glycation end products) play a crucial role in COVID-19 severity and associated complications [12,13]. Hence, RAGE might be an appropriate biomarker for prognosis of not only COVID-19 but also long COVID [14]. Interestingly, novel, non-invasive techniques like skin fluorescence are being developed to assess accumulation of AGEs in various chronic diseases. Exploring the utility of skin fluorescence for detecting AGEs in the context of long COVID might open newer avenues to diagnose and proactively manage long COVID repercussions.
Although RH-UCO consumption and long COVID are independently associated with multi-system complications, the likelihood of RH-UCO consumption as a critical risk factor for long COVID warrants further research. On the other side, considering the magnitude of RH-UCO consumption among Indians, the probability of these entities creating a synchronized and “silent” public health menace [7,15] should be not overlooked.
Ethical approval
No ethical approval was required.
Sources of funding
No sources of funding were received.
Author contribution
ArunSundar MohanaSundaram - conceptualization, manuscript writing. Shanmugarajan Thukani Sathanantham - conceptualization, editing. Ravichandiran Velayutham - conceptualization, review.
Guarantor
The Guarantor is the one or more people who accept full responsibility for the work and/or the conduct of the study, had access to the data, and controlled the decision to publish. Please note that providing a guarantor is compulsory.
ArunSundar MohanaSundaram.
Data statement
The data in this article is accessible to the public and is not sensitive in nature.
Provenance and peer review
Not commissioned, internally peer-reviewed.
Declaration of competing interest
No conflicts of interest to declare.
References
- 1.Groff D., Sun A., Ssentongo A.E., Djibril M.B., Parsons N., Poudel G.R., et al. Short-term and long-term rates of postacute sequelae of SARS-CoV-2 infection: a systematic review. JAMA Netw. Open. 2021;4 doi: 10.1001/jamanetworkopen.2021.28568. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Steenhuysen J., Rigby J. Reuters; 2022. Long COVID's Link to Suicide: Scientists Warn of Hidden Crisis.https://www.reuters.com/business/healthcare-pharmaceuticals/long-covids-link-suicide-scientists-warn-hidden-crisis-2022-09-08/ September 9. [Google Scholar]
- 3.Crook H., Raza S., Nowell J., Young M., Edison P. Long covid-mechanisms, risk factors, and management. BMJ. 2021;374:n1648. doi: 10.1136/bmj.n1648. [DOI] [PubMed] [Google Scholar]
- 4.Hanson S.W., Abbafati C., Aerts J.G., Al-Aly Z., Ashbaugh C., Ballouz T. A global systematic analysis of the occurrence, severity, and recovery pattern of long COVID in 2020 and 202. medRxiv. 2022 doi: 10.1101/2022.05.26.22275532. 2022.05.26.22275532. (Preprint) [DOI] [Google Scholar]
- 5.Kambhampati N.T., Chithira, PillaiM G.K., Ts D., Moni M. Assessment of post-covid symptoms in Covid-19 Recovered patients: a prospective cohort study in a tertiary care centre of south India. J. Assoc. Phys. India. 2022;70:11–12. [Google Scholar]
- 6.Pawar B.P. Press Information Bureau, Government of India; 2022. Status of Non-communicable Diseases (NCDs) in India.https://pib.gov.in/PressReleaseIframePage.aspx?PRID=1796435 February 8. [Google Scholar]
- 7.Goveas N., Kurian O.C., Mona, Mukhopadhyay A., Niharika, Sarkar D. Observer Research Foundation; 2022. Diversion of Used Cooking Oil into the Food Stream: a Study of Four Indian Cities.https://www.orfonline.org/research/diversion-of-used-cooking-oil-into-the-food-stream/ August 22. [Google Scholar]
- 8.Zhang Q., Wang Y., Fu L. Dietary advanced glycation end-products: perspectives linking food processing with health implications. Compr. Rev. Food Sci. Food Saf. 2020;19:2559–2587. doi: 10.1111/1541-4337.12593. [DOI] [PubMed] [Google Scholar]
- 9.Ganesan K., Sukalingam K., Xu B. Impact of consumption of repeatedly heated cooking oils on the incidence of various cancers - a critical review. Crit. Rev. Food Sci. Nutr. 2019;59:488–505. doi: 10.1080/10408398.2017.1379470. [DOI] [PubMed] [Google Scholar]
- 10.Ku S.K., Ruhaifi M.S.M., Fatin S.S., Saffana M., Anna K.T., Das S., Kamsiah J. The harmful effects of consumption of repeatedly heated edible oils: a short review. Clin. Ter. 2014;165:217–221. doi: 10.7417/CT.2014.1737. [DOI] [PubMed] [Google Scholar]
- 11.Bucala R., Makita Z., Vega G., Grundy S., Koschinsky T., Cerami A., Vlassara H. Modification of low density lipoprotein by advanced glycation end products contributes to the dyslipidemia of diabetes and renal insufficiency. Proc. Natl. Acad. Sci. U. S. A. 1994;91:9441–9445. doi: 10.1073/pnas.91.20.9441. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Curran C.S., Kopp J.B. RAGE pathway activation and function in chronic kidney disease and COVID-19. Front. Med. 2022;9 doi: 10.3389/fmed.2022.970423. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Rojas A., Lindner C., Gonzàlez I., Morales M.A. Advanced-glycation end-products axis: a contributor to the risk of severe illness from COVID-19 in diabetes patients. World J. Diabetes. 2021;12:590–602. doi: 10.4239/wjd.v12.i5.590. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Lim A., Radujkovic A., Weigand M.A., Merle U. Soluble receptor for advanced glycation end products (sRAGE) as a biomarker of COVID-19 disease severity and indicator of the need for mechanical ventilation, ARDS and mortality. Ann. Intensive Care. 2021;11:50. doi: 10.1186/s13613-021-00836-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.India's Silent Epidemic: Impact of Toxic Used Cooking Oil Diversion into the Food Stream on Public Health. ETHealthworld; August 25, 2022. https://health.economictimes.indiatimes.com/news/industry/indias-silent-epidemic-impact-of-toxic-used-cooking-oil-diversion-into-the-food-stream-on-public-health/93761162 [Google Scholar]