Telomere Length and COVID-19 Outcomes: A Two-Sample Bidirectional Mendelian Randomization Study

Jiang, Li; Tang, Beisha; Guo, Jifeng; Li, Jin‐chen

doi:10.3389/fgene.2022.805903

Cited by 7 publications

(13 citation statements)

References 34 publications

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“…In the studies carried out by a group of authors, it was hypothesized that not a genetic component but exposome is a decisive factor in the association of shorter telomeres with the regenerative potential of an individual (Jiang et al, 2022). At the same time, a number of researchers noted that the length of telomeres by its nature should be a more powerful informative marker of complications with COVID-19 than the gender or the presence of hypertension in a patient with COVID-19.…”

Section: Resultsmentioning

confidence: 99%

Analysis of Relative Average Length of Telomeres in Leukocytes of Women with COVID-19

et al. 2022

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Coronavirus disease (COVID-19) is an acute infectious disease of the respiratory tract caused by a new SARS-CoV-2 coronavirus. A global vaccination program against SARS-CoV-2 continues, and the incidence of COVID-19 worldwide is significantly decreasing. However, among millions of those who survived COVID-19, numerous groups will need assistance due to increased clinical consequences after COVID-19. Currently, there is a need to search for molecular biomarkers for monitoring the onset and progression of post-COVID syndrome. For this purpose, the relative average length of chromosome regions was studied in the groups of women of reproductive age: in the group of patients ( n = 64) recovered from COVID-19 and in the control group ( n = 42) of women of the same age. The analysis was carried out using a method of multiplex monochrome quantitative real-time PCR on DNA samples isolated from the peripheral blood leukocytes. According to the results of the study, it was established that the relative average length of chromosomes in the peripheral blood leukocytes was statistically significantly lower in the group of patients with COVID-19 than in the control group ( p < 0.05). The results obtained allow one to state that the observed shortening of the relative average length of telomeres in the group of patients that recovered from COVID-19 can indicate that SARS-CoV-2 infection can directly cause the erosion of telomeres in the blood cells, particularly, in leukocytes. Thus, the determination of the relative average length of telomeres can be an informative prognostic marker for estimating the risk of the severity of COVID-19 disease and the development of post-COVID syndrome.

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Section: Resultsmentioning

confidence: 99%

Analysis of Relative Average Length of Telomeres in Leukocytes of Women with COVID-19

et al. 2022

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“…It also seems that the DNA damage response (DDR) increases with age-related telomere shortening, which seems to increase ACE2 expression [ 186 ]. In contrast, genetically predicted short telomere lengths have also been shown not to be related to severity [ 187 ]. This may indicate that telomere length alone, especially if genetically determined, is not enough to explain it—indicating there is a strong age and environmental element.…”

Section: Discussionmentioning

confidence: 99%

Understanding Long COVID; Mitochondrial Health and Adaptation—Old Pathways, New Problems

Nunn

Guy²,

Brysch

et al. 2022

Biomedicines

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Many people infected with the SARS-CoV-2 suffer long-term symptoms, such as “brain fog”, fatigue and clotting problems. Explanations for “long COVID” include immune imbalance, incomplete viral clearance and potentially, mitochondrial dysfunction. As conditions with sub-optimal mitochondrial function are associated with initial severity of the disease, their prior health could be key in resistance to long COVID and recovery. The SARs virus redirects host metabolism towards replication; in response, the host can metabolically react to control the virus. Resolution is normally achieved after viral clearance as the initial stress activates a hormetic negative feedback mechanism. It is therefore possible that, in some individuals with prior sub-optimal mitochondrial function, the virus can “tip” the host into a chronic inflammatory cycle. This might explain the main symptoms, including platelet dysfunction. Long COVID could thus be described as a virally induced chronic and self-perpetuating metabolically imbalanced non-resolving state characterised by mitochondrial dysfunction, where reactive oxygen species continually drive inflammation and a shift towards glycolysis. This would suggest that a sufferer’s metabolism needs to be “tipped” back using a stimulus, such as physical activity, calorie restriction, or chemical compounds that mimic these by enhancing mitochondrial function, perhaps in combination with inhibitors that quell the inflammatory response.

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“…Common, low-frequency, rare, and ultra-rare coding variants were also found to contribute to COVID-19 severity [ 15 ]. Limited data are now available regarding telomere length and COVID-19 progression [ 16 , 17 ]; RTEL1 variants, however, have never been investigated as a possible mechanistic connection between the two. This study aims to describe the clinical characteristics of an Italian cohort of COVID-19 patients, either bearing ultra-rare variants of RTEL1 or not.…”

Section: Introductionmentioning

confidence: 99%

Ultra-rare RTEL1 gene variants associate with acute severity of COVID-19 and evolution to pulmonary fibrosis as a specific long COVID disorder

Bergantini¹,

Baldassarri²,

d’Alessandro³

et al. 2023

Respir Res

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Background Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a novel coronavirus that caused an ongoing pandemic of a pathology termed Coronavirus Disease 19 (COVID-19). Several studies reported that both COVID-19 and RTEL1 variants are associated with shorter telomere length, but a direct association between the two is not generally acknowledged. Here we demonstrate that up to 8.6% of severe COVID-19 patients bear RTEL1 ultra-rare variants, and show how this subgroup can be recognized. Methods A cohort of 2246 SARS-CoV-2-positive subjects, collected within the GEN-COVID Multicenter study, was used in this work. Whole exome sequencing analysis was performed using the NovaSeq6000 System, and machine learning methods were used for candidate gene selection of severity. A nested study, comparing severely affected patients bearing or not variants in the selected gene, was used for the characterisation of specific clinical features connected to variants in both acute and post-acute phases. Results Our GEN-COVID cohort revealed a total of 151 patients carrying at least one RTEL1 ultra-rare variant, which was selected as a specific acute severity feature. From a clinical point of view, these patients showed higher liver function indices, as well as increased CRP and inflammatory markers, such as IL-6. Moreover, compared to control subjects, they present autoimmune disorders more frequently. Finally, their decreased diffusion lung capacity for carbon monoxide after six months of COVID-19 suggests that RTEL1 variants can contribute to the development of SARS-CoV-2-elicited lung fibrosis. Conclusion RTEL1 ultra-rare variants can be considered as a predictive marker of COVID-19 severity, as well as a marker of pathological evolution in pulmonary fibrosis in the post-COVID phase. This notion can be used for a rapid screening in hospitalized infected people, for vaccine prioritization, and appropriate follow-up assessment for subjects at risk. Trial Registration NCT04549831 (www.clinicaltrial.org)

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Telomere Length and COVID-19 Outcomes: A Two-Sample Bidirectional Mendelian Randomization Study

Cited by 7 publications

References 34 publications

Analysis of Relative Average Length of Telomeres in Leukocytes of Women with COVID-19

Analysis of Relative Average Length of Telomeres in Leukocytes of Women with COVID-19

Understanding Long COVID; Mitochondrial Health and Adaptation—Old Pathways, New Problems

Ultra-rare RTEL1 gene variants associate with acute severity of COVID-19 and evolution to pulmonary fibrosis as a specific long COVID disorder

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