Is COVID-19 severity associated with telomere length? A systematic review and meta-analysis.

Telomere shortening, a marker of cellular aging, has been linked to hospitalization and the severity of COVID-19. In this systematic review and meta-analysis, the mean difference in telomere length between non-severe and severe COVID-19 individuals was pooled to determine the association between short telomeres and COVID-19 severity. Relevant studies were retrieved through searches conducted in PubMed-Medline, Scopus, EMBASE, Medrxiv, Biorxiv, EuroPMC, and SSRN databases up to November 2022. Selected studies were systematically reviewed and assessed for risk of bias using AXIS tool. The standardized mean difference in telomere length between non-severe and severe COVID-19 was pooled using random-effects model. A total of thirteen studies were included in the review, out of which seven (1332 patients with the severe COVID-19 disease and 6321 patients with non-severe COVID-19) were eligible for meta-analysis. The estimated pooled mean difference in Leukocyte telomere length between severe COVID-19 and non-severe COVID-19 was 0.39 (95% CI - 0.02 to 0.81, I2 = 93.5%) with substantial heterogeneity. Our findings do not provide clear evidence for association of shorter telomere length and severe COVID-19 disease. More extensive studies measuring absolute telomere length with age and gender adjustments are needed to draw definitive conclusions on the potential causal association between telomere shortening and COVID-19 severity.

Hispanic/Latino Acculturation Profiles and Telomere Length: Latent Class Analysis on a Nationally Representative Sample.

Background: Acculturation profiles and their impact on telomere length among foreign-born Hispanics/Latinos living in the United States (US) are relatively unknown. The limited research available has linked acculturation with shortened telomere length. Objectives: To identify acculturation profiles among a US representative sample of Hispanics/Latinos and to then examine telomere length differences between profiles. Methods: We conducted a latent class analysis among a non-institutionalized US-representative sample of Hispanics/Latinos using the 1999-2002 National Health and Nutrition Examination Survey (N = 2,292). The latent variable of acculturation was assessed by length of time in the US and language used as a child, read and spoken, usually spoken at home, used to think, and used with friends (i.e., Spanish and/or English). Telomere length assessed from leukocytes was used as the distal continuous outcome. Results: We identified five profiles: (1) low acculturated [33.2% of sample]; (2) partially integrated [18.6% of sample]; (3) integrated [19.4% of sample]; (4) partially assimilated [15.1% of sample]; and (5) assimilated [13.7% of sample]. Acculturation profiles revealed nuanced differences in conditional probabilities with language use despite the length of time spent in the US. While telomere length did vary, there were no significant differences between profiles. Conclusion: Profiles identified revealed that possible life-course and generational effects may be at play in the partially assimilated and assimilated profiles. Our findings expand public health research using complex survey data to identify and assess the dynamic relationship of acculturation profiles and health biomarkers, while being among the first to examine this context using a person-centered approach.

Telomere Shortening and Its Association with Cell Dysfunction in Lung Diseases.

Telomeres are localized at the end of chromosomes to provide genome stability; however, the telomere length tends to be shortened with each cell division inducing a progressive telomere shortening (TS). In addition to age, other factors, such as exposure to pollutants, diet, stress, and disruptions in the shelterin protein complex or genes associated with telomerase induce TS. This phenomenon favors cellular senescence and genotoxic stress, which increases the risk of the development and progression of lung diseases such as idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, SARS-CoV-2 infection, and lung cancer. In an infectious environment, immune cells that exhibit TS are associated with severe lymphopenia and death, whereas in a noninfectious context, naïve T cells that exhibit TS are related to cancer progression and enhanced inflammatory processes. In this review, we discuss how TS modifies the function of the immune system cells, making them inefficient in maintaining homeostasis in the lung. Finally, we discuss the advances in drug and gene therapy for lung diseases where TS could be used as a target for future treatments.

Epigenetic Clocks Are Not Accelerated in COVID-19 Patients.

Age is a major risk factor for severe outcome of the 2019 coronavirus disease (COVID-19). In this study, we followed the hypothesis that particularly patients with accelerated epigenetic age are affected by severe outcomes of COVID-19. We investigated various DNA methylation datasets of blood samples with epigenetic aging signatures and performed targeted bisulfite amplicon sequencing. Overall, epigenetic clocks closely correlated with the chronological age of patients, either with or without acute respiratory distress syndrome. Furthermore, lymphocytes did not reveal significantly accelerated telomere attrition. Thus, these biomarkers cannot reliably predict higher risk for severe COVID-19 infection in elderly patients.

Evidence for Biological Age Acceleration and Telomere Shortening in COVID-19 Survivors.

The SARS-CoV-2 infection determines the COVID-19 syndrome characterized, in the worst cases, by severe respiratory distress, pulmonary and cardiac fibrosis, inflammatory cytokine release, and immunosuppression. This condition has led to the death of about 2.15% of the total infected world population so far. Among survivors, the presence of the so-called persistent post-COVID-19 syndrome (PPCS) is a common finding. In COVID-19 survivors, PPCS presents one or more symptoms: fatigue, dyspnea, memory loss, sleep disorders, and difficulty concentrating. In this study, a cohort of 117 COVID-19 survivors (post-COVID-19) and 144 non-infected volunteers (COVID-19-free) was analyzed using pyrosequencing of defined CpG islands previously identified as suitable for biological age determination. The results show a consistent biological age increase in the post-COVID-19 population, determining a DeltaAge acceleration of 10.45 ± 7.29 years (+5.25 years above the range of normality) compared with 3.68 ± 8.17 years for the COVID-19-free population (p < 0.0001). A significant telomere shortening parallels this finding in the post-COVID-19 cohort compared with COVID-19-free subjects (p < 0.0001). Additionally, ACE2 expression was decreased in post-COVID-19 patients, compared with the COVID-19-free population, while DPP-4 did not change. In light of these observations, we hypothesize that some epigenetic alterations are associated with the post-COVID-19 condition, particularly in younger patients (< 60 years).

Shorter telomere lengths in patients with severe COVID-19 disease.

The incidence of severe manifestations of COVID-19 increases with age with older patients showing the highest mortality, suggesting that molecular pathways underlying aging contribute to the severity of COVID-19. One mechanism of aging is the progressive shortening of telomeres, which are protective structures at chromosome ends. Critically short telomeres impair the regenerative capacity of tissues and trigger loss of tissue homeostasis and disease. The SARS-CoV-2 virus infects many different cell types, forcing cell turn-over and regeneration to maintain tissue homeostasis. We hypothesize that presence of short telomeres in older patients limits the tissue response to SARS-CoV-2 infection. We measure telomere length in peripheral blood lymphocytes COVID-19 patients with ages between 29 and 85 years-old. We find that shorter telomeres are associated to increased severity of the disease. Individuals within the lower percentiles of telomere length and higher percentiles of short telomeres have higher risk of developing severe COVID-19 pathologies.

The Nexus Between Telomere Length and Lymphocyte Count in Seniors Hospitalized With COVID-19.

Profound T-cell lymphopenia is the hallmark of severe coronavirus disease 2019 (COVID-19). T-cell proliferation is telomere length (TL) dependent and telomeres shorten with age. Older COVID-19 patients, we hypothesize, are, therefore, at a higher risk of having TL-dependent lymphopenia. We measured TL by the novel Telomere Shortest Length Assay (TeSLA), and by Southern blotting (SB) of the terminal restriction fragments in peripheral blood mononuclear cells of 17 COVID-19 and 21 non-COVID-19 patients, aged 87 ± 8 (mean ± SD) and 87 ± 9 years, respectively. TeSLA tallies and measures single telomeres, including short telomeres undetected by SB. Such telomeres are relevant to TL-mediated biological processes, including cell viability and senescence. TeSLA yields 2 key metrics: the proportions of telomeres with different lengths (expressed in %) and their mean (TeSLA mTL), (expressed in kb). Lymphocyte count (109/L) was 0.91 ± 0.42 in COVID-19 patients and 1.50 ± 0.50 in non-COVID-19 patients (p < .001). In COVID-19 patients, but not in non-COVID-19 patients, lymphocyte count was inversely correlated with the proportion of telomeres shorter than 2 kb (p = .005) and positively correlated with TeSLA mTL (p = .03). Lymphocyte count was not significantly correlated with SB mTL in either COVID-19 or non-COVID-19 patients. We propose that compromised TL-dependent T-cell proliferative response, driven by short telomere in the TL distribution, contributes to COVID-19 lymphopenia among old adults. We infer that infection with SARS-CoV-2 uncovers the limits of the TL reserves of older persons. Clinical Trials Registration Number: NCT04325646.

Influence of NAD+ as an ageing-related immunomodulator on COVID 19 infection: A hypothesis.

The aging-associated decline of biological functions represents an important contributor to the increase in morbidity and mortality of human beings. Of these biological functions deterioration; there is a significant decline in the heart function, impairments in the lungs gas exchange, and impairments in the immune function. Many alterations in the body humeral and cellular immune response were observed with ageing process: The circulating pro-inflammatory cytokines are increased, the naive lymphocytes are decreased, the numbers of the antigen-presenting cells areelevated and the overall response is impaired. In addition, ageing is associated with a progressive restriction in the telomere length. Telomeres are located at chromosomes ends and play an essential role in preserving chromosome stability. Also, telomere length is very important to the immune system, because of the high sensitivity of the immune cells to the shortening of telomeres. Telomeres shortening adversely affect the immune cells' function and developments. These adverse changes increased the susceptibility for severe infection, risk of hospitalization, and even death. Elderly COVID-19 patients are at a real risk of complications due to impaired immune function, cytokine storm and defective respiratory function. Administration of anti-ageing immunomodulation factors like Nicotinamide Adenine Dinucleotide NAD+ can minimize these changes through its potent immunomodulation and longevity effects. NAD+ has a direct inhibitory effect on PARP-1 and can prevent pro-inflammatory cytokines over-activation. Increasing the NAD+ level will also result in stabilizing telomeres and this has a positive impact on immune cells function.