New research conducted at the Spanish National Cancer Research Centre (CNIO) in collaboration with the COVID-IFEMA Field Hospital has found patients suffering from severe COVID-19 have shortened telomere lengths.
Telomeres are specific DNA-protein structures that are found on both ends of each of our 46 chromosomes, considered "protective caps". They help to preserve information in our genome via protective features that prevent unnecessary DNA damage when our cells undergo division.
As DNA undergoes replication, a little bit of structure is lost every time a cell divides. Telomeres help protect DNA on the chromosome, and hence as a consequence, telomeres become shorter as we age. This is also the reason diseases with a DNA underpinning – such as cancer – are more likely to occur at an older age, as when these telomeres become shorter they are less able to protect the DNA, and more errors can occur.
Now, researchers led by Dr Maria A. Blasco at CNIO have published a new paper in the journal Aging that suggests there might be a link between shorter telomere lengths and the severity of COVID-19.
The authors of the study wrote in the journal paper: “It caught our attention that a common outcome of SARS-CoV-2 infection seems to be induction of fibrosis-like phenotypes in the lung and kidney, suggesting that the viral infection maybe exhausting the regenerative potential of tissues.”
Lung fibrosis occurs when cells in the lungs undergo prolonged damage and decrease their regenerating capacity while scar tissue starts to form. This results in the lung tissue becoming stiff and causes difficulties breathing, a common clinical presentation in patients with severe COVID-19.
"When I read that type II alveolar pneumocytes were involved in COVID-19, I immediately thought that telomeres might be involved," said Dr Maria A. Blasco, lead author of the study, in a press release.
The study assessed 89 patients (61 female, 28 male) that were admitted to the IFEMA Hospital in Madrid. The patients all presented with different COVID-19 severities, some were very mild forms, whilst some were very acute and severe COVID-19 pathologies.
Accounting for the age of the patients, and the fact that telomeres normally decrease in length the older you are, the research demonstrated that there was a strong correlation between patients with shorter telomere lengths and their COVID-19 severity. Irrespective of age, patients that were the most seriously ill had the shortest telomeres.
If the research hypothesis holds true, it suggests that shorter telomeres may contribute to the decreased ability of the lungs to regenerate, and cause more severe COVID-19 pathologies.
Human cells with long telomeres (left) and short telomeres (right). Top and lower panels show cells in interphase and metaphase, respectively. Image Credit: CNIO
Interestingly the researchers also found that the women in the study on average had longer telomere lengths compared to the men, accounting for age, hinting at yet another possible explanation as to why men might be harder hit with COVID-19.
Going further, the researchers even speculated on a potential therapeutic approach to deal with some of the pathological consequences of COVID-19 such as lung fibrosis in the future.
"Given that short telomeres can be made longer again by telomerase, and given that in previous studies we have shown that telomerase activation has a therapeutic effect on diseases related to short telomeres, such as pulmonary fibrosis, it is tempting to speculate that this therapy could improve some of the pathologies that remain in COVID-19 patients once the viral infection has been overcome, such as pulmonary fibrosis," said the researchers.
More research needs to be done to confirm the link between telomere lengths and COVID-19 severity, as the current study had a small sample size with a limited demographic of the patients. It is also important to remember the correlation does not always equal causation.
Nevertheless, this study has shown that telomeres might be important in COVID-19 severity, and that there might even be therapeutic options on the horizon that could address this in the future.