Even though a high body mass index is a risk factor for COVID-19, the progression of the disease does not solely depend on the fat percentage of a person. What actually matters is the wellbeing of the adipose tissue. According to an international study conducted with the participation of Estonians, this may also explain why COVID-19 is milder in women.
“As far as we currently know, adipose tissue does not alter the likelihood of contraction [of the coronavirus – ed.], but it may play a role in determining the course of the disease,” said Priit Jõers, an Associate Professor of biochemistry at the University of Tartu, and Indrikis Krams, a visiting Professor of biology at the UT. Together with the co-authors Severi Luoto, Markus Rantala and Tatjana Krama, they studied the effect of human adipose tissue on the progression of the new coronavirus.
Body mass index, but not only
According to Priit Jõers and Indrikis Krams, the course of COVID-19 is affected by the underlying health conditions of a person. For example, people with cardiovascular diseases, metabolic syndrome and diabetes are at risk of developing more serious symptoms of COVID‑19. As these diseases are associated with obesity, the authors do not find it surprising that compared to normal-weight people, people with a high body mass index (BMI) are more likely to end up in the hospital with COVID-19.
At the same time, BMI is not a panacea for predicting the course of the coronavirus as it might not correctly reflect the metabolic “health” of the adipose tissue. Namely, people have two types of adipose tissue: subcutaneous fat and visceral fat that surrounds internal organs. “As the latter is located in the abdominal region, it significantly contributes to the expansion of waist circumference,” say Jõers and Krams. Visceral adipose tissue dysfunctions are significantly more harmful than is the case with subcutaneous adipose tissue, as its inflammation releases signal molecules that have a highly negative effect to organism’s overall health.
“Therefore, it is not surprising that according to available data, an increase in visceral adipose tissue and/or disturbances in its function have an unequivocally negative effect on people suffering from COVID-19, aggravating the course of the disease,” note the researchers. Disturbances in the visceral adipose tissue do not always raise the body mass index, so BMI does not always help predict the severity of COVID-19.
Health of visceral adipose tissue = health of a patient with COVID-19
Even though a higher body mass index is a risk factor according to Priit Jõers and Indrikis Krams, the metabolic ‘health’ of visceral adipose tissue may be even more important in predicting the course of the coronavirus than BMI. Therefore, everything that has an adverse effect on the health of the visceral adipose tissue of a patient with coronavirus has an adverse effect on the patient, such as overeating, excess alcohol and environmental poisons.
“It is possible that the ‘health’ of the visceral adipose tissue is also the reason why COVID-19 is generally milder in women than in men,” note the authors since visceral adipose tissue tends to be healthier in women.
According to Jõers and Krams, the characteristics of visceral adipose tissue may explain the noticeable differences in the course of COVID-19 between members of different ethnical groups. “In different parts of the world, the percentage of COVID-19 patients with a severely developing disease is different,” they say, “as is the ‘health’ of visceral fat in people of different ethnic backgrounds.” However, the authors warn that there is not enough data yet to make any profound conclusions.
As mentioned above, adipose tissue may determine the progression of the disease in a patient with the coronavirus. Here, Priit Jõers and Indrikis Krams refer to the obesity paradox, i.e. the link between high BMI and certain pathologies, e.g. cardiovascular diseases. “Overweight people may have a less severe form of the disease and have fewer complications than normal-weight people,” explain Jõers and Krams.
Based on the paradox, a ‘fat-but-fit’ theory has been formulated, which states that the course of the disease depends on the condition of the person’s adipose tissue and not on its volume, i.e. the body mass index.
Good little ACE2
According to Jõers and Krams, such connection may also exist between adipose tissue and the new coronavirus. In that case, the key to the link lies in the outwardly directed protein ACE2 on the surface of the cells. “Its task is to change a certain protein hormone – angiotensin – found in blood,” the authors explained introducing the protein ACE2.
More specifically, ACE2 influences the progression of the coronavirus by removing some amino acids from the longer form of angiotensin (Ang II). Thus, we are left with the shorter form of angiotensin (Ang 1–7). The longer and the shorter form however work in completely opposing ways. The longer form promotes the development of inflammations and aggravates the effects of the coronavirus, while the shorter form alleviates inflammation.
“ACE2 is currently of great interest, as this protein is at least one of the ‘doors’ for the SARS-CoV-2 virus to enter the cell,” add Jõers and Krams. When the cells of the internal lining of the lung are infected with the virus, the amount of ACE2 decreases on the surface of these cells. Due to this, there is less ACE2 than before and balance between two types of angiotensins swings towards inflammation-promoting long form.
According to the authors, the normal operation of ACE2 is hindered by the coronavirus itself, but also by several other comorbid pathologies. If ACE2’s function is disturbed and/or its levels have decreased in the body by these disorders, the shift toward harmful Ang II is greater, meaning that the person suffers from the coronavirus more severely. The link also works in reverse: if there is an abundance of ACE2 in the body, more of Ang II gets degraded into Ang 1-7 and the COVID-19 illness is less severe for the patient.
Even though ACE2 is found on the surface of several tissues in the body, this surface protein is especially abundant in adipose tissue and particularly in visceral adipose tissue. “Thus, a person with a high body mass index, but with metabolically ‘healthy’ adipose tissue may have a large reservoir of normally functioning ACE2, which is why their COVID-19 symptoms are milder,” said the authors.
In light of all of the above, they recommend people to pay attention to their health in a broader sense during the second wave of COVID-19. “A very simple and cheap way of stopping and reversing the negative processes taking place in adipose tissue, is physical exercise,” they noted. Even though adipose tissue accumulation is promoted by people’s genes, everyone can maintain moderate physical activity and thus ensure that in the event of infection with the coronavirus, the course of the disease would be as easy as possible.
Priit Jõers, Indriks Krams and their co-authors write about their observations in the journal Pathogens.
The translation of this article from Estonian Public Broadcasting science news portal Novaator was funded by the European Regional Development Fund through Estonian Research Council.