Pancreatic Involvement in COVID-19: What Do We Know?

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MADRID — There is increasing evidence of the impact that SARS-CoV-2 infection has on patients with diabetes. It involves the relationship between COVID-19 and new diagnoses of diabetes and blood glucose disorders, among others, in the post–COVID-19 period. These topics were addressed at the XXXIII National Congress of the Spanish Diabetes Society (SED). They were also the central theme of the inaugural conference, Pancreatic Involvement During COVID-19: From Preclinical Studies to Clinical Relevance, which was led by Alexander Kleger, MD, PhD, head of the Department of Pancreatology at the Ulm University Clinic for Internal Medicine, Ulm, Germany.

The chair of the Scientific Committee of the Congress, Franz Martín, MD, launched the conference by noting that the work of Kleger and his team has made it possible to ascertain that SARS-CoV-2 can infect pancreatic beta cells that produce insulin. This observation may help in understanding why patients with COVID-19 sometimes experience symptoms related to greater difficulty regulating blood glucose.

"In addition, the German expert and his group have described the abnormalities that occur in beta cells when they are infected by SARS-CoV-2, something especially important, given that knowledge of these abnormalities may be of great importance to understanding the possible appearance of more cases of diabetes in the future," Martín added.

"Our data identify the human pancreas as a target of SARS-CoV-2 infection and suggest that pancreatic beta cell involvement could contribute to the metabolic dysregulation seen in COVID-19 patients," Kleger pointed out.

In his speech, Kleger reviewed the evidence on the effects of SARS-CoV-2 that has been garnered since the start of the pandemic, and he presented his research group's findings on the impact at the pancreatic level.

"Since March 2020, it has been seen that COVID-19 affected the pancreas, and studies published in August of that same year clearly spoke of both a worsening of diabetes and an increase in new cases of this disease diagnosed after SARS-CoV-2 infection. Also, the data showed how hospitalized patients with no previous history of diabetes experienced rapid increases in glucose levels 5 days after admission," said the specialist.

Angiotensin-Converting Enzyme 2

As an example of the pace at which evidence on the pancreatic impact of this virus has been evolving, Kleger referred to early studies that found no angiotensin-converting enzyme 2 receptor on cells of the endocrine and exocrine pancreas. "To our surprise, in our work, we did observe the obvious presence of angiotensin-converting enzyme 2 specifically expressed in human pancreatic beta cells, something confirmed by other investigations. Another surprising aspect was verifying that the viral infection lasts longer in the pancreas than in the lungs," said the expert.

These findings caused the researchers to realize that SARS-CoV-2 may be directly or indirectly associated with diabetes. "It is currently the subject of debate whether it may be a direct effect, infecting or directly reaching the pancreatic beta cells, or whether this involvement is a result of the effect of the infection at systemic level, in the context of the cytokine storm and the proinflammatory environment derived from it. Our current challenge is to confirm whether this virus can really replicate in pancreatic beta cells and to assess the possible existence of reinfections, among other aspects," said Kleger.

Along with these "developing areas of knowledge," there are several certainties regarding the link between diabetes and COVID-19. Kleger summarized the most relevant one. "Preexisting diabetes is known to be a highly prevalent comorbidity seen in 11% to 22% of patients and increases the risk of severe disease and mortality.

"SARS-CoV-2 infection has also been shown to affect the exocrine pancreas, manifesting as pancreatitis in 5% of critically ill patients with COVID-19, as well as enlargement of the pancreas and abnormal levels of amylase or lipase in 7.5% to 17% of patients.

"Furthermore, it is obvious that SARS-CoV-2 infection produces glycometabolic dysfunction in these patients, with increased hyperglycemia in people with type 2 diabetes and ketoacidosis in 2% to 6.4% of patients with and without diabetes."

After Recovery

The most recent research reveals the persistence of this dysregulation long after recovery from COVID-19. "We've seen that in a significant proportion of patients, hyperglycemia is maintained for some time; in the specific case of hospitalized patients (without the need for assisted ventilation or other intensive care requirements), for up to more than 2 months after overcoming the illness.

"In the same way, there are studies that have shown that insulin resistance and hyperstimulation of pancreatic beta cells remain at pathological levels in the post–COVID-19 phase. And in line with increased insulin resistance, signs of hyperinflammation have also been detected in these patients."

Kleger noted that another research area is the increased incidence of newly diagnosed diabetes after recovery from SARS-CoV-2 infection, "something that seems to be correlated with how severely the disease has been experienced and also depending on whether hospitalization or intensive care was needed. Likewise, retrospective studies have shown that the risk of developing type 2 diabetes is higher in COVID-19 patients, compared to those with other respiratory infections. Regarding the incidence of type 1 diabetes, there is evidence, particularly in the case of children, of a clear correlation between the pandemic waves and the increase in cases.

"Therefore, and in view of this data, we could say that with regard to the involvement of SARS-CoV-2 in pancreatic beta cells, something is up, but we are not yet able to fully understand what it is. What can be confirmed based on the numerous studies carried out in this regard is that COVID-19 produces a metabolic dysregulation (hyperglycemia, insulin resistance, diabetic ketoacidosis) which in turn favors the development of diabetes in patients with no history of this disease," said Kleger.

"Likewise, everything points to the existence of a definitively feasible infection in pancreatic beta cells associated with SARS-CoV-2, but there are still unknown aspects of the physiology that explain this effect that remain the subject of debate and deserve future studies," he concluded.

Consequences of the Pandemic

The experts agreed that although COVID-19 is no longer at the center of specialist care, it is still a subject of investigation. On the conference's opening day, an update was made on the approach to diabetes.

Care activity is gradually recovering as the time that professionals devote to COVID-19 care is reduced, "but it will take time to catch up with the care activities not carried out during the pandemic, and, unfortunately, in the coming years, we will see the repercussion of the lack or reduction of care during these years," stressed the SED chair, Antonio Pérez Pérez, MD, director of endocrinology and nutrition of Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.

The specialist stressed that the pandemic has revealed health system deficiencies in diabetes care. He added that the impact of COVID-19 on diabetes (resulting from the effects of the infection itself or from the inadequacy of prevention, diagnosis, and treatment measures) fostered a deterioration of metabolic control and a delay in the diagnosis of the disease and its complications.

"All this contributes to the fact that we currently continue to see patients with complications, especially in the case of type 2 diabetes, with more serious decompensations and diagnoses in more advanced stages of the disease. This impact has been more significant in older people from disadvantaged areas and with less capacity for self-monitoring and self-adjustment of treatment," he added.

Describing lessons learned through the experiences accumulated in diabetes care during the pandemic, Pérez highlighted the push for virtual consultations, accessibility to drugs prescribed in electronic prescriptions, and the use of educational resources online and of telemedicine tools. "The need to invest in the health sector has also been assumed, endowing it with robustness in well-trained health personnel, to promote health education, boost efficient health organization, and invest in innovation aimed at facilitating care," he concluded.

Kleger and Pérez have disclosed no relevant financial relationships.

Follow Carla Nieto of Medscape Spanish Edition on Twitter: @carlanmartinez.

This article was translated from the Medscape Spanish edition.

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