A novel coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has affected over 2.3 million people, claiming more than 160000 lives in over 200 countries worldwide. Although COVID-19 can be asymptomatic, the primary presentation in symptomatic patients is in the form of viral pneumonia, sometimes complicated by acute respiratory distress syndrome and/or sepsis. In addition, myocarditis and acute kidney injury have also been described in COVID-19. On the contrary, endocrinological manifestations have not yet been reported in patients with COVID-19.
The pathogenesis of COVID-19 entails entry of SARS-CoV-2 via the respiratory system and lodgement in the lung parenchyma. Thereafter, it uses angiotensin-converting enzyme 2 (ACE2) as a receptor for ingress into host pneumocytes. In addition, the viral ribonucleic acid (RNA) has also been detected in the plasma or serum of COVID-19 patients, suggestive of viremia [1]. This implies that apart from pneumocytes, the virus is freely available to interact with ACE2 expressed in other tissues. As a matter of fact, a number of endocrine organs do express ACE2, namely pancreas, thyroid, testis, ovary, adrenal glands and pituitary [2]. Even though one could expect endocrine repercussions due to interaction of SARS-CoV-2 with ACE2 expressed on these organs, there are no clinical/pre-clinical data as of yet. However, based on observations drawn partly from studies pertaining to the prior SARS outbreak (in 2003) and partly from animal models, we aim to explore the possible effects of COVID-19 on the endocrine system.
COVID-19 and endocrine pancreas
ACE2 is expressed in pancreas with mRNA levels being higher in pancreas than in the lungs. The expression is seen on the exocrine pancreas as well as on the islets. Exocrine pancreatic injury is manifested as elevated serum amylase and/or lipase in 1–2% and 17% of patients with non-severe and severe COVID-19, respectively [2]. Although any major illness can be associated with stress-related hyperglycemia, Yang et al. had reported that patients with SARS (caused by SARS-CoV, the ‘cousin’ of SARS-CoV-2) who had never received glucocorticoids had significantly higher fasting plasma glucose levels as compared to patients with non-SARS pneumonia [3]. In another study, SARS-CoV-mediated damage of the pancreatic β-cells was proposed as the plausible mechanism behind the development of ‘acute diabetes’ in patients with SARS [4]. In fact, immunohistochemistry and in situ hybridization have identified SARS-CoV in the pancreas of patients who died of SARS [5]. Thus, although coronavirus does not feature in the list of viruses implicated in the etiopathogenesis of type 1 diabetes mellitus (T1DM), SARS-CoV (and perhaps SARS-CoV-2) could be potential environmental triggers for the development of T1DM. Apart from direct β-cell damage, alterations in self-antigens and subsequent immune-mediated destruction of β-cells could be implicated. In addition, infection of the surrounding exocrine pancreas by SARS-CoV and SARS-CoV-2 might cause a bystander β-cell death via release of mediators such as tumor-necrosis factor-α (TNFα) and interferon-γ [6]. A systemic pro-inflammatory milieu, as evident by high amounts of interleukin-1β, monocyte chemoattractant protein-1 (MCP-1) and inducible protein-10 even in patients with mild COVID-19 might play an additional role to accentuate the process.
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A novel coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has affected over 2.3 million people, claiming more than 160000 lives in over 200 countries worldwide. Although COVID-19 can be asymptomatic, the primary presentation in symptomatic patients is in the form of viral pneumonia, sometimes complicated by acute respiratory distress syndrome and/or sepsis. In addition, myocarditis and acute kidney injury have also been described in COVID-19. On the contrary, endocrinological manifestations have not yet been reported in patients with COVID-19.
The pathogenesis of COVID-19 entails entry of SARS-CoV-2 via the respiratory system and lodgement in the lung parenchyma. Thereafter, it uses angiotensin-converting enzyme 2 (ACE2) as a receptor for ingress into host pneumocytes. In addition, the viral ribonucleic acid (RNA) has also been detected in the plasma or serum of COVID-19 patients, suggestive of viremia [1]. This implies that apart from pneumocytes, the virus is freely available to interact with ACE2 expressed in other tissues. As a matter of fact, a number of endocrine organs do express ACE2, namely pancreas, thyroid, testis, ovary, adrenal glands and pituitary [2]. Even though one could expect endocrine repercussions due to interaction of SARS-CoV-2 with ACE2 expressed on these organs, there are no clinical/pre-clinical data as of yet. However, based on observations drawn partly from studies pertaining to the prior SARS outbreak (in 2003) and partly from animal models, we aim to explore the possible effects of COVID-19 on the endocrine system.
COVID-19 and endocrine pancreas
ACE2 is expressed in pancreas with mRNA levels being higher in pancreas than in the lungs. The expression is seen on the exocrine pancreas as well as on the islets. Exocrine pancreatic injury is manifested as elevated serum amylase and/or lipase in 1–2% and 17% of patients with non-severe and severe COVID-19, respectively [2]. Although any major illness can be associated with stress-related hyperglycemia, Yang et al. had reported that patients with SARS (caused by SARS-CoV, the ‘cousin’ of SARS-CoV-2) who had never received glucocorticoids had significantly higher fasting plasma glucose levels as compared to patients with non-SARS pneumonia [3]. In another study, SARS-CoV-mediated damage of the pancreatic β-cells was proposed as the plausible mechanism behind the development of ‘acute diabetes’ in patients with SARS [4]. In fact, immunohistochemistry and in situ hybridization have identified SARS-CoV in the pancreas of patients who died of SARS [5]. Thus, although coronavirus does not feature in the list of viruses implicated in the etiopathogenesis of type 1 diabetes mellitus (T1DM), SARS-CoV (and perhaps SARS-CoV-2) could be potential environmental triggers for the development of T1DM. Apart from direct β-cell damage, alterations in self-antigens and subsequent immune-mediated destruction of β-cells could be implicated. In addition, infection of the surrounding exocrine pancreas by SARS-CoV and SARS-CoV-2 might cause a bystander β-cell death via release of mediators such as tumor-necrosis factor-α (TNFα) and interferon-γ [6]. A systemic pro-inflammatory milieu, as evident by high amounts of interleukin-1β, monocyte chemoattractant protein-1 (MCP-1) and inducible protein-10 even in patients with mild COVID-19 might play an additional role to accentuate the process.