Review on acute pancreatitis attributed to COVID-19 infection

Abstract

The coronavirus disease 2019 (COVID-19) is known to cause gastrointestinal symptoms. Recent studies have revealed COVID-19-attributed acute pancreatitis (AP). However, clinical characteristics of COVID-19-attributed AP remain unclear. We performed a narrative review to elucidate relation between COVID-19 and AP using the PubMed database. Some basic and pathological reports revealed expression of angiotensin-converting enzyme 2 and transmembrane protease serine 2, key proteins that aid in the entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into the pancreas. The experimental and pathological evaluation suggested that SARS-CoV-2 infects human endocrine and exocrine pancreas cells, and thus, SARS-CoV-2 may have a direct involvement in pancreatic disorders. Additionally, systemic inflammation, especially in children, may cause AP. Levels of immune mediators associated with AP, including interleukin (IL)-1β, IL-10, interferon-γ, monocyte chemotactic protein 1, and tumor necrosis factor-α are higher in the plasma of patients with COVID-19, that suggests an indirect involvement of the pancreas. In real-world settings, some clinical features of AP complicate COVID-19, such as a high complication rate of pancreatic necrosis, severe AP, and high mortality. However, clinical features of COVID-19-attributed AP remain uncertain due to insufficient research on etiologies of AP. Therefore, high-quality clinical studies and case reports that specify methods for differential diagnoses of other etiologies of AP are needed.

Keywords: COVID-19; Etiology; Pancreatitis; Prognosis; Revised atlanta classification; SARS-CoV-2.

Figure 1

Direct and indirect pathways of pancreatic injury caused by severe acute respiratory syndrome coronavirus-2. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) disseminates through the bloodstream mainly to the pancreas. SARS-CoV-2 may be transported to the pancreas via the gastrointestinal tract. The pancreas expresses angiotensin converting enzyme-2 (ACE2) and the transmembrane protease serine 2 (TMPRSS2). SARS-CoV-2 binds to ACE2 after the viral spike (S) protein is primed by TMPRSS2 for cell entry. Therefore, SARS-CoV-2 may potentially cause direct pancreatic injury, including acute pancreatitis. However, indirect pancreatic injury may also be caused by systemic inflammatory responses from respiratory failure induced by SARS-CoV-2 infection. Levels of proinflammatory immune mediators associated with pancreatitis, including interleukin (IL)-1β, IL-6, IL-10, interferon-γ, monocyte chemotactic protein-1, and tumor necrosis factor-α are higher in the plasma of patients with coronavirus disease 2019. These mediators may indirectly cause pancreatic injury. An increase in lipase activity triggers lipolysis in the adipose tissues, and enhances levels of serum unsaturated fatty acids (UFA). UFA may cause an increase in levels of proinflammatory immune mediators that lead to systemic inflammation. SARS-CoV-2: Severe acute respiratory syndrome coronavirus-2; ACE2: Angiotensin converting enzyme-2; TMPRSS2: Transmembrane protease serine 2; IL: Interleukin, IFN-γ: Interferon-γ; MCP-1: Monocyte chemotactic protein-1; TNF-α: Tumor necrosis factor-α; UFA: Unsaturated fatty acids.

Figure 2

The probability of other etiologies of acute pancreatitis in cases with concurrent coronavirus disease 2019 and acute pancreatitis. The potential of other etiologies, including alcoholism, biliary, hypertriglyceridemia, hypercalcemia, drug-induced, acute aggravation on chronic pancreatitis, ischemia/reperfusion, and trauma/anatomy. In children, the potential of genetic and multisystemic inflammatory syndrome in children/pediatric inflammatory multisystem syndrome-induced acute pancreatitis (AP) are also evaluated. Moreover, these causes are regarded as inapplicable etiologies of AP in adults. The probability of AP is disregarded in cases with insufficient information on the etiologies of AP. Some etiologies of AP, such as alcohol, acute aggravation on chronic pancreatitis, and trauma/anatomy are well verified. Furthermore, the etiological workup for infections and hypercalcemia is insufficient. Moreover, some cases of AP may have been caused by drug and biliary disease as it may be difficult to exclude them from the etiology of AP. MIS-C: Multisystemic inflammatory syndrome in children; PIMS: Pediatrics inflammatory multisystem syndrome; AP: Acute pancreatitis.