Rare Case of Macroamylasemia in a Patient with SARS-CoV-2-Infection

Medical News: Macroamylasemia is a rare but benign medical condition characterized by an abnormally high level of amylase in the blood without a corresponding increase in urine amylase levels. Amylase, an enzyme essential for digesting carbohydrates, is typically produced by the pancreas and salivary glands. However, in macroamylasemia, amylase molecules bind with other serum proteins, primarily immunoglobulins, forming large complexes that are too big to be filtered by the kidneys. This results in a persistently high amylase level in the bloodstream without any signs of pancreatic disease.


Rare Case of Macroamylasemia in a Patient with SARS-CoV-2-Infection

While macroamylasemia has been identified in about 0.5% to 1.5% of the general population, it is often misdiagnosed due to its rarity. A recent case report from researchers at the National Hospital of Sri Lanka sheds new light on the connection between this condition and SARS-CoV-2 infection. This Medical News report discusses the case in detail, highlighting the implications of this unexpected association.
 
Case of a COVID 19 Patient with Persistent High Amylase Levels
The case involves a 70-year-old man with a history of hypertension and asthma who was being treated for mild COVID-19. The patient, who was on regular medication including Losartan and an inhaler containing Fluticasone Propionate and Salmeterol, initially exhibited no alarming symptoms apart from those related to COVID-19. However, by the third day of hospitalization, he began experiencing burning epigastric pain.
 
Routine blood tests revealed an unexpected elevation in serum amylase levels. While this is often associated with acute pancreatitis, further examination ruled out any pancreatic involvement. Over the following months, despite the resolution of his COVID-19 symptoms, the patient continued to exhibit persistently high amylase levels. This unusual trend prompted an in-depth investigation into the underlying cause of his condition.
 
Diagnostic Journey and Key Findings
Doctors conducted a comprehensive series of tests to determine the source of the elevated amylase levels. The patient’s renal function and other basic metabolic markers remained within normal ranges, eliminating common causes such as kidney or liver dysfunction. Further, an abdominal CT scan and an MRI revealed no signs of pancreatic disease or malignancies.
 
The critical diagnostic breakthrough came through specialized amylase testing. The amylase-creatinine clearance ratio, a key indicator for differentiating macroamylasemia from other causes of hyperamylasemia, was found to be 0.2% - a strong indicator of macroamylasemia. Additional tests using polyethylene glycol (PEG) precipitation confirmed the presence of macromolecular amylase complexes, further solidifying the diagnosis.
 
Possible Link Between SARS-CoV-2 and Macroamylasemia
COVID-19 is primarily known for its impact on the respiratory system, but researchers are increasingly recognizing its ability to trigger immune system d ysregulation. Following infection, the body produces immunoglobulin A (IgA), immunoglobulin M (IgM), and immunoglobulin G (IgG) antibodies against the virus’s spike (S) and nucleocapsid (N) proteins. These antibodies play a vital role in fighting the virus but can also have unintended consequences.
 
In this case, scientists theorize that the patient’s immune response to SARS-CoV-2 may have contributed to the formation of macromolecular amylase complexes. Since these immunoglobulins can bind with amylase molecules, they potentially create macromolecules that are too large to be filtered out through the kidneys, resulting in persistently high blood amylase levels. This immune-mediated process had never been documented in a COVID-19 patient before, making this case particularly significant.
 
How Common is This Condition in COVID 19 Patients
Elevated amylase levels have been observed in COVID-19 patients before, but macroamylasemia itself is extremely rare. Studies suggest that among mild to moderate COVID-19 cases, 1-2% of patients show elevated amylase, while the rate rises to 17% in severe cases. A study in the United States reported that 0.27% of hospitalized COVID-19 patients developed acute pancreatitis, but the majority of cases were of unknown origin. Until now, there had been no previously reported cases linking COVID-19 to macroamylasemia.
 
Diagnostic Challenges and Clinical Significance
Because macroamylasemia is not widely recognized, patients with persistently high amylase levels often undergo unnecessary and costly investigations to rule out serious conditions like pancreatitis, kidney disease, and malignancies. The identification of macroamylasemia as a benign and self-limiting condition is crucial in preventing unnecessary medical interventions.
 
The simplest and most cost-effective test to screen for macroamylasemia is the amylase-creatinine clearance ratio. A result of less than 1% suggests macroamylasemia, while levels above 5% point to acute pancreatitis. Confirmatory tests, such as PEG precipitation or electrophoresis, can provide definitive diagnosis.
 
What This Means for Future Medical Investigations
This case highlights the importance of considering macroamylasemia in patients with unexplained hyperamylasemia, especially in the context of COVID-19. The interaction between viral infections and immune responses remains an area of active research, and this case suggests that SARS-CoV-2 may play a role in previously unrecognized metabolic and enzymatic disturbances.
 
While macroamylasemia itself does not require treatment, recognizing the condition early can spare patients from unnecessary anxiety and medical procedures. Physicians should be aware of this possibility, especially in post-COVID-19 patients presenting with persistent hyperamylasemia without pancreatic symptoms.
 
Conclusion
This case represents the first documented occurrence of macroamylasemia in a COVID-19 patient. The findings suggest that immune dysregulation triggered by SARS-CoV-2 infection may contribute to the formation of amylase-immunoglobulin complexes, leading to persistently high amylase levels. By increasing awareness of macroamylasemia among healthcare professionals, unnecessary testing and hospitalizations can be minimized, ensuring better patient management.
 
Medical practitioners should consider macroamylasemia as a differential diagnosis in cases of unexplained hyperamylasemia, particularly in post-COVID-19 patients. A simple amylase-creatinine clearance test, followed by PEG precipitation, can provide a definitive diagnosis and prevent misdiagnosis of serious pancreatic conditions. This case underscores the importance of continued research into the long-term metabolic effects of COVID-19.
 
The study findings were published in the peer-reviewed journal: BMC Infectious Diseases.
https://link.springer.com/article/10.1186/s12879-025-10642-x
 
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