Macroamylasemia: An Uncommon Culprit of Elevated Amylase Levels in COVID-19 Patients


The COVID-19 pandemic has shed light on various clinical manifestations and complications associated with the SARS-CoV-2 virus.

Among the myriad of challenges faced by healthcare professionals, one lesser-known but significant concern is the occurrence of elevated amylase levels in COVID-19 patients.

While this phenomenon remains relatively rare, it is crucial to understand the implications and diagnostic strategies surrounding it. In this article, we delve into the intriguing world of macroamylasemia, its potential link to COVID-19, and its impact on clinical management.

Understanding Amylase Levels in COVID-19 Patients

As we navigate the complexities of the COVID-19 pandemic, it is noteworthy that approximately 1-2% of mild to moderate COVID-19 cases and a striking 17% of severe COVID-19 cases exhibit acutely elevated amylase levels (7). The implications of elevated amylase levels in these patients can be perplexing, as they may signify various underlying conditions, including but not limited to acute pancreatitis, acute appendicitis, and bowel ischemia.

These conditions carry significant morbidity and mortality rates, which in turn can worsen the prognosis of COVID-19 patients.

A Case Study

To shed light on this matter, consider the case of a patient with mild COVID-19 who presented with elevated amylase levels and abdominal pain. In such scenarios, it becomes imperative to systematically exclude other potential causes of abdominal pain, especially those with high mortality rates. In the case under consideration, the patient did not meet the modified Atlantic criteria for acute pancreatitis, and a comprehensive evaluation ruled out other common causes of abdominal pain (Table 2). However, it is essential to underline the importance of excluding other factors contributing to elevated serum amylase levels.

Diagnostic Tools: Amylase-Creatinine Clearance Ratio

In the pursuit of identifying macroamylasemia, healthcare professionals can turn to diagnostic tools such as the amylase-creatinine clearance ratio. This simple and cost-effective test helps in screening for macroamylasemia. The normal range for this ratio falls between 3 and 5%. A ratio of less than 1% suggests the presence of macroamylasemia, while a ratio exceeding 5% hints at acute pancreatitis (2).

Confirmatory Tests: Electrophoresis and Polyethylene Glycol Precipitation

Once the amylase-creatinine clearance ratio raises suspicions of macroamylasemia, confirmatory tests are necessary. The gold standard methods for detecting macroamylase complexes involve electrophoresis and polyethylene glycol (PEG) precipitation tests.

The latter, PEG precipitation, stands out as the method of choice for identifying macroamylase complexes efficiently. This technique involves precipitating macromolecules in concentrated solutions of polyethylene glycol. The beauty of PEG precipitation lies in its swiftness; results can be obtained in as little as 10 minutes. Following precipitation, serum amylase levels can be accurately determined by subtracting the macroamylase concentration from the total amylase count (10).

The Immune Connection: SARS-CoV-2 and Dysregulation of Immune Tolerance

To unravel the enigma of macroamylasemia development in the context of SARS-CoV-2 infection, one must delve into the intricacies of the immune response. After the virus’s entry into the body, immunoglobulin A (IgA), immunoglobulin M (IgM), and immunoglobulin G (IgG) against the S and N proteins of SARS-CoV-2 begin to develop within 1-2 weeks after symptom onset.

Early on, the antigen-specific IgA levels surpass those of IgM. As time progresses, specific COVID-19 IgG antibodies rise, remaining elevated for extended periods, often exceeding a year. Intriguingly, these immunoglobulins can cross-react with alpha amylase molecules, forming macromolecules that can induce macroamylasemia. This phenomenon occurs due to the prolonged half-life of amylase, attributed to reduced renal clearance, likely resulting from immune system dysregulation (8).

Unraveling the Diagnostic Challenge

Patients with elevated amylase levels often find themselves undergoing a battery of extensive investigations. Astonishingly, a study revealed that 13.7% of such patients ultimately receive no specific diagnosis after exhaustive evaluations (9). This underscores the importance of identifying macroamylasemia, as doing so can bring significant value to both the healthcare system and the patient. Elevated amylase levels frequently lead to repeated, often unnecessary, and extensive investigations, which can be emotionally taxing and financially burdensome.


In conclusion, macroamylasemia may be a rare condition, but it is one that healthcare professionals should bear in mind when dealing with patients exhibiting high amylase levels, particularly in the context of COVID-19. The amylase-creatinine clearance ratio serves as a straightforward and cost-effective screening tool, enabling the timely identification of macroamylasemia. Diagnosing macroamylasemia holds great significance for both the healthcare system and the patient, as it can spare individuals from repeated hospital admissions and the physical, emotional, and financial toll of unnecessary and extensive investigations.

As the world continues to grapple with the multifaceted challenges posed by the COVID-19 pandemic, staying vigilant and informed about such less-recognized complications is crucial to providing comprehensive care and improving patient outcomes.

in deep…

Macroamylasemia is a condition in which there is an abnormally high level of amylase in the blood. Amylase is an enzyme that helps to break down carbohydrates in food. It is normally produced by the pancreas and salivary glands.

In macroamylasemia, the amylase is bound to a protein, making it too large to be filtered by the kidneys. This results in high levels of amylase in the blood, even though the pancreas is not damaged.

Macroamylasemia is a rare condition, affecting about 2-3% of people with hyperamylasemia (high blood amylase levels). It is more common in women than in men.

The most common cause of macroamylasemia is an autoimmune disorder called Waldenström’s macroglobulinemia. This disorder causes the production of abnormal antibodies that bind to amylase.

Other causes of macroamylasemia include:

  • Infections, such as mumps, pneumonia, and HIV
  • Cancer, such as lymphoma and leukemia
  • Medications, such as dilantin and ceftriaxone
  • Kidney disease
  • Cirrhosis of the liver

Macroamylasemia is usually asymptomatic, meaning that it does not cause any symptoms. However, in some cases, it can lead to symptoms similar to those of pancreatitis, such as abdominal pain, nausea, and vomiting.

The diagnosis of macroamylasemia is made by measuring the levels of amylase in the blood and urine. The blood amylase level will be high, but the urine amylase level will be normal. This is because the large amylase-protein complex is not filtered by the kidneys.

Macroamylasemia is usually treated by treating the underlying condition. If there is no underlying condition, then no treatment is necessary.

The prognosis for macroamylasemia is good. The condition is usually not serious and does not cause any long-term complications.

Here are some additional things to know about macroamylasemia:

  • It is more common in women than in men.
  • It is usually asymptomatic, but in some cases, it can cause symptoms similar to those of pancreatitis.
  • The diagnosis is made by measuring the levels of amylase in the blood and urine.
  • It is usually treated by treating the underlying condition.
  • The prognosis is good.

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