Acute Phase Reactants and COVID-19

It goes without saying that 2020 was an interesting year for Medical Laboratory Professionals. I was just a fledgling Medical Laboratory Scientist when the pandemic really began progressing in the United States.

While I know this was only a few short months ago, I already feel like I have learned and grown so much in this field, and I am in love with how fast-paced and progressive laboratory medicine is.

We have been learning and adapting alongside our fellow healthcare professionals to tackle COVID one case at a time.

Acute Phase Reactants

Working in the core lab, I began to notice a steady increase in the number of orders for ferritin, C-reactive protein, procalcitonin, ESR, and fibrinogens (D-dimers too, but perhaps that is a topic for another time).

I was familiar with the term “acute phase reactants” from class, but I couldn’t really say I understood them well. So I became curious: what significance could these general inflammation markers have for this mysterious respiratory illness?

Well, quite a lot, as it turns out. The first hurdle to overcome was developing reliable COVID tests, and then the issue became delegating resources and manpower to actually perform these tests.

Of course, there was plenty of controversy over symptoms and severity. With limited access to reliable diagnostic testing that sometimes led to confusing results, healthcare workers and researchers came up with a creative way to monitor COVID cases by measuring acute phase reactants.

Acute phase reactants (APR’s) are physiological markers that exhibit a significant change in concentration as a result of inflammation. This process is initiated by inflammatory cytokines produced by cells of the immune system. 

APRs are classified as positive or negative depending on whether they are upregulated or downregulated during inflammation. I’d like to highlight some of the APRs that are frequently seen in the chemistry lab.


Ferritin is a protein involved in the regulation and storage of iron. Typically, ferritin is ordered alongside tests such as serum iron and total iron-binding capacity (TIBC), either for routine screening or to help physicians determine possible causes of anemia.

In regard to inflammation, ferritin levels will increase in response to infections or malignancy as a defense mechanism. The increased ferritin sequesters free iron so that pathogens or tumor cells cannot access it as easily.


Procalcitonin is a precursor to the hormone calcitonin and is involved in calcium homeostasis. Under normal conditions, procalcitonin is only produced by parafollicular cells in the thyroid. However, other tissues will produce procalcitonin in response to inflammation, and it will not be converted to calcitonin.

Procalcitonin is unique in that its secretion is stimulated by inflammation related to bacterial infection, and is typically not elevated due to viral infection. This makes it an extremely useful laboratory test for monitoring the progression of infections.

Physicians have been using procalcitonin to help determine if a patient’s pneumonia is bacterial or viral in nature, and if procalcitonin levels increase during the hospital stay, in can be indicative of a bacterial co-infection.

C-Reactive Protein (CRP)

CRP acts as an opsonin and is involved in activating the complement pathway. It is a sensitive marker that can be used to directly measure the extent of an inflammatory response.

In health, CRP concentrations are very low (<1.0 mg/dL) but can increase 100- to 1000-fold in a matter of hours during acute inflammation.

APR and COVID-19

A study released by researchers at St. Jude suggests that fatality or severe complications from a COVID-19 infection can be attributed to a cytokine storm caused by the body’s immune response to the virus.

Essentially, the initial respiratory infection leads to the excessive production of inflammatory cytokines that can cause systemic tissue damage. With this in mind, it is easy to see the significance of monitoring APRs in COVID patients.

As cytokine production increases, APRs will increase as well, notifying the physician that the patient’s prognosis is worsening.

This is information that we can provide to clinicians despite the shortage of COVID testing. So keep those chemistry analyzers stocked up!

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