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In practice, doctors may use these terms synonymously.

We are in the midst of a COVID-19 global pandemic that is changing the world as we know it. Most COVID-19 patients may not need acute inpatient care admission. Only the sickest will. These are the patients who undergo a cytokine storm (aka cytokine release syndrome, or CRS) and develop secondary hemophagocytic lymphohistiocytosis (sHLH), which causes acute respiratory distress syndrome (ARDS). ARDS causes ~50 percent mortality in these patients. Cytokine storms are seen in sepsis, non-infectious SIRS, macrophage activation syndrome (MAS), and secondary hemophagocytic lymphohistiocytosis. There are specific codes for those, but they follow similar pathophysiology and can be confused for one another.

In practice, doctors may use these terms synonymously. For example, they may use the term “septic shock” for patients who go into shock for non-infectious SIRS. When clinical documentation specialists and coders see “septic shock,” they may come to the wrong conclusion that a patient has sepsis, when it’s really non-infectious SIRS. The same scenario can happen in COVID-19 with sHLH, which may lead to confusion, queries, and inappropriate coding of CRS and sepsis, in their mission to capture more severity of illness (SOI) and major complications/comorbid conditions (MCCs). When one sees a patient with fever and organ failure(s) who satisfies sepsis criteria, they are already conditioned to think and ask for sepsis! 

You may ask, “so what?” Well, modes of therapy will be different, and mortality rates are also different. See the following excerpt from a National Institutes of Health (NIH) article (https://pubmed.ncbi.nlm.nih.gov/19325510/):

SHLH features “can also commonly be found in patients with sepsis, systemic inflammatory response syndrome (SIRS), multi-organ dysfunction syndrome (MODS), and macrophage activation syndrome (MAS). Nevertheless, the therapeutic options for these are radically different.

Chemotherapy and bone marrow transplant have been used for treatment of HLH/SHLH, whereas antibiotics and supportive treatment are used in severe sepsis/SIRS and MODS. MAS is treated with limited immune suppression. Outcomes are also different; SHLH has a mortality rate around 50 percent, whereas pediatric septic shock and MODS have a mortality of 10.3 percent and 18 percent, respectively, and severe sepsis in previously healthy children has a mortality rate of 2 percent. MAS has a mortality rate between 8 percent and 22 percent.”

To summarize, cytokine release syndromes (CRS) have different types (e.g., sepsis, non-infectious SIRS, MAS, sHLH, etc.) with similar pathogenesis, but they need to be delineated in data.

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