Episode 40- “The Perfect Storm:” Part 1: COVID, corticosteroids, and strongyloides
In Part 1 of this “Mini Grand Rounds” series, we discuss corticosteroid use in COVID as well as the pathogenesis of strongyloides.
“‘The Perfect Storm’: Part 1: COVID, corticosteroids, and strongyloides“:
– The “RECOVERY” trial showed lower all-cause mortality rates in patients with COVID randomized to 6 mg dexamethasone PO/IV daily x 10 days (22.9% vs 25.7%, P < 0.001). This effect was even greater in patients needing mechanical ventilation (29.3% vs 41.4 %) and supplemental oxygenation (23.3% vs 26.2%). However, there was no benefit in patients that were not requiring supplemental oxygen
– The CDC now recommends dexamethasone (or equivalent dosing of other corticosteroids) for this patient population. They also recommend appropriate screening and treatment to reduce the risk of strongyloides hyperinfection syndrome prior to initiating corticosteroids
– Strongyloides is a roundworm that causes strongyloidiasis. It’s estimated that hundreds of millions of people are infected with strongyloides worldwide. In the US, the highest rates (between 15%-almost 50%) are found in immigrant populations- specifically those from Southeast Asia
– The signs and symptoms of an acute strongyloides infection are mild and non-specific and include rashes, cough, and GI symptoms. Many patients, especially those with chronic strongyloidiasis, remain asymptomatic
– Strongyloides can be life-threatening in immunocompromised patients, such as those taking corticosteroids, among others
– These patients can develop the very deadly “hyperinfection syndrome”- which we’ll discuss next week
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Parasites-strongyloides. CDC. Accessed 12/16/2020. Last updated 12/31/2019. available at: https://www.cdc.gov/parasites/strongyloides/
Hello and welcome to Episode 40 of “ER-Rx.” In part one of our Strongyloides “Mini Grand Rounds” series, we’ll quickly review the use of corticosteroids in the setting of COVID and discuss the pathogenesis of strongyloides and how it relates to corticosteroid use. Next week, we’ll finish up by discussing prevention and treatment of strongyloides and strongyloides hyperinfection syndrome.
Why do we use corticosteroids in patients with COVID? The thought is that patients with severe COVID can develop a systemic inflammatory response that leads to lung injury and multisystem organ failure, and that corticosteroids can mitigate this. Remember that corticosteroids in general have had very mixed results in other settings, including in other respiratory viruses such as SARS and MERS, where corticosteroids showed reduced viral clearance. In the setting of ARDS, we are still trying to figure out if corticosteroids are indicated, with some trials showing benefit and others not showing benefit.
Well, in the “RECOVERY” trial, the authors found that in the setting of COVID, corticosteroids were beneficial. This multi-center, open-label trial randomized patients with COVID to either dexamethasone 6 mg (IV/PO) daily for 10 days or until hospital discharge (2,104 patients) or to standard of care (4,321 patients). They found that all-cause mortality was lower in the dexamethasone group at 22.9% vs 25.7% (RR 0.83, CI 0.75-0.93, P < 0.001). This effect was even greater in patients needing mechanical ventilation (29.3% vs 41.4 %) and supplemental oxygenation (23.3% vs 26.2%). However, there was no benefit in patients that were not requiring supplemental oxygen. Based on the results of this trial, the CDC recommends dexamethasone for hospitalized patients requiring supplemental oxygen, mechanical ventilation, or ECMO. Of course, we can use equivalent doses of other corticosteroids if needed. If you dig through the CDC’s guidelines, you run across Table 3b, which discusses immune-based therapy for COVID. This table discusses known side effects of corticosteroids such as hyperglycemia, psychiatric disturbances, and increased blood pressure. But it also discusses the risk of reactivating latent infections such as hepatitis B, tuberculosis, HSV, and strongyloides. They go on to say that when initiating dexamethasone, appropriate screening and treatment to reduce the risk of strongyloides hyperinfection should be considered.
What in the world is strongyloides and hyperinfection syndrome? Strongyloides is a small roundworm that causes strongyloidiasis. There are over 40 species in this genus (strongyloides stercoralis being the one that infects humans). This worm causes infection through contact with soil that is contaminated with larvae. It’s diagnosed with a blood test or microscopic examination of the stool. But there are a lot of drawbacks with these diagnostic tests. The blood test is sensitive, but it’s very non-specific and antibodies can remain positive for a while. Serial examination of the stool is the gold standard test, but it’s still not ideal, since it can take up to 7 exams to reach a sensitivity of 100%. To note, up to 75% of people with chronic strongyloidiasis have elevated eosinophil or IgE levels, but a lack of eosinophilia does not exclude infection. Overall, it is relatively difficult to screen and diagnose these patients. This is something that will come up again in the next episode.
It’s estimated that strongyloides infects hundreds of millions of people worldwide. In the US, strongyloides is mostly associated with veterans returning from Asia during WWII or the Vietnam War, but outside of this, the highest rates are documented in immigrant populations. The prevalence in this population ranges from 15- almost 50%, with a high prevalence in Southeast Asian refugees- particularly the Hmong population. The Hmong are a Southeast Asian ethnic group mostly located in Southern China, Vietnam, and Thailand. So, if you work in an area with a large Hmong population, as I do, it’s only a matter of time before you encounter strongyloides in your practice.
The signs and symptoms of an acute strongyloides infection are mild and very non-specific. Actually, a large majority of patients are asymptomatic or have very general complaints. These include cough, which develops as the larvae migrate from the lungs and up through the trachea; GI symptoms such as epigastric pain, heartburn, diarrhea, and even hemorrhage, and cutaneous symptoms. Rashes at the site of skin penetration are often the first sign. Larva currens is a rash that develops along the buttocks, perineum, and the thighs, and this rash can advance up to 10 cm/ hour! Patients with chronic strongyloidiasis are often asymptomatic, with GI and cutaneous symptoms being most common.
The thing to remember with strongyloides infection is that it can be life-threatening in immunocompromised patients, such as those taking corticosteroids (at any dose or any duration of time), those who have hematologic malignancies, or if they are transplant recipients, among others. These patients can develop the very deadly “hyperinfection syndrome”- which we’ll discuss next week.
As always, thank you so much for your time. If you can, please remember to leave a review of the show on Apple Podcasts—I’ll post a direct link to Apple Podcasts in the Show Notes. Also, you can take a deeper dive into the references I used by checking out one of my favorite apps: Read by QxMD. I created a personalized collection on errxpodcast.com that I think listeners will find very useful.