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July 30, 2020

COVID-19 and Dexamethasone: A Potential Strategy to Avoid Steroid-Related Strongyloides Hyperinfection

Author Affiliations
  • 1Center for Global Health and Social Responsibility, University of Minnesota, Minneapolis
  • 2Department of Medicine, Global Medicine, University of Minnesota, Minneapolis
  • 3HealthPartners Institute, Bloomington, Minnesota
  • 4HealthPartners Travel and Tropical Medicine Center, St Paul, Minnesota
JAMA. Published online July 30, 2020. doi:10.1001/jama.2020.13170

A widely publicized press release and subsequent preliminary report of the RECOVERY trial, a randomized study conducted in the UK, noted a survival benefit with the use of dexamethasone in hospitalized patients with coronavirus disease 2019 (COVID-19).1 The use of dexamethasone for management of COVID-19 has already increased, particularly given the recent National Institutes of Health COVID-19 Treatment Panel guidelines that recommend its use.2

Although clinicians are familiar with the most common adverse effects associated with dexamethasone, a corticosteroid, they may be less familiar with a potentially severe, but preventable, less common complication: Strongyloides hyperinfection or dissemination syndrome (hyperinfection).3

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    2 Comments for this article
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    Ivermectin in Latin America
    Carlos Alvarez, MD; FIDSA; PhD; DTM&H | Porfessor of Medicine at Infectious Diseases at Tropical medicine. Facultad de Medicina; Universidad Nacional de Colombia. Clinica Universitaria Colombia, Clinica Colsanitas
    I have carefully read the Viewpoint on use of ivermectin proposed by Dr. Stauffer et al. to avoid the hyperinfection of Strongyloides stercoralis (S. stercoralis). In countries endemic for this intestinal parasitosis it is mandatory to start deworming before starting the use of steroids, since the presence of cases of S. stercoralis hyperinfestation is not uncommon. Besides, given the endemicity, the use of serological tests is not useful, and the usefulness of the stool test is weak due to its sensitivity to detect this parasite (1,2). At this time when regions such as Latin America are on the epidemic curve of COVID-19, clinical practice guidelines of several countries have routinely introduced using dexamethasone based on the data from the RECOVERY trial, and previous administration of ivermectin is recommended as an antiparasitic encouraged by the title of a paper recently published in Antiviral Research, "The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro" (3). The study reports that ivermectin, a medication widely used for treatment of certain parasitic diseases in humans, inhibits replication of SARS-CoV-2 in cell culture. The search for a simple therapeutic treatment of COVID-19 has led to extensive use of ivermectin not only as a treatment but also as a prophylactic in several Latin American countries, and in countries like Peru and Honduras the drug is promoted in national clinical guidelines; This has led to a shortage in some regions of ivermectin, including veterinary presentations. Since its use and method of administration for this indication is not clear, despite the safety of ivermectin, its administration at high doses or repeated use could lead to unexpected consequences. Finally, I consider that repurposing ivermectin for COVID-19 could be encouraging, but this cannot be massively recommended without having carried out controlled clinical studies

    REFERENCES
    1. Kalantari N, Chehrazi M, Ghaffari S, Gorgani-Firouzjaee T. Serological assays for the diagnosis of Strongyloides stercoralis infection: a systematic review and meta-analysis of diagnostic test accuracy. Trans R Soc Trop Med Hyg. 2020;114(6):459-469.
    2. Campo Polanco L, Gutiérrez LA, Cardona Arias J. Infección por Strongyloides stercoralis: metanálisis sobre evaluación de métodos diagnósticos convencionales (1980-2013) [Diagnosis of Strongyloides Stercoralis infection: meta-analysis on evaluation of conventional parasitological methods (1980-2013)]. Rev Esp Salud Publica. 2014;88(5):581-600.
    3. Caly L, Druce JD, Catton MG, Jans DA, Wagstaff KM. The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro. Antiviral Res. 2020;178:104787. doi:10.1016/j.antiviral.2020.104787
    CONFLICT OF INTEREST: None Reported
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    Strongyloides Hyperinfection Prophylaxis Is Not Necessary in COVID-19 Patients Given Dexamethasone
    Joseph Santos, MD; PhD | Unidade de Terapia Intensiva, Hospital Governador Israel Pinheiro - IPSEMG - Hospital Universitário Ciências Médicas - FELUMA - Belo horizonte Minas Gerais - Brazil
    Dr. Stauffer et al. proposes the use of ivermectin as a potential strategy to avoid steroid-related Strongyloides hyperinfection in patients with severe COVID-19 treated with dexamethasone (6mg per day for 10 days), as demonstrated in the RECOVERY trial. However in several other clinical situations corticosteroids are used without such prophylaxis as in the case of hydrocortisone for treatment of septic shock. The guidelines of the Surviving Sepsis Campaign (SSC) do not recommend such prophylaxis for patients given hydrocortisone, which has been widely used for sepsis worldwide for almost 20 years (1). The recommended dose in the SSC guideline, 200 mg hydrocortisone per day, is equivalent to the dose of 6.7 mg of dexamethasone, similar to that used by the RECOVERY study. It is estimated that 48.9 million cases of sepsis occur worldwide, and that 2 to 20% progress to septic shock, and a significant number of them use hydrocortisone, without prophylaxis for strongyloides hyperinfection (1). Studies that tested hydrocortisone in septic shock considered the occurrence of strongyloides hyperinfection to be irrelevant in this situation, so much so that they did not include the use of antiparasitic agents in the research protocols prior to its use, and in these same studies there was no report of any case (2). Systematic reviews of the use of corticosteroids in sepsis do not mention an indication for the use of prophylaxis for strongyloides hyperinfection. Furthermore, we did not find any report in the literature of strongyloides hyperinfection in patients who received hydrocortisone in order to treat septic shock. On the contrary, systematic reviews of case studies of strongyloides hyperinfection show no reports in septic patients who used corticosteroids, but only in patients who received immunosuppressive therapy with corticosteroids, or in patients who used high doses (equivalent dose of prednisone above 30 mg / day) and for a prolonged period (greater than 4 weeks) (3). These data show that if there is any case of strongyloides hyperinfection in patients with septic shock, this is an extremely rare event. A guideline for the treatment of patients with COVID-19, recently published, does not provide a recommendation for prophylaxis in patients who need corticosteroids (4). As a concluding remark, there is no need or indication for the use of any antiparasitic to prevent strongyloides hyperinfection in patients with COVID-19 using dexamethasone.

    REFERÊNCIAS:
    1 – Rhodes A, Evans L, Alhazzani W, et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016, Crit Care Medicine. 2017. 45(3):486-552
    2 – Sprung CL, Annane D, Keh D, et al. Hydrocortisone therapy for patients with septic shock. N Engl J Med 2008;358:111-24
    3 - Geri, G., Rabbat, A., Mayaux, J. et al. Strongyloides stercoralis hyperinfection syndrome: a case series and a review of the literature. Infection. 2015. 43:691–698
    4 – Alhazzani W, Møller M H, Arabi, YM, et al. Surviving Sepsis Campaign: Guidelines on the Management of Critically Ill Adults with Coronavirus Disease 2019 (COVID-19), Crit Care Medicine. 2020. 48(6):e440-e469
    CONFLICT OF INTEREST: None Reported
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