Corral, Marcelo Andreetta

Gryschek, Ronaldo Cesar Borges

Mastandrea, Giovanna Ribeiro Achur

Medeiros, Ana Clara Cassine de Souza

Paula, Fabiana Martins de

Pereira, Carolina Victoria Marcitelli

English

Cadernos Espinosanos (E-Journal)

COVID-19 and strongyloidiasis: what to expect fromthis coinfection?Carolina Victoria Marcitelli Pereira0000-0000-0000-0000 ,I Giovanna Ribeiro Achur Mastandrea0000-0000-0000-0000 ,I Ana Clara Cassinede Souza Medeiros0000-0000-0000-0000 ,I Ronaldo Cesar Borges Gryschek0000-0000-0000-0000 ,II,III Fabiana Martins de Paula0000-0000-0000-0000 ,II,IIIMarcelo Andreetta Corral0000-0000-0000-0000 I,II,III,*I Faculdade de Medicina, Universidade Santo Amaro, Sao Paulo, SP, BR. II Laboratorio de Investigacao Medica (LIM06-Laboratorio de Imunopatologia daEquistossomose), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BR. III Secao de Helmintologia, Institutode Medicina Tropical (IMT), Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, SP, BR.Pereira CVM, Mastandrea GRA, Medeiros ACCS, Gryschek RCB, Paula FM, Corral MA. COVID-19 and strongyloidiasis: what to expect from this coinfection?Clinics (Sao Paulo). 2021;76:e3528*Corresponding author. E-mail: mcorral@prof.unisa.brStrongyloidiasis is a parasitic infection caused by theintestinal nematode Strongyloides stercoralis. It is a chronicand asymptomatic parasite in most immunocompetentindividuals. In immunocompromised patients, especiallythose undergoing corticotherapy, the disease can progressto advanced stages, such as hyperinfection syndrome anddisseminated disease (1). Corticosteroids are metabolized inthe liver to chemical compounds structurally similar toecdysone and are used by helminths for oviposition andlarval ecdysis stimulation, promoting an accelerated auto-infection cycle (2).The coronavirus disease (COVID-19) pandemic remainsa health challenge for society worldwide. The advancingknowledge of the physiopathology suggests that a rapidreplication of severe acute respiratory syndrome coronavirus2 (SARS-CoV-2) may lead to an exacerbated immuneresponse involving many cytokines (cytokine storm), trigger-ing a severe inflammatory response in the lungs. Usingcorticosteroids and anticoagulants in such cases has pro-duced beneficial results (3-5), with dexamethasone andmethylprednisolone being used most frequently (6-7).The impact of the COVID-19 pandemic on S. stercoralisinfection remains to be elucidated. However, there are fewreports of severe strongyloidiasis in patients with COVID-19after undergoing treatment with corticosteroids (8-12);currently, only six cases of coinfection with S. stercoralisand COVID-19 have been reported (Figure 1). Clinical dataof these patients are incipient or partial; however, generally,the majority of the reported cases tended to be in maleindividuals (66.7%), with an average age of 61.3 years. Theseindividuals were admitted to the hospital for COVID-19treatment, were released from the hospital, and returnedafter 22.8 days on average with skin signs and symptoms,such as dermatitis, followed by respiratory and intestinalmanifestations. The diagnosis of S. stercoralis infection wasconfirmed by parasitic stool examination in one case (16.7%),enzyme-linked immunosorbent assay in two (33.3%), micro-scopic stool and serological methods in two (33.3%), andmicroscopic sputum in one (16.7%).Different therapeutic regimens (Figure 1) were used totreat SARS-CoV-2 infection with methylprednisolone anddexamethasone. In parallel with corticosteroids, antiviraldrugs were also used. For S. stercoralis infection, ivermectinwas used in 50% of the patients, albendazole in 16.7%, andthe combination of both in 33.3%. All patients survivedCOVID-19 and strongyloidiasis. It is important to highlightthat 83.3% of the described cases occurred in non-endemicareas (1,13) for S. stercoralis infection, possibly indicating alink to immigration flows.Oliveira (6) reported the importance of the identification ofS. stercoralis infection using diagnostic methods for parasitedetection, especially cultures, or even serological screening.Once the helminth parasite is detected, anti-helminthictreatment is recommended before corticosteroid therapy isadministered. De Wilton et al. (5) proposed an algorithm forscreening the risk of S. stercoralis exposure in patientssamples with COVID-19 at a hospital in England. In general,all patients who had travelled or immigrated from endemicareas and those with a high risk of S. stercoralis infectionunderwent a diagnostic test and treatment with ivermectin.Although England is not considered an endemic area for S.stercoralis infection, there is a concern about the developmentof severe forms of this parasitosis when associated withcorticosteroid therapy, especially in immigrants.Unlike in the countries that reported cases of coinfection,the reality of strongyloidiasis in Brazil is distinct, with anestimated occurrence varying between 5.5% and 20% basedon the microscopic parasitic examination of stool. Whenother diagnostic methods are analyzed, these numbers maybe significantly higher since directly detecting larval forms isnot needed (13,14). Pandemic situations, such as COVID-19,bring awareness to the scientific community worldwide tothe need for studies on other non-viral infectious agents forthe prevention of fatal consequences of possible associations.In this scenario, the possibility of asymptomatic infection byS. stercoralis becoming symptomatic and severe with the useof corticosteroids is evident.DOI: 10.6061/clinics/2021/e3528Copyright & 2021 CLINICS – This is an Open Access article distributed under theterms of the Creative Commons License (http://creativecommons.org/licenses/by/4.0/) which permits unrestricted use, distribution, and reproduction in anymedium or format, provided the original work is properly cited.No potential conflict of interest was reported.1COMMENTSThere is a need to apply and to implement more sensitiveand specific diagnostic techniques for strongyloidiasis thatcould be used in immunocompetent and immunocompro-mised individuals (5,6). The public health systems need toconsider the construction and validation of a diagnosticprotocol. Many diagnostic methods have been reportedin the literature (15) based on the direct detection of theparasite by agar plate culture or molecular methods, or eventhe indirect detection of antibodies, antigens, or immunecomplexes; however, none of these methods are available inthe Brazilian national health system, only for research.Therefore, strongyloidiasis continues to be considered oneof the most neglected parasitic diseases worldwide. Therapid identification of positive cases could minimizethe occurrence of severe cases resulting from coinfection;in Brazil, this would demonstrate the real situation ofthe condition in the country since it has high incidencerates of this important parasitosis.’ REFERENCES1. Toledo R, Muñoz-Antoli C, Esteban JG. Strongyloidiasis with emphasison human infections and its different clinical forms. Adv Parasitol.2015;88:165-241. https://doi.org/10.1016/bs.apar.2015.02.0052. Marty FM, Lowry CM, Rodriguez M, Milner DA, Pieciak WS, Sinha A,et al. Treatment of human disseminated strongyloidiasis with a parenteralveterinary formulation of ivermectin. Clin Infect Dis. 2005;41(1):e5-e8.https://doi.org/10.1086/4308273. Formiga FR, Leblanc R, de Souza Rebouças J, Farias LP, de Oliveira RN,Pena L. Ivermectin: an award-winning drug with expected antiviralactivity against COVID-19. J Control Release. 2021;329:758-61. https://doi.org/10.1016/j.jconrel.2020.10.0094. Tilli M, Olliaro P, Gobbi F, Bisoffi Z, Bartoloni A, Zammarchi L. Neglectedtropical diseases in non-endemic countries in the era of COVID-19 pan-demic: the greath forgotten. J Travel Med. 2021;28(1):taaa179. https://doi.org/10.1093/jtm/taaa1795. De Wilton A, Nabarro LE, Godbole GS, Chiodini PL, Boyd A, Woods K.Risk of Strongyloides Hyperinfection Syndrome when prescribing dexa-methasone in severe COVID-19. Travel Med Infect Dis. 2021;40:101981.https://doi.org/10.1016/j.tmaid.2021.1019816. Olivera MJ. Dexamethasone and COVID-19: Strategies in Low- andMiddle-Income Countries to Tackle Steroid-Related StrongyloidesHyperinfection. Am J Trop Med Hyg. 2021;104(5):1611-2. https://doi.org/10.4269/ajtmh.20-10857. Stauffer WM, Alpern JD, Walker PF. COVID-19 and Dexamethasone:A Potential Strategy to Avoid Steroid-Related Strongyloides Hyperinfec-tion. JAMA. 2020;324(7):623-4. https://doi.org/10.1001/jama.2020.131708. Pintos-Pascual I, López-Dosil M, Castillo-Núñez C, Múñez-Rubio E.Eosinophilia and abdominal pain after severe pneumonia due to COVID19. Enferm Infecc Microbiol Clin (Engl Ed). 2020;S0213-005X(20)30332-3.https://doi.org/10.1016/j.eimce.2021.08.0079. Lier AJ, Tuan JJ, Davis MW, Paulson N, McManus D, Campbell S, et al.Case Report: Disseminated Strongyloidiasis in a Patient with COVID-19.Am J Trop Med Hyg. 2020;103(4):1590-2. https://doi.org/10.4269/ajtmh.20-069910. Feria L, Torrado M, Anton-Vazquez V. Reactivation of Strongyloidesstercoralis in patients with SARS-CoV-2 pneumonia receiving dexa-methasone. Med Clin (Barc). 2021;27:S0025-7753(21)00292-X. https://doi.org/10.1016/j.medcli.2021.05.00411. Gautam D, Gupta A, Meher A, Siddiqui F, Singhai A. Corticosteroids inCovid-19 pandemic have the potential to unearth hidden burden ofstrongyloidiasis. IDCases. 2021;25:e01192. https://doi.org/10.1016/j.idcr.2021.e0119212. Marchese V, Crosato V, Gulletta M, Castelnuovo F, Cristini G, Matteelli A,et al. Strongyloides infection manifested during immunosuppres-sive therapy for SARS-CoV-2 pneumonia. Infection. 2021;49(3):539-42.https://doi.org/10.1007/s15010-020-01522-413. Paula FM, Costa-Cruz JM. Epidemiological aspects of strongyloidiasis inBrazil. Parasitology. 2011;138(11):1331-40. https://doi.org/10.1017/S003118201100120X14. Buonfrate D, Mena MA, Angheben A, Requena-Mendez A, Muñoz J,Gobbi F, et al. Prevalence of strongyloidiasis in Latin America: a sys-tematic review of the literature. Epidemiol Infect. 2015;143(3):452-60.https://doi.org/10.1017/S095026881400156315. Costa IN, Bosqui LR, Corral MA, Costa-Cruz JM, Gryschek RCB, de PaulaFM. Diagnosis of human strongyloidiasis: Application in clinical practice.Acta Trop. 2021;223:106081. https://doi.org/10.1016/j.actatropica.2021.106081Figure 1 - Timeline of the main events related to SARS-CoV-2 and S. stercoralis coinfections.2COVID-19 and strongyloidiasisPereira CVM et al.CLINICS 2021;76:e3528

COVID-19 and strongyloidiasis: what to expect from this coinfection?

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COVID-19 and strongyloidiasis: what to expect from this coinfection?

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