Ivermectin Effect on In-Hospital Mortality and Need for Respiratory Support in COVID-19 Pneumonia: Propensity Score-Matched Retrospective Study.

INTRODUCTION: There is negligible evidence on the efficacy of ivermectin for treating COVID-19 pneumonia. This study aimed to assess the efficacy of ivermectin for pre-emptively treating Strongyloides stercoralis hyperinfection syndrome in order to reduce mortality and the need for respiratory support in patients hospitalized for COVID-19. METHODS: This single-center, observational, retrospective study included patients admitted with COVID-19 pneumonia at Hospital Vega Baja from 23 February 2020 to 14 March 2021. Because strongyloidiasis is endemic to our area, medical criteria support empiric administration of a single, 200 µg/kg dose of ivermectin to prevent Strongyloides hyperinfection syndrome. The outcome was a composite of all-cause in-hospital mortality and the need for respiratory support. RESULTS: Of 1167 patients in the cohort, 96 received ivermectin. After propensity score matching, we included 192 patients. The composite outcome of in-hospital mortality or need for respiratory support occurred in 41.7% of the control group (40/96) and 34.4% (33/96) of the ivermectin group. Ivermectin was not associated with the outcome of interest (adjusted odds ratio [aOR] 0.77, 95% confidence interval [CI] 0.35, 1.69; p = 0.52). The factors independently associated with this endpoint were oxygen saturation (aOR 0.78, 95% CI 0.68, 0.89, p < 0.001) and C-reactive protein at admission (aOR: 1.09, 95% CI 1.03, 1.16, p < 0.001). CONCLUSIONS: In hospitalized patients with COVID-19 pneumonia, ivermectin at a single dose for pre-emptively treating Strongyloides stercoralis is not effective in reducing mortality or the need for respiratory support measures.

Strongyloidiasis-related lung involvement: too much of a bad thing.

PURPOSE OF REVIEW: Strongyloidiasis is a soil-transmitted helminthiasis, a neglected tropical disease that affects 300-900 million individuals globally. Strongyloides stercoralis is associated with cutaneous, respiratory, and gastrointestinal clinical manifestations. Chronicity is due to an autoinfective cycle, and host immunosuppression can lead to severe and fatal disease. Lung involvement is significant in severe strongyloidiasis, and Strongyloides has a complex association with a number of lung diseases, which will be discussed in this review. RECENT FINDINGS: The treatment of chronic lung diseases such as asthma and chronic obstructive pulmonary disease with corticosteroids is an important risk factor for Strongyloides hyperinfection syndrome (SHS)/disseminated strongyloidiasis. The use of corticosteroids in the treatment of coronavirus disease 2019 (COVID-19) and potentially COVID-19-induced eosinopenia are risk factors for severe strongyloidiasis. Recent findings have demonstrated a significant immunomodulatory role of Strongyloides in both latent and active pulmonary tuberculosis associated to an impaired immune response and poor outcomes in active pulmonary tuberculosis. SUMMARY: Strongyloides lung involvement is a common finding in severe infection. Prompt recognition of Strongyloides infection as well as prevention of severe disease by screening or presumptive treatment are important goals in order to improve Strongyloides outcomes in at-risk population.

Chronic Strongyloides stercoralis infection increases presence of the Ruminococcus torques group in the gut and alters the microbial proteome.

We explored the impact of chronic Strongyloides stercoralis infection on the gut microbiome and microbial activity in a longitudinal study. At baseline (time-point T0), 42 fecal samples from matched individuals (21 positive for strongyloidiasis and 21 negative) were subjected to microbiome 16S-rRNA sequencing. Those positive at T0 (untreated then because of COVID19 lockdowns) were retested one year later (T1). Persistent infection in these individuals indicated chronic strongyloidiasis: they were treated with ivermectin and retested four months later (T2). Fecal samples at T1 and T2 were subjected to 16S-rRNA sequencing and LC-MS/MS to determine microbial diversity and proteomes. No significant alteration of indices of gut microbial diversity was found in chronic strongyloidiasis. However, the Ruminococcus torques group was highly over-represented in chronic infection. Metaproteome data revealed enrichment of Ruminococcus torques mucin-degrader enzymes in infection, possibly influencing the ability of the host to expel parasites. Metaproteomics indicated an increase in carbohydrate metabolism and Bacteroidaceae accounted for this change in chronic infection. STITCH interaction networks explored highly expressed microbial proteins before treatment and short-chain fatty acids involved in the synthesis of acetate. In conclusion, our data indicate that chronic S. stercoralis infection increases Ruminococcus torques group and alters the microbial proteome.

Clinical Characteristics of Strongyloidiasis during the COVID-19 Pandemic: Systematic Scoping Review.

The clinical impact of Strongyloides stercoralis hyperinfection secondary to immunosuppressive therapy for coronavirus disease 2019 (COVID-19) has been an emerging topic of interest, although characteristics of Strongyloides infection in COVID-19 patients are not yet well characterized. This study summarizes the existing evidence of Strongyloides infection in COVID-19 patients and recommends future areas of research. According to the PRISMA Extension for Scoping Reviews, we performed a search on MEDLINE and EMBASE for articles with keywords including "Strongyloides," "Strongyloidiasis," and "COVID-19" from the inception of these databases to June 5, 2022. A total of 104 articles were found. After excluding duplication and thorough reviews, 11 articles, including two observational studies, one conference abstract, and nine case reports or series, were included. Two observational studies focused on revealing the prevalence of Strongyloides screening in COVID-19 patients and clinical follow-up. Among the included cases, patients were mostly from low- or middle-income countries and suffered from severe or critical COVID-19. Strongyloides hyperinfection and disseminated infection were reported in 60% and 20%, respectively. Interestingly, 40% did not have eosinophilia, a hallmark of parasitic infection, potentially leading to delay in diagnosis of strongyloidiasis. This systematic review summarizes the clinical characteristics of strongyloidiasis in COVID-19 infection. Although further studies to identify risks and precipitants associated with the onset of strongyloidiasis are crucial, increased awareness of the critical condition is warranted.

Strongyloidiasis Hyperinfection Syndrome in COVID-19 Positive Migrants Treated with Corticosteroids.

The aim of this study is to highlight the potentially fatal risk of Strongyloidiasis Hyperinfection Syndrome for hospitalized immigrant patients with moderate to severe COVID-19 disease and undiagnosed Strongyloidiasis. We reviewed electronic medical records of immigrants from 2010 to 2022 and extracted the number of patients with eosinophilia, strongyloidiasis and COVID-19 infection, outpatient and hospitalized. While 885 outpatients were diagnosed with eosinophilia, only 356 (40.2%) were tested for strongyloidiasis and 160 (44.9%) yielded a reactive serology. COVID-19 infection was reported in 6,412 patients. 1135 (17.7%) of these patients sought hospital care. Patients with undiagnosed strongyloidiasis are at risk for a potentially fatal parasitosis if treated with systemic corticosteroids for COVID-19. This supports clinical guidelines in hospital settings for those with severe COVID-19. Strongyloidiasis should be considered by taking a thorough travel or migration history and testing before giving immunosuppressive drugs.

Strongyloidiasis - diagnostic and therapeutic dilemmas in hyperinfection patients: a case series.

The helminth infection caused by Strongyloides stercoralis is widespread in tropical regions, but rare in European countries. Unfamiliarity with the disease and diagnostic obstacles could contribute to its lethal outcome. Frequent use of corticosteroids during the COVID-19 pandemic could increase its significance. The aim of this retrospective descriptive study was to explore disease patterns and discuss clinical dilemmas in patients with S. stercoralis hyperinfection treated at the University Hospital for Infectious Diseases 'Dr. Fran Mihaljevic' in Zagreb, Croatia, between 2010 and 2021. Five out of 22 (22.7%) immunosuppressed patients treated due to strongyloidiasis developed hyperinfection. All patients were male, median 64 years; four were immunosuppressed by corticosteroids (although ileum resection could have been the trigger in one) and one by rituximab. The diagnosis was established after a median of 1.5 months of symptom duration, accidentally in all patients, by visualizing the parasite in the gastric/duodenal mucosa in four cases, and bronchial aspirate in one. All patients were cachectic, four out of five had severe hypoalbuminemia and all suffered secondary bacterial/fungal infection. Despite combined antibiotic, antifungal and antihelmintic therapy, three out of five of the patients died, after failing to clear living parasites from stool samples. We can conclude that significant delays in diagnosis and lack of clinical suspicion were observed among our patients with the most severe clinical presentations of strongyloidiasis. Although being beyond diagnostic recommendations for strongyloidiasis, an early upper gastrointestinal endoscopy with mucosal sample analysis could expedite diagnosis in severe, immunosuppressed patients. The persistence of viable parasites in the stool despite antihelmintic therapy should be further investigated.

Coinfection with Strongyloides and Ascaris in a COVID-19-positive male presenting with acute abdomen: a case report.

Ascaris lumbricoides and Strongyloides stercoralis are soil-transmitted helminthic infections usually seen in people with poor socioeconomic conditions, hygiene and fecal sanitation living in endemic countries. Here, we present a case of coinfection in a COVID-positive older adult male presenting to our facility with symptoms of acute abdomen. Investigative workup guided timely diagnosis of the case. Prompt initiation of antihelminthic drugs together with antibiotics/antivirals for COVID symptoms resulted in favorable outcome in the case. A high index of suspicion on the part of the treating and diagnosing doctor is required in the COVID era. This will help not only in diagnosis but will also give an understanding of the exact pathogenesis for better patient outcome.

Strongyloides Hyperinfection Syndrome among COVID-19 Patients Treated with Corticosteroids.

Widespread use of corticosteroids for COVID-19 treatment has led to Strongyloides reactivation and severe disease in patients from endemic areas. We describe a US patient with COVID-19 and Strongyloides hyperinfection syndrome and review other reported cases. Our findings highlight the need for Strongyloides screening and treatment in high-risk populations.

Strongyloides stercoralis.

Strongyloidiasis has been estimated to affect over 600 million people worldwide. It is caused by Strongyloides stercoralis, a roundworm endemic to the tropics and subtropics, especially areas where sanitation is suboptimal Autochthonous transmission has been documented in rural areas of the USA and Europe. Humans are infected when larvae penetrate the skin or are ingested. Autoinfection, in which larvae generated in the host go on to re-infect the host, leads to a state of chronic asymptomatic infection often with eosinophilia. Hyperinfection syndrome may develop when patients develop immune suppression, due to medications such as corticosteroids or following solid-organ transplantation. Hyperinfection is characterized by exponential increase in parasitic burden, leading to tissue invasion and life-threatening disease and associated bloodstream infections due to enteric organisms. Cases following use of corticosteroids for COVID-19 pneumonia have been described. Strongyloidiasis can be diagnosed by direct visualization of larvae in stool or other body fluids, or by serology. Ivermectin is highly effective in treating the disease. Patients with exposure to endemic areas and those expected to become immune suppressed should be screened and treated before starting immune suppressive agents. Empiric treatment should be considered when timely testing is not readily available.

Time of incubation of agar-plate culture for the diagnosis of Strongyloides stercoralis infection.

PURPOSE: Agar-plate culture (APC) remains the most sensitive parasitological technique for S. stercoralis diagnosis. Although it was first described three decades ago, the time of incubation of the plates is neither a commonly described feature nor usually standardized. The aim of the study was to analyze the required time to detect S. stercoralis larvae in APC. METHODS: A prospective laboratory-based study including all patients with at least one positive APC was performed. The plates were incubated at room temperature for 7 days. Clinical, analytical and parasitological features including results of the direct visualization of the stool (DV) after formalin-ether concentration and time-to-detection (TTD) of the larvae in APC were recorded. RESULTS: A total of 141 samples from 75 patients had a positive APC. In 49 of them (65.3%) three or more stool samples were processed for direct visualization (DV) and APC. Of these 49 patients, 8 (16.3%) were also diagnosed with DV and 41 (83.7%) were diagnosed only with APC. In 38 samples from 23 (30.7%) patients, the TTD was below 2 days, while in 27 samples from 13 (17.3%) patients, the larvae were detected on the 6th and 7th day. CONCLUSION: Direct visualization failed to detect S. stercoralis in most of the patients that were diagnosed with APC. Incubation periods below 2 and 5 days would miss an important percentage of infections. At least 7 days of incubation of the APC are required to detect presumably low-burden chronic infections in non-endemic countries.

Influence of the drugs used in migrant patients with severe acute respiratory syndrome coronavirus 2 and the development of symptomatic strongyloidiasis.

BACKGROUND: The use of dexamethasone in patients infected with Strongyloides stercoralis can cause severe complications. It is necessary to investigate the relationship between coronavirus disease 2019 (COVID-19) and strongyloidiasis infection. METHODS: A retrospective, longitudinal, descriptive study was undertaken to review all patients admitted with a diagnosis of COVID-19 infection at the Complejo Asistencial Universitario de Salamanca, Spain, during 1 March-31 December 2020. RESULTS: A total of 2567 patients received a diagnosis of COVID-19. Eighty-six patients from endemic areas were included. Seven patients had strongyloidiasis. Five patients were female. The mean age (±SD) was 39 (±10.8) y. Six patients were Latin-American and only one patient was from Africa. Six patients had previous symptoms compatible with strongyloidiasis infections. Only three patients received dexamethasone (6 mg once daily) for 10 d. In all cases, the clinical courses of the patients were satisfactory. No patient died or was admitted to the ICU. CONCLUSIONS: Screening programmes using serological techniques should be implemented in COVID-19 patients to prevent strongyloidiasis. Our study suggested that drugs used against COVID-19 in patients with strongyloidiasis did not affect the evolution of the disease. However, more studies are necessary to elucidate the role of dexamethasone in COVID-19 patients infected with Strongyloides.

Dexamethasone and COVID-19: Strategies in Low- and Middle-Income Countries to Tackle Steroid-Related Strongyloides Hyperinfection.

COVID-19 can trigger a systemic inflammatory response that in some cases leads to severe lung involvement, multisystem dysfunction, and death. Dexamethasone therapy, because of its potent anti-inflammatory effects, has been proposed for the management of hospitalized patients with severe COVID-19. The subject of this article is to discuss potential strategies to tackle Strongyloides hyperinfection in hospitalized patients with COVID-19 receiving dexamethasone therapy in low- and middle-income countries. In this context, dexamethasone treatment has been found to be generally safe. However, its use in people coinfected with undetected Strongyloides stercoralis increases the risk for Strongyloides hyperinfection/dissemination a potentially fatal complication. Infection caused by S. stercoralis may remain asymptomatic or with mild symptoms in humans for several years. Early detection and specific treatment prevent a fatal evolution of this complication, but the challenge is to screen before corticosteroid therapy. In some cases, presumptive treatment may be justified. Ivermectin is the gold standard for treatment.

Eosinophilic appendicitis due to Strongyloides stercoralis: a challenging differential diagnosis for clinicians.

A 45-year-old man presents with 48-hour status of high temperature, cough and dyspnoea. In the context of pandemic, the patient is initially diagnosed with COVID-19 syndrome. Later, the laboratory and ultrasound study supported acute appendicitis diagnosis. Appendicectomy was performed. The histopathology study confirmed eosinophilic appendicitis and that a parasitic infection was suspected. The stool sample was positive for Strongyloides stercoralis The diagnosis of a S stercoralis is a rare finding in Spain. S. stercoralis simulates clinical findings of inflammatory bowel disease or eosinophilic gastroenteritis, which may lead to the wrong therapeutic choice. Since in inflammatory diseases corticosteroid treatments are considered the initial choice in many cases, in the case of S. stercoralis infection, the administration of this therapy can be fatal. In Spain, the number of diagnoses is much lower than in the past decade, although it is highly probable that the infection has been underdiagnosed due to low clinical awareness among Spanish population.