Enhancing screening adherence for strongyloides infection in latinx inpatients with COVID-19: a local protocol implementation study

ABSTRACT

Strongyloides stercoralis hyperinfection syndrome has been observed in immunosuppressed coronavirus disease 2019 (COVID-19) patients. Detecting and treating asymptomatic Strongyloides infection in individuals from endemic areas can effectively prevent hyperinfection. Unfortunately, many clinicians are unaware of this neglected infection. Therefore, we aimed to evaluate whether including Strongyloides screening in COVID-19 management protocols would encourage this practice. To accomplish this, we conducted a retrospective single-center study at ‘Hospital Universitario 12 de Octubre’ in Madrid, Spain, comparing two consecutive cohorts. The first cohort comprised all Latinx patients over 18 years old who were admitted for COVID-19 between March 1^st and April 30^th, 2020. The second cohort consisted of Latinx patients admitted between July 1^st and December 31^st, 2020, following an amendment to the COVID-19 management protocol that recommended screening for strongyloidiasis in at-risk patients. We identified 559 and 795 patients in the first and second periods, respectively. The percentage of individuals screened increased significantly from 8.8% to 51.6% after the screening recommendation was included in the protocol (odds ratio [OR] 11.08, 95% confidence interval [CI] 8.01–15.33). In both periods, the screening rate was significantly higher among those receiving immunosuppression than those who did not receive steroids and/or tocilizumab. No other factors influenced the screening rate. In conclusion, including strongyloidiasis screening recommendations in COVID-19 management protocols led to its increased implementation. However, the overall screening rate remained low, emphasizing the need for further efforts to enhance screening practices.

Introduction

Strongyloides stercoralis is a soil-transmitted helminth that is capable of completing its entire life cycle within the human host [1]. As a result, chronic asymptomatic infection can persist for decades, even after individuals have left rural areas of tropical and subtropical regions, where the parasite is endemic [2]. Conditions that lead to host immunosuppression (e.g. steroid use) may promote larval reproduction, so that clinical manifestations and even hyperinfection syndrome can arise long after the initial infection because, in this scenario, the host is reinfected without an environmental stage [3].

Coronavirus disease 2019 (COVID-19) is a respiratory infection caused by the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first identified in December 2019 in Wuhan, China, and subsequently leading to a global pandemic [4]. While most COVID-19 cases follow a mild-to-moderate course, a small proportion of patients develop severe infections characterized by acute respiratory distress syndrome (ARDS) [5]. Due to the hyperinflammatory state associated with the pathogenesis of severe COVID-19 [6], various immunomodulatory therapies have been employed to mitigate this detrimental inflammatory response. These therapies include corticosteroids and the anti-interleukin (IL)-6 receptor monoclonal antibody tocilizumab [7,8].

Cases of Strongyloides hyperinfection have been reported in patients with COVID-19 who are undergoing immunosuppressive treatment [9–11]. Consequently, screening for asymptomatic chronic strongyloidiasis and subsequent treatment with a single dose of ivermectin among infected patients can help prevent the potentially fatal complications of strongyloidiasis [12,13]. As the central region of Spain, where Madrid is located, is not an endemic area for strongyloidiasis, clinicians may not consider the possibility of this infection when treating patients from endemic regions. Some authors have proposed strategies to prevent steroid-associated Strongyloides hyperinfection when prescribing dexamethasone for severe COVID-19 [14,15]. However, to our knowledge, no study has evaluated physician adherence to such approaches.

This study aimed to assess whether including a recommendation for screening chronic asymptomatic Strongyloides infection in COVID-19 management protocols would encourage adopting this practice.

Materials and methods

Study design and population

We conducted a retrospective single-center cohort study at the Hospital Universitario 12 de Octubre (Madrid, Spain), which is a 1,300-bed tertiary-care university-affiliated hospital. Using a review of electronic medical records, we identified all patients over 18 years old who were born in Central and South America, including the Caribbean islands, and were admitted for COVID-19 during the first wave of the pandemic, specifically from March 1^st to April 30^th, 2020.

In March 2020, our hospital implemented a protocol for managing COVID-19, which was periodically updated based on the latest knowledge of the disease. In July 2020 the protocol was amended, recommending Strongyloides stercoralis infection screening for all patients from areas endemic to this parasite. The protocol included a map indicating the endemic countries to help clinicians easily identify at-risk patients (Figure 1) [17].

Figure 1.

Map showing countries where Strongyloidiasis is endemic. Source: European Centre for Disease Prevention and Control (ECDC) [16].

To investigate whether the inclusion of this recommendation in the protocol modified Strongyloides infection screening rates, we identified all Latinx individuals who were admitted for COVID-19 from July 1^st to December 31^st, 2020. Although the protocol recommended screening for all patients coming from Strongyloides endemic areas, we focused our study on patients from Latin America because they represent over 85% of the immigrant population attending our hospital. By narrowing our study to Latinx individuals, we aimed to minimize potential diagnostic suspicion bias, as the intensity of the diagnostic process for neglected diseases could be higher for immigrants from other continents, which are rarely encountered in our daily practice.

The study protocol (reference 20/117) was approved by the Clinical Research Ethics Committee and a waiver of informed consent was granted due to the observational nature of the study design.

Strongyloides screening procedure

The protocol proposed a ‘screen and treat’ strategy. Screening for Strongyloides stercoralis was carried out through serology when requested by the attending clinician. Serum IgG antibodies to Strongyloides stercoralis were detected using a commercial enzyme-linked immunosorbent assay technique (SciMedx® Corporation, Denville, NJ, U.S.A.). A positive result was defined as an optic density (DO) of ≥ 0.2, while a negative result indicated a DO of < 0.2.

The protocol did not recommend stool testing approaches, such as direct vision and agar plate culture as screening techniques. This decision was based on their lower sensitivity, as well as their higher time and resource requirements. Furthermore, concerns regarding the potential transmission of SARS-CoV-2 through aerosolization during sample processing due to the presence of viral particles in feces led to the exclusion of stool handling by laboratory staff [16]. Stool PCR was also not recommended due to its unavailability in our center.

The protocol recommended treatment with a single dose of ivermectin at 200 mcg/kg for cases with positive serology.

Immunomodulatory therapies for COVID-19 treatment

Immunomodulatory therapies for COVID-19 treatment included corticosteroids and tocilizumab. In the initial period analyzed, various corticosteroid dosing regimens were considered, including oral prednisone at doses of 0.5 to 1 mg/kg daily for 5 to 7 days, oral or intravenous (IV) methylprednisolone at 0.5–1 mg/kg daily for 5 to 7 days, or IV methylprednisolone pulses of 125–250 mg for 3 days. In the subsequent period, oral dexamethasone at a dose of 6 mg/day for 10 days was utilized. Tocilizumab was administered as a single IV dose of 400 mg (if body weight <75 kg) or 600 mg (if body weight ≥75 kg).

Statistical analysis

Quantitative data were presented as mean and standard deviation (SD) or median with interquartile range (IQR). Qualitative variables were reported as absolute and relative frequencies. The chi-squared test or Fisher’s exact test was used to compare categorical variables. For continuous variables, the Student’s t-test or Mann-Whitney U-test was employed. Statistical significance was defined as p < 0.05. All significance tests were two-tailed. SPSS v.22.0 (IBM Corporation®, Armonk, NY, U.S.A.) was used for statistical analysis.

Results

A total of 559 Latinx patients were identified during the initial period of the study, and 795 were identified during the second period after the hospital protocol had been modified to include a recommendation for Strongyloides infection screening for the at-risk population. All patients had been admitted for COVID-19, indicating a severe SARS-CoV2 infection that required hospitalization due to pneumonia, respiratory insufficiency, or underlying comorbidities predisposing them to complicated COVID-19. The mean age of the patients was 49.1 (SD ± 12.8) years old in the first period and 48.9 (SD ± 12.9) years old in the second period (p = 0.901). Table 1 displays the comorbidities and demographics of the patients included in both periods. The first period exhibited significantly higher numbers of active smokers and immunosuppressed patients than the second period. No disparities were observed in the distribution of nationalities, as immigrants from Ecuador constituted the largest group admitted in both periods, followed by those from Peru, Colombia, and Bolivia.

Table 1.

Characteristics, immunosuppressive treatment for COVID-19 and strongyloidiasis screening among the included population in each study period.

	First period (n = 559)	Second period (n = 795)	p-value
Characteristics of the population
Age, years (mean, ±SD)	49.1 (±12.8)	48.9 (±12.9)	0.901
Sex, male (n, %)	287 (51.5%)	415 (52.2%)	0.807
Comorbidities (n, %) Active smoking Hypertension Diabetes Obesity Cardiac disease Chronic respiratory disease* Chronic renal disease Cancer HIV Immunosuppression**	25 (4.5%) 70 (12.5%) 69 (12.3%) 94 (16.8%) 6 (1.1%) 56 (10%) 26 (4.7%) 23 (4.1%) 7(1.3%) 20 (3.6%)	16 (2%) 97 (12.2%) 98 (12.3%) 147 (18.5%) 7 (0.9%) 66 (8.3%) 24 (3%) 25 (3.1%) 4 (0.5%) 13 (1.6%)	0.009 0.860 0.993 0.428 0.720 0.278 0.117 0.342 0.217 0.022
Country of origin (n, %) Ecuador Peru Colombia Bolivia Dominican Republic Venezuela Honduras Other countries	174 (31.1%) 133 (23.8%) 67 (12.0%) 45 (8.1%) 35 (6.3%) 27 (4.8%) 25 (4.5%) 53 (9.5%)	276 (34.9%) 136 (17.2%) 98 (12.4%) 87 (11.0%) 55 (7.0%) 37 (4.7%) 41 (5.2%) 60 (7.6%)	0.061
Anti-inflammatory treatment for SARS-COV2 infection
None (n, %) Steroids monotherapy (n, %) Tocilizumab monotherapy (n, %) Steroids + tocilizumab (n, %)	280 (50.4%) 101 (18.2%) 60 (10.8%) 115 (20.7%)	189 (23.8%) 476 (59.9%) 0 130 (16.4%)	<0.001
Screening of Strongyloides stercoralis infection
Patients screened (n, %)	49 (8.8%)	410 (51.6%)	<0.001
Country of origin among those screened (n, %)  Ecuador  Peru  Colombia  Bolivia  Dominican Republic  Venezuela  Honduras  Other countries	18 (36.7%) 12 (24.5%) 8 (16.3%) 3 (6.1%) 2 (4.1%) 2 (4.1%) 2 (4.1%) 2 (4.1%)	151 (37%) 70 (17.2%) 48 (11.8%) 53 (13.0%) 17 (4.2%) 17 (4.2%) 22 (5.4%) 30 (7.4%)	0.714
Median eosinophil count on admission among those screened, cell/mm3	0 cell/mm3	0 cell/mm3	0.654
Positivity of Strongyloides serology among those screened (n, %)	11 (22.4%)	19 (4.6%)	<0.001

SD: standard deviation.

*Including asthma, chronic obstructive pulmonary disease, and sleep obstructive apnea.

**Including solid organ transplant recipients, active treatment for cancer, rheumatologic diseases treated with immunosuppressive drugs, and acquired immunodeficiency syndrome (AIDS).

The percentage of strongyloidiasis screening significantly increased following the implementation of the updated protocol, rising from 8.8% during the initial period to 51.6% during the second period (p < 0.001) (Table 1). This indicates that the odds ratio (OR) of being screened after the protocol modification was 11.08 (95% CI 8.01–15.33). It is important to note that all the screened patients were asymptomatic with respect to Strongyloides infection.

There were no significant differences in the distribution of comorbidities among the screened and non-screened patients in any of the analyzed periods. Table 2 illustrates that the distribution of nationalities was similar between the screened and non-screened individuals in both periods. In the first period, there was a significant difference in the length of hospital stay between those who underwent screening and those who did not (23.6 days [SD ± 21.1] vs. 11.4 [SD ± 10.8] days, p < 0.001). However, this disparity was not observed in the second period, as the length of hospital stay was comparable between the two groups (9.2 days [SD ± 7.8] vs. 8.3 days [SD ± 8.6], p = 0.108).

Table 2.

Comparison between characteristics of screened and non-screened patients during the first and second periods.

	First period			Second period
	Screened (n = 49)	Non-screened (n = 510)	p-value	Screened (n = 410)	Non-screened (n = 385)	p-value
Age (mean, ±SD)	51.7 (±11.9)	48.8 (±12.8)	0.127	50.3 (±12.4)	47.6 (±13.5)	0.003
Comorbidities (n, %) Active smoking Hypertension Diabetes Obesity Cardiac disease Chronic respiratory disease* Chronic renal disease Cancer HIV Immunosuppression**	4 (8.2%) 9 (18.4%) 4 (8.2%) 10 (20.4%) 1 (2.0%) 4 (8.2%) 3 (6.1%) 3 (6.1%) 0 (0%) 2 (4.1%)	45 (8.8%) 61 (12.0%) 65 (12.7%) 84 (16.5%) 5 (1.0%) 52 (10.2%) 23 (4.5%) 20 (3.9%) 7 (1.4%) 18 (3.5%)	1.000 0.196 0.352 0.481 0.425 0.806 0.490 0.443 1.000 0.692	12 (2.9%) 49 (12.0%) 45 (11%) 77 (18.8%) 4 (1.0%) 33 (8.0%) 13 (3.2%) 11 (2.7%) 2 (0.5%) 8 (2.0%)	4 (1.0%) 48 (12.5%) 53 (13.8%) 70 (18.2%) 3 (0.8%) 33 (8.6%) 11 (2.9%) 14 (3.6%) 2 (0.5%) 5 (1.3%)	0.058 0.824 0.232 0.828 1.000 0.790 0.796 0.441 1.000 0.468
Country of origin (n, %) Ecuador Peru Colombia Bolivia Dominican Republic Venezuela Honduras	18 (36.7%) 12 (24.5%) 8 (16.3%) 3 (6.1%) 2 (4.1%) 2 (4.1%) 2 (4.1%)	156 (30.6%) 121 (23.7%) 59 (11.6%) 42 (8.2%) 33 (6.5%) 25 (4.9%) 23 (4.5%)	0.375 0.904 0.327 0.787 0.758 1.000 1.000	151 (37.0%) 70 (17.2%) 48 (11.8%) 53 (13.0%) 17 (4.2%) 17 (4.2%) 22 (5.4%)	125 (32.7%) 66 (17.3%) 50 (13.1%) 34 (8.9%) 38 (9.9%) 20 (5.2%) 19 (5.0%)	0.197 0.979 0.583 0.063 0.001 0.483 0.784
Eosinophil count on admission (mean, ±SD)	63.3 (±358.6)	48.1 (±85.4)	0.770	39.9 (±144.2)	49.2 (±92.7)	0.316
Length of hospital stay, days (mean, ±SD)	23.6 (±21.1)	11.4 (±10.8)	<0.001	9.2 (±7.8)	8.3 (±8.6)	0.108
Anti-inflammatory treatment for COVID-19 (n, %) None Steroids monotherapy Tocilizumab monotherapy Steroids + tocilizumab	4 (8.2%) 9 (18.4%) 8 (16.3%) 28 (57.1%)	276 (54.4%) 92 (18.1%) 52 (10.3%) 87 (17.2%)	<0.001	59 (14.4%) 273 (66.6%) - 78 (19%)	130 (33.8%) 203 (52.7%) - 52 (13.5%)	<0.001

SD: standard deviation.

*Including asthma, chronic obstructive pulmonary disease, and sleep obstructive apnea. **Including solid organ transplant recipients, active treatment for cancer, rheumatologic diseases treated with immunosuppressive drugs, and acquired immunodeficiency syndrome (AIDS).

The screening rate showed a significant increase among patients who received immunosuppressive therapy compared to those who did not receive steroids and/or tocilizumab, as illustrated in Figure 2. In the first period, the screening rate rose from 1.4% in those non-immunosuppressed to 24.3% in patients treated with steroids and tocilizumab (p < 0.001). Similarly, in the second period, a significant increase was observed, with the screening rate escalating from 31.2% in non-immunosuppressed to 57.4% in those treated with steroids (p < 0.001) and reaching 60% among those receiving a combination of steroids and tocilizumab (p < 0.001).

Figure 2.

Proportion of the population screened for Strongyloides stercoralis according to the immunosuppressive therapy received.

No differences were observed in the eosinophil count upon admission between the screened and non-screened individuals in any of the periods (Table 2). Furthermore, among those who underwent screening, the median eosinophil count upon admission was 0 eosinophils/mm³ in both periods (p = 0.654) (Table 1). Only one patient screened during the first period (1/49, 2.0%) and two screened during the second period (2/410, 0.5%) presented significant eosinophilia with values greater than 1000/mm³ (p = 0.288). Notably, all three individuals with elevated eosinophil levels had a positive Strongyloides serology.

Upon analyzing the screening results, it was found that the percentage of positive serology for Strongyloides was 22.4% in the first period, whereas it was 4.6% in the second period (p < 0.001). HTLV I/II serology was performed in 73.3% of the cases with a positive Strongyloides serology, and all results were negative. HIV serology was conducted for all patients diagnosed with strongyloidiasis, but no positive cases were identified. As per the protocol, all Strongyloides-positive patients received treatment with ivermectin. None of the Latinx patients included in the study developed Strongyloides hyperinfection syndrome during their hospitalization.

Discussion

The present study highlights that, within our context, clinicians seldom actively search for Strongyloides stercoralis infection in at-risk patients, with a spontaneous screening rate of less than 10% during the initial period analyzed. However, we have demonstrated that incorporating the recommendation to screen for strongyloidiasis into hospital protocols for managing COVID-19 significantly enhances this practice. In fact, the screening rate increased to 51% during the subsequent period examined. This indicates that implementing the screening recommendation in the clinical protocol resulted in an eleven-fold increase in the likelihood of undergoing screening.

Our study confirms clinicians often lack awareness of this neglected parasitic infection, primarily because it is usually asymptomatic or presents with nonspecific symptoms. Although peripheral eosinophilia may be associated with strongyloidiasis its sensitivity, specificity, and predictive value are poor, especially in predicting hyperinfection syndrome [18,19]. Additionally, eosinopenia, a common laboratory finding in SARS-CoV-2 infection, can further complicate the diagnosis. Eosinopenia is caused by the inhibition of eosinophilic stimulation, apoptosis induced by type 1 interferon, and eosinophil consumption due to eosinophil antiviral actions [20,21]. Approximately 50% to 70% of hospitalized patients with COVID-19 experience eosinopenia [22], which was also observed in our cohort, where the median eosinophil count upon admission among those screened was 0 eosinophils/mm³. Furthermore, the use of steroids can mask eosinophilia, which could otherwise serve as a potential indicator of asymptomatic strongyloidiasis. Therefore, suspicion of this infection should rely on epidemiological factors, such as country of origin or long-term residence in an endemic area, regardless of the duration spent outside such areas, as the infection can persist lifelong [1,2].

The significance of actively searching for asymptomatic Strongyloides infection lies in the fact that severe disease can manifest in immunosuppressed individuals [3]. Consequently, screening for strongyloidiasis has been previously recommended for various groups of immunosuppressed patients, such as transplant recipients or those with inflammatory rheumatic diseases [23,24]. Strongyloides hyperinfection has been linked to the use of steroids, with an average prednisone dose of 40 mg/day [25]. However, cases have been reported within five days of administering prednisone at doses as low as 20 mg/day and even following a single dose of dexamethasone. This has led experts to conclude that hyperinfection syndrome can occur irrespective of the dose, duration, and route of steroid administration [18].

Following the publication of the results from the RECOVERY trial [7], dexamethasone at a daily dose of 6 mg (equivalent to 40 mg of prednisone) became the recommended treatment for patients with SARS-COV2 infection who required supplemental oxygen [26]. As a result, the use of steroids significantly increased among hospitalized COVID-19 patients, as we observed in our cohort. The utilization of steroids, either in monotherapy or in combination with tocilizumab, rose from approximately 40% in the first period to as high as 75% in the second period. This increased steroid use poses a risk for complications related to Strongyloides infection [9–11].

Notably, despite the extremely low percentage of spontaneous screening during the initial period of our study, it was significantly higher among those receiving any form of immunosuppression. Furthermore, following the implementation of the screening recommendations, patients receiving steroids, with or without tocilizumab, were also more frequently tested for asymptomatic strongyloidiasis. This likely reflects clinicians’ increased concern about potential complications in immunosuppressed patients. The longer hospital stays observed in individuals screened during the first period, before the recommendation of routine screening strategies, may represent an indirect indicator of more severe forms of COVID-19 necessitating immunomodulatory therapy. However, it is also possible that these patients were attended to by multiple physicians throughout their prolonged admission, and, at some point, one of them recognized the risk of Strongyloides infection and subsequently ordered serological testing. Other factors that might have prompted clinicians to request Strongyloides serology among Latinx patients, such as country of origin, preexisting comorbidities, or eosinophil count, could not be identified. Therefore, it is crucial to develop tools that facilitate systematic screening.

Unfortunately, despite the improvement in strongyloidiasis screening rates following the inclusion of the recommendation in the protocol, the rates remained lower than expected. Several factors could explain this. Firstly, there may have been less-than-expected protocol dissemination due to the significant workload during the pandemic, which limited the ability to conduct frequent training sessions. Additionally, in the context of a public health emergency, healthcare providers focused their efforts on managing the direct effects of COVID-19 and were less attentive to preventive strategies. Another study has previously highlighted cognitive overload as a significant barrier to screening implementation, as clinicians perceive it as an additional task among numerous competing clinical priorities [27]. Moreover, the perceived rarity of Strongyloides hyperinfection syndrome may also contribute to suboptimal adherence to protocol recommendations. Developing an informatics tool that automatically includes a Strongyloides serology request alongside routine blood tests in at-risk patients (identified through the country of origin recorded in the electronic medical records) could have been beneficial to improve screening rates.

Regarding the prevalence of strongyloidiasis in our cohorts, there was a discrepancy between the two analyzed periods, with a prevalence of 22.5% during the first period compared to 4.6% during the second period. These findings differ from previously reported prevalence rates. A meta-analysis conducted in 2019 found a prevalence of 11.4% among migrants from Latin America and the Caribbean region [28], similar to a recent meta-analysis focusing on immigrants in Spain, which reported a prevalence of 14% among Latinx individuals [29]. Several factors may account for these differences. Firstly, it is possible that those who were instinctively screened during the first period before implementing the recommendations constituted a subgroup of patients with a higher likelihood of being infected. It cannot be ruled out that some of them had chronic gastrointestinal symptoms or cutaneous lesions suggestive of larva currens, although this information was not documented in the medical records. Additionally, we only recorded the eosinophil counts upon admission and not during the entire hospital stay. Therefore, we cannot exclude the possibility that those who were screened had elevated eosinophil count at some point during their hospitalization, prompting the attending physician to request serology. Furthermore, during the second period, some patients may have received prior treatment with ivermectin during the summer of 2020, which could have led to a decrease in the overall percentage of positive serology results. This treatment may have been initiated either after a positive serology was detected during contact with the healthcare system or as a result of self-administered treatment, influenced by the widespread media coverage of studies suggesting the effectiveness of ivermectin against SARS-CoV-2 [30,31]. Moreover, the more frequent use of immunosuppressive therapies during the second period could have impacted the sensitivity of serology testing if screening was performed while patients were under these treatments. Finally, it is challenging to determine the true percentage of positive cases, since the entire cohort was not screened in either period.

Although no cases of Strongyloides hyperinfection were reported in our cohort, it is possible that they were underdiagnosed. Some symptoms of hyperinfection, such as pulmonary infiltrates and ARDS, can be challenging to distinguish from those seen in patients with severe COVID-19. In our retrospective review, we identified at least two non-screened patients who died in the Intensive Care Unit (ICU), and the possibility of strongyloidiasis hyperinfection could not be excluded in their cases. One patient had ARDS with 1,000 eosinophils/mm³ in the bronchoalveolar lavage, while the other presented with ARDS, gram-negative sepsis, and 1,700 eosinophils/mm³ in peripheral blood. However, even with a proper diagnosis, the mortality rate for complicated strongyloidiasis is high, reaching 60% [23]. Therefore, the most proactive approach to mitigate the risk of iatrogenic strongyloidiasis hyperinfection is to address the infection in asymptomatic individuals before initiating immunosuppressive therapy, particularly with steroids.

In our study, we implemented a ‘screen and treat’ strategy for strongyloidiasis. However, the availability of serology testing may be limited, requiring practitioners to send samples to reference centers, resulting in delays in obtaining results. A recent survey assessing strongyloidiasis screening in Spain during the SARS-CoV-2 pandemic found that less than 35% of centers had serological techniques available in their laboratories [32]. To overcome this limitation, hospital protocols can adapt their recommendations based on resource availability and propose preemptive treatment with ivermectin, an effective and well-tolerated drug, for patients at risk of Strongyloides infection, considering their epidemiological factors. This approach can be applied universally or specifically target the subgroup of patients receiving corticosteroids or other immunosuppressive drugs, as suggested by other expert groups [14,15]. It would be valuable to compare the different strategies in terms of adherence and cost-effectiveness in future studies to determine the optimal screening approach. Notably, a previous study concluded that presumptive treatment for Strongyloides infection in all immunosuppressed migrants from endemic areas could be a cost-saving strategy, but the model has yet to be prospectively validated [33].

Our study has several limitations that need to be considered. Firstly, the retrospective design introduced the possibility of missing information, as acknowledged in the discussion. Furthermore, our analysis was conducted retrospectively after the peak influx of COVID-19 patients had subsided, which limited our ability to precisely assess the reasons for the low adherence to the protocol recommendations during the second period. It would have been valuable to include a subgroup of physicians in focus group sessions to explore the barriers and facilitators to screening performance. Lastly, the unavailability of stored serum samples from ICU-admitted patients with suspected Strongyloides hyperinfection syndrome prevented us from confirming this hypothesis. Confirming such cases would have provided stronger evidence regarding the importance of screening to prevent potentially life-threatening complications of Strongyloides infection.

In conclusion, including strongyloidiasis screening recommendations in COVID-19 management protocols has shown a significant improvement in this practice. However, the overall screening rates remained lower than anticipated, highlighting the ongoing neglect of this parasitic infection. It is imperative to undertake urgent efforts to increase clinicians’ awareness of the potential complications associated with Strongyloides infection and to enhance the screening performance, accordingly.

Contributions

MAPJA, IL, ML, and FLM proposed the study. MAPJA, MDC, and BDD designed the analysis. All the authors contributed to data collection. APA oversaw the performance of the microbiological assays. MAPJA, MDC, and BDD performed the analyses. MAPJA, MDC, BDD, JH, and AL interpreted data. MAPJA wrote the manuscript. All the authors accomplished a critical review of the manuscript and approved the final version. MAPJA had full access to the data and acted as a guarantor for the report.

Correction Statement

This article has been corrected with minor changes. These changes do not impact the academic content of the article.

Funding Statement

This work was supported by Instituto de Salud Carlos III, Ministry of Science and Innovation, Spain (COVID-19 call COV20/00181) — co-financed by the European Development Regional Fund A Way to achieve Europe. IL is supported by “Centro de Excelencia Severo Ochoa 2019-2023” Program (CEX2018-000806-S), from the Spanish Ministry of Science and Innovation and State Research Agency.

Disclosure statement

No potential conflict of interest was reported by the author(s).