Relationship between Helicobacter pylori infection and risk of metabolic dysfunction-associated steatotic liver disease: An updated meta-analysis.

BACKGROUND: Recent observational studies examining the association between Helicobacter pylori infection and the risk of metabolic dysfunction-associated steatotic liver disease (MASLD) have reported conflicting results. We performed a meta-analysis to quantify the magnitude of the association between H. pylori infection and the risk of MASLD. METHODS: We systematically searched three large electronic databases to identify eligible observational studies (published up to 30 November 2023) in which liver biopsy, imaging methods or blood-based biomarkers/scores were used for diagnosing MASLD. Data from selected studies were extracted, and meta-analysis was performed using common and random-effects modelling. Statistical heterogeneity among published studies, subgroup analyses, meta-regression analyses and publication bias were assessed. RESULTS: A total of 28 observational studies (24 cross-sectional and 4 longitudinal studies) were identified, including 231 291 middle-aged individuals of predominantly Asian ethnicity (~95%). Meta-analysis of cross-sectional studies showed that H. pylori infection was significantly associated with a small increase in the risk of prevalent MASLD (n = 24 studies; random-effects odds ratio 1.11, 95% CI 1.05-1.18; I2 = 63%). Meta-analysis of data from longitudinal studies showed that H. pylori infection was significantly associated with an increased risk of developing incident MASLD over a mean 5-year follow-up (n = 4 studies; random-effects odds ratio 1.20, 95%CI 1.08-1.33; I2 = 44%). Sensitivity analyses did not modify these results. The funnel plot did not reveal any significant publication bias. CONCLUSIONS: H. pylori infection is associated with a mildly increased risk of prevalent and incident MASLD. Further well-designed prospective and mechanistic studies are required to better decipher the complex link between H. pylori infection and the risk of MASLD.

Evaluation of the accuracy of a multi-infection screening test based on a multiplex immunoassay targeting imported diseases common in migrant populations.

BACKGROUND: We aimed to evaluate the performance of a novel multiplex serological assay, able to simultaneously detect IgG of six infections, as a screening tool for imported diseases in migrants. METHODS: Six panels of 40 (n = 240) anonymized serum samples with confirmed infections were used as positive controls to assess the multiplex assay's sensitivity. One panel of 40 sera from non-infected subjects was used to estimate the seropositivity cutoffs, and 32 non-infected sera were used as negative controls to estimate each serology's sensitivity and specificity. The multi-infection screening test was validated in a prospective cohort of 48 migrants from endemic areas. The sensitivity of the Luminex assay was calculated as the proportion of positive results over all positive samples identified by reference tests. The specificity was calculated using 32 negative samples. Uncertainty was quantified with 95 % confidence intervals using receiver operating characteristic analyses. RESULTS: The sensitivity/specificity were 100 %/100 % for HIV (gp41 antigen), 97.5 %/100 % for Hepatitis B virus (HBV-core antigen), 100 %/100 % for Hepatitis C virus (HCV-core antigen), 92.5 %/90.6 % for strongyloidiasis [31-kDa recombinant antigen (NIE)], 97.5 %/100 % for schistosomiasis (combined serpin Schistosoma mansoni and S.haematobium antigens) and 95 %/90.6 % for Chagas disease [combined Trypanosoma cruzi kinetoplastid membrane protein-11 (KMP11) and paraflagellar rod proteins 2 (PFR2) antigens]. In the migrant cohort, antibody response to the combination of the T.cruzi antigens correctly identified 100 % individuals, whereas HBV-core antigen correctly identified 91.7 % and Strongyloides-NIE antigen 86.4 %. CONCLUSIONS: We developed a new, robust and accurate 8-plex Luminex assay that could facilitate the implementation of screening programmes targeting migrant populations.

Progress towards the implementation of control programmes for strongyloidiasis in endemic areas: estimation of number of adults in need of ivermectin for strongyloidiasis.

The World Health Organization has started a process to issue guidelines for the control of strongyloidiasis. The guidelines might recommend to implement preventive chemotherapy (PC) at community level (i.e. to all individuals above 5 years of age), over a defined prevalence threshold. We previously estimated the number of school-age children (SAC) who would need PC. Here we estimate the number of people above 15 years of age who might be included in PC for strongyloidiasis. Based on previous Strongyloides prevalence estimates and on countries' age distribution, we retrieved the number of adults in need of PC. We then subtracted the number of people already involved in ivermectin mass distribution for the elimination of onchocerciasis and lymphatic filariasis and people living in countries where Loa loa is endemic. The number of adults to be involved in PC was estimated at 905.4 (95% confidence interval (CI): 520.6-1177.2), 660.2 (95% CI: 512.7-1214.9), and 512.1 (95% CI: 276-719.4) million people, when the strongyloidiasis prevalence threshold for implementing PC was set to 10%, 15% and 20%, respectively. Estimates at country level are also provided.These estimates might help endemic countries wishing to implement PC for strongyloidiasis to allocate resources to include adults in addition to SAC in control programmes. This article is part of the Theo Murphy meeting issue 'Strongyloides: omics to worm-free populations'.

Human strongyloidiasis: complexities and pathways forward.

Strongyloidiasis is a World Health Organization neglected tropical disease usually caused by Strongyloides stercoralis, a parasitic worm with a complex life cycle. Globally, 300-600 million people are infected through contact with fecally contaminated soil. An autoinfective component of the life cycle can lead to chronic infection that may be asymptomatic or cause long-term symptoms, including malnourishment in children. Low larval output can limit the sensitivity of detection in stool, with serology being effective but less sensitive in immunocompromise. Host immunosuppression can trigger catastrophic, fatal hyperinfection/dissemination, where large numbers of larvae pierce the bowel wall and disseminate throughout the organs. Stable disease is effectively treated by single-dose ivermectin, with disease in immunocompromised patients treated with multiple doses. Strategies for management include raising awareness, clarifying zoonotic potential, the development and use of effective diagnostic tests for epidemiological studies and individual diagnosis, and the implementation of treatment programs with research into therapeutic alternatives and medication safety.

Malaria parasite prevalence among migrants: a systematic review and meta-analysis.

BACKGROUND: Asymptomatic malaria infections are highly prevalent in endemic areas. OBJECTIVES: This systematic review aimed to estimate the pooled prevalence of malaria parasites in migrants screened in non-endemic areas. DATA SOURCES: MEDLINE-Ovid, EMBASE, Web of Science, Global Health, Lilacs, Cochrane, and MedRxiv. STUDY ELIGIBILITY CRITERIA: Cross-sectional studies and observational prospective or retrospective cohort studies conducted in Europe, USA, Canada, Australia, or New Zealand regardless of language or publication status. Studies should include prevalence data on malaria in migrants that were recruited through a systematic screening approach. We excluded studies where people were tested because of malaria symptoms. PARTICIPANTS: Migrant individuals exposed to malaria infection ASSESSMENT OF RISK OF BIAS: A standardized and validated appraisal instrument was used for studies reporting prevalence data (Joanna Briggs Institute Manual for Evidence Synthesis). METHODS OF DATA SYNTHESIS: Pooled estimates of the parasite prevalence by PCR, microscopy, and rapid diagnostic test (RDT) were calculated with a random-effects model. Heterogeneity was explored by stratification by age, region of origin, period of study, and quality of studies. RESULTS: Of 1819 studies retrieved, 23 studies were included with in total 4203 participant PCR data, 3186 microscopy and 4698 RDT data, respectively. Migrants from sub-Saharan Africa had a malaria parasite prevalence of 8.3% (95% CI 5.1-12.2) by PCR, 4.3% (1.5-8.2) by RDT, and 3.1% (0.7-6.8) by microscopy. For migrants from Asia and Latin America, the prevalence with PCR was 0% (0.0-0.08) and 0.4% (0.0-1.8), respectively. Migrants from the Central African Region had the highest PCR prevalence (9.3% [6.0-13.0]), followed by West African migrants (2.0% [0.0-7.7]). Restricting the analysis to sub-Saharan Africa migrants arriving to the host country within the previous year, the PCR-based prevalence was 11.6% (6.9-17.4). CONCLUSION: We provide estimates on the malaria parasite prevalence in migrants in non-endemic setting. Despite heterogeneity between settings, these findings can contribute to inform screening strategies and guidelines targeting malaria in migrants.

A multi-country analysis of COVID-19 hospitalizations by vaccination status.

BACKGROUND: Individuals vaccinated against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), when infected, can still develop disease that requires hospitalization. It remains unclear whether these patients differ from hospitalized unvaccinated patients with regard to presentation, coexisting comorbidities, and outcomes. METHODS: Here, we use data from an international consortium to study this question and assess whether differences between these groups are context specific. Data from 83,163 hospitalized COVID-19 patients (34,843 vaccinated, 48,320 unvaccinated) from 38 countries were analyzed. FINDINGS: While typical symptoms were more often reported in unvaccinated patients, comorbidities, including some associated with worse prognosis in previous studies, were more common in vaccinated patients. Considerable between-country variation in both in-hospital fatality risk and vaccinated-versus-unvaccinated difference in this outcome was observed. CONCLUSIONS: These findings will inform allocation of healthcare resources in future surges as well as design of longer-term international studies to characterize changes in clinical profile of hospitalized COVID-19 patients related to vaccination history. FUNDING: This work was made possible by the UK Foreign, Commonwealth and Development Office and Wellcome (215091/Z/18/Z, 222410/Z/21/Z, 225288/Z/22/Z, and 220757/Z/20/Z); the Bill & Melinda Gates Foundation (OPP1209135); and the philanthropic support of the donors to the University of Oxford's COVID-19 Research Response Fund (0009109). Additional funders are listed in the "acknowledgments" section.

Evaluation of IL-35, as a Possible Biomarker for Follow-Up after Therapy, in Chronic Human Schistosoma Infection.

The host response to helminth infections is characterized by systemic and tissue-related immune responses that play a crucial role in pathological diseases. Recently, experimental studies have highlighted the role of regulatory T (Tregs) and B (Bregs) cells with secreted cytokines as important markers in anti-schistosomiasis immunity. We investigated the serical levels of five cytokines (TNFα, IFN-γ, IL-4, IL-10 and IL-35) in pre- and post-treatment samples from chronic Schistosoma infected patients to identify potential serological markers during follow-up therapy. Interestingly, we highlighted an increased serum level of IL-35 in the pre-therapy samples (median 439 pg/mL for Schistosoma haematobium and 100.5 pg/mL for Schistsoma mansoni infected patients) compared to a control group (median 62 pg/mL and 58 pg/mL, respectively, p ≤ 0.05), and a significantly lower concentration in post-therapy samples (181 pg/mL for S. haematobium and 49.5 pg/mL for S. mansoni infected patients, p ≤ 0.05). The present study suggests the possible role of IL-35 as a novel serological biomarker in the evaluation of Schistosoma therapy follow-up.

Humoral Effect of SARS-CoV-2 mRNA vaccination with booster dose in solid tumor patients with different anticancer treatments.

Introduction: Cancer patients are at risk for serious complications in case of SARS-CoV-2 infection. In these patients SARS-CoV-2 vaccination is strongly recommended, with the preferential use of mRNA vaccines. The antibody response in cancer patients is variable, depending on the type of cancer and antitumoral treatment. In solid tumor patients an antibody response similar to healthy subjects has been confirmed after the second dose. Only few studies explored the duration of immunization after the two doses and the effect of the third dose. Methods: In our study we explored a cohort of 273 solid tumor patients at different stages and treated with different anticancer therapies. Results and Discussion: Our analysis demonstrated that the persistence of the neutralizing antibody and the humoral response after the booster dose of vaccine was not dependent on either the tumor type, the stage or type of anticancer treatment.

Two-Year Cohort Study of SARS-CoV-2, Verona, Italy, 2020‒2022.

We performed a follow-up of a previously reported SARS-CoV-2 prevalence study (April‒May 2020) in Verona, Italy. Through May 2022, only <1.1% of the city population had never been infected or vaccinated; 8.8% was the officially reported percentage. Limiting protection measures and vaccination boosters to elderly and frail persons seems justified.

Subjects who developed SARS-CoV-2 specific IgM after vaccination show a longer humoral immunity and a lower frequency of infection.

BACKGROUND: We have previously shown that eliciting SARS-CoV-2-specific IgM after vaccination is associated with higher levels of SARS-CoV-2 neutralizing IgG. This study aims to assess whether IgM development is also associated with longer-lasting immunity. METHODS: We analysed anti-SARS-CoV-2 spike protein IgG and IgM (IgG-S, IgM-S), and anti-nucleocapsid IgG (IgG-N) in 1872 vaccinees at different time points: before the first dose (D1; w0), before the second dose (D2; w3) at three (w6) and 23 weeks (w29) after D2; moreover, 109 subjects were further tested at the booster dose (D3, w44), at 3 weeks (w47) and 6 months (w70) after D3. Two-level linear regression models were used to evaluate the differences in IgG-S levels. FINDINGS: In subjects who had no evidence of a previous infection at D1 (non-infected, NI), IgM-S development after D1 and D2 was associated with higher IgG-S levels at short (w6, p < 0.0001) and long (w29, p < 0.001) follow-up. Similar IgG-S levels were observed after D3. The majority (28/33, 85%) of the NI subjects who had developed IgM-S in response to vaccination did not experience infection. INTERPRETATION: The development of anti-SARS-CoV-2 IgM-S following D1 and D2 is associated with higher IgG-S levels. Most individuals who developed IgM-S never became infected, suggesting that IgM elicitation may be associated with a lower risk of infection. FUNDING: "Fondi Ricerca Corrente" and "Progetto Ricerca Finalizzata" COVID-2020 (Italian Ministry of Health); FUR 2020 Department of Excellence 2018-2022 (MIUR, Italy); the Brain Research Foundation Verona.

Monkeypox 2022 outbreak in non-endemic countries: Open questions relevant for public health, nonpharmacological intervention and literature review.

Starting from mid-May 2022, cases of human monkeypox started to rise in several non-endemic countries. By mid-July, more than 17000 confirmed/suspect cases have been reported by at least 82 countries worldwide, with a regular incremental trend. In order to contain the disease diffusion, risk evaluation is crucial to undertake informed decisions and effective communication campaigns. However, since orthopoxvirus infections so far have attracted low attention, due to the eradication of smallpox 40 years ago, and to the confinement of human monkeypox almost exclusively to endemic areas, several unresolved issues concerning natural history, ecology and pathogenesis remain. To this respect, we identified some open questions and reviewed the relevant literature on monkeypoxvirus and/or related orthopoxviruses. The results will be discussed in the perspective of their relevance to public health decisions, particularly those related to non-pharmacological interventions.

STArS (STrain-Amplicon-Seq), a targeted nanopore sequencing workflow for SARS-CoV-2 diagnostics and genotyping.

Diagnostic tests based on reverse transcription-quantitative polymerase chain reaction (RT-qPCR) are the gold standard approach to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection from clinical specimens. However, unless specifically optimized, this method is usually unable to recognize the specific viral strain responsible of coronavirus disease 2019, a crucial information that is proving increasingly important in relation to virus spread and treatment effectiveness. Even if some RT-qPCR commercial assays are currently being developed for the detection of viral strains, they focus only on single/few genetic variants that may not be sufficient to uniquely identify a specific strain. Therefore, genome sequencing approaches remain the most comprehensive solution for virus genotyping and to recognize viral strains, but their application is much less widespread due to higher costs. Starting from the well-established ARTIC protocol coupled to nanopore sequencing, in this work, we developed STArS (STrain-Amplicon-Seq), a cost/time-effective sequencing-based workflow for both SARS-CoV-2 diagnostics and genotyping. A set of 10 amplicons was initially selected from the ARTIC tiling panel, to cover: (i) all the main biologically relevant genetic variants located on the Spike gene; (ii) a minimal set of variants to uniquely identify the currently circulating strains; (iii) genomic sites usually amplified by RT-qPCR method to identify SARS-CoV-2 presence. PCR-amplified clinical samples (both positive and negative for SARS-CoV-2 presence) were pooled together with a serially diluted exogenous amplicon at known concentration and sequenced on a MinION device. Thanks to a scoring rule, STArS had the capability to accurately classify positive samples in agreement with RT-qPCR results, both at the qualitative and quantitative level. Moreover, the method allowed to effectively genotype strain-specific variants and thus also return the phylogenetic classification of SARS-CoV-2-postive samples. Thanks to the reduced turnaround time and costs, the proposed approach represents a step towards simplifying the clinical application of sequencing for viral genotyping, hopefully aiding in combatting the global pandemic.

The diagnosis of human and companion animal Strongyloides stercoralis infection: Challenges and solutions. A scoping review.

Strongyloidiasis is the infection caused by soil-transmitted nematodes of Strongyloides species, infecting humans and some animals. Strongyloides stercoralis is the species with most clinical and epidemiological relevance in humans and dogs, due to its high prevalence and its capacity of inducing a life-threatening hyperinfection. Diagnosis of strongyloidiasis is challenging, due to the absence of a single reference standard test with high sensitivity and specificity, which also hampers the estimation of the accuracy of other diagnostic tests. In this chapter, we review the deployment and performance of the parasitological, immunological, molecular tests for the diagnosis of strongyloidiasis in humans and in dogs. Further, we comment the available evidence from genotyping studies that have addressed the zoonotic potential of S. stercoralis. Finally, we discuss the use of different diagnostic methods in relation to the purpose (i.e., screening, individual diagnosis, inclusion in a clinical trial) and the setting (endemic/non-endemic areas) and report the accuracy figures reported by systematic reviews on either parasitological, serological or molecular techniques published in literature.

Identification of miRNAs of Strongyloides stercoralis L1 and iL3 larvae isolated from human stool.

Strongyloidiasis is a neglected tropical disease caused by the soil-transmitted nematode by Strongyloides stercoralis, that affects approximately 600 million people worldwide. In immunosuppressed individuals disseminated strongyloidiasis can rapidly lead to fatal outcomes. There is no gold standard for diagnosing strongyloidiasis, and infections are frequently misdiagnosed. A better understanding of the molecular biology of this parasite can be useful for example for the discovery of potential new biomarkers. Interestingly, recent evidence showed the presence of small RNAs in Strongyloididae, but no data was provided for S. stercoralis. In this study, we present the first identification of miRNAs of both L1 and iL3 larval stages of S. stercoralis. For our purpose, the aims were: (i) to analyse the miRNome of L1 and iL3 S. stercoralis and to identify potential miRNAs of this nematode, (ii) to obtain the mRNAs profiles in these two larval stages and (iii) to predict potential miRNA target sites in mRNA sequences. Total RNA was isolated from L1 and iL3 collected from the stool of 5 infected individuals. For the miRNAs analysis, we used miRDeep2 software and a pipeline of bio-informatic tools to construct a catalog of a total of 385 sequences. Among these, 53% were common to S. ratti, 19% to S. papillosus, 1% to Caenorhabditis elegans and 44% were novel. Using a differential analysis between the larval stages, we observed 6 suggestive modulated miRNAs (STR-MIR-34A-3P, STR-MIR-8397-3P, STR-MIR-34B-3P and STR-MIR-34C-3P expressed more in iL3, and STR-MIR-7880H-5P and STR-MIR-7880M-5P expressed more in L1). Along with this analysis, we obtained also the mRNAs profiles in the same samples of larvae. Multiple testing found 81 statistically significant mRNAs of the total 1553 obtained (FDR < 0.05; 32 genes expressed more in L1 than iL3; 49 genes expressed more in L3 than iL1). Finally, we found 33 predicted mRNA targets of the modulated miRNAs, providing relevant data for a further validation to better understand the role of these small molecules in the larval stages and their valuein clinical diagnostics.

SARS-CoV-2 vaccination elicits unconventional IgM specific responses in naïve and previously COVID-19-infected individuals.

BACKGROUND: Currently, evaluation of the IgG antibodies specific for the SARS-CoV-2 Spike protein following vaccination is used worldwide to estimate vaccine response. Limited data are available on vaccine-elicited IgM antibodies and their potential implication in immunity to SARS-CoV-2. METHODS: We performed a longitudinal study to quantify anti-S SARS-CoV-2 IgG and IgM (IgG-S and IgM-S) in health care worker (HCW) recipients of the BNT162b2 vaccine. Samples were collected before administration (T0), at the second dose (T1) and three weeks after T1 (T2). The cohort included 1584 immunologically naïve to SARS-CoV-2 (IN) and 289 with history of previous infection (PI). FINDINGS: IN showed three patterns of responses: (a) IgG positive/IgM negative (36.1%), (b) coordinated IgM-S/IgG-S responses appearing at T1 (37.4%) and (c) IgM appearing after IgG (26.3%). Coordinated IgM-S/IgG-S responses were associated with higher IgG titres. In IgM-S positive PI, 64.5% were IgM-S positive before vaccination, whereas 32% and 3.5% developed IgM-S after the first and second vaccine dose, respectively. IgM-S positive sera had higher pseudovirus neutralization titres compared to the IgM-S negative. INTERPRETATION: Coordinated expression of IgG-S and IgM-S after vaccination was associated with a significantly more efficient response in both antibody levels and virus-neutralizing activity. The unconventional IgG-S positive/IgM-S negative responses may suggest a recruitment of cross coronaviruses immunity by vaccination, warranting further investigation. FUNDING: Italian Ministry of Health under "Fondi Ricerca Corrente"- L1P5 and "Progetto Ricerca Finalizzata COVID-2020-12371675"; FUR 2020 Department of Excellence 2018-2022, MIUR, Italy; The Brain Research Foundation Verona.

Different decay of antibody response and VOC sensitivity in naïve and previously infected subjects at 15 weeks following vaccination with BNT162b2.

BACKGROUND: COVID-19 vaccines have demonstrated effectiveness in reducing SARS-CoV-2 mild and severe outcomes. In vaccinated subjects with SARS-CoV-2 history, RBD-specific IgG and pseudovirus neutralization titers were rapidly recalled by a single BTN162b2 vaccine dose to higher levels than those in naïve recipients after the second dose, irrespective of waning immunity. In this study, we inspected the long-term kinetic and neutralizing responses of S-specific IgG induced by two administrations of BTN162b2 vaccine in infection-naïve subjects and in subjects previously infected with SARS-CoV-2. METHODS: Twenty-six naïve and 9 previously SARS-CoV-2 infected subjects during the second wave of the pandemic in Italy were enrolled for this study. The two groups had comparable demographic and clinical characteristics. By means of ELISA and pseudotyped-neutralization assays, we investigated the kinetics of developed IgG-RBD and their neutralizing activity against both the ancestral D614G and the SARS-CoV-2 variants of concern emerged later, respectively. The Wilcoxon matched pair signed rank test and the Kruskal-Wallis test with Dunn's correction for multiple comparison were applied when needed. RESULTS: Although after 15 weeks from vaccination IgG-RBD dropped in all participants, naïve subjects experienced a more dramatic decline than those with previous SARS-CoV-2 infection. Neutralizing antibodies remained higher in subjects with SARS-CoV-2 history and conferred broad-spectrum protection. CONCLUSIONS: These data suggest that hybrid immunity to SARS-CoV-2 has a relevant impact on the development of IgG-RBD upon vaccination. However, the rapid decay of vaccination-elicited antibodies highlights that the administration of a third dose is expected to boost the response and acquire high levels of cross-neutralizing antibodies.

High-dose ivermectin for early treatment of COVID-19 (COVER study): a randomised, double-blind, multicentre, phase II, dose-finding, proof-of-concept clinical trial.

High concentrations of ivermectin demonstrated antiviral activity against SARS-CoV-2 in vitro. The aim of this study was to assess the safety and efficacy of high-dose ivermectin in reducing viral load in individuals with early SARS-CoV-2 infection. This was a randomised, double-blind, multicentre, phase II, dose-finding, proof-of-concept clinical trial. Participants were adults recently diagnosed with asymptomatic/oligosymptomatic SARS-CoV-2 infection. Exclusion criteria were: pregnant or lactating women; CNS disease; dialysis; severe medical condition with prognosis <6 months; warfarin treatment; and antiviral/chloroquine phosphate/hydroxychloroquine treatment. Participants were assigned (ratio 1:1:1) according to a randomised permuted block procedure to one of the following arms: placebo (arm A); single-dose ivermectin 600 µg/kg plus placebo for 5 days (arm B); and single-dose ivermectin 1200 µg/kg for 5 days (arm C). Primary outcomes were serious adverse drug reactions (SADRs) and change in viral load at Day 7. From 31 July 2020 to 26 May 2021, 32 participants were randomised to arm A, 29 to arm B and 32 to arm C. Recruitment was stopped on 10 June because of a dramatic drop in cases. The safety analysis included 89 participants and the change in viral load was calculated in 87 participants. No SADRs were registered. Mean (S.D.) log10 viral load reduction was 2.9 (1.6) in arm C, 2.5 (2.2) in arm B and 2.0 (2.1) in arm A, with no significant differences (P = 0.099 and 0.122 for C vs. A and B vs. A, respectively). High-dose ivermectin was safe but did not show efficacy to reduce viral load.