A genome sequence for Biomphalaria pfeifferi, the major vector snail for the human-infecting parasite Schistosoma mansoni.

BACKGROUND: Biomphalaria pfeifferi is the world's most widely distributed and commonly implicated vector snail species for the causative agent of human intestinal schistosomiasis, Schistosoma mansoni. In efforts to control S. mansoni transmission, chemotherapy alone has proven insufficient. New approaches to snail control offer a way forward, and possible genetic manipulations of snail vectors will require new tools. Towards this end, we here offer a diverse set of genomic resources for the important African schistosome vector, B. pfeifferi. METHODOLOGY/PRINCIPAL FINDINGS: Based largely on PacBio High-Fidelity long reads, we report a genome assembly size of 772 Mb for B. pfeifferi (Kenya), smaller in size than known genomes of other planorbid schistosome vectors. In a total of 505 scaffolds (N50 = 3.2Mb), 430 were assigned to 18 large linkage groups inferred to represent the 18 known chromosomes, based on whole genome comparisons with Biomphalaria glabrata. The annotated B. pfeifferi genome reveals a divergence time of 3.01 million years with B. glabrata, a South American species believed to be similar to the progenitors of B. pfeifferi which undertook a trans-Atlantic colonization < five million years ago. CONCLUSIONS/SIGNIFICANCE: The genome for this preferentially self-crossing species is less heterozygous than related species known to be preferential out-crossers; its smaller genome relative to congeners may similarly reflect its preference for selfing. Expansions of gene families with immune relevance are noted, including the FReD gene family which is far more similar in its composition to B. glabrata than to Bulinus truncatus, a vector for Schistosoma haematobium. Provision of this annotated genome will help better understand the dependencies of trematodes on snails, enable broader comparative insights regarding factors contributing to susceptibility/ resistance of snails to schistosome infections, and provide an invaluable resource with respect to identifying and manipulating snail genes as potential targets for more specific snail control programs.

A randomized, controlled Phase 1b trial of the Sm-TSP-2 Vaccine for intestinal schistosomiasis in healthy Brazilian adults living in an endemic area.

BACKGROUND: Recombinant Schistosoma mansoni Tetraspanin-2 formulated on Alhydrogel (Sm-TSP-2/Alhydrogel) is being developed to prevent intestinal and hepatic disease caused by S. mansoni. The tegumentary Sm-TSP-2 antigen was selected based on its unique recognition by cytophilic antibodies in putatively immune individuals living in areas of ongoing S. mansoni transmission in Brazil, and preclinical studies in which vaccination with Sm-TSP-2 protected mice following infection challenge. METHODS: A randomized, observer-blind, controlled, Phase 1b clinical trial was conducted in 60 healthy adults living in a region of Brazil with ongoing S. mansoni transmission. In each cohort of 20 participants, 16 were randomized to receive one of two formulations of Sm-TSP-2 vaccine (adjuvanted with Alhydrogel only, or with Alhydrogel plus the Toll-like receptor-4 agonist, AP 10-701), and 4 to receive Euvax B hepatitis B vaccine. Successively higher doses of antigen (10 µg, 30 µg, and 100 µg) were administered in a dose-escalation fashion, with progression to the next dose cohort being dependent upon evaluation of 7-day safety data after all participants in the preceding cohort had received their first dose of vaccine. Each participant received 3 intramuscular injections of study product at intervals of 2 months and was followed for 12 months after the third vaccination. IgG and IgG subclass antibody responses to Sm-TSP-2 were measured by qualified indirect ELISAs at pre- and post-vaccination time points through the final study visit. RESULTS: Sm-TSP-2/Alhydrogel administered with or without AP 10-701 was well-tolerated in this population. The most common solicited adverse events were mild injection site tenderness and pain, and mild headache. No vaccine-related serious adverse events or adverse events of special interest were observed. Groups administered Sm-TSP-2/Alhydrogel with AP 10-701 had higher post-vaccination levels of antigen-specific IgG antibody. A significant dose-response relationship was seen in those administered Sm-TSP-2/Alhydrogel with AP 10-701. Peak anti-Sm-TSP-2 IgG levels were observed approximately 2 weeks following the third dose, regardless of Sm-TSP-2 formulation. IgG levels fell to low levels by Day 478 in all groups except the 100 µg with AP 10-701 group, in which 57% of subjects (4 of 7) still had IgG levels that were ≥4-fold higher than baseline. IgG subclass levels mirrored those of total IgG, with IgG1 being the predominant subclass response. CONCLUSIONS: Vaccination of adults with Sm-TSP-2/Alhydrogel in an area of ongoing S. mansoni transmission was safe, minimally reactogenic, and elicited significant IgG and IgG subclass responses against the vaccine antigen. These promising results have led to initiation of a Phase 2 clinical trial of this vaccine in an endemic region of Uganda. TRIAL REGISTRATION: NCT03110757.

Impact of the COVID-19 pandemic on the actions of the Schistosomiasis Control Program in an endemic area in Northeastern Brazil.

Schistosomiasis remains a serious public health concern in Brazil and the Schistosomiasis Control Program (PCE) was elaborated to assist in the control of the disease. Nevertheless, the irruption of the COVID-19 pandemic may have impacted the program. Herein, we assessed the impact of the pandemic on PCE actions in an endemic area in the region with the highest positivity rate for schistosomiasis in Brazil. We conducted an ecological, population-based study using data from the PCE of the state of Alagoas, between 2015 and 2021, to calculate the percentage of change. The temporal trend analysis was performed using the segmented log-linear regression model. To evaluate the spatial distribution of the data, choropleth maps were made showing the values of the% of change. Moran maps was elaborated to indicate the critical areas. Our analysis showed a decrease in the population surveyed in 2020 (-41.00%) and 2021 (-18.42%). Likewise, there was a reduction in the number of Kato-Katz tests performed (2020 = -43.45%; and in 2021 = -19.63%) and, consequently, a drop in the rate of positive tests (-37.98% in 2020 and -26.14% in 2021). Importantly, treatment of positive cases was lower than 80% (77.44% in 2020 and 77.38% in 2021). Additionally, spatial clusters with negative percentage values of up to -100% of the PCE indicators were identified mostly in the municipalities of the coastal areas that are historically most affected by schistosomiasis. Taken together, our analyzes corroborate that PCE actions in endemic municipalities of Alagoas were impacted by the COVID-19 pandemic.

Secondary bacterial infections & extensively drug-resistant bacteria among COVID-19 hospitalized patients at the University Hospital in Kraków (preprint)

Introduction: Healthcare-associated infections (HAI) and bacterial antimicrobial resistance posed a therapeutic risk during the coronavirus disease 2019 (COVID-19) pandemic. The aim of this study was to analyze the HAIs in COVID-19 patients in the Intensive Care Unit (ICU) and non-ICU at the University Hospital in Krakow (UHK) with an emphasis on the susceptibility of the most frequently isolated pathogens and the prevalence of extensively drug resistant (XDR) microorganisms. Methods: This laboratory-based study was carried out at the University Hospital in Krakow in the ICU and non-ICUs dedicated to COVID-19 patients between May 2021 and January 2022. All isolates of Klebsiella pneumoniae were analyzed using PFGE protocol. Results: 288 independent HAI cases were identified, with the predominance of urinary tract infections (UTI), especially in the non-ICU setting. The most common ICU syndrome was pneumonia (PNA). The prevalence of XDR organisms was 29.1% in the ICU and 26.4% in non-ICUs among all isolates. The incidence of carbapenem-resistant Enterobacteriaceae infection was 24.8 cases per 10,000 hospitalizations and the carbapenem-resistant A. baumannii infection incidence was 208.8 cases per 10,000 hospitalizations. The prevalence of XDR strains was highest in Acinetobacter spp, in PNA cases. The PFGE typing demonstrated that almost all XDR strains varied widely from each other. Conclusions: In this study, there was a high incidence of HAI in COVID-19 patients. Similarly, the prevalence of XDR microorganisms, especially XDR-A.baumannii, was also high. PFGE did not confirm the horizontal spread of any organism strains.

Reduced mortality among COVID-19 ICU patients after treatment with HemoClear convalescent plasma in Suriname (preprint)

Convalescent plasma is a promising therapy for coronavirus disease 2019 (COVID-19), but its efficacy in intensive care unit (ICU) patients in a low and middle income country setting such as Suriname is unknown. Bedside plasma separation using the HemoClear device made convalescent plasma therapy accessible as treatment option in Suriname. Two hundred patients with severe SARS-CoV-2 infection requiring intensive care were recruited. Fifty eight patients (29%) received COVID-19 convalescent plasma (CCP) treatment in addition to standard of care (SOC). The CCP treatment and SOC groups were matched by age, sex, and disease severity scores. Mortality in the CCP treatment group was significantly lower than in the SOC group (21% versus 39%; Fisher's exact P = 0.0133). Multivariate analysis using ICU days showed that CCP treatment reduced mortality (hazard ratio [HR], 0.35; 95% CI, 0.18-0.66; P = 0.001), while complication of acute renal failure (creatinine levels >110 mol/L; HR, 4.45; 95%CI, 2.54-7.80; P < 0.0001) was independently associated with death. Decrease in chest X-ray score in the CCP treatment group (median -3 points, IQR -4 to -1) was significantly greater than in the SOC group (median -1 point, IQR -3 to 1, Mann Whitney P = 0.0004). Improvement in PaO2/FiOs ratio was also significantly greater in the CCP treatment group (median 83, IQR 8 to 140) than in the SOC group (median 35, IQR -3 to 92, Mann Whitney P = 0.0234). Further research is needed for HemoClear-produced CCP as therapy in SARS-CoV-2 infections together with adequately powered, randomized controlled trials.

Impact of Rotational Thromboelastometry (ROTEM) on Clinical Course and Outcomes of COVID -19 Critically Ill Patients: A Retrospective Single Center Observational Study (preprint)

BACKGROUND The severity of coagulation derangement correlates with poor prognosis in COVID-19 patients. However, the clinical impact of coagulation alterations detected with rotational thromboelastometry (ROTEM) in intensive care unit (ICU) COVID-19 patients is not completely defined. The study aimed to identify the correlation between ROTEM parameters and adverse ICU outcomes. The relationship between COVID-19 associated coagulopathy (CAC) and ROTEM alterations and possible risk factors for ICU mortality were also investigated.  METHODS COVID-19 patients admitted to ICU between October 1, 2020 and May 31, 2021, were retrospectively enrolled. The sample was subsequently divided into subgroups (survivors vs. non-survivors, mechanical ventilation (MV) vs. non-invasive ventilation (NIV), venous thromboembolism (VTE) vs. NO-VTE, CAC vs. NO-CAC) among which ROTEM parameters and standard coagulation tests were compared.  RESULTS One hundred ICU patients were enrolled. High D-dimer (DD) (5089 ± 1035 ng/ml) and fibrinogen levels (640 ± 112 mg/dl) and an increase in maximum clot firmness (MCF) were revealed. The non-survivors (n=50, 50%) had higher DD levels and lower platelet counts as well as lower clot lysis rates than survivors. EXTEM maximum lysis (ML) resulted lower in the MV subgroup than in NIV treated patients. Patients with thrombotic complications had higher DD levels than patients without VTE whereas ROTEM parameters were not different. Similarly no coagulation or ROTEM differences were identified in the subgroup of CAC patients (n=29, 29%). Reduced ML values in EXTEM and INTEM resulted as possible risk factors for ICU mortality.  CONCLUSIONS In critically ill COVID-19 patients, hypofibrinolysis and not hypercoagulability seems to be correlated with unfavourable ICU prognosis.

Reliability of point-of-care circulating cathodic antigen assay for diagnosing schistosomiasis mansoni in urine samples from an endemic area of Brazil after one year of storage at -20 degrees Celsius.

BACKGROUND: The World Health Organization recommends reliable point-of-care (POC) diagnostic testing to eliminate schistosomiasis. Lateral flow immunoassay that detects schistosome circulating cathodic antigen (CCA) in urine to establish prevalence thresholds for intervention in endemic areas is recommended. Stored urine may be useful if surveying at-risk populations is delayed or interrupted by unforeseen circumstances, such as the current COVID-19 pandemic. This study evaluated the manufacturer's claim that Schistosoma mansoni infection can be reliably diagnosed in urine samples stored at -20°C for one year. METHODS: Two-hundred-forty-two subjects from an endemic site in Brazil provided one urine sample each for testing with URINE CCA (SCHISTO) ECO TESTE® (POC-ECO) and one stool sample each for testing with Kato-Katz (KK) and Helmintex® (HTX) as a robust reference standard for infection status. At least 2 ml of urine from each participant was stored at -20°C; after one year, 76 samples were randomly selected for POC-ECO retesting. RESULTS: The POC-ECO agreement between freshly collected and stored urine was inadequate considering trace results as positive (Cohen's kappa coefficient κ = 0.08) and negative (κ = 0.36). POC-ECO accuracy was not significantly greater than that of routine KK (54%; 95% confidence interval: 42.1%-65.5%). CONCLUSIONS: The precision and accuracy of POC-ECO have to be optimized in both freshly collected and stored urine before it can be recommended for use in control programs in Brazil.

Disruptions to schistosomiasis programmes due to COVID-19: an analysis of potential impact and mitigation strategies.

BACKGROUND: The 2030 goal for schistosomiasis is elimination as a public health problem (EPHP), with mass drug administration (MDA) of praziquantel to school-age children (SAC) as a central pillar of the strategy. However, due to coronavirus disease 2019, many mass treatment campaigns for schistosomiasis have been halted, with uncertain implications for the programmes. METHODS: We use mathematical modelling to explore how postponement of MDA and various mitigation strategies affect achievement of the EPHP goal for Schistosoma mansoni and S. haematobium. RESULTS: For both S. mansoni and S. haematobium in moderate- and some high-prevalence settings, the disruption may delay the goal by up to 2 y. In some high-prevalence settings, EPHP is not achievable with current strategies and so the disruption will not impact this. Here, increasing SAC coverage and treating adults can achieve the goal. The impact of MDA disruption and the appropriate mitigation strategy varies according to the baseline prevalence prior to treatment, the burden of infection in adults and the stage of the programme. CONCLUSIONS: Schistosomiasis MDA programmes in medium- and high-prevalence areas should restart as soon as is feasible and mitigation strategies may be required in some settings.

Associations of DMT Therapies with COVID-19 Severity in Multiple Sclerosis: An International Cohort Study (preprint)

Background: People with multiple sclerosis (MS) may be a vulnerable group for severe COVID-19, particularly those taking immunosuppressive disease-modifying therapies (DMTs).Objectives: To examine characteristics of COVID-19 severity in an international sample of people with MS.Methods: Clinician and patient-reported data from 82 countries were aggregated into two datasets of 1,625 and 7,365 patients, respectively. Characteristics of hospitalisation, admission to Intensive Care Unit (ICU), requiring artificial ventilation, and death were assessed in patients with suspected/confirmed COVID-19 using log-binomial regression.Findings: Only clinician-reported data were used for all analyses. Of 1,625 patients, 481 (29·6%) with suspected and 811 (49·9%) with confirmed COVID-19 were included. Older age, progressive MS, and higher disability were positively associated with worse COVID-19 outcomes. Anti-CD20 DMTs (ocrelizumab/rituximab) were positively associated with hospitalisation (aPR=1·31, 95%CI=0·88-1·95; aPR=1·63, 95%CI=1·08-2·46), ICU admission (aPR=3·38, 95%CI=1·01-11·32; aPR=3·85, 95%CI=1·13-13·11), and ventilation (aPR=2·78, 95%CI=0·61-12·65; aPR=6·73, 95%CI=1·57-28·84) vs dimethyl fumarate, as well as pooled anti-CD20 DMTs vs all other DMTs (hospitalisation aPR=1·59, 95%CI=1·24-2·03; ICU aPR=2·63, 95%CI=1·48-4·68; ventilation aPR=3·18, 95%CI=1·54-6·58) and vs natalizumab (hospitalisation aPR=1·79, 95%CI=1·07-3·01; ICU aPR=2·03, 95%CI=0·66-6·24; ventilation aPR=2·34, 95%CI=0·57-9·63). Importantly, associations persisted on restriction to confirmed COVID-19 cases. No associations were observed between DMTs and death.Interpretation: Using the largest cohort of people with MS and COVID-19 available, we demonstrated consistent associations of anti-CD20 DMTs with increased risk of hospitalisation, ICU admission, and need for artificial ventilation, suggesting their use may be a risk factor for more severe COVID-19.Funding: Operational costs were funded by the Multiple Sclerosis International Federation (MSIF) and the Multiple Sclerosis Data Alliance (MSDA), acting under the European Charcot Foundation. MSDA and MSIF receive income from a range of corporate sponsors. This research received funding from the Flemish Government under the Onderzoeksprogramma Artificiële Intelligentie Vlaanderen programme. The central platform was provided by QMENTA and computational resources were provided by Amazon.Declaration of Interests: TK has served on scientific advisory boards for Roche, Sanofi-Genzyme, Novartis, Merck and Biogen, steering committee for Brain Atrophy Initiative by Sanofi-Genzyme, received conference travel support and/or speaker honoraria from WebMD Global, Novartis, Biogen, Sanofi-Genzyme, Teva, BioCSL and Merck and received research support from Biogen. NR & CW have no personal pecuniary interests to disclose, other than being an employee of MSIF, which receives income from a range of corporate sponsors, recently including: Biogen, BristolMyersSquibb (formerly Celgene), Genzyme, Med-Day, Merck, Mylan, Novartis, Roche. JH has received honoraria for serving on advisory boards for Biogen, Celgene, Sanofi-Genzyme, Merck KGaA, Novartis and Sandoz and speaker’s fees from Biogen, Novartis, Merck KGaA, Teva and Sanofi-Genzyme, has served as principal investigator for projects, or received unrestricted research support from Biogen, Celgene, Merck KGaA, Novartis, Roche and Sanofi-Genzyme, and his MS research was funded by the Swedish Research Council and the Swedish Brain foundation. GE has received consulting/speaking fees and research support from Bayer, Novartis, Teva, Sanofi Genzyme, Merck Serono, Biogen Idec, and Roche. TS has served on scientific advisory boards for Biogen. RMcB & HS, work for the Accelerated Cure Project for MS (ACP), which has received grants, collaboration funding, payments for use of assets, or in-kind contributions from the following companies: EMD Serono, Sanofi/Genzyme, Biogen, Genentech, AbbVie, Octave, GlycoMinds, Pfizer, MedDay, AstraZeneca, Teva, Mallinckrodt, MSDx, Regeneron Genetics Center, BC Platforms, and Celgene. ACP has also received funding from the Patient-Centered Outcomes Research Institute (PCORI) and the National MS Society (NMSS). RMcB. has received consulting payments from EMD Serono, which have been donated to ACP. AB has received consulting fees from and is an advisory board/speaker/other activities for NeuroTransData, and has worked on project management/clinical studies for and received travel expenses from Novartis and Servier. AS has no personal pecuniary interests to disclose, other than being the lead of the German MSRegistry, which receives funding from a range of public and corporate sponsors, recently including The German Innovation Fund (G-BA), The German MS Trust, Biogen, German MS Society, Celgene (BMS), Merck and Novartis. RM has received no personal funding from any sources, but works for the UK MS Register which is funded by the UK MS Society and has received funding for specific projects from Novartis, Sanofi-Genzyme and Merck KGaA. RJF has received personal consulting fees from Actelion, Biogen, Celgene, EMD Serono, Genentech, Immunic, Novartis, Sanofi, Teva, and TG Therapeutics, and has served on advisory committees for Actelion, Biogen, Immunic, and Novartis, and received clinical trial contract and research grant funding from Biogen and Novartis. AvdW has received honoraria and unrestricted research funding from Novartis, Biogen, Roche, Merck and Sanofi. JIR has received honoraria from Novartis as a scientific advisor, and has received travel grants and attended courses and conferences on behalf of Merck-Serono Argentina, Novartis Argentina. GSdO has received honoraria for lecturing and support for congress participation from Biogen, Merck, Novartis, Sanofi/Genzyme, EMS and Roche. MM has served on scientific advisory board for Biogen, Sanofi, Roche, Novartis, Merck, Abbvie, has received honoraria for lecturing from Biogen, Merck, Novartis, Sanofi, Genzyme, and has received research support and support for congress participation from Biogen, Genzyme, Roche, Merck, Novartis. RA has received honoraria from Novartis as a scientific advisor, travel grants and attended courses and conferences on behalf of Merck-Serono Argentina, Biogen Argentina, Genzyme Argentina, Roche Argentina and Novartis Argentina. RN has received honoraria from Novartis, Roche and Biogen for advisory boards. AZ has received travel expenses for scientific meetings from Biogen, Novartis, and Genzyme, speaking honoraria from Eisai, and a study grant from Novartis. GA has received compensation for consulting services or participation in advisory boards from Sanofi, Merck and Roche; research support from Novartis; travel expenses for scientific meetings from Novartis, Roche, Stendhal, and ECTRIMS; speaking honoraria from Sanofi and Merck; and is a member of the International Women in Multiple Sclerosis (iWiMS) network executive committee. GC has received consulting and speaking fees from Novartis, Teva Pharmaceutical Industries Ltd, Teva Italia Srl, Sanofi Genzyme, Genzyme Corporation, Genzyme Europe, Merck KGgA, Merck Serono SpA, Celgene Group, Biogen Idec, Biogen Italia Srl, F. Hoffman-La Roche, Roche SpA, Almirall SpA, Forward Pharma, Medday and Excemed. LMP has no personal pecuniary interests to disclose, other than being the chair of The MS Data Alliance (MSDA), which receives income from a range of corporate sponsors, recently including Biogen, BristolMyersSquibb (formerly Celgene), Canopy Growth Corporation, Genzyme, Icometrix, Merck, Mylan, Novartis, QMENTA, Quanterix, Roche. SSY, EDB, YM, LG, TP, CG, NL, AP, AA, LEF, AG, SB, AS, IvDM, NN, RI, AED, DG, MFM, JB, AF, and AC have no conflicts of interests to disclose.Ethics Approval Statement: This study was approved by the ethical committee of Hasselt University [CME2020/025]. Individual data sources obtained additional ethics approval as required.

First Wave of COVID-19 Hospital Admissions in Denmark: A Nationwide Population-Based Cohort Study (preprint)

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its associated disease coronavirus disease 2019 (COVID-19), is a worldwide emergency. Demographic, clinical and laboratory factors associated with mortality in Danish patients hospitalised with COVID-19 is limited.Methods: National health registries were used to identify all hospitalized patients with a COVID-19 diagnosis. We obtained demographics, Charlson Comorbidity Index (CCI), and laboratory results on admission and explored prognostic factors for death using multivariate Cox proportional hazard regression and competing risk survival analysis.Results: Among 2,431 hospitalised patients with COVID-19 between February 27th and July 8th (median age 69 years [IQR 53–80], 54.1% males), 359 (14.8%) needed admission to an intensive care unit (ICU) and 455 (18.7%) died within 30 days of follow-up. The seven-day cumulative incidence of ICU admission was lower for females (7.9%) than for males (16.7%), (p < 0.001). Age, high CCI, elevated C-reactive protein (CRP), ferritin, D-dimer, lactate dehydrogenase (LDH), urea, creatinine, lymphopenia, neutrophilia, and thrombocytopenia within 24-hours of admission were independently associated with death within the first week in the multivariate analysis. Conditional upon surviving the first week, male sex, age, high CCI, elevated CRP, LDH, creatinine, urea and neutrophil count were associated with death within 30 days. Males presented with more pronounced laboratory abnormalities on admission. Conclusions: Advanced age, male sex, comorbidity, higher levels of systemic inflammation and cell-turnover were prognostic factors for mortality. Age was the strongest predictor for death, moderate to high level of comorbidity were associated with a nearly two-fold increase in mortality. Mortality was significantly higher for males after surviving the first week.  

Rationale and Study Design of an Early Care, Therapeutic Education, and Psychological Intervention for the Management of Post-intensive Care Syndrome and Chronic Pain After Coronavirus Disease 2019 (PAIN-COVID): Study protocol for a randomized controlled trial (preprint)

Background: Critically ill patients with COVID-19 disease are an especially susceptible population to develop Post-intensive Care Syndrome (PICS) due to acute respiratory distress syndrome (ARDS). Patients can suffer acute severe pain and may have long-term deterioration in mental, cognitive, and functional health after discharge. However, few controlled trials are evaluating interventions for the prevention and treatment of PICS. The study hypothesis is that a specific care program based on early therapeutic education and a psychological intervention improves the quality of life of patients at risk of developing PICS and chronic pain after COVID-19 disease. The primary objective is to determine if the program is superior to standard-of-care on health-related life quality at six months after hospital discharge. The secondary objectives are to determine if the intervention is superior to standard care, evaluating the health-related life quality, the incidence of chronic pain and the degree of functional limitation, the incidence of anxiety, depression, and post-traumatic stress syndrome at 3 and 6 months after hospital discharge.Methods: The PAINCOVID trial is a unicentric randomized, controlled, patient blinded superiority trial with two parallel groups. The primary endpoint is the health-related quality of life at six months after hospital discharge, and randomization will be performed with a 1:1 allocation. This paper details the methodology and statistical analysis plan of the trial and was submitted before outcome data were available.The sample size calculated is 84 patients, 42 for each arm. Estimating a loss of follow up of 20%, a sample size of 102 patients is necessary (51 each group). Discussion: This is the first randomized clinical trial assessing the effectiveness of an early care therapeutic education, and psychological intervention for the management of PICS and Chronic Pain after COVID-19. The intervention will serve as a sample of the need to implement early care programs on early stages, having an incalculable impact given the current scenario of the pandemic.Trial registration: This study is being in accordance with the tenets of the Helsinki Declaration, and has been approved by the authors’ institutional review board Comité Ético de Investigación Clínica del Hospital Clinic de Barcelona (approval number: HCB/2020/0549) and was registered on May 9, 2020 at  clinicaltrials.gov (NCT04394169).

An outbreak of intestinal schistosomiasis, alongside increasing urogenital schistosomiasis prevalence, in primary school children on the shoreline of Lake Malawi, Mangochi District, Malawi (preprint)

Background: Intestinal schistosomiasis was not considered endemic in Lake Malawi until November 2017 when populations of Biomphalaria pfeifferi were first reported; in May 2018, emergence of intestinal schistosomiasis was confirmed. This emergence was in spite of ongoing control of urogenital schistosomiasis by preventive chemotherapy. Our current study sought to ascertain whether intestinal schistosomiasis is transitioning from emergence to outbreak, to judge if stepped-up control interventions are needed. Methods: : During late-May 2019, three cross-sectional surveys of primary school children for schistosomiasis were conducted using a combination of rapid diagnostic tests, parasitological examinations and applied morbidity-markers; 1) schistosomiasis dynamics were assessed at Samama ( n = 80) and Mchoka ( n = 80) schools, where Schistosoma mansoni was first reported, 2) occurrence of S. mansoni was investigated at two non-sampled schools, Mangochi Orphan Education and Training (MOET) ( n = 60) and Koche ( n = 60) schools, where B. pfeifferi was nearby, and 3) rapid mapping of schistosomiasis, and B. pfeifferi , conducted across a further 8 shoreline schools ( n = 240). After data collection, univariate analyses and Chi-square testing were performed, followed by binary logistic regression using generalized linear models, to investigate epidemiological associations. Results: : In total, 520 children from 12 lakeshore primary schools were examined, mean prevalence of S. mansoni by ‘positive’ urine circulating cathodic antigen (CCA)-dipsticks was 31.5% (95% Confidence Interval ( CI ): 27.5–35.5). Upon comparisons of infection prevalence in May 2018, significant increases at Samama (Relative Risk (RR) = 1.7, 95% CI 1.4–2.2) and Mchoka (RR = 2.7, 95% CI 1.7–4.3) schools were observed. Intestinal schistosomiasis was confirmed at MOET (18.3%) and Koche (35.0%) schools, and in all rapid mapping schools, ranging from 10.0% to 56.7%. Several populations of B. pfeifferi were confirmed, with two new eastern shoreline locations noted. Mean prevalence of urogenital schistosomiasis was 24.0% (95% CI 20.3–27.7). Conclusions: : We notify that intestinal schistosomiasis, once considered non-endemic in Lake Malawi, is now transitioning from emergence to outbreak. Once control interventions can resume after coronavirus disease 2019 (COVID-19) suspensions, we recommend stepped-up preventive chemotherapy, with increased community-access to treatments, alongside renewed efforts in appropriate environmental control.

Identifying main and interaction effects of risk factors to predict intensive care admission in patients hospitalized with COVID-19: a retrospective cohort study in Hong Kong (preprint)

Background: The coronavirus disease 2019 (COVID-19) has become a pandemic, placing significant burdens on the healthcare systems. In this study, we tested the hypothesis that a machine learning approach incorporating hidden nonlinear interactions can improve prediction for Intensive care unit (ICU) admission. Methods: Consecutive patients admitted to public hospitals between 1st January and 24th May 2020 in Hong Kong with COVID-19 diagnosed by RT-PCR were included. The primary endpoint was ICU admission. Results: This study included 1043 patients (median age 35 (IQR: 32-37; 54% male). Nineteen patients were admitted to ICU (median hospital length of stay (LOS): 30 days, median ICU LOS: 16 days). ICU patients were more likely to be prescribed angiotensin converting enzyme inhibitors/angiotensin receptor blockers, anti-retroviral drugs lopinavir/ritonavir and remdesivir, ribavirin, steroids, interferon-beta and hydroxychloroquine. Significant predictors of ICU admission were older age, male sex, prior coronary artery disease, respiratory diseases, diabetes, hypertension and chronic kidney disease, and activated partial thromboplastin time, red cell count, white cell count, albumin and serum sodium. A tree-based machine learning model identified most informative characteristics and hidden interactions that can predict ICU admission. These were: low red cells with 1) male, 2) older age, 3) low albumin, 4) low sodium or 5) prolonged APTT. A five-fold cross validation confirms superior performance of this model over baseline models including XGBoost, LightGBM, random forests, and multivariate logistic regression. Conclusions: A machine learning model including baseline risk factors and their hidden interactions can accurately predict ICU admission in COVID-19.

Fat mass prevalence and influence on nutritional status in ICU COVID-19 patients (preprint)

Background: Obesity and steatosis are associated with COVID-19 severe pneumonia. Elevated levels of pro-inflammatory cytokines and reduced immune response are typical of these patients. In particular, adipose tissue is the organ playing the crucial role. So, it is necessary to evaluate fat mass and not simpler body mass index (BMI), because BMI leaves a portion of the obese population unrecognized. The aim is to evaluate the relationship between FM% and immune-inflammatory response, after 10th days in ICU.Methods: Prospective observational study in single cohort of 22 adult patients, affected by COVID-19 pneumonia and admitted to the Intensive Care Unit (ICU) and classified (10) lean and (12) obese, according to Percentage of Fat Mass (FM%) and age (De Lorenzo classification). Patients were analyzed at admission in ICU and at 10th day.Results: Obese have steatosis, impaired hepatic function, compromise immune response and higher inflammation. In addition, they have a reduced prognostic nutritional index (PNI), nutritional survival index for ICU patients.Conclusion: This is the first study evaluating FM% in COVID-19 patient. We underlined obese characteristic with likely poorly prognosis and an important misclassification of obesity. A not negligible number of patients with normal BMI could actually have an excess of adipose tissue and therefore have an unfavorable outcome such as an obese. Is fundamental personalized patients nutrition basing on disease phases.

COVID-19: the key role of pulmonary capillary leakage. An observational cohort study (preprint)

Background: COVID-19 induces progressive hypoxemic respiratory failure and acute respiratory distress syndrome, mostly due to a dysregulated inflammatory response. Since the first observations of COVID-19 patients, significant hypoalbuminemia was detected. This study aimed to investigate the hypothesis that hypoalbuminemia in COVID-19 patients is due to pulmonary capillary leakage and to test its correlation with indicators of respiratory function. Methods: 174 COVID-19 patients, 92 admitted to the Intermediate Medicine ward (IMW), and 82 to the Intensive Care Unit (ICU) at Luigi Sacco Hospital in Milan were included in this study. Findings: Serum albumin concentration was decreased in the whole cohort, with ICU patients displaying lower values than IMW patients [20 (18-23) vs 28 (24-33) g/L, p<0.0001]. Lower albumin values were found in patients belonging to a more compromised group (lower PaO2 to FiO2 ratio and worst chest X-ray findings). In a subset of 26 patients, analysis of bronchoalveolar lavage fluid (BALF) highlighted high protein concentrations, which were correlated to Interleukin-8 and Interleukin-10 BALF concentration. The length of hospitalisation [20 (15-29) vs 8 (5-14) days, p<0.0001] and death rate (52.4% vs 21.7%, p<0.0001) were higher in ICU than in IMW patients, while a strict relation between hypoalbuminemia and 30 day-survival was detected in the whole cohort. Electron microscopy examinations of eight out of ten autopsy lung tissues showed diffuse loosening of interendothelial junctional complex. Interpretation: The degree of hypoalbuminemia can be considered as a useful severity marker in hospitalised COVID-19 patients. Pulmonary capillary leak syndrome secondary to the hyperinflammatory state plays a key role in the pathogenesis of COVID-19 respiratory dysfunction and should be regarded as a therapeutic target.

Epidemiological and clinical features of 201 COVID-19 patients in Changsha city, Hunan, China (preprint)

Background: In December 2019, a cluster of coronavirus Disease 2019 (COVID-19) occurred in Wuhan, Hubei Province, China. With the advent of the Chinese Spring Festival, this disease spread rapidly throughout the country. The information about the clinical characteristics of COVID-19 patients outside of Wuhan is limited.Methods: All of the patients with confirmed COVID-19 were admitted to the First Hospital of Changsha City, the designated hospital for COVID-19 assigned by the Changsha City Government. The clinical and epidemiological characteristics, data of laboratory, radiological picture, treatment, and outcomes records of 201 COVID-19 patients were collected using electronic medical records.Results: This study population consisted of 201 hospitalized patients with laboratory-confirmed COVID-19 in Changsha by April 28, 2020. The median age of the patients was 45 years (IQR 34–59). About half (50.7%) of the patients were male, and most of the infected patients were staff (96 [47.8%]). Concerning the epidemiologic history, the number of patients linked to Wuhan was 92 (45.8%). The most common symptoms were fever (125 [62.2%]), dry cough (118 [58.7%]), fatigue (65 [32.3%]), and pharyngalgia (31 [15.4%]). One hundred and forty-four (71.6%) enrolled patients showed bilateral pneumonia. Fifty-four (26.9%) patients showed unilateral involvement, and three (1.5%) patients showed no abnormal signs or symptoms. The laboratory findings differed significantly between the Intensive Care Unit (ICU) and non-ICU groups. Compared with non-ICU patients, ICU patients had depressed white blood cell (WBC), neutrocytes, lymphocytes, and prolonged prothrombin time (PT). Moreover, higher plasma levels of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), procalcitonin (PCT), alanine aminotransferase (ALA), aspartate aminotransferase (AST), creatine kinase (CK), creatine kinase-MB (CK-MB), creatinine (CREA), and lactate dehydrogenase (LDH) were detected in the ICU group.Conclusions: In this single-center study of 201 COVID-19 patients in Changsha, China, 22.4% of patients were admitted to ICU. Based on our findings, we propose that the risk of cellular immune deficiency, hepatic injury, and kidney injury should be monitored. Previous reports focused on the clinical features of patients from Wuhan, China. With the global epidemic of COVID-19, we should pay more attention to the clinical and epidemiological characteristics of patients outside of Wuhan.

COVID-19 Outbreak Situations in Bangladesh: An Empirical Analysis (preprint)

COVID-19 disease, as popularly known as Coronavirus 2019 disease, has been emerged from Wuhan, China in December 2019 and now is a pandemic for almost every nation in the earth. It affects every country without considering country's race, nationality and economic status. This paper aims at analysing primarily the current situations of Bangladesh and predicting infections and deaths for moderated term intervals by a proposed projection technique called Infection Trajectory-Pathway Strategy (ITPS) and for short term intervals prediction for total infections, deaths along with total number of severe patients and Intensive Care Unit (ICU) patients by polynomial regression modeling approach. Since April 7, Bangladesh has started to face critical situations as the number of infections has accelerated very fast in the following days. However, the fatality rate decreases considerably from 15.7 on April 1 to 4.9 on April 14, which is still high among the south asian countries. Of the 1012 cases reported on April 14, almost 70\% are the male, 42\% are from the capital Dhaka. We have found that the potential pathway of infections for Bangldesh would be the similar pathways that are experienced by Austria, Netherlands, Israel, France and United Kingdom. These countries are ahead a number of weeks and days in terms of infection cases since their 100-th confirmed cases. Our proposed projection method ITPS suggests that by May 10, Bangladesh will cross 12000 incidences and 720 deaths which, by May 16 will be 27000 and 1644 respectively. On the other hand, the regression model suggests that by the end of April, total number of infections, deaths, severe patients and ICU patients will be 5780, 347, 775, and 694 respectively. This study will be favorable for the administrative units of Bangladesh to plan for the next few weeks and to consider various aspects related to the control of COVID-19 outspread in Bangladesh

Epidemiological and clinical features of 201 COVID-19 patients in Changsha, China (preprint)

Background In December 2019, a cluster of coronavirus Disease 2019 (COVID-19) occurred in Wuhan, Hubei Province, China. With the advent of the Chinese Spring Festival, this disease spread rapidly throughout the country. The information about the clinical characteristics of COVID-19 patients outside of Wuhan is limited. Methods All of the patients with confirmed COVID-19 were admitted to the First Hospital of Changsha City, the designated hospital for COVID-19 assigned by the Changsha City Government. The clinical and epidemiological characteristics, data of laboratory, radiological picture, treatment, and outcomes records of 201 COVID-19 patients were collected using electronic medical records. Results This study population consisted of 201 hospitalized patients with laboratory-confirmed COVID-19 in Changsha by February 15, 2020. The median age of the patients was 45 years (IQR 34–59). About half (50.7%) of the patients were male, and most of the infected patients were staff (96 [47.8%]). Concerning the epidemiologic history, the number of patients linked to Wuhan was 92 (45.8%). The most common symptoms were fever (125 [62.2%]), dry cough (118 [58.7%]), fatigue (65 [32.3%]), and pharyngalgia (31 [15.4%]). One hundred and forty-four (71.6%) enrolled patients showed bilateral pneumonia. Fifty-four (26.9%) patients showed unilateral involvement, and three (1.5%) patients showed no abnormal signs or symptoms. The laboratory findings differed significantly between the Intensive Care Unit (ICU) and non-ICU groups. Compared with non-ICU patients, ICU patients had depressed white blood cell (WBC), neutrocytes, lymphocytes, and prolonged prothrombin time (PT). Moreover, higher plasma levels of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), procalcitonin (PCT), alanine aminotransferase (ALA), aspartate aminotransferase (AST), creatine kinase (CK), creatine kinase-MB (CK-MB), creatinine (CREA), and lactate dehydrogenase (LDH) were detected in the ICU group. Conclusions In this single-center study of 201 COVID-19 patients in Changsha, China, 22.4% of patients were admitted to ICU. Based on our findings, we propose that the risk of cellular immune deficiency, hepatic injury, and kidney injury should be monitored. Previous reports focused on the clinical features of patients from Wuhan, China. With the global epidemic of COVID-19, we should pay more attention to the clinical and epidemiological characteristics of patients outside of Wuhan.