Crimean-Congo Hemorrhagic Fever, Spain, 2013-2021.

Crimean-Congo hemorrhagic fever (CCHF) is a viral infectious disease for which distribution of the main vector, Hyalomma spp. ticks, is expanding. We analyzed all 10 cases of CCHF diagnosed in Spain during 2013-2021; case-patient median age was 56.5 years, and 7 were men. We identified CCHF virus genotypes III and V. Six case-patients acquired the infection in urban areas. Sixty percent of patients were infected in summer and 40% in spring. Two patients met criteria for hemophagocytic syndrome. Seven patients survived. The epidemiologic pattern of CCHF in Spain is based on occasional cases with an elevated mortality rate. Genotype III and, to a less extent also genotype V, CCHF circulates in humans in a common geographic area in Spain. Those data suggest that the expansion pathways are complex and may change over time. Physicians should remain alert to the possibility of new CCHF cases.

Immune cell kinetics and antibody response in COVID-19 patients with low-count monoclonal B-cell lymphocytosis.

Low-count monoclonal B-cell lymphocytosis (MBLlo ) has been associated with an underlying immunodeficiency and has recently emerged as a new risk factor for severe COVID-19. Here, we investigated the kinetics of immune cell and antibody responses in blood during COVID-19 of MBLlo versus non-MBL patients. For this study, we analyzed the kinetics of immune cells in blood of 336 COVID-19 patients (74 MBLlo and 262 non-MBL), who had not been vaccinated against SARS-CoV-2, over a period of 43 weeks since the onset of infection, using high-sensitivity flow cytometry. Plasma levels of anti-SARS-CoV-2 antibodies were measured in parallel by ELISA. Overall, early after the onset of symptoms, MBLlo COVID-19 patients showed increased neutrophil, monocyte, and particularly, plasma cell (PC) counts, whereas eosinophil, dendritic cell, basophil, and lymphocyte counts were markedly decreased in blood of a variable percentage of samples, and with a tendency toward normal levels from week +5 of infection onward. Compared with non-MBL patients, MBLlo COVID-19 patients presented higher neutrophil counts, together with decreased pre-GC B-cell, dendritic cell, and innate-like T-cell counts. Higher PC levels, together with a delayed PC peak and greater plasma levels of anti-SARS-CoV-2-specific antibodies (at week +2 to week +4) were also observed in MBLlo patients. In summary, MBLlo COVID-19 patients share immune profiles previously described for patients with severe SARS-CoV-2 infection, associated with a delayed but more pronounced PC and antibody humoral response once compared with non-MBL patients.

Epidemiological of cat scratch disease among inpatients in the Spanish health system (1997-2015).

Cat scratch disease, whose causative agent is Bartonella henselae, is an anthropozoonosis with a worldwide distribution that causes significant public health problems. Although it is an endemic disease in Spain, the available data are very limited. The aim of our study was to describe cat scratch disease inpatients in the National Health System (NHS) of Spain. This was a retrospective descriptive study using the minimum basic data set (CMBD in Spanish) in patients admitted to hospitals of the NHS between 1997 and 2015 with a diagnosis of cat scratch disease (ICD-9: 078.3). We found 781 hospitalized patients diagnosed with cat scratch disease. The mean age (± SD) was 30.7 ± 25.3 years old. The male/female ratio was 1.1:1. The incidence rate over the study period was 0.93 (95% CI, 0.86-0.99) cases per million person-years. The incidence rate in men was 0.98 cases per million person-years and that in women was 0.88 cases per million person-years. The cases were more frequent from September to January. A total of 652 (83.5%) cases were urgent hospital admissions. The average hospital stay was 8.4 ± 8.9 days. The overall lethality rate of the cohort was 1.3%. We have demonstrated that CSD causes a substantial burden of disease in Spain, affecting both adult and pediatric patients with a stable incidence rate. Our data suggest that CSD is benign and self-limited, with low mortality, and its incidence is possibly underestimated. Finally, there is a need for a common national strategy for data collection, monitoring, and reporting, which would facilitate a more accurate picture and the design of more strategic control measures. Hospital discharge records (HDRs) could be a good database for the epidemiological analysis of the hospital management of CSD.

Epidemiological assessment of 5598 brucellosis inpatients in Spain (1997-2015).

Brucellosis remains one of the main zoonoses worldwide. Epidemiological data on human brucellosis in Spain are scarce. The objective of this study was to assess the epidemiological characteristics of inpatient brucellosis in Spain between 1997 and 2015. A retrospective longitudinal descriptive study was performed. Data were requested from the Health Information Institute of the Ministry of Health and Equality, which provided us with the Minimum Basic Data Set of patients admitted to the National Health System. We also obtained data published in the System of Obligatory Notifiable Diseases. A total of 5598 cases were registered. The period incidence rate was 0.67 (95% CI 0.65-0.68) cases per 100 000 person-years. We observed a progressive decrease in the number of cases and annual incidence rates. A total of 3187 cases (56.9%) came from urban areas. The group most at risk comprised men around the fifth decade of life. The average (±s.d.) hospital stay was 12.6 days (±13.1). The overall lethality rate of the cohort was 1.5%. The number of inpatients diagnosed with brucellosis decreased exponentially. The group of patients with the highest risk of brucellosis in our study was males under 45 years of age and of urban origin. The lethality rate has reduced to minimum values. It is probable that hospital discharge records could be a good database for the epidemiological analysis of the hospital management of brucellosis and offer a better information collection system than the notifiable diseases system (EDO in Spanish).

Epidemiology of aspergillosis in hospitalised Spanish patients-A 21-year retrospective study.

BACKGROUND: Aspergillosis is a serious infection, and in Spain, the influence of epidemiology and climate on the resulting expenses of aspergillosis is not well established. AIM: A retrospective descriptive study using the Minimum Basic Data Set was performed on records of patients admitted to hospitals of the National Health System between 1997 and 2017 with a diagnosis of aspergillosis. The weather parameters were obtained from the State Agency of Meteorology from Spain. RESULTS: A total of 32,960 patients were identified, of whom 22,383 were men (68%). The mean age (±SD) was 61.1 ± 19.1 years. The mean incidence rate for all diagnoses was 3.54 cases per 100,000 person-years (95% CI, 3.50-3.57). The incidence rate in men was twice as high as that in women, 4.89 (95% CI, 4.82-4.95) vs. 2.24 (95% CI, 2.19-2.27) cases per 100,000 person-years (p > .001). The highest incidence rates were concentrated in northern Spain. One in four patients died (8,080 cases; 25%). There was a moderate positive linear association between rainfall and incidence rate (rP  = .508; p = .026). In contrast, the Pearson's correlation coefficient indicated a moderate negative linear relationship between temperature and incidence rate (rP  = -.447; p = .050). We observed a higher incidence in the months with higher humidity and rainfall. CONCLUSIONS: Our study supports a high burden of aspergillosis in Spain, with an increase in cases in the past two decades. Additionally, the influence of climatological factors on the incidence of aspergillosis is highlighted. Despite preemptive treatment strategies, this infection still has a high mortality.

Medical treatment of cystic echinococcosis: systematic review and meta-analysis.

BACKGROUND: Cystic echinococcosis (CE) is a well-known neglected parasitic disease. However, evidence supporting the four current treatment modalities is inadequate, and treatment options remain controversial. The aim of this work is to analyse the available data to answer clinical questions regarding medical treatment of CE. METHODS: A thorough electronic search of the relevant literature without language restrictions was carried out using PubMed (Medline), Cochrane Central Register of Controlled Trials, BioMed, Database of Abstracts of Reviews of Effects, and Cochrane Plus databases up to February 1, 2017. All descriptive studies reporting an assessment of CE treatment and published in a peer-reviewed journal with available full-text were considered for a qualitative analysis. Randomized controlled trials were included in a quantitative meta-analysis. We used the standard methodological procedures established by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. RESULTS: We included 33 studies related to the pharmacological treatment of CE in humans. Of these, 22 studies with levels of evidence 2 to 4 were qualitatively analysed, and 11 randomized controlled trials were quantitatively analysed by meta-analysis. CONCLUSIONS: Treatment outcomes are better when surgery or PAIR (Puncture, Aspiration, Injection of protoscolicidal agent and Reaspiration) is combined with benzimidazole drugs given pre- and/or post-operation. Albendazole chemotherapy was found to be the primary pharmacological treatment to consider in the medical management of CE. Nevertheless, combined treatment with albendazole plus praziquantel resulted in higher scolicidal and anti-cyst activity and was more likely to result in cure or improvement relative to albendazole alone.

Recurrence of cystic echinococcosis in an endemic area: a retrospective study.

BACKGROUND: Cystic echinococcosis (CE) is a chronic, complex and neglected zoonotic disease. CE occurs worldwide. In humans, it may result in a wide spectrum of clinical manifestations, ranging from asymptomatic infection to fatal disease. Clinical management procedures have evolved over decades without adequate evaluation. Despite advances in surgical techniques and the use of chemotherapy, recurrence remains one of the major problems in the management of hydatid disease. The aim of this study was to determine the frequency of CE recurrence and the risk factors involved in recurrence. METHODS: A descriptive longitudinal-retrospective study was designed. We reviewed all patients diagnosed with CE according to ICD-9 (code 122-0 to 122-9) criteria admitted at Complejo Asistencial Universitario de Salamanca, Spain, between January 1998 and December 2015. RESULTS: Among the 217 patients studied, 25 (11.5%) had a hydatid recurrence after curative intention treatment. Median duration of recurrence's diagnosis was 12.35 years (SD: ±9.31). The likelihood of recurrence was higher [OR = 2.7; 95% CI, 1.1-7.1; p < 0.05] when the cyst was located in organs other than liver and lung, 22.6% (7/31) vs 14.2% (31/217) in the cohort. We detected a chance of recurrence [OR = 2.3; 95% CI, 1.4-6.5; p > 0.05] that was two times higher in those patients treated with a combination of antihelminthic treatments and surgical intervention (20/141, 14.2%) than in patients treated with surgical intervention alone (5/76, 6.6%). CONCLUSIONS: Despite advances in diagnosis and therapeutic techniques in hydatid disease, recurrence remains one of the major problems in the management of hydatid disease. The current management and treatment of recurrences is still largely based on expert opinion and moderate-to-poor quality of evidence. Consequently, large prospective and multicenter studies will be needed to provide definitive recommendations for its clinical management.

[Epidemiological update of hydatid disease in hospitals in the public health system of Extremadura (2003-2012)]. / Situación epidemiológica de la hidatidosis en los centros hospitalarios del sistema público de salud de Extremadura (2003-2012).

INTRODUCTION: Echinococcosis is a zoonotic infection with a worldwide distribution, and is still an important health problem in many areas of the world, including the Mediterranean basin. At present the epidemiological situation is unclear in certain regions of Spain. The aim of this study was to update the epidemiological situation in Extremadura through an analysis of hospitalised patients in the public health system diagnosed with hydatid disease. METHODS: A longitudinal retrospective study was conducted between 2003 and 2012 on hospitalised patients with a diagnosis of hydatidosis (ICD 122.0-122.9) in hospitals of the public health service of Extremadura. RESULTS: During the period of study, 876 patients were diagnosed with hydatid disease. Of these 536 (61%) of cases were male, with a mean age of 65.53±17.8 years. More importantly, 19 (2.2%) of patients were 19 years old, with 17 cases between 2003-2007 versus 2 cases between 2008-2012 (OR=7.83; 95%CI: 1.79-34.11; P=.001). A total of 141 (16.0%) were younger than 45 years. The primary diagnosis was most frequently reported in the younger population <45 years, whereas the secondary diagnosis was usually found in the elderly population >70 years (P<.05). The incidence rate of hydatid disease obtained from Hospital Discharge Records (HDRs) was significantly higher compared to the incidence that was declared in the Notifiable Disease System of Extremadura (8.02 cases per 10(5) person-years vs. 1.88 cases per 10(5) person-years [P<.05]). CONCLUSION: In Extremadura hydatid disease is still frequent. With a clear decrease in the number of paediatric cases. The number of cases obtained from HDRs regarding Notification System Diseases Extremadura suggests the need for modifications to improve surveillance and control of hydatid disease.

Fever of unknown origin as the first manifestation of colonic pathology.

Fever of unknown origin (FUO) is an entity caused by more than 200 diseases. Haematologic neoplasms are the most common malignant cause of FUO. Fever as a first symptom of colonic tumour pathology, both benign and malignant, is a rare form of presentation. Our work is a descriptive study of a series of 23 patients with colonic tumoral pathology who presented with fever of unknown origin. The mean age was 67.6 years; 56.5% of patients were men and 43.5% were women. Primary malignant neoplasia was the most common diagnosis. Blood cultures were positive in 45% of the samples. Coagulase-negative staphylococci were the most common cause of bacteraemia. Nine of 10 faecal occult blood tests performed were positive. Fever secondary to colon neoplasms, both benign and malignant, usually presents with a bacteraemic pattern, with positive results for blood-culture tests in a high percentage of cases.

Is babesiosis a rare zoonosis in Spain? Its impact on the Spanish Health System over 23 years.

BACKGROUND: Babesiosis is a zoonosis caused by an intraerythrocytic protozoan of the genus Babesia and transmitted mainly by ticks of the Ixodes spp. complex. There is no comprehensive global incidence in the literature, although the United States, Europe and Asia are considered to be endemic areas. In Europe, the percentage of ticks infected with Babesia spp. ranges from 0.78% to 51.78%. The incidence of babesiosis in hospitalized patients in Spain is 2.35 cases per 10,000,000 inhabitants/year. The mortality rate is estimated to be approximately 9% in hospitalized patients but can reach 20% if the disease is transmitted by transfusion. OBJECTIVE: To analyze the epidemiological impact of inpatients diagnosed with babesiosis on the National Health System (NHS) of Spain between 1997 and 2019. METHODOLOGY: A retrospective longitudinal descriptive study that included inpatients diagnosed with babesiosis [ICD-9-CM code 088.82, ICD-10 code B60.0, cases ap2016-2019] in public Spanish NHS hospitals between 1 January 1997 and 31 December 2019 was developed. Data were obtained from the minimum basic dataset (CMBD in Spanish), which was provided by the Ministerio de Sanidad, Servicios Sociales e Igualdad after the receipt of a duly substantiated request and the signing of a confidentiality agreement. MAIN FINDINGS: Twenty-nine inpatients diagnosed with babesiosis were identified in Spain between 1997 and 2019 (IR: 0.28 cases/10,000,000 person-years). A total of 82.8% of the cases were men from urban areas who were approximately 46 years old. The rate of primary diagnoses was 55.2% and the number of readmissions was 79.3%. The mean hospital stay was 20.3±19.2 days, with an estimated cost of €186,925.66. Two patients, both with secondary diagnoses of babesiosis, died in our study. CONCLUSIONS: Human babesiosis is still a rare zoonosis in Spain, with an incidence rate that has been increasing over the years. Most cases occurred in middle-aged men from urban areas between summer and autumn. The Castilla-La-Mancha and Extremadura regions recorded the highest number of cases. Given the low rate of primary diagnoses (55.2%) and the high number of readmissions (79.3%), a low clinical suspicion is likely. There was a 6.9% mortality in our study. Both patients who died were patients with secondary diagnoses of the disease.

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

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

How Has the Aspergillosis Case Fatality Rate Changed over the Last Two Decades in Spain?

(1) Background: Aspergillus produces high morbidity and mortality, especially in at-risk populations. In Spain, the evolution of mortality in recent years due to this fungus is not well established. The aim of this study was to estimate the case fatality rate of aspergillosis in inpatients from 1997 to 2017 in Spain. (2) Methodology: A retrospective descriptive study was conducted with records of inpatients admitted to the National Health System with a diagnosis of aspergillosis. (3) Principal findings: Of 32,960 aspergillosis inpatients, 24.5% of deaths were registered, and 71% of the patients who died were men. The percentage of deaths increased progressively with age. The case fatality rate progressively decreased over the period, from 25.4 and 27.8% in 1997-1998 to values of 20.6 and 20.8% in 2016 and 2017. Influenza and pneumonia occurrence/association significantly increased case fatality rates in all cases. (4) Conclusions: Our study shows that lethality significantly decreased in the last two decades despite the increase in cases. This highlights the fact that patients with solid and/or hematological cancer do not have a much higher mortality rate than the group of patients with pneumonia or influenza alone, these two factors being the ones that cause the highest CFRs. We also need studies that analyze the causes of mortality to decrease it and studies that evaluate the impact of COVID-19.

Low molecular weight heparin is useful in adult COVID-19 inpatients. Experience during the first Spanish wave: observational study.

BACKGROUND: The intensity of the thromboprophylaxis needed as a potential factor for preventing inpatient mortality due to coronavirus disease-19 (COVID-19) remains unclear. OBJECTIVE: To explore the association between anticoagulation intensity and COVID-19 survival. DESIGN AND SETTING: Retrospective observational study in a tertiary-level hospital in Spain. METHODS: Low-molecular-weight heparin (LMWH) status was ascertained based on prescription at admission. To control for immortal time bias, anticoagulant use was analyzed as a time-dependent variable. RESULTS: 690 patients were included (median age, 72 years). LMWH was administered to 615 patients, starting from hospital admission (89.1%). 410 (66.7%) received prophylactic-dose LMWH; 120 (19.5%), therapeutic-dose LMWH; and another 85 (13.8%) who presented respiratory failure, high D-dimer levels (> 3 mg/l) and non-worsening of inflammation markers received prophylaxis of intermediate-dose LMWH. The overall inpatient-mortality rate was 38.5%. The anticoagulant nonuser group presented higher mortality risk than each of the following groups: any LMWH users (HR 2.1; 95% CI: 1.40-3.15); the prophylactic-dose heparin group (HR 2.39; 95% CI, 1.57-3.64); and the users of heparin dose according to biomarkers (HR 6.52; 95% CI, 2.95-14.41). 3.4% of the patients experienced major hemorrhage. 2.8% of the patients developed an episode of thromboembolism. CONCLUSIONS: This observational study showed that LMWH administered at the time of admission was associated with lower mortality among unselected adult COVID-19 inpatients. The magnitude of the benefit may have been greatest for the intermediate-dose subgroup. Randomized controlled trials to assess the benefit of heparin within different therapeutic regimes for COVID-19 patients are required.

Use of noninvasive ventilation on internal wards for elderly patients with limitations to respiratory care: a cohort study.

BACKGROUND: The use of noninvasive positive pressure ventilation (NPPV) outside the intensive wards has been evaluated in patients with no limitation on life-sustaining support. Our aim was to evaluate its usefulness in general wards for patients with NPPV as the ceiling of ventilator care when admission to the intensive care unit (ICU) has been withheld. MATERIALS AND METHODS: Noninvasive positive pressure ventilation was used in 44 patients with acute respiratory failure (ARF) and limitations to respiratory care- 22 with chronic obstructive pulmonary disease (COPD) exacerbations and 22 with acute cardiogenic pulmonary oedema (CPE). Survival at hospital discharge, and survival and readmission rate at 12 months were assessed. RESULTS: Sixty-three per cent of COPD and 55% of CPE patients survived hospital discharge; and 50% and 37% respectively, were alive after 1 year. The cause of the in-hospital mortality was related to the admission diagnosis in 88% of cases. Cancer in COPD patients [P = 0·040, odds ratio (OR) = 15, 95% CI = 1·14-198] and the completion of NPPV treatment in both diseases (P = 0·008, OR = 0·03, 95% CI = 0·00-0·39 for COPD and P = 0·010, OR = 0·04, 95% CI = 0·00-0·45 for CPE) were related to in-hospital mortality. Fifty-six per cent of COPD and 33% of CPE patients that survived hospital admission were readmitted. CONCLUSIONS: Our study suggests that the use of NPPV in general wards could be a safe and effective option, as a last choice treatment, in patients with NPPV as the ceiling of ventilator care when admission to ICU has been withheld.

Portal Hypertension as a Complication of Cystic Echinococcosis: A 20-Year Cohort Analysis.

Cystic echinococcosis (CE) is a parasitic disease caused by the larval forms of species of the tapeworm Echinococcus. The most common location is the liver. To assess the frequency and clinical characteristics of portal hypertension (PH) and the risk factors for PH development, we performed a retrospective observational study of inpatients diagnosed with hepatic CE and PH from January 1998 to December 2018, at Complejo Asistencial Universitario de Salamanca, Spain. Of 362 patients analyzed with hepatic CE, 15 inpatients (4.1%) had a portal vein diameter ≥ 14 mm, and the mean diameter of the portal vein was 16.9 (standard deviation [SD] ±2.1) mm. Twelve patients were men. The mean age was 59.5 years (SD ± 17.8 years). Four patients had ascites (26.6%), four had collateral circulation (26.6%), 14 had hepatosplenomegaly (93.3%), five had esophageal varices (33.3%), four had hematemesis, and three had jaundice. Other causes of PH included hepatitis B virus (1 patient) and hepatitis C virus (1 patient) infections and alcohol abuse (1 patient). The host variables associated with PH development were male sex (odds ratio, 4.6; 95% confidence interval, 1.1-20.9; P = 0.030) and larger cyst size (10.8 ± 6.3 versus 7.6 ± 4.1; P = 0.004). Hepatic CE is an infrequent cause of PH that usually occurs without indications of liver failure. Larger cyst size and male sex were the main risk factors associated with this complication. Mortality was higher for patients with hepatic CE with PH than for patients with hepatic CE without PH.

Clinical Spectrum of Schistosomiasis: An Update.

Schistosomiasis is a helminthic infection and one of the neglected tropical diseases (NTDs). It is caused by blood flukes of the genus Schistosoma. It is an important public health problem, particularly in poverty-stricken areas, especially those within the tropics and subtropics. It is estimated that at least 236 million people worldwide are infected, 90% of them in sub-Saharan Africa, and that this disease causes approximately 300,000 deaths annually. The clinical manifestations are varied and affect practically all organs. There are substantial differences in the clinical presentation, depending on the phase and clinical form of schistosomiasis in which it occurs. Schistosomiasis can remain undiagnosed for a long period of time, with secondary clinical lesion. Here, we review the clinical profile of schistosomiasis. This information may aid in the development of more efficacious treatments and improved disease prognosis.

Detection of SARS-CoV-2 RNA in Urine by RT-LAMP: A Very Rare Finding.

Detection of SARS-CoV-2 is routinely performed in naso/oropharyngeal swabs samples from patients via RT-qPCR. The RT-LAMP technology has also been used for viral RNA detection in respiratory specimens with both high sensitivity and specificity. Recently, we developed a novel RT-LAMP test for SARS-CoV-2 RNA detection in nasopharyngeal swab specimens (named, N15-RT-LAMP) that can be performed as a single-tube colorimetric method, in a real-time platform, and as dry-LAMP. To date, there has been very little success in detecting SARS-CoV-2 RNA in urine by RT-qPCR, and the information regarding urine viral excretion is still scarce and not comprehensive. Here, we tested our N15-RT-LAMP on the urine of 300 patients admitted to the Hospital of Salamanca, Spain with clinical suspicion of COVID-19, who had a nasopharyngeal swab RT-qPCR-positive (n = 100), negative (n = 100), and positive with disease recovery (n = 100) result. The positive group was also tested by RT-qPCR for comparison to N15-RT-LAMP. Only a 4% positivity rate was found in the positive group via colorimetric N15-RT-LAMP and 2% via RT-qPCR. Our results are consistent with those obtained in other studies that the presence of SARS-CoV-2 RNA in urine is a very rare finding. The absence of SARS-CoV-2 RNA in urine in the recovered patients might suggest that the urinary route is very rarely used for viral particle clearance.

Development of a severity of disease score and classification model by machine learning for hospitalized COVID-19 patients.

BACKGROUND: Efficient and early triage of hospitalized Covid-19 patients to detect those with higher risk of severe disease is essential for appropriate case management. METHODS: We trained, validated, and externally tested a machine-learning model to early identify patients who will die or require mechanical ventilation during hospitalization from clinical and laboratory features obtained at admission. A development cohort with 918 Covid-19 patients was used for training and internal validation, and 352 patients from another hospital were used for external testing. Performance of the model was evaluated by calculating the area under the receiver-operating-characteristic curve (AUC), sensitivity and specificity. RESULTS: A total of 363 of 918 (39.5%) and 128 of 352 (36.4%) Covid-19 patients from the development and external testing cohort, respectively, required mechanical ventilation or died during hospitalization. In the development cohort, the model obtained an AUC of 0.85 (95% confidence interval [CI], 0.82 to 0.87) for predicting severity of disease progression. Variables ranked according to their contribution to the model were the peripheral blood oxygen saturation (SpO2)/fraction of inspired oxygen (FiO2) ratio, age, estimated glomerular filtration rate, procalcitonin, C-reactive protein, updated Charlson comorbidity index and lymphocytes. In the external testing cohort, the model performed an AUC of 0.83 (95% CI, 0.81 to 0.85). This model is deployed in an open source calculator, in which Covid-19 patients at admission are individually stratified as being at high or non-high risk for severe disease progression. CONCLUSIONS: This machine-learning model, applied at hospital admission, predicts risk of severe disease progression in Covid-19 patients.

Date of Admission during COVID-19 Pandemic Impacted Patient Outcomes in Addition to the Higher Efficacy of Tocilizumab Plus High-Dose Corticosteroid Therapy Compared to Tocilizumab Alone.

BACKGROUND: The evidence for the efficacy of glucocorticoids combined with tocilizumab (TCZ) in COVID-19 comes from observational studies or subgroup analysis. Our aim was to compare outcomes between hospitalized COVID-19 patients who received high-dose corticosteroid pulse therapy and TCZ and those who received TCZ. METHODS: A retrospective single-center study was performed on consecutive hospitalized patients with severe COVID-19 between 1 March and 23 April 2020. Patients treated with either TCZ (400-600 mg, one to two doses) and methylprednisolone pulses (MPD-TCZ group) or TCZ alone were analyzed for the occurrence of a combined endpoint of death and need for invasive mechanical ventilation during admission. The independence of both treatment groups was tested using machine learning classifiers, and relevant variables that were potentially different between the groups were measured through a mean decrease accuracy algorithm. RESULTS: An earlier date of admission was significantly associated with worse outcomes regardless of treatment type. Twenty patients died (27.0%) in the TCZ group, and 33 (44.6%) died or required intubation (n = 74), whereas in the MPD-TCZ group, 15 (11.0%) patients died and 29 (21.3%) patients reached the combined endpoint (n = 136; p = 0.006 and p < 0.001, respectively). Machine learning methodology using a random forest classifier confirmed significant differences between the treatment groups. CONCLUSIONS: MPD and TCZ improved outcomes (death and invasive mechanical ventilation) among hospitalized COVID-19 patients, but confounding variables such as the date of admission during the COVID-19 pandemic should be considered in observational studies.