More than what meets the eye in COVID-19 critical illness: A case report of bilateral femoral neuropathy due to psoas hematomas.

Bilateral femoral neuropathy is rare, especially that caused by bilateral compressive iliopsoas, psoas, or iliacus muscle hematomas. We present a case of bilateral femoral neuropathy due to spontaneous psoas hematomas developed during COVID-19 critical illness. A 41-year-old patient developed COVID-19 pneumonia, and his condition deteriorated rapidly. A decrease in the hemoglobin level prompted imaging studies during his intensive care unit (ICU) stay. Bilateral psoas hematomas were identified as the source of bleeding. Thereafter, the patient complained of weakness in both upper and lower limbs and numbness in the lower limb. He was considered to have critical illness neuropathy and was referred to rehabilitation. Electrodiagnostic testing suggested bilateral femoral neuropathy because of compression due to hematomas developed during the course of his ICU stay. The consequences of iliopsoas hematomas occurring in the critically ill can be catastrophic, ranging from hemorrhagic shock to severe weakness, highlighting the importance of recognizing this entity.

Long-Term Taste and Smell Outcomes After COVID-19.

Importance: Self-report surveys suggest that long-lasting taste deficits may occur after SARS-CoV-2 infection, influencing nutrition, safety, and quality of life. However, self-reports of taste dysfunction are inaccurate, commonly reflecting deficits due to olfactory not taste system pathology; hence, quantitative testing is needed to verify the association of post-COVID-19 condition with taste function. Objective: To use well-validated self-administered psychophysical tests to investigate the association of COVID-19 with long-term outcomes in taste and smell function. Design, Setting, and Participants: This nationwide cross-sectional study included individuals with and without a prior history of COVID-19 recruited from February 2020 to August 2023 from a social media website (Reddit) and bulletin board advertisements. In the COVID-19 cohort, there was a mean of 395 days (95% CI, 363-425 days) between diagnosis and testing. Exposure: History of COVID-19. Main Outcomes and Measures: The 53-item Waterless Empirical Taste Test (WETT) and 40-item University of Pennsylvania Smell Identification Test (UPSIT) were used to assess taste and smell function. Total WETT and UPSIT scores and WETT subtest scores of sucrose, citric acid, sodium chloride, caffeine, and monosodium glutamate were assessed for groups with and without a COVID-19 history. The association of COVID-19 with taste and smell outcomes was assessed using analysis of covariance, χ2, and Fisher exact probability tests. Results: Tests were completed by 340 individuals with prior COVID-19 (128 males [37.6%] and 212 females [62.4%]; mean [SD] age, 39.04 [14.35] years) and 434 individuals with no such history (154 males [35.5%] and 280 females [64.5%]; mean (SD) age, 39.99 [15.61] years). Taste scores did not differ between individuals with and without previous COVID-19 (total WETT age- and sex-adjusted mean score, 33.41 [95% CI, 32.37-34.45] vs 33.46 [95% CI, 32.54-34.38]; P = .94). In contrast, UPSIT scores were lower in the group with previous COVID-19 than the group without previous COVID-19 (mean score, 34.39 [95% CI, 33.86-34.92] vs 35.86 [95% CI, 35.39-36.33]; P < .001]); 103 individuals with prior COVID-19 (30.3%) and 91 individuals without prior COVID-19 (21.0%) had some degree of dysfunction (odds ratio, 1.64 [95% CI, 1.18-2.27]). The SARS-CoV-2 variant present at the time of infection was associated with smell outcomes; individuals with original untyped and Alpha variant infections exhibited more loss than those with other variant infections; for example, total to severe loss occurred in 10 of 42 individuals with Alpha variant infections (23.8%) and 7 of 52 individuals with original variant infections (13.5%) compared with 12 of 434 individuals with no COVID-19 history (2.8%) (P < .001 for all). Conclusions and Relevance: In this study, taste dysfunction as measured objectively was absent 1 year after exposure to COVID-19 while some smell loss remained in nearly one-third of individuals with this exposure, likely explaining taste complaints of many individuals with post-COVID-19 condition. Infection with earlier untyped and Alpha variants was associated with the greatest degree of smell loss.

Patients hospitalized with active tuberculosis and Covid-19 coinfection: A matched case-control from the Brazilian Covid-19 Registry.

Although control of Covid-19 has improved, the virus continues to cause infections, such as tuberculosis, that is still endemic in many countries, representing a scenario of coinfection. To compare Covid-19 clinical manifestations and outcomes between patients with active tuberculosis infection and matched controls. This is a matched case-control study based on data from the Brazilian Covid-19 Registry, in hospitalized patients aged 18 or over with laboratory confirmed Covid-19 from March 1, 2020, to March 31, 2022. Cases were patients with tuberculosis and controls were Covid-19 patients without tuberculosis. From 13,636 Covid-19, 36 also had active tuberculosis (0.0026%). Pulmonary fibrosis (5.6% vs 0.0%), illicit drug abuse (30.6% vs 3.0%), alcoholism (33.3% vs 11.9%) and smoking (50.0% vs 9.7%) were more common among patients with tuberculosis. They also had a higher frequency of nausea and vomiting (25.0% vs 10.4%). There were no significant differences in in-hospital mortality, mechanical ventilation, need for dialysis and ICU stay. Patients with TB infection presented a higher frequency of pulmonary fibrosis, abuse of illicit drugs, alcoholism, current smoking, symptoms of nausea and vomiting. The outcomes were similar between them.

Clinical characteristics and prognosis of patients with COVID-19 on mechanical ventilation undergoing continuous renal replacement therapy.

BACKGROUND: The coronavirus disease (COVID-19) pandemic has significantly strained global healthcare, particularly in the management of patients requiring mechanical ventilation (MV) and continuous renal replacement therapy (CRRT). This study investigated the characteristics and prognoses of these patients. METHODS: This multicenter retrospective cohort study gathered data from patients with COVID-19 across 26 medical centers. Logistic analysis was used to identify the factors associated with CRRT implementation. RESULTS: Of the 640 patients with COVID-19 who required MV, 123 (19.2%) underwent CRRT. Compared to the non-CRRT group, the CRRT group was older and exhibited higher sequential organ failure assessment scores. The incidence of hypertension, diabetes, cardiovascular disease, chronic neurological disease, and chronic kidney disease was also higher in the CRRT group. Moreover, the CRRT group had higher intensive care unit (ICU) (75.6% vs. 26.9%, p < 0.001) and in-hospital (79.7% vs. 29.6%, p < 0.001) mortality rates. CRRT implementation was identified as an independent risk factor for both ICU mortality (hazard ratio [HR]:1.833, 95% confidence interval [CI]:1.342-2.505, p < 0.001) and in-hospital mortality (HR: 2.228, 95% CI: 1.648-3.014, p < 0.001). Refractory respiratory failure (n = 99, 19.1%) was the most common cause of death in the non-CRRT death group, and shock with multi-organ failure (n = 50, 40.7%) was the most common cause of death in the CRRT death group. Shock with multi-organ failure and cardiac death were significantly more common in the CRRT death group, compared to non-CRRT death group. CONCLUSION: This study indicates that CRRT is associated with higher ICU and in-hospital mortality rates in patients with COVID-19 who require MV. Notably, the primary cause of death in the CRRT group was shock with multi-organ failure, emphasizing the severe clinical course for these patients, while refractory respiratory failure was most common in non-CRRT patients.

Coronavirus infection and systemic inflammatory reaction syndrome.

OBJECTIVE: Aim: The purpose of this study was a clinical approbation of the Kometad drug (international non-proprietary name sodium colistimethate), an antibiotic from the polymyxin group in patients with severe course of confirmed сoronavirus infection in the intensive care unit of the Branch of the I. Zhekenova Municipal Clinical Infectious Diseases Hospital.. PATIENTS AND METHODS: Materials and Methods: The methodology is based on both theoretical and empirical methods of scientific cognition. During the study, the features of the Coronavirus infection and the inflammatory reaction syndrome were considered, which became quite a big problem during the pandemic. RESULTS: Results: The main indications for the tested drug and the consequences of its use for one age group were also determined. CONCLUSION: Conclusions: The conclusion was made about the positive dynamics of the patients' health status, and recommendations were given for further research in this area. The practical significance of this study lies in the first clinical approbation of the Kometad drug, which can be used in medicine to reduce the severity of the systemic inflammatory reaction syndrome and improve the patient's health as a result of the disease of Coronavirus infection, after further clinical trials of the drug with different age groups of patients.

Mortality risk in patients with obesity and COVID-19 infection: a systematic review and meta-analysis.

Obesity is a risk factor for severe respiratory diseases, including COVID-19 infection. Meta-analyses on mortality risk were inconsistent. We systematically searched 3 databases (Medline, Embase, CINAHL) and assessed the quality of studies using the Newcastle-Ottawa tool (CRD42020220140). We included 199 studies from US and Europe, with a mean age of participants 41.8-78.2 years, and a variable prevalence of metabolic co-morbidities of 20-80 %. Exceptionally, one third of the studies had a low prevalence of obesity of <20 %. Compared to patients with normal weight, those with obesity had a 34 % relative increase in the odds of mortality (p-value 0.002), with a dose-dependent relationship. Subgroup analyses showed an interaction with the country income. There was a high heterogeneity in the results, explained by clinical and methodologic variability across studies. We identified one trial only comparing mortality rate in vaccinated compared to unvaccinated patients with obesity; there was a trend for a lower mortality in the former group. Mortality risk in COVID-19 infection increases in parallel to an increase in BMI. BMI should be included in the predictive models and stratification scores used when considering mortality as an outcome in patients with COVID-19 infections. Furthermore, patients with obesity might need to be prioritized for COVID-19 vaccination.

Neutrophil extracellular traps induce persistent lung tissue damage via thromboinflammation without altering virus resolution in a mouse coronavirus model.

BACKGROUND: During infection, neutrophil extracellular traps (NETs) are associated with severity of pulmonary diseases such as acute respiratory disease syndrome. NETs induce subsequent immune responses, are directly cytotoxic to pulmonary cells, and are highly procoagulant. Anticoagulation treatment was shown to reduce in-hospital mortality, indicating thromboinflammatory complications. However, data are sparsely available on the involvement of NETs in secondary events after virus clearance, which can lead to persistent lung damage and postacute sequelae with chronic fatigue and dyspnea. OBJECTIVES: This study focuses on late-phase events using a murine model of viral lung infection with postacute sequelae after virus resolution. METHODS: C57BL/6JRj mice were infected intranasally with the betacoronavirus murine coronavirus (MCoV, strain MHV-A95), and tissue samples were collected after 2, 4, and 10 days. For NET modulation, mice were pretreated with OM-85 or GSK484 and DNase I were administered intraperitoneally between days 2 to 5 and days 4 to 7, respectively. RESULTS: Rapid, platelet-attributed thrombus formation was followed by a second, late phase of thromboinflammation. This phase was characterized by negligible virus titers but pronounced tissue damage, apoptosis, oxidative DNA damage, and presence of NETs. Inhibition of NETs during the acute phase did not impact virus burden but decreased lung cell apoptosis by 67% and oxidative stress by 94%. Prevention of neutrophil activation by immune training before virus infection reduced damage by 75%, NETs by 31%, and pulmonary thrombi by 93%. CONCLUSION: NETs are detrimental inducers of tissue damage during respiratory virus infection but do not contribute to virus clearance.

Complications of the Central Nervous System in Pediatric Patients With Common Cold Coronavirus Infection During 2014-2019.

BACKGROUND: In pediatric patients, the common cold coronavirus (ccCoV) usually causes mild respiratory illness. There are reports of coronavirus causing central nervous system (CNS) infection in experimental animal models. Some immunocompromised patients have also been reported to have fatal CNS infections with ccCoV. The aim of this study was to investigate the clinical characteristics of CNS complications related to ccCoV infection. METHODS: From January 2014 to December 2019, a retrospective analysis was performed of medical records from hospitalized patients under 19 years of age whose ccCoV was detected through polymerase chain reaction in respiratory specimens. The CNS complications were defined as clinically diagnosed seizure, meningitis, encephalopathy, and encephalitis. RESULTS: A total of 436 samples from 420 patients were detected as ccCoV. Among the 420 patients, 269 patients were immunocompetent and 151 patients were immunocompromised. The most common type of ccCoV was OC43 (52% in immunocompetent, 37% in immunocompromised). CNS complications were observed in 9.4% (41/436). The most common type of CNS complication was the fever-provoked seizure under pre-existing neurologic disease (42% in immunocompetent and 60% in immunocompromised patients). Among patients with CNS complications, two immunocompetent patients required intensive care unit admission due to encephalitis. Three patients without underlying neurological disease started anti-seizure medications for the first time at this admission. There was no death related to ccCoV infection. CONCLUSION: ccCoV infection may cause severe clinical manifestations such as CNS complications or neurologic sequelae, even in previously healthy children.

Ablation of microglia following infection of the central nervous system with a neurotropic murine coronavirus infection leads to increased demyelination and impaired remyelination.

Intracranial inoculation of susceptible mice with a glial-tropic strain of mouse hepatitis virus (JHMV), a murine coronavirus, results in an acute encephalomyelitis followed by viral persistence in white matter tracts accompanied by chronic neuroinflammation and demyelination. Microglia are the resident immune cell of the central nervous system (CNS) and are considered important in regulating events associated with neuroinflammation as well as influencing both white matter damage and remyelination. To better understand mechanisms by which microglia contribute to these immune-mediated events, JHMV-infected mice with established demyelination were treated with the small molecular inhibitor of colony stimulating factor 1 receptor (CSF1R), PLX5622, to deplete microglia. Treatment with PLX5622 did not affect viral replication within the CNS yet the severity of demyelination was increased and remyelination impaired compared to control mice. Gene expression analysis revealed that targeting microglia resulted in altered expression of genes associated with immune cell activation and phagocytosis of myelin debris. These findings indicate that microglia are not critical in viral surveillance in persistently JHMV-infected mice yet restrict white matter damage and remyelination, in part, by influencing phagocytosis of myelin debris.

Distinct phenotypes of multisystem inflammatory syndrome in children: a cohort study.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a severe disease with an unpredictable course and a substantial risk of cardiogenic shock. Our objectives were to (a) compare MIS-C phenotypes across the COVID-19 pandemic, (b) identify features associated with intensive care need and treatment with biologic agents. METHODS: Youth aged 0-18 years, fulfilling the World Health Organization case definition of MIS-C, and admitted to the Alberta Children's Hospital during the first four waves of the COVID-19 pandemic (May 2020-December 2021) were included in this cohort study. Demographic, clinical, biochemical, imaging, and treatment data were captured. RESULTS: Fifty-seven MIS-C patients (median age 6 years, range 0-17) were included. Thirty patients (53%) required intensive care. Patients in the third or fourth wave (indicated as phase 2 of the pandemic) presented with higher peak ferritin (µg/l, median (IQR) = 1134 (409-1806) vs. 370 (249-629), P = 0.001), NT-proBNP (ng/l, median (IQR) = 12,217 (3013-27,161) vs. 3213 (1216-8483), P = 0.02) and D-dimer (mg/l, median (IQR) = 4.81 (2.24-5.37) vs. 2.01 (1.27-3.34), P = 0.004) levels, and higher prevalence of liver enzyme abnormalities (n(%) = 17 (68) vs. 11 (34), P = 0.02), hypoalbuminemia (n(%) = 24 (100) vs. 25 (81), P = 0.03) and thrombocytopenia (n(%) 18 (72) vs. 11 (34), P = 0.007) compared to patients in the first two waves (phase 1). These patients had a higher need of non-invasive/mechanical ventilation (n(%) 4 (16) vs. 0 (0), P = 0.03). Unsupervised clustering analyses classified 47% of the patients in the correct wave and 74% in the correct phase of the pandemic. NT-proBNP was the only significant contributor to the need for intensive care in all applied multivariate regression models. Treatment with biologic agents was significantly associated with peak CRP (mg/l (median, IQR = 240.9 (132.9-319.4) vs. 155.8 (101.0-200.7), P = 0.02) and ferritin levels (µg/l, median (IQR) = 1380 (509-1753) vs. 473 (280-296)). CONCLUSIONS: MIS-C patients in a later stage of the pandemic displayed a more severe phenotype, reflecting the impact of distinct SARS-CoV-2 variants. NT-proBNP emerged as the most crucial feature associated with intensive care need, underscoring the importance of monitoring.

SARS-CoV-2 infections in pediatric and young adult recipients of chimeric antigen receptor T-cell therapy: an international registry report.

BACKGROUND: Immunocompromised patients are at increased risk of SARS-CoV-2 infections. Patients undergoing chimeric antigen receptor (CAR) T-cell therapy for relapsed/refractory B-cell malignancies are uniquely immunosuppressed due to CAR T-mediated B-cell aplasia (BCA). While SARS-CoV-2 mortality rates of 33%-40% are reported in adult CAR T-cell recipients, outcomes in pediatric and young adult CAR T-cell recipients are limited. METHODS: We created an international retrospective registry of CAR T recipients aged 0-30 years infected with SARS-CoV-2 within 2 months prior to or any time after CAR T infusion. SARS-CoV-2-associated illness was graded as asymptomatic, mild, moderate, or severe COVID-19, or multisystem inflammatory syndrome in children (MIS-C). To assess for risk factors associated with significant SARS-CoV-2 infections (infections requiring hospital admission for respiratory distress or supplemental oxygen), univariate and multivariable regression analyses were performed. RESULTS: Nine centers contributed 78 infections in 75 patients. Of 70 SARS-CoV-2 infections occurring after CAR T infusion, 13 (18.6%) were classified as asymptomatic, 37 (52.9%) mild, 11 (15.7%) moderate, and 6 (8.6%) severe COVID-19. Three (4.3%) were classified as MIS-C. BCA was not significantly associated with infection severity. Prior to the emergence of the Omicron variant, of 47 infections, 19 (40.4%) resulted in hospital admission and 7 (14.9%) required intensive care, while after the emergence of the Omicron variant, of 23 infections, only 1 (4.3%) required admission and the remaining 22 (95.7%) had asymptomatic or mild COVID-19. Death occurred in 3 of 70 (4.3%); each death involved coinfection or life-threatening condition. In a multivariable model, factors associated with significant SARS-CoV-2 infection included having two or more comorbidities (OR 7.73, CI 1.05 to 74.8, p=0.048) and age ≥18 years (OR 9.51, CI 1.90 to 82.2, p=0.014). In the eight patients infected with SARS-CoV-2 before CAR T, half of these patients had their CAR T infusion delayed by 15-30 days. CONCLUSIONS: In a large international cohort of pediatric and young adult CAR-T recipients, SARS-CoV-2 infections resulted in frequent hospital and intensive care unit admissions and were associated with mortality in 4.3%. Patients with two or more comorbidities or aged ≥18 years were more likely to experience significant illness. Suspected Omicron infections were associated with milder disease.

Immunological and virological triggers of type 1 diabetes: insights and implications.

Type 1 diabetes (T1D) is caused by an autoimmune process which culminates in the destruction of insulin-producing beta cells in the pancreas. It is widely believed that a complex and multifactorial interplay between genetic and environmental factors, such as viruses, play a crucial role in the development of the disease. Research over the past few decades has shown that there is not one single viral culprit, nor one single genetic pathway, causing the disease. Rather, viral infections, most notably enteroviruses (EV), appear to accelerate the autoimmune process leading to T1D and are often seen as a precipitator of clinical diagnosis. In support of this hypothesis, the use of anti-viral drugs has recently shown efficacy in preserving beta cell function after onset of diabetes. In this review, we will discuss the various pathways that viral infections utilize to accelerate the development of T1D. There are three key mechanisms linking viral infections to beta-cell death: One is modulated by the direct infection of islets by viruses, resulting in their impaired function, another occurs in a more indirect fashion, by modulating the immune system, and the third is caused by heightened stress on the beta-cell by interferon-mediated increase of insulin resistance. The first two aspects are surprisingly difficult to study, in the case of the former, because there are still many questions about how viruses might persist for longer time periods. In the latter, indirect/immune case, viruses might impact immunity as a hit-and-run scenario, meaning that many or all direct viral footprints quickly vanish, while changes imprinted upon the immune system and the anti-islet autoimmune response persist. Given the fact that viruses are often associated with the precipitation of clinical autoimmunity, there are concerns regarding the impact of the recent global coronavirus-2019 (COVID-19) pandemic on the development of autoimmune disease. The long-term effects of COVID-19 infection on T1D will therefore be discussed, including the increased development of new cases of T1D. Understanding the interplay between viral infections and autoimmunity is crucial for advancing our knowledge in this field and developing targeted therapeutic interventions. In this review we will examine the intricate relationship between viral infections and autoimmunity and discuss potential considerations for prevention and treatment strategies.

Differential transcriptomic changes in the central nervous system and urinary bladders of mice infected with a coronavirus.

Multiple sclerosis (MS) often leads to the development of neurogenic lower urinary tract symptoms (LUTS). We previously characterized neurogenic bladder dysfunction in a mouse model of MS induced by a coronavirus, mouse hepatitis virus (MHV). The aim of the study was to identify genes and pathways linking neuroinflammation in the central nervous system with urinary bladder (UB) dysfunction to enhance our understanding of the mechanisms underlying LUTS in demyelinating diseases. Adult C57BL/6 male mice (N = 12) received either an intracranial injection of MHV (coronavirus-induced encephalomyelitis, CIE group), or sterile saline (control group). Spinal cord (SC) and urinary bladders (UB) were collected from CIE mice at 1 wk and 4 wks, followed by RNA isolation and NanoString nCounter Neuroinflammation assay. Transcriptome analysis of SC identified a significantly changed expression of >150 genes in CIE mice known to regulate astrocyte, microglia and oligodendrocyte functions, neuroinflammation and immune responses. Two genes were significantly upregulated (Ttr and Ms4a4a), and two were downregulated (Asb2 and Myct1) only in the UB of CIE mice. Siglec1 and Zbp1 were the only genes significantly upregulated in both tissues, suggesting a common transcriptomic link between neuroinflammation in the CNS and neurogenic changes in the UB of CIE mice.

Síndrome inflamatória multissistêmica em crianças infectadas por coronavírus: uma revisão integrativa / Multisystemic inflamatory syndrome in children infected by coronavirus: an integrative review / Síndrome inflamatorio multisistémico en niños infectados por coronavirus: una revisión integradora

Durante a pandemia de COVID-19, foram observadas manifestações atípicas em pacientes pediátricos em diversas regiões do mundo, e o conjunto desses sintomas caracterizou uma nova patologia denominada Síndrome Inflamatória Multissistêmica em Crianças (MIS-C), ou Síndrome Inflamatória Multissistêmica Pediátrica Temporariamente associada ao COVID-19 (PIMS- TS). O objetivo desta revisão foi analisar as manifestações clínicas e as possíveis complicações relacionadas a tal quadro inflamatório. Foi realizada uma busca por artigos científicos nas bases de dados Embase, PubMed e Web of Science, por meio da combinação dos descritores "MIS-C", "PIMS- TS" e "COVID-19". Após a análise dos artigos encontrados, e considerando critérios de inclusão e exclusão, foram selecionados 15 estudos para compor esta revisão. A maioria dos estudos mencionaram complicações gastrointestinais, cardiovasculares, respiratórias e mucocutâneas. Ademais, foram encontrados marcadores que indicavam estado inflamatório generalizado e coagulopatia. Assim, concluiu-se que MIS-C provavelmente é uma síndrome manifestada após a infecção por SARS-CoV-2, podendo ocasionar quadros mais graves, mas com baixas taxas de mortalidade.

During the COVID-19 pandemic, atypical manifestations were observed in pediatric patients in different regions of the world, and the set of these symptoms characterized a new pathology called Multisystemic Inflammatory Syndrome in Children (MIS-C), or Pediatric Multisystemic Inflammatory Syndrome Temporarily associated with COVID-19 (PIMS-TS). The purpose of this review was to analyze the clinical manifestations and possible complications related to such an inflammatory condition. A search for scientific articles was carried out in the databases Embase, PubMed and Web of Science, by combining the descriptors "MIS-C", "PIMS-TS" and "COVID-19". After analyzing the articles found, and considering inclusion and exclusion criteria, 15 studies were selected to compose this review. Most studies mentioned gastrointestinal, cardiovascular, respiratory and mucocutaneous complications. In addition, markers were found that indicated generalized inflammatory status and coagulopathy. Thus, it was concluded that MIS-C is probably a syndrome manifested after infection by SARS-CoV-2, which can cause more severe conditions, but with low mortality rates.

Durante la pandemia de COVID-19 se observaron manifestaciones atípicas en pacientes pediátricos de diferentes regiones del mundo, y el conjunto de estos síntomas caracterizó una nueva patología denominada Síndrome Inflamatorio Multisistémico en Niños (SMI-C), o Síndrome Inflamatorio Multisistémico Pediátrico Asociado Temporalmente a COVID-19 (SIPM-TS). El propósito de esta revisión fue analizar las manifestaciones clínicas y las posibles complicaciones relacionadas con dicha condición inflamatoria. Se realizó una búsqueda de artículos científicos en las bases de datos Embase, PubMed y Web of Science, combinando los descriptores "MIS-C", "PIMS- TS" y "COVID-19". Tras analizar los artículos encontrados, y teniendo en cuenta los criterios de inclusión y exclusión, se seleccionaron 15 estudios para componer esta revisión. La mayoría de los estudios mencionaron complicaciones gastrointestinales, cardiovasculares, respiratorias y mucocutáneas. Además, se encontraron marcadores que indicaban un estado inflamatorio generalizado y coagulopatía. Así pues, se concluyó que el SMI-C es probablemente un síndrome que se manifiesta tras la infección por el SARS-CoV-2, que puede causar cuadros más graves, pero con bajas tasas de mortalidad.

Una revisión de literatura del síndrome pos-COVID-19 / A literature review about post-COVID-19 syndrome

Introducción: El COVID-19 es una enfermedad vírica que ha generado gran afectación en la salud de la población global. Varios estudios han demostrado que después de dos o tres meses de la infección por coronavirus los pacientes continúan refiriendo sintomatología: la fatiga, la disnea y el dolor de cabeza son los más frecuentes. Objetivo: Exponer información relevante de carácter científico sobre el síndrome pos-COVID. Desarrollo: Se hizo una revisión de la literatura entre noviembre de 2019 y febrero de 2021, que comprendió las fases de planeación, diseño y gestión, análisis, elaboración y formalización. Se realizó la búsqueda estratégica mediante ScienceDirect, PubMed/Medline, NusrginsOvid, SciELO y Google Académico, a través de la combinación de los operadores OR, AND y NOT. Se consideraron textos completos, en español, inglés y portugués, entre 2019 y 2021. Después de realizada la selección y revisión profunda se obtuvieron 38 artículos que cumplieron con el objetivo planeado, los cuales fueron sometidos a la metodología PRISMA. Conclusiones: Existe un síndrome pos-COVID, el cual se relaciona de forma directa con un proceso de inflamación multisistémico, lo que evidencia síntomas en pacientes después de tres meses de culminado el proceso infeccioso. Entre estos, la fatiga, la disnea y el dolor de cabeza resultan los más frecuentes; además de consecuencias cardíacas, psicológicas y neurobiológicas(AU)

Introduction: COVID-19 is a viral disease that has caused great affectation in the health of the global population. Several studies have shown that two to three months after coronavirus infection patients continue to report symptoms, fatigue, dyspnea and headache being the most frequent. Objective: To present relevant scientific information on post-COVID-19 syndrome. Development: A literature review was conducted between November 2020 and February 2021, consisting of the phases of planning, design and management, analysis, elaboration and formalization. The strategic search was carried out using ScienceDirect, PubMed/Medline, NusrginsOvid, SciELO and Google Scholar, through the combination of the Boolean operators OR, AND and NOT. Full texts were considered, in Spanish, English and Portuguese, from 2019 to 2021. After the selection and an in-depth review, 38 articles were obtained that met the set objective, which were processed with the PRISMA methodology. Conclusions: There is a post-COVID-19 syndrome, directly related to a multisystem inflammatory process, which shows symptoms in patients three months after the end of the infectious process. Among these, fatigue, dyspnea and headache are the most frequent, in addition to cardiac, psychological and neurobiological consequences(AU)

Lethal Swine Acute Diarrhea Syndrome Coronavirus Infection in Suckling Mice.

Swine acute diarrhea syndrome coronavirus (SADS-CoV) is a recently emerging bat-borne coronavirus responsible for high mortality rates in piglets. In vitro studies have indicated that SADS-CoV has a wide tissue tropism in different hosts, including humans. However, whether this virus potentially threatens other animals remains unclear. Here, we report the experimental infection of wild-type BALB/c and C57BL/6J suckling mice with SADS-CoV. We found that mice less than 7 days old are susceptible to the virus, which caused notable multitissue infections and damage. The mortality rate was the highest in 2-day-old mice and decreased in older mice. Moreover, a preliminary neuroinflammatory response was observed in 7-day-old SADS-CoV-infected mice. Thus, our results indicate that SADS-CoV has potential pathogenicity in young hosts. IMPORTANCE SADS-CoV, which likely has originated from bat coronaviruses, is highly pathogenic to piglets and poses a threat to the swine industry. Little is known about its potential to disseminate to other animals. No efficient treatment is available, and the quarantine strategy is the only preventive measure. In this study, we demonstrated that SADS-CoV can efficiently replicate in suckling mice younger than 7 days. In contrast to infected piglets, in which intestinal tropism is shown, SADS-CoV caused infection and damage in all murine tissues evaluated in this study. In addition, neuroinflammatory responses were detected in some of the infected mice. Our work provides a preliminary cost-effective model for the screening of antiviral drugs against SADS-CoV infection.

Risk factors for COVID-19 case fatality rate in people with type 1 and type 2 diabetes mellitus: A nationwide retrospective cohort study of 235,248 patients in the Russian Federation.

The aim: To study the association of demographic, clinical, and laboratory factors and the use of glucose-lowering drugs and anti-coronavirus disease (COVID-19) vaccination with the COVID-19-related case fatality rate (CFR) in diabetes mellitus (DM) patients. Methods: This study is a nationwide observational cohort study based on the data from the National Diabetes Register (NDR) that is the database containing online clinical information about the population with DM. The outcomes (death or recovery) for COVID-19 were registered in 235,248 patients with DM [type 1 diabetes mellitus (T1DM), n = 11,058; type 2 diabetes mellitus (T2DM), n = 224,190] from March 20, 2020, until November 25, 2021. The unadjusted odds ratio (OR) and 95% confidence interval (CI) were used to estimate the risk factors for CFR. Then the ranging of significant factors was performed and the most vulnerable groups of factors for the lethal outcome were chosen. Results: The CFR due to COVID-19 was 8.1% in T1DM and 15.3% in T2DM. Increased CFR was associated with the male population [OR = 1.25 (95% CI: 1.09-1.44) in T1DM and 1.18 (95% CI: 1.15-1.21) in T2DM], age ≥65 years [OR = 4.44 (95% CI: 3.75-5.24) in T1DM and 3.18 (95% CI: 3.09-3.26) in T2DM], DM duration ≥10 years [OR = 2.46 (95% CI: 2.06-2.95) in T1DM and 2.11 (95% CI: 2.06-2.16) in T2DM], body mass index (BMI) ≥30 kg/m2 [OR = 1.95 (95% CI: 1.52-2.50)] in T1DM, HbA1c ≥7% [OR = 1.35 (95% CI: 1.29-1.43)] in T2DM. The atherosclerotic cardiovascular disease (ASCVD) and chronic kidney disease (CKD) were associated with higher CFR in T1DM but not in T2DM. The pre-COVID-19 glucose-lowering therapy in T2DM was differently associated with CFR (OR): 0.61 (95% CI: 0.59-0.62) for metformin, 0.59 (95% CI: 0.57-0.61) for dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors), 0.46 (95% CI: 0.44-0.49) for sodium-glucose co-transporter-2 (SGLT2) inhibitors, 0.38 (95% CI: 0.29-0.51) for glucagon-like peptide-1 receptor agonists (arGLP-1), 1.34 (95% CI: 1.31-1.37) for sulfonylurea (SU), and 1.47 (95% CI: 1.43-1.51) for insulin. Anti-COVID-19 vaccination was associated with a lower fatality risk in both DM types: OR = 0.07 (95% CI: 0.03-0.20) in T1DM and OR = 0.19 (95% CI: 0.17-0.22) in T2DM. Conclusions: The results of our study suggest that increased COVID-19-related fatality risk in both T1DM and T2DM patients associated with the male population, older age, longer DM duration, and absence of anti-COVID-19 vaccination. In T2DM, pre-COVID-19 glucose-lowering therapy with metformin, DPP-4 inhibitors, SGLT2 inhibitors, and arGLP-1 had a positive effect on the risk of death. The most vulnerable combination of risk factors for lethal outcome in both DM types was vaccine absence + age ≥65 years + DM duration ≥10 years.

Coinfection with PEDV and BVDV induces inflammatory bowel disease pathway highly enriched in PK-15 cells.

BACKGROUND: From the 1078 diarrhea stools tested in our survey from 2017 to 2020 in local area of China, PEDV was the key pathogen that was closely related to the death of piglets with diarrhea. In addition, coinfection of PEDV-positive samples with BVDV reached 17.24%. Although BVDV infection in swine is typically subclinical, the effect of PEDV and BVDV coinfection on disease severity and the potential molecular mechanism of coinfection with these two viruses remain unknown. METHODS: In this study, we developed a model of coinfection with porcine epidemic diarrhea virus (PEDV) and bovine viral diarrhea virus (BVDV) in PK15 cells, and a tandem mass tag (TMT) combined with LC-MS/MS proteomic approach was used to identify differential protein expression profiles. Additionally, we performed drug experiments to explore the inflammatory response induced by PEDV or BVDV mono- or coinfection. RESULTS: A total of 1094, 1538, and 1482 differentially expressed proteins (DEPs) were identified upon PEDV monoinfection, BVDV monoinfection and PEDV/BVDV coinfection, respectively. KEGG pathway analysis revealed that PEDV and BVDV coinfection led to a highly significantly enrichment of the inflammatory bowel disease (IBD) pathway. In addition, the NF-κB signaling pathway was more intensively activated by PEDV and BVDV coinfection, which induced higher production of inflammatory cytokines, than PEDV or BVDV monoinfection. CONCLUSIONS: Our study indicated that cattle pathogens might play synergistic roles in the pathogenesis of porcine diarrhea, which might also improve our understanding of the pathogenesis of multiple infections in diarrhea.

Mono-articular idiopathic heterotopic ossification in a Coronavirus infected patient admitted in the intensive care unit.

Heterotopic ossification (HO) designates a bone tissue formation within an atypical anatomical location and is commonly diagnosed in patients whom have suffered major traumas. The following case report presents a non-traumatic source of HO. A causality is deduced between the HO formation and an important inflammatory reaction originating from a Coronavirus infection. In contrast to other studies not only is the source non traumatic but the HO formation is unilateral. In systemic inflammatory reactions vigilance towards HO should be enhanced especially in patients treated during prolonged periods of time in intensive care units (ICU).

Medium-Term Cardiac Outcomes in Young People with Multi-system Inflammatory Syndrome: The Era of COVID-19.

Multi-system inflammatory syndrome in children (MIS-C) causes widespread inflammation including a pancarditis in the weeks following a COVID infection. As we prepare for further coronavirus surges, understanding the medium-term cardiac impacts of this condition is important for allocating healthcare resources. A retrospective single-center study of 67 consecutive patients with MIS-C was performed evaluating echocardiographic and electrocardiographic (ECG) findings to determine the point of worst cardiac dysfunction during the admission, then at intervals of 6-8 weeks and 6-8 months. Worst cardiac function occurred 6.8 ± 2.4 days after the onset of fever with mean 3D left ventricle (LV) ejection fraction (EF) 50.5 ± 9.8%. A pancarditis was typically present: 46.3% had cardiac impairment; 31.3% had pericardial effusion; 26.8% demonstrated moderate (or worse) valvar regurgitation; and 26.8% had coronary dilatation. Cardiac function normalized in all patients by 6-8 weeks (mean 3D LV EF 61.3 ± 4.4%, p < 0.001 compared to presentation). Coronary dilatation resolved in all but one patient who initially developed large aneurysms at presentation, which persisted 6 months later. ECG changes predominantly featured T-wave changes resolving at follow-up. Adverse events included need for ECMO (n = 2), death as an ECMO-related complication (n = 1), LV thrombus formation (n = 1), and subendocardial infarction (n = 1). MIS-C causes a pancarditis. In the majority, discharge from long-term follow-up can be considered as full cardiac recovery is expected by 8 weeks. The exception includes patients with medium sized aneurysms or greater as these may persist and require on-going surveillance.