Существует ли связь между средним уровнем mIDkIne и прогнозом заболевания COVID-19?

   The objective was aimed to measure plasma midkine (MK)* levels in patients with COVID-19 and assess its clinical significance.   Materials and Methods. 88 patients observed in our hospital with a diagnosis of COVID-19 were included in the study. The patients’ demographic characteristics, clinical, and laboratory data were studied, and the relationship between MK levels, prognosis, and other parameters was investigated.   Results. Of the 88 patients included in the study, 43 (48.9 %) were female and 45 (51.1%) were male. 24 (27%) patients died. The mean age of non-survivors was 70 ± 12.3 years and the survivors were 61.9 ± 18.2 years. Mortality predictors such as D-dimer, ferritin, troponin, LDH, CRP, and procalcitonin were significantly higher in non-survivors than in survivors (p < 0.05). The median MK level (IR) was 152.5 ± 125 pg/ml in all patients, 143 ± 149 pg/ml in survivors, and 165.5 ± 76 pg/ml in non-survivors (p = 0.546). The difference between these two groups was not statistically significant. The area under the ROC curve was found to be 0.542 (95% CI 0.423–0.661, p = 0.546).   Conclusion. MK is not a biomarker that can replace or reinforce known predictors of mortality in COVID-19 patients.   Цель. Исследование направлено на измерение уровня Midkine (MK)* в плазме крови у пациентов с COVID-19 и оценку его клинической значимости.   Материалы и методы. В исследование включены 88 пациентов, наблюдавшихся в клинике с диагнозом COVID-19. Изучены демографические характеристики пациентов, клинические и лабораторные данные, а также исследована взаимосвязь между уровнями MK, прогнозом и другими параметрами.   Результаты. Из 88 пациентов, включенных в исследование, 43 (48,9 %) были женщинами и 45 (51,1 %) – мужчинами. 24 (27 %) пациента умерли. Средний возраст невыживших составил 70 ± 12,3 года, а выживших – 61,9 ± 18,2 года. Предикторы смертности, такие как D-димер, ферритин, тропонин, ЛДГ, СРБ и прокальцитонин, были значительно выше у умерших, чем у выживших (р < 0,05). Медиана уровня МК (IR) составила 152,5 ± 125 пг/мл у всех пациентов, 143 ± 149 пг/мл у выживших и 165,5 ± 76 пг/мл у умерших (р = 0,546). Разница между этими 2 группами была незначима. Было обнаружено, что площадь под кривой ROC составляет 0,542 (95 % ДИ 0,423–0,661, р = 0,546).   Вывод. МК не является биомаркером, который может заменить или усилить известные предикторы смертности у пациентов с COVID-19

Case Series of Headache Characteristics in COVID-19: Headache Can Be an Isolated Symptom

Headache was reported in up to one-third of the hospitalized patients; yet, the clinical characteristics of headache associated with coronavirus disease 2019 (COVID-19) have not been defined. This observational case study included patients who were consulted to headache unit due to headache and had COVID-19 illness. Headache features in 13 PCR-confirmed COVID-19 patients with mild symptoms were reported. Headache was the isolated symptom of the COVID-19 in 3 patients and emerged as an early symptom during the disease course in all patients. Patients specified severe, rapid onset, unrelenting headache with migraine-like features, as well as unusual sensory symptoms such as anosmia, and gastrointestinal symptoms such as diarrhea and loss of appetite and weight. Headache lasted up to 3 days in 70\% of the patients and resolved in all patients within 2 weeks. Despite the fact that most of the patients were female and headache characteristics were suggestive of migraine, majority of patients were not suffering from primary headaches. It was concluded that headache could be an isolated symptom of COVID-19, which might possibly be ignored in asymptomatic patients. Headaches associated with COVID-19 included features resembling migraine and/or atypical symptoms including anosmia and diarrhea

Identification and Characterization of Novel Rat Polyomavirus 2 in a Colony of X-SCID Rats by P-PIT assay

ABSTRACT Polyomaviruses (PyVs) are known to infect a wide range of vertebrates and invertebrates and are associated with a broad spectrum of diseases, including cancers, particularly in immune-suppressed hosts. A novel polyomavirus, designated rat polyomavirus 2 (RatPyV2), was identified from a breeding colony of rats having X-linked severe combined immunodeficiency. Using a human panpolyomavirus immunohistochemistry test (P-PIT), RatPyV2 was initially detected in the parotid salivary gland of a colony member. Rolling circle amplification using DNA from harderian and parotid glands identified a novel 5.1-kb polyomavirus genome closely related to human Washington University (WU) and Karolinska Institute (KI) and vole polyomaviruses but notably divergent from Rattus norvegicus PyV1 (RnorPyV1; also designated RatPyV1). Further screening showed RatPyV2 inclusion body infection in the lung epithelium and variably in other respiratory, reproductive, and glandular tissues of 12/12 (100%) rats. IMPORTANCE Although P-PIT was developed to detect diseases associated with known human polyomaviruses, the identification of a new polyomavirus in rats suggests that it may have utility as a broad-based screen for new, as well as known polyomaviruses. Our findings suggest that RatPyV2 may be a commensal infection of laboratory rats that can lead to disseminated disease in T cell immune-deficient rats. Infection of the X-SCID rats with RatPyV2 and Pneumocystis carinii is a potential model for coinfection pathogenesis and treatment options during transplant preclinical studies

Antibody-mediated neutralization of authentic SARS-CoV-2 B.1.617 variants harboring L452R and T478K/E484Q

The capacity of convalescent and vaccine-elicited sera and monoclonal antibodies (mAb) to neutralize SARS-CoV-2 variants is currently of high relevance to assess the protection against infections. We performed a cell culture-based neutralization assay focusing on authentic SARS-CoV-2 variants B.1.617.1 (Kappa), B.1.617.2 (Delta), B.1.427/B.1.429 (Epsilon), all harboring the spike substitution L452R. We found that authentic SARS-CoV-2 variants harboring L452R had reduced susceptibility to convalescent and vaccine-elicited sera and mAbs. Compared to B.1, Kappa and Delta showed a reduced neutralization by convalescent sera by a factor of 8.00 and 5.33, respectively, which constitutes a 2-fold greater reduction when compared to Epsilon. BNT2b2 and mRNA1273 vaccine-elicited sera were less effective against Kappa, Delta, and Epsilon compared to B.1. No difference was observed between Kappa and Delta towards vaccine-elicited sera, whereas convalescent sera were 1.51-fold less effective against Delta, respectively. Both B.1.617 variants Kappa (+E484Q) and Delta (+T478K) were less susceptible to either casirivimab or imdevimab. In conclusion, in contrast to the parallel circulating Kappa variant, the neutralization efficiency of convalescent and vaccine-elicited sera against Delta was moderately reduced. Delta was resistant to imdevimab, which, however, might be circumvented by combination therapy with casirivimab together

The prevalence of mixed genotype infections in Turkish patients with hepatitis c: a multicentered assessment

AKTAS, OSMAN/0000-0002-7762-4108; Karsligil, Tekin/0000-0001-7672-3625; cekin, yesim/0000-0003-4393-5618; Sayiner, Ayca/0000-0001-6750-2353; Altindis, Mustafa/0000-0003-0411-9669WOS: 000463988900008PubMed: 30969089Background: HCV virus infections are one of the major health problems in the world that can cause cirrhosis and liver cancer at a higher rate than other hepatitis data. The aim of this study was to determine the prevalence of mixed infections with different HCV genotypes in Turkey and also to evaluate the current HCV genot pe and subtype distributions by a multicentered assessment. Methods: The HCV genotype data of 17,578 hepatitis C patients collected from 23 centers from different geographic regions covering all Turkey were collected. The data included information about the HCV genotypes in the last 10 years (bail een 2007 and 2016), demographic properties of the patients and the methods/systems used to determine the genotypes. Results: Two hundred twenty-eight of the patients (1.3%) had mixed genotype. The most common mixed genotype combination was 1b + 4 (0.83%) followed by 1a + 1b (0.26%). Genotype distribution varies according to geographical regions. However, genotype 1 (82.92%) was the most common genotype in all regions and all years. This was followed by genotype 3 (7.07%) and genotype 4 (5.43%). A variety of methods were used by the centers including sequencing, pyrosequencing, real-time PCR, in-house RFLP, reverse hybridization (LIPA), and hybridization. Conclusions: Infection with mixed HCV genotypes in Turkey is uncommon. Genotype distribution varies according to geographic regions; the most common genotype 1 is encountered all oN er the country, while genotypes 3 and 4 are only in some of the centers. Since there is limited information about mixed HCV infection, further investigations are needed to determine the clinical importance of mixed HCV infection

Macavirus latency-associated protein evades immune detection through regulation of protein synthesis in cis depending upon its glycin/glutamate-rich domain

Alcelaphine herpesvirus 1 (AlHV-1) is a γ-herpesvirus (γ-HV) belonging to the macavirus genus that persistently infects its natural host, the wildebeest, without inducing any clinical sign. However, cross-transmission to other ruminant species causes a deadly lymphoproliferative disease named malignant catarrhal fever (MCF). AlHV-1 ORF73 encodes the latency-associated nuclear antigen (LANA)-homolog protein (aLANA). Recently, aLANA has been shown to be essential for viral persistence in vivo and induction of MCF, suggesting that aLANA shares key properties of other γ-HV genome maintenance proteins. Here we have investigated the evasion of the immune response by aLANA. We found that a glycin/glutamate (GE)-rich repeat domain was sufficient to inhibit in cis the presentation of an epitope linked to aLANA. Although antigen presentation in absence of GE was dependent upon proteasomal degradation of aLANA, a lack of GE did not affect protein turnover. However, protein self-synthesis de novo was downregulated by aLANA GE, a mechanism directly associated with reduced antigen presentation in vitro. Importantly, codon-modification of aLANA GE resulted in increased antigen presentation in vitro and enhanced induction of antigen-specific CD8+ T cell responses in vivo, indicating that mRNA constraints in GE rather than peptidic sequence are responsible for cis-limitation of antigen presentation. Nonetheless, GE-mediated limitation of antigen presentation in cis of aLANA was dispensable during MCF as rabbits developed the disease after virus infection irrespective of the expression of full-length or GE-deficient aLANA. Altogether, we provide evidence that inhibition in cis of protein synthesis through GE is likely involved in long-term immune evasion of AlHV-1 latent persistence in the wildebeest natural host, but dispensable in MCF pathogenesis