The Magnitude of Covid-19 Effect on Melanoma Diagnosis, Histopathologic Features and Stage of the Disease in University Hospital of Split

Introduction: Due to the COVID-19 pandemic, some planned medical activities have been postponed, for both national directives and out of concern of the patients who were afraid to go to hospitals. Skin cancers, especially melanomas, diagnosed during lockdown also differed from pre-lockdown tumors in several notable ways, such as number of newly diagnosed patients and histopathologic features. The primary tumor thickness (mm), ulceration (%), anatomic localization, and regional lymph node involvements are important elements for determining the melanoma staging and prognosis. Aim(s): The aim of this report was to investigate the difference in number of newly diagnosed melanoma patients, histopathological features and melanoma TNM-staging between comparable pre-pandemic (March 2019 until March 2020) and pandemic periods (March 2020 until March 2021). Method(s): We collected the data from hospital clinical and pathohistological databases on the total number of newly diagnosed patients with melanoma in University Hospital of Split. Comparative analyses were performed in a pre-pandemic and a pandemic cohort. Result(s): Comparing the first year of the pandemic (N=57) with the same period one year before (N=69), 17,4% decrease of melanoma cases was observed. Cohort analysis showed no differences in the distribution of age and sex. The median age of the melanoma patients in a pre-pandemic cohort was 66 years (29-86), and in pandemic cohort 68 years (31-88). The male gender predominated among melanoma patients. In a pre-pandemic cohort, 63,8% of melanoma patients were man, and in pandemic cohort 68,4%. Cohort analysis showed differences in the primary localization of skin melanoma. In pre-pandemic cohort, primary localization of melanoma were head and neck in 17 patients (25%), trunk in 26 patients (38%), upper extremities in 13 patients (19,1%), lower extremities in 10 patients (14.7%) and unknown primary site in 2 patients (2,9%). In pandemic cohort, primary localization of melanoma were head and neck in 10 patients (17,5%), trunk in 32 patients (56,1%), upper extremities in 8 patients (14%), lower extremities in 5 patients (8,8%) and unknown primary site in 2 patients (3,5%). Cohort analysis showed no differences in the pathohistological subtypes. The most common pathohistological subtypes in both cohorts were superficial spreading subtype (21,7% vs 25,8%), unclassified (21,7% vs 17,5%) and nodular subtype (14,5% vs 17,5%). In pandemic cohort we diagnosed patients with increased tumor thickness and positive lymph nodes. In pre-pandemic cohorts we had more patients with thickness less than 1 mm (40,6% vs 31,6%). We found more patients with tumor thickness between 1 to 2 mm (17,5% vs 4,3%) and more than 4 mm (25% vs 20%) in pandemic. Accordingly, in pandemic cohort we found more patients with positive lymph nodes then in pre-pandemic (22,9% vs 5,9%), and more patients with initially metastatic disease (22,8% vs 15,9%). We did not observed any differences in presence of ulceration among the studied cohorts (26% vs 28%). Conclusion(s): In the analysis conducted in University Hospital of Split, we observed a marked decrease of newly diagnosed melanoma patients in the first year of the pandemic compared to the same period before the pandemic. We observed increased tumor thickness, more patients with lymph nodes involvements and initially metastatic disease in post-lockdown period. These findings may be the result of delays in diagnosis due to the disruptions in routine dermatologic and oncologic care during Covid-19 pandemic. The further analyses are needed to fully understand the impact of the Covid-19 pandemic on melanoma outcomes.

Influenza surveillance in Ezhou city, Hubei Province, 2016-2021

ObjectiveTo analyze the influenza surveillance data in Ezhou City, Hubei Province from 2016 to 2021, determine the epidemiological characteristics and etiological trend of influenza like illness (ILI), and to provide scientific evidence for influenza prevention and control. MethodsThe ILI surveillance data were reported by Ezhou influenza sentinel hospitals and etiological examination results were collected by network laboratory. Influenza surveillance data from 2016 to 2021 were analyzed. ResultsFrom 2016 to 2021, the percentage of ILI visits (ILI%) in Ezhou city was 2.81% and increased over years. Majority (55.55%) of ILI cases were 0-4 years. A total of 7 716 ILI samples were examined from 2016 to 2021, of which 1 467 tested positive with a positive rate of 19.01%. Influenza A H1N1 was mainly concentrated in January-April, A H3N2 mainly in August-December, B Victoria mainly in April-July and December-March, and B Yamagata mainly in December-February. Influenza network laboratory isolated influenza virus from the 1 467 positive samples by using MDCK cells and SPF chicken embryos. The overall isolation rate was 32.78%, which was 26.93% by MDCK cells and 5.86% by SPF chicken embryos. From 2016 to 2021, a total of 13 ILI outbreaks were reported in Ezhou City. Temporally, the outbreaks mainly occurred in winter and spring. Spatially, they were mainly in primary schools, middle schools and kindergartens. ConclusionThe winter and spring are the key time period of influenza prevention and control in Ezhou City, as they are susceptible to influenza outbreaks. Children aged 0-14 are the key population of prevention and control. Diverse subtypes of influenza virus alternate by years, which warrants continually strengthening monitoring. Additionally, certain countermeasures against COVID-19 may be recommended in the prevention and control of influenza.

Risk assessment of public health emergencies concerned in China, February 2023

Objective: To assess the risk of public health emergencies occurring in China (except Hong Kong, Macao Special Administrative Regions and Taiwan Province, the same below) or possibly imported from outside China in February 2023. Methods: Based on various data and departmental notification information on domestic and foreign public health emergencies reports and surveillance of key infectious diseases, the expert consultation method was used and experts from provincial (autonomous regions and municipalities directly under the central government) centers for disease prevention and control were invited to participate in the assessment by video conference. Results: The number of public health emergencies to be reported in February 2023 is expected to increase compared to former month. In February 2023, affected by immune escape and reinfection of Omicron variants XBB, CH and other possible emerging subtypes, it is expected that the COVID-19 may become endemic in more areas of the world. In China, because of the increased flow of people after the Spring Festival and the opening of schools, the possibility of the spread of the virus will increase. The influenza viruses activity level may increase in February, and influenza A (H1N1) is more likely to be the main influenza virus. Conclusion: Special attention is given to COVID-19, and general attention is given to seasonal influenza.

Acute necrotising encephalopathy: A rare complication providing a clue for the outbreak of H1N1 among medical students in Kanpur, India.

Kanpur, India, recently witnessed an outbreak of undifferentiated febrile illness among medical students. Several students developed high-grade fever with altered sensorium within 2-3 days after the index case. Surprisingly, this outbreak coincided with the death of several pigs in the vicinity. Acute necrotising encephalitis, although rare, was noted in some patients. When correlated with each other, all of these incidents were suggestive of an outbreak of H1N1.

Influenza A(H3N2) infection followed by separate COVID-19 infection.

This study describes the case of a health professional infected first by influenza virus A(H3N2) and then by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 11 days later. Respiratory samples and clinical data were collected from the patient and from close contacts. RNA was extracted from samples and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to investigate the viruses. The patient presented with two different illness events: the first was characterized by fever, chest and body pain, prostration and tiredness, which ceased on the ninth day; RT-qPCR was positive only for influenza virus A(H3N2). Eleven days after onset of the first symptoms, the patient presented with sore throat, nasal congestion, coryza, nasal itching, sneezing and coughing, and a second RT-qPCR test was positive only for SARS-CoV-2; in the second event, symptoms lasted for 11 days. SARS-CoV-2 sequencing identified the Omicron BA.1 lineage. Of the patient's contacts, one was coinfected with influenza A(H3N2) and SARS-CoV-2 lineage BA.1.15 and the other two were infected only with SARS-CoV-2, one also with Omicron BA.1.15 and the other with BA.1.1. Our findings reinforce the importance of testing for different viruses in cases of suspected respiratory viral infection during routine epidemiological surveillance because common clinical manifestations of COVID-19 mimic those of other viruses, such as influenza.

Este estudio describe el caso de un profesional de la salud que contrajo la infección primero por el virus de la gripe A (H3N2) y a continuación por el coronavirus 2 del síndrome respiratorio agudo grave (SARS-CoV-2) 11 días después. Se recogieron muestras respiratorias y datos clínicos del paciente y sus contactos cercanos. Se extrajo ARN de muestras y se utilizó la reacción en cadena de la polimerasa cuantitativa con transcripción inversa (RT-qPCR, por su sigla en inglés) para investigar los virus. El paciente presentó dos procesos infecciosos distintos: el primero se caracterizó por fiebre, dolor corporal y torácico, postración y cansancio, que cesó en el noveno día. La prueba mediante RT-qPCR solo fue positiva en el virus de la gripe A (H3N2). Once días después del inicio de los primeros síntomas, el paciente manifestó dolor de garganta, congestión nasal, catarro, picazón nasal, estornudos y tos. Una segunda prueba mediante RT-qPCR solo fue positiva para el SARS-CoV-2 y durante este segundo proceso los síntomas duraron 11 días. La secuenciación del SARS-CoV-2 identificó el linaje ómicron BA.1. De los contactos del paciente, uno presentaba una coinfección por el virus de la gripe A (H3N2) y el linaje BA.1.15 del SARS-COV-2, y los otros dos presentaban infecciones únicamente por SARS-CoV-2, uno también del linaje ómicron BA.1.15 y el otro de BA.1.1. Estos hallazgos refuerzan la importancia de realizar pruebas para detectar diferentes virus en casos de sospecha de infección viral respiratoria durante la vigilancia epidemiológica de rutina porque las manifestaciones clínicas comunes de COVID-19 son similares a las de otros virus, como en el caso de la gripe.

Este estudo descreve o caso de uma profissional de saúde infectada primeiro pelo vírus influenza A (H3N2) e, 11 dias depois, pelo coronavírus da síndrome respiratória aguda grave 2 (SARS-CoV-2). Amostras respiratórias e dados clínicos foram coletados da paciente e de contatos próximos. RNA foi extraído das amostras, e o método de reação em cadeia da polimerase via transcriptase reversa quantitativa (RT-qPCR) foi utilizado para investigar os vírus. A paciente apresentou dois quadros clínicos distintos. O primeiro foi caracterizado por febre, dor no peito e no corpo, prostração e fadiga, que cessou no nono dia. A RT-qPCR foi positiva apenas para o vírus da influenza A (H3N2). Onze dias após o início dos primeiros sintomas, a paciente apresentou dor de garganta, congestão nasal, coriza, prurido nasal, espirros e tosse. Um segundo teste de RT-qPCR foi positivo apenas para SARS-CoV-2. No segundo evento, os sintomas duraram 11 dias. O sequenciamento do SARS-CoV-2 identificou a cepa Ômicron BA.1. Dentre os contatos da paciente, um teve coinfeção por influenza A (H3N2) e SARS-COV-2 (cepa BA.1.15), e os outros dois foram infectados apenas por SARS-CoV-2 (um também pela cepa Ômicron BA.1.15 e o outro pela BA.1.1). Nossos achados reforçam a importância de testes para a detecção de diferentes vírus em casos de suspeita de infecção viral respiratória durante a vigilância epidemiológica de rotina, visto que as manifestações clínicas comuns da COVID-19 imitam as de outros vírus, como o vírus influenza.

Comparative approach between COVID-19 and Spanish flu

Introduction: throughout history, several diseases have put mankind "in stress" and due to the accelerated and extensive spread have been labeled as pandemics. Background: to assess similarities and differences between COVID-19 and the Spanish influenza. Method: a literature review was carried out in December 2021. Using several Academic search engines, like (Pubmed, Google and Google Scholar). It was assessed several Articles published in Spanish;those that did not meet these conditions were excluded;89 bibliographic references were studied, of which 25 were cited in this article. Development: COVID-19 and Spanish flu are similar for arising respiratory symptoms at first, clinical characteristic of a common cold. The earliest documented case of Spanish flu was in the United States of America and it was caused by the H1N1 influenza A virus and it's not identified as a zoonosis, however, COVID-19 first cases were documented in China and it was caused by the virus of SARS-CoV-2, virus identified as a zoonosis that affect most commonly older adults, whereas the Spanish flu affected more young adults. It has been attributed some protective immunity to those who became ill with the Spanish flu, however, the coronavirus does not leave person with immunization levels after been infected. Conclusion: Spanish flu and coronavirus are the two great pandemics of history which have many similarities and differences from clinical, epidemiological and social point of view.

The evolution of the influNet surveillance system in Italy After the SARS-CoV-2 pandemic

This article discussed the evolution of the InfluNet surveillance system in Italy, which was originally developed in 1999-2000 for monitoring flu-like syndromes and the circulation of influenza viruses. After the 2009-2010 subtype A/H1N1pdm09 influenza pandemic, InfluNet became an integrated surveillance system, including epidemiological and virological surveillance, as well as other sources of data to monitor the impact of influenza. The system proved to be a useful tool for assessing vaccine efficacy and preventing serious and severe forms of flu, especially in frail subjects. The SARS-CoV-2 pandemic introduced further innovations in InfluNet surveillance, and starting from the 2020-2021 season, InfluNet became a respiratory virus surveillance system. The article also described the trends of the 2021-2022 influenza season, with a low incidence of ILI and limited circulation of influenza viruses compared to seasons prior to 2020, as well as the impact of RSV. The article emphasized the importance of vaccination programs and the need for integrated surveillance systems to prevent the spread of respiratory diseases and deal with future pandemics.

HIV-1 Tat amino acid residues that influence Tat-TAR binding affinity: a scoping review.

HIV-1 remains a global health concern and to date, nearly 38 million people are living with HIV. The complexity of HIV-1 pathogenesis and its subsequent prevalence is influenced by several factors including the HIV-1 subtype. HIV-1 subtype variation extends to sequence variation in the amino acids of the HIV-1 viral proteins. Of particular interest is the transactivation of transcription (Tat) protein due to its key function in viral transcription. The Tat protein predominantly functions by binding to the transactivation response (TAR) RNA element to activate HIV-1 transcriptional elongation. Subtype-specific Tat protein sequence variation influences Tat-TAR binding affinity. Despite several studies investigating Tat-TAR binding, it is not clear which regions of the Tat protein and/or individual Tat amino acid residues may contribute to TAR binding affinity. We, therefore, conducted a scoping review on studies investigating Tat-TAR binding. We aimed to synthesize the published data to determine (1) the regions of the Tat protein that may be involved in TAR binding, (2) key Tat amino acids involved in TAR binding and (3) if Tat subtype-specific variation influences TAR binding. A total of thirteen studies met our inclusion criteria and the key findings were that (1) both N-terminal and C-terminal amino acids outside the basic domain (47-59) may be important in increasing Tat-TAR binding affinity, (2) substitution of the amino acids Lysine and Arginine (47-59) resulted in a reduction in binding affinity to TAR, and (3) none of the included studies have investigated Tat subtype-specific substitutions and therefore no commentary could be made regarding which subtype may have a higher Tat-TAR binding affinity. Future studies investigating Tat-TAR binding should therefore use full-length Tat proteins and compare subtype-specific variations. Studies of such a nature may help explain why we see differential pathogenesis and prevalence when comparing HIV-1 subtypes.

Towards a Better Understanding of the Complexities of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Long COVID.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex condition arising in susceptible people, predominantly following viral infection, but also other stressful events. The susceptibility factors discussed here are both genetic and environmental although not well understood. While the dysfunctional physiology in ME/CFS is becoming clearer, understanding has been hampered by different combinations of symptoms in each affected person. A common core set of mainly neurological symptoms forms the modern clinical case definition, in the absence of an accessible molecular diagnostic test. This landscape has prompted interest in whether ME/CFS patients can be classified into a particular phenotype/subtype that might assist better management of their illness and suggest preferred therapeutic options. Currently, the same promising drugs, nutraceuticals, or behavioral therapies available can be beneficial, have no effect, or be detrimental to each individual patient. We have shown that individuals with the same disease profile exhibit unique molecular changes and physiological responses to stress, exercise and even vaccination. Key features of ME/CFS discussed here are the possible mechanisms determining the shift of an immune/inflammatory response from transient to chronic in ME/CFS, and how the brain and CNS manifests the neurological symptoms, likely with activation of its specific immune system and resulting neuroinflammation. The many cases of the post viral ME/CFS-like condition, Long COVID, following SARS-CoV-2 infection, and the intense research interest and investment in understanding this condition, provide exciting opportunities for the development of new therapeutics that will benefit ME/CFS patients.

gp120 Envelope Glycoproteins of HIV-1 Group M Subtype A and Subtype B Differentially Affect Gene Expression in Human Vascular Endothelial Cells.

Cardiovascular complications are seen among human immunodeficiency virus (HIV)-positive individuals, who now survive longer due to successful antiretroviral therapies. Pulmonary arterial hypertension (PAH) is a fatal disease characterized by increased blood pressure in the lung circulation. The prevalence of PAH in the HIV-positive population is dramatically higher than that in the general population. While HIV-1 Group M Subtype B is the most prevalent subtype in western countries, the majority of HIV-1 infections in eastern Africa and former Soviet Union countries are caused by Subtype A. Research on vascular complications in the HIV-positive population in the context of subtype differences, however, has not been rigorous. Much of the research on HIV has focused on Subtype B, and information on the mechanisms of Subtype A is nonexistent. The lack of such knowledge results in health disparities in the development of therapeutic strategies to prevent/treat HIV complications. The present study examined the effects of HIV-1 gp120 of Subtypes A and B on human pulmonary artery endothelial cells by performing protein arrays. We found that the gene expression changes caused by gp120s of Subtypes A and B are different. Subtype A is a more potent downregulator of perostasin, matrix metalloproteinase-2, and ErbB than Subtype B, while Subtype B is more effective in downregulating monocyte chemotactic protein-2 (MCP-2), MCP-3, and thymus- and activation-regulated chemokine proteins. This is the first report of gp120 proteins affecting host cells in an HIV subtype-specific manner, opening up the possibility that complications occur differently in HIV patients throughout the world.

Two-Stage Deep Learning Model for Automated Segmentation and Classification of Splenomegaly.

Splenomegaly is a common cross-sectional imaging finding with a variety of differential diagnoses. This study aimed to evaluate whether a deep learning model could automatically segment the spleen and identify the cause of splenomegaly in patients with cirrhotic portal hypertension versus patients with lymphoma disease. This retrospective study included 149 patients with splenomegaly on computed tomography (CT) images (77 patients with cirrhotic portal hypertension, 72 patients with lymphoma) who underwent a CT scan between October 2020 and July 2021. The dataset was divided into a training (n = 99), a validation (n = 25) and a test cohort (n = 25). In the first stage, the spleen was automatically segmented using a modified U-Net architecture. In the second stage, the CT images were classified into two groups using a 3D DenseNet to discriminate between the causes of splenomegaly, first using the whole abdominal CT, and second using only the spleen segmentation mask. The classification performances were evaluated using the area under the receiver operating characteristic curve (AUC), accuracy (ACC), sensitivity (SEN), and specificity (SPE). Occlusion sensitivity maps were applied to the whole abdominal CT images, to illustrate which regions were important for the prediction. When trained on the whole abdominal CT volume, the DenseNet was able to differentiate between the lymphoma and liver cirrhosis in the test cohort with an AUC of 0.88 and an ACC of 0.88. When the model was trained on the spleen segmentation mask, the performance decreased (AUC = 0.81, ACC = 0.76). Our model was able to accurately segment splenomegaly and recognize the underlying cause. Training on whole abdomen scans outperformed training using the segmentation mask. Nonetheless, considering the performance, a broader and more general application to differentiate other causes for splenomegaly is also conceivable.

Multiple Fibroblast Subtypes Contribute to Matrix Deposition in Pulmonary Fibrosis.

Progressive pulmonary fibrosis results from a dysfunctional tissue repair response and is characterized by fibroblast proliferation, activation, and invasion and extracellular matrix accumulation. Lung fibroblast heterogeneity is well recognized. With single-cell RNA sequencing, fibroblast subtypes have been reported by recent studies. However, the roles of fibroblast subtypes in effector functions in lung fibrosis are not well understood. In this study, we incorporated the recently published single-cell RNA-sequencing datasets on murine lung samples of fibrosis models and human lung samples of fibrotic diseases and analyzed fibroblast gene signatures. We identified and confirmed the novel fibroblast subtypes we reported recently across all samples of both mouse models and human lung fibrotic diseases, including idiopathic pulmonary fibrosis, systemic sclerosis-associated interstitial lung disease, and coronavirus disease (COVID-19). Furthermore, we identified specific cell surface proteins for each fibroblast subtype through differential gene expression analysis, which enabled us to isolate primary cells representing distinct fibroblast subtypes by flow cytometry sorting. We compared matrix production, including fibronectin, collagen, and hyaluronan, after profibrotic factor stimulation and assessed the invasive capacity of each fibroblast subtype. Our results suggest that in addition to myofibroblasts, lipofibroblasts and Ebf1+ (Ebf transcription factor 1+) fibroblasts are two important fibroblast subtypes that contribute to matrix deposition and also have enhanced invasive, proliferative, and contraction phenotypes. The histological locations of fibroblast subtypes are identified in healthy and fibrotic lungs by these cell surface proteins. This study provides new insights to inform approaches to targeting lung fibroblast subtypes to promote the development of therapeutics for lung fibrosis.

Viral reactivation after hcv-positive renal allograft transplantation

Case Report: A 48y/o man with a history of ESRD secondary to FSGS was found to have hepatitis-C virus (HCV) reactivation after kidney transplantation (KT) with an HCV-positive allograft. The patient was HCV-negative before transplantation in July 2021. He was negative for hepatitis-B virus (HBV) core antibodies but had evidence of prior HBV vaccination and was negative for HIV 1/2. His induction therapy included thymoglobulin, and his maintenance immunosuppressive regimen included mycophenolate mofetil (MMF), tacrolimus, and prednisone. Aweek after KT, the patient tested positive for HCV genotype 1a, and he was started on sofosbuvir/velpatasvir in August 2021. Lab monitoring showed decreasing levels of HCV viral load (VL) until it was undetectable 2 months later. In January 2022, renal function remained stable, and urinalysis and hepatic function tests remained unremarkable. However, HCV viral load was positive in February 2022 and the HCV genotypewas 1a, as before. This result raised the possibility of reactivation of HCV from his allograft more than 6 months post KT. Additionally, despite negative BK polyoma VL initially, he was positive in January 2022 and discontinued his MMF. He was also positive for COVID-19 in January 2022 as well. Given his recurrence of HCV VL, he initiated sofosbuvir/velpatasvir/ voxilaprevir in April 2022 and completed therapy in July 2022, and maintained sustained viral response (SVR) as of October 2022. His BK VL was negative in May 2022. Recent guidelines on preventing HCV reactivation in allograft-positive KT recipients state that individuals should achieve SVR after 8-12 weeks of a course of direct-acting antiviral (DAA) therapy. The patient completed DAA therapy post-transplantation with a successful negative viral load 2 months later. However, he did not achieve SVR because his VL was again positive 3 months after completion of therapy. Reactivation of BKV, a DNA virus that establishes lifelong infection in renal tubular and uroepithelial cells, is common among KT recipients, but there is insufficient evidence to establish a causal association between BKV reactivation and HCV reactivation. There is no consensus on a chemotherapeutic maintenance regimen to prevent HCV reactivation. This case highlights the importance of close follow-up monitoring for HCV and BKV among KT recipients and the need to explore the relationship between BKV reactivation, HCV reactivation, and immunosuppression regimen. Copyright © 2023 Southern Society for Clinical Investigation.

Clinical and epidemiological differences and similarities of viral pneumonias in two pandemics

Background: In a decade, we faced two pandemic viruses, influenza A H1N1pdm09 and SARS CoV-2, whose most serious manifestation is pneumonia. Aim: To compare the clinical, epidemiological and management aspects of pneumonias caused by each pandemic virus in adults requiring hospitalization. Material and methods: Comparative, observational study carried out at a regional Chilean hospital, including 75 patients with influenza A H1N1pdm09 prospectively studied in 2009 and 142 patients with SARS CoV-2 studied in 2020.

Identification and phylogenetic analysis of two canine coronavirus strains.

Canine coronavirus (CCoV), a member of the genus Alphacoronavirus, is an enveloped, single-stranded positive-sense RNA virus that responsible for gastroenteritis in dogs. In this study, two CCoV isolates were successfully propagated from 53 CCoV-positive clinical specimens by serial passaging in A-72 cells. These two strains, CCoV JS1706 and CCoV JS1712, caused cytopathic effects in A-72 cells. The sizes of virus plaque formed by them differed in early passages. Electron microscopy revealed a large quantity of typical coronavirus particles with 80-120 nm in diameter in cell culture media and cytoplasm of infected cells, in which they appeared as inclusion bodies. RT-PCR analysis of S gene indicated that these two isolates were belonged to CCoV IIa subtype. Homology of RdRp, S, M and N proteins between the two strains were 100, 99.6, 99.2 and 100.0%, respectively, whereas they were 99.4-100%, 83.1-95.2%, 88.5-99.2% and 91.9-99.7% identity compared to CCoV II reference strains. Phylogenetic analysis of RdRp, S, M and N protein showed that they were closely related to CCoV II strains. These two subtype IIa isolates will be useful for evaluating the pathogenesis and evolution of CCoV and for developing diagnostic reagents and vaccines.

Subtyping of major SARS-CoV-2 variants reveals different transmission dynamics based on 10 million genomes.

SARS-CoV-2 continues to evolve, causing waves of the pandemic. Up to May 2022, 10 million genome sequences have accumulated, which are classified into five major variants of concern. With the growing number of sequenced genomes, analysis of the big dataset has become increasingly challenging. Here we developed systematic approaches based on sets of correlated single nucleotide variations (SNVs) for comprehensive subtyping and pattern recognition of transmission dynamics. The approach outperformed single-SNV and spike-centric scans. Moreover, the derived subtypes elucidate the relationship of signature SNVs and transmission dynamics. We found that different subtypes of the same variant, including Delta and Omicron exhibited distinct temporal trajectories. For example, some Delta and Omicron subtypes did not spread rapidly, while others did. We identified sets of characteristic SNVs that appeared to enhance transmission or decrease efficacy of antibodies for some subtypes. We also identified a set of SNVs that appeared to suppress transmission or increase viral sensitivity to antibodies. For the Omicron variant, the dominant type in the world, we identified the subtypes with enhanced and suppressed transmission in an analysis of eight million genomes as of March 2022 and further confirmed the findings in a later analysis of ten million genomes as of May 2022. While the "enhancer" SNVs exhibited an enriched presence on the spike protein, the "suppressor" SNVs are mainly elsewhere. Disruption of the SNV correlation largely destroyed the enhancer-suppressor phenomena. These results suggest the importance of fine subtyping of variants, and point to potential complex interactions among SNVs.

[Ethiopathogenetic features and course of ischemic stroke associated with COVID-19]. / Etiopatogeneticheskie osobennosti i techenie ishemicheskogo insul'ta, assotsiirovannogo s COVID-19.

OBJECTIVE: To analyze etiopathogenetic factors and course of ischemic stroke associated with new coronavirus infection (COVID-19). MATERIAL AND METHODS: A retrospective clinical study of 173 patients with ischemic stroke and COVID-19 (main group) and 86 patients with ischemic stroke without COVID-19 (comparison group) was carried out. There were no statistically significant differences in age and gender. All patients underwent standard clinical-instrumental, laboratory and neuroimaging assessments. RESULTS: Compared with the comparison group, patients with COVID-19 were less likely to have cardiovascular risk factors, the difference being statistically significant. Stroke in the main group was more severe than in the comparison group. According to the TOAST classification, an unknown stroke subtype significantly predominated in the main group. Laboratory data in the main group indicated the significance of an increase in renal-hepatic markers (creatinine, aspartate aminotransferase) and systemic inflammatory response syndrome (C-reactive protein). CONCLUSION: The development of cardiovascular diseases in patients with COVID-19 is an important negative prognostic factor that requires further study to determine the optimal management strategy.

Current Research Status of Metronomic Chemotherapy in Combination Treatment of Breast Cancer.

BACKGROUND: Metronomic chemotherapy (MCT), termed sustained low-dose administration with minimal toxicity, is a new modality of conventional chemotherapy, a verified therapy alternative, and has acquired significant recognition and interest in oncology. Numerous clinical trials of MCT in combination with other treatments, including targeted therapies, biologics, and endocrine therapy, are in progress to obtain better results. SUMMARY: We comprehensively described the clinical benefits of MCT in combination with other treatments in different molecular subtypes of breast cancer and assessed the feasibility of its adoption in varying phases of treatment. Due to the promising preclinical and clinical investigations, it is expected that MCT in combination with other treatments will enhance the advantages of this strategy and apply it to clinical practice. KEY MESSAGE: MCT, in combination with other therapeutic interventions, will fully exploit the benefits of this strategy, ushering in a new paradigm in oncology treatment and driving the transformation of cancer into a more manageable chronic disease using newly developed treatment approaches.

Research of Epidemiologic Feature and Control of SARS-CoV-2 Omicron Subvariants BA.4 and BA.5

The global COVID-19 is still in a pandemic state, and Omicron is still the dominant variant in the world, accounting for about 99% of the global gene sequence. Many regions around the world are experiencing the seventh wave of the epidemic. This round of epidemics is mainly caused by Omicron subvariants BA.4 and BA.5, but the epidemiological characteristics of Omicron subvariants BA.4 and BA.5 are still unclear, bringing great challenges to the prevention and control of the epidemic in countries and regions. In this study, discovery and epidemic status, the incubation period, transmissibility, clinical symptoms, case fatality rate, and the protective effect of vaccines of Omicron subvariants BA.4 and BA.5 were reviewed, in order to provide reference for scientific prevention and control of Omicron subvariants BA.4 and BA.5. © 2022 Chinese General Practice. All rights reserved.