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The pandemic of coronavirus disease (COVID)-19 is a global threat, causing high mortality, especially in the elderly. The main symptoms and the primary cause of death are related to interstitial pneumonia. Viral entry also into myocardial cells mainly via the angiotensin converting enzyme type 2 (ACE2) receptor and excessive production of pro-inflammatory cytokines, however, also make the heart susceptible to injury. In addition to the immediate damage caused by the acute inflammatory response, the heart may also suffer from long-term consequences of COVID-19, potentially causing a post-pandemic increase in cardiac complications. Although the main cause of cardiac damage in COVID-19 remains coagulopathy with micro- (and to a lesser extent macro-) vascular occlusion, open questions remain about other possible modalities of cardiac dysfunction, such as direct infection of myocardial cells, effects of cytokines storm, and mechanisms related to enhanced coagulopathy. In this opinion paper, we focus on these lesser appreciated possibilities and propose experimental approaches that could provide a more comprehensive understanding of the cellular and molecular bases of cardiac injury in COVID-19 patients. We first discuss approaches to characterize cardiac damage caused by possible direct viral infection of cardiac cells, followed by formulating hypotheses on how to reproduce and investigate the hyperinflammatory and pro-thrombotic conditions observed in the heart of COVID-19 patients using experimental in vitro systems. Finally, we elaborate on strategies to discover novel pathology biomarkers using omics platforms. [ABSTRACT FROM AUTHOR]

The cardiovascular system is significantly affected in coronavirus disease-19 (COVID-19). Microvascular injury, endothelial dysfunction, and thrombosis resulting from viral infection or indirectly related to the intense systemic inflammatory and immune responses are characteristic features of severe COVID-19. Pre-existing cardiovascular disease and viral load are linked to myocardial injury and worse outcomes. The vascular response to cytokine production and the interaction between severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and angiotensin-converting enzyme 2 receptor may lead to a significant reduction in cardiac contractility and subsequent myocardial dysfunction. In addition, a considerable proportion of patients who have been infected with SARS-CoV-2 do not fully recover and continue to experience a large number of symptoms and post-acute complications in the absence of a detectable viral infection. This conditions often referred to as 'post-acute COVID-19' may have multiple causes. Viral reservoirs or lingering fragments of viral RNA or proteins contribute to the condition. Systemic inflammatory response to COVID-19 has the potential to increase myocardial fibrosis which in turn may impair cardiac remodelling. Here, we summarize the current knowledge of cardiovascular injury and post-acute sequelae of COVID-19. As the pandemic continues and new variants emerge, we can advance our knowledge of the underlying mechanisms only by integrating our understanding of the pathophysiology with the corresponding clinical findings. Identification of new biomarkers of cardiovascular complications, and development of effective treatments for COVID-19 infection are of crucial importance. [ABSTRACT FROM AUTHOR]

A novel Corona virus disease 2019 (COVID-19) outbreak is declared as the international public health emergency concern by the World Health Organization in the month of March 2020. This viral disease invented from China in the month of December 2019 has previously caused havoc around the world, including India. In this paper, efficient mathematical models using Gustafson–Kessel fuzzy clustering approach for the transmission of the COVID-19 are developed by considering the actual reported cases in the state of Tamil Nadu, India. The results proved a good concord between the reported data and the estimated data given by the proposed models. Moreover, the developed models are also capable to predict the requirements of beds in hospitals on the month of August 2020 in Tamil Nadu, India. Also, this work suggests strictly implementing/extending the complete lockdown for at least 21 days in the month of August 2020 and immediate separation of infected cases are the positive steps to reduce the spread of novel corona virus in Tamil Nadu state, India. [ABSTRACT FROM AUTHOR]

Objectives Isatis indigotica Fort. (I. indigotica) is an herbaceous plant belonging to Cruciferae family. Its leaf (IIL) and root (IIR) are commonly used in traditional Chinese medicines (TCMs) with good clinical efficacies such as clearing away heat and detoxification, cooling blood and reducing swelling. This review aimed to provide a systematic summary on the phytochemistry, pharmacology and clinical applications of I. indigotica. Key findings This plant contains alkaloids, organic acids, flavonoids, lignans, nucleosides, amino acids, and steroids. Previous pharmacological researches indicated that I. indigotica possesses promising antivirus, antibacterial, immunoregulatory, anti-inflammation, and cholagogic effects. Importantly, it can inhibit various viruses, such as influenza, hepatitis B, mumps, herpes simplex, cytomegalovirus, and coxsachievirus. Clinically, it is frequently used to treat various viral diseases like viral influenza, parotitis and viral hepatitis. Consequently, I. indigotica may be beneficial for the prevention and treatment of coronavirus disease 2019 (COVID-19). Summary This paper reviewed the chemical constituents, pharmacological effects and clinical applications of I. indigotica which may guide further research and application of this plant. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) is a rising respiratory sickness. It causes harsh pneumonia and is considered to cover higher collisions in the healthcare domain. The diagnosis at an early stage is more complex to get accurate treatment for reducing the stress in the clinical sector. Chest X-ray scan is the standard imaging diagnosis test employed for pneumonia disease. Automatic detection of COVID-19 helps to control the community outbreak but tracing this viral infection through X-ray results in a challenging task in the medical community. To automatically detect the viral disease in order to reduce the mortality rate, an effective COVID-19 detection method is modelled in this research by the proposed manta-ray multi-verse optimization-based hierarchical attention network (MRMVO-based HAN) classifier. Accordingly, the MRMVO is the incorporation of manta-ray foraging optimization and multi-verse optimizer. Based on the segmented lung lobes, the features are acquired from segmented regions in such a way that the process of COVID-19 detection mechanism is carried out with the features acquired from interested lobe regions. The proposed method has good performance with the measures, such as accuracy, true positive rate and true negative rate with the values of 93.367, 89.921 and 95.071%. [ABSTRACT FROM AUTHOR]

Identifying linked cases of infection is a critical component of the public health response to viral infectious diseases. In a clinical context, there is a need to make rapid assessments of whether cases of infection have arrived independently onto a ward, or are potentially linked via direct transmission. Viral genome sequence data are of great value in making these assessments, but are often not the only form of data available. Here, we describe A2B-COVID, a method for the rapid identification of potentially linked cases of COVID-19 infection designed for clinical settings. Our method combines knowledge about infection dynamics, data describing the movements of individuals, and evolutionary analysis of genome sequences to assess whether data collected from cases of infection are consistent or inconsistent with linkage via direct transmission. A retrospective analysis of data from two wards at Cambridge University Hospitals NHS Foundation Trust during the first wave of the pandemic showed qualitatively different patterns of linkage between cases on designated COVID-19 and non-COVID-19 wards. The subsequent real-time application of our method to data from the second epidemic wave highlights its value for monitoring cases of infection in a clinical context. [ABSTRACT FROM AUTHOR]

preVIEW is a freely available semantic search engine for Coronavirus disease (COVID-19)-related preprint publications. Currently, it contains >43 800 documents indexed with >4000 semantic concepts, annotated automatically. During the last 2 years, the dynamic situation of the corona crisis has demanded dynamic development. Whereas new semantic concepts have been added over time—such as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of interest—the service has been also extended with several features improving the usability and user friendliness. Most importantly, the user is now able to give feedback on detected semantic concepts, i.e. a user can mark annotations as true positives or false positives. In addition, we expanded our methods to construct search queries. The presented version of preVIEW also includes links to the peer-reviewed journal articles, if available. With the described system, we participated in the BioCreative VII interactive text-mining track and retrieved promising user-in-the-loop feedback. Additionally, as the occurrence of long-term symptoms after an infection with the virus SARS-CoV-2—called long COVID—is getting more and more attention, we have recently developed and incorporated a long COVID classifier based on state-of-the-art methods and manually curated data by experts. The service is freely accessible under https://preview.zbmed.de [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has precipitated a global health crisis of unprecedented proportions. Because of its severe impact, multiple COVID-19 vaccines are being rapidly developed, approved and manufactured. Among them, mRNA vaccines are considered as ideal candidates with special advantages to meet this challenge. However, some serious adverse events have been reported after their application, significantly increasing concerns about the safety and efficacy of the vaccines and doubts about the necessity of vaccination. Although several fertility societies have announced that COVID-19 mRNA vaccines are unlikely to affect fertility, there is no denying that the current evidence is very limited, which is one of the reasons for vaccine hesitancy in the population, especially in pregnant women. Herein, we provide an in-depth discussion on the involvement of the male and female reproductive systems during SARS-CoV-2 infection or after vaccination. On one hand, despite the low risk of infection in the male reproductive system or fetus, COVID-19 could pose an enormous threat to human reproductive health. On the other hand, our review indicates that both men and women, especially pregnant women, have no fertility problems or increased adverse pregnancy outcomes after vaccination, and, in particular, the benefits of maternal antibodies transferred through the placenta outweigh any known or potential risks. Thus, in the case of the rapid spread of COVID-19, although further research is still required, especially a larger population-based longitudinal study, it is obviously a wise option to be vaccinated instead of suffering from serious adverse symptoms of virus infection. [ABSTRACT FROM AUTHOR]

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become pandemic and the duration of protective immunity to the virus is unknown. Cases of persons reinfected with the virus are being reported with increasing frequency. At present it is unclear how common reinfection with SARS-CoV-2 is and how long serum antibodies and virus-specific T cells persist after infection. For many other respiratory virus infections, including influenza and the seasonal coronaviruses that cause colds, serum antibodies persist for only months to a few years and reinfections are very common. Here we review what is known about the duration of immunity and reinfection with coronaviruses, including SARS-CoV-2, as well as the duration of immunity to other viruses and virus vaccines. These findings have implications for the need of continued protective measures and for vaccines for persons previously infected with SARS-CoV-2. [ABSTRACT FROM AUTHOR]

Infection of the heart muscle with cardiotropic viruses is one of the major aetiologies of myocarditis and acute and chronic inflammatory cardiomyopathy (DCMi). However, viral myocarditis and subsequent dilated cardiomyopathy is still a challenging disease to diagnose and to treat and is therefore a significant public health issue globally. Advances in clinical examination and thorough molecular genetic analysis of intramyocardial viruses and their activation status have incrementally improved our understanding of molecular pathogenesis and pathophysiology of viral infections of the heart muscle. To date, several cardiotropic viruses have been implicated as causes of myocarditis and DCMi. These include, among others, classical cardiotropic enteroviruses (Coxsackieviruses B), the most commonly detected parvovirus B19, and human herpes virus 6. A newcomer is the respiratory virus that has triggered the worst pandemic in a century, SARS-CoV-2, whose involvement and impact in viral cardiovascular disease is under scrutiny. Despite extensive research into the pathomechanisms of viral infections of the cardiovascular system, our knowledge regarding their treatment and management is still incomplete. Accordingly, in this review, we aim to explore and summarize the current knowledge and available evidence on viral infections of the heart. We focus on diagnostics, clinical relevance and cardiovascular consequences, pathophysiology, and current and novel treatment strategies. [ABSTRACT FROM AUTHOR]

Aging and comorbidities make individuals at greatest risk of COVID-19 serious illness and mortality due to senescence-related events and deleterious inflammation. Long-living individuals (LLIs) are less susceptible to inflammation and develop more resiliency to COVID-19. As demonstrated, LLIs are characterized by high circulating levels of BPIFB4, a protein involved in homeostatic response to inflammatory stimuli. Also, LLIs show enrichment of homozygous genotype for the minor alleles of a 4 missense single-nucleotide polymorphism haplotype (longevity-associated variant [LAV]) in BPIFB4, able to counteract progression of diseases in animal models. Thus, the present study was designed to assess the presence and significance of BPIFB4 level in COVID-19 patients and the potential therapeutic use of LAV-BPIFB4 in fighting COVID-19. BPIFB4 plasma concentration was found significantly higher in LLIs compared to old healthy controls while it significantly decreased in 64 COVID-19 patients. Further, the drop in BPIFB4 values correlated with disease severity. Accordingly to the LAV-BPIFB4 immunomodulatory role, while lysates of SARS-CoV-2-infected cells induced an inflammatory response in healthy peripheral blood mononuclear cells in vitro, the co-treatment with recombinant protein (rh) LAV-BPIFB4 resulted in a protective and self-limiting reaction, culminating in the downregulation of CD69 activating-marker for T cells (both TCD4+ and TCD8+) and in MCP-1 reduction. On the contrary, rhLAV-BPIFB4 induced a rapid increase in IL-18 and IL-1b levels, shown largely protective during the early stages of the virus infection. This evidence, along with the ability of rhLAV-BPIFB4 to counteract the cytotoxicity induced by SARS-CoV-2 lysate in selected target cell lines, corroborates BPIFB4 prognostic value and open new therapeutic possibilities in more vulnerable people. [ABSTRACT FROM AUTHOR]

Drug-target interaction (DTI) prediction has drawn increasing interest due to its substantial position in the drug discovery process. Many studies have introduced computational models to treat DTI prediction as a regression task, which directly predict the binding affinity of drug-target pairs. However, existing studies (i) ignore the essential correlations between atoms when encoding drug compounds and (ii) model the interaction of drug-target pairs simply by concatenation. Based on those observations, in this study, we propose an end-to-end model with multiple attention blocks to predict the binding affinity scores of drug-target pairs. Our proposed model offers the abilities to (i) encode the correlations between atoms by a relation-aware self-attention block and (ii) model the interaction of drug representations and target representations by the multi-head attention block. Experimental results of DTI prediction on two benchmark datasets show our approach outperforms existing methods, which are benefit from the correlation information encoded by the relation-aware self-attention block and the interaction information extracted by the multi-head attention block. Moreover, we conduct the experiments on the effects of max relative position length and find out the best max relative position length value |$k \in \{3, 5\}$|⁠. Furthermore, we apply our model to predict the binding affinity of Corona Virus Disease 2019 (COVID-19)-related genome sequences and |$3137$| FDA-approved drugs. [ABSTRACT FROM AUTHOR]

Summary: Coronavirus 19 (COVID‐19) has been associated with both transient and persistent systemic symptoms that do not appear to be a direct consequence of viral infection. The generation of autoantibodies has been proposed as a mechanism to explain these symptoms. To understand the prevalence of autoantibodies associated with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection, we investigated the frequency and specificity of clinically relevant autoantibodies in 84 individuals previously infected with SARS‐CoV‐2, suffering from COVID‐19 of varying severity in both the acute and convalescent setting. These were compared with results from 32 individuals who were on the intensive therapy unit (ITU) for non‐COVID reasons. We demonstrate a higher frequency of autoantibodies in the COVID‐19 ITU group compared with non‐COVID‐19 ITU disease control patients and that autoantibodies were also found in the serum 3–5 months post‐COVID‐19 infection. Non‐COVID patients displayed a diverse pattern of autoantibodies; in contrast, the COVID‐19 groups had a more restricted panel of autoantibodies including skin, skeletal muscle and cardiac antibodies. Our results demonstrate that respiratory viral infection with SARS‐CoV‐2 is associated with the detection of a limited profile of tissue‐specific autoantibodies, detectable using routine clinical immunology assays. Further studies are required to determine whether these autoantibodies are specific to SARS‐CoV‐2 or a phenomenon arising from severe viral infections and to determine the clinical significance of these autoantibodies. [ABSTRACT FROM AUTHOR]