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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]

Background COVID-19 is the most rapidly expanding coronavirus outbreak in the past 2 decades. To provide a swift response to a novel outbreak, prior knowledge from similar outbreaks is essential. Results Here, we study the volume of research conducted on previous coronavirus outbreaks, specifically SARS and MERS, relative to other infectious diseases by analyzing >35 million articles from the past 20 years. Our results demonstrate that previous coronavirus outbreaks have been understudied compared with other viruses. We also show that the research volume of emerging infectious diseases is very high after an outbreak and decreases drastically upon the containment of the disease. This can yield inadequate research and limited investment in gaining a full understanding of novel coronavirus management and prevention. Conclusions Independent of the outcome of the current COVID-19 outbreak, we believe that measures should be taken to encourage sustained research in the field. [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]

Background: While risk of outdoor transmission of respiratory viral infections is hypothesized to be low, there are limited data on SARS-CoV-2 transmission in outdoor compared to indoor settings.Methods: We conducted a systematic review of peer-reviewed papers indexed in PubMed, EMBASE, and Web of Science and preprints in Europe PMC through 12 August 2020 that described cases of human transmission of SARS-CoV-2. Reports of other respiratory virus transmission were included for reference.Results: Five identified studies found a low proportion of reported global SARS-CoV-2 infections occurred outdoors (<10%) and the odds of indoor transmission was very high compared to outdoors (18.7 times; 95% confidence interval, 6.0-57.9). Five studies described influenza transmission outdoors and 2 adenovirus transmission outdoors. There was high heterogeneity in study quality and individual definitions of outdoor settings, which limited our ability to draw conclusions about outdoor transmission risks. In general, factors such as duration and frequency of personal contact, lack of personal protective equipment, and occasional indoor gathering during a largely outdoor experience were associated with outdoor reports of infection.Conclusions: Existing evidence supports the wide-held belief that risk of SARS-CoV-2 transmission is lower outdoors but there are significant gaps in our understanding of specific pathways. [ABSTRACT FROM AUTHOR]

STUDY QUESTION Does maternal infection with severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) in first trimester pregnancy have an impact on the fetal development as measured by nuchal translucency thickness and pregnancy loss? SUMMARY ANSWER Nuchal translucency thickness at the first trimester scan was not significantly different in pregnant women with versus without SARS-CoV-2 infection in early pregnancy and there was no significantly increased risk of pregnancy loss in women with SARS-CoV-2 infection in the first trimester. WHAT IS KNOWN ALREADY Pregnant women are more vulnerable to viral infections. Previous coronavirus epidemics have been associated with increased maternal morbidity, mortality and adverse obstetric outcomes. Currently, no evidence exists regarding possible effects of SARS-CoV-2 in first trimester pregnancies. STUDY DESIGN, SIZE, DURATION Cohort study of 1019 women with a double test taken between 17 February and 23 April 2020, as a part of the combined first trimester risk assessment, and 36 women with a first trimester pregnancy loss between 14 April and 21 May 2020, prior to the double test. The study period was during the first SARS-CoV-2 epidemic wave in Denmark. PARTICIPANTS/MATERIALS, SETTING, METHODS Cohort 1 included pregnant women with a double test taken within the study period. The excess serum from each double test was analyzed for SARS-CoV-2 antibodies. Results were correlated to the nuchal translucency thickness and the number of pregnancy losses before or at the time of the first trimester scan. Cohort 2 included women with a pregnancy loss before the gestational age for double test sample. Serum from a blood test taken the day the pregnancy loss was identified was analyzed for SARS-CoV-2 antibodies. The study was conducted at a public university hospital serving ∼12% of pregnant women and births in Denmark. All participants in the study provided written informed consent. MAIN RESULTS AND THE ROLE OF CHANCE Eighteen (1.8%) women had SARS-CoV-2 antibodies in the serum from the double test suggestive of SARS-CoV-2 infection in early pregnancy. There was no significant difference in nuchal translucency thickness for women testing positive for previous SARS-CoV-2 infection (n = 16) versus negative (n = 966) (P  = 0.62). There was no significantly increased risk of pregnancy loss for women with antibodies (n = 1) (OR 3.4, 0.08–24.3 95% CI, P  = 0.27). None of the women had been hospitalized due to SARS-CoV-2 infection. None of the women with pregnancy loss prior to the double test (Cohort 2) had SARS-CoV-2 antibodies. LIMITATIONS, REASONS FOR CAUTION These results may only apply to similar populations and to patients who do not require hospitalization due to SARS-CoV-2 infection. A limitation of the study is that only 1.8% of the study population had SARS-CoV-2 antibodies suggestive of previous infection. WIDER IMPLICATION OF THE FINDINGS Maternal SARS-CoV-2 infection had no effect on the nuchal translucency thickness and there was no significantly increased risk of pregnancy loss for women with SARS-CoV-2 infection in first trimester pregnancy. Evidence concerning COVID-19 in pregnancy is still limited. These data indicate that infection with SARS-CoV-2 in not hospitalized women does not pose a significant threat in first trimester pregnancies. Follow-up studies are needed to establish any risk to a fetus exposed to maternal SARS-CoV-2 infection. STUDY FUNDING/COMPETING INTEREST(S) Prof. H.S.N. and colleagues received a grant from the Danish Ministry of Research and Education for research of COVID-19 among pregnant women. The Danish government was not involved in the study design, data collection, analysis, interpretation of data, writing of the report or decision to submit the paper for publication. A.I. J.O.-L. J.B.-R. D.M.S. J.E.-F. and E.R.H. received funding from a Novo Nordisk Foundation (NNF) Young Investigator Grant (NNF15OC0016662) and a Danish National Science Foundation Center Grant (6110-00344B). A.I. received a Novo Scholarship. J.O.-L. is funded by an NNF Pregraduate Fellowship (NNF19OC0058982). D.W. is funded by the NNF (NNF18SA0034956, NNF14CC0001, NNF17OC0027594). A.M.K. is funded by a grant from the Rigshospitalet's research fund. H.S.N. has received speaker's fees from Ferring Pharmaceuticals, Merck Denmark A/S and Ibsa Nordic (outside the submitted work). N.l.C.F. has received a grant from Gedeon Richter (outside the submitted work). A.M.K. has received speaker's fee from Merck (outside the submitted work). The other authors did not report any potential conflicts of interest. TRIAL REGISTRATION NUMBER N/A [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]

Objectives Viral outbreaks are a frequent concern for humans. A great variety of drugs has been used to treat viral diseases, which are not always safe and effective and may induce adverse effects, indicating the need for new antiviral drugs extracted from natural sources. Propolis is a beemade product exhibiting many biological properties. An overview of viruses, antiviral immunity, propolis safety and its immunomodulatory and antiviral action is reported, as well as perspectives for coronavirus disease 2019 (COVID-19) treatment. PubMed platform was used for data collection, searching for the keywords "propolis", "virus", "antiviral", "antimicrobial" and "coronavirus". Key findings Propolis is safe and exerts antiviral and immunomodulatory activity; however, clinical trials should investigate its effects on individuals with viral diseases, in combination or not with antiviral drugs or vaccines. Summary Regarding COVID-19, the effects of propolis should be investigated directly on the virus in vitro or on infected individuals alone or in combination with antiviral drugs, due to its immunomodulatory and anti-inflammatory action. Propolis administration simultaneously with vaccines should be analyzed, due to its adjuvant properties, to enhance the individuals' immune response. The search for therapeutic targets may be useful to find out how propolis can help to control COVID-19. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has spread in nearly 200 countries in less than 4 months since its first identification; accordingly, the coronavirus disease 2019 (COVID 2019) has affirmed itself as a clinical challenge. The prevalence of pre-existing cardiovascular diseases in patients with COVID19 is high and this dreadful combination dictates poor prognosis along with the higher risk of intensive care mortality. In the setting of chronic heart failure, SARS-CoV-2 can be responsible for myocardial injury and acute decompensation through various mechanisms. Given the clinical and epidemiological complexity of COVID-19, patiens with heart failure may require particular care since the viral infection has been identified, considering an adequate re-evaluation of medical therapy and a careful monitoring during ventilation. [ABSTRACT FROM AUTHOR]

Objective Coronavirus disease 2019 (COVID-19) is a fatal and fast-spreading viral infection. To date, the number of COVID-19 patients worldwide has crossed over six million with over three hundred and seventy thousand deaths (according to the data from World Health Organization; updated on 2 June 2020). Although COVID-19 can be rapidly diagnosed, efficient clinical treatment of COVID-19 remains unavailable, resulting in high fatality. Some clinical trials have identified vitamin C (VC) as a potent compound pneumonia management. In addition, glycyrrhizic acid (GA) is clinically as an anti-inflammatory medicine against pneumonia-induced inflammatory stress. We hypothesized that the combination of VC and GA is a potential option for treating COVID-19. Methods The aim of this study was to determine pharmacological targets and molecular mechanisms of VC + GA treatment for COVID-19, using bioinformational network pharmacology. Results We uncovered optimal targets, biological processes and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of VC + GA against COVID-19. Our findings suggested that combinatorial VC and GA treatment for COVID-19 was associated with elevation of immunity and suppression of inflammatory stress, including activation of the T cell receptor signaling pathway, regulation of Fc gamma R-mediated phagocytosis, ErbB signaling pathway and vascular endothelial growth factor signaling pathway. We also identified 17 core targets of VC + GA, which suggest as antimicrobial function. Conclusions For the first time, our study uncovered the pharmacological mechanism underlying combined VC and GA treatment for COVID-19. These results should benefit efforts to address the most pressing problem currently facing the world. [ABSTRACT FROM AUTHOR]

As of 15 August 2020, Coronavirus disease 2019 (COVID-19) has been reported in >21 million people world-wide and is responsible for more than 750,000 deaths. The occurrence of acute kidney injury (AKI) in patients hospitalized with COVID-19 has been reported to be as high as 43%. This is comparable to AKI in other forms of pneumonia requiring hospitalization, as well as in non-infectious conditions like cardiac surgery. The impact of AKI on COVID-19 outcomes is difficult to assess at present but, similar to other forms of sepsis, AKI is strongly associated with hospital mortality. Indeed, mortality is reported to be very low in COVID-19 patients without AKI. Given that AKI contributes to fluid and acid–base imbalances, compromises immune response and may impair resolution of inflammation, it seems likely that AKI contributes to mortality in these patients. The pathophysiologic mechanisms of AKI in COVID-19 are thought to be multifactorial including systemic immune and inflammatory responses induced by viral infection, systemic tissue hypoxia, reduced renal perfusion, endothelial damage and direct epithelial infection with Severe Acute Respiratory Syndrome Coronavirus 2. Mitochondria play a central role in the metabolic deregulation in the adaptive response to the systemic inflammation and are also found to be vital in response to both direct viral damage and tissue reperfusion. These stress conditions are associated with increased glycolysis and reduced fatty acid oxidation. Thus, there is a strong rationale to target AKI for therapy in COVID-19. Furthermore, many approaches that have been developed for other etiologies of AKI such as sepsis, inflammation and ischemia–reperfusion, have relevance in the treatment of COVID-19 AKI and could be rapidly pivoted to this new disease. [ABSTRACT FROM AUTHOR]

The chest CT findings that can distinguish patients with corona virus disease 2019 (COVID-19) from those with clinically suspected COVID-19 but subsequently found to be COVID-19 negative have not previously been described in detail. The purpose of this study was to determine the distinctions among patients with COVID-19 by comparing the imaging findings of patients with suspected confirmed COVID-19 and those of patients initially suspected to have COVID-19 who were ultimately negative for the disease. 28 isolated suspected in-patients with COVID-19 were enrolled in this retrospective study from January 22, 2020 to February 6, 2020. 12 patients were confirmed to have positive severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) RNA results, and 16 patients had negative results. The thin-section CT imaging findings and clinical and laboratory data of all the patients were evaluated. There were no significant differences between the 12 confirmed COVID-19 (SARS-Cov-2-positive) patients and 16 SARS-CoV-2-negative patients in epidemiology and most of the clinical features or laboratory data. The CT images showed that the incidence of pure/mixed ground-glass opacities (GGOs) was not different between COVID-19 and SARS-CoV-2-negative patients [9/12 (75.0%) vs 10/16 (62.5%), p = 0.687], but pure/mixed GGOs in the peripheral were more common in patients with COVID-19 [11/12 (91.7%) vs 6/16 (37.5%), p = 0.006]. There were no significant differences in the number of lesions, bilateral lung involvement, large irregular/patchy opacities, rounded opacities, linear opacities, crazy-paving patterns, halo signs, interlobular septal thickening or air bronchograms. Although peripheral pure/mixed GGOs on CT may help distinguish patients with COVID-19 from clinically suspected but negative patients, CT cannot replace RT-PCR testing. Peripheral pure/mixed GGOs on-chest CT findings can be helpful in distinguishing patients with COVID-19 from those with clinically suspected COVID-19 but subsequently found to be COVID-19 negative. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a rapidly emerging viral infection causing coronavirus disease 2019 (COVID-19). Hydroxychloroquine and chloroquine have garnered unprecedented attention as potential therapeutic agents against COVID-19 following several small clinical trials, uncontrolled case series, and public figure endorsements. While there is a growing body of scientific data, there is also concern for harm, particularly QTc prolongation and cardiac arrhythmias. Here, we perform a rapid narrative review and discuss the strengths and limitations of existing in vitro and clinical studies. We call for additional randomized controlled trial evidence prior to the widespread incorporation of hydroxychloroquine and chloroquine into national and international treatment guidelines. [ABSTRACT FROM AUTHOR]