COVID-19 vaccination produces exercise-responsive SARS-CoV-2 specific T-cells regardless of infection history

Background:The mobilization and redistribution of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)specific T-cells and neutralizing antibodies(nAbs)during exercise is purported to increase immune surveillance and protect against severe coronavirus disease 2019(COVID-19).We sought to determine if COVID-19 vaccination would elicit exercise-responsive SARS-CoV-2 T-cells and transiently alter nAb titers.Methods:Eighteen healthy participants completed a 20-min bout of graded cycling exercise before and/or after receiving a COVID-19 vaccine.All major leukocyte subtypes were enumerated before,during,and after exercise by flow cytometry,and immune responses to SARS-CoV-2 were determined using whole blood peptide stimulation assays,T-cell receptor(TCR)-βsequencing,and SARS-CoV-2 nAb serology.Results:COVID-19 vaccination had no effect on the mobilization or egress of major leukocyte subsets in response to intensity-controlled graded exercise.However,non-infected participants had a significantly reduced mobilization of CD4+and CD8+naive T-cells,as well as CD4+central memory T-cells,after vaccination(synthetic immunity group);this was not seen after vaccination in those with prior SARS-CoV-2 infection(hybrid immunity group).Acute exercise after vaccination robustly mobilized SARS-CoV-2 specific T-cells to blood in an intensity-dependent manner.Both groups mobilized T-cells that reacted to spike protein;however,only the hybrid immunity group mobilized T-cells that reacted to membrane and nucleocapsid antigens.nAbs increased significantly during exercise only in the hybrid immunity group.Conclusion:These data indicate that acute exercise mobilizes SARS-CoV-2 specific T-cells that recognize spike protein and increases the redistribution of nAbs in individuals with hybrid immunity.

Genomic Profile of SARS-COV-2 Associated with COVID-19 Outbreaks in N’Djamena, Chad

Background: SARS-CoV-2 has circulated worldwide with dramatic consequences. In Chad, we have no data reported of variants. The aim of this study was to identify the SARS-CoV-2 variants that circulated during the epidemic from 2020 to 2021. Methods: This is a cross-sectional, descriptive study carried out between 2020 and 2021. Samples from patients with suspected COVID-19 were tested in five laboratories in N’Djamena. One hundred quality samples of the positives were sequenced in Kinshasa using Oxford nanopore technologies minion and the Protocol Midnight SARS-CoV2. Data were processed using Excel version 16 software. Results: Of the 100 samples sequenced, 77 (77%) produced sequences, 23 (23%) did not. The genomic profiles were wild-type Wuhan and minor mutations (19A, 19B (A), 20A (B.1, B.2), 20B (AV.1), 20D (B.1.1.1 /C.36), 20C), variant of concern Alpha (20I), variant of concern Delta (21A/J), variant of interest Eta (21D), variant of concern Omicron (21K) and unclassified variant under surveillance (B.1.640). Of these variants, the maximums were detected in patients aged 26 - 35 with 30.26% and 25.26% in 36 - 45. However, 24.67% were in travelers and 75.32% in residents, 35.06% in those vaccinated against COVID-19 and 62.33% in non-vaccinates. The estimated case-fatality rate was 2.44% (107/4374). Conclusion: This work has provided preliminary data on COVID-19 and SARS-CoV-2 variants circulating during the 2020-2021 epidemics in Chad.

自然杀伤(NK)细胞与2019冠状病毒病(COVID-19)发生发展的研究进展

自然杀伤(NK)细胞在清除病毒,执行免疫调节方面发挥着重要的作用,它通过分泌趋化因子以及与其他天然免疫细胞协同作用,被赋予天然免疫调节功能和获得性免疫反应。随着对严重急性呼吸综合征冠状病毒2(SARS-CoV-2)感染的2019冠状病毒病(COVID-19)的研究深入,发现NK细胞在其中发挥着重要作用。SARS-CoV-2感染会影响NK细胞的分布和效应功能,NK细胞的免疫应答或可影响新冠肺炎患者的预后。本文总结了近年来NK细胞在COVID-19感染中作用的研究现状,并且讨论了以NK细胞作为治疗剂的可能性,以期为防治SARS-CoV-2的免疫损害提供潜在思路。

Hepatic angiotensin-converting enzyme 2 expression in metabolic dysfunction-associated steatotic liver disease and in patients with fatal COVID-19

BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD),characterised by hepatic lipid accumulation,causes inflammation and oxidative stress accompanied by cell damage and fibrosis.Liver injury(LI)is also frequently reported in patients hospitalised with coronavirus disease 2019(COVID-19),while preexisting MASLD increases the risk of LI and the development of COVID-19-associated cholangiopathy.Mechanisms of injury at the cellular level remain unclear,but it may be significant that severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)which causes COVID-19,uses angiotensin-converting expression enzyme 2(ACE2),a key regulator of the‘anti-inflammatory’arm of the renin-angiotensin system,for viral attachment and host cell invasion.AIM To determine if hepatic ACE2 levels are altered during progression of MASLD and in patients who died with severe COVID-19.METHODS ACE2 protein levels and localisation,and histological fibrosis and lipid droplet accumulation as markers of MASLD were determined in formalin-fixed liver tissue sections across the MASLD pathological spectrum(isolated hepatocellular steatosis,metabolic dysfunction-associated steatohepatitis(MASH)+/-fibrosis,end-stage cirrhosis)and in post-mortem tissues from patients who had died with severe COVID-19,using ACE2 immunohistochemistry and haematoxylin and eosin and picrosirius red staining of total collagen and lipid droplet areas,followed by quantification using machine learning-based image pixel classifiers.RESULTS ACE2 staining is primarily intracellular and concentrated in the cytoplasm of centrilobular hepatocytes and apical membranes of bile duct cholangiocytes.Strikingly,ACE2 protein levels are elevated in non-fibrotic MASH compared to healthy controls but not in the progression to MASH with fibrosis and in cirrhosis.ACE2 protein levels and histological fibrosis are not associated,but ACE2 and liver lipid droplet content are significantly correlated across the MASLD spectrum.Hepatic ACE2 levels are also increased in COVID-19 patients,especially those showing evidence of LI,but are not correlated with the presence of SARS-CoV-2 virus in the liver.However,there is a clear association between the hepatic lipid droplet content and the presence of the virus,suggesting a possible functional link.CONCLUSION Hepatic ACE2 levels were elevated in nonfibrotic MASH and COVID-19 patients with LI,while lipid accumulation may promote intra-hepatic SARS-CoV-2 replication,accelerating MASLD progression and COVID-19-mediated liver damage.

Role of renin-angiotensin system/angiotensin converting enzyme-2 mechanism and enhanced COVID-19 susceptibility in type 2 diabetes mellitus

Coronavirus disease 2019(COVID-19)is a disease that caused a global pandemic and is caused by infection of severe acute respiratory syndrome coronavirus 2 virus.It has affected over 768 million people worldwide,resulting in approx-imately 6900000 deaths.High-risk groups,identified by the Centers for Disease Control and Prevention,include individuals with conditions like type 2 diabetes mellitus(T2DM),obesity,chronic lung disease,serious heart conditions,and chronic kidney disease.Research indicates that those with T2DM face a hei-ghtened susceptibility to COVID-19 and increased mortality compared to non-diabetic individuals.Examining the renin-angiotensin system(RAS),a vital regulator of blood pressure and pulmonary stability,reveals the significance of the angiotensin-converting enzyme(ACE)and ACE2 enzymes.ACE converts angiotensin-I to the vasoconstrictor angiotensin-II,while ACE2 counters this by converting angiotensin-II to angiotensin 1-7,a vasodilator.Reduced ACE2 exp-ression,common in diabetes,intensifies RAS activity,contributing to conditions like inflammation and fibrosis.Although ACE inhibitors and angiotensin receptor blockers can be therapeutically beneficial by increasing ACE2 levels,concerns arise regarding the potential elevation of ACE2 receptors on cell membranes,potentially facilitating COVID-19 entry.This review explored the role of the RAS/ACE2 mechanism in amplifying severe acute respiratory syndrome cor-onavirus 2 infection and associated complications in T2DM.Potential treatment strategies,including recombinant human ACE2 therapy,broad-spectrum antiviral drugs,and epigenetic signature detection,are discussed as promising avenues in the battle against this pandemic.

Recurrent stroke admissions with vs without COVID-19 and associated in-hospital mortality: A United States nationwide analysis, 2020

BACKGROUND Coronavirus disease 2019(COVID-19)has been shown to increase the risk of stroke.However,the prevalence and risk of recurrent stroke in COVID-19 patients with prior stroke/transient ischemic attack(TIA),as well as its impact on mor-tality,are not established.AIM To evaluate the impact of COVID-19 on in-hospital mortality,length of stay,and healthcare costs in patients with recurrent strokes.METHODS We identified admissions of recurrent stroke(current acute ischemic stroke admissions with at least one prior TIA or stroke)in patients with and without COVID-19 using ICD-10-CM codes using the National Inpatient Sample(2020).We analyzed the impact of COVID-19 on mortality following recurrent stroke admissions by subgroups.RESULTS Of 97455 admissions with recurrent stroke,2140(2.2%)belonged to the COVID-19-positive group.The COVID-19-positive group had a higher prevalence of diabetes and chronic kidney disease vs the COVID-19 negative group(P<0.001).Among the subgroups,patients aged>65 years,patients aged 45–64 years,Asians,Hispanics,whites,and blacks in the COVID-19 positive group had higher rates of all-cause mortality than the COVID-19 negative group(P<0.01).Higher odds of in-hospital mortality were seen in the group aged 45-64(OR:8.40,95%CI:4.18-16.91)vs the group aged>65(OR:7.04,95%CI:5.24-9.44),males(OR:7.82,95%CI:5.38-11.35)compared to females(OR:6.15,95%CI:4.12-9.18),and in Hispanics(OR:15.47,95%CI:7.61-31.44)and Asians/Pacific Islanders(OR:14.93,95%CI:7.22-30.87)compared to blacks(OR:5.73,95%CI:3.08-10.68),and whites(OR:5.54,95%CI:3.79-8.09).CONCLUSION The study highlights the increased risk of all-cause in-hospital mortality in recurrent stroke patients with COVID-19,with a more pronounced increase in middle-aged patients,males,Hispanics,or Asians.

SARS-CoV-2 proteins show great binding affinity to resin composite monomers and polymerized chains

BACKGROUND Due to saliva and salivary glands are reservoir to severe acute respiratory syndrome-coronavirus 2(SARS-CoV-2),aerosols and saliva droplets are primary sources of cross-infection and are responsible for the high human–human transmission of SARS-CoV-2.However,there is no evidence about how SARSCoV-2 interacts with oral structures,particularly resin composites.AIM To evaluate the interaction of SARS-CoV-2 proteins with monomers present in resin composites using in silico analysis.METHODS Four SARS-CoV-2 proteins[i.e.main protease,3C-like protease,papain-like protease(PLpro),and glycoprotein spike]were selected along with salivary amylase as the positive control,and their binding affinity with bisphenol-A glycol dimethacrylate,bisphenol-A ethoxylated dimethacrylate,triethylene glycol dimethacrylate,and urethane dimethacrylate was evaluated.Molecular docking was performed using AutoDock Vina and visualised in Chimera UCSF 1.14.The best ligand–protein model was identified based on the binding energy(ΔG–kcal/moL).RESULTS Values for the binding energies ranged from-3.6 kcal/moL to-7.3 kcal/moL.The 3-monomer chain had the lowest binding energy(i.e.highest affinity)to PLpro and the glycoprotein spike.Non-polymerised monomers and polymerised chains interacted with SARS-CoV-2 proteins via hydrogen bonds and hydrophobic interactions.Those findings suggest an interaction between SARS-CoV-2 proteins and resin composites.CONCLUSION SARS-CoV-2 proteins show affinity to non-polymerised and polymerised resin composite chains.

Angiotensin-converting enzyme 2 and hepatic SARS-CoV-2 infection:Regulation,association,and therapeutic implications

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)enters host cells via the angiotensin-converting enzyme 2(ACE2)receptor.Mounting evidence has indicated the presence of hepatic SARS-CoV-2 infection and liver injury in pa-tients with coronavirus disease 2019(COVID-19).Understanding the mechanisms of hepatic SARS-CoV-2 infection is crucial for addressing COVID-19–related liver pathology and developing targeted therapies.This editorial discusses the signi-ficance of ACE2 in hepatic SARS-CoV-2 infection,drawing on the research by Jacobs et al.Their findings indicate that hepatic ACE2 expression,frequency of hepatic SARS-CoV-2 infection,and severity of liver injury are elevated in patients with pre-existing chronic liver diseases.These data suggest that hepatic ACE2 could be a promising therapeutic target for COVID-19.

E3 Ligases and COVID-19:Insights into Viral Control andTherapeutic Potential

The COVID-19 pandemic,caused by the newly emerged coronavirus SARS-CoV-2,has resulted in unprecedented global health challenges,including millions of infections and deaths.While the direct effects of the virus are critical,the interplay between SARS-CoV-2 and cellular host factors significantly impacts the replication cycle of the virus and the clinical severity of COVID-19.This review provides a comprehensive analysis of hostpathogen interactions,focusing on the functional roles and regulatory mechanisms of SARS-CoV-2 viral proteins.We systematically review the literature to detail how SARS-CoV-2 engages with host cellular machinery,with a specific emphasis on their modulation by E3 ubiquitin ligases.By dissecting these intricate interactions and the impact of E3 ligases on SARS-CoV-2 infection,we aimto uncover novel therapeutic opportunities and strategies to effectively combat COVID-19.

Extracellular vesicles and angiotensin-converting enzyme 2 in COVID-19 disease

Extracellular vesicles(EVs)are membranous vesicular structures released from almost all eukaryotic cell types under different physiological or pathological conditions.Growing evidence demonstrates that EVs can serve as mediators of intercellular communication between donor and recipient cells or microorganism-infected and noninfected cells.Coronavirus disease 2019(COVID-19)disease is caused by infection of the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)of host cells in the respiratory system and various extra-pulmonary tissue/organs,resulting in complications of multiple organ systems.As the cell surface receptor,angiotensin-converting enzyme 2(ACE2)mediates cellular entry of SARS-CoV-2 into the host cells in patients with COVID-19.Recent studies have found that ACE2 can be released with EVs,which have been shown to interfere with the entry of the virus into host cells and thus may be involved in COVID-19 pathophysiology.In addition,ACE2,neprilysin(NEP),and thimet oligopeptidase(TOP)are the key enzymes that regulate angiotensin metabolism by converting angiotensin II or angiotensin I to angiotensin 1-7,the latter of which has protective effects in counterbalancing the harmful effects of angiotensin II in COVID-19 disease.This review summarizes the recent research progress regarding EV-associated ACE2,NEP,and TOP and the perspectives of their potential involvement in the pathophysiology of COVID-19 disease.

COVID-19-like symptoms observed in Chinese tree shrews infected with SARS-CoV-2

Thecoronavirusdisease2019(COVID-19)pandemic continues to pose a global threat to the human population. Identifying animal species susceptible to infection with the SARS-CoV-2/HCoV-19 pathogen is essential for controlling the outbreak and for testing valid prophylactics or therapeutics based on animal model studies. Here,different aged Chinese tree shrews(adult group, 1 year old;old group, 5–6 years old), which are close relatives to primates, were infected with SARS-CoV-2. X-ray, viral shedding, laboratory, and histological analyses were performed on different days postinoculation(dpi). Results showed that Chinese tree shrews could be infected by SARS-CoV-2. Lung infiltrates were visible in X-ray radiographs in most infected animals. Viral RNA was consistently detected in lung tissues from infected animals at 3,5, and 7 dpi, along with alterations in related parameters from routine blood tests and serum biochemistry, including increased levels of aspartate aminotransferase(AST) and blood urea nitrogen(BUN). Histological analysis of lung tissues from animals at 3 dpi(adult group) and 7 dpi(old group) showed thickened alveolar septa and interstitial hemorrhage. Several differences were found between the two different aged groups in regard to viral shedding peak. Our results indicate that Chinese tree shrews have the potential to be used as animal models for SARS-CoV-2 infection.

Structural basis of SARS-CoV-2 3CL^pro and anti-COVID-19 drug discovery from medicinal plants

The recent pandemic of coronavirus disease 2019(COVID-19)caused by SARS-CoV-2 has raised global health concerns.The viral 3-chymotrypsin-like cysteine protease(3CL^pro)enzyme controls coronavirus replication and is essential for its life cycle.3CL^pro is a proven drug discovery target in the case of severe acute respiratory syndrome coronavirus(SARS-CoV)and Middle East respiratory syndrome coronavirus(MERS-CoV).Recent studies revealed that the genome sequence of SARS-CoV-2 is very similar to that of SARS-CoV.Therefore,herein,we analysed the 3CL^pro sequence,constructed its 3D homology model,and screened it against a medicinal plant library containing 32,297 potential anti-viral phytochemicals/traditional Chinese medicinal compounds.Our analyses revealed that the top nine hits might serve as potential anti-SARS-CoV-2 lead molecules for further optimisation and drug development process to combat COVID-19.

Potential Treatment of COVID-19 with Traditional Chinese Medicine: What Herbs Can Help Win the Battle with SARS-CoV-2?

Traditional Chinese medicine(TCM)has been successfully applied worldwide in the treatment of coronavirus disease 2019(COVID-19),which is caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).However,the pharmacological mechanisms underlying this success remain unclear.Hence,the aim of this review is to combine pharmacological assays based on the theory of TCM in order to elucidate the potential signaling pathways,targets,active compounds,and formulas of herbs that are involved in the TCM treatment of COVID-19,which exhibits combatting viral infections,immune regulation,and amelioration of lung injury and fibrosis.Extensive reports on target screening are elucidated using virtual prediction via docking analysis or network pharmacology based on existing data.The results of these reports indicate that an intricate regulatory mechanism is involved in the pathogenesis of COVID-19.Therefore,more pharmacological research on the natural herbs used in TCM should be conducted in order to determine the association between TCM and COVID-19 and account for the observed therapeutic effects of TCM against COVID-19.

COVID-19 and the gastrointestinal tract:Source of infection or merely a target of the inflammatory process following SARS-CoV-2 infection?

Gastrointestinal(GI)symptoms have been described in a conspicuous percentage of coronavirus disease 2019(COVID-19)patients.This clinical evidence is supported by the detection of viral RNA in stool,which also supports the hypothesis of a possible fecal-oral transmission route.The involvement of GI tract in severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection is corroborated by the theoretical assumption that angiotensin converting enzyme 2,which is a SARS-CoV-2 target receptor,is present along the GI tract.Studies have pointed out that gut dysbiosis may occur in COVID-19 patients,with a possible correlation with disease severity and with complications such as multisystem inflammatory syndrome in children.However,the question to be addressed is whether dysbiosis is a consequence or a contributing cause of SARS-CoV-2 infection.In such a scenario,pharmacological therapies aimed at decreasing GI permeability may be beneficial for COVID-19 patients.Considering the possibility of a fecal-oral transmission route,water and environmental sanitation play a crucial role for COVID-19 containment,especially in developing countries.

Clinical features of SARS-CoV-2-associated encephalitis and meningitis amid COVID-19 pandemic

BACKGROUND Since the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)epidemic,numerous studies have been published on SARS-CoV-2-related encephalitis/meningitis,but it has not been established if there are specific clinical characteristics of encephalitis/meningitis associated with SARS-CoV-2 infection.AIM To identify the specific clinical features of cases of encephalitis/meningitis associated with SARS-CoV-2 infection in the context of this virus infection pandemic and investigate their relationship with SARS-CoV-2 infection.METHODS We searched PubMed,and included single case reports and case series with full text in English,reporting original data of coronavirus disease-19(COVID-19)patients with encephalitis/meningitis and a confirmed recent SARS-CoV-2 infection.Clinical data were extracted.RESULTS We identified 22 articles(18 single case reports and 4 case series)reporting on a total of 32 encephalitis/meningitis patients with confirmed SARS-CoV-2 infection.SARS-CoV-2 infection was confirmed through reverse transcriptase-polymerasechain-reaction(RT-PCR)in 96.88%of cases.A total of 22(68.75%)patients had symptoms of SARS-CoV-2 infection in about 1 wk(7.91 d)preceding the onset of neurologic symptoms.The most common neurological symptoms were consciousness disturbance(59.38%),seizure(21.88%),delirium(18.75%),and headache(18.75%).Four cases were confirmed by positive RT-PCR results in cerebrospinal fluid(CSF),one was confirmed by positive RT-PCR results in postoperative brain tissue,and one by the presence of SARS-CoV-2 antibodies in CSF.The mainly damaged targets identified by neuroimaging included the temporal lobe(15.63%),white matter(12.5%),frontal lobe(9.38%),corpus callosum(9.38%),and cervical spinal cord(9.38%).Eighty percent of patients had electroencephalograms that showed a diffuse slow wave.Twenty-eight(87.5%)patients were administered with specific treatment.The majority(65.63%)of patients improved following systemic therapy.CONCLUSION Encephalitis/meningitis is the common neurological complication in patients with COVID-19.The appropriate use of definitions and exclusion of potential similar diseases are important to reduce over-diagnosis of SARS-CoV-2 associated encephalitis or meningitis.

One disease, many faces-typical and atypical presentations of SARS-CoV-2 infection-related COVID-19 disease

Since the appearance of the novel coronavirus(severe acute respiratory syndrome-coronavirus-2)and related coronavirus disease 2019(COVID-19)in China in December 2019,a very high number of small and large patient series have been published in literature from around the world.Even though the classical presentation of COVID-19 is one with respiratory symptoms with or without pneumonia that can be self-limiting or evolve into severe respiratory distress syndrome with multiple organ failure,and secondary bacterial sepsis,a large body of evidence suggests a plethora of other types of clinical presentation.In this exhaustive review,we reviewed all of the published literature on COVID-19 to identify different types of clinical presentations affecting various organ systems,to provide an in-depth analysis that may prove useful for clinicians and health-workers on the frontline,battling the severe pandemic.

SARS-Cov-2 Delayed Tokyo 2020 Olympics: Very Recent Advances in COVID-19 Detection, Treatment, and Vaccine Development Useful Conducting the Games in 2021

The novel coronavirus (SARS-Cov-2) delayed the Tokyo 2020 Games. The traveling by air, rail, road, and sea inside and outside the countries has stopped to contain the virus. The amount of money lost and assistance needed to reschedule and conduct the Games in 2021 have been estimated. With more than one billion population is under the semi-locked down and movement of people is restricted, athletes cannot prepare at home and participate in the Games. The COVID-19 outbreak has spread around the world;it has already infected 5.7 million people and caused 355,000 deaths reported on May 28, 2020 and the figures increasing every day. The publication of this article is important as the postponement of the Olympics has costed Japan $6 billion and the organizers have worked very hard for seven years. If the Games are conducted in 2021, it will be the—beginning of the world recovery—from big COVID-19 pandemic. In this communication, the development in testing, treatment, and vaccine preparation for SARS-Cov-2 have occurred so far in different countries and companies have been discussed to know the possibilities if the pandemic can be overcome and the Games can be conducted in 2021.

High fecal calprotectin levels are associated with SARS-CoV-2 intestinal shedding in COVID-19 patients:A proof-of-concept study

BACKGROUND One third of coronavirus disease 2019(COVID-19)patients have gastrointestinal symptoms.Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)RNA has been detected in stool samples of approximately 50%of COVID-19 individuals.Fecal calprotectin is a marker of gastrointestinal inflammation in the general population.AIM To investigate if fecal calprotectin correlates with SARS-CoV-2 intestinal shedding in COVID-19 patients with pneumonia.METHODS Patients with SARS-CoV-2 pneumonia admitted to the Infectious Disease Unit(University Hospital of Trieste,Italy)from September to November 2020 were consecutively enrolled in the study.Fecal samples were collected and analyzed for quantification of fecal calprotectin(normal value<50 mg/kg)and SARS-CoV-2 RNA presence by polymerase chain reaction(PCR).Inter-group differences were determined between patients with and without diarrhea and patients with and without detection of fecal SARS-CoV-2.RESULTS We enrolled 51 adults(40 males)with SARS-CoV-2 pneumonia.Ten patients(20%)presented with diarrhea.Real-time-PCR of SARS-CoV-2 in stools was positive in 39 patients(76%),in all patients with diarrhea(100%)and in more than two thirds(29/41,71%)of patients without diarrhea.Obesity was one of the most common comorbidities(13 patients,25%);all obese patients(100%)(P=0.021)tested positive for fecal SARS-CoV-2.Median fecal calprotectin levels were 60 mg/kg[interquartile range(IQR)21;108];higher fecal calprotectin levels were found in the group with SARS-CoV-2 in stools(74 mg/kg,IQR 29;132.5)compared to the group without SARS-CoV-2(39 mg/kg,IQR 14;71)(P<0.001).CONCLUSION High fecal calprotectin levels among COVID-19 patients correlate with SARSCoV-2 detection in stools supporting the hypothesis that this virus can lead to bowel inflammation and potentially to the‘leaky gut’syndrome.

Ocular manifestations and SARS-CoV-2 detection in tears and conjunctival scrape from non-severe COVID-19 patients

AIM:To explore the ocular features of corona virus disease(COVID)-19 and severe acute respiratory syndrome coronavirus(SARS-CoV)-2 detection in tears and conjunctival scrapes in non-severe COVID-19 patients.METHODS:This is a multicenter observational clinical study with no intervention conducted from Jan 25th to March 1st,2020.Clinical data and samples of tears and conjunctival scraping were collected in consecutive laboratory-confirmed,non-severe COVID-19 patients from three hospitals.COVID-19 virus was analyzed by real-time reverse transcriptase polymerase chain reaction(RT-PCR)kits.RESULTS:Totally 255 laboratory-confirmed,non-severe COVID-19 patients were recruited for ocular manifestation investigation.Of them,54.9%were females,with a mean age of 49.4 y.None of the patients has evidence of uveitis;11 patients(4.3%)complained of mild asthenopia;2(0.8%)had mild conjunctival congestion and serous secretion.Twenty-five of them had performed tears and conjunctival scrape for COVID-19 virus detection,with 4 yield possible positive results in the nucleoprotein gene.One of them were asymptomatic with normal chest CT and positive pharyngeal swab result.CONCLUSION:Ocular manifestations are neither common nor specific in non-severe COVID-19 patients.Meanwhile,COVID-19 virus nucleotides can be detected in the tears and conjunctival scrape samples,warranting further research on the transmissibility by the ocular route.

ANALYSIS OF THE GENOMIC DISTANCE BETWEEN BAT CORONAVIRUS RATG13 AND SARS-COV-2 REVEALS MULTIPLE ORIGINS OF COVID-19

The severe acute respiratory syndrome COVID-19 was discovered on December 31,2019 in China.Subsequently,many COVID-19 cases were reported in many other countries.However,some positive COVID-19 samples had been reported earlier than those officially accepted by health authorities in other countries,such as France and Italy.Thus,it is of great importance to determine the place where SARS-CoV-2 was first transmitted to human.To this end,we analyze genomes of SARS-CoV-2 using k-mer natural vector method and compare the similarities of global SARS-CoV-2 genomes by a new natural metric.Because it is commonly accepted that SARS-CoV-2 is originated from bat coronavirus RaTG13,we only need to determine which SARS-CoV-2 genome sequence has the closest distance to bat coronavirus RaTG13 under our natural metric.From our analysis,SARS-CoV-2 most likely has already existed in other countries such as France,India,Netherland,England and United States before the outbreak at Wuhan,China.