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1.
Trends Microbiol ; 2022 Oct 24.
Article in English | MEDLINE | ID: covidwho-2083104

ABSTRACT

The epidemiology of COVID-19 has dramatically changed since the beginning of the pandemic as we witnessed significant changes in transmissibility and pathogenicity with the emergence of SARS-CoV-2 variants of concern (VoCs). Here I present and comment on working hypotheses about the evolutionary dynamics of the emergence of VoCs.

2.
Biochemistry (Mosc) ; 86(4): 389-396, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-2078751

ABSTRACT

The novel coronavirus disease-2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been a major public health emergency worldwide with over 118.27-million confirmed COVID-19 cases and 2.62-million deaths recorded, as of March 12, 2021. Although this disease primarily targets lungs, damages in other organs, such as heart, kidney, liver, and testis, may occur. Testis is the cornerstone of male reproduction, while reproductive health is the most valuable resource for continuity of the human race. Given the unique nature of SARS-CoV-2, the mechanisms of its impact on the testes have yet to be fully explored. Notably, coronaviruses have been found to invade target cells through the angiotensin-converting enzyme 2 receptor, which can be found in the respiratory, gastrointestinal, cardiovascular, urinary tract, and reproductive organs, such as testes. Coronavirus studies have suggested that testes might be a potential target for SARS-CoV-2 infection. The first etiopathogenic concept proposed by current hypotheses indicates that the virus can invade testes through the angiotensin-converting enzyme 2 receptor. Next, the activated inflammatory response in the testes, disease-associated fever, and COVID-19 medications might be implicated in testicular alterations. Although evidence regarding the presence of SARS-CoV-2 mRNA in semen remains controversial, this emphasizes the need for researchers to pay closer attention to sexually transmitted diseases and male fertility after recovering from COVID-19. In this review the latest updates regarding COVID-19-associated testicular dysfunction are summarized and possible pathogenic mechanisms are discussed.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , COVID-19/metabolism , Fertility , Pandemics , SARS-CoV-2/metabolism , Testis/metabolism , COVID-19/mortality , COVID-19/pathology , Humans , Male , Testis/pathology , Testis/virology
3.
Chest ; 162(4):A488, 2022.
Article in English | EMBASE | ID: covidwho-2060607

ABSTRACT

SESSION TITLE: Not the Normal Host: Infections Still Matter SESSION TYPE: Rapid Fire Original Inv PRESENTED ON: 10/17/2022 12:15 pm - 1:15 pm PURPOSE: Community Acquired Respiratory Viruses (CARVs) are associated with poor outcome in Solid Organ Transplant (SOT) recipients. We reviewed some of these outcomes such as respiratory support, length of stay (LOS), ICU admission, steroid use & 30-day all-cause mortality. METHODS: Multihospital, single center, retrospective review of electronic health records from 01/01/2014-12/31/2019. RESULTS: 23 SOT recipients (M=20, F=3) who tested positive for CARVs were identified. SOT distribution was heart=2, kidney=4, liver=3, lung=11, heart-lung=1, lung-kidney=1 & heart-kidney=1. Mean age at admission was 60 years, average LOS was 8 days with 2 pts needing >2 weeks. 6 pts required intensive care unit;8 pts required supplemental oxygen support. 16 pts had infiltrates on chest imaging. 15 pts had a 90-day readmission with respiratory complaints. 8 pts had bronchoscopy & 20 had positive nasal swab. 3 pts had a negative nasal swab but positive Bronchoalveolar lavage (BAL) for CARV while 2 pts had negative BAL but positive nasal swab. CARV distribution was Rhinovirus 48%, Parainfluenza 29%, Metapneumovirus 12%, Respiratory syncytial virus 0.03%, Adenovirus 0.03% & Non-novel Coronavirus 0.06%. 5 pts had bacterial coinfection (Pseudomonas aeruginosa, Corynebacterium striatum & Stenotrophomonas maltophilia). All pts were immunosuppressed, intravenous immunoglobulins (IVIG) were used in 3 pts, antivirals in 7 pts (ribavirin in 6 & oseltamivir in 1) & steroids in 10 pts. 12 pts had transplant organ biopsy with 5 showing acute cellular rejection. 11 pts had underlying Coronary artery disease and 17 pts had hematologic disorders (Post-transplant lymphoproliferative disorder, leukemia, Myelodysplastic syndrome, & multiple myeloma). 35% pts died within 1 year (2 during same admit). Cause of death was refractory septic shock (1), respiratory failure (3), cardiac arrest (3) & chronic lung allograft dysfunction (CLAD) (1). CONCLUSIONS: In this cohort, we assessed the SOT recipients positive for CARVs who required admission & evaluated the impact on their clinical course. This analysis noted a significant rate of acute & chronic rejections, bronchiolitis obliterans and CLAD in these patients. Newer tests like multiplex NAT & (semi) quantitative NAT (QNAT) can diagnose CARVs in addition to Human Influenza Virus. Patients can present with wheezing, croup, bronchiolitis, pneumonitis & pneumonia. Impact of CARVs seems to vary by the type of organ transplant, level of neutropenia/lymphopenia, upper versus lower respiratory infection and intrinsic pathogenicity of virus. Various preventive & therapeutic measures were employed in an attempt to improve outcomes in these patients. CLINICAL IMPLICATIONS: Transplant receipients are at a high risk of infections especially CARVs which may increase morbidity and mortality. This analysis emphasizes the value of timely diagnosis and treatment in this specific patient population who are immunocompromised. DISCLOSURES: No relevant relationships by Supriya Singh

4.
Environmental and Molecular Mutagenesis ; 63:7, 2022.
Article in English | EMBASE | ID: covidwho-2059392

ABSTRACT

The world population is getting older, but a great challenge is how to increase health span and not only lifespan. What is the role of genetics versus environment? Several recent breakthroughs such as the human genome project, the IPS stem-cells and the CRISPR technology for gene editing will allow a revolution in gene therapy, precision and regenerative medicine and xenotransplantation. Aiming to contribute to a healthier longevity, our group is developing several projects including the characterization of the genome of our elderly highly admixed population. We have performed whole genome sequencing of about 1500 healthy Brazilians older than 60, which represents the largest genome databank in Latin America. Our aims were a) to have a database from our population in order to improve the interpretation of pathogenicity of rare unknown variants in patients with undiagnosed genetic disorders and precision medicine b) identify “protective” variants underlying healthy longevity. We found 2 million genetic variants which were not present in the international databanks (Naslavsky et al., 2022). Since the advent of COVID-19 pandemic, we are investigating genetic variants in individuals, who were exposed to SARS-Cov-2 and remained asymptomatic. To address this question, we investigated discordant couples where one was infected and develop COVID-19 while the partner remained asymptomatic and serum negative. We collected samples from nonagenarians and centenarians who survived COVID-19 or remained asymptomatic. We will infect different IPS derived cell lines from “resistant” centenarians with SARS-Cov2 in an attempt to increase our understanding on “resistant genetic variants and mechanisms”.

5.
Inflammation ; 2022 Oct 10.
Article in English | MEDLINE | ID: covidwho-2059940

ABSTRACT

Hyper-transmissibility with decreased disease severity is a typical characteristic of the SARS-CoV-2 Omicron variant. To understand this phenomenon, we used various bioinformatics approaches to analyze randomly selected genome sequences (one each) of the Gamma, Delta, and Omicron variants submitted to NCBI from December 15 to 31, 2021. We report that the pathogenicity of SARS-CoV-2 variants decreases in the order of Wuhan > Gamma > Delta > Omicron; however, the antigenic property follows the order of Omicron > Gamma > Wuhan > Delta. The Omicron spike RBD shows lower pathogenicity but higher antigenicity than other variants. The reported decreased disease severity by the Omicron variant may be due to its decreased pro-inflammatory and IL-6 stimulation and increased IFN-γ and IL-4 induction efficacy. The mutations in the N protein are probably associated with this decreased IL-6 induction and human DDX21-mediated increased IL-4 production for Omicron. Due to the mutations, the stability of S, M, N, and E proteins decreases in the order of Omicron > Gamma > Delta > Wuhan. Although a stronger spike RBD-hACE2 binding of Omicron increases its transmissibility, the lowest stability of its spike protein makes spike RBD-hACE2 interaction weak for systemic infection and for causing severe disease. Finally, the highest instability of the Omicron E protein may also be associated with decreased viral maturation and low viral load, leading to less severe disease and faster recovery. Our findings will contribute to the understanding of the dynamics of SARS-CoV-2 variants and the management of emerging variants. This minimal genome-based method may be used for other similar viruses avoiding robust analysis.

6.
Egyptian Journal of Aquatic Biology and Fisheries ; 26(5):93-116, 2022.
Article in English | Scopus | ID: covidwho-2056756

ABSTRACT

All continents across the world are being affected by the COVID-19 pandemic, even though some continents such as Africa witnessed a dramatic impact due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) than the others. Respiratory viruses spread from an infected individual to vulnerable people i) by contact counting coordinated person-to-person transfer of infectious secretions and indirect transfer of discharges through fomites, ii) by the ballistic spray of large droplets delivered amid coughing and sneezing (short-range transmission) and iii) by inhalation of small airborne droplets or aerosol (long-range transmission). The objective of this study was to make an overview of the route of transmission of SARS-CoV 2 especially if there is a role for water and food in virus transmission. Also, the role of water systems, and management in controlling viral frequency in developing countries. WASH is commonly known as water, sanitation, and hygiene which is currently in critical condition due to the poor sanitation systems and improper sewage disposal. These poor WASH conditions are considered one of the routes to the transmission of the Covid-19 pandemic in Africa. Generally, the unhygienic conditions, and inadequate sanitary and sewage systems cause a lot of disease outbreaks. Africa is in big need of managed wastewater treatment facilities efficiently and on the other hand, separating the sewage system and wastewater treatment facilities of healthcare centers from urban systems or treating on-site to ensure the viral removal during disinfection must be made. Also, efficient methods to eliminate face masks must be taken into consideration. © 2022, Egyptian Society for the Development of Fisheries and Human Health. All rights reserved.

7.
J Virol ; 96(17): e0096122, 2022 09 14.
Article in English | MEDLINE | ID: covidwho-2053119

ABSTRACT

Omicron (B.1.1.529) is the most recent SARS-CoV-2 variant of concern, which emerged in late 2021 and rapidly achieved global predominance by early 2022. In this study, we compared the infection dynamics, tissue tropism, and pathogenesis and pathogenicity of SARS-CoV-2 D614G (B.1), Delta (B.1.617.2), and Omicron BA.1.1 (B.1.1.529) variants in a highly susceptible feline model of infection. Although D614G- and Delta-inoculated cats became lethargic and showed increased body temperatures between days 1 and 3 postinfection (pi), Omicron-inoculated cats remained subclinical and, similar to control animals, gained weight throughout the 14-day experimental period. Intranasal inoculation of cats with D614G- and the Delta variants resulted in high infectious virus shedding in nasal secretions (up to 6.3 log10 TCID50.Ml-1), whereas strikingly lower level of viruses shedding (<3.1 log10 TCID50.Ml-1) was observed in Omicron-inoculated animals. In addition, tissue distribution of the Omicron variant was markedly reduced in comparison to the D614G and Delta variants, as evidenced by lower in situ viral RNA detection, in situ viral immunofluorescence staining, and viral loads in tissues on days 3, 5, and 14 pi. Nasal turbinate, trachea, and lung were the main-but not the only-sites of replication for all three viral variants. However, only scarce virus staining and lower viral titers suggest lower levels of viral replication in tissues from Omicron-infected animals. Notably, while D614G- and Delta-inoculated cats presented pneumonia, histologic examination of the lungs from Omicron-infected cats revealed mild to modest inflammation. Together, these results demonstrate that the Omicron variant BA.1.1 is less pathogenic than D614G and Delta variants in a highly susceptible feline model. IMPORTANCE The SARS-CoV-2 Omicron (B.1.1.529) variant of concern emerged in South Africa late in 2021 and rapidly spread across the world causing a significant increase in the number of infections. Importantly, this variant was also associated with an increased risk of reinfections. However, the number of hospitalizations and deaths due to COVID-19 did not follow the same trends. These early observations suggested effective protection conferred by immunizations and/or overall lower virulence of the highly mutated variant virus. In this study we present novel evidence demonstrating that the Omicron BA.1.1 variant of concern presents a lower pathogenicity when compared to D614G- or Delta variants in cats. Clinical, virological, and pathological evaluations revealed lower disease severity, viral replication, and lung pathology in Omicron-infected cats when compared with D614G and Delta variant inoculated animals, confirming that Omicron BA.1.1 is less pathogenic in a highly susceptible feline model of infection.


Subject(s)
COVID-19/virology , SARS-CoV-2 , Animals , Cats , Disease Models, Animal , Humans , SARS-CoV-2/pathogenicity , Virulence , Virus Replication
8.
Transbound Emerg Dis ; 69(5): e1445-e1459, 2022 Sep.
Article in English | MEDLINE | ID: covidwho-2052989

ABSTRACT

The Mexican lineage H5N2 low pathogenic avian influenza viruses (LPAIVs) were first detected in 1994 and mutated to highly pathogenic avian influenza viruses (HPAIVs) in 1994-1995 causing widespread outbreaks in poultry. By using vaccination and other control measures, the HPAIVs were eradicated but the LPAIVs continued circulating in Mexico and spread to several other countries. To get better resolution of the phylogenetics of this virus, the full genome sequences of 44 H5N2 LPAIVs isolated from 1994 to 2011, and 6 detected in 2017 and 2019, were analysed. Phylogenetic incongruence demonstrated genetic reassortment between two separate groups of the Mexican lineage H5N2 viruses between 2005 and 2010. Moreover, the recent H5N2 viruses reassorted with previously unidentified avian influenza viruses. Bayesian phylogeographic results suggested that mechanical transmission involving human activity is the most probable cause of the virus spillover to Central American, Caribbean, and East Asian countries. Increased infectivity and transmission of a 2011 H5N2 LPAIV in chickens compared to a 1994 virus demonstrates improved adaptation to chickens, while low virus shedding, and limited contact transmission was observed in mallards with the same 2011 virus. The sporadic increase in basic amino acids in the HA cleavage site, changes in potential N-glycosylation sites in the HA, and truncations of PB1-F2 should be further examined in relation to the increased infectivity and transmission in poultry. The genetic changes that occur as this lineage of H5N2 LPAIVs continues circulating in poultry is concerning not only because of the effect of these changes on vaccination efficacy, but also because of the potential of the viruses to mutate to the highly pathogenic form. Continued vigilance and surveillance efforts, and the pathogenic and genetic characterization of circulating viruses, are required for the effective control of this virus.


Subject(s)
Influenza A Virus, H5N2 Subtype , Influenza A virus , Influenza in Birds , Amino Acids, Basic/genetics , Animals , Bayes Theorem , Chickens , Humans , Influenza A Virus, H5N2 Subtype/genetics , Influenza A virus/genetics , Mexico/epidemiology , Phylogeny , Poultry
9.
Virol Sin ; 2022 Sep 28.
Article in English | MEDLINE | ID: covidwho-2050059

ABSTRACT

During the two-year pandemic of coronavirus disease 2019 (COVID-19), its causative agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been evolving. SARS-CoV-2 Delta, a variant of concern, has become the dominant circulating strain worldwide within just a few months. Here, we performed a comprehensive analysis of a new B.1.617.2 Delta strain (Delta630) compared with the early WIV04 strain (WIV04) in vitro and in vivo, in terms of replication, infectivity, pathogenicity, and transmission in hamsters. When inoculated intranasally, Delta630 led to more pronounced weight loss and more severe disease in hamsters. Moreover, 40% mortality occurred about one week after infection with 104 PFU of Delta630, whereas no deaths occurred even after infection with 105 PFU of WIV04 or other strains belonging to the Delta variant. Moreover, Delta630 outgrew over WIV04 in the competitive aerosol transmission experiment. Taken together, the Delta630 strain showed increased replication ability, pathogenicity, and transmissibility over WIV04 in hamsters. To our knowledge, this is the first SARS-CoV-2 strain that causes death in a hamster model, which could be an asset for the efficacy evaluation of vaccines and antivirals against infections of SARS-CoV-2 Delta strains. The underlying molecular mechanisms of increased virulence and transmission await further analysis.

10.
Chinese Journal of Virology ; 36(6):1157-1164, 2020.
Article in Chinese | GIM | ID: covidwho-2040434

ABSTRACT

SARS-CoV-2, which caused a pandemic, is a new coronavirus pathogen that can spread rapidly from person to person. The spike protein (S) on the surface of coronavirus plays an important role in determining the host specificity. pathogenicity and interspecies transmission of the virus. S protein is the most studied SARS - CoV-2 protein after the outbreak of SARS-CoV-2. S protein is also the most important antigenic protein for the development of SAES - CoV -2 vaccine and the important target of antiviral drugs. Here the latest research progress of SARS-CoV-2 S protein was reviewed, and the problems and challenges in current research were discussed. .

11.
Cell ; 185(21): 3992-4007.e16, 2022 Oct 13.
Article in English | MEDLINE | ID: covidwho-2031185

ABSTRACT

After the global spread of the SARS-CoV-2 Omicron BA.2, some BA.2 subvariants, including BA.2.9.1, BA.2.11, BA.2.12.1, BA.4, and BA.5, emerged in multiple countries. Our statistical analysis showed that the effective reproduction numbers of these BA.2 subvariants are greater than that of the original BA.2. Neutralization experiments revealed that the immunity induced by BA.1/2 infections is less effective against BA.4/5. Cell culture experiments showed that BA.2.12.1 and BA.4/5 replicate more efficiently in human alveolar epithelial cells than BA.2, and particularly, BA.4/5 is more fusogenic than BA.2. We further provided the structure of the BA.4/5 spike receptor-binding domain that binds to human ACE2 and considered how the substitutions in the BA.4/5 spike play roles in ACE2 binding and immune evasion. Moreover, experiments using hamsters suggested that BA.4/5 is more pathogenic than BA.2. Our multiscale investigations suggest that the risk of BA.2 subvariants, particularly BA.4/5, to global health is greater than that of original BA.2.


Subject(s)
Angiotensin-Converting Enzyme 2 , COVID-19 , Antibodies, Viral , Humans , Peptidyl-Dipeptidase A/genetics , Peptidyl-Dipeptidase A/metabolism , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/metabolism
12.
Zoonoses ; 1(13), 2021.
Article in English | CAB Abstracts | ID: covidwho-2025746

ABSTRACT

As the novel coronavirus SARS-CoV-2 spread around the world, multiple waves of variants emerged, thus leading to local or global population shifts during the pandemic. A new variant named Omicron (PANGO lineage B.1.1.529), which was first discovered in southern Africa, has recently been proposed by the World Health Organization to be a Variant of Concern. This variant carries an unusually large number of mutations, particularly on the spike protein and receptor binding domain, in contrast to other known major variants. Some mutation sites are associated with enhanced viral transmission, infectivity, and pathogenicity, thus enabling the virus to evade the immune protective barrier. Given that the emergence of the Omicron variant was accompanied by a sharp increase in infection cases in South Africa, the variant has the potential to trigger a new global epidemic peak. Therefore, continual attention and a rapid response are required to decrease the possible risks to public health.

13.
Animals (Basel) ; 12(17)2022 Aug 25.
Article in English | MEDLINE | ID: covidwho-2023064

ABSTRACT

Since 2010, a variant of porcine epidemic diarrhea virus (PEDV) has re-emerged in several provinces of China, resulting in severe economic losses for the pork industry. Here, we isolated and identified a variant PEDV strain, SC-YB73, in Guangdong Province, China. The pathological observations of jejunum showed atrophy of villi and edema in the lamina propria. The sequence analysis of the viral genome identified a six-nucleotide insertion in the E gene, which has not previously been detected in PEDV strains. Furthermore, 50 nucleotide sites were unique in SC-YB73 compared with 27 other PEDV strains. The phylogenetic analysis based on the complete genome showed that SC-YB73 was clustered in variant subgroup GII-a, which is widely prevalent in the Chinese pig population. The recombination analysis suggested that SC-YB73 originated from the recombination of GDS47, US PEDV prototype-like strains TW/Yunlin550/2018, and COL/Cundinamarca/2014. In the present study, we isolated and genetically characterized a variant PEDV strain, thus providing essential information for the control of PED outbreaks in China.

14.
Chinese Journal of Nosocomiology ; 32(4):635-640, 2022.
Article in Chinese | GIM | ID: covidwho-2012933

ABSTRACT

The coronavirus disease(COVID-19) is a respiratory disease caused by the new severe acute respiratory syndrome coronavirus 2(SARS-CoV-2), which has posed a major threat to global health. Given the current emergence of asymptomatic infections, and the recent Delta new crown variants have strong transmission power, short incubation period of infection, strong pathogenicity and rapid onset of disease. The importance of efficient laboratory diagnostic techniques and methods has become increasingly prominent. Rapid, simple and large-scale testing plays a key role in controlling the spread of SARS-CoV-2 and management of patients. The relevant laboratory testing techniques and methods are reviewed in the this article, which provides diagnostic support for clinicians, public health and control of infection.

15.
Microb Pathog ; 170: 105703, 2022 Sep.
Article in English | MEDLINE | ID: covidwho-2015853

ABSTRACT

Porcine epidemic diarrhea virus (PEDV) frequently causes diarrhea outbreaks. However, whether newly discovered enteric viruses such as porcine kobuvirus (PKV) and porcine astroviruses (PAstVs) are also correlated with diarrhea is still unclear. Diarrhea outbreaks were reported in a PEDV-vaccinated pig farm in Xinjiang Uygur Autonomous Region of China from 2019 to 2020. PEDV was a common pathogen detected in fecal samples by routine RT-PCR assays. The PEDV positive fecal sample was used for pathogenic analysis due to the failure isolation of PEDV. The challenged neonatal piglets appeared watery diarrhea within one day post infection (dpi) and all died within 6 dpi. Histopathological and immunohistochemical examinations supported that PEDV is a major pathogen causing intestinal lesions. To further explore enteric viruses associated with neonatal piglet diarrhea, metagenomics sequencing was performed for the diarrheic piglets. Remarkably, PKV was the most abundant virus (58.33%) followed by PEDV (34.45%) and PAstVs (7.22%), which were also confirmed by real-time RT-PCR assays. Significant in vivo replications of PEDV and PKV could only be observed in challenged piglets whilst PAstVs maintained similar virus loads in both challenged and mock infected piglets. Overall, this study provides first pathogenic and metagenomic evidence that significant proliferations of PEDV and PKV are closely associated with severe diarrhea in neonatal piglets, while PAstVs likely play limited roles in neonatal piglet diarrhea.


Subject(s)
Coronavirus Infections , Kobuvirus , Porcine epidemic diarrhea virus , Swine Diseases , Animals , Diarrhea/epidemiology , Kobuvirus/genetics , Mamastrovirus , Metagenomics , Porcine epidemic diarrhea virus/genetics , Swine
16.
Profilakticheskaya Meditsina ; 25(8):98-104, 2022.
Article in Russian | EMBASE | ID: covidwho-2010548

ABSTRACT

The SARS-CoV-2 virus is the cause of the COVID-19 pandemic. It was first discovered in Wuhan, China, in December 2019. The COVID-19 pandemic has become a serious challenge for all humanity. Although most patients develop respiratory symptoms, the neurological manifestations due to central and peripheral nervous system involvement are quite common. Objective of the review. To analyze and systematize current data on the COVID-19 effect on the central and peripheral nervous system. Material and methods. The material for the study was more than 70 papers published between 2019—2022 and indexed in the international databases Scopus, Web of Science, and PubMed. Results. Analysis of the relevant literature on the pathogenesis of COVID-19 and some neurological complications was performed. It was observed that in addition to the respiratory system, SARS-CoV-2 affects the central nervous system, the peripheral nervous system, and the muscular system, resulting in neurological disorders. Understanding the pathogenesis of nervous system damage contributes to improved diagnosis of neurological complications. In general, according to the literature, patients with severe new coronavirus infection are prone to neurological complications. Conclusion. Since most studies currently focus on respiratory symptoms, the prevalence of neurological effects of COVID-19 may be underestimated. A detailed analysis of the mechanisms of both central and peripheral nervous system damage is needed.

17.
Cell Rep Med ; 3(9): 100743, 2022 09 20.
Article in English | MEDLINE | ID: covidwho-2004613

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron BA.2 was a dominant circulating SARS-CoV-2 variant worldwide. Recent reports hint that BA.2 is similarly potent regarding antibody evasion but may be more transmissible than BA.1. The pathogenicity of BA.2 remains unclear and is of critical public health significance. Here we investigated the virological features and pathogenicity of BA.2 with in vitro and in vivo models. We show that BA.2 is less dependent on transmembrane protease serine 2 (TMPRSS2) for virus entry in comparison with BA.1 in vitro. In K18-hACE2 mice, BA.2 replicates more efficiently than BA.1 in the nasal turbinates and replicates marginally less efficiently in the lungs, leading to decreased body weight loss and improved survival. Our study indicates that BA.2 is similarly attenuated in lungs compared with BA.1 but is potentially more transmissible because of its better replication at the nasal turbinates.


Subject(s)
COVID-19 , SARS-CoV-2 , Animals , Humans , Mice , SARS-CoV-2/genetics , Serine , Virulence
18.
Pediatrics ; 149, 2022.
Article in English | EMBASE | ID: covidwho-2003505

ABSTRACT

Introduction: Acute necrotizing encephalopathy (ANE) is a rare condition often triggered by infection and characterized by febrile prodromal illness, seizures, altered mental status and bilateral brain lesions. While many cases are isolated, a recurrent familial pattern has been linked to missense mutation of the gene encoding RAN binding protein 2 (RANBP2). Early administration of high dose steroids has been associated with improved outcomes, while IVIG and tocilizumab have also shown benefit. Case Description: A two-year-old male presented with vomiting, somnolence and seizure-like activity. Evaluation revealed positive SARS-CoV2, adenovirus and rhinovirus/enterovirus PCR by nasopharyngeal swab, and Mycoplasma pneumoniae IgM. MRI showed numerous foci of restricted diffusion and microhemorrhage as well as necrotic change in the internal capsules. He was diagnosed with ANE. He recovered to neurologic baseline following treatment with IVIG and corticosteroids. After six months, the patient presented with similar symptoms. SARS-CoV2 IgG was positive, but no new infectious pathogens were identified. Cerebrospinal fluid (CSF) analysis showed elevated IL-6 and IL-8 levels, suggestive of inflammatory breakdown of the blood-brain barrier. Brain MRI demonstrated worsened bilateral T2/fluid attenuated inversion reduction signal abnormalities and necrosis within the midbrain and pons bilaterally, concerning for recurrent ANE. Following multidisciplinary consultation, the patient was treated with corticosteroids and IVIG. Tocilizumab was later added due to elevated CSF IL-6. Worsening MRI findings (Figure 1) coupled with decrease in strength and spontaneous movement prompted plasma exchange (PLEX) therapy. While his exam improved after PLEX, treatment was discontinued due to development of a pericardial effusion. The patient steadily improved neurologically and was transitioned to inpatient rehabilitation with an ongoing steroid taper, monthly IVIG, and tocilizumab therapy. Given recurrence of ANE, an epilepsy genetic sequencing panel was ordered and revealed heterozygous mutation in RANBP2 (c.1966A>G p.Ile656Val). Discussion: During the patient's initial presentation, it was reasonable to conclude an infectious trigger for ANE given the presence of several potential inciting pathogens. Upon recurrence, investigation of underlying genetic predisposition was warranted. This patient exhibited the classic clinical and radiographic findings of recurrent ANE and was found to have RANBP2 mutation. Available literature suggests pathogenicity of the same mutation identified in this case due to its location in a highly conserved genetic region and its presence in affected members of a family with ANE. To our knowledge, this is the second report of this specific RANBP2 mutation in association with ANE. Conclusion: While ANE may present as a singular event following infection, recurrence is rare and should prompt evaluation of underlying genetic predisposition. Consideration of familial ANE with testing for RANBP2 mutation may lead to early genetic counseling. Our case also provides additional support for the pathogenicity of the RANBP2 (p.Ile656Val) mutation. (Figure Presented).

19.
Archives of Razi Institute ; 77(5):1611-1619, 2022.
Article in English | CAB Abstracts | ID: covidwho-2002783

ABSTRACT

Infectious bronchitis (IB) disease, avian Infectious Bronchitis disease in one of the major cause of respiratory problems and economic loss in poultry industry, even in developed countries with good biosecurity practice. Since the first isolation of the virus in 1931, a lot of serotypes and genotypes of the virus have been reported around the world. The GI-1 lineage, including Massachusetts (Mass) serotype viruses, is one of the most widely spread types worldwide. Moreover, the GI-23 lineage with a growing incidence rate was reported approximately 20 years ago in the Middle East, with no or little homologues vaccine use. The genotype was previously restricted to the Middle East;now, there is evidence that it has spread to European countries, raising concerns regarding potential outbreaks. In the present study, our attempt was to phylogenetically analyze the S1 gene of six isolates from Massachusetts and variant 2 genotypes, which were isolated from broiler and broiler breeder flocks in Iran. The variant 2 viruses were compared to other reported variant 2 viruses from neighboring countries and they had more than 98% identity with the latest reported Iranian variant 2. In addition, Three Mass type viruses were similar to vaccine strains which may be shows continuous circulation of vaccine viruses in the field. This event can cause increasing the risk of their mutation or even reversion to virulence after several passages in natural host, furthermore circulating viruses may recombinant with virulent field viruses and cause emergence of new variants. Considering the variable nature of IB viruses in which few changes lead to important differences, continuous epidemiological surveillance along with clinical studies of new isolates, are crucial to a better understanding of their pathogenicity and subsequent disease control.

20.
EBioMedicine ; 83: 104232, 2022 Sep.
Article in English | MEDLINE | ID: covidwho-1996121

ABSTRACT

BACKGROUND: The Omicron BA.2 sublineage has replaced BA.1 worldwide and has comparable levels of immune evasion to BA.1. These observations suggest that the increased transmissibility of BA.2 cannot be explained by the antibody evasion. METHODS: Here, we characterized the replication competence and respiratory tissue tropism of three Omicron variants (BA.1, BA.1.1, BA.2), and compared these with the wild-type virus and Delta variant, in human nasal, bronchial and lung tissues cultured ex vivo. FINDINGS: BA.2 replicated more efficiently in nasal and bronchial tissues at 33°C than wild-type, Delta and BA.1. Both BA.2 and BA.1 had higher replication competence than wild-type and Delta viruses in bronchial tissues at 37°C. BA.1, BA.1.1 and BA.2 replicated at a lower level in lung parenchymal tissues compared to wild-type and Delta viruses. INTERPRETATION: Higher replication competence of Omicron BA.2 in the human upper airway at 33°C than BA.1 may be one of the reasons to explain the current advantage of BA.2 over BA.1. A lower replication level of the tested Omicron variants in human lung tissues is in line with the clinical manifestations of decreased disease severity of patients infected with the Omicron strains compared with other ancestral strains. FUNDING: This work was supported by US National Institute of Allergy and Infectious Diseases and the Theme-Based Research Scheme under University Grants Committee of Hong Kong Special Administrative Region, China.


Subject(s)
COVID-19 , SARS-CoV-2 , Bronchi , Humans , SARS-CoV-2/genetics , Viral Tropism , Virus Replication
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