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1.
Viruses ; 14(2)2022 01 18.
Article in English | MEDLINE | ID: covidwho-1625960

ABSTRACT

Bats have been recognized as an exceptional viral reservoir, especially for coronaviruses. At least three bat zoonotic coronaviruses (SARS-CoV, MERS-CoV and SARS-CoV-2) have been shown to cause severe diseases in humans and it is expected more will emerge. One of the major features of CoVs is that they are all highly prone to recombination. An extreme example is the insertion of the P10 gene from reoviruses in the bat CoV GCCDC1, first discovered in Rousettus leschenaultii bats in China. Here, we report the detection of GCCDC1 in four different bat species (Eonycteris spelaea, Cynopterus sphinx, Rhinolophus shameli and Rousettus sp.) in Cambodia. This finding demonstrates a much broader geographic and bat species range for this virus and indicates common cross-species transmission. Interestingly, one of the bat samples showed a co-infection with an Alpha CoV most closely related to RsYN14, a virus recently discovered in the same genus (Rhinolophus) of bat in Yunnan, China, 2020. Taken together, our latest findings highlight the need to conduct active surveillance in bats to assess the risk of emerging CoVs, especially in Southeast Asia.


Subject(s)
Chiroptera/virology , Coronaviridae Infections/veterinary , Coronaviridae/classification , Coronaviridae/genetics , Disease Reservoirs/veterinary , Disease Reservoirs/virology , Phylogeography , Recombination, Genetic , Animals , Cambodia/epidemiology , China/epidemiology , Chiroptera/classification , Coronaviridae/isolation & purification , Coronaviridae Infections/epidemiology , Coronaviridae Infections/transmission , Evolution, Molecular , Genome, Viral , Phylogeny
2.
Clin Infect Dis ; 73(9): e2932-e2942, 2021 11 02.
Article in English | MEDLINE | ID: covidwho-1500989

ABSTRACT

BACKGROUND: Key knowledge gaps remain in the understanding of viral dynamics and immune response of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. METHODS: We evaluated these characteristics and established their association with clinical severity in a prospective observational cohort study of 100 patients with PCR-confirmed SARS-CoV-2 infection (mean age, 46 years; 56% male; 38% with comorbidities). Respiratory samples (n = 74) were collected for viral culture, serum samples for measurement of IgM/IgG levels (n = 30), and plasma samples for levels of inflammatory cytokines and chemokines (n = 81). Disease severity was correlated with results from viral culture, serologic testing, and immune markers. RESULTS: Fifty-seven (57%) patients developed viral pneumonia, of whom 20 (20%) required supplemental oxygen, including 12 (12%) with invasive mechanical ventilation. Viral culture from respiratory samples was positive for 19 of 74 patients (26%). No virus was isolated when the PCR cycle threshold (Ct) value was >30 or >14 days after symptom onset. Seroconversion occurred at a median (IQR) of 12.5 (9-18) days for IgM and 15.0 (12-20) days for IgG; 54/62 patients (87.1%) sampled at day 14 or later seroconverted. Severe infections were associated with earlier seroconversion and higher peak IgM and IgG levels. Levels of IP-10, HGF, IL-6, MCP-1, MIP-1α, IL-12p70, IL-18, VEGF-A, PDGF-BB, and IL-1RA significantly correlated with disease severity. CONCLUSIONS: We found virus viability was associated with lower PCR Ct value in early illness. A stronger antibody response was associated with disease severity. The overactive proinflammatory immune signatures offer targets for host-directed immunotherapy, which should be evaluated in randomized controlled trials.


Subject(s)
COVID-19 , Pneumonia, Viral , Antibodies, Viral , Female , Humans , Immunoglobulin M , Male , Middle Aged , Prospective Studies , SARS-CoV-2 , Seroconversion
3.
ACS Nano ; 15(10): 15754-15770, 2021 10 26.
Article in English | MEDLINE | ID: covidwho-1454714

ABSTRACT

Multiple successful vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are urgently needed to address the ongoing coronavirus disease 2019 (Covid-19) pandemic. In the present work, we describe a subunit vaccine based on the SARS-CoV-2 spike protein coadministered with CpG adjuvant. To enhance the immunogenicity of our formulation, both antigen and adjuvant were encapsulated with our proprietary artificial cell membrane (ACM) polymersome technology. Structurally, ACM polymersomes are self-assembling nanoscale vesicles made up of an amphiphilic block copolymer comprising poly(butadiene)-b-poly(ethylene glycol) and a cationic lipid, 1,2-dioleoyl-3-trimethylammonium-propane. Functionally, ACM polymersomes serve as delivery vehicles that are efficiently taken up by dendritic cells (DC1 and DC2), which are key initiators of the adaptive immune response. Two doses of our formulation elicit robust neutralizing antibody titers in C57BL/6 mice that persist at least 40 days. Furthermore, we confirm the presence of functional memory CD4+ and CD8+ T cells that produce T helper type 1 cytokines. This study is an important step toward the development of an efficacious vaccine in humans.


Subject(s)
COVID-19 Vaccines/immunology , Spike Glycoprotein, Coronavirus/immunology , Animals , Antibodies, Neutralizing , Antibodies, Viral , CD8-Positive T-Lymphocytes , COVID-19/prevention & control , Humans , Mice , Mice, Inbred C57BL , Nanoparticles , Protein Subunits , SARS-CoV-2 , Vaccines, Subunit
4.
Proc Natl Acad Sci U S A ; 118(39)2021 09 28.
Article in English | MEDLINE | ID: covidwho-1428995

ABSTRACT

Bats are responsible for the zoonotic transmission of several major viral diseases, including those leading to the 2003 SARS outbreak and likely the ongoing COVID-19 pandemic. While comparative genomics studies have revealed characteristic adaptations of the bat innate immune system, functional genomic studies are urgently needed to provide a foundation for the molecular dissection of the viral tolerance in bats. Here we report the establishment of genome-wide RNA interference (RNAi) and CRISPR libraries for the screening of the model megabat, Pteropus alecto. We used the complementary RNAi and CRISPR libraries to interrogate P. alecto cells for infection with two different viruses: mumps virus and influenza A virus, respectively. Independent screening results converged on the endocytosis pathway and the protein secretory pathway as required for both viral infections. Additionally, we revealed a general dependence of the C1-tetrahydrofolate synthase gene, MTHFD1, for viral replication in bat cells and human cells. The MTHFD1 inhibitor, carolacton, potently blocked replication of several RNA viruses, including SARS-CoV-2. We also discovered that bats have lower expression levels of MTHFD1 than humans. Our studies provide a resource for systematic inquiry into the genetic underpinnings of bat biology and a potential target for developing broad-spectrum antiviral therapy.


Subject(s)
Aminohydrolases/genetics , COVID-19/genetics , Formate-Tetrahydrofolate Ligase/genetics , Methylenetetrahydrofolate Dehydrogenase (NADP)/genetics , Multienzyme Complexes/genetics , Pandemics , Aminohydrolases/antagonists & inhibitors , Animals , Antiviral Agents/therapeutic use , COVID-19/drug therapy , COVID-19/virology , Cell Line , Chiroptera/genetics , Chiroptera/virology , Formate-Tetrahydrofolate Ligase/antagonists & inhibitors , Humans , Methylenetetrahydrofolate Dehydrogenase (NADP)/antagonists & inhibitors , Minor Histocompatibility Antigens , Multienzyme Complexes/antagonists & inhibitors , RNA Viruses/genetics , SARS-CoV-2/pathogenicity , Virus Replication/genetics
5.
Emerg Infect Dis ; 27(2): 663-666, 2021 02.
Article in English | MEDLINE | ID: covidwho-1389113

ABSTRACT

Antibody response against nucleocapsid and spike proteins of SARS-CoV-2 in 11 persons with mild or asymptomatic infection rapidly increased after infection. At weeks 18-30 after diagnosis, all remained seropositive but spike protein-targeting antibody titers declined. These data may be useful for vaccine development.


Subject(s)
COVID-19/immunology , Immunity, Humoral , SARS-CoV-2/immunology , Adolescent , Adult , Antibodies, Viral/blood , Antibodies, Viral/immunology , Asymptomatic Infections , COVID-19/blood , COVID-19/virology , Child , Female , Humans , Longitudinal Studies , Male , Middle Aged , Nucleocapsid Proteins/blood , Nucleocapsid Proteins/immunology , Spike Glycoprotein, Coronavirus/blood , Spike Glycoprotein, Coronavirus/immunology , Time Factors , Vietnam , Young Adult
6.
mSphere ; 5(1)2020 01 29.
Article in English | MEDLINE | ID: covidwho-1383493

ABSTRACT

Coronaviruses (CoVs) of bat origin have caused two pandemics in this century. Severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV both originated from bats, and it is highly likely that bat coronaviruses will cause future outbreaks. Active surveillance is both urgent and essential to predict and mitigate the emergence of these viruses in humans. Next-generation sequencing (NGS) is currently the preferred methodology for virus discovery to ensure unbiased sequencing of bat CoVs, considering their high genetic diversity. However, unbiased NGS is an expensive methodology and is prone to missing low-abundance CoV sequences due to the high background level of nonviral sequences present in surveillance field samples. Here, we employ a capture-based NGS approach using baits targeting most of the CoV species. Using this technology, we effectively reduced sequencing costs by increasing the sensitivity of detection. We discovered nine full genomes of bat CoVs in this study and revealed great genetic diversity for eight of them.IMPORTANCE Active surveillance is both urgent and essential to predict and mitigate the emergence of bat-origin CoV in humans and livestock. However, great genetic diversity increases the chance of homologous recombination among CoVs. Performing targeted PCR, a common practice for many surveillance studies, would not reflect this diversity. NGS, on the other hand, is an expensive methodology and is prone to missing low-abundance CoV sequences. Here, we employ a capture-based NGS approach using baits targeting all CoVs. Our work demonstrates that targeted, cost-effective, large-scale, genome-level surveillance of bat CoVs is now highly feasible.


Subject(s)
Chiroptera/virology , Coronavirus/classification , Coronavirus/isolation & purification , High-Throughput Nucleotide Sequencing/methods , Animals , Genetic Variation , Genome, Viral
8.
Nat Commun ; 12(1): 5113, 2021 08 25.
Article in English | MEDLINE | ID: covidwho-1373413

ABSTRACT

SARS-CoV-2 is a major threat to global health. Here, we investigate the RNA structure and RNA-RNA interactions of wildtype (WT) and a mutant (Δ382) SARS-CoV-2 in cells using Illumina and Nanopore platforms. We identify twelve potentially functional structural elements within the SARS-CoV-2 genome, observe that subgenomic RNAs can form different structures, and that WT and Δ382 virus genomes fold differently. Proximity ligation sequencing identify hundreds of RNA-RNA interactions within the virus genome and between the virus and host RNAs. SARS-CoV-2 genome binds strongly to mitochondrial and small nucleolar RNAs and is extensively 2'-O-methylated. 2'-O-methylation sites are enriched in viral untranslated regions, associated with increased virus pair-wise interactions, and are decreased in host mRNAs upon virus infection, suggesting that the virus sequesters methylation machinery from host RNAs towards its genome. These studies deepen our understanding of the molecular and cellular basis of SARS-CoV-2 pathogenicity and provide a platform for targeted therapy.


Subject(s)
COVID-19/virology , Host Microbial Interactions , RNA, Viral/metabolism , RNA/metabolism , SARS-CoV-2/physiology , COVID-19/genetics , COVID-19/metabolism , COVID-19/physiopathology , DNA Methylation , Genome, Viral , Humans , Nucleic Acid Conformation , RNA/chemistry , RNA/genetics , RNA, Viral/chemistry , RNA, Viral/genetics , SARS-CoV-2/chemistry , SARS-CoV-2/genetics
9.
Methods Mol Biol ; 2327: 119-137, 2021.
Article in English | MEDLINE | ID: covidwho-1363726

ABSTRACT

Outbreak analysis and transmission surveillance of viruses can be performed via whole-genome sequencing after viral isolation. Such techniques have recently been applied to characterize and monitor SARS-CoV-2 , the etiological agent of the COVID-19 pandemic. However, the isolation and culture of SARS-CoV-2 is time consuming and requires biosafety level 3 containment, which is not ideal for many resource-constrained settings. An alternate method, bait capture allows target enrichment and sequencing of the entire SARS-CoV-2 genome eliminating the need for viral culture. This method uses a set of hybridization probes known as "baits" that span the genome and provide sensitive, accurate, and minimal off-target hybridization. Baits can be designed to detect any known virus or bacteria in a wide variety of specimen types, including oral secretions. The bait capture method presented herein allows the whole genome of SARS-CoV-2 in saliva to be sequenced without the need to culture and provides an outline of bait design and bioinformatic analysis to guide a bioinformatician.


Subject(s)
Genome, Viral , SARS-CoV-2/genetics , Saliva/virology , Whole Genome Sequencing/methods , Computational Biology , DNA, Complementary/genetics , Humans , Molecular Probes/genetics , Polymerase Chain Reaction/methods , SARS-CoV-2/isolation & purification , Specimen Handling/methods , Streptavidin , Whole Genome Sequencing/instrumentation
10.
Front Immunol ; 12: 674279, 2021.
Article in English | MEDLINE | ID: covidwho-1266662

ABSTRACT

An accurate depiction of the convalescent COVID-19 immunome will help delineate the immunological milieu crucial for disease resolution and protection. Using mass cytometry, we characterized the immune architecture in patients recovering from mild COVID-19. We identified a virus-specific immune rheostat composed of an effector T (Teff) cell recall response that is balanced by the enrichment of a highly specialized regulatory T (Treg) cell subset. Both components were reactive against a peptide pool covering the receptor binding domain (RBD) of the SARS-CoV-2 spike glycoprotein. We also observed expansion of IFNγ+ memory CD4+ T cells and virus-specific follicular helper T (TFH) cells. Overall, these findings pinpoint critical immune effector and regulatory mechanisms essential for a potent, yet harmless resolution of COVID-19 infection.


Subject(s)
COVID-19/immunology , SARS-CoV-2/immunology , Adolescent , Adult , CD4-Positive T-Lymphocytes/immunology , Child , Child, Preschool , Female , Humans , Male , Spike Glycoprotein, Coronavirus/immunology , T Follicular Helper Cells/immunology , T-Lymphocytes, Regulatory/immunology , Young Adult
11.
EBioMedicine ; 66: 103319, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1174196

ABSTRACT

BACKGROUND: Host determinants of severe coronavirus disease 2019 include advanced age, comorbidities and male sex. Virologic factors may also be important in determining clinical outcome and transmission rates, but limited patient-level data is available. METHODS: We conducted an observational cohort study at seven public hospitals in Singapore. Clinical and laboratory data were collected and compared between individuals infected with different SARS-CoV-2 clades. Firth's logistic regression was used to examine the association between SARS-CoV-2 clade and development of hypoxia, and quasi-Poisson regression to compare transmission rates. Plasma samples were tested for immune mediator levels and the kinetics of viral replication in cell culture were compared. FINDINGS: 319 patients with PCR-confirmed SARS-CoV-2 infection had clinical and virologic data available for analysis. 29 (9%) were infected with clade S, 90 (28%) with clade L/V, 96 (30%) with clade G (containing D614G variant), and 104 (33%) with other clades 'O' were assigned to lineage B.6. After adjusting for age and other covariates, infections with clade S (adjusted odds ratio (aOR) 0·030 (95% confidence intervals (CI): 0·0002-0·29)) or clade O (B·6) (aOR 0·26 (95% CI 0·064-0·93)) were associated with lower odds of developing hypoxia requiring supplemental oxygen compared with clade L/V. Patients infected with clade L/V had more pronounced systemic inflammation with higher concentrations of pro-inflammatory cytokines, chemokines and growth factors. No significant difference in the severity of clade G infections was observed (aOR 0·95 (95% CI: 0·35-2·52). Though viral loads were significantly higher, there was no evidence of increased transmissibility of clade G, and replicative fitness in cell culture was similar for all clades. INTERPRETATION: Infection with clades L/V was associated with increased severity and more systemic release of pro-inflammatory cytokines. Infection with clade G was not associated with changes in severity, and despite higher viral loads there was no evidence of increased transmissibility.


Subject(s)
COVID-19/etiology , COVID-19/transmission , SARS-CoV-2/genetics , SARS-CoV-2/pathogenicity , Adult , Age Factors , Aged , COVID-19/epidemiology , COVID-19/immunology , Comorbidity , Female , Humans , Hypoxia/therapy , Hypoxia/virology , Male , Middle Aged , Singapore/epidemiology , Viral Load
12.
China CDC Wkly ; 3(7): 153-155, 2021 Feb 12.
Article in English | MEDLINE | ID: covidwho-1084960
13.
Nature ; 589(7842): 363-370, 2021 01.
Article in English | MEDLINE | ID: covidwho-1039649

ABSTRACT

There have been several major outbreaks of emerging viral diseases, including Hendra, Nipah, Marburg and Ebola virus diseases, severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS)-as well as the current pandemic of coronavirus disease 2019 (COVID-19). Notably, all of these outbreaks have been linked to suspected zoonotic transmission of bat-borne viruses. Bats-the only flying mammal-display several additional features that are unique among mammals, such as a long lifespan relative to body size, a low rate of tumorigenesis and an exceptional ability to host viruses without presenting clinical disease. Here we discuss the mechanisms that underpin the host defence system and immune tolerance of bats, and their ramifications for human health and disease. Recent studies suggest that 64 million years of adaptive evolution have shaped the host defence system of bats to balance defence and tolerance, which has resulted in a unique ability to act as an ideal reservoir host for viruses. Lessons from the effective host defence of bats would help us to better understand viral evolution and to better predict, prevent and control future viral spillovers. Studying the mechanisms of immune tolerance in bats could lead to new approaches to improving human health. We strongly believe that it is time to focus on bats in research for the benefit of both bats and humankind.


Subject(s)
Chiroptera/immunology , Chiroptera/virology , Disease Reservoirs/veterinary , Viral Zoonoses/immunology , Viral Zoonoses/transmission , Animals , Asymptomatic Diseases , Disease Reservoirs/virology , Evolution, Molecular , Humans , Immune Tolerance , Viral Zoonoses/virology
14.
Nat Biotechnol ; 38(9): 1073-1078, 2020 09.
Article in English | MEDLINE | ID: covidwho-1023948

ABSTRACT

A robust serological test to detect neutralizing antibodies to SARS-CoV-2 is urgently needed to determine not only the infection rate, herd immunity and predicted humoral protection, but also vaccine efficacy during clinical trials and after large-scale vaccination. The current gold standard is the conventional virus neutralization test requiring live pathogen and a biosafety level 3 laboratory. Here, we report a SARS-CoV-2 surrogate virus neutralization test that detects total immunodominant neutralizing antibodies targeting the viral spike (S) protein receptor-binding domain in an isotype- and species-independent manner. Our simple and rapid test is based on antibody-mediated blockage of the interaction between the angiotensin-converting enzyme 2 (ACE2) receptor protein and the receptor-binding domain. The test, which has been validated with two cohorts of patients with COVID-19 in two different countries, achieves 99.93% specificity and 95-100% sensitivity, and differentiates antibody responses to several human coronaviruses. The surrogate virus neutralization test does not require biosafety level 3 containment, making it broadly accessible to the wider community for both research and clinical applications.


Subject(s)
Betacoronavirus/pathogenicity , Coronavirus Infections/genetics , Peptidyl-Dipeptidase A/genetics , Pneumonia, Viral/genetics , Spike Glycoprotein, Coronavirus/genetics , Angiotensin-Converting Enzyme 2 , Antibodies/immunology , Antibodies/pharmacology , Betacoronavirus/genetics , COVID-19 , Coronavirus Infections/immunology , Coronavirus Infections/pathology , Coronavirus Infections/virology , Humans , Neutralization Tests , Pandemics , Pneumonia, Viral/immunology , Pneumonia, Viral/pathology , Pneumonia, Viral/virology , Protein Interaction Domains and Motifs/genetics , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/chemistry
15.
Ann Acad Med Singap ; 49(11): 857-869, 2020 11.
Article in English | MEDLINE | ID: covidwho-1001259

ABSTRACT

INTRODUCTION: Pregnant women are reported to be at increased risk of severe coronavirus disease 2019 (COVID-19) due to underlying immunosuppression during pregnancy. However, the clinical course of COVID-19 in pregnancy and risk of vertical and horizontal transmission remain relatively unknown. We aim to describe and evaluate outcomes in pregnant women with COVID-19 in Singapore. METHODS: Prospective observational study of 16 pregnant patients admitted for COVID-19 to 4 tertiary hospitals in Singapore. Outcomes included severe disease, pregnancy loss, and vertical and horizontal transmission. RESULTS: Of the 16 patients, 37.5%, 43.8% and 18.7% were infected in the first, second and third trimesters, respectively. Two gravidas aged ≥35 years (12.5%) developed severe pneumonia; one patient (body mass index 32.9kg/m2) required transfer to intensive care. The median duration of acute infection was 19 days; one patient remained reverse transcription polymerase chain reaction (RT-PCR) positive >11 weeks from diagnosis. There were no maternal mortalities. Five pregnancies produced term live-births while 2 spontaneous miscarriages occurred at 11 and 23 weeks. RT-PCR of breast milk and maternal and neonatal samples taken at birth were negative; placenta and cord histology showed non-specific inflammation; and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific immunoglobulins were elevated in paired maternal and umbilical cord blood (n=5). CONCLUSION: The majority of COVID-19 infected pregnant women had mild disease and only 2 women with risk factors (obesity, older age) had severe infection; this represents a slightly higher incidence than observed in age-matched non-pregnant women. Among the women who delivered, there was no definitive evidence of mother-to-child transmission via breast milk or placenta.


Subject(s)
COVID-19/epidemiology , Pregnancy Complications, Infectious/epidemiology , Pregnancy Outcome/epidemiology , Abortion, Spontaneous/epidemiology , Adult , COVID-19/physiopathology , COVID-19/transmission , COVID-19 Nucleic Acid Testing , COVID-19 Serological Testing , Cohort Studies , Disease Transmission, Infectious/statistics & numerical data , Female , Fetal Blood/immunology , Humans , Infectious Disease Transmission, Vertical/statistics & numerical data , Live Birth/epidemiology , Maternal Age , Milk, Human/chemistry , Milk, Human/virology , Obesity, Maternal/epidemiology , Placenta/pathology , Pregnancy , Pregnancy Complications, Infectious/physiopathology , Pregnancy Trimester, First , Pregnancy Trimester, Second , Prospective Studies , RNA, Viral/analysis , Risk Factors , SARS-CoV-2 , Severity of Illness Index , Singapore/epidemiology , Umbilical Cord/pathology , Young Adult
16.
PLoS Pathog ; 16(12): e1009130, 2020 12.
Article in English | MEDLINE | ID: covidwho-962381

ABSTRACT

The novel coronavirus SARS-CoV-2 is the causative agent of Coronavirus Disease 2019 (COVID-19), a global healthcare and economic catastrophe. Understanding of the host immune response to SARS-CoV-2 is still in its infancy. A 382-nt deletion strain lacking ORF8 (Δ382 herein) was isolated in Singapore in March 2020. Infection with Δ382 was associated with less severe disease in patients, compared to infection with wild-type SARS-CoV-2. Here, we established Nasal Epithelial cells (NECs) differentiated from healthy nasal-tissue derived stem cells as a suitable model for the ex-vivo study of SARS-CoV-2 mediated pathogenesis. Infection of NECs with either SARS-CoV-2 or Δ382 resulted in virus particles released exclusively from the apical side, with similar replication kinetics. Screening of a panel of 49 cytokines for basolateral secretion from infected NECs identified CXCL10 as the only cytokine significantly induced upon infection, at comparable levels in both wild-type and Δ382 infected cells. Transcriptome analysis revealed the temporal up-regulation of distinct gene subsets during infection, with anti-viral signaling pathways only detected at late time-points (72 hours post-infection, hpi). This immune response to SARS-CoV-2 was significantly attenuated when compared to infection with an influenza strain, H3N2, which elicited an inflammatory response within 8 hpi, and a greater magnitude of anti-viral gene up-regulation at late time-points. Remarkably, Δ382 induced a host transcriptional response nearly identical to that of wild-type SARS-CoV-2 at every post-infection time-point examined. In accordance with previous results, Δ382 infected cells showed an absence of transcripts mapping to ORF8, and conserved expression of other SARS-CoV-2 genes. Our findings shed light on the airway epithelial response to SARS-CoV-2 infection, and demonstrate a non-essential role for ORF8 in modulating host gene expression and cytokine production from infected cells.


Subject(s)
COVID-19/virology , Nasal Mucosa/virology , SARS-CoV-2/genetics , SARS-CoV-2/pathogenicity , Viral Proteins/genetics , Chemokine CXCL10/immunology , Epithelial Cells/immunology , Epithelial Cells/metabolism , Epithelial Cells/virology , Host-Pathogen Interactions/physiology , Humans , Kinetics , Nasal Mucosa/immunology , Nasal Mucosa/metabolism , Transcriptome , Viral Proteins/immunology , Virus Replication/physiology
18.
19.
Ocul Immunol Inflamm ; 28(8): 1280-1284, 2020 Nov 16.
Article in English | MEDLINE | ID: covidwho-817307

ABSTRACT

PURPOSE: To report bilateral follicular conjunctivitis in two confirmed Coronavirus (COVID-19) patients with the presence of Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) in conjunctival swab specimens. PARTICIPANTS AND METHODS: Two unrelated patients with confirmed SARS-CoV-2 infection and bilateral acute conjunctivitis were examined. Conjunctival swabs were assessed for the presence of SARS-CoV-2 by quantitative real-time polymerase chain reaction (RT-PCR) and viral culture. RESULTS: Both patients developed eye redness 3 days after the onset of COVID-19 symptoms. Slit lamp examination showed bilateral acute follicular conjunctivitis, which was resolved within 6 days. RT-PCR demonstrated the presence of viral RNA in conjunctival specimens from both eyes, which was unrelated to viral RNA from throat swabs. CONCLUSION: SARS-CoV-2 may cause ocular manifestations such as viral conjunctivitis. Conjunctival sampling may be useful for infected patients with conjunctivitis and fever. Precautionary measures are recommended when examining infected patients throughout the clinical course of the infection.


Subject(s)
Betacoronavirus/genetics , Conjunctivitis, Viral/virology , Coronavirus Infections/epidemiology , Eye Infections, Viral/virology , Pneumonia, Viral/epidemiology , RNA, Viral/analysis , Adult , COVID-19 , Conjunctivitis, Viral/epidemiology , Coronavirus Infections/transmission , Eye Infections, Viral/epidemiology , Humans , Incidence , Male , Pandemics , Pneumonia, Viral/transmission , Real-Time Polymerase Chain Reaction , SARS-CoV-2 , Singapore/epidemiology
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