Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 29
Filter
2.
J Virol ; 96(4): e0157821, 2022 02 23.
Article in English | MEDLINE | ID: covidwho-1759290

ABSTRACT

The ongoing SARS-CoV-2 pandemic poses a severe global threat to public health, as do influenza viruses and other coronaviruses. Here, we present chimpanzee adenovirus 68 (AdC68)-based vaccines designed to universally target coronaviruses and influenza. Our design is centered on an immunogen generated by fusing the SARS-CoV-2 receptor-binding domain (RBD) to the conserved stalk of H7N9 hemagglutinin (HA). Remarkably, the constructed vaccine effectively induced both SARS-CoV-2-targeting antibodies and anti-influenza antibodies in mice, consequently affording protection from lethal SARS-CoV-2 and H7N9 challenges as well as effective H3N2 control. We propose our AdC68-vectored coronavirus-influenza vaccine as a universal approach toward curbing respiratory virus-causing pandemics. IMPORTANCE The COVID-19 pandemic exemplifies the severe public health threats of respiratory virus infection and influenza A viruses. The currently envisioned strategy for the prevention of respiratory virus-causing diseases requires the comprehensive administration of vaccines tailored for individual viruses. Here, we present an alternative strategy by designing chimpanzee adenovirus 68-based vaccines which target both the SARS-CoV-2 receptor-binding-domain and the conserved stalk of influenza hemagglutinin. When tested in mice, this strategy attained potent neutralizing antibodies against wild-type SARS-CoV-2 and its emerging variants, enabling an effective protection against lethal SARS-CoV-2 challenge. Notably, it also provided complete protection from lethal H7N9 challenge and efficient control of H3N2-induced morbidity. Our study opens a new avenue to universally curb respiratory virus infection by vaccination.


Subject(s)
COVID-19/prevention & control , Influenza A Virus, H7N9 Subtype/immunology , Influenza Vaccines , Orthomyxoviridae Infections/prevention & control , SARS-CoV-2/immunology , Animals , COVID-19/epidemiology , COVID-19/genetics , COVID-19/immunology , /immunology , Female , HEK293 Cells , Humans , Influenza A Virus, H7N9 Subtype/genetics , Influenza Vaccines/genetics , Influenza Vaccines/immunology , Influenza Vaccines/pharmacology , Mice , Mice, Inbred BALB C , Mice, Inbred ICR , Mice, Transgenic , Orthomyxoviridae Infections/epidemiology , Orthomyxoviridae Infections/genetics , Orthomyxoviridae Infections/immunology , Pandemics , SARS-CoV-2/genetics
3.
Signal Transduct Target Ther ; 7(1): 91, 2022 03 18.
Article in English | MEDLINE | ID: covidwho-1751707

ABSTRACT

Currently, there is no effective drugs for treating clinically COVID-19 except dexamethasone. We previously revealed that human identical sequences of SARS-CoV-2 promote the COVID-19 progression by upregulating hyaluronic acid (HA). As the inhibitor of HA synthesis, hymecromone is an approved prescription drug used for treating biliary spasm. Here, we aimed to investigate the relation between HA and COVID-19, and evaluate the therapeutic effects of hymecromone on COVID-19. Firstly, HA was closely relevant to clinical parameters, including lymphocytes (n = 158; r = -0.50; P < 0.0001), C-reactive protein (n = 156; r = 0.55; P < 0.0001), D-dimer (n = 154; r = 0.38; P < 0.0001), and fibrinogen (n = 152; r = 0.37; P < 0.0001), as well as the mass (n = 78; r = 0.43; P < 0.0001) and volume (n = 78; r = 0.41; P = 0.0002) of ground-glass opacity, the mass (n = 78; r = 0.48; P < 0.0001) and volume (n = 78; r = 0.47; P < 0.0001) of consolidation in patient with low level of hyaluronan (HA < 48.43 ng/mL). Furthermore, hyaluronan could directly cause mouse pulmonary lesions. Besides, hymecromone remarkably reduced HA via downregulating HAS2/HAS3 expression. Moreover, 89% patients with hymecromone treatment had pulmonary lesion absorption while only 42% patients in control group had pulmonary lesion absorption (P < 0.0001). In addition, lymphocytes recovered more quickly in hymecromone-treated patients (n = 8) than control group (n = 5) (P < 0.05). These findings suggest that hymecromone is a promising drug for COVID-19 and deserves our further efforts to determine its effect in a larger cohort.


Subject(s)
COVID-19 , Hyaluronic Acid , Animals , COVID-19/drug therapy , Humans , Hymecromone/metabolism , Hymecromone/pharmacology , Mice , Prescriptions , SARS-CoV-2
4.
EBioMedicine ; 76: 103861, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1734342

ABSTRACT

BACKGROUND: Since late 2019, SARS-CoV-2 infection has resulted in COVID-19 accompanied by diverse clinical manifestations. However, the underlying mechanism of how SARS-CoV-2 interacts with host and develops multiple symptoms is largely unexplored. METHODS: Bioinformatics analysis determined the sequence similarity between SARS-CoV-2 and human genomes. Diverse fragments of SARS-CoV-2 genome containing Human Identical Sequences (HIS) were cloned into the lentiviral vector. HEK293T, MRC5 and HUVEC were infected with laboratory-packaged lentivirus or transfected with plasmids or antagomirs for HIS. Quantitative RT-PCR and chromatin immunoprecipitation assay detected gene expression and H3K27ac enrichment, respectively. UV-Vis spectroscopy assessed the interaction between HIS and their target locus. Enzyme-linked immunosorbent assay evaluated the hyaluronan (HA) levels of culture supernatant and plasma of COVID-19 patients. FINDINGS: Five short sequences (24-27 nt length) sharing identity between SARS-CoV-2 and human genome were identified. These RNA elements were highly conserved in primates. The genomic fragments containing HIS were predicted to form hairpin structures in silico similar to miRNA precursors. HIS may function through direct genomic interaction leading to activation of host enhancers, and upregulation of adjacent and distant genes, including cytokine genes and hyaluronan synthase 2 (HAS2). HIS antagomirs and Cas13d-mediated HIS degradation reduced HAS2 expression. Severe COVID-19 patients displayed decreased lymphocytes and elevated D-dimer, and C-reactive proteins, as well as increased plasma hyaluronan. Hymecromone inhibited hyaluronan production in vitro, and thus could be further investigated as a therapeutic option for preventing severe outcome in COVID-19 patients. INTERPRETATION: HIS of SARS-CoV-2 could promote COVID-19 progression by upregulating hyaluronan, providing novel targets for treatment. FUNDING: The National Key R&D Program of China (2018YFC1005004), Major Special Projects of Basic Research of Shanghai Science and Technology Commission (18JC1411101), and the National Natural Science Foundation of China (31872814, 32000505).


Subject(s)
Gene Regulatory Networks/genetics , Genome, Human , Hyaluronic Acid/metabolism , RNA, Viral/genetics , SARS-CoV-2/genetics , Antagomirs/metabolism , Argonaute Proteins/genetics , Base Sequence , COVID-19/pathology , COVID-19/virology , Cell Line , Disease Progression , Enhancer Elements, Genetic/genetics , Humans , Hyaluronan Synthases/genetics , Hyaluronan Synthases/metabolism , Hyaluronic Acid/blood , MicroRNAs/genetics , RNA, Viral/chemistry , SARS-CoV-2/isolation & purification , SARS-CoV-2/pathogenicity , Up-Regulation
5.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-324633

ABSTRACT

The receptor-binding domain (RBD) variants of SARS-CoV-2 could impair antibody-mediated neutralization of the virus by host immunity;thus, prospective surveillance for such antibody escape mutants is urgently needed. Here, we comprehensively profiled four antigenic sites of the RBD and mapped the binding hot spots for a panel of RBD-specific monoclonal antibodies isolated from COVID-19 convalescents, especially dominant VH3-53/3–66 antibodies, which are valuable indicators of antigenic changes in the RBD. We further demonstrated that several natural mutations, namely, K417N, F486L, N450K, L452R, E484K, F490S and R346S, significantly decreased the neutralizing activity of multiple human monoclonal antibodies and of human convalescent plasma obtained in the early stage of the COVID-19 pandemic. Of note, among the natural escape mutations, L452R enhanced ACE2 binding affinity, indicating that it potentially increased virulence. Overall, the in-depth maps may have far-reaching value for surveillance of SARS-CoV-2 immune escape variants and guidance of vaccine design.

6.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-313391

ABSTRACT

Background: Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), spreads rapidly and has attracted worldwide attention. Methods: : To improve the forecast accuracy and investigate the spread of SARS-CoV-2, we constructed four mathematical models to numerically estimate the spread of SARS-CoV-2 and the efficacy of eradication strategies. Results: : Using the Susceptible-Exposed-Infected-Removed (SEIR) model, and including measures such as city closures and extended leave policies implemented by the Chinese government that effectively reduced the β value, we estimated that the β value and basic transmission number, R 0 , of SARS-CoV-2 was 0.476/6.66 in Wuhan, 0.359/5.03 in Korea, and 0.400/5.60 in Italy. Considering medicine and vaccines, an advanced model demonstrated that the emergence of vaccines would greatly slow the spread of the virus. Our model predicted that 100,000 people would become infected assuming that the isolation rate α in Wuhan was 0.30. If quarantine measures were taken from March 10, 2020, and the quarantine rate of α was also 0.3, then the final number of infected people was predicted to be 11,426 in South Korea and 147,142 in Italy. Conclusions: : Our mathematical models indicate that SARS-CoV-2 eradication depends on systematic planning, effective hospital isolation, and SARS-CoV-2 vaccination, and some measures including city closures and leave policies should be implemented to ensure SARS-CoV-2 eradication.

7.
Cell Discov ; 8(1): 9, 2022 Feb 01.
Article in English | MEDLINE | ID: covidwho-1661959

ABSTRACT

Safe, effective, and economical vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are needed to achieve adequate herd immunity and end the pandemic. We constructed a novel SARS-CoV-2 vaccine, CoVac501, which is a self-adjuvanting peptide vaccine conjugated with Toll-like receptor 7 (TLR7) agonists. The vaccine contains immunodominant peptides screened from the receptor-binding domain (RBD) and is fully chemically synthesized. It has been formulated in an optimized nanoemulsion formulation and is stable at 40 °C for 1 month. In non-human primates (NHPs), CoVac501 elicited high and persistent titers of protective neutralizing antibodies against multiple RBD mutations, SARS-CoV-2 original strain, and variants (B.1.1.7 and B.1.617.2). Specific peptides booster immunization against the B.1.351 variant has also been shown to be effective in improving protection against B.1.351. Meanwhile, CoVac501 elicited the increase of memory T cells, antigen-specific CD8+ T-cell responses, and Th1-biased CD4+ T-cell immune responses in NHPs. Notably, at an extremely high SARS-CoV-2 challenge dose of 1 × 107 TCID50, CoVac501 provided near-complete protection for the upper and lower respiratory tracts of cynomolgus macaques.

8.
Front Nutr ; 8: 789242, 2021.
Article in English | MEDLINE | ID: covidwho-1639197

ABSTRACT

Boosting and prolonging SARS-CoV-2 vaccine-elicited immunity is paramount for containing the COVID-19 pandemic, which wanes substantially within months after vaccination. Here we demonstrate that the unique strain of probiotic Lactobacillus plantarum GUANKE (LPG) could promote SARS-CoV-2-specific immune responses in both effective and memory phases through enhancing interferon signaling and suppressing apoptotic and inflammatory pathways. Interestingly, oral LPG administration promoted SARS-CoV-2 neutralization antibodies even 6 months after immunization. Furthermore, when LPG was given immediately after SARS-CoV-2 vaccine inoculation, specific neutralization antibodies could be boosted >8-fold in bronchoalveolar lavage (BAL) and >2-fold in sera, T-cell responses were persistent and stable for a prolonged period both in BAL and the spleen. Transcriptional analyses showed that oral application of LPG mobilized immune responses in the mucosal and systemic compartments; in particular, gut-spleen and gut-lung immune axes were observed. These results suggest that LPG could be applied in combination with SARS-CoV-2 vaccines to boost and prolong both the effective and memory immune responses in mucosal and systemic compartments, thereby improving the efficacy of SARS-CoV-2 vaccination.

9.
Proc Natl Acad Sci U S A ; 118(50)2021 12 14.
Article in English | MEDLINE | ID: covidwho-1555255

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), binds to host receptor angiotensin-converting enzyme 2 (ACE2) through its spike (S) glycoprotein, which mediates membrane fusion and viral entry. However, the expression of ACE2 is extremely low in a variety of human tissues, especially in the airways. Thus, other coreceptors and/or cofactors on the surface of host cells may contribute to SARS-CoV-2 infection. Here, we identified nonmuscle myosin heavy chain IIA (MYH9) as an important host factor for SARS-CoV-2 infection of human pulmonary cells by using APEX2 proximity-labeling techniques. Genetic ablation of MYH9 significantly reduced SARS-CoV-2 pseudovirus infection in wild type (WT) A549 and Calu-3 cells, and overexpression of MYH9 enhanced the pseudovirus infection in WT A549 and H1299 cells. MYH9 was colocalized with the SARS-CoV-2 S and directly interacted with SARS-CoV-2 S through the S2 subunit and S1-NTD (N-terminal domain) by its C-terminal domain (designated as PRA). Further experiments suggested that endosomal or myosin inhibitors effectively block the viral entry of SARS-CoV-2 into PRA-A549 cells, while transmembrane protease serine 2 (TMPRSS2) and cathepsin B and L (CatB/L) inhibitors do not, indicating that MYH9 promotes SARS-CoV-2 endocytosis and bypasses TMPRSS2 and CatB/L pathway. Finally, we demonstrated that loss of MYH9 reduces authentic SARS-CoV-2 infection in Calu-3, ACE2-A549, and ACE2-H1299 cells. Together, our results suggest that MYH9 is a candidate host factor for SARS-CoV-2, which mediates the virus entering host cells by endocytosis in an ACE2-dependent manner, and may serve as a potential target for future clinical intervention strategies.


Subject(s)
COVID-19/virology , Myosin Heavy Chains/metabolism , SARS-CoV-2/physiology , Angiotensin-Converting Enzyme 2/metabolism , Cell Line , Cell Membrane/metabolism , Humans , Lung/metabolism , Middle East Respiratory Syndrome Coronavirus/physiology , Myosin Heavy Chains/chemistry , Myosin Heavy Chains/genetics , Protein Binding , Protein Domains , SARS Virus/physiology , Spike Glycoprotein, Coronavirus/metabolism , Virus Internalization
10.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-296092

ABSTRACT

The recurrent outbreak of coronaviruses and variants underscores the need for broadly reactive antivirals and vaccines. Here, a novel broad-spectrum human antibody named 76E1 was isolated from a COVID-19 convalescent patient and showed broad neutralization activity against multiple α- and β-coronaviruses, including the SARS-CoV-2 variants and also exhibited the binding breath to peptides containing the epitope from γ- and δ- coronaviruses. 76E1 cross-protects mice from SARS-CoV-2 and HCoV-OC43 infection in both prophylactic and treatment models. The epitope including the fusion peptide and S2’ cleavage site recognized by 76E1 was significantly conserved among α-, β-, γ- and δ- coronaviruses. We uncovered a novel mechanism of antibody neutralization that the epitope of 76E1 was proportionally less exposed in the prefusion trimeric structure of spike protein but could be unmasked by binding to the receptor ACE2. Once the epitope exposed, 76E1 inhibited S2’ cleavage, thus blocked the membrane fusion process. Our data demonstrate a key epitope targeted by broadly-neutralizing antibodies and will guide next-generation epitope-based pan-coronavirus vaccine design.

11.
Genome Med ; 13(1): 164, 2021 10 14.
Article in English | MEDLINE | ID: covidwho-1542128

ABSTRACT

BACKGROUND: The receptor-binding domain (RBD) variants of SARS-CoV-2 could impair antibody-mediated neutralization of the virus by host immunity; thus, prospective surveillance of antibody escape mutants and understanding the evolution of RBD are urgently needed. METHODS: Using the single B cell cloning technology, we isolated and characterized 93 RBD-specific antibodies from the memory B cells of four COVID-19 convalescent individuals in the early stage of the pandemic. Then, global RBD alanine scanning with a panel of 19 selected neutralizing antibodies (NAbs), including several broadly reactive NAbs, was performed. Furthermore, we assessed the impact of single natural mutation or co-mutations of concern at key positions of RBD on the neutralization escape and ACE2 binding function by recombinant proteins and pseudoviruses. RESULTS: Thirty-three amino acid positions within four independent antigenic sites (1 to 4) of RBD were identified as valuable indicators of antigenic changes in the RBD. The comprehensive escape mutation map not only confirms the widely circulating strains carrying important immune escape RBD mutations such as K417N, E484K, and L452R, but also facilitates the discovery of new immune escape-enabling mutations such as F486L, N450K, F490S, and R346S. Of note, these escape mutations could not affect the ACE2 binding affinity of RBD, among which L452R even enhanced binding. Furthermore, we showed that RBD co-mutations K417N, E484K, and N501Y present in B.1.351 appear more resistant to NAbs and human convalescent plasma from the early stage of the pandemic, possibly due to an additive effect. Conversely, double mutations E484Q and L452R present in B.1.617.1 variant show partial antibody evasion with no evidence for an additive effect. CONCLUSIONS: Our study provides a global view of the determinants for neutralizing antibody recognition, antigenic conservation, and RBD conformation. The in-depth escape maps may have value for prospective surveillance of SARS-CoV-2 immune escape variants. Special attention should be paid to the accumulation of co-mutations at distinct major antigenic sites. Finally, the new broadly reactive NAbs described here represent new potential opportunities for the prevention and treatment of COVID-19.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19 , Immune Evasion , Mutation , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Adult , Aged , B-Lymphocytes/immunology , COVID-19/genetics , COVID-19/immunology , Female , Humans , Immunologic Memory , Male , Middle Aged , SARS-CoV-2/genetics , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology
12.
Cell Res ; 32(1): 24-37, 2022 01.
Article in English | MEDLINE | ID: covidwho-1537308

ABSTRACT

Host cellular receptors play key roles in the determination of virus tropism and pathogenesis. However, little is known about SARS-CoV-2 host receptors with the exception of ACE2. Furthermore, ACE2 alone cannot explain the multi-organ tropism of SARS-CoV-2 nor the clinical differences between SARS-CoV-2 and SARS-CoV, suggesting the involvement of other receptor(s). Here, we performed genomic receptor profiling to screen 5054 human membrane proteins individually for interaction with the SARS-CoV-2 capsid spike (S) protein. Twelve proteins, including ACE2, ASGR1, and KREMEN1, were identified with diverse S-binding affinities and patterns. ASGR1 or KREMEN1 is sufficient for the entry of SARS-CoV-2 but not SARS-CoV in vitro and in vivo. SARS-CoV-2 utilizes distinct ACE2/ASGR1/KREMEN1 (ASK) receptor combinations to enter different cell types, and the expression of ASK together displays a markedly stronger correlation with virus susceptibility than that of any individual receptor at both the cell and tissue levels. The cocktail of ASK-related neutralizing antibodies provides the most substantial blockage of SARS-CoV-2 infection in human lung organoids when compared to individual antibodies. Our study revealed an interacting host receptome of SARS-CoV-2, and identified ASGR1 and KREMEN1 as alternative functional receptors that play essential roles in ACE2-independent virus entry, providing insight into SARS-CoV-2 tropism and pathogenesis, as well as a community resource and potential therapeutic strategies for further COVID-19 investigations.


Subject(s)
COVID-19 , Spike Glycoprotein, Coronavirus , Asialoglycoprotein Receptor , Humans , Membrane Proteins , Protein Binding , Receptors, Virus/metabolism , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/metabolism , Virus Internalization
13.
Vaccine ; 39(48): 7001-7011, 2021 11 26.
Article in English | MEDLINE | ID: covidwho-1488001

ABSTRACT

COVID-19 pandemic has severely impacted the public health and social economy worldwide. A safe, effective, and affordable vaccine against SARS-CoV-2 infections/diseases is urgently needed. We have been developing a recombinant vaccine based on a prefusion-stabilized spike trimer of SARS-CoV-2 and formulated with aluminium hydroxide and CpG 7909. The spike protein was expressed in Chinese hamster ovary (CHO) cells, purified, and prepared as a stable formulation with the dual adjuvant. Immunogenicity studies showed that candidate vaccines elicited robust neutralizing antibody responses and substantial CD4+ T cell responses in both mice and non-human primates. And vaccine-induced neutralizing antibodies persisted at high level for at least 6 months. Challenge studies demonstrated that candidate vaccine reduced the viral loads and inflammation in the lungs of SARS-CoV-2 infected golden Syrian hamsters significantly. In addition, the vaccine-induced antibodies showed cross-neutralization activity against B.1.1.7 and B.1.351 variants. These data suggest candidate vaccine is efficacious in preventing SARS-CoV-2 infections and associated pneumonia, thereby justifying ongoing phase I/II clinical studies in China (NCT04982068 and NCT04990544).


Subject(s)
COVID-19 Vaccines , COVID-19 , Alum Compounds , Aluminum Hydroxide , Animals , Antibodies, Neutralizing , Antibodies, Viral , CHO Cells , Cricetinae , Cricetulus , Humans , Mice , Pandemics , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/genetics
14.
Emerg Microbes Infect ; 10(1): 1555-1573, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1324547

ABSTRACT

To curb the pandemic of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), multiple platforms have been employed toward a safe and highly effective vaccine. Here, we develop a novel cell-based vaccine candidate, namely K562-S, by utilizing human cell K562 as a cellular carrier to display Spike (S) protein of SARS-CoV-2 on the membrane. Analogous to the traditional inactivated vaccine, K562-S cells can be propagated to a large scale by culturing and completely lose their viability after exposure to X-ray irradiation or formalin. We in turn demonstrated high immunogenicity of formalin-inactivated K562-S vaccine in both mouse and non-human primates and its protective efficacy in mice. In mice, immunization with inactivated K562-S vaccines can elicit potent neutralizing antibody (nAb) responses persisting longer than 5 months. We consequently showed in a hACE2 mouse model of SARS-CoV-2 infection that a two-shot vaccination with adjuvanted K562-S rendered greater than 3 log reduction in viral lung load and concomitant ameliorated lung pathology. Of importance, the administration of the same regimen in non-human primates was able to induce a neutralizing antibody titer averaging three-fold higher relative to human convalescent serum. These results together support the promise of K562-based, S-protein-expressing vaccines as a novel vaccination approach against SARS-CoV-2. Importantly, with a powerful capacity to carry external genes for cell-based vectors, this platform could rapidly generate two- and multiple-valent vaccines by incorporating SARS-CoV-2 mutants, SARS-CoV, or MERS-CoV.


Subject(s)
Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19 Vaccines/immunology , COVID-19/prevention & control , Immunogenicity, Vaccine , SARS-CoV-2/immunology , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/immunology , Animals , Animals, Genetically Modified , COVID-19 Vaccines/administration & dosage , Female , HEK293 Cells , Humans , K562 Cells , Macaca mulatta , Mice , Mice, Inbred C57BL , Mice, Inbred ICR , Primates , Specific Pathogen-Free Organisms , Spike Glycoprotein, Coronavirus/administration & dosage , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , Vaccination/methods , Vaccines, Inactivated/administration & dosage , Vaccines, Inactivated/immunology
15.
Front Public Health ; 9: 672215, 2021.
Article in English | MEDLINE | ID: covidwho-1282422

ABSTRACT

Coronavirus disease 2019 (COVID-19) pneumonia is caused by the virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has rapidly become a global public health concern. As the new type of betacoronavirus, SARS-CoV-2 can spread across species and between populations and has a greater risk of transmission than other coronaviruses. To control the spread of SARS-CoV-2, it is vital to have a rapid and effective means of diagnosing asymptomatic SARS-CoV-2-positive individuals and patients with COVID-19, an early isolation protocol for infected individuals, and effective treatments for patients with COVID-19 pneumonia. In this review, we will summarize the novel diagnostic tools that are currently available for coronavirus, including imaging examinations and laboratory medicine by next-generation sequencing (NGS), real-time reverse transcriptase-polymerase chain reaction (rRT-PCR) analysis, immunoassay for COVID-19, cytokine and T cell immunoassays, biochemistry and microbiology laboratory parameters in the blood of the patients with COVID-19, and a field-effect transistor-based biosensor of COVID-19. Specifically, we will discuss the effective detection rate and assay time for the rRT-PCR analysis of SARS-CoV-2 and the sensitivity and specificity of different antibody detection methods, such as colloidal gold and ELISA using specimen sources obtained from the respiratory tract, peripheral serum or plasma, and other bodily fluids. Such diagnostics will help scientists and clinicians develop appropriate strategies to combat COVID-19.


Subject(s)
COVID-19 Testing , COVID-19 , COVID-19/diagnosis , Clinical Laboratory Techniques , Humans , SARS-CoV-2 , Sensitivity and Specificity
16.
Disease Surveillance ; 35(12):1068-1072, 2020.
Article in Chinese | GIM | ID: covidwho-1190519

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a natural emerging virus, with rapid virus replication, wide cell tropism, and strong survival ability. Its epidemic characteristics are similar to those of influenza virus. Asymptomatic infections are widespread in a covert way, and the virus has adapted to human population, making it difficult to control the transmission. The global epidemic in 2020/2021 may further deteriorate before the SARS-CoV-2 vaccines are widely applied and show protective effectiveness, and China will still face the risk of continuous overseas multi-channel import and local outbreaks or recurrence of the epidemic. Therefore, it is necessary to carry out further surveillance about the prevalence and infection of SARS-CoV-2 in the population and the corresponding environment of the high-risk areas in China, and establish a national super mobile SARS-CoV-2 detection network laboratory for performing ultra-large-scale testing tasks;implement differentiated vaccination strategies and closely follow up and monitor the effectiveness and efficiency of vaccination;and continue to strengthen effective public health measures such as wearing masks, washing hands frequently, keeping social distances, opening windows frequently, and reducing gatherings. The coronavirus disease 2019 (COVID-19) epidemic warns us once again that the continuous emergence of new infectious diseases caused by unknown pathogens of wild animal origin has become the new normal status. It is necessary to systematically carry out unknown microbial discovery and reverse pathogenic etiology research in a prospective manner, and actively defend against emerging infectious diseases in the future.

17.
J Infect Dis ; 223(4): 568-580, 2021 02 24.
Article in English | MEDLINE | ID: covidwho-1101847

ABSTRACT

BACKGROUND: The immune protective mechanisms during severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection remain to be deciphered for the development of an effective intervention approach. METHODS: We examined early responses of interleukin 37 (IL-37), a powerful anti-inflammatory cytokine, in 254 SARS-CoV-2-infected patients before any clinical intervention and determined its correlation with clinical prognosis. RESULTS: Our results demonstrated that SARS-CoV-2 infection causes elevation of plasma IL-37. Higher early IL-37 responses were correlated with earlier viral RNA negative conversion, chest computed tomographic improvement, and cough relief, consequently resulted in earlier hospital discharge. Further assays showed that higher IL-37 was associated with lower interleukin 6 and interleukin 8 (IL-8) and higher interferon α responses and facilitated biochemical homeostasis. Low IL-37 responses predicted severe clinical prognosis in combination with IL-8 and C-reactive protein. In addition, we observed that IL-37 administration was able to attenuate lung inflammation and alleviate respiratory tissue damage in human angiotensin-converting enzyme 2-transgenic mice infected with SARS-CoV-2. CONCLUSIONS: Overall, we found that IL-37 plays a protective role by antagonizing inflammatory responses while retaining type I interferon, thereby maintaining the functionalities of vital organs. IL-37, IL-8, and C-reactive protein might be formulated as a precise prediction model for screening severe clinical cases and have good value in clinical practice.


Subject(s)
COVID-19/immunology , Cytokine Release Syndrome/virology , Interleukin-1/blood , Adult , Animals , C-Reactive Protein/metabolism , COVID-19/blood , Female , Humans , Inflammation/immunology , Inflammation/virology , Interleukin-8/blood , Male , Mice , Mice, Transgenic , Middle Aged
18.
EClinicalMedicine ; 25: 100478, 2020 Aug.
Article in English | MEDLINE | ID: covidwho-1047557

ABSTRACT

BACKGROUND: The outbreak of a new coronavirus (SARS-CoV-2) poses a great challenge to global public health. New and effective intervention strategies are urgently needed to combat the disease. METHODS: We conducted an open-label, non-randomized, clinical trial involving moderate COVID-19 patients according to study protocol. Patients were assigned in a 1:2 ratio to receive either aerosol inhalation treatment with IFN-κ and TFF2, every 48 h for three consecutive dosages, in addition to standard treatment (experimental group), or standard treatment alone (control group). The end point was the time to discharge from the hospital. This study is registered with chictr.org.cn, ChiCTR2000030262. FINDINGS: A total of thirty-three eligible COVID-19 patients were enrolled from February 1, 2020 to April 6, 2020, eleven were assigned to the IFN-κ plus TFF2 group, and twenty-two to the control group. Safety and efficacy were evaluated for both groups. No treatment-associated severe adverse effects (SAE) were observed in the group treated with aerosol inhalation of IFN-κ plus TFF2, and no significant differences in the safety evaluations were observed between experimental and control groups. CT imaging was performed in all patients with the median improvement time of 5.0 days (IQR 3.0-9.0) in the experimental group versus 8.5 days (IQR 3.0-17.0) in the control group (p<0.05). In addition, the experimental group had a significant shorten median time in cough relief (4.5 days [IQR 2.0-7.0]) than the control group did (10.0 days [IQR 6.0-21.0])(p<0.005), in viral RNA reversion of 6.0 days (IQR 2.0-13.0) in the experimental group vs 9.5 days (IQR 3.0-23.0) in the control group (p < 0.05), and in the median hospitalization stays of 12.0 days (IQR 7.0-20.0) in the experimental group vs 15.0 days (IQR 10.0-25.0) in the control group (p<0.001), respectively. INTERPRETATION: Aerosol inhalation of IFN-κ plus TFF2 is a safe treatment and is likely to significantly facilitate clinical improvement, including cough relief, CT imaging improvement, and viral RNA reversion, thereby achieves an early release from hospitalization. These data support to explore a scale-up trial with IFN-κ plus TFF2. FUNDING: National Major Project for Control and Prevention of Infectious Disease in China, Shanghai Science and Technology Commission, Shanghai Municipal Health Commission.

19.
EClinicalMedicine ; 27: 100547, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-898762

ABSTRACT

BACKGROUND: Epidemic outbreaks caused by SARS-CoV-2 are worsening around the world, and there are no target drugs to treat COVID-19. IFN-κ inhibits the replication of SARS-CoV-2; and TFF2 is a small secreted polypeptide that promotes the repair of mucosal injury and reduces the inflammatory responses. We used the synergistic effect of both proteins to treat COVID-19. METHODS: We conducted an open-label, randomized, clinical trial involving patients with moderate COVID-19. Patients were assigned in a 1:1 ratio to receive either aerosol inhalation treatment with IFN-κ and TFF2 every 24 h for six consecutive dosages in addition to standard care (experimental group) or standard care alone (control group). The primary endpoint was the time until a viral RNA negative conversion for SARS-CoV-2 in all clinical samples. The secondary clinical endpoint was the time of CT imaging improvement. Data analysis was performed per protocol. This study was registered with chictr.org.cn, ChiCTR2000030262. FINDINGS: Between March 23 and May 23 of 2020, 86 COVID-19 patients with symptoms of moderate illness were recruited, and 6 patients were excluded due to not matching the inclusion criteria (patients with pneumonia through chest radiography). Among the remaining 80 patients, 40 patients were assigned to experimental group, and the others were assigned to control group to only receive standard care. Efficacy and safety were evaluated for both groups. The time of viral RNA negative conversion in experimental group (Mean, 3·80 days, 95% CI 2·07-5·53), was significantly shorter than that in control group (7·40 days, 95% CI 4·57 to 10·23) (p = 0.031), and difference between means was 3·60 days. The percentage of patients in experimental group with reversion to negative viral RNA was significantly increased compared with control group on all sampling days (every day during the 12-day observation period) (p = 0·037). For the secondary endpoint, the experimental group had a significantly shorter time until improvement was seen by CT (Mean 6·21 days, N = 38/40, 95% CI 5·11-7·31) than that in control group (8·76 days, N = 34/40, 95% CI 7·57-9·96) (p = 0.002), and difference between means was 2·55 days. No discomfort or complications during aerosol inhalation were reported to the nurses by any experimental patients. INTERPRETATION: In conclusion, we found that aerosol inhalation of IFN-κ plus TFF2 in combination with standard care is safe and superior to standard care alone in shortening the time up to viral RNA negative conversion in all clinical samples. In addition, the patients in experimental group had a significantly shortened CT imaging improvement time than those in control group. This study suggested that this combination treatment is able to facilitate clinical improvement (negative for virus, improvement by CT, reduced hospitalization stay) and thereby result in an early release from the hospital. These data support the need for exploration with a large-scale trial of IFN-κ plus TFF2 to treat COVID-19. FUNDING: Funding was provided by the National Natural Science Foundation of China, National Major Project for Control and Prevention of Infectious Disease in China, Shanghai Science and Technology Commission, Shanghai Municipal Health Commission.

20.
Biosens Bioelectron ; 171: 112685, 2021 Jan 01.
Article in English | MEDLINE | ID: covidwho-891295

ABSTRACT

The spread of SARS-CoV-2 virus in the ongoing global pandemic has led to infections of millions of people and losses of many lives. The rapid, accurate and convenient SARS-CoV-2 virus detection is crucial for controlling and stopping the pandemic. Diagnosis of patients in the early stage infection are so far limited to viral nucleic acid or antigen detection in human nasopharyngeal swab or saliva samples. Here we developed a method for rapid and direct optical measurement of SARS-CoV-2 virus particles in one step nearly without any sample preparation using a spike protein specific nanoplasmonic resonance sensor. As low as 370 vp/mL were detected in one step within 15 min and the virus concentration can be quantified linearly in the range of 0 to 107 vp/mL. Measurements shown on both generic microplate reader and a handheld smartphone connected device suggest that our low-cost and rapid detection method may be adopted quickly under both regular clinical environment and resource-limited settings.


Subject(s)
Betacoronavirus/isolation & purification , Biosensing Techniques/instrumentation , Clinical Laboratory Techniques , Coronavirus Infections/diagnosis , Pneumonia, Viral/diagnosis , Point-of-Care Testing , Virion/isolation & purification , Antibodies, Immobilized/chemistry , Biosensing Techniques/economics , COVID-19 , COVID-19 Testing , Clinical Laboratory Techniques/economics , Coronavirus Infections/economics , Equipment Design , Humans , Limit of Detection , Models, Molecular , Pandemics , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/analysis , Time Factors
SELECTION OF CITATIONS
SEARCH DETAIL