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1.
Preprint in English | medRxiv | ID: ppmedrxiv-22279589

ABSTRACT

BACKGROUNDThe rising breakthrough infections caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, especially Omicron and its sub-lineages, have raised an urgent need to develop broad-spectrum vaccines against coronavirus disease 2019 (COVID-19). We have developed a mosaic-type recombinant vaccine candidate, named NVSI-06-09, having immune potentials against a broad range of SARS-CoV-2 variants. METHODSAn ongoing randomized, double-blind, controlled phase 2 trial was conducted to evaluate the safety and immunogenicity of NVSI-06-09 as a booster dose in subjects aged 18 years and older from the United Arab Emirates (UAE), who had completed two or three doses of BBIBP-CorV vaccinations at least 6 months prior to the enrollment. The participants were randomly assigned with 1:1 to receive a booster dose of NVSI-06-09 or BBIBP-CorV. The primary outcomes were immunogenicity and safety against SARS-CoV-2 Omicron variant, and the exploratory outcome was cross-immunogenicity against other circulating strains. RESULTSA total of 516 participants received booster vaccination. Interim results showed a similar safety profile between NVSI-06-09 and BBIBP-CorV booster groups, with low incidence of adverse reactions of grade 1 or 2. For immunogenicity, by day 14 after the booster vaccination, the fold rises in neutralizing antibody geometric mean titers (GMTs) from baseline level elicited by NVSI-06-09 were remarkably higher than those by BBIBP-CorV against the prototype strain (19.67 vs 4.47-fold), Omicron BA.1.1 (42.35 vs 3.78-fold), BA.2 (25.09 vs 2.91-fold), BA.4 (22.42 vs 2.69-fold), and BA.5 variants (27.06 vs 4.73-fold). Similarly, the neutralizing GMTs boosted by NVSI-06-09 against Beta and Delta variants were also 6.60-fold and 7.17-fold higher than those boosted by BBIBP-CorV. CONCLUSIONSA booster dose of NVSI-06-09 was well-tolerated and elicited broad-spectrum neutralizing responses against SARS-CoV-2 prototype strain and immune-evasive variants, including Omicron and its sub-lineages. The immunogenicity of NVSI-06-09 as a booster vaccine was superior to that of BBIBP-CorV. (Funded by LIBP and BIBP of Sinopharm; ClinicalTrials.gov number, NCT05293548).

2.
J Med Chem ; 65(3): 2558-2570, 2022 02 10.
Article in English | MEDLINE | ID: covidwho-1895561

ABSTRACT

Safe and effective vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants are the best approach to successfully combat the COVID-19 pandemic. The receptor-binding domain (RBD) of the viral spike protein is a major target to develop candidate vaccines. α-Galactosylceramide (αGalCer), a potent invariant natural killer T cell (iNKT) agonist, was site-specifically conjugated to the N-terminus of the RBD to form an adjuvant-protein conjugate, which was anchored on the liposome surface. This is the first time that an iNKT cell agonist was conjugated to the protein antigen. Compared to the unconjugated RBD/αGalCer mixture, the αGalCer-RBD conjugate induced significantly stronger humoral and cellular responses. The conjugate vaccine also showed effective cross-neutralization to all variants of concern (B.1.1.7/alpha, B.1.351/beta, P.1/gamma, B.1.617.2/delta, and B.1.1.529/omicron). These results suggest that the self-adjuvanting αGalCer-RBD has great potential to be an effective COVID-19 vaccine candidate, and this strategy might be useful for designing various subunit vaccines.


Subject(s)
COVID-19 Vaccines/therapeutic use , COVID-19/therapy , Galactosylceramides/therapeutic use , Peptide Fragments/therapeutic use , SARS-CoV-2/immunology , Vaccines, Conjugate/therapeutic use , Adjuvants, Immunologic/chemistry , Adjuvants, Immunologic/therapeutic use , Animals , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19 Vaccines/chemistry , COVID-19 Vaccines/immunology , Female , Galactosylceramides/chemistry , Galactosylceramides/immunology , Immunity, Humoral/drug effects , Immunity, Innate/drug effects , Interferon-gamma/metabolism , Liposomes/chemistry , Liposomes/immunology , Liposomes/therapeutic use , Mice, Inbred BALB C , Peptide Fragments/chemistry , Peptide Fragments/immunology , Protein Domains , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/immunology , Spike Glycoprotein, Coronavirus/therapeutic use , Vaccines, Conjugate/chemistry , Vaccines, Conjugate/immunology
3.
BMC Psychiatry ; 22(1): 336, 2022 05 15.
Article in English | MEDLINE | ID: covidwho-1846812

ABSTRACT

OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic, a major public health crisis, harms individuals' mental health. This 3-wave repeated survey aimed to examine the prevalence and correlates of suicidal ideation at different stages of the COVID-19 pandemic in a large sample of college students in China. METHODS: Using a repeated cross-sectional survey design, we conducted 3 online surveys of college students during the COVID-19 pandemic at 22 universities in Guandong, China. The 3 surveys were conducted during the outbreak period (T1: 3 February to 10 February 2020, N = 164,101), remission period (T2: 24 March to 3 April 2020, N = 148,384), and normalized prevention and control period (T3: 1 June to 15 June 2020, N = 159,187). Suicidal ideation was measured by the ninth item of the Patient Health Questionnaire-9. A range of suicide-related factors was assessed, including sociodemographic characteristics, depression, anxiety, insomnia, pre-existing mental health problems, and COVID-19-related factors. RESULTS: The prevalence of suicidal ideation was 8.5%, 11.0% and 12.6% at T1, T2, and T3, respectively. Male sex (aOR: 1.35-1.44, Ps < 0.001), poor self-perceived mental health (aOR: 2.25-2.81, Ps < 0.001), mental diseases (aOR: 1.52-2.09, P < 0.001), prior psychological counseling (aOR: 1.23-1.37, Ps < 0.01), negative perception of the risk of the COVID-19 epidemic (aOR: 1.14-1.36, Ps < 0.001), depressive symptoms (aOR: 2.51-303, Ps < 0.001) and anxiety symptoms (aOR: 1.62-101.11, Ps < 0.001) were associated with an increased risk of suicidal ideation. CONCLUSION: Suicidal ideation appeared to increase during the COVID-19 pandemic remission period among college students in China. Multiple factors, especially mental health problems, are associated with suicidal ideation. Psychosocial interventions should be implemented during and after the COVID-19 pandemic to reduce suicide risk among college students.


Subject(s)
COVID-19 , COVID-19/epidemiology , China/epidemiology , Cross-Sectional Studies , Depression/epidemiology , Depression/psychology , Humans , Male , Pandemics , Prevalence , Risk Factors , SARS-CoV-2 , Students/psychology , Suicidal Ideation
4.
Stem Cell Reports ; 17(5): 1089-1104, 2022 05 10.
Article in English | MEDLINE | ID: covidwho-1799706

ABSTRACT

Humanized mouse models and mouse-adapted SARS-CoV-2 virus are increasingly used to study COVID-19 pathogenesis, so it is important to learn where the SARS-CoV-2 receptor ACE2 is expressed. Here we mapped ACE2 expression during mouse postnatal development and in adulthood. Pericytes in the CNS, heart, and pancreas express ACE2 strongly, as do perineurial and adrenal fibroblasts, whereas endothelial cells do not at any location analyzed. In a number of other organs, pericytes do not express ACE2, including in the lung where ACE2 instead is expressed in bronchial epithelium and alveolar type II cells. The onset of ACE2 expression is organ specific: in bronchial epithelium already at birth, in brain pericytes before, and in heart pericytes after postnatal day 10.5. Establishing the vascular localization of ACE2 expression is central to correctly interpret data from modeling COVID-19 in the mouse and may shed light on the cause of vascular COVID-19 complications.


Subject(s)
Angiotensin-Converting Enzyme 2 , COVID-19 , Pericytes , Angiotensin-Converting Enzyme 2/metabolism , Animals , COVID-19/complications , Cardiovascular Diseases/virology , Endothelial Cells , Mice , Pericytes/metabolism , SARS-CoV-2
5.
Protein Cell ; 13(12): 920-939, 2022 12.
Article in English | MEDLINE | ID: covidwho-1773029

ABSTRACT

SARS-CoV-2 infection causes complicated clinical manifestations with variable multi-organ injuries, however, the underlying mechanism, in particular immune responses in different organs, remains elusive. In this study, comprehensive transcriptomic alterations of 14 tissues from rhesus macaque infected with SARS-CoV-2 were analyzed. Compared to normal controls, SARS-CoV-2 infection resulted in dysregulation of genes involving diverse functions in various examined tissues/organs, with drastic transcriptomic changes in cerebral cortex and right ventricle. Intriguingly, cerebral cortex exhibited a hyperinflammatory state evidenced by significant upregulation of inflammation response-related genes. Meanwhile, expressions of coagulation, angiogenesis and fibrosis factors were also up-regulated in cerebral cortex. Based on our findings, neuropilin 1 (NRP1), a receptor of SARS-CoV-2, was significantly elevated in cerebral cortex post infection, accompanied by active immune response releasing inflammatory factors and signal transmission among tissues, which enhanced infection of the central nervous system (CNS) in a positive feedback way, leading to viral encephalitis. Overall, our study depicts a multi-tissue/organ transcriptomic landscapes of rhesus macaque with early infection of SARS-CoV-2, and provides important insights into the mechanistic basis for COVID-19-associated clinical complications.


Subject(s)
COVID-19 , SARS-CoV-2 , Animals , COVID-19/genetics , Macaca mulatta , SARS-CoV-2/genetics , Transcriptome
6.
Preprint in English | medRxiv | ID: ppmedrxiv-22272062

ABSTRACT

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with immune escape ability raises the urgent need for developing cross-neutralizing vaccines against the virus. NVSI-06-08 is a potential broad-spectrum recombinant COVID-19 vaccine that integrates the antigens from multiple SARS-CoV-2 strains into a single immunogen. Here, we evaluated the safety and immunogenicity of NVSI-06-08 as a heterologous booster dose in adults previously vaccinated with the inactivated vaccine BBIBP-CorV in a randomized, double-blind, controlled, phase 2 trial conducted in the United Arab Emirates (NCT05069129). Three groups of healthy adults over 18 years of age (600 participants per group) who had administered two doses of BBIBP-CorV 4-6-month, 7-9-month and >9-month earlier, respectively, were vaccinated with either a homologous booster of BBIBP-CorV or a heterologous booster of NVSI-06-08. The primary outcome was immunogenicity and safety of booster vaccinations. The exploratory outcome was cross-reactive immunogenicity against multiple SARS-CoV-2 variants of concerns (VOCs). The incidence of adverse reactions was low in both booster vaccinations, and the overall safety profile of heterologous boost was quite similar to that of homologous boost. Heterologous NVSI-06-08 booster was immunogenically superior to homologous booster of BBIBP-CorV. Both Neutralizing and IgG antibodies elicited by NVSI-06-08 booster were significantly higher than by the booster of BBIBP-CorV against not only SARS-CoV-2 prototype strain but also multiple VOCs. Especially, the neutralizing activity induced by NVSI-06-08 booster against the immune-evasive Beta variant was no less than that against the prototype strain, and a considerable level of neutralizing antibodies against Omicron (GMT: 367.67; 95%CI, 295.50-457.47) was induced by heterologous booster, which was substantially higher than that boosted by BBIBP-CorV (GMT: 45.03; 95%CI, 36.37-55.74). Our findings showed that NVSI-06-08 was safe and immunogenic as a booster dose following two doses of BBIBP-CorV, which was immunogenically superior to homologous boost with another dose of BBIBP-CorV. Our study also indicated that the design of hybrid antigen may provide an effective strategy for broad-spectrum vaccine developments.

7.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-315947

ABSTRACT

The ongoing outbreak of the novel coronavirus pneumonia (also known as COVID-19) has triggered a series of stringent control measures in China, such as city closure, traffic restrictions, contact tracing and household quarantine. These containment efforts often lead to changes in the contact pattern among individuals of the population. Many existing compartmental epidemic models fail to account for the effects of contact structure. In this paper, we devised a pairwise epidemic model to analyze the COVID-19 outbreak in China based on confirmed cases reported during the period February 3rd--17th, 2020. By explicitly incorporating the effects of family clusters and contact tracing followed by household quarantine and isolation, our model provides a good fit to the trajectory of COVID-19 infections and is useful to predict the epidemic trend. We obtained the average of the reproduction number $R=1.494$ ($95\%$ CI: $1.483-1.507$) for Hubei province and $R=1.178$ ($95\%$ CI: $1.145-1.158$) for China (except Hubei), suggesting that some existing studies may have overestimated the reproduction number by neglecting the dynamical correlations and clustering effects. We forecasted that the COVID-19 epidemic would peak on February 13th ($95\%$ CI: February $9-17$th) in Hubei and 6 days eariler in the regions outside Hubei. Moreover the epidemic was expected to last until the middle of March in China (except Hubei) and late April in Hubei. The sensitivity analysis shows that ongoing exposure for the susceptible and population clustering play an important role in the disease propagation. With the enforcement of household quarantine measures, the reproduction number $R$ effectively reduces and epidemic quantities decrease accordingly. Furthermore, we gave an answer to the public concern on how long the stringent containment strategies should maintain. Through numerical analysis, we suggested that the time for the resumption of work and production in China (except Hubei) and Hubei would be the middle of March and the end of April, 2020, respectively. These constructive suggestions may bring some immeasurable social-economic benefits in the long run.

8.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-312630

ABSTRACT

Background: Since December 2019, COVID-19 has been confirmed in more than18.8 million patients and leads to 0.70 million deaths worldwide. The mortality and disease severity predictors of COVID-19 have been investigated in many studies. However, they are based on early or partial datasets from high epidemic areas. Here, we retrospect benign clinical and epidemiological outcomes-associated factors from a solved epidemic in a low epidemic area. Methods: : All 98 laboratory-confirmed COVID-19 patients in a local epidemic (Zhuhai, China) from January 17, 2020 to March 10, 2020 were enrolled. Data were updated until all patients having final outcomes. Results: : Patients were all hospitalized. The case fatality rate was 1.0%. There were no local secondary infection cases. The median age was 46.3 years. Underlying diseases were found in 33.7% patients. The severe/critical rate was 19.4%. The mean period from disease onset to admission was 4.4 days. Compared with serious/critical cases, mild/common cases on admission were much younger, lacks of comorbidities and normal in functions of vital organs and indicators of secondary bacterial infections. The lymphocyte counts in serious/critical cases began to be significantly lower 3 days before their identification dates. The absence of lymphopenia before the eighth day from disease onset can exclude the possibility of 78.5% to be serious/critical ill. Most patients (88.8%) received antiviral treatments. Early antiviral treatment significantly shortened the viral RNA-negative conversion time. The delayed antiviral treatment was associated with critical patients. Conclusions: : Younger age, lack of aging-related diseases and early hospitalization of all patients to conduct antiviral treatment and prevention of secondary epidemic were the important benign clinical and epidemiological outcomes-associated factors of COVID-19. In combating COVID-19, the active intervention strategies are crucial in low epidemic areas and the continuous monitoring of lymphocytes may be useful to sort patients reasonably in high epidemic areas.

9.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-308223

ABSTRACT

Background: Novel coronavirus (COVID-19) is a new viral species that causes pneumonia. Currently, RT-PCR and IgM/IgG antibody assays have been recommended for the diagnosis of COVID-19 infection. However, the correlation between RT-PCR status and antibody (IgG, IgM) response remains unknown. Methods: : Consecutive COVID-19 patients admitted to our department between February 10, 2020 and March 10, 2020, were diagnosed by guidelines issued by the World Health Organization (WHO) and included in this study. RT-PCR and antibody (IgM/IgG) assays for COVID-19 infection were performed for all patients according to the manufactures’ protocols. Other data, such as demographic, clinical, laboratory, as well as treatment and outcome, were collected using data collection tables from electronic medical records. Results: : During the study period, a total of 103 patients were diagnosed as having a moderate type of COVID-19 at our department, including 55 males and 48 females, with an average age of 57.53 ± 1.65 years old (range 23 to 90 years old). The peak level of SARS-CoV-2 IgM antibody (243.10 ± 89.84 AU/ml) was reported 4 days after the negative RT-PCR (-) (all P < 0.05). Subsequently, the IgM decreased to 42.69 ± 22.39 AU/ml 21 days after RT-PCR (-). However, the IgG was maintained at a high level 4 days before RT-PCR (-) and later. The lymphocyte count was at the lowest level on day7 before the RT-PCR(-) result (P<0.05), and then elevated after RT-PCR conversion (viral clearance). Conclusions: : SARS-CoV-2 IgM/IgG levels did not correlate with RT-PCR status in our study sample. We found that SARS-CoV-2 IgM/IgG could be a potential biomarker to monitor clinical course, determine discharge, and assess recovery of those infected patients with the novel coronavirus. Trial registration: A prospective, open label, randomized, control trial for chloroquine or hydroxychloroquine in patients with mild and common novel coronavirus pulmonary (COVIP-19). ChiCTR2000030054. Registered 18 Feb,2020. http://www.chictr.org.cn/edit.aspx?pid=49869&htm=4

11.
Preprint in English | medRxiv | ID: ppmedrxiv-21268499

ABSTRACT

BackgroundThe increased coronavirus disease 2019 (COVID-19) breakthrough cases pose the need of booster vaccinations. In this study, we reported the safety and immunogenicity of a heterologous boost with a recombinant COVID-19 vaccine (CHO cells), named NVSI-06-07, as a third dose in participants who have previously received two doses of the inactivated vaccine (BBIBP-CorV) at pre-specified time intervals. Using homologous boost with BBIBP-CorV as control, the safety and immunogenicity of the heterologous boost with NVSI-06-07 against various SARS-CoV-2 strains, including Omicron, were characterized. MethodsThis study is a single-center, randomised, double-blinded, controlled phase 2 trial for heterologous boost of NVSI-06-07 in BBIBP-CorV recipients from the United Arab Emirates (UAE). Healthy adults (aged [≥]18 years) were enrolled and grouped by the specified prior vaccination interval of BBIBP-CorV, i.e., 1-3 months, 4-6 months or [≥]6 months, respectively, with 600 individuals per group. For each group, participants were randomly assigned at 1:1 ratio to receive either a heterologous boost of NVSI-06-07 or a homologous booster dose of BBIBP-CorV. The primary outcome was to comparatively assess the immunogenicity between heterologous and homologous boosts at 14 and 28 days post-boosting immunization, by evaluation of the geometric mean titers (GMTs) of IgG and neutralizing antibodies as well as the corresponding seroconversion rate ([≥]4-fold rise in antibody titers). The secondary outcomes were the safety profile of the boosting strategies within 30 days post vaccination. The exploratory outcome was the immune efficacy against Omicron and other variants of concern (VOCs) of SARS-CoV-2. This trial is registered with ClinicalTrials.gov, NCT05033847. FindingsA total of 1800 individuals who have received two doses of BBIBP-CorV were enrolled, of which 899 participants received a heterologous boost of NVSI-06-07 and 901 received a homologous boost for comparison. No vaccine-related serious adverse event (SAE) and no adverse events of special interest (AESI) were reported. 184 (20{middle dot}47%) participants in the heterologous boost groups and 177 (19{middle dot}64%) in the homologous boost groups reported at least one adverse reaction within 30 days. Most of the local and systemic adverse reactions reported were grades 1 (mild) or 2 (moderate), and there was no significant difference in the overall safety between heterologous and homologous boosts. Immunogenicity assays showed that the seroconversion rates in neutralizing antibodies against prototype SARS-CoV-2 elicited by heterologous boost were 89{middle dot}96% - 97{middle dot}52% on day 28 post-boosting vaccination, which was much higher than what was induced by homologous boost (36{middle dot}80% - 81{middle dot}75%). Similarly, in heterologous NVSI-06-07 booster groups, the neutralizing geometric mean titers (GMTs) against the prototype strain increased by 21{middle dot}01 - 63{middle dot}85 folds from baseline to 28 days post-boosting vaccination, whereas only 4{middle dot}20 - 16{middle dot}78 folds of increases were observed in homologous BBIBP-CorV booster group. For Omicron variant, the neutralizing antibody GMT elicited by the homologous boost of BBIBP-CorV was 37{middle dot}91 (95%CI, 30{middle dot}35-47{middle dot}35), however, a significantly higher level of neutralizing antibodies with GMT 292{middle dot}53 (95%CI, 222{middle dot}81-384{middle dot}07) was induced by the heterologous boost of NVSI-06-07, suggesting that it may serve as an effective boosting strategy combating the pandemic of Omicron. The similar results were obtained for other VOCs, including Alpha, Beta and Delta, in which the neutralizing response elicited by the heterologous boost was also significantly greater than that of the homologous boost. In the participants primed with BBIBP-CorV over 6 months, the largest increase in the neutralizing GMTs was obtained both in the heterologous and homologous boost groups, and thus the booster vaccination with over 6 months intervals was optimal. InterpretationOur findings indicated that the heterologous boost with NVSI-06-07 was safe, well-tolerated and immunogenic in adults primed with a full regimen of BBIBP-CorV. Compared to homologous boost with a third dose of BBIBP-CorV, incremental increases in immune responses were achieved by the heterologous boost with NVSI-06-07 against SARS-CoV-2 prototype strain, Omicron variant, and other VOCs. The heterologous BBIBP-CorV/NVSI-06-07 prime-boosting vaccination may be valuable in preventing the pandemic of Omicron. The optimal booster strategy was the heterologous boost with NVSI-06-07 over 6 months after a priming with two doses of BBIBP-CorV. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSWe searched PubMed for clinical trials or prospective/cohort studies involving heterologous booster vaccination in non-immunocompromised population published up to Dec 25, 2021, using the term "(COVID) AND (vaccin*) AND (clinical trial OR cohort OR prospective) AND (heterologous) AND (booster OR prime-boost OR third dose)" with no language restrictions. Nine studies of heterologous prime-boost vaccinations with adenovirus-vector vaccines (ChAdOx1 nCov-19, Oxford-AstraZeneca, Ad26.COV2.S, Janssen) and mRNA vaccines (BNT162b2, Pfizer-BioNtech; mRNA1273, Moderna) were identified. The adenovirus-vector and mRNA heterologous prime-boost vaccination was found to be well tolerated and immunogenic. In individuals primed with adenovirus-vector vaccine, mRNA booster vaccination led to greater immune response than homologous boost. However, varied results were obtained on whether heterologous boost was immunogenically superior to the homologous mRNA prime-boost vaccination. Besides that, A preprint trial in population previously immunized with inactivated vaccines (CoronaVac, Sinovac Biotech) showed that the heterologous boost with adenovirus-vector vaccine (Convidecia, CanSino Biologicals) was safe and induced higher level of live-virus neutralizing antibodies than by the homogeneous boost. A pilot study reported that boosting with BNT162b2 in individuals primed with two doses of inactivated vaccines (BBIBP-CorV) was significantly more immunogenic than homologous vaccination with two-dose of BNT162b2. In addition, a preprint paper demonstrated that heterologous boost of ZF2001, a recombinant protein subunit vaccine, after CoronaVac or BBIBP-CorV vaccination potently improved the immunogenicity. But only a small size of samples was tested in this study and the live-virus neutralization was not detected. Till now, it is still lacking a formal clinical trial to evaluate the immunogenicity and safety of the heterologous prime-boost vaccination with an inactivated vaccine followed by a recombinant protein subunit-based vaccine. Added value of this studyTo our knowledge, this is the first reported result of a large-scale randomised, controlled clinical trial of heterologous prime-boost vaccination with an inactivated vaccine followed by a recombinant protein subunit vaccine. This trial demonstrated that the heterologous prime-booster vaccination with BBIBP-CorV/NVSI-06-07 is safe and immunogenic. Its immunoreactivity is similar to that of homologous vaccination with BBIBP-CorV. Compared to homologous boost, heterologous boost with NVSI-06-07 in BBIBP-CorV recipients elicited significantly higher immunogenicity not only against the SARS-CoV-2 prototype strain but also against Omicron and other variants of concern (VOCs). Implications of all the available evidenceBooster vaccination is considered an effective strategy to improve the protection efficacy of COVID-19 vaccines and control the epidemic waves of SARS-CoV-2. Data from our trial suggested that the booster vaccination of NVSI-06-07 in BBIBP-CorV recipients significantly improved the immune responses against various SARS-CoV-2 strains, including Omicron. Due to no Omicron-specific vaccine available currently, the BBIBP-CorV/NVSI-06-07 heterologous prime-boost might serve as an effective strategy combating Omicron variant. Besides that, BBIBP-CorV has been widely inoculated in population, and thus further boosting vaccination with NVSI-06-07 is valuable in preventing the COVID-19 pandemic. But further studies are needed to assess the long-term protection of BBIBP-CorV/NVSI-06-07 prime-booster vaccination.

12.
Signal Transduct Target Ther ; 6(1): 414, 2021 12 06.
Article in English | MEDLINE | ID: covidwho-1556321

ABSTRACT

Azvudine (FNC) is a nucleoside analog that inhibits HIV-1 RNA-dependent RNA polymerase (RdRp). Recently, we discovered FNC an agent against SARS-CoV-2, and have taken it into Phase III trial for COVID-19 patients. FNC monophosphate analog inhibited SARS-CoV-2 and HCoV-OC43 coronavirus with an EC50 between 1.2 and 4.3 µM, depending on viruses or cells, and selective index (SI) in 15-83 range. Oral administration of FNC in rats revealed a substantial thymus-homing feature, with FNC triphosphate (the active form) concentrated in the thymus and peripheral blood mononuclear cells (PBMC). Treating SARS-CoV-2 infected rhesus macaques with FNC (0.07 mg/kg, qd, orally) reduced viral load, recuperated the thymus, improved lymphocyte profiles, alleviated inflammation and organ damage, and lessened ground-glass opacities in chest X-ray. Single-cell sequencing suggested the promotion of thymus function by FNC. A randomized, single-arm clinical trial of FNC on compassionate use (n = 31) showed that oral FNC (5 mg, qd) cured all COVID-19 patients, with 100% viral ribonucleic acid negative conversion in 3.29 ± 2.22 days (range: 1-9 days) and 100% hospital discharge rate in 9.00 ± 4.93 days (range: 2-25 days). The side-effect of FNC is minor and transient dizziness and nausea in 16.12% (5/31) patients. Thus, FNC might cure COVID-19 through its anti-SARS-CoV-2 activity concentrated in the thymus, followed by promoted immunity.


Subject(s)
Antiviral Agents/administration & dosage , Azides/administration & dosage , COVID-19/drug therapy , Deoxycytidine/analogs & derivatives , SARS-CoV-2/metabolism , Thymus Gland , Adult , Aged , Aged, 80 and over , Animals , Coronavirus OC43, Human/metabolism , Deoxycytidine/administration & dosage , Female , Humans , Male , Middle Aged , Rats , Thymus Gland/metabolism , Thymus Gland/virology
13.
Front Psychol ; 12: 712703, 2021.
Article in English | MEDLINE | ID: covidwho-1551531

ABSTRACT

Cyberchondria is considered "the anxiety-amplifying effects of online health-related searches." During the COVID-19 pandemic, people are likely to search health-related information online for reassurance because of fear and related physical symptoms, while cyberchondria may be triggered due to the escalation of health anxiety, different online seeking behavior preference, information overload, and insufficient e-health literacy. This study aimed to investigate the status and influencing factors of cyberchondria in residents in China during the epidemic period of COVID-19. The participants were 674 community residents of Nanyang city surveyed from February 1 to 15, 2020. We administered online measures, including the Chinese Short Form of the Cyberchondria Severity Scale (C-CSS-12), Short Health Anxiety Inventory (SHAI), eHealth Literacy Scale (eHEALS), Patient Health Questionnaire-15 (PHQ-15), and COVID-19-related online information seeking behavior questionnaire. In our study, the average C-CSS-12 total score of residents was 30.65 ± 11.53 during the virus epidemic; 25% of participants scored 22 or below, 50% scored 23 to 38, and 21.9% scored 39 to 60. The SHAI total score (ß = 0.598 > 0, P < 0.001), the use of general search engines (ß = 1.867 > 0, P = 0.039), and searching for information on how to diagnose COVID-19 (ß = 2.280 > 0, P = 0.020) were independent risk factors for cyberchondria, while searching lasting less than 10 min each (ß = -2.992 < 0, P = 0.048), the use of traditional media digital platforms (ß = -1.650 < 0, P = 0.024) and professional medical communication platforms (ß = -4.189 < 0, P = 0.007) were independent protective factors. Our findings showed that nearly a quarter of the participants scored 39 or higher on the C-CSS-12 in Nanyang city during the pandemic, which should be taken seriously. Health anxiety and COVID-19-related online information seeking behavior including online duration, topics and choice on different information channels were important influencing factors of cyberchondria. These findings have implications for further research and clinical practice on cyberchondria in China.

14.
Infect Dis Model ; 6: 643-663, 2021.
Article in English | MEDLINE | ID: covidwho-1174266

ABSTRACT

Nonpharmaceutical interventions (NPIs), particularly contact tracing isolation and household quarantine, play a vital role in effectively bringing the Coronavirus Disease 2019 (COVID-19) under control in China. The pairwise model, has an inherent advantage in characterizing those two NPIs than the classical well-mixed models. Therefore, in this paper, we devised a pairwise epidemic model with NPIs to analyze COVID-19 outbreak in China by using confirmed cases during February 3rd-22nd, 2020. By explicitly incorporating contact tracing isolation and family clusters caused by household quarantine, our model provided a good fit to the trajectory of COVID-19 infections. We calculated the reproduction number R = 1.345 (95% CI: 1.230 - 1.460) for Hubei province and R = 1.217 (95% CI: 1.207 - 1.227) for China (except Hubei). We also estimated the peak time of infections, the epidemic duration and the final size, which are basically consistent with real observation. We indicated by simulation that the traced high-risk contacts from incubated to susceptible decrease under NPIs, regardless of infected cases. The sensitivity analysis showed that reducing the exposure of the susceptible and increasing the clustering coefficient bolster COVID-19 control. With the enforcement of household quarantine, the reproduction number R and the epidemic prevalence declined effectively. Furthermore, we obtained the resumption time of work and production in China (except Hubei) on 10th March and in Hubei at the end of April 2020, respectively, which is broadly in line with the actual time. Our results may provide some potential lessons from China on the control of COVID-19 for other parts of the world.

15.
Preprint in English | medRxiv | ID: ppmedrxiv-21252822

ABSTRACT

To unravel the source of SARS-CoV-2 introduction and the pattern of its spreading and evolution in the United Arab Emirates, we conducted meta-transcriptome sequencing of 1,067 nasopharyngeal swab samples collected between May 9th and Jun 29th, 2020 during the first peak of the local COVID-19 epidemic. We identified global clade distribution and eleven novel genetic variants that were almost absent in the rest of the world defined five subclades specific to the UAE viral population. Cross-settlement human-to-human transmission was related to the local business activity. Perhaps surprisingly, at least 5% of the population were co-infected by SARS-CoV-2 of multiple clades within the same host. We also discovered an enrichment of cytosine-to-uracil mutation among the viral population collected from the nasopharynx, that is different from the adenosine-to-inosine change previously reported in the bronchoalveolar lavage fluid samples and a previously unidentified upregulation of APOBEC4 expression in nasopharynx among infected patients, indicating the innate immune host response mediated by ADAR and APOBEC gene families could be tissue-specific. The genomic epidemiological and molecular biological knowledge reported here provides new insights for the SARS-CoV-2 evolution and transmission and points out future direction on host-pathogen interaction investigation.

16.
Chin Med J (Engl) ; 133(16): 1900-1907, 2020 Aug 20.
Article in English | MEDLINE | ID: covidwho-1050187

ABSTRACT

BACKGROUND: Total and differential white blood cell counts are important for the diagnostic evaluation of suspected diseases. To facilitate the interpretation of total and differential white blood cell counts in pediatric patients, the present study investigated age-dependent changes in total and differential white blood cell counts in healthy reference children. METHODS: Data were obtained from the Pediatric Reference Intervals in China study (PRINCE), which aims to establish and verify pediatric reference intervals for Chinese children based on a nationwide multicenter cross-sectional study from January 2017 to December 2018. Quantile curves were calculated using the generalized additive models for location, shape, and scale method. The 2.5th, 50th, and 97.5th quantile curves were calculated for both total and differential white blood counts. Percents of stacked area charts were used to demonstrate the proportions of differential white blood cells. All statistical analyses were performed using R software. RESULTS: Both 50th and 97.5th quantiles of total white blood cell count and monocyte count were highest at birth, then rapidly decreased in the first 6 months of life; relatively slow reduction continued until 2 years of age. The lymphocyte count was low during infancy and increased to its highest level at 6 months of age; it then exhibited moderate and continuous reduction until approximately 9 years of age. The pattern of neutrophil count changed with age in a manner opposite to that of lymphocyte count. Besides, there were two inter-sections of lymphocyte count and neutrophil count during infancy and at approximately 5 years of age, based on locally weighted regression (LOESS) analysis. There were no apparent age-related changes in eosinophil or basophil counts. CONCLUSION: These data regarding age-related changes in total and differential white blood cell counts can be used to assess the health of pediatric patients and guide clinical decisions.


Subject(s)
Neutrophils , Child , China , Cross-Sectional Studies , Humans , Infant, Newborn , Leukocyte Count , Lymphocyte Count , Reference Values
17.
Cell Res ; 31(1): 17-24, 2021 01.
Article in English | MEDLINE | ID: covidwho-953056

ABSTRACT

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a pandemic worldwide. Currently, however, no effective drug or vaccine is available to treat or prevent the resulting coronavirus disease 2019 (COVID-19). Here, we report our discovery of a promising anti-COVID-19 drug candidate, the lipoglycopeptide antibiotic dalbavancin, based on virtual screening of the FDA-approved peptide drug library combined with in vitro and in vivo functional antiviral assays. Our results showed that dalbavancin directly binds to human angiotensin-converting enzyme 2 (ACE2) with high affinity, thereby blocking its interaction with the SARS-CoV-2 spike protein. Furthermore, dalbavancin effectively prevents SARS-CoV-2 replication in Vero E6 cells with an EC50 of ~12 nM. In both mouse and rhesus macaque models, viral replication and histopathological injuries caused by SARS-CoV-2 infection are significantly inhibited by dalbavancin administration. Given its high safety and long plasma half-life (8-10 days) shown in previous clinical trials, our data indicate that dalbavancin is a promising anti-COVID-19 drug candidate.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , Antiviral Agents , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/metabolism , Teicoplanin/analogs & derivatives , Animals , Antiviral Agents/pharmacokinetics , Antiviral Agents/pharmacology , Caco-2 Cells , Chlorocebus aethiops , Disease Models, Animal , Humans , Mice , Mice, Transgenic , Protein Binding/drug effects , Teicoplanin/pharmacokinetics , Teicoplanin/pharmacology , Vero Cells
18.
Iran J Basic Med Sci ; 23(5): 623-628, 2020 May.
Article in English | MEDLINE | ID: covidwho-683202

ABSTRACT

OBJECTIVES: Interleukin-36 receptor antagonist (IL-36Ra) is a new member of the IL-1 family that exhibits anti-inflammatory activity in a variety of inflammatory and immune diseases. Our purpose was to determine the effect of IL-36Ra on liver injury in a mouse hepatitis model induced by concanavalin A (ConA). MATERIALS AND METHODS: Mice were treated with IL-36Ra DNA or pcDNA3.1 control plasmid using a hydrodynamic gene delivery approach. RESULTS: Our data reveal that treatment with IL-36Ra decreased liver inflammation and serum level of aminotransferases. Furthermore, IL-36Ra reduced ConA-induced pro-inflammatory cytokines (interferon-γ, tumor necrosis factor-α, and IL-17A) production when compared to control plasmid. CONCLUSION: Our results demonstrated that IL-36Ra is a critical protector against ConA-induced liver injury.

19.
J Allergy Clin Immunol Pract ; 8(8): 2585-2591.e1, 2020 09.
Article in English | MEDLINE | ID: covidwho-609222

ABSTRACT

BACKGROUND: The clinical management of coronavirus disease 2019 (COVID-19) is dependent on understanding the underlying factors that contribute to the disease severity. In the absence of effective antiviral therapies, other host immunomodulatory therapies such as targeting inflammatory response are currently being used without clear evidence of their effectiveness. Because inflammation is an essential component of host antiviral mechanisms, therapies targeting inflammation may adversely affect viral clearance and disease outcome. OBJECTIVE: To understand whether the persistent presence of the virus is a key determinant in the disease severity during COVID-19 and to determine whether the viral reactivation in some patients is associated with infectious viral particles. METHODS: The data for patients were available including the onset of the disease, duration of viral persistence, measurements of inflammatory markers such as IL-6 and C-reactive protein, chest imaging, disease symptoms, and their durations among others. Follow-up tests were performed to determine whether the viral negative status persists after their recovery. RESULTS: Our data show that patients with persistent viral presence (>16 days) have more severe disease outcomes including extensive lung involvement and requirement of respiratory support. Two patients who died of COVID-19 were virus-positive at the time of their death. Four patients demonstrated virus-positive status on the follow-up tests, and these patient samples were sent to viral culture facility where virus culture could not be established. CONCLUSIONS: These data suggest that viral persistence is the key determining factor of the disease severity. Therapies that may impair the viral clearance may impair the host recovery from COVID-19.


Subject(s)
Coronavirus Infections/physiopathology , Inflammation/physiopathology , Pneumonia, Viral/physiopathology , Adolescent , Adult , Aged , Betacoronavirus , C-Reactive Protein/immunology , COVID-19 , Child , Child, Preschool , Comorbidity , Coronavirus Infections/diagnostic imaging , Coronavirus Infections/epidemiology , Coronavirus Infections/immunology , Female , Glucocorticoids/therapeutic use , Humans , Infant , Inflammation/epidemiology , Inflammation/immunology , Inflammation Mediators/immunology , Interleukin-6/immunology , Male , Middle Aged , Pandemics , Pneumonia, Viral/diagnostic imaging , Pneumonia, Viral/epidemiology , Pneumonia, Viral/immunology , Real-Time Polymerase Chain Reaction , Respiration, Artificial , SARS-CoV-2 , Severity of Illness Index , Young Adult
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