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1.
arxiv; 2023.
Preprint in English | PREPRINT-ARXIV | ID: ppzbmed-2305.17833v1

ABSTRACT

Unfolding different gender roles is preceding the efforts to reduce gender inequality. This paper analyzes COVID-19 family clusters outside Hubei Province in mainland China during the 2020 outbreak, revealing significant differences in spreading patterns across gender and family roles. Results show that men are more likely to be the imported cases of a family cluster, and women are more likely to be infected within the family. This finding provides new supportive evidence of the men as breadwinner and women as homemaker (MBWH) gender roles in China. Further analyses reveal that the MBWH pattern is stronger in eastern than in western China, stronger for younger than for elder people. This paper offers not only valuable references for formulating gender-differentiated epidemic prevention policies but also an exemplification for studying group differences in similar scenarios.


Subject(s)
COVID-19
2.
researchsquare; 2023.
Preprint in English | PREPRINT-RESEARCHSQUARE | ID: ppzbmed-10.21203.rs.3.rs-2930798.v1

ABSTRACT

Background COVID-19 pandemic has become a serious global public health problem. Although the use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor type 1 blockers (ARBs) has been recommended in patients with COVID-19 and cardiovascular diseases (CVDs), according to the results of some small-sample retrospective analyses; however, there is still a lack of sufficient evidence to validate their efficacy. This multicenter retrospective study investigated whether ACEI/ARB administration was beneficial in patients with COVID-19 and CVDs.Methods A total of 11,231 patients with confirmed COVID-19 and CVDs, from 138 hospitals in Hubei Province, were included in this multicenter retrospective study. We compared the clinical characteristics and outcomes between the ARB and non-ARB groups and analyzed the risk factors for in-hospital death using univariate and multivariate Cox regression analyses and Kaplan–Meier curves.Results In the multivariate Cox regression model, after adjusting for age, gender, comorbidities, and in-hospital medications, ARB use was associated with lower all-cause mortality (adjusted HR, 0.53; 95% CI, 0.38–0.73; P < 0.001). After propensity score-matched analysis, the adjusted HR for the use of ARB associated with all-cause mortality was 0.62 (95% CI, 0.40–0.88; P = 0.02). Further subgroup analyses found that the adjusted HRs for the use of ARB associated with all-cause mortality were 0.52 (95% CI, 0.30–0.89; P = 0.016), 0.37 (95% CI, 0.21–0.64; P < 0.001), 0.42 (95% CI, 0.28–0.64; P < 0.001), and 0.55 (95% CI, 0.37–0.84; P = 0.005) in patients with heart failure, diabetes, and hypercholesterolemia, and severe COVID-19, respectively.Conclusions ARB administration was significantly associated with a lower risk of all-cause mortality in patients with COVID-19 and CVDs.Trial registration ClinicalTrials.gov NCT05615792.


Subject(s)
Heart Failure , Cardiovascular Diseases , Diabetes Mellitus , Hypercholesterolemia , COVID-19
4.
Journalism & Mass Communication Educator ; 2022.
Article in English | EuropePMC | ID: covidwho-2125207

ABSTRACT

Using text mining and semantic network analysis, this study analyzed the job descriptions of 34,787 positions about media analytics from Indeed.com to compare how the in-person and remote jobs differ to inform educators about integrating analytics in the media and communications curriculum. We found that the in-person positions emphasized more on the skills of verbal, interpersonal, and organizational communication, whereas the remote positions asked more for written communication. While the in-person positions had higher expectations of using general data management and analysis tools, the remote positions emphasized more on the use of social media analytics and digital marketing tools.

5.
Chinese Journal of Virology ; 37(6):1283-1291, 2021.
Article in Chinese | GIM | ID: covidwho-2081013

ABSTRACT

On December 15, 2020, four dock workers tested positive for severe acute respiratory syndrome-coronavirus 2 (SARS-COV-2) nucleic acids and were reported by Dalian. Up until then, Dalian City had not reported local cases for 136 consecutive days. In this coronavirus disease 2019 (COVID-19) outbreak (referred to as the "Dalian COVID-19 outbreak"), samples from all infected persons (83) and part from the ship cargoes in contact With them during December 15, 2020 to January 8, 2021 were collected. Confirmed cases accounted for 61.45% (51/83) and asymptomatic infections accounted for 38.55% (32/83). Through high-throughput sequencing, 76 SARS-CoV-2 whole-genome sequences were obtained, of which 72 (86.75%) were from clinical samples, and 4 from cold-chain food packaging surface samples on cargo ship A of country R. Refer to Wuhan reference strain (NC_045512), genome analysis revealed 12-16 nucleotide mutations in 76 whole genomes sharing 12 nucleotide mutations and belong to the SARS-CoV-2 branch of B.1.1. Viral genomics and field epidemiological investigations showed that the Dalian COVID-19 outbreak was a local epidemic caused by dock workers infected with imported cold - chain products contaminated with SARS - CoV - 2. During transmission, 3 Virus generations and three relatively independent transmission chains were formed.

6.
medrxiv; 2022.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2022.09.05.22279589

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).


Subject(s)
Coronavirus Infections , Breakthrough Pain , COVID-19
7.
medrxiv; 2022.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2022.08.29.22279351

ABSTRACT

The serial interval distribution is used to approximate the generation time distribution, an essential parameter to predict the effective reproductive number "Rt", a measure of transmissibility. However, serial interval distributions may change as an epidemic progresses rather than remaining constant. Here we show that serial intervals in Hong Kong varied over time, closely associated with the temporal variation in COVID-19 case profiles and public health and social measures that were implemented in response to surges in community transmission. Quantification of the variation over time in serial intervals led to improved estimation of Rt, and provided additional insights into the impact of public health measures on transmission of infections. One-Sentence SummaryReal-time estimates of serial interval distributions can improve assessment of COVID-19 transmission dynamics and control.


Subject(s)
COVID-19
8.
medrxiv; 2022.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2022.08.05.22278461

ABSTRACT

Background The generation time distribution, reflecting the time between successive infections in transmission chains, is one of the fundamental epidemiological parameters for describing COVID-19 transmission dynamics. However, because exact infection times are rarely known, it is often approximated by the serial interval distribution, reflecting the time between illness onsets of infector and infectee. This approximation holds under the assumption that infectors and infectees share the same incubation period distribution, which may not always be true. Methods We analyzed data on observed incubation period and serial interval distributions in China, during January and February 2020, under different sampling approaches, and developed an inferential framework to estimate the generation time distribution that accounts for variation over time due to changes in epidemiology, sampling biases and public health and social measures. Results We analyzed data on a total of 2989 confirmed cases for COVID-19 during January 1 to February 29, 2020 in Mainland China. During the study period, the empirical forward serial interval decreased from a mean of 8.90 days to 2.68 days. The estimated mean backward incubation period of infectors increased from 3.77 days to 9.61 days, and the mean forward incubation period of infectees also increased from 5.39 days to 7.21 days. The estimated mean forward generation time decreased from 7.27 days (95% confidence interval: 6.42, 8.07) to 4.21 days (95% confidence interval: 3.70, 4.74) days by January 29. We used simulations to examine the sensitivity of our modelling approach to a number of assumptions and alternative dynamics. Conclusions The proposed method can provide more reliable estimation of the temporal variation in the generation time distribution, enabling proper assessment of transmission dynamics.


Subject(s)
COVID-19
9.
researchsquare; 2022.
Preprint in English | PREPRINT-RESEARCHSQUARE | ID: ppzbmed-10.21203.rs.3.rs-1765213.v1

ABSTRACT

Developing multiplex PCR assays requires an extensive amount of experimental testing, the number of which exponentially increases by the number of multiplexed targets. Dedicated efforts must be devoted to the design of optimal multiplex assays for specific and sensitive identification of multiple analytes in a single well reaction. Inspired by data-driven approaches, we reinvent the way of designing and developing multiplex assays by proposing a hybrid, easy-to-use workflow, named Smart-Plexer, which couples empirical testing of singleplex assays and computer simulation of multiplexing. The Smart-Plexer leverages kinetic inter-target distances among amplification curves to generate optimal multiplex PCR primer sets for accurate multi-pathogen identification. The optimal single-channel assays, together with a novel data-driven approach, Amplification Curve Analysis (ACA), were demonstrated to be capable of classifying the presence of desired targets in a single test for seven common respiratory infection pathogens.

10.
biorxiv; 2022.
Preprint in English | bioRxiv | ID: ppzbmed-10.1101.2022.06.06.494494

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may keep patients in a clinically asymptomatic state by blocking cellular innate antiviral immunity, but the molecular mechanism remains unclear. Here, we screened the viral proteins of SARS-CoV-2 and found that the spike (S) protein inhibits the activation of interferon-stimulated genes (ISGs) and even reduces the expression of these genes to below background values. Mechanistically, the S protein interacted with STAT1, STAT2, and IRF9 and impedes the phosphorylation of STAT1/STAT2, thus preventing the formation of the interferon-stimulating gene factor 3 (ISGF3) complex and inhibiting the downstream production of Interferon-stimulated genes (ISGs). Remarkably, we also have found that the inhibitory mechanism of the S protein was conservative among SARS-CoV-2 variants and other human coronaviruses, including SARS-CoV, MERS-CoV, HCoV-229E, HCoV-NL63, and HCoV-HKU1. Truncation studies indicated that the most conserved S2 domain played a major inhibitory role. Altogether, our findings unveil a new mechanism by which SARS-CoV-2 S protein attenuated the host's antiviral immune response and provide new insights into the pathogenic mechanism of coronavirus.


Subject(s)
Coronavirus Infections , Severe Acute Respiratory Syndrome
12.
BMJ : British Medical Journal (Online) ; 368, 2020.
Article in English | ProQuest Central | ID: covidwho-1837197

ABSTRACT

ObjectiveTo delineate the clinical characteristics of patients with coronavirus disease 2019 (covid-19) who died.DesignRetrospective case series.SettingTongji Hospital in Wuhan, China.ParticipantsAmong a cohort of 799 patients, 113 who died and 161 who recovered with a diagnosis of covid-19 were analysed. Data were collected until 28 February 2020.Main outcome measuresClinical characteristics and laboratory findings were obtained from electronic medical records with data collection forms.ResultsThe median age of deceased patients (68 years) was significantly older than recovered patients (51 years). Male sex was more predominant in deceased patients (83;73%) than in recovered patients (88;55%). Chronic hypertension and other cardiovascular comorbidities were more frequent among deceased patients (54 (48%) and 16 (14%)) than recovered patients (39 (24%) and 7 (4%)). Dyspnoea, chest tightness, and disorder of consciousness were more common in deceased patients (70 (62%), 55 (49%), and 25 (22%)) than in recovered patients (50 (31%), 48 (30%), and 1 (1%)). The median time from disease onset to death in deceased patients was 16 (interquartile range 12.0-20.0) days. Leukocytosis was present in 56 (50%) patients who died and 6 (4%) who recovered, and lymphopenia was present in 103 (91%) and 76 (47%) respectively. Concentrations of alanine aminotransferase, aspartate aminotransferase, creatinine, creatine kinase, lactate dehydrogenase, cardiac troponin I, N-terminal pro-brain natriuretic peptide, and D-dimer were markedly higher in deceased patients than in recovered patients. Common complications observed more frequently in deceased patients included acute respiratory distress syndrome (113;100%), type I respiratory failure (18/35;51%), sepsis (113;100%), acute cardiac injury (72/94;77%), heart failure (41/83;49%), alkalosis (14/35;40%), hyperkalaemia (42;37%), acute kidney injury (28;25%), and hypoxic encephalopathy (23;20%). Patients with cardiovascular comorbidity were more likely to develop cardiac complications. Regardless of history of cardiovascular disease, acute cardiac injury and heart failure were more common in deceased patients.ConclusionSevere acute respiratory syndrome coronavirus 2 infection can cause both pulmonary and systemic inflammation, leading to multi-organ dysfunction in patients at high risk. Acute respiratory distress syndrome and respiratory failure, sepsis, acute cardiac injury, and heart failure were the most common critical complications during exacerbation of covid-19.

13.
biorxiv; 2022.
Preprint in English | bioRxiv | ID: ppzbmed-10.1101.2022.04.11.487847

ABSTRACT

ABSTRACT Real-time digital PCR (qdPCR) coupled with artificial intelligence has shown the potential of unlocking scientific breakthroughs, particularly in the field of molecular diagnostics for infectious diseases. One of the most promising applications is the use of machine learning (ML) methods to enable single fluorescent channel PCR multiplex by extracting target-specific kinetic and thermodynamic information contained in amplification curves. However, the robustness of such methods can be affected by the presence of undesired amplification events and nonideal reaction conditions. Therefore, here we proposed a novel framework to filter non-specific and low efficient reactions from qdPCR data using outlier detection algorithms purely based on sigmoidal trends of amplification curves. As a proof-of-concept, this framework is implemented to improve the classification performance of the recently reported ML-based Amplification Curve Analysis (ACA), using available data from a previous publication where the ACA method was used to screen carbapenemase-producing organisms in clinical isolates. Furthermore, we developed a novel strategy, named Adaptive Mapping Filter (AMF), to consider the variability of positive counts in digital PCR. Over 152,000 amplification events were analyzed. For the positive reactions, filtered and unfiltered amplification curves were evaluated by comparing against melting peak distribution, proving that abnormalities (filtered out data) are linked to shifted melting distribution or decreased PCR efficiency. The ACA was applied to compare classification accuracies before and after AMF, showing an improved sensitivity of 1.18% for inliers and 20% for outliers (p-value < 0.0001). This work explores the correlation between kinetics of amplification curves and thermodynamics of melting curves and it demonstrates that filtering out non-specific or low efficient reactions can significantly improve the classification accuracy for cutting edge multiplexing methodologies.


Subject(s)
Space Motion Sickness , Communicable Diseases
14.
biorxiv; 2022.
Preprint in English | bioRxiv | ID: ppzbmed-10.1101.2022.03.29.486173

ABSTRACT

Large-scale populations in the world have been vaccinated with COVID-19 vaccines, however, breakthrough infections of SARS-CoV-2 are still growing rapidly due to the emergence of immune-evasive variants, especially Omicron. It is urgent to develop effective broad-spectrum vaccines to better control the pandemic of these variants. Here, we present a mosaic-type trimeric form of spike receptor-binding domain (mos-tri-RBD) as a broad-spectrum vaccine candidate, which carries the key mutations from Omicron and other circulating variants. Tests in rats showed that the designed mos-tri-RBD, whether used alone or as a booster shot, elicited potent cross-neutralizing antibodies against not only Omicron but also other immune-evasive variants. Neutralizing antibody titers induced by mos-tri-RBD were substantially higher than those elicited by homo-tri-RBD (containing homologous RBDs from prototype strain) or the inactivated vaccine BBIBP-CorV. Our study indicates that mos-tri-RBD is highly immunogenic, which may serve as a broad-spectrum vaccine candidate in combating SARS-CoV-2 variants including Omicron.


Subject(s)
COVID-19 , Breakthrough Pain
15.
researchsquare; 2022.
Preprint in English | PREPRINT-RESEARCHSQUARE | ID: ppzbmed-10.21203.rs.3.rs-1446612.v1

ABSTRACT

Autologous stem cell transplantation (ASCT) is standard of care in biologically fit, newly diagnosed multiple myeloma (MM) patients, offering better therapeutic outcomes and improved quality of life (QoL). However, with the UK’s 1st national lockdown on 23/03/2020, several guidelines recommended deferring ASCT due to risks of infection, with resource limitations forcing some units to suspend ASCT entirely. Such changes to patients’ treatment plans inevitably altered their lived experience during these uncertain times with expected impact on QoL. We conducted a qualitative study using semi-structured interviews to gain insight into MM patients’ understanding of their disease, initial therapy and ASCT, and their response to therapy changes. A clinical snapshot of how COVID-19 affected the MM ASCT service in a single UK institution is also provided, including changes to chemotherapy treatment plans, timing, and prioritisation of ASCT. Framework analysis identified 6 overarching themes: 1) beliefs about ASCT, 2) perceptions of information provided about MM and ASCT, 3) high levels of fear and anxiety due to COVID-19, 4) feelings about ASCT disruption or delay due to COVID-19, 5) perceptions of care and 6) importance of social support. Example subthemes were beliefs that ASCT would provide a long-remission/best chance of normality including freedom from chemotherapy and associated side-effects, disappointment, and devastation at COVID-related treatment delays (despite high anxiety about infection) and exceptionally high levels of trust in the transplant team. Such insights will help us adjust our service and counselling approaches to be more in tune with patients’ priorities and expectations.


Subject(s)
COVID-19
16.
medrxiv; 2022.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2022.03.08.22272062

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.


Subject(s)
Coronavirus Infections , COVID-19
17.
medrxiv; 2022.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2022.03.07.22272036

ABSTRACT

Importance: Ruling out pulmonary embolism (PE) among patients presenting to the Emergency Department (ED) with suspected or confirmed SARS-COV-2 is challenging due to symptom overlap, known increased pro-thrombotic risk, and unclear D-dimer test interpretation. Objective: Our primary objective was to assess the diagnostic accuracy of standard and age-adjusted D-dimer test thresholds for predicting 30-day pulmonary embolism (PE) diagnosis in patients with suspected SARS-COV-2 infection. Design, Setting, and Participants: This was a retrospective observational study using data from 50 sites enrolling patients into the Canadian COVID-19 ED Rapid Response Network (CCEDRRN) registry between March 1, 2020 to July 2, 2021. Adults ([≥]18 years) with SARS-COV-2 testing performed at index ED visit were included if they had any of the following presenting complaints: chest pain, shortness of breath, hypoxia, syncope/presyncope, or hemoptysis. We excluded patients with duplicate records or no valid provincial healthcare number. Main Outcomes and Measures: Our primary end point was 30-day PE diagnosis based on a positive computed tomography pulmonary angiogram (CTPA) or hospital discharge diagnosis code of PE. The outcome measure was the diagnostic accuracy of an age adjusted D-dimer strategy as compared to absolute D-dimer thresholds (500 - 5000 ng/mL). Results: 52,038 patients met inclusion criteria. Age-adjusted D-dimer had a sensitivity (SN) of 96% (95% CI 93-98%) and a specificity (SP) of 48% (95% CI 48-49%) which was comparable to the most sensitive absolute threshold of 500 ng/mL (SN 98%, 95% CI 96-99%; SP 41%, 95% CI 40-42%). Other absolute D-dimer thresholds did not perform well enough for clinical reliability (SN <90%). Both age-adjusted and absolute D-dimer performed better in SARS-COV-2 negative patients as compared to SARS-COV-2 positive patients for predicting 30-day PE diagnosis (c-statistic 0.88 vs 0.80). Conclusions and Relevance: In this large Canadian cohort of ED patients with suspected SARS-COV-2 infection, an age-adjusted D-dimer strategy had similar sensitivity and superior specificity to the most sensitive D-dimer threshold of 500 ng/mL for predicting 30-day PE diagnosis irrespective of SARS-COV-2 infection status. Adopting an age-adjusted D-dimer strategy in patients with suspected SARS-COV-2 may help avoid unnecessary CTPA testing without compromising safety.


Subject(s)
Pulmonary Embolism , Dyspnea , Chest Pain , Hypoxia , Syncope , COVID-19
18.
researchsquare; 2022.
Preprint in English | PREPRINT-RESEARCHSQUARE | ID: ppzbmed-10.21203.rs.3.rs-1266195.v1

ABSTRACT

As the world continues to experience the COVID-19 pandemic, seasonal influenza remain a cause of severe morbidity and mortality globally. Worse yet, coinfection with SARS-CoV-2 and influenza A virus (IAV) leads to more severe clinical outcomes. The development of a combined vaccine against both COVID-19 and influenza is thus of high priority. Based on our established lipid nanoparticle (LNP)-encapsulated mRNA vaccine platform, we developed and characterized a novel mRNA vaccine encoding the HA antigen of influenza A (H1N1) virus, termed ARIAV. Then, ARIAV was combined with our COVID-19 mRNA vaccine ARCoV, which encodes the receptor binding domain (RBD) of the SARS-CoV-2 S protein, to formulate the final combined vaccine, AR-CoV/IAV. Further characterization demonstrated that immunization with two doses of AR-CoV/IAV elicited robust protective antibodies as well as antigen-specific cellular immune responses against SARS-CoV-2 and IAV. More importantly, AR-CoV/IAV immunization protected mice from coinfection with IAV and the SARS-CoV-2 Alpha and Delta variants. Our results highlight the potential of the LNP-mRNA vaccine platform in preventing COVID-19 and influenza, as well as other respiratory diseases.


Subject(s)
COVID-19
19.
medrxiv; 2022.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2021.12.29.21268499

ABSTRACT

Background: The 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. Methods: This 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. Findings: A 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 (20.47%) participants in the heterologous boost groups and 177 (19.64%) 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 89.96% - 97.52% on day 28 post-boosting vaccination, which was much higher than what was induced by homologous boost (36.80% - 81.75%). Similarly, in heterologous NVSI-06-07 booster groups, the neutralizing geometric mean titers (GMTs) against the prototype strain increased by 21.01 - 63.85 folds from baseline to 28 days post-boosting vaccination, whereas only 4.20 - 16.78 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 37.91 (95%CI, 30.35-47.35), however, a significantly higher level of neutralizing antibodies with GMT 292.53 (95%CI, 222.81-384.07) 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. Interpretation: Our 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.


Subject(s)
COVID-19 , Drug-Related Side Effects and Adverse Reactions
20.
biorxiv; 2021.
Preprint in English | bioRxiv | ID: ppzbmed-10.1101.2021.12.21.473594

ABSTRACT

SARS-CoV-2 continued to spread globally along with different variants. Here, we systemically analyzed viral infectivity and immune-resistance of SARS-CoV-2 variants to explore the underlying rationale of viral mutagenesis. We found that the Beta variant harbors both high infectivity and strong immune resistance, while the Delta variant is the most infectious with only a mild immune-escape ability. Remarkably, the Omicron variant is even more immune-resistant than the Beta variant, but its infectivity increases only in Vero E6 cells implying a probable preference for the endocytic pathway. A comprehensive analysis revealed that SARS-CoV-2 spike protein evolved into distinct evolutionary paths of either high infectivity plus low immune resistance or low infectivity plus high immune resistance, resulting in a narrow spectrum of the current single-strain vaccine. In light of these findings and the phylogenetic analysis of 2674 SARS-CoV-2 S-protein sequences, we generated a consensus antigen (S6) taking the most frequent mutations as a pan-vaccine against heterogeneous variants. As compared to the ancestry SWT vaccine with significantly declined neutralizations to emerging variants, the S6 vaccine elicits broadly neutralizing antibodies and full protections to a wide range of variants. Our work highlights the importance and feasibility of a universal vaccine strategy to fight against antigen drift of SARS-CoV-2.

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