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1.
Frontiers in immunology ; 13, 2022.
Article in English | EuropePMC | ID: covidwho-1958142

ABSTRACT

The receptor-binding domain (RBD) of the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds to the human angiotensin-converting enzyme 2 (ACE2) receptor, which is a prerequisite for the virus to enter the cell. C-reactive protein (CRP) is an important marker of inflammation and is a putative soluble pattern recognition receptor. Clinical elevation of CRP levels in patients with COVID-19 is one of the characteristics of the disease;however, whether CRP is involved in COVID-19 pathogenesis is unknown. Here, we report that monomeric CRP (mCRP) can bind to the SARS-CoV-2 spike RBD and competitively inhibit its binding to ACE2. Furthermore, truncated mutant peptide competition assays and surface plasmon resonance binding experiments showed that the cholesterol-binding sequence (CBS, amino acids 35-47) in mCRP was critical for mediating the binding of mCRP to spike RBD. In a cell model of spike RBD and ACE2 interaction, the CBS motif effectively reduced the binding of spike RBD to ACE2 overexpressed on the cell surface. Thus, this study highlights the pattern recognition function of mCRP in innate immunity and provides a preliminary theoretical basis for the development of the CBS motif in mCRP into a functional peptide with both diagnostic significance and potential therapeutic capabilities.

2.
Preprint in English | medRxiv | ID: ppmedrxiv-22272732

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is known to present with pulmonary and extra-pulmonary organ complications. In comparison with the 2009 pandemic (pH1N1), SARS-CoV-2 infection is likely to lead to more severe disease, with multi-organ effects, including cardiovascular disease. SARS-CoV-2 has been associated with acute and long-term cardiovascular disease, but the molecular changes govern this remain unknown. In this study, we investigated the landscape of cardiac tissues collected at rapid autopsy from SARS-CoV-2, pH1N1, and control patients using targeted spatial transcriptomics approaches. Although SARS-CoV-2 was not detected in cardiac tissue, host transcriptomics showed upregulation of genes associated with DNA damage and repair, heat shock, and M1-like macrophage infiltration in the cardiac tissues of COVID-19 patients. The DNA damage present in the SARS-CoV-2 patient samples, were further confirmed by {gamma}-H2Ax immunohistochemistry. In comparison, pH1N1 showed upregulation of Interferon-stimulated genes (ISGs), in particular interferon and complement pathways, when compared with COVID-19 patients. These data demonstrate the emergence of distinct transcriptomic profiles in cardiac tissues of SARS-CoV-2 and pH1N1 influenza infection supporting the need for a greater understanding of the effects on extra-pulmonary organs, including the cardiovascular system of COVID-19 patients, to delineate the immunopathobiology of SARS-CoV-2 infection, and long term impact on health.

3.
Preprint in English | bioRxiv | ID: ppbiorxiv-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.

4.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-322986

ABSTRACT

Background: Coronavirus disease 2019 (COVID-19) is a worldwide public health pandemic with a high mortality rate, among severe cases. The disease is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. It is important to ensure early detection of the virus to curb disease progression to severe COVID-19. This study aimed to establish a clinical-nomogram model to predict the progression to severe COVID-19 in a timely, efficient manner. Methods This retrospective study included 202 patients with COVID-19 who were admitted to the Fifth Affiliated Hospital of Sun Yat-sen University and Shiyan Taihe Hospital from January 17 to April 30, 2020. The patients were randomly assigned to the training dataset (n = 163, with 43 progressing to severe COVID-19) or the validation dataset (n = 39, with 10 progressing to severe COVID-19) at a ratio of 8:2. The optimal subset algorithm was applied to filter for the clinical factors most relevant to the disease progression. Based on these factors, the logistic regression model was fit to distinguish severe (including severe and critical cases) from non-severe (including mild and moderate cases) COVID-19. Sensitivity, specificity, and area under the curve (AUC) were calculated using the R software package to evaluate prediction performance. A clinical nomogram was established and performance assessed with the discrimination curve. Results Risk factors, including demographics data, symptoms, laboratory and image findings were recorded for the 202 patients. Eight of the 52 variables that were entered into the selection process were selected via the best subset algorithm to establish the predictive model;they included gender, age, BMI, CRP, D-dimer, TP, ALB, and involved-lobe. Sensitivity, specificity and AUC were 0.91, 0.84 and 0.86 for the training dataset, and 0.87, 0.66, and 0.80 for the validation dataset. Conclusions We established an efficient and reliable clinical nomogram model which showed that gender, age, and initial indexes including BMI, CRP, D-dimer, involved-lobe, TP, and ALB could predict the risk of progression to severe COVID-19.

5.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-321465

ABSTRACT

Background: Previous studies showed that the effect of antivirals for COVID-19 was promising but varied across patient population, and was modest among severe cases. Chinese Medicine (CM) was extensively used and reported effective in China, awaiting further evidence support. We aimed to evaluate the real-world effectiveness of add-on semi-individualized.Methods: A retrospective total sampling cohort of 1788 adult confirmed COVID-19 patients were recruited from all 2235 consecutive records retrieved from 5 hospitals in Wuhan during15 January to 13 March 2020. Consultation notes, laboratory/imaging investigations, pharmacy and prognosis records were linked by an electronic medical record system and verified by at least 2 researchers independently. The mortality of add-on semi-individualized CM users and non-users was compared by weighted hazard ratios of multivariable Cox regression and by propensity score matching. Change of biomarkers was compared between groups and the frequency of CMs used was analysed. Subgroup analysis was performed to stratify disease severity and dose of CM exposure. Sensitivity analyses were conducted to test the robustness.Findings: The crude mortality was 3.8% in the semi-individualized CM user group and 17.0% among the non-users. Add-on CM was associated with a significant mortality reduction of 58% (HR=0.42, 95%CI: 0.23 to 0.77, p=0.005) and 66% (HR=0.34, 95%CI: 0.15 to 0.76, p=0.009) among all and severe/critical COVID-19 cases with dose-dependent response, after inversely weighted with propensity score calculated by age, gender, history of hypertension, diabetes, coronary artery disease and disease severity. The result was robust in various stratified, weighted, matched, adjusted and sensitivity analyses. Severe/critical patients received add-on CM had a trend of stabilized D-dimer level after 3-7 days of admission compared to baseline.Interpretation: Add-on semi-individualized CM was associated with reduced mortality demonstrating dose-dependent response, especially among severe/critical COVID-19 patients. Chinese medicine could be considered as an add-on regimen for trial use.Funding Statement: This work is partially supported by the National Key Research and Development Program (2017YFC1703506 and 2020YFC0841600). Declaration of Interests: No financial relationships with any organisations that might have an interest in the submitted work in the previous three years;no other relationships or activities that could appear to have influenced the submitted work.Ethics Approval Statement: This study was approved by the ethics review board of Hubei Provincial Hospital of Traditional Chinese Medicine (HBZY2020-C01-01). Written consent was waived due to the retrospective nature.

6.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-315347

ABSTRACT

The coronavirus disease (COVID-19) is an infectious disease caused by the most recently discovered coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study aims to investigate associations between sunlight and vitamin D, using latitude as an indicator, with COVID-19 cases and related deaths in the United States. General regression and Chi-square test were used to examine the associations between latitude and COVID-19 cases and deaths. The analyses indicated that latitudes were marginally associated with cases (p = 0.0792) and deaths (p = 0.0599), with an increase of 2491 cases and 189 deaths of the total numbers in the mainland of US for every unit of increase of the latitude. When the states were classified into high latitude (>N 370) and low latitude (<N 370) groups, both the cases (702 vs 255 cases/100k population) and deaths (43 vs 11 deaths/100k population) were significantly different (p < 0.001) between the two categories. The results suggested that sunlight and vitamin D, with latitude as an indicator, might be associated with decreased risks for both COVID-19 cases and deaths. These findings warranted urgent needs of large cohort, clinical and pre-clinical studies to assess the impact of VD on the prevention of COVID-19.

7.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-315216

ABSTRACT

Objective: To determine the prevalance and features of olfactory and taste disorders in coronavirus disease of 2019(CoVID-19)patients in China. Methods: A cross-sectional study was performed from 3 April to 15 April 2020 in Wuhan. A total of 187 patients with confirmed severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection completed face-to-face interviews or telephone follow-up. Patients information including epidemiological, clinical, imaging, and serological records and treatment and outcomes data. Patients were further evaluated using questionnaires and visual analogue scale. Statistical analysis was performed with SPSS software (version 22.0). Results: The enrolled 187 patients, 23 (12.3%) reported olfactory disorders, 42 (22.46%) reported taste disorders. Females are more prone to olfactory and taste disorders. Among patients that can clearly describe the fluctuation of olfactory and taste disfunctions, 4 (20.0%) and 7(18.92%) cases occurred before other symptoms appeared, the average number of days in advance was 3.5 and 3.57, respectively. The majority of patients can return to normal or basic normal, but in 4(17.39%) and 9(21.43%) cases olfactory and taste can not fully recoveried during the research period. Conclusions: Prevalence of olfactory and taste disorders substantially lower in China cohorts compared to abroad COVID-19 cohorts. The prevalence of olfactory and taste disorders in COVID-19 patients was higher in females than in males. In some patients, olfactory and taste disorders precede other symptoms and can be used as a symbol for early screening and warning. The restoration of olfactory and taste function was independent of age;females recover more easily than males;olfactory or taste disorders was not easily recovered for patients with clinically classified as severe;when olfactory or taste disorders itself was serious, it was not easy to recover;olfactory or taste disorders occured early in the disease were more likely to be recovered, otherwise they were hard to be recovered.

8.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-312637

ABSTRACT

Background: Tianmen had the highest case-fatality rate (CFR) among all the cities in China early in the transmission of SARS-CoV-2, but little is known about the details of the epidemic in Tianmen. Our study aims to reveal the causes of the high CFR from the aspects of clinical features, medical resources, and epidemic situation.Methods In this study, we report the admission and outcomes of 341 patients with confirmed COVID-19 who were admitted and hospitalized in the hospital (The First People's Hospital of Tianmen) from January 14 to February 25, 2020. Epidemic information and medical resources across different regions were collected and compared. Results All deaths from COVID-19 in Tianmen occurred in the hospital, and the proportion of patients with critical (8.5%) symptoms in the hospital is higher than the average in China. In addition, the number of affected patients in Tianmen is quite low, but the hospital and the whole city had the highest CFR in the early stage of the epidemic. Completely different from the stable CFR in Hubei Province, the CFR of COVID-19 in the hospital and city dropped dramatically, from the largest value in China to a more average level, within a few days. Analysis of government public documents showed that the per capita medical resources in Tianmen are worse than those of Wuhan and Hubei. Conclusions Our findings suggest that the inadequate capacity to respond to public health emergencies caused by relatively scarce health-care resources is a crucial factor contributing to the higher CFR of infectious diseases in regions with lower economic levels. Such countries and territories should implement strategies earlier to minimize the danger of COVID-19.

9.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-325272

ABSTRACT

Background: The coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly spread throughout China and all over the world. Little is known about the dynamic changes in the patient immune responses to SARS-CoV-2, and how different responses are correlated with disease severity and outcomes. Method: 74 patients with confirmed COVID-19 were enrolled in this prospective research. The demographic information, medical history, symptoms, signs and laboratory results were analyzed and compared between severe and non-severe patients. The leukocytes, lymphocyte subsets and inflammatory cytokines were longitudinally collected. Results: : Of the 74 patients included, 17 suffered from severe disease. The severe patients tended be older (65.29 ± 12.33 years vs. 45.37 ± 18.66 years), and had a greater degree of underlying disease (41.18% vs. 24.56%) , lower baseline lymphocytes counts (0.69 ± 0.36 × 10⁹ vs. 1.46 ± 0.75 × 10⁹) , higher neutrophil-lymphocyte-ratios (NLRs;3.76 (3.15–5.51) vs. 2.07 (1.48–2.93)) and lower baseline eosinophil counts (0.01 ± 0.01 × 10⁹ vs. 0.05 ± 0.07 × 10⁹), than that in non-severe patients. The baseline helper T (Th) cells (335.47 vs. 666.46/mL), suppressor T(Ts) cells (158 vs. 334/mL), B cells (95 vs. 210/mL), and natural killer (NK) cells (52 vs. 122/mL) were significantly decreased in severe cases compared to that in non-severe cases. In addition, the baseline neutrophils and B cells were positively correlated with the severity of COVID-19 and the baseline lymphocytes and Th cells were negatively correlated with the severity of COVID-19. The dynamic change of T cells, Th cells and IFN-γ in the severe cases were parallel to the amelioration of the disease. Conclusions: : Collectively, our study provides novel information on the kinetics of the immune responses in a cohort of COVID-19 patients with different disease severities. Furthermore, our study indicates that both innate and adaptive immune responses correlate with better clinical outcomes.

10.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-324779

ABSTRACT

Backgrounds: : To determine the differences in clinical manifestations and biomarker levels of Corona Virus Disease 2019 (COVID-19) patients, including common patients and severe (serious and critical) patients. Methods: A total of 89 COVID-19 patients were diagnosed and treated at the First Affiliated Hospital of Nanchang University. We clinically classified the patients and collected data. Findings: There was a higher proportion of confirmed cases in patients with type A blood (44.8%). There were no obvious differences in number of lung lobes involved in the lesion between the patients with or without a positive nucleic acid test (p>0.05).There were obvious differences in contact history (p<0.001), duration of symptoms (p=0.004), and respiratory rate (p=0.029) between the patients with or without a positive nucleic acid test. According to the results of the nucleic acid diagnosis test, there were no obvious differences in the number of lung lobes involved in the lesion and all items of routine blood, liver, and kidney function tests between the patients with or without positive nucleic acid tests (all p>0.05). Between the common patients and severe patients, there were obvious differences in age (p=0.006), duration of symptoms (p=0.001), diastolic blood pressure (p=0.046), lymphocyte count (p<0.0001), neutrophil count (p=0.019), albumin (p=0.002), lactate dehydrogenase (p=0.007), calcium (p<0.0001), C-reactive protein (CRP) (p=0.004), erythrocyte sedimentation rate (p=0.021), international standard ratio (p=0.020), and CD3 (p=0.001), CD3+CD4 (p=0.006), and CD3+CD8 (p=0.001) levels. In patients infected with SARS-COV-2, the number of lung lobes involved in the lesion were positively correlated with lymphocytes (R=0.261, p=0.044);the body mass index (BMI) values were positively correlated with the number of lung lobes involved in the lesion (R=0.320, P=0.034);the age (R=0.391, p<0.001) and respiratory rate (R=0.352, p=0.001) were positively correlated with neutrophil count;and the age (R=0.349, p=0.001) and the number of lung lobes involved in the lesion (R=0.422, p=0.001) were positively correlated with CRP. Conclusion: Patients with blood type A may be more susceptible to SARS-COV-2. The decrease in lymphocytes may indicate the aggravation of COVID-19, whereas the number of lung lobes involved in the lesion may not be a valid criterion for COVID-19 diagnosis.

11.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-324489

ABSTRACT

We propose a classification method using the radiomics features of CT chest images to identify patients with coronavirus disease 2019 (COVID-19) and other pneumonias. The chest CT images of two groups of participants (90 COVID-19 patients and 90 other pneumonias patients) were collected, and the two groups of data were manually drawn to outline the region of interest (ROI) of pneumonias. The radiomics method was used to extract textural features and histogram features of the ROI and obtain a radiomics features vector from each sample. Finally, using the radiomics features as an input, a support vector machine (SVM) model was constructed to classify patients with COVID-19 and patients with other pneumonias. This model used 20 rounds of 10-fold cross-validation for training and testing. In the COVID-19 patients, correlation analysis (multiple comparison correction—Bonferroni correction, p<0.05/7) was also conducted to determine whether the textural and histogram features were correlated with the laboratory test index of blood, i.e., blood oxygen, white blood cell, lymphocytes, neutrophils, C-reactive protein, hypersensitive C-reactive protein, and erythrocyte sedimentation rate. The results showed that the proposed method had a classification accuracy as high as 88.33%, sensitivity of 83.56%, specificity of 93.11%, and an area under the curve of 0.947. This proved that the radiomics features were highly distinguishable, and this SVM model can effectively identify and diagnose patients with COVID-19 and other pneumonias. The correlation analysis results showed that some texture features were positively correlated with WBC, NE, and CRP and also negatively related to SPO2H and NE.

12.
World journal of clinical cases ; 10(1):104-116, 2022.
Article in English | EuropePMC | ID: covidwho-1640299

ABSTRACT

BACKGROUND Obesity is associated with a better prognosis in patients with community-acquired pneumonia (the so-called obesity survival paradox), but conflicting results have been found. AIM To investigate the relationship between all-cause mortality and body mass index in patients with community-acquired pneumonia. METHODS This retrospective study included patients with community-acquired pneumonia hospitalized in the First Hospital of Qinhuangdao from June 2013 to November 2018. The patients were grouped as underweight (< 18.5 kg/m2), normal weight (18.5-23.9 kg/m2), and overweight/obesity (≥ 24 kg/m2). The primary outcome was all-cause hospital mortality. RESULTS Among 2327 patients, 297 (12.8%) were underweight, 1013 (43.5%) normal weight, and 1017 (43.7%) overweight/obesity. The all-cause hospital mortality was 4.6% (106/2327). Mortality was lowest in the overweight/obesity group and highest in the underweight group (2.8%, vs 5.0%, vs 9.1%, P < 0.001). All-cause mortality of overweight/obesity patients was lower than normal-weight patients [odds ratio (OR) = 0.535, 95% confidence interval (CI) = 0.334-0.855, P = 0.009], while the all-cause mortality of underweight patients was higher than that of normal-weight patients (OR = 1.886, 95%CI: 1.161-3.066, P = 0.010). Multivariable analysis showed that abnormal neutrophil counts (OR = 2.38, 95%CI: 1.55-3.65, P < 0.001), abnormal albumin levels (OR = 0.20, 95%CI: 0.06-0.72, P = 0.014), high-risk Confusion-Urea-Respiration-Blood pressure-65 score (OR = 2.89, 95%CI: 1.48-5.64, P = 0.002), and intensive care unit admission (OR = 3.11, 95%CI: 1.77-5.49, P < 0.001) were independently associated with mortality. CONCLUSION All-cause mortality of normal-weight patients was higher than overweight/ obesity patients, lower than that of underweight patients. Neutrophil counts, albumin levels, Confusion-Urea-Respiration-Blood pressure-65 score, and intensive care unit admission were independently associated with mortality in patients with community-acquired pneumonia.

13.
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.

14.
Preprint in English | bioRxiv | ID: ppbiorxiv-448958

ABSTRACT

The spike (S) protein receptor-binding domain (RBD) of SARS-CoV-2 is an attractive target for COVID-19 vaccine developments, which naturally exists in a trimeric form. Here, guided by structural and computational analyses, we present a mutation-integrated trimeric form of RBD (mutI tri-RBD) as a broadly protective vaccine candidate, in which three RBDs were individually grafted from three different circulating SARS-CoV-2 strains including the prototype, Beta (B.1.351) and Kappa (B.1.617). The three RBDs were then connected end-to-end and co-assembled to possibly mimic the native trimeric arrangements in the natural S protein trimer. The recombinant expression of the mutI tri-RBD, as well as the homo-tri-RBD where the three RBDs were all truncated from the prototype strain, by mammalian cell exhibited correct folding, strong bio-activities, and high stability. The immunization of both the mutI tri-RBD and homo-tri-RBD plus aluminum adjuvant induced high levels of specific IgG and neutralizing antibodies against the SARS-CoV-2 prototype strain in mice. Notably, regarding to the "immune-escape" Beta (B.1.351) variant, mutI tri-RBD elicited significantly higher neutralizing antibody titers than homo-tri-RBD. Furthermore, due to harboring the immune-resistant mutations as well as the evolutionarily convergent hotspots, the designed mutI tri-RBD also induced strong broadly neutralizing activities against various SARS-CoV-2 variants, especially the variants partially resistant to homo-tri-RBD. Homo-tri-RBD has been approved by the China National Medical Products Administration to enter clinical trial (No. NCT04869592), and the superior broad neutralization performances against SARS-CoV-2 support the mutI tri-RBD as a more promising vaccine candidate for further clinical developments.

15.
The International Journal of Sociology and Social Policy ; 40(9/10):939-961, 2020.
Article in English | ProQuest Central | ID: covidwho-1020352

ABSTRACT

PurposeThis paper empirically investigates how cultural variations in individualism and tightness affected the containment of COVID-19 using data from 54 nations during a 30-day period of government intervention.Design/methodology/approachThe authors utilized the hierarchical regression approach to check the effects of three cultural variables – the individualism measure, taken from Hofstede’s six-dimension national culture index, and the measure of cultural tightness, based on the three tightness–looseness indexes calculated by Irem Uz (2015) and their interaction – on the changes in the prevalence rate (ΔPR) and crude mortality rate (ΔCMR) and case fatality rate (CFR) while controlling for the stringency of government responses to COVID-19, median age and population density.FindingsSignificant relationships were found between cultural variables and national performance in slowing the spread of the coronavirus, measured by ΔPR, ΔCMR and CFR. After controlling for the stringency of government responses, median age and population density, the authors found that cultural tightness and individualism as well as their interactions remain to be pivotal. Loose and individualistic cultures led to faster increases in PR and CMR and higher CFR. A four-quadrant conceptual framework is developed to categorize and discuss the national differences.Originality/valueThe paper integrated two constructs – cultural tightness–looseness and individualism–collectivism – to form a theoretical lens to guide the authors’ analyses while using the real-time COVID-19 data as a natural experiment for theorizing and testing. This study’s findings have significant policy implications in government responses, strategic planning, cultural adaptability and policy implementations for the world’s continuous battle against the pandemic.

16.
Complexity ; 2020, 2020.
Article in English | ProQuest Central | ID: covidwho-975734

ABSTRACT

Previous studies revealed that the susceptibility, contacting preference, and recovery probability markedly alter the epidemic outbreak size and threshold. The recovery probability of an infected node is closely related to its obtained resources. How to allocate limited resources to infected neighbors is extremely important for containing the epidemic spreading on complex networks. In this paper, we proposed an epidemic spreading model on complex networks, in which we assume that the node has heterogeneous susceptibility and contacting preference, and susceptible nodes are willing to share their resources to neighbors. Through a developed heterogeneous mean-field theory and a large number of numerical simulations, we find that the recovered nodes provide resources uniformly to their infected neighbor nodes, and the epidemic spreading can be suppressed optimally on homogeneous and heterogeneous networks. Besides, altering the susceptibility and contacting preference does not qualitatively change the results. The susceptibility of the node decreases, which makes the outbreak threshold of epidemic spreading increase, and the outbreak size decreases. Our theory agrees well with the numerical simulations.

17.
SSRN; 2020.
Preprint | SSRN | ID: ppcovidwho-579

ABSTRACT

Background: Tianmen as the city with the highest case-fatality rates (CFR) early in the transmission of SARS-CoV-2, but little is known about the epidemic of Ti

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