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1.
Nature Communications ; 13(1), 2022.
Article in English | ProQuest Central | ID: covidwho-1876946

ABSTRACT

Non-pharmaceutical interventions (NPIs) and vaccination are two fundamental approaches for mitigating the coronavirus disease 2019 (COVID-19) pandemic. However, the real-world impact of NPIs versus vaccination, or a combination of both, on COVID-19 remains uncertain. To address this, we built a Bayesian inference model to assess the changing effect of NPIs and vaccination on reducing COVID-19 transmission, based on a large-scale dataset including epidemiological parameters, virus variants, vaccines, and climate factors in Europe from August 2020 to October 2021. We found that (1) the combined effect of NPIs and vaccination resulted in a 53% (95% confidence interval: 42–62%) reduction in reproduction number by October 2021, whereas NPIs and vaccination reduced the transmission by 35% and 38%, respectively;(2) compared with vaccination, the change of NPI effect was less sensitive to emerging variants;(3) the relative effect of NPIs declined 12% from May 2021 due to a lower stringency and the introduction of vaccination strategies. Our results demonstrate that NPIs were complementary to vaccination in an effort to reduce COVID-19 transmission, and the relaxation of NPIs might depend on vaccination rates, control targets, and vaccine effectiveness concerning extant and emerging variants.Non-pharmaceutical interventions (NPIs) and COVID-19 vaccination have been implemented concurrently, making their relative effects difficult to measure. Here, the authors show that effects of NPIs reduced as vaccine coverage increased, but that NPIs could still be important in the context of more transmissible variants.

2.
Lancet Infect Dis ; 22(4): 483-495, 2022 04.
Article in English | MEDLINE | ID: covidwho-1839434

ABSTRACT

BACKGROUND: Large-scale vaccination against COVID-19 is being implemented in many countries with CoronaVac, an inactivated vaccine. We aimed to assess the immune persistence of a two-dose schedule of CoronaVac, and the immunogenicity and safety of a third dose of CoronaVac, in healthy adults aged 18 years and older. METHODS: In the first of two single-centre, double-blind, randomised, placebo-controlled phase 2 clinical trials, adults aged 18-59 years in Jiangsu, China, were initially allocated (1:1) into two vaccination schedule cohorts: a day 0 and day 14 vaccination cohort (cohort 1) and a day 0 and day 28 vaccination cohort (cohort 2); each cohort was randomly assigned (2:2:1) to either a 3 µg dose or 6 µg dose of CoronaVac or a placebo group. Following a protocol amendment on Dec 25, 2020, half of the participants in each cohort were allocated to receive an additional dose 28 days (window period 30 days) after the second dose, and the other half were allocated to receive a third dose 6 months (window period 60 days) after the second dose. In the other phase 2 trial, in Hebei, China, participants aged 60 years and older were assigned sequentially to receive three injections of either 1·5 µg, 3 µg, or 6 µg of vaccine or placebo, administered 28 days apart for the first two doses and 6 months (window period 90 days) apart for doses two and three. The main outcomes of the study were geometric mean titres (GMTs), geometric mean increases (GMIs), and seropositivity of neutralising antibody to SARS-CoV-2 (virus strain SARS-CoV-2/human/CHN/CN1/2020, GenBank accession number MT407649.1), as analysed in the per-protocol population (all participants who completed their assigned third dose). Our reporting is focused on the 3 µg groups, since 3 µg is the licensed formulation. The trials are registered with ClinicalTrials.gov, NCT04352608 and NCT04383574. FINDINGS: 540 (90%) of 600 participants aged 18-59 years were eligible to receive a third dose, of whom 269 (50%) received the primary third dose 2 months after the second dose (cohorts 1a-14d-2m and 2a-28d-2m) and 271 (50%) received a booster dose 8 months after the second dose (cohorts 1b-14d-8m and 2b-28d-8m). In the 3 µg group, neutralising antibody titres induced by the first two doses declined after 6 months to near or below the seropositive cutoff (GMT of 8) for cohort 1b-14d-8m (n=53; GMT 3·9 [95% CI 3·1-5·0]) and for cohort 2b-28d-8m (n=49; 6·8 [5·2-8·8]). When a booster dose was given 8 months after a second dose, GMTs assessed 14 days later increased to 137·9 (95% CI 99·9-190·4) for cohort 1b-14d-8m and 143·1 (110·8-184·7) 28 days later for cohort 2b-28d-8m. GMTs moderately increased following a primary third dose, from 21·8 (95% CI 17·3-27·6) on day 28 after the second dose to 45·8 (35·7-58·9) on day 28 after the third dose in cohort 1a-14d-2m (n=54), and from 38·1 (28·4-51·1) to 49·7 (39·9-61·9) in cohort 2a-28d-2m (n=53). GMTs had decayed to near the positive threshold by 6 months after the third dose: GMT 9·2 (95% CI 7·1-12·0) in cohort 1a-14d-2m and 10·0 (7·3-13·7) in cohort 2a-28d-2m. Similarly, in adults aged 60 years and older who received booster doses (303 [87%] of 350 participants were eligible to receive a third dose), neutralising antibody titres had declined to near or below the seropositive threshold by 6 months after the primary two-dose series. A third dose given 8 months after the second dose significantly increased neutralising antibody concentrations: GMTs increased from 42·9 (95% CI 31·0-59·4) on day 28 after the second dose to 158·5 (96·6-259·2) on day 28 following the third dose (n=29). All adverse reactions reported within 28 days after a third dose were of grade 1 or 2 severity in all vaccination cohorts. There were three serious adverse events (2%) reported by the 150 participants in cohort 1a-14d-2m, four (3%) by 150 participants from cohort 1b-14d-8m, one (1%) by 150 participants in each of cohorts 2a-28d-2m and 2b-28d-8m, and 24 (7%) by 349 participants from cohort 3-28d-8m. INTERPRETATION: A third dose of CoronaVac in adults administered 8 months after a second dose effectively recalled specific immune responses to SARS-CoV-2, which had declined substantially 6 months after two doses of CoronaVac, resulting in a remarkable increase in the concentration of antibodies and indicating that a two-dose schedule generates good immune memory, and a primary third dose given 2 months after the second dose induced slightly higher antibody titres than the primary two doses. FUNDING: National Key Research and Development Program, Beijing Science and Technology Program, and Key Program of the National Natural Science Foundation of China. TRANSLATION: For the Mandarin translation of the abstract see Supplementary Materials section.


Subject(s)
COVID-19 , Adolescent , Adult , Aged , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Double-Blind Method , Humans , Immunogenicity, Vaccine , Middle Aged , SARS-CoV-2 , Young Adult
3.
Acta Epileptologica ; 4(1), 2022.
Article in English | EuropePMC | ID: covidwho-1837919

ABSTRACT

Background This study was aimed to investigate whether patients with epilepsy (PWE) have higher depression and anxiety levels than the normal population in low-risk areas for coronavirus disease 2019 (COVID-19) in the northern part of Guizhou Province, China, during the COVID-19 epidemic, to evaluate their knowledge on COVID-19, and to analyze related factors for the psychological distress of PWE at this special time. Methods The survey was conducted online from February 28, 2020 to March 7, 2020 via a questionnaire. PWE from the outpatient clinic of epilepsy of the Affiliated Hospital of Zunyi Medical University, and healthy people matched for age and sex, participated in this study. Mental health was assessed via a generalized anxiety self-rating scale (GAD-7) and the self-rating depression scale (PHQ-9). The knowledge of COVID-19 in both groups was investigated. Results There were no significant differences in the general demographics between the PWE and healthy control groups. The scores of PHQ-9 (P < 0.01) and GAD-7 (P < 0.001) were higher in the PWE group than in the healthy group. There was a significant difference in the proportions of respondents with different severities of depression and anxiety, between the two groups, which revealed significantly higher degree of depression and anxiety in PWE than in healthy people (P = 0, P = 0). Overwhelming awareness and stressful concerns for the pandemic and female patients with epilepsy were key factors that affect the level of anxiety and depression in PWE. Further, the PWE had less accurate knowledge of COVID-19 than healthy people (P < 0.001). There was no statistically significant difference between the two groups in the knowledge of virus transmission route, incubation period, susceptible population, transmission speed, clinical characteristics, and isolation measures on COVID-19 (P > 0.05). PWE knew less about some of the prevention and control measures of COVID-19 than healthy people. Conclusions During the COVID-19 epidemic, excessive attention to the epidemic and the female sex are factors associated with anxiety and depression in PWE, even in low-risk areas.

4.
Nat Med ; 2022 May 10.
Article in English | MEDLINE | ID: covidwho-1830085

ABSTRACT

Having adopted a dynamic zero-COVID strategy to respond to SARS-CoV-2 variants with higher transmissibility since August 2021, China is now considering whether, and for how long, this policy can remain in place. The debate has thus shifted towards the identification of mitigation strategies for minimizing disruption to the healthcare system in the case of a nationwide epidemic. To this aim, we developed an age-structured stochastic compartmental susceptible-latent-infectious-removed-susceptible model of SARS-CoV-2 transmission calibrated on the initial growth phase for the 2022 Omicron outbreak in Shanghai, to project COVID-19 burden (that is, number of cases, patients requiring hospitalization and intensive care, and deaths) under hypothetical mitigation scenarios. The model also considers age-specific vaccine coverage data, vaccine efficacy against different clinical endpoints, waning of immunity, different antiviral therapies and nonpharmaceutical interventions. We find that the level of immunity induced by the March 2022 vaccination campaign would be insufficient to prevent an Omicron wave that would result in exceeding critical care capacity with a projected intensive care unit peak demand of 15.6 times the existing capacity and causing approximately 1.55 million deaths. However, we also estimate that protecting vulnerable individuals by ensuring accessibility to vaccines and antiviral therapies, and maintaining implementation of nonpharmaceutical interventions could be sufficient to prevent overwhelming the healthcare system, suggesting that these factors should be points of emphasis in future mitigation policies.

5.
Vaccines (Basel) ; 10(4)2022 Mar 28.
Article in English | MEDLINE | ID: covidwho-1822467

ABSTRACT

New vaccines are being developed in response to the coronavirus disease 2019 (COVID-19) pandemic. Vaccination provides a crucial preventive approach for managing COVID-19. We investigated adults' willingness to take COVID-19 vaccines in the Zhejiang province, and their cognitions regarding COVID-19, when the COVID-19 vaccine is authorized under Emergency Use Administration. An online survey was conducted from September to October 2020, which included social-demographic characteristics, risk perception, acceptance and influencing factors in relation to COVID-19 vaccines. Multivariate logistic regression was performed to identify the influencing factors of vaccination acceptance. Of the participants, 70% intended to be vaccinated when the COVID-19 vaccine was approved under Emergency Use Administration, among 2171 valid questionnaires. Logistic regression revealed that being male, having a high cognitive score regarding COVID-19, the belief that the COVID-19 vaccine is safe and effective, and the belief that one will be infected with SARS-CoV-2 this fall and winter, were associated with a greater probability of accepting vaccination. Respondents with junior college/university education or above were less likely to accept vaccination. Concerns about the safety and effectiveness of the vaccine were the main factors hindering vaccination acceptance. Health education is important for promoting accurate public knowledge regarding COVID-19 vaccination.

6.
J Tradit Complement Med ; 12(1): 73-89, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1814844

ABSTRACT

BACKGROUND AND AIM: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters cells through the binding of the viral spike protein with human angiotensin-converting enzyme 2 (ACE2), resulting in the development of coronavirus disease 2019 (COVID-19). To date, few antiviral drugs are available that can effectively block viral infection. This study aimed to identify potential natural products from Taiwan Database of Extracts and Compounds (TDEC) that may prevent the binding of viral spike proteins with human ACE2 proteins. METHODS: The structure-based virtual screening was performed using the AutoDock Vina program within PyRX software, the binding affinities of compounds were verified using isothermal titration calorimetry (ITC), the inhibitions of SARS-CoV-2 viral infection efficacy were examined by lentivirus particles pseudotyped (Vpp) infection assay, and the cell viability was tested by 293T cell in MTT assay. RESULTS AND CONCLUSION: We identified 39 natural products targeting the viral receptor-binding domain (RBD) of the SARS-CoV-2 spike protein in silico. In ITC binding assay, dioscin, celastrol, saikosaponin C, epimedin C, torvoside K, and amentoflavone showed dissociation constant (K d) = 0.468 µM, 1.712 µM, 6.650 µM, 2.86 µM, 3.761 µM and 4.27 µM, respectively. In Vpp infection assay, the compounds have significantly and consistently inhibition with the 50-90% inhibition of viral infection efficacy. In cell viability, torvoside K, epimedin, amentoflavone, and saikosaponin C showed IC50 > 100 µM; dioscin and celastrol showed IC50 = 1.5625 µM and 0.9866 µM, respectively. These natural products may bind to the viral spike protein, preventing SARS-CoV-2 from entering cells. SECTION 1: Natural Products. TAXONOMY CLASSIFICATION BY EVISE: SARS-CoV-2, Structure-Based Virtual Screening, Isothermal Titration Calorimetry and Lentivirus Particles Pseudotyped (Vpp) Infection Assay, in silico and in vitro study.

7.
J Affect Disord ; 307: 142-148, 2022 06 15.
Article in English | MEDLINE | ID: covidwho-1783445

ABSTRACT

BACKGROUND: The COVID-19 pandemic is associated with an increased risk of mental health problems including suicide in many subpopulations, but its influence on stable patients with major depressive disorder (MDD) has been studied fleetingly. This study examined the one-year prevalence of suicidality including suicidal ideation (SI), suicide plans (SP), and suicide attempts (SA) as well as their correlates in clinically stable MDD patients during the COVID-19 pandemic. METHODS: A cross-sectional, observational study was conducted between October 1, 2020, and October 15, 2021, in six tertiary psychiatric hospitals. Socio-demographic information, clinical data and one-year prevalence of suicidality were recorded. RESULTS: Altogether, 1718 participants who met the eligibility criteria were included. The overall one-year prevalence of suicidality during the COVID-19 pandemic was 68.04% (95% confidence intervals (CI) =65.84-70.25%), with one-year SI prevalence of 66.4% (95%CI = 64.18-68.65%), SP prevalence of 36.26% (95%CI = 33.99-38.54%), and SA prevalence of 39.35% (95%CI = 37.04-41.66%). Binary logistic regression analyses revealed male gender, married marital status, college education level and above and age were negatively associated with risk of suicidality. Urban residence, unemployed work status, experiences of cyberbullying, a history of suicide among family members or friends, and more severe fatigue, physical pain, and residual depressive symptoms were positively associated with risk of suicidality. CONCLUSIONS: Suicidality is common among clinically stable MDD patients during the COVID-19 pandemic. Regular suicide screening and preventive measures should be provided to clinically stable MDD patients during the pandemic.


Subject(s)
COVID-19 , Depressive Disorder, Major , Suicide , Cross-Sectional Studies , Depressive Disorder, Major/epidemiology , Depressive Disorder, Major/psychology , Humans , Male , Pandemics , Prevalence , Risk Factors , Suicidal Ideation
8.
Emerg Microbes Infect ; 11(1): 1205-1214, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-1774288

ABSTRACT

SARS-CoV-2 infection causes most cases of severe illness and fatality in older age groups. Over 92% of the Chinese population aged ≥12 years has been fully vaccinated against COVID-19 (albeit with vaccines developed against historical lineages). At the end of October 2021, the vaccination programme has been extended to children aged 3-11 years. Here, we aim to assess whether, in this vaccination landscape, the importation of Delta variant infections could shift COVID-19 burden from adults to children. We developed an age-structured susceptible-infectious-removed model of SARS-CoV-2 transmission to simulate epidemics triggered by the importation of Delta variant infections and project the age-specific incidence of SARS-CoV-2 infections, cases, hospitalizations, intensive care unit admissions, and deaths. In the context of the vaccination programme targeting individuals aged ≥12 years, and in the absence of non-pharmaceutical interventions, the importation of Delta variant infections could have led to widespread transmission and substantial disease burden in mainland China, even with vaccination coverage as high as 89% across the eligible age groups. Extending the vaccination roll-out to include children aged 3-11 years (as it was the case since the end of October 2021) is estimated to dramatically decrease the burden of symptomatic infections and hospitalizations within this age group (39% and 68%, respectively, when considering a vaccination coverage of 87%), but would have a low impact on protecting infants. Our findings highlight the importance of including children among the target population and the need to strengthen vaccination efforts by increasing vaccine effectiveness.


Subject(s)
COVID-19 , Vaccines , Adult , Aged , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines , Child , China/epidemiology , Humans , Infant , SARS-CoV-2 , Vaccination
9.
BMC Med ; 20(1): 130, 2022 04 04.
Article in English | MEDLINE | ID: covidwho-1770537

ABSTRACT

BACKGROUND: Hundreds of millions of doses of coronavirus disease 2019 (COVID-19) vaccines have been administered globally, but progress on vaccination varies considerably between countries. We aimed to provide an overall picture of COVID-19 vaccination campaigns, including policy, coverage, and demand of COVID-19 vaccines. METHODS: We conducted a descriptive study of vaccination policy and doses administered data obtained from multiple public sources as of 8 February 2022. We used these data to develop coverage indicators and explore associations of vaccine coverage with socioeconomic and healthcare-related factors. We estimated vaccine demand as numbers of doses required to complete vaccination of countries' target populations according to their national immunization program policies. RESULTS: Messenger RNA and adenovirus vectored vaccines were the most commonly used COVID-19 vaccines in high-income countries, while adenovirus vectored vaccines were the most widely used vaccines worldwide (180 countries). One hundred ninety-two countries have authorized vaccines for the general public, with 40.1% (77/192) targeting individuals over 12 years and 32.3% (62/192) targeting those ≥ 5 years. Forty-eight and 151 countries have started additional-dose and booster-dose vaccination programs, respectively. Globally, there have been 162.1 doses administered per 100 individuals in target populations, with marked inter-region and inter-country heterogeneity. Completed vaccination series coverage ranged from 0.1% to more than 95.0% of country target populations, and numbers of doses administered per 100 individuals in target populations ranged from 0.2 to 308.6. Doses administered per 100 individuals in whole populations correlated with healthcare access and quality index (R2 = 0.59), socio-demographic index (R2 = 0.52), and gross domestic product per capita (R2 = 0.61). At least 6.4 billion doses will be required to complete interim vaccination programs-3.3 billion for primary immunization and 3.1 billion for additional/booster programs. Globally, 0.53 and 0.74 doses per individual in target populations are needed for primary immunization and additional/booster dose programs, respectively. CONCLUSIONS: There is wide country-level disparity and inequity in COVID-19 vaccines rollout, suggesting large gaps in immunity, especially in low-income countries.


Subject(s)
COVID-19 Vaccines , COVID-19 , COVID-19/epidemiology , COVID-19/prevention & control , Humans , Immunization Programs , Policy , Vaccination Coverage
10.
SAGE Open Med ; 10: 20503121221086712, 2022.
Article in English | MEDLINE | ID: covidwho-1770146

ABSTRACT

Objective: Mental health problems among children and adolescents are increasingly observed during the outbreak of COVID-19, leading to significant healthcare concerns. Survey studies provide unique opportunities for research during this pandemic, while there are no existing systematic reviews in this setting. The objective was to summarize existing survey studies addressing the effects of the current COVID-19 pandemic on the mental health of children and adolescents. Methods: For this systematic review, we performed an electronic search in multiple databases from December 2019 to December 2020. The quality appraisal of the included studies was performed with the Critical Appraisal Skills Programme Qualitative Checklist. Because of the high methodological heterogeneity between studies, a narrative synthesis of the qualitative data was used. Results: In total, 35 survey studies with 65,508 participants, ranging from 4 to 19 years of age, are included in this review. Anxiety (28%), depression (23%), loneliness (5%), stress (5%), fear (5%), tension (3%), anger (3%), fatigue (3%), confusion (3%), and worry (3%) were the most common mental health issues reported. Children and adolescents with psychiatric and/or developmental disorders, such as severe obesity, chronic lung disease, attention deficit hyperactivity disorder, cystic fibrosis, and obsessive-compulsive disorders, were especially vulnerable to the mental health effects of the COVID-19 pandemic. Age, gender, psychological quality, and negative coping strategies were identified as risk factors for the development of mental health problems. Social and family support, along with a positive coping style, was associated with better outcomes. Conclusion: The impact of the COVID-19 pandemic on mental health of children and adolescents is multifaceted and substantial. Survey studies regarding child and adolescent mental health amid COVID-19 indicated that anxiety, depression, loneliness, stress, and tension are the most observed symptoms. Positive coping strategies with family and social support may be important to achieving better outcomes. Due to limited available evidence, more well-designed studies in this area are urgently needed.

11.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-331890

ABSTRACT

After the adoption of a dynamic zero-COVID strategy in China for nearly two years, whether and for how long this policy can remain in place is unclear. The debate has thus shifted towards the identification of mitigation strategies capable to prevent the disruption of the healthcare system, should a nationwide epidemic caused by the SARS-CoV-2 Omicron variant start to unfold. To this aim, we developed a mathematical model of SARS-CoV-2 transmission tailored to the unique immunization and epidemiological situation of China. We find that the level of immunity induced by the current vaccination campaign would be insufficient to prevent overwhelming the healthcare system and major losses of human lives. Instead, a synergetic strategy would be needed and based on 1) a heterologous booster vaccination campaign, 2) treating 50% of symptomatic cases with an antiviral with an 80% efficacy in preventing severe outcomes, and 3) the adoption of non-pharmaceutical interventions (NPIs) capable of reducing Rt to ≤2. Protecting vulnerable individuals by ensuring accessibility to vaccines and antivirals, and maintaining a certain degree of NPIs should be emphasised in a future mitigation policy, possibly supported by strengthening critical care capacity and the development of highly efficacious vaccines with long-lasting immunity.

12.
Nat Genet ; 54(4): 499-507, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1764190

ABSTRACT

Genomic surveillance has shaped our understanding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. We performed a global landscape analysis on SARS-CoV-2 genomic surveillance and genomic data using a collection of country-specific data. Here, we characterize increasing circulation of the Alpha variant in early 2021, subsequently replaced by the Delta variant around May 2021. SARS-CoV-2 genomic surveillance and sequencing availability varied markedly across countries, with 45 countries performing a high level of routine genomic surveillance and 96 countries with a high availability of SARS-CoV-2 sequencing. We also observed a marked heterogeneity of sequencing percentage, sequencing technologies, turnaround time and completeness of released metadata across regions and income groups. A total of 37% of countries with explicit reporting on variants shared less than half of their sequences of variants of concern (VOCs) in public repositories. Our findings indicate an urgent need to increase timely and full sharing of sequences, the standardization of metadata files and support for countries with limited sequencing and bioinformatics capacity.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/epidemiology , COVID-19/genetics , Genomics , Humans , Information Dissemination , SARS-CoV-2/genetics
13.
Clin Infect Dis ; 74(4): 734-742, 2022 03 01.
Article in English | MEDLINE | ID: covidwho-1707909

ABSTRACT

Recently emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants may pose a threat to immunity. A systematic landscape of neutralizing antibodies against emerging variants is needed. We systematically searched for studies that evaluated neutralizing antibody titers induced by previous infection or vaccination against SARS-CoV-2 variants and collected individual data. We identified 106 studies meeting the eligibility criteria. Lineage B.1.351 (beta), P.1 (gamma) and B.1.617.2 (delta) significantly escaped natural infection-mediated neutralization, with an average of 4.1-fold (95% confidence interval [CI]: 3.6-4.7-fold), 1.8-fold (1.4-2.4-fold), and 3.2-fold (2.4-4.1-fold) reduction in live virus neutralization assay, while neutralizing titers against B.1.1.7 (alpha) decreased slightly (1.4-fold [95% CI: 1.2-1.6-fold]). Serum from vaccinees also led to significant reductions in neutralization of B.1.351 across different platforms, with an average of 7.1-fold (95% CI: 5.5-9.0-fold) for nonreplicating vector platform, 4.1-fold (3.7-4.4-fold) for messenger RNA platform, and 2.5-fold (1.7-2.9-fold) for protein subunit platform. Neutralizing antibody levels induced by messenger RNA vaccines against SARS-CoV-2 variants were similar to, or higher, than that derived from naturally infected individuals.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19 Vaccines/immunology , COVID-19 , SARS-CoV-2 , COVID-19/immunology , COVID-19/prevention & control , Humans , Spike Glycoprotein, Coronavirus/genetics , Vaccination
14.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-323684

ABSTRACT

Background: Studies are needed to provide evidence for the immunization strategy of the COVID-19 vaccine simultaneously administered with the influenza vaccine. Methods: A randomised, open-label, controlled, phase 4 clinical trial was conducted in Zhejiang Province, east of China. Eligible healthy adults aged 18–59 years underwent randomization at a ratio of 1:1:2 to receive one dose of inactivated quadrivalent influenza vaccine (IIV4) either simultaneously with the first (SI1 subgroup, Day 0) or the second (SI2 subgroup, Day 28) dose of CoronaVac, or 14 days after the first dose of CoronaVac (SE group). The primary endpoint of the study was the non-inferiority in seroconversion rate of antibody against SARS-Cov-2 between participants who received two vaccines simultaneously and those who followed the separate vaccination schedule (clinicaltrials.gov number, NCT04801888). Findings: Overall, 480 participants were enrolled, with 120, 120, and 240 randomly assigned to the SI1, SI2, and SE groups, respectively. With the noninferiority margin set at 10%, the seroconversion of antibodies against SARS-CoV-2 in the SI group (93.11% [89.04, 96.01]) was not inferior to that in the SE group (95.15% [91.50, 97.56]) in the per-protocol set. Overall, the geometric mean titer (GMT) in the SE group was higher than that in the SI group with statistical significance (38.06 vs. 27.54, P=0.0001). Within the SI group, the GMT was significantly higher in the SI1 subgroup than that in the SI2 subgroup (32.61 vs 23.26, P=0.0153). The occurrences of vaccine related adverse reactions were comparable among different vaccination groups (16.67% vs. 19.17% and 20.00%, P=0.7568).Interpretation: Simultaneous administration of both SARS-Cov-2 inactivated vaccine and seasonal influenza vaccine would be feasible. Further studies are needed to explain the unexpected decrease of immune response against SARS-CoV-2 following the regimen that IIV4 simultaneously administered with the 2 nd dose of the SARS-CoV-2 inactivated vaccine.Trial Registration: This study was registered at: (clinicaltrials.gov number, NCT04801888).Funding: This study was funded by the Vaccine Clinical Evaluation Platform Construction Project under China National Science and Technology Major Projects [2018ZX09734004] and The Key Research and Development Program of Zhejiang Province (2021C03200).Declaration of Interest: GZ, XD and ZW are employees of Sinovac Biotech CO., Ltd. All other authors declare no competing interests.Ethical Approval: The study protocol and informed consent form were approved by the ethics committee of the Zhejiang Provincial Center for Disease Control and Prevention (ZJCDC).

15.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-323553

ABSTRACT

Background: Coronavirus Disease 2019 (COVID-19) is a novel infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan and has quickly spread across the world. The mortality rate in critically ill patients with COVID-19 is high. This study analyzed clinical and biochemical parameters between mild and severe patients, helping to identify severe or critical patients early. Methods: : In this single center, cross-sectional study, 143 patients were included and divided to mild/moderate and sever/critical groups. Correlation between the disease criticality and clinical features and peripheral blood biochemical markers was analyzed. Cut-off values for critically ill patients were speculated through the ROC curve. Results: : Significantly, disease severity was associated with age (r = 0.458, P < 0.001) , comorbidities (r = 0.445, P < 0.001) , white cell counts (r = 0.229, P = 0.006) , neutrophil count (r = 0.238, P = 0.004) , lymphocyte count (r = -0.295, P < 0.001) , albumin (r = -0.603, P < 0.001) , high-density lipoprotein cholesterol (r= -0.362, P < 0.001) , serum potassium (r = -0.237, P = 0.004) , plasma glucose (r = 0.383, P < 0.001) , total bilirubin (r = 0.340, P < 0.001) , serum amyloid A (r = 0.58, P < 0.001) , procalcitonin (r = 0.345, P < 0.001) , C-reactive protein ( r = 0.477, P < 0.001) , lactate dehydrogenase (r = 0.548, P < 0.001) , aspartate aminotransferase (r = 0.342, P < 0.001) , alanine aminotransferase (r = 0.264, P = 0.001) , erythrocyte sedimentation rate (r = 0.284, P = 0.001) and D-dimer (r = 0.477, P < 0.001) . Conclusion: With following parameters such as age > 52 years, C-reactive protein > 64.79 mg/L, lactate dehydrogenase > 245 U/L, D-dimer > 0.96 ug/mL, serum amyloid A > 100.02 mg/L, or albumin < 36 g/L, the progress of COVID-19 to critical stage should be closely observed and possibly prevented. Lymphocyte count, serum potassium and procalcitonin may also be a prognostic indicator.

16.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-323552

ABSTRACT

Background: Coronavirus disease 2019 ( COVID-19 ) is a novel infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan and has quickly spread across the world. The mortality rate in critically ill patients with COVID-19 is high. This study analyzed clinical and biochemical parameters between mild and severe patients, helping to identify severe or critical patients early. Methods: In this single center, cross-sectional study, 143 patients were included and divided to mild/moderate and sever/critical groups. Correlation between the disease criticality and clinical features and peripheral blood biochemical markers was analyzed. Cut-off values for critically ill patients were speculated through the ROC curve. Results: Significantly, disease severity was associated with age (r = 0.458, P < 0.001) , comorbidities (r = 0.445, P < 0.001) , white cell counts (r = 0.229, P = 0.006) , neutrophil count (r = 0.238, P = 0.004) , lymphocyte count (r = -0.295, P < 0.001) , albumin (r = -0.603, P < 0.001) , high-density lipoprotein cholesterol (r= -0.362, P < 0.001) , serum potassium (r = -0.237, P = 0.004) , plasma glucose (r = 0.383, P < 0.001) , total bilirubin (r = 0.340, P < 0.001) , serum amyloid A (r = 0.58, P < 0.001) , procalcitonin (r = 0.345, P < 0.001) , C-reactive protein ( r = 0.477, P < 0.001) , lactate dehydrogenase (r = 0.548, P < 0.001) , aspartate aminotransferase (r = 0.342, P < 0.001) , alanine aminotransferase (r = 0.264, P = 0.001) , erythrocyte sedimentation rate (r = 0.284, P = 0.001) and D-dimer (r = 0.477, P < 0.001) . Conclusion: With following parameters such as age > 52 years, C-reactive protein > 64.79 mg/L, lactate dehydrogenase > 245 U/L, D-dimer > 0.96 ug/mL, serum amyloid A > 100.02 mg/L, or a lbumin < 36 g/L, the progress of COVID-19 to critical stage should be closely observed and possibly prevented. Lymphocyte count, serum potassium and procalcitonin may also be a prognostic indicator .

17.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-307599

ABSTRACT

Preliminary results from the RECOVERY trial indicated that dexamethasone usage markedly reduced death rate in COVID-19 patients receiving invasive mechanical ventilation. However, the overall reduction for the entire patient cohort in that trial was much more modest, indicating highly variable effects of corticosteroid usage among COVID-19 patients. While steroid treatment is known to have both clinical efficacy and detrimental adverse-effects, defining a clinic parameter that could guide the beneficial corticosteroid usage for treating COVID-19 remains an elusive, urgent, and critical unmet need in COVID-19 therapy. Here, we undertook a multicentered retrospective study on a cohort of 12,862 confirmed COVID-19 cases from 21 hospitals in Hubei Province, China, including 3,254 received corticosteroid treatment and 9,608 received usual care without corticosteroid. We uncovered that the clinical benefits of corticosteroid use were closely associated with the neutrophil-to-lymphocyte ratio (NLR) measured at admission. Among participants with NLR > 6.12 at admission, corticosteroid treatment was significantly associated with a lower risk of 60-day all-cause mortality of COVID-19 based on both Cox model with time-varying exposure and Marginal Structural Model. However, in patients with NLR ≤ 6.12 at admission, corticosteroid treatment was no longer associated with reduced risk of all-cause death, but rather with increased risks of severe adverse effects, particularly in hyperglycemia and infection. In diabetic patients with COVID-19, corticosteroid treatment was associated with increased glycemia, but not with a higher risk of 60-day mortality. Therefore, our study has uncovered NLR as a clinical indicator to stratify COVID-19 patients in their response to corticosteroid therapy. This finding may assist clinical evaluation and future randomized controlled trials to establish proper guidelines for corticosteroid therapy in COVID-19 patients.

18.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-325293

ABSTRACT

Introduction: China is facing substantial risks of imported COVID-19 cases and a domestic resurgence in the long run, and COVID-19 vaccination is expected to be the long-lasting solution to end the pandemic. We aim to estimate the size of the target population for COVID-19 vaccination at the provincial level and summarize the current progress of vaccination programs, which could support local governments in the timely determination and adjustment of vaccination policies and promotional measures. Methods: By extracting provincial-stratified data from publicly available sources, we estimated the size of priority target groups for vaccination programs and further characterized the ongoing COVID-19 vaccination program at the provincial level, including the total doses administered, the coverage rate, and the vaccination capacity needed to achieve the target coverage of 70%. Results: The size of the target population shows large differences among provinces, ranging from 3.5 million to 115.2 million. As of June 10, the speed of vaccine roll-out differs remarkably as well, with the highest coverage occurring in Beijing and Shanghai, where 69.8% and 62.3% of the population is fully vaccinated, respectively. However, in 19 of 31 provinces, less than 40% of the population was administered at least one dose, in 9 of which the proportion was even less than 30%. Compared to the routine vaccination capacity before the COVID-19 pandemic, the COVID-19 vaccination capacity has greatly improved. Nevertheless, the current vaccination capacity is far lower than the target of 70% coverage by the end of 2021 or by mid-2022 in approximately 5%-20% of provinces, particularly the Guizhou, Yunnan, Xinjiang, Fujian and Hebei provinces. Conclusions: Large disparities exist in the target population size and vaccination progress across provinces in China. Vaccine coverage is far from meeting the herd immunity threshold, and the vaccination service capacity needs to be further improved.

19.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-324768

ABSTRACT

Strategic prioritization of COVID-19 vaccines is urgently needed, especially in light of the limited supply that is expected to last for most, if not the entire, 2021. Dynamically adapting the allocation strategy to the evolving epidemiological situation could thus be critical during this initial phase of vaccine rollout. We developed a data-driven mechanistic model of SARS-CoV-2 transmission to explore optimal vaccine prioritization strategies in China that aim at reducing COVID-19 burden measured through different metrics. We found that reactively adapting the vaccination program to the epidemiological situation (i.e., allocate vaccine to a target group before reaching full coverage of other groups with initial higher priority) can be highly beneficial as such strategies are capable to simultaneously achieve different objectives (e.g., minimizing the number of deaths and of infections). The highest priority categories are broadly consistent under different hypotheses about vaccine efficacy, differential vaccine efficacy in preventing infection vs. disease, vaccine hesitancy, and SARS-CoV-2 transmissibility. Our findings also suggest that boosting the daily capacities up to 2.5 million courses (0.17% rollout speed) or higher could greatly reduce COVID-19 burden should a new wave start to unfold in China with reproduction number equal to 1.5 or lower. Finally, we estimate that a high vaccine supply in the early phase of the vaccination campaign is key to achieve large gains of strategic prioritizations.

20.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-324469

ABSTRACT

All countries are facing decisions about which groups to prioritise for COVID-19 vaccination after the first vaccine product has been licensed, at which time supply shortages are inevitable. Here we define the key target populations and their size in China for a phased introduction of COVID-19 vaccination with evolving goals, accounting for the risk of illness and transmission. Essential workers (47.2 million) like healthcare workers could be prioritized for vaccination to maintain essential services. Subsequently, older adults, individuals with underlying health conditions and pregnant women (616.0 million) could be targeted to reduce severe COVID-19 outcomes. Then it could be further extended to target adults without underlying health conditions and children (738.7 million) to reduce symptomatic infections and/or to stop virus transmission. The proposed framework could assist Chinese policy-makers in the design of a vaccination program, and could be generalized to inform other national and regional COVID-19 vaccination strategies.

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