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1.
Dent Traumatol ; 2022 May 23.
Article in English | MEDLINE | ID: covidwho-1861304

ABSTRACT

BACKGROUND/AIMS: Pediatric oral and maxillofacial surgeons have faced severe challenges in ward management due to their high risk of exposure during the COVID-19 epidemic. The aim of this study was to analyze and summarize the treatment methods and infection prevention and control measures applied in emergency cases in the Department of Pediatric Oral and Maxillofacial Surgery, Children's Hospital of Chongqing Medical University, during the COVID-19 epidemic. METHODS: In this retrospective study, information was collected from 256 pediatric emergency patients who were treated from January 23, 2020 to August 9, 2021. The patients' data were statistically analyzed according to age, gender, disease and pathogenesis, operation time, and the main treatment applied in pediatric oral and maxillofacial emergency cases during the COVID-19 epidemic. RESULTS: During the epidemic period, 256 pediatric emergency patients were successfully treated. Among them, there were 170 boys and 86 girls. In all, 182 patients were diagnosed with oral or facial lacerations; 43 had jaw fractures; 26 had maxillofacial infections; and five had dento-alveolar fractures. A total of 246 patients underwent surgery under negative pressure with level 3 protection standards. No doctors or patients infected with COVID-19 were found throughout the stury period. CONCLUSIONS: Pediatric oral and maxillofacial emergency in-patients mainly experienced maxillofacial trauma during the COVID-19 epidemic, followed by infection. Effective diagnosis and treatment, and avoidance of COVID-19 infection can be achieved by strictly following epidemic prevention and treatment procedures.

2.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-331897

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.

3.
BMC Geriatr ; 22(1): 181, 2022 03 04.
Article in English | MEDLINE | ID: covidwho-1724420

ABSTRACT

BACKGROUND: Older adults who live alone and have difficulties in activities of daily living (ADLs) may have been more vulnerable during the COVID-19 pandemic. However, little is known about pandemic-related changes in ADL assistance (such as home care, domiciliary care) and its international variation. We examined international patterns and changes in provision of ADL assistance, and related these to country-level measures including national income and health service expenditure. METHODS: We analysed data covering 29 countries from three longitudinal cohort studies (Health and Retirement Study, English Longitudinal Study of Aging, and Survey of Health, Ageing and Retirement in Europe). Eligible people were aged ≥50 years and living alone. Outcomes included ADL difficulty status (assessed via six basic ADLs and five instrumental ADLs) and receipt of ADL assistance. Wealth-related inequality and need-related inequity in ADL assistance were measured using Erreygers' corrected concentration index (ECI). Correlations were estimated between prevalence/inequality/inequity in ADL assistance and national health-related indicators. We hypothesized these measures would be associated with health system factors such as affordability and availability of ADL assistance, as well as active ageing awareness. RESULTS: During COVID-19, 18.4% of older adults living alone reported ADL difficulties (ranging from 8.8% in Switzerland to 29.2% in the USA) and 56.8% of those reporting difficulties received ADL assistance (ranging from 38.7% in the UK to 79.8% in Lithuania). Females were more likely to receive ADL assistance than males in 16/29 countries; the sex gap increased further during the pandemic. Wealth-related ECIs indicated socioeconomic equality in ADL assistance within 24/39 countries before the pandemic, and significant favouring of the less wealthy in 18/29 countries during the pandemic. Needs-related ECIs indicated less equity in assistance with ADLs during the pandemic than before. Our hypotheses on the association between ADL provision measures and health system factors were confirmed before COVID-19, but unexpectedly disconfirmed during COVID-19. CONCLUSION: This study revealed an unequal (and in some countries, partly needs-mismatched) response from countries to older adults living alone during the COVID-19 pandemic. The findings might inform future research about, and policies for, older adults living alone, particularly regarding social protection responses during crises.


Subject(s)
Activities of Daily Living , COVID-19 , Aged , COVID-19/epidemiology , Female , Humans , Longitudinal Studies , Male , Pandemics , SARS-CoV-2
4.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-324780

ABSTRACT

Two typical features of uncontrolled inflammation, cytokine storm and lymphopenia, are associated with the severity of coronavirus disease 2019 (COVID-19), demonstrating that both innate and adaptive immune responses are involved in the development of this disease. Recent studies have explored the contribution of innate immune cells to the pathogenesis of the infection. However, the impact of adaptive immunity on this disease remains unknown. In order to clarify the role of adaptive immune response in COVID-19, we characterized the phenotypes of lymphocytes in PBMCs from patients at different disease stages using single-cell RNA sequencing (scRNA-seq) technology. Dynamics of the effector cell levels in lymphocytes revealed a distinct feature of adaptive immunity in severely affected patients, the coincidence of impaired cellular and enhanced humoral immune responses, suggesting that dysregulated adaptive immune responses advanced severe COVID-19. Excessive activation and exhaustion were observed in CD8 T effector cells, which might contribute to the lymphopenia. Interestingly, expression of Prothymosin alpha (PTMA), the proprotein of Tα1, was significantly increased in a group of CD8 T memory stem cells, but not in excessively activated T cells. We further showed that Tα1 significantly promoted the proliferation of activated T cells in vitro and relieved the lymphopenia in COVID-19 patients. Our data suggest that protection of T cells from excessive activation might be critical for the prevention of severe COVID-19.

5.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-323805

ABSTRACT

Background: Coronavirus disease 2019 is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 is highly transmissible. Early and rapid testing is necessary to effectively prevent and control the outbreak. Detection of SARS-CoV-2 antibodies with lateral flow immunoassay can achieve this goal. Antibody detection is especially effective for the detection of asymptomatic infection. Methods: In this study, SARS-CoV-2 nucleoprotein was expressed by E. coli and purified by affinity chromatography. We used the highly stable and sensitive selenium nanoparticle as the labeling probe coupled with the SARS-CoV-2 nucleoprotein to prepare a new SARS-CoV-2 antibody (IgM and IgG) detection kit. The sensitivity and specificity of the kit were verified by plasma of COVID-19 patients and health persons. Separate detection of IgM and IgG, such as in this assay, was performed in order to reduce mutual interference and improve the accuracy of the test results. Results: The SARS-CoV-2 nucleoprotein was purified on a nickel column, and the final purity was greater than 90%. The sensitivity of the kit was 94.74% and the specificity was 95.12% by 41 negative plasma samples and 19 positive plasma samples detection. Conclusions: The assay kit does not require any special device for reading the results and the readout is a simple color change that can be evaluated with the naked eye. This kit is suitable for rapid and real-time detection of the SARS-CoV-2 antibody.

6.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-315588

ABSTRACT

Medical imaging technologies, including computed tomography (CT) or chest X-Ray (CXR), are largely employed to facilitate the diagnosis of the COVID-19. Since manual report writing is usually too time-consuming, a more intelligent auxiliary medical system that could generate medical reports automatically and immediately is urgently needed. In this article, we propose to use the medical visual language BERT (Medical-VLBERT) model to identify the abnormality on the COVID-19 scans and generate the medical report automatically based on the detected lesion regions. To produce more accurate medical reports and minimize the visual-and-linguistic differences, this model adopts an alternate learning strategy with two procedures that are knowledge pretraining and transferring. To be more precise, the knowledge pretraining procedure is to memorize the knowledge from medical texts, while the transferring procedure is to utilize the acquired knowledge for professional medical sentences generations through observations of medical images. In practice, for automatic medical report generation on the COVID-19 cases, we constructed a dataset of 368 medical findings in Chinese and 1104 chest CT scans from The First Affiliated Hospital of Jinan University, Guangzhou, China, and The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China. Besides, to alleviate the insufficiency of the COVID-19 training samples, our model was first trained on the large-scale Chinese CX-CHR dataset and then transferred to the COVID-19 CT dataset for further fine-tuning. The experimental results showed that Medical-VLBERT achieved state-of-the-art performances on terminology prediction and report generation with the Chinese COVID-19 CT dataset and the CX-CHR dataset. The Chinese COVID-19 CT dataset is available at https://covid19ct.github.io/.

7.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-315331

ABSTRACT

In this paper, we describe our system for the AAAI 2021 shared task of COVID-19 Fake News Detection in English, where we achieved the 3rd position with the weighted F1 score of 0.9859 on the test set. Specifically, we proposed an ensemble method of different pre-trained language models such as BERT, Roberta, Ernie, etc. with various training strategies including warm-up,learning rate schedule and k-fold cross-validation. We also conduct an extensive analysis of the samples that are not correctly classified. The code is available at:https://github.com/archersama/3rd-solution-COVID19-Fake-News-Detection-in-English.

8.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-315318

ABSTRACT

Background: Different clinical classifications of COVID-19 pneumonia patients have different clinical and CT features, which is very important for the treatment after admission. As the epidemic situation in China continues to improve, it is particularly important to re-clarify the correlation between them. Methods: 97 confirmed patients with COVID-19 pneumonia were enrolled from January 17, 2019 to February 21, 2020, including 75 mild/ordinary cases and 22 severe/critical cases. The clinical data and initial chest CT images of the patients were reviewed and compared. The risk factors associated with disease severity were analyzed. Results: Compared with the mild/ordinary patients, the severe/critical patients had older ages, higher incidence of comorbidities, first CT positive, CT always negative and fever. Mild/ordinary patients had lower body temperature than mild/ordinary patients. The incidences of large/multiple GGO in severe/critical patients were significantly higher than those of the mild/ordinary patients, furthermore, severe/critical patients showed higher incidences of 4-5 lobe infections than the ordinary patients. The CT scores of severe/critical patients were significantly higher than those of the ordinary patients ( P < 0.001). The clinical factors of age, sex, comorbidities, hypertension, diabetes mellitus, heart disease, pharyngeal discomfort, abdominal pain/diarrhea, temperature and CT score were risk factors for severe/critical COVID-19 pneumonia. Conclusion: The initial clinical and CT characteristics have certain significance for the clinical classification of COVID-19 respiratory infection. Especially in terms of CT score, it can predict the trend of clinical classification of patients to a certain extent.

9.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-315317

ABSTRACT

AIMTo summarize the chest CT and clinical features of COVID-19 pneumonia patients with hypertension comorbidities.METHODSThe initial chest CT imaging and clinical data of 15 confirmed COVID-19 patients with hypertension comorbidities treated in our hospital were analyzed retrospectively from January 1, 2019 to February 14, 2020. The chest CT images and clinical data were reviewed and their relationship of the disease was analyzed.RESULTSTotally 15 COVID-19 patients diagnosed with hypertension comorbidities were included. In terms of clinical characteristics, 14/15 (93.3%) of patients had characteristics of clustering onset, and the positive rates of the first RT-PCR test and the initial CT were 80% and 93% respectively. The most frequent CT abnormality observed was ground glass opacity (GGO) (13/15, 86.7%), including patchy/ punctate GGO and large/multiple GGO. Most of the lesions were multiple, and 60% of them involved 4-5 lobes. Most patients present with bilateral CT onset (12,80.0%), and most present with subpleural distribution (10,66.7%). The average CT score is 13.7, and 40% of the patients exceeded 20 points.CONCLUSIONThe common chest CT findings in COVID-19 patients with hypertension comorbidities are GGO, most of which at present with bilateral CT onset and subpleural distribution. CT is indispensable in the diagnosis and evaluation of this global health emergency.

10.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-315314

ABSTRACT

Purpose: To compare and analyze the clinical and CT features of coronavirus disease 2019 (COVID-19) among different four age groups. Methods: : 97 patients with chest CT examination and positive reverse transcriptase polymerase chain reaction test (RT-PCR) from January 17, 2019 to February 21, 2020 were reviewed. The first clinical symptoms of each patient were collected and their first chest CT images were observed by dividing them into 4 groups according to age: junior, young, middle-age, and senior. Results: Comorbidities are more common in the senior group. Cluster onset is more common in junior group and senior group. Older patients have shown higher incidence with the highest clinical classification of severe or critical in these 4 groups. Senior patients have a higher incidence of large/multiple ground-glass opacity (GGO). Junior patients are mostly negative for chest CT or involve only one lobe of the lung. While in elderly patients, older patients have a higher incidence of involvement of 4 or 5 lung lobes. The frequency of lobe involvement also has significant differences in 4 different age groups. Conclusion: The clinical and imaging features of patients in different age groups are significantly different. Understanding of these features correctly and making the correct diagnosis promptly is of great significance for the scanning, diagnosis and prevention of COVID-19.

11.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-313410

ABSTRACT

The transmission dynamics of COVID-19 is investigated in this study. A SINDy-LM modeling method that can effectively balance model complexity and prediction accuracy is proposed based on data-driven technique. First, the Sparse Identification of Nonlinear Dynamical systems (SINDy) method is used to discover and describe the nonlinear functional relationship between the dynamic terms in the model in accordance with the observation data of the COVID-19 epidemic. Moreover, the Levenberg–Marquardt (LM) algorithm is utilized to optimize the obtained model for improving the accuracy of the SINDy algorithm. Second, the obtained model, which is consistent with the logistic model in mathematical form with small errors and high robustness, is leveraged to review the epidemic situation in China. Otherwise, the evolution of the epidemic in Australia and Egypt is predicted, which demonstrates that this method has universality for constructing the global COVID-19 model. The proposed model is also compared with the extreme learning machine (ELM), which shows that the prediction accuracy of the SINDy-LM method outperforms that of the ELM method and the generated model has higher sparsity.

12.
Preprint in English | medRxiv | ID: ppmedrxiv-22268891

ABSTRACT

AO_SCPLOWBSTRACTC_SCPLOWO_ST_ABSIntroductionC_ST_ABSOver the past two decades, vaccination programmes for vaccine-preventable diseases (VPDs) have expanded across low- and middle-income countries (LMICs). However, the rise of COVID-19 resulted in global disruption to routine immunisation (RI) activities. Such disruptions could have a detrimental effect on public health, leading to more deaths from VPDs, particularly without mitigation efforts. Hence, as RIs resume, it is important to estimate the effectiveness of different approaches for recovery. MethodsWe apply an impact extrapolation method developed by the Vaccine Impact Modelling Consortium to estimate the impact of COVID-19-related disruptions with different recovery scenarios for ten VPDs across 112 LMICs. We focus on deaths averted due to RIs occurring in the years 2020-2030 and investigate two recovery scenarios relative to a no-COVID-19 scenario. In the recovery scenarios, we assume a 10% COVID-19-related drop in RI coverage in the year 2020. We then linearly interpolate coverage to the year 2030 to investigate two routes to recovery, whereby the immunization agenda (IA2030) targets are reached by 2030 or fall short by 10%. ResultsWe estimate that falling short of the IA2030 targets by 10% leads to 11.26% fewer fully vaccinated persons (FVPs) and 11.34% more deaths over the years 2020-2030 relative to the no-COVID-19 scenario, whereas, reaching the IA2030 targets reduces these proportions to 5% fewer FVPs and 5.22% more deaths. The impact of the disruption varies across the VPDs with diseases where coverage expands drastically in future years facing a smaller detrimental effect. ConclusionOverall, our results show that drops in RI coverage could result in more deaths due to VPDs. As the impact of COVID-19-related disruptions is dependent on the vaccination coverage that is achieved over the coming years, the continued efforts of building up coverage and addressing gaps in immunity are vital in the road to recovery. SUMMARYO_ST_ABSWhat is already known?C_ST_ABSO_LIThe impact of vaccination programmes without COVID-19-related disruption has been assessed by the Vaccine Impact Modelling Consortium. C_LIO_LIThe COVID-19 pandemic has disrupted vaccination programmes resulting in a decline in coverage in the year 2020, the ramifications of this is unclear. C_LI What are the new findings?O_LIWe estimate the impact of disruptions to routine immunisation coverage and different routes to recovery. We compare to a scenario without COVID-19-related disruptions (assuming no drops in immunisation coverage). C_LIO_LIWe estimate that reaching the Immunization Agenda (IA2030) targets leads to 5% fewer FVPs and 5.22% more deaths over the years 2020 to 2030 relative to the scenario with no COVID-19-related disruptions, whereas falling short of the IA2030 targets by 10% leads to 11.26% fewer fully vaccinated persons (FVPs) and 11.34% more deaths. C_LIO_LIThe impact of the disruption varies across the vaccine-preventable diseases with those forecasted to have vast expansions in coverage post-2020 able to recover more. C_LI What do the new findings imply?O_LIA drop in vaccination coverage results in fewer vaccinated individuals and thus more deaths due to vaccine-preventable diseases. To mitigate this, building up coverage of routine immunisations and addressing immunity gaps with activities such as catch-up campaigns are vital in the road to recovery. C_LI

13.
Cureus ; 13(10): e19156, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1513131

ABSTRACT

Background National guidance stipulates the essential components of a safe handover. Shift-based work and the COVID-19 pandemic has led to an increased turnover and re-deployment of staff into new clinical areas, creating challenges in delivering effective handovers. Aim The aim of this quality improvement project (QIP) was to improve adherence to a local standardised handover proforma to improve the quality and consistency of handovers. Methods Handovers were assessed by measuring the completion rates of the essential components of a safe handover as outlined in the national guidance. Data were collected from an electronic handover system which follows the Situation, Background, Assessment and Recommendations (SBAR) structure, and percentage completion rates obtained for each component assessed. Following baseline measurement, four Plan-Do-Study-Act (PDSA) cycles were completed between August 2020 and February 2021 across two junior doctor rotations and during a COVID surge rota. Results A total of 710 handovers were assessed across the four PDSA cycles. There were overall improvements in the percentage completion rates of each component compared to baseline: Under 'Situation', admission dates increased by 13.7%, estimated discharge date by 33.3% and 100% completion rate maintained for the presenting complaint. Under 'Background', past medical history remained static, with a 12.1% increase in documentation of a social history. Under 'Assessment', escalation status increased by 335%, issues list by 242% and important updates by 35.2%. Under 'Recommendations', completion rate for plans was maintained at 100%. Conclusions Our findings demonstrated an overall improvement in the majority of components of the handover proforma. Challenges remain with the rotation of junior doctors through different specialties leading to a loss of institutional knowledge and reduced longevity of the intervention's effect, exacerbated by the introduction of the COVID surge rota. A long-lasting improvement may require a shift to a completely electronic patient records system (ePR) which incorporates a handover tool.

14.
Preprint in English | bioRxiv | ID: ppbiorxiv-455523

ABSTRACT

SARS-CoV-2 infection is initiated with Spike glycoprotein binding to the receptor of human angiotensin converting enzyme 2 via its receptor binding domain. Blocking this interaction is considered as an effective approach to inhibit virus infection. Here we report the discovery of a neutralizing nanobody, VHH60, directly produced from a humanized synthetic nanobody library. VHH60 competes with human ACE2 to bind the receptor binding domain of the Spike protein with a KD of 2.56 nM, inhibits infections of both live SARS-CoV-2 and pseudotyped viruses harboring wildtype, escape mutations and prevailing variants at nanomolar level. VHH60 also suppresses SARS-CoV-2 infection and propagation 50-fold better and protects mice from death two times longer than that of control group after live virus inoculation on mice. VHH60 therefore is a powerful synthetic nanobody with a promising profile for disease control against COVID19.

15.
International Journal of Clinical Pharmacology and Therapeutics ; 58(10):568, 2020.
Article in English | ProQuest Central | ID: covidwho-1287167
16.
Curr Med Sci ; 41(2): 306-311, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1193159

ABSTRACT

This retrospective study aimed to investigate the clinical characteristics and neonatal outcomes of pregnant women with SARS-COV-2 in Wuhan Children's Hospital and further suggested a possible management strategy for infected pregnant women under epidemic situation. In this study, 8 pregnant women with SARS-COV-2 who were admitted into Wuhan Children's Hospital, China from February 1, 2020 to March 30, 2020 and the clinical features, laboratory data, maternal and neonatal outcomes were analyzed. The mean age of the women at the time of admission was 30.6 years. The mean gestational age of the women was 37 weeks+4 days, and one woman presented with dichorionic diamniotic (DCDA) twin pregnancy. Except for one woman who was febrile, others had no typical clinical symptoms. For all pregnant women, the count of white blood cells and lymphocytes appeared normal, but 6 had a lower percentage of lymphocytes. C-reactive protein (CRP) levels were normal for all the women. One neonate was tested positive for the coronavirus IgG and IgM antibodies. The clinical symptoms of the pregnant women with SARS-COV-2 were mild, and the laboratory data showed similar characteristics to those of non-infected pregnant women. Since one neonate was tested positive for coronavirus, there is a possibility of vertical transmission of SARS-CoV-2. Prompt and efficient screening, triage, and isolation of pregnant women are effective management strategies to reduce nosocomial infection during the SARS-COV-2 epidemic.


Subject(s)
COVID-19/epidemiology , Pregnancy Complications, Infectious/epidemiology , SARS-CoV-2/pathogenicity , Adult , COVID-19/complications , COVID-19/physiopathology , COVID-19/virology , China/epidemiology , Female , Humans , Immunoglobulin M/blood , Infant , Infectious Disease Transmission, Vertical/prevention & control , Pregnancy , Pregnancy Complications, Infectious/blood , Pregnancy Complications, Infectious/physiopathology , Pregnancy Complications, Infectious/virology , Pregnant Women , Retrospective Studies
17.
Preprint in English | medRxiv | ID: ppmedrxiv-21250489

ABSTRACT

BackgroundChildhood immunisation services have been disrupted by COVID-19. WHO recommends considering outbreak risk using epidemiological criteria when deciding whether to conduct preventive vaccination campaigns during the pandemic. MethodsWe used 2-3 models per infection to estimate the health impact of 50% reduced routine vaccination coverage and delaying campaign vaccination for measles, meningococcal A and yellow fever vaccination in 3-6 high burden countries per infection. ResultsReduced routine coverage in 2020 without catch-up vaccination may increase measles and yellow fever disease burden in the modelled countries. Delaying planned campaigns may lead to measles outbreaks and increases in yellow fever burden in some countries. For meningococcal A vaccination, short term disruptions in 2020 are unlikely to have a significant impact. ConclusionThe impact of COVID-19-related disruption to vaccination programs varies between infections and countries. FundingBill & Melinda Gates Foundation and Gavi, the Vaccine Alliance Impact statementRoutine and campaign vaccination disruption in 2020 may lead to measles outbreaks and yellow fever burden increases in some countries, but is unlikely to greatly increase meningococcal A burden. SummaryO_ST_ABSBackgroundC_ST_ABSChildhood immunisation services have been disrupted by the COVID-19 pandemic. WHO recommends considering outbreak risk using epidemiological criteria when deciding whether to conduct preventive vaccination campaigns during the pandemic. MethodsWe used 2-3 models per infection to estimate the health impact of 50% reduced routine vaccination coverage in 2020 and delay of campaign vaccination from 2020 to 2021 for measles vaccination in Bangladesh, Chad, Ethiopia, Kenya, Nigeria, and South Sudan, for meningococcal A vaccination in Burkina Faso, Chad, Niger, and Nigeria, and for yellow fever vaccination in the Democratic Republic of Congo, Ghana, and Nigeria. Our counterfactual comparative scenario was sustaining immunisation services at coverage projections made prior to COVID-19 (i.e. without any disruption). FindingsReduced routine vaccination coverage in 2020 without catch-up vaccination may lead to an increase in measles and yellow fever disease burden in the modelled countries. Delaying planned campaigns in Ethiopia and Nigeria by a year may significantly increase the risk of measles outbreaks (both countries did complete their supplementary immunisation activities (SIAs) planned for 2020). For yellow fever vaccination, delay in campaigns leads to a potential disease burden rise of >1 death per 100,000 people per year until the campaigns are implemented. For meningococcal A vaccination, short term disruptions in 2020 are unlikely to have a significant impact due to the persistence of direct and indirect benefits from past introductory campaigns of the 1 to 29-year-old population, bolstered by inclusion of the vaccine into the routine immunisation schedule accompanied by further catch-up campaigns. InterpretationThe impact of COVID-19-related disruption to vaccination programs varies between infections and countries. Planning and implementation of campaigns should consider country and infection-specific epidemiological factors and local immunity gaps worsened by the COVID-19 pandemic when prioritising vaccines and strategies for catch-up vaccination. FundingBill & Melinda Gates Foundation and Gavi, the Vaccine Alliance

20.
Preprint in English | medRxiv | ID: ppmedrxiv-20209114

ABSTRACT

Antibody-dependent enhancement (ADE) has been reported in several virus infections including dengue fever virus, severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronavirus infection. To study whether ADE is involved in COVID-19 infections, in vitro pseudotyped SARS-CoV-2 entry into Raji cells, K562 cells, and primary B cells mediated by plasma from recovered COVID-19 patients were employed as models. The enhancement of SARS-CoV-2 entry into cells was more commonly detected in plasma from severely-affected elderly patients with high titers of SARS-CoV-2 spike protein-specific antibodies. Cellular entry was mediated via the engagement of Fc{gamma}RII receptor through virus-cell membrane fusion, but not by endocytosis. Peptide array scanning analyses showed that antibodies which promote SARS-CoV-2 infection targeted the variable regions of the RBD domain. To further characterize the association between the spike-specific antibody and ADE, an RBD-specific monoclonal antibody (7F3) was isolated from a recovered patient, which potently inhibited SARS-Cov-2 infection of ACE-2 expressing cells and also mediated ADE in Raji cells. Site-directed mutagenesis the spike RBD domain reduced the neutralization activity of 7F3, but did not abolish its binding to the RBD domain. Structural analysis using cryo-electron microscopy (Cryo-EM) revealed that 7F3 binds to spike proteins at a shift-angled pattern with one "up" and two "down" RBDs, resulting in partial overlapping with the receptor binding motif (RBM), while a neutralizing monoclonal antibody that lacked ADE activity binds to spike proteins with three "up" RBDs, resulting in complete overlapping with RBM. Our results revealed that ADE mediated by SARS-CoV-2 spike-specific antibodies could result from binding to the receptor in slightly different pattern from antibodies mediating neutralizations. Studies on ADE using antibodies from recovered patients via cell biology and structural biology technology could be of use for developing novel therapeutic and preventive measures for control of COVID-19 infection.

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