Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 38
Filter
1.
Computational and mathematical methods in medicine ; 2022, 2022.
Article in English | EuropePMC | ID: covidwho-1989755

ABSTRACT

COVID-19 has become the largest public health event worldwide since its outbreak, and early detection is a prerequisite for effective treatment. Chest X-ray images have become an important basis for screening and monitoring the disease, and deep learning has shown great potential for this task. Many studies have proposed deep learning methods for automated diagnosis of COVID-19. Although these methods have achieved excellent performance in terms of detection, most have been evaluated using limited datasets and typically use a single deep learning network to extract features. To this end, the dual asymmetric feature learning network (DAFLNet) is proposed, which is divided into two modules, DAFFM and WDFM. DAFFM mainly comprises the backbone networks EfficientNetV2 and DenseNet for feature fusion. WDFM is mainly for weighted decision-level fusion and features a new pretrained network selection algorithm (PNSA) for determination of the optimal weights. Experiments on a large dataset were conducted using two schemes, DAFLNet-1 and DAFLNet-2, and both schemes outperformed eight state-of-the-art classification techniques in terms of classification performance. DAFLNet-1 achieved an average accuracy of up to 98.56% for the triple classification of COVID-19, pneumonia, and healthy images.

2.
Preprint in English | bioRxiv | ID: ppbiorxiv-502029

ABSTRACT

Summary ParagraphDespite effective countermeasures, SARS-CoV-2 persists worldwide due to its ability to diversify and evade human immunity1. This evasion stems from amino-acid substitutions, particularly in the receptor-binding domain of the spike, that confer resistance to vaccines and antibodies 2-16. To constrain viral escape through resistance mutations, we combined antibody variable regions that recognize different receptor binding domain (RBD) sites17,18 into multispecific antibodies. Here, we describe multispecific antibodies, including a trispecific that prevented virus escape >3000-fold more potently than the most effective clinical antibody or mixtures of the parental antibodies. Despite being generated before the evolution of Omicron, this trispecific antibody potently neutralized all previous variants of concern and major Omicron variants, including the most recent BA.4/BA.5 strains at nanomolar concentrations. Negative stain electron microscopy revealed that synergistic neutralization was achieved by engaging different epitopes in specific orientations that facilitated inter-spike binding. An optimized trispecific antibody also protected Syrian hamsters against Omicron variants BA.1, BA.2 and BA.5, each of which uses different amino acid substitutions to mediate escape from therapeutic antibodies. Such multispecific antibodies decrease the likelihood of SARS-CoV-2 escape, simplify treatment, and maximize coverage, providing a strategy for universal antibody therapies that could help eliminate pandemic spread for this and other pathogens.

3.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-335237

ABSTRACT

Summary Background People living with chronic disease, particularly seniors older than 60 years old, are lagging behind in the national vaccination campaign in China due to uncertainty of safety and effectiveness. However, this special population made up of most severe symptom and death cases among infected patients and should be prioritized in vaccination program. In this retrospective study, we assessed the safety and immunogenicity of the CoronaVac inactivated vaccines in people with underlying medical conditions to address the vaccine hesitation in this special population. Methods In this cohort study, volunteers aged 40 years and older, had received two doses of CoronaVac inactivated vaccines (3-5 weeks interval), been healthy or with at least one of the six diseases: coronary heart disease (CAD), hypertension, diabetes mellitus (DM), chronic respiratory disease (CRD), obesity and cancer, were recruited from 4 study sites in China. The primary safety outcome was the incidence of adverse events within 14 days after each dose of vaccination. The primary immunogenic outcome was geometric mean titer (GMT) of neutralizing antibodies to living SARS-CoV-2 virus at 14-28 days, 3 months, and 6 months after full two-dose vaccination. This study is registered with ChiCTR.org.cn (ChiCTR2200058281) and is active but no longer recruiting. Findings Among 1,302 volunteers screened between Jul 5 and Dec 30, 2021, 969 were eligible and enrolled in our cohort, including 740 living with underlying medical conditions and 229 as healthy control. All of them formed the safety cohort. The overall incidence of adverse reactions was 150 (20.27%) of 740 in the comorbidities group versus 32 (13.97%) of 229 in the healthy group, with significant difference (P=0.0334). The difference was mainly contributed by fatigue and injection-site pain in some groups. Most adverse reactions were mild (Grade 1). We did not observe any serious adverse events related to vaccination. By day 14-28 post vaccination, the seroconversion rates and GMT of neutralizing antibody showed no significant difference between disease group and healthy group, except CAD group (P=0.03) and CRD group (P=0.04) showed slight reduction. By day 90, the neutralizing antibody GMTs were significantly reduced in each group, with no significant difference between diseases and healthy group. By day 180, the neutralizing antibody continued to decrease in each group, but with slower declination. Interpretation For people living with chronic disease especially seniors older than 60 years, the CoronaVac vaccines are as safe as in healthy people. Although the immunogenicity is slightly different in subgroup of some diseases compared with that of the healthy population, the overall trend was consistent. Our findings highlight the evidence to address vaccine hesitancy for seniors and people living with chronic diseases. Funding Yunnan Provincial Science and Technology Department (202102AA100051 and 202003AC100010, China), Sinovac Biotech Ltd (PRO-nCOV-4004).

4.
Preprint in English | bioRxiv | ID: ppbiorxiv-486152

ABSTRACT

An important consequence of infection with a SARS-CoV-2 variant is protective humoral immunity against other variants. The basis for such cross-protection at the molecular level is incompletely understood. Here we characterized the repertoire and epitope specificity of antibodies elicited by Beta, Gamma and ancestral variant infection and assessed their cross-reactivity to these and the more recent Delta and Omicron variants. We developed a high-throughput approach to obtain immunoglobulin sequences and produce monoclonal antibodies for functional assessment from single B cells. Infection with any variant elicited similar cross-binding antibody responses exhibiting a remarkably conserved hierarchy of epitope immunodominance. Furthermore, convergent V gene usage and similar public B cell clones were elicited regardless of infecting variant. These convergent responses despite antigenic variation may represent a general immunological principle that accounts for the continued efficacy of vaccines based on a single ancestral variant.

5.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-324523

ABSTRACT

Despite tremendous efforts, it is very challenging to generate a robust model to assist in the accurate quantification assessment of COVID-19 on chest CT images. Due to the nature of blurred boundaries, the supervised segmentation methods usually suffer from annotation biases. To support unbiased lesion localisation and to minimise the labeling costs, we propose a data-driven framework supervised by only image-level labels. The framework can explicitly separate potential lesions from original images, with the help of a generative adversarial network and a lesion-specific decoder. Experiments on two COVID-19 datasets demonstrate the effectiveness of the proposed framework and its superior performance to several existing methods.

6.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-324166

ABSTRACT

Utilizing computed tomography (CT) images to quickly estimate the severity of cases with COVID-19 is one of the most straightforward and efficacious methods. Two tasks were studied in this present paper. One was to segment the mask of intact lung in case of pneumonia. Another was to generate the masks of regions infected by COVID-19. The masks of these two parts of images then were converted to corresponding volumes to calculate the physical proportion of infected region of lung. A total of 129 CT image set were herein collected and studied. The intrinsic Hounsfiled value of CT images was firstly utilized to generate the initial dirty version of labeled masks both for intact lung and infected regions. Then, the samples were carefully adjusted and improved by two professional radiologists to generate the final training set and test benchmark. Two deep learning models were evaluated: UNet and 2.5D UNet. For the segment of infected regions, a deep learning based classifier was followed to remove unrelated blur-edged regions that were wrongly segmented out such as air tube and blood vessel tissue etc. For the segmented masks of intact lung and infected regions, the best method could achieve 0.972 and 0.757 measure in mean Dice similarity coefficient on our test benchmark. As the overall proportion of infected region of lung, the final result showed 0.961 (Pearson's correlation coefficient) and 11.7% (mean absolute percent error). The instant proportion of infected regions of lung could be used as a visual evidence to assist clinical physician to determine the severity of the case. Furthermore, a quantified report of infected regions can help predict the prognosis for COVID-19 cases which were scanned periodically within the treatment cycle.

7.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-322243

ABSTRACT

Chest computed tomography (CT) becomes an effective tool to assist the diagnosis of coronavirus disease-19 (COVID-19). Due to the outbreak of COVID-19 worldwide, using the computed-aided diagnosis technique for COVID-19 classification based on CT images could largely alleviate the burden of clinicians. In this paper, we propose an Adaptive Feature Selection guided Deep Forest (AFS-DF) for COVID-19 classification based on chest CT images. Specifically, we first extract location-specific features from CT images. Then, in order to capture the high-level representation of these features with the relatively small-scale data, we leverage a deep forest model to learn high-level representation of the features. Moreover, we propose a feature selection method based on the trained deep forest model to reduce the redundancy of features, where the feature selection could be adaptively incorporated with the COVID-19 classification model. We evaluated our proposed AFS-DF on COVID-19 dataset with 1495 patients of COVID-19 and 1027 patients of community acquired pneumonia (CAP). The accuracy (ACC), sensitivity (SEN), specificity (SPE) and AUC achieved by our method are 91.79%, 93.05%, 89.95% and 96.35%, respectively. Experimental results on the COVID-19 dataset suggest that the proposed AFS-DF achieves superior performance in COVID-19 vs. CAP classification, compared with 4 widely used machine learning methods.

8.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-315381

ABSTRACT

How to fast and accurately assess the severity level of COVID-19 is an essential problem, when millions of people are suffering from the pandemic around the world. Currently, the chest CT is regarded as a popular and informative imaging tool for COVID-19 diagnosis. However, we observe that there are two issues -- weak annotation and insufficient data that may obstruct automatic COVID-19 severity assessment with CT images. To address these challenges, we propose a novel three-component method, i.e., 1) a deep multiple instance learning component with instance-level attention to jointly classify the bag and also weigh the instances, 2) a bag-level data augmentation component to generate virtual bags by reorganizing high confidential instances, and 3) a self-supervised pretext component to aid the learning process. We have systematically evaluated our method on the CT images of 229 COVID-19 cases, including 50 severe and 179 non-severe cases. Our method could obtain an average accuracy of 95.8%, with 93.6% sensitivity and 96.4% specificity, which outperformed previous works.

9.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-309728

ABSTRACT

Purpose: Persistent negative results (at least 3 times) of reverse transcription–polymerase chain reaction (RT-PCR) from pharyngeal swabs are not rare in coronavirus disease 2019 (COVID-19) patients, but their characteristics have not yet been well studied. Methods: PCR confirmed, serum antibody confirmed with persistent negative PCR results, and clinically diagnosed patients hospitalized in two medical centers during February and March 2020 were included. Differences in clinical, imaging and laboratory characteristics as well as factors affecting their prognosis were analyzed. Results: There were 114 PCR confirmed, 17 serology confirmed and 21 clinically diagnosed patients included. Time from onset of disease to the first PCR and admission were similar among the groups. Compared with PCR-confirmed patients, serology-confirmed patients were older and likely to have hypertension, vomiting, or symptoms of chest pain and dyspnea. Regarding imaging manifestations, serology-confirmed patients were more prone to pleural effusion. In addition, higher levels of C-reactive protein, neutrophil-to-lymphocyte ratio, total bilirubin, D-dimer, fibrinogen, troponin, interleukin-6 and IL-8 were also found. Although with similar mortality, serology confirmed patients were more likely to have disease progression. High levels of D-dimer and IL-6 were possibly the underlying factors leading to their worse prognosis. On the other hand, clinically diagnosed patients were more similar to PCR-confirmed patients. Conclusion: Serology confirmed COVID-19 patients with at least three negative PCR results had different clinical characteristics and were likely to have disease progression, possibly due to more severe hypercoagulation status and cytokine storm.

10.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-325060

ABSTRACT

Background: In December 2019, the outbreak of a disease subsequently termed COVID-19 occurred in Wuhan, China. The number of cases increased rapidly and spread to six continents. However, there is limited information on the chest computed tomography (CT) results of affected patients. Chest CT can assess the severity of COVID-19 and has sufficient sensitivity to assess changes in response to glucocorticoid therapy. Objective: Analyze COVID-19 patients to determine the relationships of clinical characteristics, chest CT score, and levels of inflammatory mediators . Methods: : This retrospective, single-center case series of 108 consecutive hospitalized patients with confirmed COVID-19 at Tongji Hospital, Tongji Medical College of HUST (Wuhan, China) examined patients admitted from January 1 to January 28, 2020. Patient demographics, comorbidities, clinical findings, chest CT results, and CT scores of affected lung parenchyma were recorded. The relationships between chest CT score with levels of systemic inflammatory mediators were determined. Results: : All patients exhibited signs of significant systemic inflammation, including increased levels of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), procalcitonin, chest CT score, and a decreased lymphocyte (LY) count. Chest CT score had positive associations with white blood cell (WBC) count, CRP, ESR, procalcitonin, and abnormal coagulation function, and a negative association with LY count. Treatment with a glucocorticoid increased the LY count, reduced the CT score and CRP level, and improved coagulation function. Conclusions: : COVID-19 infection is characterized by a systemic inflammatory response that affects the lungs, blood, digestive system, and circulatory systems. The chest CT score is a good indicator of the extent of systemic inflammation. Glucocorticoid treatment appears to reduce systemic inflammation in these patients.

11.
J Clin Sleep Med ; 18(2): 541-551, 2022 02 01.
Article in English | MEDLINE | ID: covidwho-1675134

ABSTRACT

STUDY OBJECTIVES: The applicability of sleep-related scales to frontline medical staff for the COVID-19 pandemic has not been fully proved, so sleep survey results lack credibility and accuracy, creating difficulties for the guidance and treatment of frontline medical staff with sleep disorders, which is not conducive to the prevention and control of COVID-19. This study sought to analyze the reliability and validity of the Pittsburgh Sleep Quality Index (PSQI) among frontline medical staff fighting the COVID-19 pandemic. METHODS: A network questionnaire survey was used to investigate the PSQI among frontline medical staff who fought COVID-19 in Wuhan, China from March 19 to April 15, 2020. Combined with classical test theory and item response theory, the content validity, internal consistency, construct validity, and other aspects of the PSQI were evaluated. RESULTS: According to classical test theory, content validity, criterion validity, and construct validity of the PSQI were good. But the internal consistency was better after the deletion of the "daytime dysfunction" subscale. With regard to item response theory, difficulty, the differential item function, and the Wright map performed well. CONCLUSIONS: The original PSQI showed acceptable applicability in frontline COVID-19 medical staff, and its characteristics moderately improved after the "daytime dysfunction" subscale was removed. CITATION: Wang L, Wu Y-X, Lin Y-Q, et al. Reliability and validity of the Pittsburgh Sleep Quality Index among frontline COVID-19 health care workers using classical test theory and item response theory. J Clin Sleep Med. 2022;18(2):541-551.


Subject(s)
COVID-19 , Health Personnel , Humans , Pandemics , Reproducibility of Results , SARS-CoV-2 , Surveys and Questionnaires
12.
Preprint in English | bioRxiv | ID: ppbiorxiv-479037

ABSTRACT

SARS-CoV-2 Omicron is highly transmissible and has substantial resistance to antibody neutralization following immunization with ancestral spike-matched vaccines. It is unclear whether boosting with Omicron-specific vaccines would enhance immunity and protection. Here, nonhuman primates that received mRNA-1273 at weeks 0 and 4 were boosted at week 41 with mRNA-1273 or mRNA-Omicron. Neutralizing antibody titers against D614G were 4760 and 270 reciprocal ID50 at week 6 (peak) and week 41 (pre-boost), respectively, and 320 and 110 for Omicron. Two weeks after boost, titers against D614G and Omicron increased to 5360 and 2980, respectively, for mRNA-1273 and 2670 and 1930 for mRNA-Omicron. Following either boost, 70-80% of spike-specific B cells were cross-reactive against both WA1 and Omicron. Significant and equivalent control of virus replication in lower airways was observed following either boost. Therefore, an Omicron boost may not provide greater immunity or protection compared to a boost with the current mRNA-1273 vaccine.

13.
Preprint in English | bioRxiv | ID: ppbiorxiv-477770

ABSTRACT

Immunization with SARS-CoV-2 spike elicits diverse antibodies, but can any of these neutralize broadly? Here, we report the isolation and characterization of antibody WS6, from a mouse immunized with mRNA encoding the SARS-CoV-2 spike. WS6 bound diverse beta-coronavirus spikes and neutralized SARS-CoV-2 variants, SARS-CoV, and related sarbecoviruses. Epitope mapping revealed WS6 to target a region in the S2 subunit, which was conserved among SARS-CoV-2, MERS-CoV, and hCoV-OC43. The crystal structure at 2-[A] resolution of WS6 with its S2 epitope revealed recognition to center on a conserved helix, which was occluded in both prefusion and post-fusion spike conformations. Structural and neutralization analyses indicated WS6 to neutralize by inhibiting fusion, post-viral attachment. Comparison of WS6 to other antibodies recently identified from convalescent donors or mice immunized with diverse spikes indicated a stem-helical supersite - centered on hydrophobic residues Phe1148, Leu1152, Tyr1155, and Phe1156 - to be a promising target for vaccine design. HighlightsO_LISARS-CoV-2 spike mRNA-immunized mouse elicited an antibody, WS6, that cross reacts with spikes of diverse human and bat beta-coronaviruses C_LIO_LIWS6 neutralizes SARS-CoV-2 variants, SARS-CoV, and related viruses C_LIO_LICrystal structure at 2-[A] resolution of WS6 in complex with a conserved S2 peptide reveals recognition of a helical epitope C_LIO_LIWS6 neutralizes by inhibition of fusion, post-viral attachment C_LIO_LIWS6 recognizes a supersite of vulnerability also recognized by other recently identified antibodies C_LIO_LIHelical supersite of vulnerability comprises a hydrophobic cluster spanning three helical turns, with acid residues framing the center turn C_LIO_LIGenetic and structural analysis indicate supersite recognition to be compatible with diverse antibody ontogenies C_LI

14.
Frontiers in psychiatry ; 12, 2021.
Article in English | EuropePMC | ID: covidwho-1609848

ABSTRACT

Background: The purpose of this study was to assess the mental health status of medical students engaged in online learning at home during the pandemic, and explore the potential risk factors of mental health. Methods: A cross-sectional study was conducted via an online survey among 5,100 medical students from Wannan Medical College in China. The Depression, Anxiety and Stress scale (DASS-21) was used to measure self-reported symptoms of depression, anxiety, and stress among medical students during online learning in the pandemic. Results: In total, 4,115 participants were included in the study. The prevalence symptoms of depression, anxiety, and stress were 31.9, 32.9, and 14.6%, respectively. Depression was associated with gender, grade, length of schooling, relationship with father, students' daily online learning time, and students' satisfaction with online learning effects. Anxiety was associated with gender, length of schooling, relationship with father, relationship between parents, students' daily online learning time, and students' satisfaction with online learning effects. Stress was associated with grade, relationship with father, relationship between parents, students' daily online learning time, and students' satisfaction with online learning effects. Conclusions: Nearly one-third of medical students survived with varying degrees of depression, anxiety, and stress symptoms during online learning of the COVID-19 pandemic. Gender, grade, length of schooling, family environment, and online learning environment play vital roles in medical students' mental health. Families and schools should provide targeted psychological counseling to high-risk students (male, second-year and third-year, four-year program). The findings of this study can provide reference for educators to cope with the psychological problems and formulate the mental health curriculum construction among medical students during online learning.

15.
Preprint in English | bioRxiv | ID: ppbiorxiv-474307

ABSTRACT

With B.1.1.529 SARS-CoV-2 variants rapid spread and substantially increased resistance to neutralization by vaccinee and convalescent sera, monoclonal antibodies with potent neutralization are eagerly sought. To provide insight into effective neutralization, we determined cryo-EM structures and evaluated potent receptor-binding domain (RBD) antibodies for their ability to bind and neutralize this new variant. B.1.1.529 RBD mutations altered 16% of the RBD surface, clustering on a ridge of this domain proximal to the ACE2-binding surface and reducing binding of most antibodies. Significant inhibitory activity was retained, however, by select monoclonal antibodies including A19-58.1, B1-182.1, COV2-2196, S2E12, A19-46.1, S309 and LY-CoV1404, which accommodated these changes and neutralized B.1.1.529 with IC50s between 5.1-281 ng/ml, and we identified combinations of antibodies with potent synergistic neutralization. Structure-function analyses delineated the impact of resistance mutations and revealed structural mechanisms for maintenance of potent neutralization against emerging variants. Summary SentenceWe show potent B.1.1.529 neutralization by select antibodies and use EM structures to reveal how potency can be retained.

16.
Non-conventional in English | [Unspecified Source], Grey literature | ID: grc-750455

ABSTRACT

BACKGROUND AND OBJECTIVES: Public health interventions were associated with reduction in coronavirus disease 2019 (COVID-19) transmission in China, but their impacts on COVID-19 epidemiology in other countries are unclear. We examined the associations of stay-at-home order (SAHO) and face-masking recommendation with epidemiology of laboratory-confirmed COVID-19 in the United States. METHODS: In this quasi-experimental study, we modeled the temporal trends in daily new cases and deaths of COVID-19, and COVID-19 time-varying reproduction numbers (Rt) in the United States between March 1 and April 20, 2020, and conducted simulation studies. RESULTS: The number and proportion of U.S. residents under SAHO increased between March 19 and April 7, and plateaued at 29,0829,980 and 88.6%, respectively. Trends in COVID-19 daily cases and Rt reduced after March 23 (P<0.001) and further reduced on April 3 (P<0.001), which was associated with implementation of SAHO by 10 states on March 23, and face-masking recommendation on April 3, respectively. The estimates of Rt eventually fell below/around 1.0 on April 13. Similar turning points were identified in the trends of daily deaths with a lag time. Early implementation and early-removal of SAHO would be associated with significantly reduced and increased daily new cases and deaths, respectively.

17.
Science ; 374(6573): 1343-1353, 2021 Dec 10.
Article in English | MEDLINE | ID: covidwho-1483979

ABSTRACT

Neutralizing antibody responses gradually wane against several variants of concern (VOCs) after vaccination with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine messenger RNA-1273 (mRNA-1273). We evaluated the immune responses in nonhuman primates that received a primary vaccination series of mRNA-1273 and were boosted about 6 months later with either homologous mRNA-1273 or heterologous mRNA-1273.ß, which encompasses the spike sequence of the B.1.351 Beta variant. After boost, animals had increased neutralizing antibody responses across all VOCs, which was sustained for at least 8 weeks after boost. Nine weeks after boost, animals were challenged with the SARS-CoV-2 Beta variant. Viral replication was low to undetectable in bronchoalveolar lavage and significantly reduced in nasal swabs in all boosted animals, suggesting that booster vaccinations may be required to sustain immunity and protection.


Subject(s)
/immunology , COVID-19 Vaccines/immunology , COVID-19/prevention & control , Immunogenicity, Vaccine , SARS-CoV-2/immunology , /administration & dosage , Animals , Antibodies, Neutralizing/blood , Antibodies, Viral/analysis , Antibodies, Viral/blood , Bronchoalveolar Lavage Fluid/immunology , Bronchoalveolar Lavage Fluid/virology , COVID-19/immunology , COVID-19/virology , COVID-19 Vaccines/administration & dosage , Immunity, Mucosal , Immunization, Secondary , Macaca mulatta , Nose/immunology , Nose/virology , RNA, Viral/analysis , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification , SARS-CoV-2/physiology , T Follicular Helper Cells/immunology , Th1 Cells/immunology , Virus Replication
18.
Preprint in English | bioRxiv | ID: ppbiorxiv-465542

ABSTRACT

mRNA-1273 vaccine efficacy against SARS-CoV-2 Delta wanes over time; however, there are limited data on the impact of durability of immune responses on protection. We immunized rhesus macaques at weeks 0 and 4 and assessed immune responses over one year in blood, upper and lower airways. Serum neutralizing titers to Delta were 280 and 34 reciprocal ID50 at weeks 6 (peak) and 48 (challenge), respectively. Antibody binding titers also decreased in bronchoalveolar lavage (BAL). Four days after challenge, virus was unculturable in BAL and subgenomic RNA declined [~]3-log10 compared to control animals. In nasal swabs, sgRNA declined 1-log10 and virus remained culturable. Anamnestic antibody responses (590-fold increase) but not T cell responses were detected in BAL by day 4 post-challenge. mRNA-1273-mediated protection in the lungs is durable but delayed and potentially dependent on anamnestic antibody responses. Rapid and sustained protection in upper and lower airways may eventually require a boost.

19.
Preprint in English | bioRxiv | ID: ppbiorxiv-456015

ABSTRACT

Neutralizing antibody responses gradually wane after vaccination with mRNA-1273 against several variants of concern (VOC), and additional boost vaccinations may be required to sustain immunity and protection. Here, we evaluated the immune responses in nonhuman primates that received 100 {micro}g of mRNA-1273 vaccine at 0 and 4 weeks and were boosted at week 29 with mRNA-1273 (homologous) or mRNA-1273.{beta} (heterologous), which encompasses the spike sequence of the B.1.351 (beta or {beta}) variant. Reciprocal ID50 pseudovirus neutralizing antibody geometric mean titers (GMT) against live SARS-CoV-2 D614G and the {beta} variant, were 4700 and 765, respectively, at week 6, the peak of primary response, and 644 and 553, respectively, at a 5-month post-vaccination memory time point. Two weeks following homologous or heterologous boost {beta}-specific reciprocal ID50 GMT were 5000 and 3000, respectively. At week 38, animals were challenged in the upper and lower airway with the {beta} variant. Two days post-challenge, viral replication was low to undetectable in both BAL and nasal swabs in most of the boosted animals. These data show that boosting with the homologous mRNA-1273 vaccine six months after primary immunization provides up to a 20-fold increase in neutralizing antibody responses across all VOC, which may be required to sustain high-level protection against severe disease, especially for at-risk populations. One-sentence summarymRNA-1273 boosted nonhuman primates have increased immune responses and are protected against SARS-CoV-2 beta infection.

20.
Explor Res Hypothesis Med ; : 1-10, 2020 Jul 08.
Article in English | MEDLINE | ID: covidwho-1207927

ABSTRACT

BACKGROUND AND OBJECTIVES: Public health interventions have reduced coronavirus disease 2019 (COVID-19) transmission in several countries, but their impacts on COVID-19 epidemics in the USA are unclear. We examined associations of stay-at-home order (SAHO) and face-masking recommendation with COVID-19 epidemics in the USA. METHODS: In this quasi-experimental interrupted time-series study, we modeled temporal trends in daily new cases and deaths of laboratory-confirmed COVID-19 cases, and COVID-19 time-varying reproduction numbers in the USA between March 1 and April 20, 2020. In addition, we conducted simulation analyses. RESULTS: The number of residents under SAHO increased since March 19 and plateaued at 290,829,980 (88.6% of the U.S. population) on April 7. Trends in COVID-19 time-varying reproduction numbers peaked on March 23, further reduced on April 3, and fell below/around 1.0 on April 13. Early-implementation and early-lift of SAHO would reduce and increase COVID-19 epidemics, respectively. Multivariable piecewise log-linear regression revealed the states' neighboring relationship with New York was linked to COVID-19 daily new cases and deaths. There were two turning points in daily new-case trend, being March 28 (slope-changes = -0.09) and April 3 (slope-changes = -0.09), which appeared to be associated with implementation of SAHO on March 28 (affecting 48.5% of the US population in 22 states and District of Columbia), and face-masking recommendation on April 3, respectively. There were also two turning points in daily new-death trend, being April 9 (slope-changes = -0.06) and April 19 (slope-changes = -0.90). CONCLUSIONS: We identified two turning points of COVID-19 daily new cases or deaths in the USA, which seem to be linked to implementation of SAHO and the Center for Disease Control's face-masking recommendation.

SELECTION OF CITATIONS
SEARCH DETAIL