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1.
Journal of Evidence-Based Social Work ; : 1-17, 2022.
Article in English | Taylor & Francis | ID: covidwho-1730569
2.
Vet Pathol ; : 3009858211071016, 2022 Jan 29.
Article in English | MEDLINE | ID: covidwho-1662392

ABSTRACT

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes severe viral pneumonia and is associated with a high fatality rate. A substantial proportion of patients infected by SARS-CoV-2 suffer from mild hyposmia to complete loss of olfactory function, resulting in anosmia. However, the pathogenesis of the olfactory dysfunction and comparative pathology of upper respiratory infections with SARS-CoV-2 are unknown. We describe the histopathological, immunohistochemical, and in situ hybridization findings from rodent models of SARS-CoV-2 infection. The main histopathological findings in the olfactory epithelia of K8-hACE2 Tg mice, hACE2 Tg mice, and hamsters were varying degrees of inflammatory lesions, including disordered arrangement, necrosis, exfoliation, and macrophage infiltration of the olfactory epithelia, and inflammatory exudation. On the basis of these observations, the nasal epithelia of these rodent models appeared to develop moderate, mild, and severe rhinitis, respectively. Correspondingly, SARS-CoV-2 viral RNA and antigen were mainly identified in the olfactory epithelia and lamina propria. Moreover, viral RNA was abundant in the cerebrum of K18-hACE2 Tg mice, including the olfactory bulb. The K8-hACE2 Tg mouse, hACE2 Tg mouse, and hamster models could be used to investigate the pathology of SARS-CoV-2 infection in the upper respiratory tract and central nervous system. These models could help to provide a better understanding of the pathogenic process of this virus and to develop effective medications and prophylactic treatments.

3.
Innovation in Aging ; 5(Supplement_1):261-261, 2021.
Article in English | PMC | ID: covidwho-1584694

ABSTRACT

This symposium presents a collection of papers that examine the concept of social support and its effect on custodial grandparents’ (CG) mental health state. Each paper explores a different perspective about grandparents’ access to and/or use of social support networks and mental health outcomes;several papers view social support within the context of the COVID-19 pandemic. Nadorff and colleagues explore social support by middle-generation family members and its effects on grandparents’ stress and depressive symptoms. Musil and colleagues report on psychosocial and social support predictors of self-appraised healthcare and financial security by CG during the Covid-19 pandemic. Whitley and Kelley describe current social networks relied upon by a preliminary sample of CG while managing the daily stresses and strains associated with COVID-19 and its restrictive mandates. The final two papers report the use of specialized technology and support services delivered to homebound CG during the COVID-19 pandemic. Lee and colleagues describe a telemental health model using Solution-Focused Brief Therapy to serve socially isolated grandparents experiencing mental health distress as during the pandemic. Mendoza and Park report on program challenges and outcomes of implementing a support service for grandparents living under COVID-19 restrictions. The highlights of the papers will be discussed by Yanfeng Xu and give attention to the ways scholars and practitioners can build upon these works to maximize the mental health outcomes of CG, while managing to live in socially restrictive and challenging environments.

4.
Innovation in Aging ; 5(Supplement_1):495-495, 2021.
Article in English | PMC | ID: covidwho-1584522

ABSTRACT

COVID-19 has increased economic hardship for many families, including custodial grandparent-headed families. We aim to examine latent classes of material hardship among custodial grandparent-headed families, to assess predictors associated with identified classes, and to investigate associations with grandchildren’s physical and mental health outcomes during COVID-19. Data was collected from a cross-sectional survey in June 2020. The sample comprised of 362 grandparents. Latent class analysis and logistic regression were conducted. Three latent classes of material hardship were identified: Class 1 (n = 232;64.1%) low overall hardship with high medical hardship, class 2 (n = 52;14.4%) moderate overall hardship with high utility hardship, and class 3 (n = 78;21.5%) severe overall hardship. Factors, such as race, household income, labor force status, financial assistance status, and trigger events to raise grandchildren, were associated with class membership. Class 2 (OR = 0.19, p < 0.05) compared to Class 1 was significantly associated with grandchildren’s physical health. Our findings suggest that material hardship is heterogeneous among custodial grandparents during COVID-19, and children in households experiencing utility hardship have a higher risk for poorer physical health outcomes. Results highlight the needs to meet grandparents’ material needs and call for future research to examine the mechanism that explains the link between material hardship and grandchildren’s outcomes.

5.
Children and Youth Services Review ; : 106340, 2021.
Article in English | ScienceDirect | ID: covidwho-1568571

ABSTRACT

COVID-19 has increased economic hardship for many families, including custodial grandparent-headed families. We aim to examine latent classes of material hardship among custodial grandparent-headed families, to assess predictors associated with identified classes, and to investigate associations with grandchildren’s physical and mental health outcomes during COVID-19. A cross-sectional survey was administered via Qualtrics Panels in June 2020. The sample comprised of 362 grandparents. Latent class analysis and multinomial and binary logistic regression were conducted. Three latent classes of material hardship were identified: Class 1 low overall hardship with high medical hardship, class 2 moderate overall hardship with high utility hardship, and class 3 severe overall hardship. Factors, including race, household income, labor force status, years of care, and financial assistance status, were associated with class membership. Class 2 was significantly associated with grandchildren’s physical health. Our findings suggest that material hardship is heterogeneous among custodial grandparents during COVID-19, and children in households experiencing utility hardship have a higher risk for poorer physical health outcomes. Results highlight the need to meet grandparents’ material needs and call for future research to examine possible mechanisms that explain the link between material hardship and grandchildren’s outcomes.

6.
Signal Transduct Target Ther ; 6(1): 337, 2021 09 06.
Article in English | MEDLINE | ID: covidwho-1402050

ABSTRACT

SARS-CoV-2 has been reported to show a capacity for invading the brains of humans and model animals. However, it remains unclear whether and how SARS-CoV-2 crosses the blood-brain barrier (BBB). Herein, SARS-CoV-2 RNA was occasionally detected in the vascular wall and perivascular space, as well as in brain microvascular endothelial cells (BMECs) in the infected K18-hACE2 transgenic mice. Moreover, the permeability of the infected vessel was increased. Furthermore, disintegrity of BBB was discovered in the infected hamsters by administration of Evans blue. Interestingly, the expression of claudin5, ZO-1, occludin and the ultrastructure of tight junctions (TJs) showed unchanged, whereas, the basement membrane was disrupted in the infected animals. Using an in vitro BBB model that comprises primary BMECs with astrocytes, SARS-CoV-2 was found to infect and cross through the BMECs. Consistent with in vivo experiments, the expression of MMP9 was increased and collagen IV was decreased while the markers for TJs were not altered in the SARS-CoV-2-infected BMECs. Besides, inflammatory responses including vasculitis, glial activation, and upregulated inflammatory factors occurred after SARS-CoV-2 infection. Overall, our results provide evidence supporting that SARS-CoV-2 can cross the BBB in a transcellular pathway accompanied with basement membrane disrupted without obvious alteration of TJs.


Subject(s)
Basement Membrane/metabolism , Blood-Brain Barrier/metabolism , COVID-19/metabolism , SARS-CoV-2/metabolism , Tight Junctions/metabolism , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/metabolism , Animals , Basement Membrane/pathology , Basement Membrane/virology , Blood-Brain Barrier/pathology , Blood-Brain Barrier/virology , COVID-19/genetics , COVID-19/pathology , Chlorocebus aethiops , Disease Models, Animal , Humans , Matrix Metalloproteinase 9/genetics , Matrix Metalloproteinase 9/metabolism , Mice , Mice, Transgenic , SARS-CoV-2/genetics , Tight Junctions/genetics , Tight Junctions/pathology , Tight Junctions/virology , Vero Cells
7.
Child Abuse Negl ; 121: 105258, 2021 11.
Article in English | MEDLINE | ID: covidwho-1363928

ABSTRACT

BACKGROUND: COVID-19 has exacerbated material hardship among grandparent-headed kinship families. Grandparent-headed kinship families receive financial assistance, which may mitigate material hardship and reduce child neglect risk. OBJECTIVE: This study aims to examine (1) the association between material hardship and child neglect risk; and (2) whether financial assistance moderates this association in a sample of kinship grandparent-headed families during COVID-19. PARTICIPANTS AND SETTING: Cross-sectional survey data were collected from a convenience sample of grandparent-headed kinship families (not necessarily child welfare involved) (N = 362) in the United States via Qualtrics Panels online survey. METHODS: Descriptive, bivariate, and negative binomial regression were conducted using STATA 15.0. RESULTS: Experiencing material hardship was found to be associated with an increased risk of child neglect, and receiving financial assistance was associated with a decreased risk of child neglect in the full sample and a subsample with household income > $30,000. Receiving financial assistance buffered the negative effect of material hardship on child neglect risk across analytic samples, and receiving SNAP was a significant moderator in the full sample. Among families with a household income ≤ $30,000, receiving SNAP and foster care payments was associated with a decreased risk of child neglect, while receiving TANF and unemployment insurance was associated with an increased risk of child neglect. Among families with household income > $30,000, only receiving SNAP was associated with a decreased risk of child neglect. CONCLUSIONS: This study suggests the potential importance of providing concrete financial assistance, particularly SNAP and foster care payments, to grandparent-headed kinship families in efforts to decrease child neglect risk during COVID-19.


Subject(s)
COVID-19/psychology , Child Abuse , Financial Stress , Grandparents , COVID-19/epidemiology , Child , Child, Foster , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , SARS-CoV-2 , United States/epidemiology
8.
Child Fam Soc Work ; 2021 Jul 24.
Article in English | MEDLINE | ID: covidwho-1322730

ABSTRACT

COVID-19 and its related policy measures have increased the psychological distress of individuals, including grandparent kinship caregivers. Guided by the Resilience Model of Family Stress, Adjustment, and Adaptation, this study examines relationships between material hardship, parenting stress, social support, resilience and psychological distress of grandparent kinship caregivers during the COVID-19 pandemic, as well as the moderating role of kinship license status on these relationships. Kinship care licensing is a prerequisite to receiving financial assistance and other supporting services from the government. We administered a cross-sectional survey of grandparent kinship caregivers (N = 362) in the United States. Logistic regression results indicated that material hardship was associated with higher odds of experiencing psychological distress, whereas resilience and social support were associated with lower odds. Kinship license status moderated the relationships of social support and resilience with psychological distress. Results suggest that additional emergency funds and more tailored financial services should be provided to meet material needs, and interventions with a focus on resilience and social support are particularly needed. The moderating effects of license status indicate that some interventions should be specifically implemented among licensed kinship caregivers, whereas parallel services should be provided to kinship caregivers regardless of their license status.

9.
Signal Transduct Target Ther ; 6(1): 200, 2021 05 20.
Article in English | MEDLINE | ID: covidwho-1237988

ABSTRACT

Influenza A virus may circulate simultaneously with the SARS-CoV-2 virus, leading to more serious respiratory diseases during this winter. However, the influence of these viruses on disease outcome when both influenza A and SARS-CoV-2 are present in the host remains unclear. Using a mammalian model, sequential infection was performed in ferrets and in K18-hACE2 mice, with SARS-CoV-2 infection following H1N1. We found that co-infection with H1N1 and SARS-CoV-2 extended the duration of clinical manifestation of COVID-19, and enhanced pulmonary damage, but reduced viral shedding of throat swabs and viral loads in the lungs of ferrets. Moreover, mortality was increased in sequentially infected mice compared with single-infection mice. Compared with single-vaccine inoculation, co-inoculation of PiCoVacc (a SARS-CoV-2 vaccine) and the flu vaccine showed no significant differences in neutralizing antibody titers or virus-specific immune responses. Combined immunization effectively protected K18-hACE2 mice against both H1N1 and SARS-CoV-2 infection. Our findings indicated the development of systematic models of co-infection of H1N1 and SARS-CoV-2, which together notably enhanced pneumonia in ferrets and mice, as well as demonstrated that simultaneous vaccination against H1N1 and SARS-CoV-2 may be an effective prevention strategy for the coming winter.


Subject(s)
COVID-19 , Coinfection , Influenza A Virus, H1N1 Subtype/immunology , Orthomyxoviridae Infections , SARS-CoV-2/immunology , Animals , COVID-19/immunology , COVID-19/pathology , COVID-19/virology , Coinfection/immunology , Coinfection/pathology , Coinfection/virology , Disease Models, Animal , Ferrets , Humans , Male , Mice , Mice, Transgenic , Orthomyxoviridae Infections/immunology , Orthomyxoviridae Infections/pathology , Orthomyxoviridae Infections/virology
10.
J Appl Gerontol ; 40(9): 923-933, 2021 09.
Article in English | MEDLINE | ID: covidwho-1192095

ABSTRACT

Involuntary job loss during the COVID-19 pandemic adds challenges, especially for custodial grandparents that are taking care of grandchildren. Grandparents are relatively vulnerable, and they need more attention and support when facing the negative impacts of COVID-19. This study analyzed cross-sectional survey data collected from 234 custodial grandparents via Qualtrics Panels in June 2020 in the United States. After using the propensity score weighting adjustment, results from logistic and ordinary least squares regression showed that compared with grandparents that did not lose their job during the pandemic, grandparents that did had more parenting stress and worse mental health. Moderation analysis also showed that social support was a significant moderator of the relationship between job loss and mental health, but not the relationship between job loss and parenting stress. The findings and implications are discussed.


Subject(s)
COVID-19 , Child Custody , Grandparents/psychology , Mental Health , Parenting/psychology , Stress, Psychological , COVID-19/economics , COVID-19/epidemiology , COVID-19/psychology , Child , Child Custody/economics , Child Custody/statistics & numerical data , Female , Humans , Intergenerational Relations , Male , Middle Aged , Needs Assessment , Psychosocial Functioning , Social Support , Stress, Psychological/economics , Stress, Psychological/etiology , Unemployment , United States/epidemiology
12.
J Fam Violence ; : 1-13, 2020 Nov 23.
Article in English | MEDLINE | ID: covidwho-947044

ABSTRACT

Grandparent kinship caregivers may experience increased parenting stress and mental distress during the COVID-19 pandemic. It may lead to risky parenting behaviors, such as psychological aggression, corporal punishment, and neglectful behaviors towards their grandchildren. This study aims to examine (1) the relationships between parenting stress, mental health, and grandparent kinship caregivers' risky parenting practices, such as psychological aggression, corporal punishment, and neglectful behaviors towards their grandchildren during the COVID-19 pandemic, and (2) whether grandparent kinship caregivers' mental health is a potential mediator between parenting stress and caregivers' psychological aggression, corporal punishment, and neglectful behaviors. A cross-sectional survey among grandparent kinship caregivers (N = 362) was conducted in June 2020 in the United States. Descriptive analyses, negative binomial regression analyses, and mediation analyses were conducted using STATA 15.0. We found that (1) grandparent kinship caregivers' high parenting stress and low mental health were associated with more psychological aggression, corporal punishment, and neglectful parenting behaviors during COVID-19; and (2) grandparent kinship caregivers' mental health partially mediated the relationships between parenting stress and their psychological aggression, corporal punishment, and neglectful behaviors. Results suggest that decreasing grandparent kinship caregivers' parenting stress and improving their mental health are important for reducing child maltreatment risk during COVID-19.

13.
Biochem Pharmacol ; 183: 114302, 2021 01.
Article in English | MEDLINE | ID: covidwho-893616

ABSTRACT

Baicalein is the main active compound of Scutellaria baicalensis Georgi, a medicinal herb with multiple pharmacological activities, including the broad anti-virus effects. In this paper, the preclinical study of baicalein on the treatment of COVID-19 was performed. Results showed that baicalein inhibited cell damage induced by SARS-CoV-2 and improved the morphology of Vero E6 cells at a concentration of 0.1 µM and above. The effective concentration could be reached after oral administration of 200 mg/kg crystal form ß of baicalein in rats. Furthermore, baicalein significantly inhibited the body weight loss, the replication of the virus, and relieved the lesions of lung tissue in hACE2 transgenic mice infected with SARS-CoV-2. In LPS-induced acute lung injury of mice, baicalein improved the respiratory function, inhibited inflammatory cell infiltration in the lung, and decreased the levels of IL-1ß and TNF-α in serum. In conclusion, oral administration of crystal form ß of baicalein could reach its effective concentration against SARS-CoV-2. Baicalein could inhibit SARS-CoV-2-induced injury both in vitro and in vivo. Therefore, baicalein might be a promising therapeutic drug for the treatment of COVID-19.


Subject(s)
Antioxidants/therapeutic use , COVID-19/drug therapy , COVID-19/pathology , Flavanones/therapeutic use , Acute Lung Injury/drug therapy , Acute Lung Injury/metabolism , Acute Lung Injury/pathology , Animals , Antioxidants/pharmacokinetics , COVID-19/metabolism , Chlorocebus aethiops , Dose-Response Relationship, Drug , Female , Flavanones/pharmacokinetics , Inflammation Mediators/antagonists & inhibitors , Inflammation Mediators/metabolism , Male , Mice , Mice, Inbred BALB C , Mice, Transgenic , Random Allocation , Rats , Rats, Sprague-Dawley , Treatment Outcome , Vero Cells
14.
Developmental Child Welfare ; : 2516103220967937, 2020.
Article in English | Sage | ID: covidwho-883551

ABSTRACT

The risk of child maltreatment is heightened during the pandemic due to multiple COVID-19 related stressors, such as physical and mental health concerns, economic stress, challenges in homeschooling, marital conflicts and intimate personal violence, and intensified child?parent relationships. Both parental internal (e.g., parenting styles) and external resources (e.g., social support), and parental perceptions toward stressors will affect how parents cope with these stressors, which may exacerbate or mitigate the risk of child maltreatment. Guided by family stress theory, this article identifies COVID-19 related stressors at the family level, and further elaborates on how these stressors are associated with child maltreatment via parents? resources, perceptions, and coping strategies. Implications for future practice and research are discussed.

15.
Animal Model Exp Med ; 3(1): 93-97, 2020 Mar.
Article in English | MEDLINE | ID: covidwho-847791

ABSTRACT

BACKGROUND: Since December 2019, an outbreak of the Corona Virus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2) in Wuhan, China, has become a public health emergency of international concern. The high fatality of aged cases caused by SARS-CoV-2 was a need to explore the possible age-related phenomena with non-human primate models. METHODS: Three 3-5 years old and two 15 years old rhesus macaques were intratracheally infected with SARS-CoV-2, and then analyzed by clinical signs, viral replication, chest X-ray, histopathological changes and immune response. RESULTS: Viral replication of nasopharyngeal swabs, anal swabs and lung in old monkeys was more active than that in young monkeys for 14 days after SARS-CoV-2 challenge. Monkeys developed typical interstitial pneumonia characterized by thickened alveolar septum accompanied with inflammation and edema, notably, old monkeys exhibited diffuse severe interstitial pneumonia. Viral antigens were detected mainly in alveolar epithelial cells and macrophages. CONCLUSION: SARS-CoV-2 caused more severe interstitial pneumonia in old monkeys than that in young monkeys. Rhesus macaque models infected with SARS-CoV-2 provided insight into the pathogenic mechanism and facilitated the development of vaccines and therapeutics against SARS-CoV-2 infection.

16.
Nat Commun ; 11(1): 4400, 2020 09 02.
Article in English | MEDLINE | ID: covidwho-744370

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is highly transmitted through the respiratory route, but potential extra-respiratory routes of SARS-CoV-2 transmission remain uncertain. Here we inoculated five rhesus macaques with 1 × 106 TCID50 of SARS-CoV-2 conjunctivally (CJ), intratracheally (IT), and intragastrically (IG). Nasal and throat swabs collected from CJ and IT had detectable viral RNA at 1-7 days post-inoculation (dpi). Viral RNA was detected in anal swabs from only the IT group at 1-7 dpi. Viral RNA was undetectable in tested swabs and tissues after intragastric inoculation. The CJ infected animal had a higher viral load in the nasolacrimal system than the IT infected animal but also showed mild interstitial pneumonia, suggesting distinct virus distributions. This study shows that infection via the conjunctival route is possible in non-human primates; further studies are necessary to compare the relative risk and pathogenesis of infection through these different routes in more detail.


Subject(s)
Betacoronavirus/physiology , Conjunctiva/virology , Coronavirus Infections/virology , Disease Models, Animal , Pneumonia, Viral/virology , Animals , Antibodies, Viral , Betacoronavirus/genetics , Betacoronavirus/isolation & purification , COVID-19 , Coronavirus Infections/pathology , Intestine, Large/virology , Lung/pathology , Lung/virology , Macaca mulatta , Male , Nasal Cavity/virology , Pandemics , Pneumonia, Viral/pathology , RNA, Viral/analysis , RNA, Viral/genetics , SARS-CoV-2 , Trachea/virology , Viral Load , Virus Replication
17.
Child Abuse Negl ; 110(Pt 2): 104700, 2020 12.
Article in English | MEDLINE | ID: covidwho-726456

ABSTRACT

BACKGROUND: The COVID-19 pandemic has exposed the vulnerability of many families, including grandparent kinship families, to deal with a health/economic crisis. The fear of COVID-19 plus stay-at-home orders have increased individuals' psychological distress. Moreover, school closures and homeschooling further increased parenting stress among caregivers. OBJECTIVES: This study examined the relationship between material hardship and parenting stress among grandparent kinship providers, and assessed grandparents' mental health as a potential mediator to this relationship during the COVID-19 pandemic in the United States. PARTICIPANTS AND SETTING: Grandparent kinship providers (N = 362) that took primary care of their grandchildren participated in a cross-sectional survey via Qualtrics Panels in June 2020 in the United States. METHODS: Descriptive and bivariate analyses, binary logistic regression, and mediation analyses were conducted using STATA 15.0. RESULTS: Suffering material hardship was significantly associated with higher odds of experiencing parenting stress among grandparent kinship providers, and grandparents' mental health partially mediated this association. CONCLUSIONS: Addressing material and mental health needs among grandparent kinship providers is critical to decreasing their parenting stress.


Subject(s)
COVID-19/economics , COVID-19/psychology , Grandparents/psychology , Mental Health , Parenting/psychology , Stress, Psychological , Caregivers/psychology , Child , Cross-Sectional Studies , Economic Factors , Female , Humans , Intergenerational Relations , Logistic Models , Male , Middle Aged , Models, Economic , Models, Psychological , Multivariate Analysis , Pandemics , Stress, Psychological/etiology , United States
18.
J Infect Dis ; 222(4): 551-555, 2020 07 23.
Article in English | MEDLINE | ID: covidwho-704462

ABSTRACT

We simulated 3 transmission modes, including close-contact, respiratory droplets and aerosol routes, in the laboratory. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can be highly transmitted among naive human angiotensin-converting enzyme 2 (hACE2) mice via close contact because 7 of 13 naive hACE2 mice were SARS-CoV-2 antibody seropositive 14 days after being introduced into the same cage with 3 infected-hACE2 mice. For respiratory droplets, SARS-CoV-2 antibodies from 3 of 10 naive hACE2 mice showed seropositivity 14 days after introduction into the same cage with 3 infected-hACE2 mice, separated by grids. In addition, hACE2 mice cannot be experimentally infected via aerosol inoculation until continued up to 25 minutes with high viral concentrations.


Subject(s)
Betacoronavirus , Coronavirus Infections/transmission , Pneumonia, Viral/transmission , Aerosols , Anal Canal/virology , Angiotensin-Converting Enzyme 2 , Animals , Antibodies, Viral/blood , Betacoronavirus/genetics , Betacoronavirus/immunology , Betacoronavirus/isolation & purification , COVID-19 , Chlorocebus aethiops , Female , Humans , Immunoglobulin G/blood , Lung/pathology , Lung/virology , Male , Mice , Mice, Transgenic , Pandemics , Peptidyl-Dipeptidase A/genetics , Pharynx/virology , RNA, Viral/isolation & purification , Respiratory System/virology , Risk , SARS-CoV-2 , Specific Pathogen-Free Organisms , Time Factors , Vero Cells , Viral Load , Weight Loss
19.
Nature ; 586(7830): 572-577, 2020 10.
Article in English | MEDLINE | ID: covidwho-691301

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a respiratory disease called coronavirus disease 2019 (COVID-19), the spread of which has led to a pandemic. An effective preventive vaccine against this virus is urgently needed. As an essential step during infection, SARS-CoV-2 uses the receptor-binding domain (RBD) of the spike protein to engage with the receptor angiotensin-converting enzyme 2 (ACE2) on host cells1,2. Here we show that a recombinant vaccine that comprises residues 319-545 of the RBD of the spike protein induces a potent functional antibody response in immunized mice, rabbits and non-human primates (Macaca mulatta) as early as 7 or 14 days after the injection of a single vaccine dose. The sera from the immunized animals blocked the binding of the RBD to ACE2, which is expressed on the cell surface, and neutralized infection with a SARS-CoV-2 pseudovirus and live SARS-CoV-2 in vitro. Notably, vaccination also provided protection in non-human primates to an in vivo challenge with SARS-CoV-2. We found increased levels of RBD-specific antibodies in the sera of patients with COVID-19. We show that several immune pathways and CD4 T lymphocytes are involved in the induction of the vaccine antibody response. Our findings highlight the importance of the RBD domain in the design of SARS-CoV-2 vaccines and provide a rationale for the development of a protective vaccine through the induction of antibodies against the RBD domain.


Subject(s)
Antibodies, Viral/immunology , Betacoronavirus/immunology , Coronavirus Infections/immunology , Coronavirus Infections/prevention & control , Pandemics/prevention & control , Pneumonia, Viral/immunology , Pneumonia, Viral/prevention & control , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/immunology , Viral Vaccines/immunology , Animals , Antibodies, Neutralizing/immunology , COVID-19 , COVID-19 Vaccines , Humans , Macaca mulatta/immunology , Macaca mulatta/virology , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Models, Animal , Models, Molecular , Protein Domains , SARS-CoV-2 , Serum/immunology , Spleen/cytology , Spleen/immunology , T-Lymphocytes/immunology , Vaccination
20.
Science ; 369(6505): 818-823, 2020 08 14.
Article in English | MEDLINE | ID: covidwho-631755

ABSTRACT

Coronavirus disease 2019 (COVID-19), which is caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic. It is unclear whether convalescing patients have a risk of reinfection. We generated a rhesus macaque model of SARS-CoV-2 infection that was characterized by interstitial pneumonia and systemic viral dissemination mainly in the respiratory and gastrointestinal tracts. Rhesus macaques reinfected with the identical SARS-CoV-2 strain during the early recovery phase of the initial SARS-CoV-2 infection did not show detectable viral dissemination, clinical manifestations of viral disease, or histopathological changes. Comparing the humoral and cellular immunity between primary infection and rechallenge revealed notably enhanced neutralizing antibody and immune responses. Our results suggest that primary SARS-CoV-2 exposure protects against subsequent reinfection in rhesus macaques.


Subject(s)
Betacoronavirus , Coronavirus Infections/immunology , Coronavirus Infections/virology , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , Anal Canal/virology , Animals , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , B-Lymphocyte Subsets/immunology , Betacoronavirus/immunology , Betacoronavirus/isolation & purification , Betacoronavirus/physiology , COVID-19 , Coronavirus Infections/pathology , Coronavirus Infections/physiopathology , Disease Models, Animal , Host Microbial Interactions , Immunity, Cellular , Immunity, Humoral , Lung/diagnostic imaging , Lung/immunology , Lung/pathology , Lung/virology , Lung Diseases, Interstitial/immunology , Lung Diseases, Interstitial/pathology , Lung Diseases, Interstitial/virology , Macaca mulatta , Nasopharynx/virology , Pandemics , Pneumonia, Viral/pathology , Pneumonia, Viral/physiopathology , Recurrence , SARS-CoV-2 , T-Lymphocyte Subsets/immunology , Viral Load , Virus Replication
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