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1.
Allergy ; 2020 Nov 13.
Article in English | MEDLINE | ID: covidwho-1140086

ABSTRACT

The pandemic of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused an unprecedented global social and economic impact, and high numbers of deaths. Many risk factors have been identified in the progression of COVID-19 into a severe and critical stage, including old age, male gender, underlying comorbidities such as hypertension, diabetes, obesity, chronic lung diseases, heart, liver and kidney diseases, tumors, clinically apparent immunodeficiencies, local immunodeficiencies, such as early type I interferon secretion capacity, and pregnancy. Possible complications include acute kidney injury, coagulation disorders, thoromboembolism. The development of lymphopenia and eosinopenia are laboratory indicators of COVID-19. Laboratory parameters to monitor disease progression include lactate dehydrogenase, procalcitonin, high-sensitivity C-reactive protein, proinflammatory cytokines such as interleukin (IL)-6, IL-1ß, Krebs von den Lungen-6 (KL-6), and ferritin. The development of a cytokine storm and extensive chest computed tomography imaging patterns are indicators of a severe disease. In addition, socioeconomic status, diet, lifestyle, geographical differences, ethnicity, exposed viral load, day of initiation of treatment, and quality of health care have been reported to influence individual outcomes. In this review, we highlight the scientific evidence on the risk factors of severity of COVID-19.

2.
Animal Model Exp Med ; 4(1): 2-15, 2021 03.
Article in English | MEDLINE | ID: covidwho-1122088

ABSTRACT

Background: Cardiovascular diseases (CVDs) and diabetes mellitus (DM) are top two chronic comorbidities that increase the severity and mortality of COVID-19. However, how SARS-CoV-2 alters the progression of chronic diseases remain unclear. Methods: We used adenovirus to deliver h-ACE2 to lung to enable SARS-CoV-2 infection in mice. SARS-CoV-2's impacts on pathogenesis of chronic diseases were studied through histopathological, virologic and molecular biology analysis. Results: Pre-existing CVDs resulted in viral invasion, ROS elevation and activation of apoptosis pathways contribute myocardial injury during SARS-CoV-2 infection. Viral infection increased fasting blood glucose and reduced insulin response in DM model. Bone mineral density decreased shortly after infection, which associated with impaired PI3K/AKT/mTOR signaling. Conclusion: We established mouse models mimicked the complex pathological symptoms of COVID-19 patients with chronic diseases. Pre-existing diseases could impair the inflammatory responses to SARS-CoV-2 infection, which further aggravated the pre-existing diseases. This work provided valuable information to better understand the interplay between the primary diseases and SARS-CoV-2 infection.

3.
J Infect Dis ; 223(8): 1313-1321, 2021 04 23.
Article in English | MEDLINE | ID: covidwho-1091239

ABSTRACT

Domestic cats, an important companion animal, can be infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). This has aroused concern regarding the ability of domestic cats to spread the virus that causes coronavirus disease 2019. We systematically demonstrated the pathogenesis and transmissibility of SARS-CoV-2 in cats. Serial passaging of the virus between cats dramatically attenuated the viral transmissibility, likely owing to variations of the amino acids in the receptor-binding domain sites of angiotensin-converting enzyme 2 between humans and cats. These findings provide insight into the transmissibility of SARS-CoV-2 in cats and information for protecting the health of humans and cats.


Subject(s)
/transmission , /pathogenicity , Amino Acids/metabolism , Animals , Cats , Cell Line , Chlorocebus aethiops , Female , Humans , Male , Vero Cells
5.
Medicine (Baltimore) ; 99(41): e22592, 2020 Oct 09.
Article in English | MEDLINE | ID: covidwho-933921

ABSTRACT

BACKGROUND: DM is a common chronic metabolic disease. COVID-19 is a large-scale infectious disease. Some studies have shown that DM is an independent risk factor that increases COVID-19 mortality or other adverse outcomes. There is currently no specific and effective drug treatment. More and more people realize that DPP-4 inhibitors may play a huge role in fighting COVID-19 combined with diabetes. However, there is no evidence-based medicine to confirm the effectiveness and safety of DPP-4 inhibitors in the treatment of COVID-19 patients with diabetes. Therefore, we will conduct a systematic review and meta-analysis to synthesize the existing clinical evidence. METHODS AND ANALYSIS: Electronic databases include CNKI, Wanfang, VIP, CBM database, Cochrane Library, PubMed, Web of Science, EMBASE, etc. We will retrieve each database from December 2019 to September 2020. At the same time, we will look for clinical trial registration and gray literature. This study only included clinical randomized controlled trials. The reviewers independently conduct literature selection, data analysis, quality analysis, and evaluation. The primary outcomes include mortality rate, morbidity, interleukin-6, tumor necrosis factor-alpha, clinical improvement, symptoms improvement, fasting blood glucose, 2-hour postprandial blood glucose, glycosylated hemoglobin, fasting insulin, adverse reactions, etc. Finally, we will conducted a meta-analysis through Review Manager Software version 5.3. RESULTS: The results will be published in peer-reviewed journals and presented at a relevant conference. CONCLUSION: This study will explore the effectiveness and safety of DPP-4 inhibitors in the treatment of COVID-19 patients with diabetes. It will provide evidence-based medical evidence for DPP-4 inhibitors in the treatment of diabetes with COVID-19. REGISTRATION NUMBER: INPLASY202090015.


Subject(s)
Coronavirus Infections/drug therapy , Diabetes Complications/drug therapy , Dipeptidyl-Peptidase IV Inhibitors/therapeutic use , Pneumonia, Viral/drug therapy , Betacoronavirus , Humans , Meta-Analysis as Topic , Pandemics , Systematic Reviews as Topic
6.
Clin Gastroenterol Hepatol ; 2020 Jun 15.
Article in English | MEDLINE | ID: covidwho-932803

ABSTRACT

BACKGROUND & AIMS: Coronavirus disease 2019 (COVID-19) is a major global health threat. We aimed to describe the characteristics of liver function in patients with SARS-CoV-2 and chronic hepatitis B virus (HBV) co-infection. METHODS: We enrolled all adult patients with SARS-CoV-2 and chronic HBV co-infection admitted to Tongji Hospital from February 1 to February 29, 2020. Data of demographic, clinical characteristics, laboratory tests, treatments, and clinical outcomes were collected. The characteristics of liver function and its relation with the severity and prognosis of disease were described. RESULTS: Of 105 SARS-CoV-2 and chronic HBV co-infected patients, elevated levels of liver test were seen in several patients at admission, including elevated levels of alanine aminotransferase (22, 20.95%), aspartate aminotransferase (29, 27.62%), total bilirubin (7, 6.67%), gamma-glutamyl transferase (7, 6.67%), and alkaline phosphatase (1, 0.95%). The values of the indices mentioned above increased substantially during hospitalization (all P < .05). Fourteen (13.33%) patients developed liver injury. Most of them (10, 71.43%) recovered after 8 (range 6-21) days. Notably, 4 (28.57%) patients rapidly progressed to acute-on-chronic liver failure. The proportion of severe COVID-19 was higher in patients with liver injury (P = .042). Complications including ACLF, acute cardiac injury and shock happened more frequently in patients with liver injury (all P < .05). The mortality was higher in individuals with liver injury (28.57% vs 3.30%, P = .004). CONCLUSION: Liver injury in patients with SARS-CoV-2 and chronic HBV co-infection was associated with severity and poor prognosis of disease. During the treatment of COVID-19 in chronic HBV-infected patients, liver function should be taken seriously and evaluated frequently.

8.
China Tropical Medicine ; 20(8):772-775, 2020.
Article in Chinese | WHO COVID | ID: covidwho-860915

ABSTRACT

Objective: To analyze the clinical characteristics, cardiac injury characteristics and early warning indexes of severe type in patients with COVID-19, so as to provide data for the evaluation, clinical treatment and prognosis of COVID-19 patients

9.
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.

10.
Preprint | SSRN | ID: ppcovidwho-756

ABSTRACT

Background: The 2019 coronavirus disease (COVID-19) represents a significant public health threat globally Here we describe efforts to compare the dynamic tran

11.
12.
Clin J Am Soc Nephrol ; 15(11): 1549-1556, 2020 11 06.
Article in English | MEDLINE | ID: covidwho-781834

ABSTRACT

BACKGROUND AND OBJECTIVES: Coronavirus disease 2019 is spreading rapidly across the world. This study aimed to assess the characteristics of kidney injury and its association with disease progression and death of patients with coronavirus disease 2019. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This is a retrospective study. Two representative cohorts were included. Cohort 1 involved severe and critical patients with coronavirus disease 2019 from Wuhan, China. Cohort 2 was all patients with coronavirus disease 2019 in Shenzhen city (Guangdong province, China). Any kidney injury was defined as the presence of any of the following: hematuria, proteinuria, in-hospital AKI, or prehospital AKI. AKI was defined according to the Kidney Disease Improving Global Outcomes (KDIGO) creatinine criteria. The primary outcome was death at the end of follow-up. The secondary outcome was progression to critical illness during the study period. RESULTS: A total of 555 patients were enrolled; 42% of the cases (229 of 549) were detected with any kidney injury, 33% of the cases (174 of 520) were detected with proteinuria, 22% of the cases (112 of 520) were detected with hematuria, and 6% of the cases (29 of 520) were detected with AKI. Of the 29 patients with AKI, 21 cases were recognized as in-hospital AKI, and eight were recognized as prehospital AKI. Altogether, 27 (5%) patients died at the end of follow-up. The death rate was 11% (20 of 174) in patients with proteinuria, 16% (18 of 112) in patients with hematuria, and 41% (12 of 29) in the AKI settings. Multivariable Cox regression analysis showed that proteinuria (hazard ratio, 4.42; 95% confidence interval, 1.22 to 15.94), hematuria (hazard ratio, 4.71; 95% confidence interval, 1.61 to 13.81), and in-hospital AKI (hazard ratio, 6.84; 95% confidence interval, 2.42 to 19.31) were associated with death. Among the 520 patients with noncritical illness at admission, proteinuria (hazard ratio, 2.61; 95% confidence interval, 1.22 to 5.56) and hematuria (hazard ratio, 2.50; 95% confidence interval, 1.23 to 5.08) were found to be associated with progression to critical illness during the study period. CONCLUSIONS: Kidney injury is common in coronavirus disease 2019, and it is associated with poor clinical outcomes. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2020_09_18_CJN04780420.mp3.


Subject(s)
Acute Kidney Injury/epidemiology , Coronavirus Infections/complications , Hematuria/epidemiology , Pneumonia, Viral/complications , Proteinuria/epidemiology , Acute Kidney Injury/mortality , Acute Kidney Injury/virology , Adult , Aged , Betacoronavirus , China/epidemiology , Critical Illness , Disease Progression , Female , Hematuria/mortality , Hematuria/virology , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Pandemics , Prevalence , Proportional Hazards Models , Proteinuria/mortality , Proteinuria/virology , Retrospective Studies , Survival Rate
13.
J Biosaf Biosecur ; 2020 Sep 19.
Article in English | MEDLINE | ID: covidwho-779304

ABSTRACT

A biosafety laboratory is a prerequisite for studying emerging infectious diseases. Safe and effective operation in laboratories and the handling of pathogens determine the safety of the personnel, pathogens, and the environment in the laboratory, which are among the key factors for successful experimentation. In this article, we aimed to provide ideas for the emergency management of biosafety laboratories, including a discussion on the urgency of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) related experimental activities, tracking clinical information, taking emergency measures, revision of the risk assessment process, and standardization of personal protective equipment and personnel behavior standards.

14.
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 , 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 , Trachea/virology , Viral Load , Virus Replication
15.
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 , Animals , Antibodies, Viral/blood , Betacoronavirus/genetics , Betacoronavirus/immunology , Betacoronavirus/isolation & purification , 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 , Specific Pathogen-Free Organisms , Time Factors , Vero Cells , Viral Load , Weight Loss
16.
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 , Humans , Macaca mulatta/immunology , Macaca mulatta/virology , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Models, Animal , Models, Molecular , Protein Domains , Serum/immunology , Spleen/cytology , Spleen/immunology , T-Lymphocytes/immunology , Vaccination
17.
Science ; 369(6499): 77-81, 2020 07 03.
Article in English | MEDLINE | ID: covidwho-667322

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in an unprecedented public health crisis. Because of the novelty of the virus, there are currently no SARS-CoV-2-specific treatments or vaccines available. Therefore, rapid development of effective vaccines against SARS-CoV-2 are urgently needed. Here, we developed a pilot-scale production of PiCoVacc, a purified inactivated SARS-CoV-2 virus vaccine candidate, which induced SARS-CoV-2-specific neutralizing antibodies in mice, rats, and nonhuman primates. These antibodies neutralized 10 representative SARS-CoV-2 strains, suggesting a possible broader neutralizing ability against other strains. Three immunizations using two different doses, 3 or 6 micrograms per dose, provided partial or complete protection in macaques against SARS-CoV-2 challenge, respectively, without observable antibody-dependent enhancement of infection. These data support the clinical development and testing of PiCoVacc for use in humans.


Subject(s)
Antibodies, Neutralizing/blood , Antibodies, Viral/blood , Betacoronavirus/immunology , Coronavirus Infections/prevention & control , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Viral Vaccines , Animals , Antibodies, Neutralizing/biosynthesis , Antibodies, Neutralizing/immunology , Antibodies, Viral/biosynthesis , Antibodies, Viral/immunology , Betacoronavirus/isolation & purification , Chlorocebus aethiops , Coronavirus Infections/immunology , Coronavirus Infections/virology , Dose-Response Relationship, Immunologic , Female , Immunogenicity, Vaccine , Immunoglobulin G/biosynthesis , Immunoglobulin G/blood , Immunoglobulin G/immunology , Macaca mulatta , Male , Mice , Mice, Inbred BALB C , Pilot Projects , Pneumonia, Viral/virology , Rats , Rats, Wistar , Vaccines, Inactivated/administration & dosage , Vaccines, Inactivated/adverse effects , Vaccines, Inactivated/immunology , Vero Cells , Viral Load , Viral Vaccines/administration & dosage , Viral Vaccines/adverse effects , Viral Vaccines/immunology
18.
Lancet ; 395(10223): 497-506, 2020 02 15.
Article in English | MEDLINE | ID: covidwho-665705

ABSTRACT

BACKGROUND: A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients. METHODS: All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by WHO and the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not. FINDINGS: By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0-58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0-13·0]). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα. INTERPRETATION: The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies. FUNDING: Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission.


Subject(s)
Coronavirus Infections/diagnosis , Coronavirus Infections/epidemiology , Pneumonia, Viral/diagnosis , Pneumonia, Viral/epidemiology , Adult , Age Distribution , Aged , China/epidemiology , Comorbidity , Coronavirus Infections/complications , Coronavirus Infections/transmission , Cough/epidemiology , Cough/virology , Female , Fever/epidemiology , Fever/virology , Hospitalization/statistics & numerical data , Humans , Intensive Care Units/statistics & numerical data , Male , Middle Aged , Myalgia/epidemiology , Myalgia/virology , Pneumonia, Viral/complications , Pneumonia, Viral/transmission , Prognosis , Radiography, Thoracic , /virology , Time Factors , Tomography, X-Ray Computed , Young Adult
19.
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 , 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 , T-Lymphocyte Subsets/immunology , Viral Load , Virus Replication
20.
Cell ; 182(3): 713-721.e9, 2020 08 06.
Article in English | MEDLINE | ID: covidwho-549043

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) threatens global public health. The development of a vaccine is urgently needed for the prevention and control of COVID-19. Here, we report the pilot-scale production of an inactivated SARS-CoV-2 vaccine candidate (BBIBP-CorV) that induces high levels of neutralizing antibodies titers in mice, rats, guinea pigs, rabbits, and nonhuman primates (cynomolgus monkeys and rhesus macaques) to provide protection against SARS-CoV-2. Two-dose immunizations using 2 µg/dose of BBIBP-CorV provided highly efficient protection against SARS-CoV-2 intratracheal challenge in rhesus macaques, without detectable antibody-dependent enhancement of infection. In addition, BBIBP-CorV exhibits efficient productivity and good genetic stability for vaccine manufacture. These results support the further evaluation of BBIBP-CorV in a clinical trial.


Subject(s)
Betacoronavirus/immunology , Coronavirus Infections/prevention & control , Drug Evaluation, Preclinical/methods , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Vaccines, Inactivated/therapeutic use , Viral Vaccines/therapeutic use , Animals , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Betacoronavirus/genetics , Chlorocebus aethiops , Coronavirus Infections/virology , Disease Models, Animal , Female , Guinea Pigs , Immunogenicity, Vaccine , Macaca fascicularis , Macaca mulatta , Male , Mice , Mice, Inbred BALB C , Phylogeny , Pneumonia, Viral/virology , Rabbits , Rats , Rats, Wistar , Vaccines, Inactivated/adverse effects , Vero Cells , Viral Vaccines/adverse effects
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