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1.
Vaccines (Basel) ; 10(8)2022 Aug 20.
Article in English | MEDLINE | ID: covidwho-1997865

ABSTRACT

BACKGROUND: The impact of chronic health conditions (CHCs) on serostatus post-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination is unknown. METHODS: We assessed serostatus post-SARS-CoV-2 vaccination among fully vaccinated adult residents of Jefferson County, Kentucky, USA, from April 2021 to August 2021. Serostatus was determined by qualitative analysis of SARS-CoV-2-specific Spike IgG antibodies via enzyme-linked immunoassay (ELISA) in peripheral blood samples. RESULTS: Of the 5178 fully vaccinated participants, 51 were seronegative and 5127 were seropositive. Chronic kidney disease (CKD) and autoimmune disease showed the highest association with negative serostatus in fully vaccinated individuals. The absence of any CHC was strongly associated with positive serostatus. The risk of negative serostatus increased as the total number of pre-existing CHCs increased. Similarly, the use of two or more CHC-related medications was associated with seronegative status. CONCLUSIONS: The presence of any CHC, especially CKD or autoimmune disease, increased the likelihood of seronegative status among individuals who were fully vaccinated to SAR-CoV-2. This risk increased with a concurrent increase in number of comorbidities, especially with multiple medications. The absence of any CHC was protective and increased the likelihood of a positive serological response. These results will help develop appropriate guidelines for booster doses and targeted vaccination programs.

2.
Animal Model Exp Med ; 5(5): 430-435, 2022 10.
Article in English | MEDLINE | ID: covidwho-1966022

ABSTRACT

The mass inoculation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines to induce herd immunity is one of the most effective measures we can deploy in the fight against coronavirus disease 2019 (COVID-19). Pregnant women are prone to a higher risk of COVID-19, and maternal infection is a risk factor for a range of neurological disorders leading to abnormal behavior in adulthood. However, there are limited clinical data to support whether vaccination or infection post-immunization in pregnant women can affect the behavioral cognition of fetuses in adulthood. In this study, human angiotensin-converting enzyme 2 pregnant mice (F0 generation) were immunized with CoronaVac and then infected with SARS-CoV-2. Subsequently, we analyzed the behavioral cognition of their adult offspring (F1 generation) using the open-field test and Morris water maze test. The adult F1 generation did not exhibit any impairments in spontaneous locomotor activity or spatial reference memory.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Adult , Female , Mice , Pregnancy , Animals , COVID-19 Vaccines , COVID-19/prevention & control , Immunity, Herd , Vaccination
4.
Vaccine ; 40(32): 4609-4616, 2022 07 30.
Article in English | MEDLINE | ID: covidwho-1882618

ABSTRACT

The mass inoculation of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine to induce herd immunity is one of the most effective measures to fight COVID-19. The vaccination of pregnant women cannot only avoid or reduce the probability of infectious diseases, but also offers the most effective and direct protection for neonates by means of passive immunization. However, there is no randomized clinical data to ascertain whether the inactivated vaccination of pregnant women or women of childbearing age can affect conception and the fetus. We found that human angiotensin-converting enzyme 2 (hACE2) mice that were vaccinated with two doses of CoronaVac (an inactivated SARS-CoV-2 vaccine) before and during pregnancy exhibited normal weight changes and reproductive performance indices; the physical development of their offspring was also normal. Following intranasal inoculation with SARS-CoV-2, pregnant mice in the immunization group all survived; reproductive performance indices and the physical development of offspring were all normal. In contrast, mice in the non-immunization group all died before delivery. Analyses showed that inoculation of CoronaVac was safe and did not exert any significant effects on pregnancy, lactation, or the growth of offspring in hACE2 mice. Vaccination effectively protected the pregnant mice against SARS-CoV-2 infection and had no adverse effects on the growth and development of the offspring, thus suggesting that inoculation with an inactivated SARS-CoV-2 vaccine may be an effective strategy to prevent infection in pregnant women.


Subject(s)
COVID-19 Vaccines , COVID-19 , Lactation , Angiotensin-Converting Enzyme 2 , Animals , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , COVID-19 Vaccines/immunology , Female , Humans , Mice , Mice, Transgenic , Pregnancy , SARS-CoV-2 , Vaccines, Inactivated
5.
Signal Transduct Target Ther ; 7(1): 124, 2022 04 18.
Article in English | MEDLINE | ID: covidwho-1795804

ABSTRACT

Variants of concern (VOCs) like Delta and Omicron, harbor a high number of mutations, which aid these viruses in escaping a majority of known SARS-CoV-2 neutralizing antibodies (NAbs). In this study, Rhesus macaques immunized with 2-dose inactivated vaccines (Coronavac) were boosted with an additional dose of homologous vaccine or an RBD-subunit vaccine, or a bivalent inactivated vaccine (Beta and Delta) to determine the effectiveness of sequential immunization. The booster vaccination significantly enhanced the duration and levels of neutralizing antibody titers against wild-type, Beta, Delta, and Omicron. Animals administered with an indicated booster dose and subsequently challenged with Delta or Omicron variants showed markedly reduced viral loads and improved histopathological profiles compared to control animals, indicating that sequential immunization could protect primates against Omicron. These results suggest that sequential immunization of inactivated vaccines or polyvalent vaccines could be a potentially effective countermeasure against newly emerging variants.


Subject(s)
COVID-19 , SARS-CoV-2 , Animals , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/prevention & control , Macaca mulatta , SARS-CoV-2/genetics , Vaccination , Vaccines, Inactivated/genetics
6.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-330056

ABSTRACT

Background: The impact of chronic health conditions (CHC) on serostatus post-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination is unknown. Methods: We assessed serostatus post-SARS-CoV-2 vaccination among fully vaccinated participants recruited between April 2021 through August 2021 in 18 years and older residents of Jefferson County, Kentucky, USA. Serostatus was determined by measuring SARS-CoV-2 Spike protein specific immunoglobulin (Ig) G (Spike IgG) antibodies via enzyme-linked immunoassay (ELISA) in peripheral blood samples. Results: Of the 5,178 fully vaccinated participants, 51 were seronegative and 5,127 were seropositive. Chronic kidney disease (CKD) (OR=13.49;95% CI: 4.88, 37.3;P<0.0001) and autoimmune disease (OR=11.34;95% CI: 5.21, 24.69;P<0.0001) showed highest association with negative serostatus in fully vaccinated participants. The absence of any CHC was strongly associated with positive serostatus (OR=0.37;95% CI: 0.19, 0.73;P=0.003). The risk of negative serostatus increased in the presence of two CHCs (OR=2.82;95% CI: 1.14, 7) to three or more CHCs (OR=4.52;95% CI: 1.68, 12.14). Similarly, use of 2 or more CHC related medications was significantly associated with seronegative status (OR=6.08;95%: 2.01, 18.35). Conclusions: Presence of any CHC, especially CKD or autoimmune disease, increased the likelihood of seronegative status among individuals who were fully vaccinated to SAR-CoV-2. This risk increased with a concurrent increase in number of comorbidities, especially with multiple medications. Absence of any CHC was protective and increased the likelihood of a positive serological response post-vaccination. These results will help develop appropriate guidelines for booster doses and targeted vaccination programs.

7.
Chin Med J (Engl) ; 133(9): 1015-1024, 2020 May 05.
Article in English | MEDLINE | ID: covidwho-1722617

ABSTRACT

BACKGROUND: Human infections with zoonotic coronaviruses (CoVs), including severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV, have raised great public health concern globally. Here, we report a novel bat-origin CoV causing severe and fatal pneumonia in humans. METHODS: We collected clinical data and bronchoalveolar lavage (BAL) specimens from five patients with severe pneumonia from Wuhan Jinyintan Hospital, Hubei province, China. Nucleic acids of the BAL were extracted and subjected to next-generation sequencing. Virus isolation was carried out, and maximum-likelihood phylogenetic trees were constructed. RESULTS: Five patients hospitalized from December 18 to December 29, 2019 presented with fever, cough, and dyspnea accompanied by complications of acute respiratory distress syndrome. Chest radiography revealed diffuse opacities and consolidation. One of these patients died. Sequence results revealed the presence of a previously unknown ß-CoV strain in all five patients, with 99.8% to 99.9% nucleotide identities among the isolates. These isolates showed 79.0% nucleotide identity with the sequence of SARS-CoV (GenBank NC_004718) and 51.8% identity with the sequence of MERS-CoV (GenBank NC_019843). The virus is phylogenetically closest to a bat SARS-like CoV (SL-ZC45, GenBank MG772933) with 87.6% to 87.7% nucleotide identity, but is in a separate clade. Moreover, these viruses have a single intact open reading frame gene 8, as a further indicator of bat-origin CoVs. However, the amino acid sequence of the tentative receptor-binding domain resembles that of SARS-CoV, indicating that these viruses might use the same receptor. CONCLUSION: A novel bat-borne CoV was identified that is associated with severe and fatal respiratory disease in humans.


Subject(s)
Betacoronavirus , Coronavirus Infections/virology , Pneumonia, Viral/virology , Adult , Aged , Betacoronavirus/genetics , Betacoronavirus/isolation & purification , COVID-19 , Coronavirus Infections/diagnostic imaging , Coronavirus Infections/therapy , Female , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/diagnostic imaging , Pneumonia, Viral/therapy , SARS-CoV-2 , Tomography, X-Ray , Treatment Outcome
8.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-324154

ABSTRACT

To evaluate the efficacy of N95 respirators and medical masks for protection against respiratory infectious diseases, including COVID-19. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) and observational studies evaluating the use of N95 respirators and medical masks for protection against respiratory infectious diseases. We retrieved relevant articles published from January 1994 to January 2020 by searching the PubMed, EMBASE, Cochrane CENTRAL, and Web of Science databases. The study quality was evaluated using the Cochrane Risk of Bias tool with RevMan 5.3 software. Eleven RCTs adjusted for clustering were included in the meta-analysis. Compared with the control group, N95 respirators or medical masks conferred significant protection against respiratory infectious diseases (odds ratio (OR) = 0.50;95% CI: 0.29–0.84). Compared to medical masks, N95 respirators conferred significant protection against respiratory infectious diseases (OR = 0.75;95% confidence interval (CI): 0.57–0.99). Meta-analysis of 10 observational studies adjusting for clustering also suggested that N95 respirators and medical masks are effective for protection against respiratory infectious diseases (OR = 0.59;95% CI: 0.42–0.82). However, only one case report showed the effectiveness of medical masks for preventing COVID-19. Although medical masks and N95 respirators may confer significant protection against respiratory infectious diseases, there is insufficient evidence to conclude that these types of personal protective equipment offer similar protection against COVID-19. Therefore, in the absence of sufficient resources during an epidemic, medical masks and N95 respirators should be reserved for high-risk, aerosol-generating producing procedures.

9.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-321379

ABSTRACT

Background: and aims: Calcium channel blockers (CCBs) and angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) are commonly used in the treatment of hypertension. However, it is still not clear whether there are differences among different anti-hypertensive drugs in the treatment of patients with coronavirus disease 2019 (COVID-19) and hypertension. Herein, we aimed to assess the relation between different anti-hypertensive medications and COVID-19 outcomes. Materials: and methods: We conducted a retrospective analysis of 58 hypertensive patients with COVID-19 who were treated with different anti-hypertensive drugs and reviewed the clinical data obtained from electronic medical records, including epidemiological, clinical, laboratory, and the treatment and progression of the disease. Results: : There was no obvious difference in clinical prognosis after using any anti-hypertensive drugs in patients with COVID-19 and hypertension, but the different anti-hypertensive drugs were associated with the use of non-invasive ventilator treatment at admission comparing two groups between ACEIs/ARBs and CCBs+ACEIs/ARBs. Conclusion: there is no evidence showing that the different use of anti-hypertensive drugs is related to outcomes of patients with COVID-19 and hypertension, even between single drug regimen and combined therapy (with at least two anti-hypertensive drugs as combined therapy).

10.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-310871

ABSTRACT

Background: Coronavirus disease 2019 (COVID-19) has spread from its origins to the world and become a pandemic since late 2019. It predominantly damages the lungs and causes diffuse alveolar injury with edema, cellular fibroblasts and hyaline membrane formation, resulting in acute respiratory insufficiency, respiratory failure, sepsis, acute heart injury, heart failure and other severe complications. It is also reported that moxibustion can effectively modify the negative emotions and relieve the symptoms of chest distress and impaired appetite for the patient with COVID-19. The main objective of current research is to make an assessment for effectiveness and safety of the moxibustion as an important complementary and alternative therapeutic method for COVID-19. Methods: and analysis Articles for the systematic literature will be located at the MEDLINE, OVID, EMBASE, CNKI, CBM, NTR, Chi CTR databases. With no restriction about language, manual search will be conducted for potential eligible articles as supplements. Any randomized controlled trials (RCTs) with any moxibustion interventions issued by the therapeutic regimen on all patients diagnosed with COVID-19 will be included. We will include the published studies with no restriction about language. All study records of the title and abstract identified by the search strategies will be directly imported and assessed based on the eligibility criteria. Risk of individual studies for the methodological quality of eligible RCTs will be assessed with the tool from the Cochrane Collaboration’s risk of bias tool. Discussion: The purpose of this study is to conduct a systematic review and meta-analysis of the efficacy and safety of moxibustion as a complementary and alternative treatment for COVID-19.No studies have investigated whether moxibustion will relieve clinical symptoms and shorten the length of hospitalization time.To the best of our knowledge, this is the first systematic review and meta-analysis program designed to update the currently available evidence. Despite the fact of controversial views in using moxibustion, if this study confirms its efficacy and safety, it could provide a better guide for clinical practice around the world. Systematic review registration PROSPERO CRD42020176572.

11.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-324963

ABSTRACT

Background: The Coronavirus Disease 2019 (COVID-19) has been demonstrated as the cause of pneumonia. Nevertheless, it has not been reported as the cause of acute myocarditis or fulminant myocarditis. Case Presentation: A 63-year-old male was admitted with pneumonia and cardiac symptoms. He was genetically confirmed as COVID-19 by testing sputum on the first day of admission. He also had an elevated troponin-I (Trop I) level and diffuse myocardial dyskinesia along with decreased left ventricular ejection fraction (LVEF) on echocardiography. The highest level of Interleukin 6 was 272.40pg/ml. Bedside chest radiograph had typical ground-glass changes of viral pneumonia. The laboratory test results of virus that can cause myocarditis are all negative. The patient conformed to the diagnostic criteria of Chinese expert consensus statement for fulminant myocarditis. After receiving antiviral therapy and mechanical life support, the Trop I reduced to 0.10 g/L, and Interleukin 6 was 7.63 pg/ml. Meanwhile the LVEF of the patient gradually recovered to 68%. Conclusion: COVID-19 patients may develop severe cardiac complications such as myocarditis and heart failure, and this is the first case of COVID-19 infection complicated with fulminant myocarditis. The mechanism of cardiac pathology caused by COVID-19 needs further study.

12.
Frontiers in cardiovascular medicine ; 8, 2021.
Article in English | EuropePMC | ID: covidwho-1679286

ABSTRACT

Coronary artery disease (CAD) is a major contributor to morbidity and mortality worldwide. Myocardial ischemia may occur in patients with normal or non-obstructive CAD on invasive coronary angiography (ICA). The comprehensive evaluation of coronary CT angiography (CCTA) integrated with fractional flow reserve derived from CCTA (CT-FFR) to CAD may be essential to improve the outcomes of patients with non-obstructive CAD. China CT-FFR Study-2 (ChiCTR2000031410) is a large-scale prospective, observational study in 29 medical centers in China. The primary purpose is to uncover the relationship between the CCTA findings (including CT-FFR) and the outcome of patients with non-obstructive CAD. At least 10,000 patients with non-obstructive CAD but without previous revascularization will be enrolled. A 5-year follow-up will be performed. The primary endpoint is the occurrence of major adverse cardiovascular events (MACE), including all-cause mortality, non-fatal myocardial infarct, unplanned revascularization, and hospitalization for unstable angina. Clinical characteristics, laboratory and imaging examination results will be collected to analyze their prognostic value.

14.
Signal Transduct Target Ther ; 7(1): 29, 2022 01 28.
Article in English | MEDLINE | ID: covidwho-1655546

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is transmitted on mink farms between minks and humans in many countries. However, the systemic pathological features of SARS-CoV-2-infected minks are mostly unknown. Here, we demonstrated that minks were largely permissive to SARS-CoV-2, characterized by severe and diffuse alveolar damage, and lasted at least 14 days post inoculation (dpi). We first reported that infected minks displayed multiple organ-system lesions accompanied by an increased inflammatory response and widespread viral distribution in the cardiovascular, hepatobiliary, urinary, endocrine, digestive, and immune systems. The viral protein partially co-localized with activated Mac-2+ macrophages throughout the body. Moreover, we first found that the alterations in lipids and metabolites were correlated with the histological lesions in infected minks, especially at 6 dpi, and were similar to that of patients with severe and fatal COVID-19. Particularly, altered metabolic pathways, abnormal digestion, and absorption of vitamins, lipids, cholesterol, steroids, amino acids, and proteins, consistent with hepatic dysfunction, highlight metabolic and immune dysregulation. Enriched kynurenine in infected minks contributed to significant activation of the kynurenine pathway and was related to macrophage activation. Melatonin, which has significant anti-inflammatory and immunomodulating effects, was significantly downregulated at 6 dpi and displayed potential as a targeted medicine. Our data first illustrate systematic analyses of infected minks to recapitulate those observations in severe and fetal COVID-19 patients, delineating a useful animal model to mimic SARS-CoV-2-induced systematic and severe pathophysiological features and provide a reliable tool for the development of effective and targeted treatment strategies, vaccine research, and potential biomarkers.


Subject(s)
COVID-19/metabolism , Lung/metabolism , Macrophages, Alveolar/metabolism , Metabolome , Mink/virology , SARS-CoV-2/metabolism , Amino Acids/metabolism , Animals , Antiviral Agents/pharmacology , COVID-19/drug therapy , COVID-19/genetics , COVID-19/pathology , Disease Models, Animal , Female , Humans , Lung/pathology , Lung/virology , Macrophages, Alveolar/pathology , Macrophages, Alveolar/virology , Melatonin/metabolism , Metabolic Networks and Pathways/genetics , Molecular Targeted Therapy/methods , SARS-CoV-2/drug effects , SARS-CoV-2/genetics , SARS-CoV-2/pathogenicity , Sterols/metabolism , Virulence , Virus Replication/genetics
15.
Asia Pac Policy Stud ; 9(1): 5-22, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1615936

ABSTRACT

The Chinese Communist Party is consolidating one party rule under the leadership of Xi Jinping. Beijing seeks to rule by central mandate while limiting local autonomy. The central government response to the COVID-19 public health emergency reinforces this view. In January 2020 Beijing established the Central Epidemic Response Leading Group to mobilise a comprehensive nationwide policy effort to contain the virus. The exceptional nature of the COVID-19 national emergency allows the central government to project power over local authorities and leverage over citizens, but we argue that this is a short-term phenomenon because local disease control initiatives remain important, with local authorities adapting national policies to meet constituent needs. There are degrees of policy discretion and divergence at the subnational level that enable context-specific responses to the virus within China's strict bureaucratic hierarchy. Primary data derives from interviews and observations in Nancun village, Hebei Province, conducted from January to April 2020. Evidence from Nancun explains how local authorities interpret the edicts and mandates of the central government.

16.
J Cardiovasc Transl Res ; 15(1): 38-48, 2022 02.
Article in English | MEDLINE | ID: covidwho-1594479

ABSTRACT

Angiotensin-converting enzyme 2 (ACE2) is required for the cellular entry of the severe acute respiratory syndrome coronavirus 2. ACE2, via the Ang-(1-7)-Mas-R axis, is part of the antihypertensive and cardioprotective effects of the renin-angiotensin system. We studied hospitalized COVID-19 patients with hypertension and hypertensive human(h) ACE2 transgenic mice to determine the outcome of COVID-19 with or without AT1 receptor (AT1R) blocker treatment. The severity of the illness and the levels of serum cardiac biomarkers (CK, CK-BM, cTnI), as well as the inflammation markers (IL-1, IL-6, CRP), were lesser in hypertensive COVID-19 patients treated with AT1R blockers than those treated with other antihypertensive drugs. Hypertensive hACE2 transgenic mice, pretreated with AT1R blocker, had increased ACE2 expression and SARS-CoV-2 in the kidney and heart, 1 day post-infection. We conclude that those hypertensive patients treated with AT1R blocker may be at higher risk for SARS-CoV-2 infection. However, AT1R blockers had no effect on the severity of the illness but instead may have protected COVID-19 patients from heart injury, via the ACE2-angiotensin1-7-Mas receptor axis.


Subject(s)
COVID-19 , Hypertension , Animals , Humans , Hypertension/complications , Hypertension/drug therapy , Inpatients , Mice , Mice, Transgenic , Renin-Angiotensin System , SARS-CoV-2 , Virulence
17.
Int J Infect Dis ; 115: 116-125, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1560758

ABSTRACT

OBJECTIVES: A specific and sensitive automated chemiluminescent immunoassay (CLIA) was developed to detect neutralizing antibody (NAb) levels. This assay can be used for the diagnosis of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, treatment and vaccine evaluation. METHODS: The SARS-CoV-2 receptor-binding domain (RBD) and a stabilized version of the spike ectodomain as antigens were detected by CLIA. Sera NAb titers and concentrations from 860 SARS-CoV-2 vaccinees, 232 SARS-CoV-2 convalescent patients and 675 healthy individuals were tested by microneutralization test (MNT) and CLIA, respectively. Mathematical models were established to evaluate the relationship between two variables in different groups. CONCLUSIONS: With the RBD-based CLIA protocol, CLIA can be used to replace MNT to test SARS-CoV-2 NAb. Vaccine effectiveness, protectiveness and durability can be evaluated effectively by mathematical models. It is RESULTS: Analysing the relationship between NAb titers and concentrations, R2 for the decision-making tree was 0.870 and that of progressive linear fitting was 0.821. The receiver operating characteristic curve indicated specificity of 78.1%, sensitivity of 87.4%, cut-off value of 6.43 AU/mL and borderline range of 5.79-7.07 AU/mL for CLIA. Three-quarters (75.4%) of vaccinees were found to be NAb positive, and 5.35% vaccinees had NAb protective capability. The half-life of NAb in vaccinees was 10-11 weeks.for vaccinees to take a NAb assay periodically.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Neutralizing , Antibodies, Viral , Humans , Immunoassay , Vaccine Efficacy
18.
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
19.
Sci Total Environ ; 795: 148807, 2021 Nov 15.
Article in English | MEDLINE | ID: covidwho-1294228

ABSTRACT

To stop the spread of COVID-19 (2019 novel coronavirus), China placed lockdown on social activities across China since mid-January 2020. The government actions significantly affected emissions of atmospheric pollutants and unintentionally created a nationwide emission reduction scenario. In order to assess the impacts of COVID-19 on fine particular matter (PM2.5) levels, we developed a "conditional variational autoencoder" (CVAE) algorithm based on the deep learning to discern unsupervised PM2.5 anomalies in Chines cities during the COVID-19 epidemic. We show that the timeline of changes in number of cities with unsupervised PM2.5 anomalies is consistent with the timeline of WHO's response to COVID-19. Using unsupervised PM2.5 anomaly as a time node, we examine changes in PM2.5 before and after the time node to assess the response of PM2.5 to the COVID-19 lockdown. The rate of decrease of PM2.5 around the time node in northern China is 3.5 times faster than southern China, and decreasing PM2.5 levels in southern China is 3.5 times of that in northern China. Results were also compared with anomalous PM2.5 occurring in Chinese's Spring Festival from 2017 to 2019, PM2.5 anomalies during around Chinese New Year in 2020 differ significantly from 2017 to 2019. We demonstrate that this method could be used to detect the response of air quality to sudden changes in social activities.


Subject(s)
Air Pollutants , Air Pollution , COVID-19 , Epidemics , Air Pollutants/analysis , Air Pollution/analysis , China/epidemiology , Cities , Communicable Disease Control , Environmental Monitoring , Humans , Particulate Matter/analysis , SARS-CoV-2
20.
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
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