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1.
Cell Rep ; 39(11): 110955, 2022 Jun 14.
Article in English | MEDLINE | ID: covidwho-1866959

ABSTRACT

Direct myocardial and vascular injuries due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-driven inflammation is the leading cause of acute cardiac injury associated with coronavirus disease 2019 (COVID-19). However, in-depth knowledge of the injury characteristics of the heart affected by inflammation is lacking. In this study, using a quantitative spatial proteomics strategy that combines comparative anatomy, laser-capture microdissection, and histological examination, we establish a region-resolved proteome map of the myocardia and microvessels with obvious inflammatory cells from hearts of patients with COVID-19. A series of molecular dysfunctions of myocardia and microvessels is observed in different cardiac regions. The myocardia and microvessels of the left atrial are the most susceptible to virus infection and inflammatory storm, suggesting more attention should be paid to the lesion and treatment of these two parts. These results can guide in improving clinical treatments for cardiovascular diseases associated with COVID-19.


Subject(s)
COVID-19 , Heart Injuries , COVID-19/complications , Humans , Inflammation , Proteome , SARS-CoV-2
2.
International Journal of Biological Sciences ; 18(8):3237-3250, 2022.
Article in English | ProQuest Central | ID: covidwho-1842940

ABSTRACT

G protein-coupled receptors (GPCRs) are the largest family of druggable targets, and their biological functions depend on different ligands and intracellular interactomes. Some microRNAs (miRNAs) bind as ligands to RNA-sensitive toll-like receptor 7 to regulate the inflammatory response, thereby contributing to the pathogenesis of cancer or neurodegeneration. It is unknown whether miRNAs bind to angiotensin II (Ang II) type 2 receptor (AGTR2), a critical protective GPCR in cardiovascular diseases, as ligands or intracellular interactomes. Here, screening for miRNAs that bind to AGTR2, we identified and confirmed that the pre-miRNA hsa-let-7a-2 non-competitively binds to the intracellular third loop of AGTR2. Functionally, intracellular hsa-let-7a-2 overexpression suppressed the Ang II-induced AGTR2 effects such as cAMP lowering, RhoA inhibition, and activation of Src homology 2 domain-containing protein-tyrosine phosphatase 1, whereas hsa-let-7a-2 knockdown enhanced these effects. Consistently, overexpressed hsa-let-7a-2 restrained the AGTR2-induced antiproliferation, antimigration, and proapoptosis of cells, and vasodilation of mesenteric arteries. Our findings demonstrated that hsa-let-7a-2 is a novel intracellular partner of AGTR2 that negatively regulates AGTR2-activated signals.

3.
Nat Med ; 2022 May 10.
Article in English | MEDLINE | ID: covidwho-1830085

ABSTRACT

Having adopted a dynamic zero-COVID strategy to respond to SARS-CoV-2 variants with higher transmissibility since August 2021, China is now considering whether, and for how long, this policy can remain in place. The debate has thus shifted towards the identification of mitigation strategies for minimizing disruption to the healthcare system in the case of a nationwide epidemic. To this aim, we developed an age-structured stochastic compartmental susceptible-latent-infectious-removed-susceptible model of SARS-CoV-2 transmission calibrated on the initial growth phase for the 2022 Omicron outbreak in Shanghai, to project COVID-19 burden (that is, number of cases, patients requiring hospitalization and intensive care, and deaths) under hypothetical mitigation scenarios. The model also considers age-specific vaccine coverage data, vaccine efficacy against different clinical endpoints, waning of immunity, different antiviral therapies and nonpharmaceutical interventions. We find that the level of immunity induced by the March 2022 vaccination campaign would be insufficient to prevent an Omicron wave that would result in exceeding critical care capacity with a projected intensive care unit peak demand of 15.6 times the existing capacity and causing approximately 1.55 million deaths. However, we also estimate that protecting vulnerable individuals by ensuring accessibility to vaccines and antiviral therapies, and maintaining implementation of nonpharmaceutical interventions could be sufficient to prevent overwhelming the healthcare system, suggesting that these factors should be points of emphasis in future mitigation policies.

4.
Engineering (Beijing) ; 2022 Apr 20.
Article in English | MEDLINE | ID: covidwho-1796875

ABSTRACT

The rapid spread of the coronavirus disease (COVID-19) pandemic in over 200 countries poses a substantial threat to human health. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes COVID-19, can be discharged with feces into the drainage system. However, a comprehensive understanding of the occurrence, presence, and potential transmission of SARS-CoV-2 in sewers, especially in community sewers, is still lacking. This study investigated the virus occurrence by viral nucleic acid testing in vent stacks, septic tanks, and the main sewer outlets of community where confirmed patients had lived during the outbreak of the epidemic in Wuhan, China. The results indicated that the risk of long-term emission of SARS-CoV-2 to the environment via vent stacks of buildings was low after confirmed patients were hospitalized. SARS-CoV-2 were mainly detected in the liquid phase, as opposed to being detected in aerosols, and its RNA in the sewage of septic tanks could be detected for only four days after confirmed patients were hospitalized. The surveillance of SARS-CoV-2 in sewage could be a sensitive indicator for the possible presence of asymptomatic patients in the community, though the viral concentration could be diluted more than 10 times, depending on the sampling site, as indicated by the Escherichia coli (E. coli) test. The comprehensive investigation of the community sewage drainage system is helpful to understand the occurrence characteristics of SARS-CoV-2 in sewage after excretion with feces and the feasibility of sewage surveillance for COVID-19 pandemic monitoring.

5.
Emerg Microbes Infect ; 11(1): 1205-1214, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-1774288

ABSTRACT

SARS-CoV-2 infection causes most cases of severe illness and fatality in older age groups. Over 92% of the Chinese population aged ≥12 years has been fully vaccinated against COVID-19 (albeit with vaccines developed against historical lineages). At the end of October 2021, the vaccination programme has been extended to children aged 3-11 years. Here, we aim to assess whether, in this vaccination landscape, the importation of Delta variant infections could shift COVID-19 burden from adults to children. We developed an age-structured susceptible-infectious-removed model of SARS-CoV-2 transmission to simulate epidemics triggered by the importation of Delta variant infections and project the age-specific incidence of SARS-CoV-2 infections, cases, hospitalizations, intensive care unit admissions, and deaths. In the context of the vaccination programme targeting individuals aged ≥12 years, and in the absence of non-pharmaceutical interventions, the importation of Delta variant infections could have led to widespread transmission and substantial disease burden in mainland China, even with vaccination coverage as high as 89% across the eligible age groups. Extending the vaccination roll-out to include children aged 3-11 years (as it was the case since the end of October 2021) is estimated to dramatically decrease the burden of symptomatic infections and hospitalizations within this age group (39% and 68%, respectively, when considering a vaccination coverage of 87%), but would have a low impact on protecting infants. Our findings highlight the importance of including children among the target population and the need to strengthen vaccination efforts by increasing vaccine effectiveness.


Subject(s)
COVID-19 , Vaccines , Adult , Aged , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines , Child , China/epidemiology , Humans , Infant , SARS-CoV-2 , Vaccination
6.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-331890

ABSTRACT

After the adoption of a dynamic zero-COVID strategy in China for nearly two years, whether and for how long this policy can remain in place is unclear. The debate has thus shifted towards the identification of mitigation strategies capable to prevent the disruption of the healthcare system, should a nationwide epidemic caused by the SARS-CoV-2 Omicron variant start to unfold. To this aim, we developed a mathematical model of SARS-CoV-2 transmission tailored to the unique immunization and epidemiological situation of China. We find that the level of immunity induced by the current vaccination campaign would be insufficient to prevent overwhelming the healthcare system and major losses of human lives. Instead, a synergetic strategy would be needed and based on 1) a heterologous booster vaccination campaign, 2) treating 50% of symptomatic cases with an antiviral with an 80% efficacy in preventing severe outcomes, and 3) the adoption of non-pharmaceutical interventions (NPIs) capable of reducing Rt to ≤2. Protecting vulnerable individuals by ensuring accessibility to vaccines and antivirals, and maintaining a certain degree of NPIs should be emphasised in a future mitigation policy, possibly supported by strengthening critical care capacity and the development of highly efficacious vaccines with long-lasting immunity.

7.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-324768

ABSTRACT

Strategic prioritization of COVID-19 vaccines is urgently needed, especially in light of the limited supply that is expected to last for most, if not the entire, 2021. Dynamically adapting the allocation strategy to the evolving epidemiological situation could thus be critical during this initial phase of vaccine rollout. We developed a data-driven mechanistic model of SARS-CoV-2 transmission to explore optimal vaccine prioritization strategies in China that aim at reducing COVID-19 burden measured through different metrics. We found that reactively adapting the vaccination program to the epidemiological situation (i.e., allocate vaccine to a target group before reaching full coverage of other groups with initial higher priority) can be highly beneficial as such strategies are capable to simultaneously achieve different objectives (e.g., minimizing the number of deaths and of infections). The highest priority categories are broadly consistent under different hypotheses about vaccine efficacy, differential vaccine efficacy in preventing infection vs. disease, vaccine hesitancy, and SARS-CoV-2 transmissibility. Our findings also suggest that boosting the daily capacities up to 2.5 million courses (0.17% rollout speed) or higher could greatly reduce COVID-19 burden should a new wave start to unfold in China with reproduction number equal to 1.5 or lower. Finally, we estimate that a high vaccine supply in the early phase of the vaccination campaign is key to achieve large gains of strategic prioritizations.

8.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-323544

ABSTRACT

The coronavirus disease-19 (COVID-19) caused by SARS-CoV-2 infection can lead to a series of clinical settings from non-symptomatic viral carriers/spreaders to severe illness characterized by acute respiratory distress syndrome (ARDS)1,2. A sizable part of patients with COVID-19 have mild clinical symptoms at the early stage of infection, but the disease progression may become quite rapid in the later stage with ARDS as the common manifestation and followed by critical multiple organ failure, causing a high mortality rate of 7-10% in the elderly population with underlying chronic disease1-3. The pathological investigation in the lungs and other organs of fatal cases is fundamental for the mechanistic understanding of severe COVID-19 and the development of specific therapy in these cases. Gross anatomy and molecular markers allowed us to identify, in two fatal patients subject to necropsy, the main pathological features such as exudation and hemorrhage, epithelium injuries, infiltration of macrophages and fibrosis in the lungs. The mucous plug with fibrinous exudate in the alveoli and the activation of alveolar macrophages were characteristic abnormalities. These findings shed new insights into the pathogenesis of COVID-19 and justify the use of interleukin 6 (IL6) receptor antagonists and convalescent plasma with neutralizing antibodies against SARS-CoV-2 for severe patients.Authors Chaofu Wang, Jing Xie, Lei Zhao, Xiaochun Fei, Heng Zhang, and Yun Tan contributed equally to this work. Authors Chaofu Wang, Jun Cai, Rong Chen, Zhengli Shi, and Xiuwu Bian jointly supervised this work.

9.
BMC Med ; 20(1): 37, 2022 01 31.
Article in English | MEDLINE | ID: covidwho-1662418

ABSTRACT

BACKGROUND: To allow a return to a pre-COVID-19 lifestyle, virtually every country has initiated a vaccination program to mitigate severe disease burden and control transmission. However, it remains to be seen whether herd immunity will be within reach of these programs. METHODS: We developed a compartmental model of SARS-CoV-2 transmission for China, a population with low prior immunity from natural infection. Two vaccination programs were tested and model-based estimates of the immunity level in the population were provided. RESULTS: We found that it is unlikely to reach herd immunity for the Delta variant given the relatively low efficacy of the vaccines used in China throughout 2021 and the lack of prior natural immunity. We estimated that, assuming a vaccine efficacy of 90% against the infection, vaccine-induced herd immunity would require a coverage of 93% or higher of the Chinese population. However, even when vaccine-induced herd immunity is not reached, we estimated that vaccination programs can reduce SARS-CoV-2 infections by 50-62% in case of an all-or-nothing vaccine model and an epidemic starts to unfold on December 1, 2021. CONCLUSIONS: Efforts should be taken to increase population's confidence and willingness to be vaccinated and to develop highly efficacious vaccines for a wide age range.


Subject(s)
COVID-19 , Epidemics , Viral Vaccines , China/epidemiology , Humans , SARS-CoV-2
10.
Hypertens Res ; 45(5): 856-865, 2022 05.
Article in English | MEDLINE | ID: covidwho-1641956

ABSTRACT

The global coronavirus disease 2019 (COVID-19) pandemic has led to a health crisis. It remains unclear how anxiety affects blood pressure (BP) and cardiovascular risk among older patients with hypertension. In this study, we extracted longitudinal data on home BP monitored via a smartphone-based application in 3724 elderly patients with hypertension from a clinical trial (60-80 years; 240 in Wuhan and 3484 in non-Wuhan areas) to examine changes in morning BP during the COVID-19 outbreak in China. Anxiety was evaluated using Generalized Anxiety Disorder-7 item scores. Changes in morning systolic BP (SBP) were analyzed for five 30-day periods during the pandemic (October 21, 2019 to March 21, 2020), including the pre-epidemic, incubation, developing, outbreak, and plateau periods. Data on cardiovascular events were prospectively collected for one year. A total of 262 individuals (7.0%) reported an increased level of anxiety, and 3462 individuals (93.0%) did not. Patients with anxiety showed higher morning SBP than patients without anxiety, and the between-group differences in SBP change were +1.2 mmHg and +1.7 mmHg during the outbreak and plateau periods (P < 0.05), respectively. The seasonal BP variation in winter among patients with anxiety was suppressed during the pandemic. Anxious patients had higher rates of uncontrolled BP. During the 1-year follow-up period, patients with anxiety had an increased risk of cardiovascular events with a hazard ratio of 2.47 (95% confidence interval, 1.10-5.58; P = 0.03). In summary, COVID-19-related anxiety was associated with a short-term increase in morning SBP among older patients and led to a greater risk of cardiovascular events. (ClinicalTrials. gov number, NCT03015311).


Subject(s)
COVID-19 , Hypertension , Aged , Aged, 80 and over , Anxiety/epidemiology , Anxiety Disorders/epidemiology , Blood Pressure/physiology , Blood Pressure Monitoring, Ambulatory , Humans , Hypertension/complications , Hypertension/epidemiology , Middle Aged , Pandemics
11.
Nat Commun ; 13(1): 269, 2022 01 12.
Article in English | MEDLINE | ID: covidwho-1621240

ABSTRACT

A complete diagnostic autopsy is the gold-standard to gain insight into Coronavirus disease 2019 (COVID-19) pathogenesis. To delineate the in situ immune responses to SARS-CoV-2 viral infection, here we perform comprehensive high-dimensional transcriptional and spatial immune profiling in 22 COVID-19 decedents from Wuhan, China. We find TIM-3-mediated and PD-1-mediated immunosuppression as a hallmark of severe COVID-19, particularly in men, with PD-1+ cells being proximal rather than distal to TIM-3+ cells. Concurrently, lymphocytes are distal, while activated myeloid cells are proximal, to SARS-CoV-2 viral antigens, consistent with prevalent SARS-CoV-2 infection of myeloid cells in multiple organs. Finally, viral load positively correlates with specific immunosuppression and dendritic cell markers. In summary, our data show that SARS-CoV-2 viral infection induces lymphocyte suppression yet myeloid activation in severe COVID-19, so these two cell types likely have distinct functions in severe COVID-19 disease progression, and should be targeted differently for therapy.


Subject(s)
COVID-19/immunology , SARS-CoV-2/physiology , Aged , Autopsy , COVID-19/diagnosis , COVID-19/genetics , COVID-19/virology , China , Diagnosis , Female , Hepatitis A Virus Cellular Receptor 2/genetics , Hepatitis A Virus Cellular Receptor 2/immunology , Humans , Lymphocyte Activation , Lymphocytes/immunology , Male , Middle Aged , Myeloid Cells/immunology , Programmed Cell Death 1 Receptor/genetics , Programmed Cell Death 1 Receptor/immunology , SARS-CoV-2/immunology , Viral Load
12.
Nat Cell Biol ; 23(12): 1314-1328, 2021 12.
Article in English | MEDLINE | ID: covidwho-1559292

ABSTRACT

The lung is the primary organ targeted by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), making respiratory failure a leading coronavirus disease 2019 (COVID-19)-related mortality. However, our cellular and molecular understanding of how SARS-CoV-2 infection drives lung pathology is limited. Here we constructed multi-omics and single-nucleus transcriptomic atlases of the lungs of patients with COVID-19, which integrate histological, transcriptomic and proteomic analyses. Our work reveals the molecular basis of pathological hallmarks associated with SARS-CoV-2 infection in different lung and infiltrating immune cell populations. We report molecular fingerprints of hyperinflammation, alveolar epithelial cell exhaustion, vascular changes and fibrosis, and identify parenchymal lung senescence as a molecular state of COVID-19 pathology. Moreover, our data suggest that FOXO3A suppression is a potential mechanism underlying the fibroblast-to-myofibroblast transition associated with COVID-19 pulmonary fibrosis. Our work depicts a comprehensive cellular and molecular atlas of the lungs of patients with COVID-19 and provides insights into SARS-CoV-2-related pulmonary injury, facilitating the identification of biomarkers and development of symptomatic treatments.


Subject(s)
COVID-19/genetics , Lung/metabolism , Transcriptome/genetics , Alveolar Epithelial Cells/metabolism , Alveolar Epithelial Cells/pathology , Alveolar Epithelial Cells/virology , COVID-19/metabolism , Fibrosis/metabolism , Fibrosis/pathology , Fibrosis/virology , Humans , Lung/pathology , Lung/virology , Proteomics/methods , SARS-CoV-2/pathogenicity
13.
2021.
Preprint in English | Other preprints | ID: ppcovidwho-295323

ABSTRACT

Background To allow a return to a pre-COVID-19 lifestyle, virtually every country has initiated a vaccination program to mitigate severe disease burden and control transmission. However, it remains to be seen whether herd immunity will be within reach of these programs. Methods We developed a data-driven model of SARS-CoV-2 transmission for China, a population with low prior immunity from natural infection. The model is calibrated considering COVID-19 natural history and the estimated transmissibility of the Delta variant. Three vaccination programs are tested, including the one currently enacted in China and model-based estimates of the herd immunity level are provided. Results We found that it is unlike to reach herd immunity for the Delta variant given the relatively low efficacy of the vaccines used in China throughout 2021, the exclusion of underage individuals from the targeted population, and the lack of prior natural immunity. We estimate that, assuming a vaccine efficacy of 90% against the infection, vaccine-induced herd immunity would require a coverage of 93% or higher of the Chinese population. However, even when vaccine-induced herd immunity is not reached, we estimated that vaccination programs can reduce SARS-CoV-2 infections by 53-58% in case of an epidemic starts to unfold in the fall of 2021. Conclusions Efforts should be taken to increase population’s confidence and willingness to be vaccinated and to guarantee highly efficacious vaccines for a wider age range.

14.
Journal of Food Safety and Quality ; 11(10):3335-3338, 2020.
Article in Chinese | CAB Abstracts | ID: covidwho-1406949

ABSTRACT

Before the Spring Festival of 2020, the outbreak of pneumonia caused by new coronavirus infection in China spread to the whole country and other countries and regions in a short term. The epidemic has greatly affected China's food industry, especially the catering industry. In view of the considerable maturity of China's Internet industry, online food sales have been recognized by majority consumers. China can make full use of this advantage in combining food safety supervision and information technology. This will provides means for food safety supervision in special periods as well as solve the plight of food companies at such times. It can benefit in enterprise assistance work and supervisory work at the same time.

15.
Chinese Journal of Contemporary Pediatrics ; 22(10):1119-1124, 2020.
Article in English | PMC | ID: covidwho-1389767

ABSTRACT

Objective To study the expression of angiotensin-converting enzyme 2 (ACE2) and other key molecules of the RAS pathway in normal mice at different developmental stages, and to provide ideas for understanding the infection mechanism of coronavirus disease 2019 (COVID-19) as well as the diagnosis and treatment of children with COVID-19. Methods The mice at different developmental stages were enrolled, including fetal mice (embryonic days 14.5 and 18.5), neonatal mice (0, 3, 7, 14, and 21 days old), young mice (28 and 42 days old), and adult mice (84 days old). The lung tissues of all fetal mice from 4 pregnant mice were collected at each time point in the fetal group. Four mice were sampled in other age groups at each time point. Whole transcriptome resequencing was used to measure the mRNA expression of AGT, ACE, ACE2, Renin, Agtr1a, Agtr1b, Agtr2, and Mas1 in mouse lung tissue. Results The expression of ACE2 in the lungs showed changes from embryonic stage to adult stage. It increased gradually after birth, reached a peak on day 3 after birth, and reached a nadir on day 14 after birth (P<0.05). The expression of AGT reached a peak on days 0 and 7 after birth and reached a nadir on day 21 after birth (P<0.05). The expression of ACE increased rapidly after birth and reached a peak on day 21 after birth (P<0.05). Agtr1a expression reached a peak on day 21 after birth (P<0.05). Agtr2 expression gradually decreased to a low level after birth. Renin, Agtr1b, and Mas1 showed low expression in lung tissues at all developmental stages. Conclusions At different developmental stages of mice, ACE2 has dynamic expression changes, with high expression in early neonatal and adult mice. The other key molecules of the RAS pathway have their own expression patterns. These suggest that the difference in clinical features between children and adults with COVID-19 might be associated with the different expression levels of ACE2 in the different stages, and further studies are needed for the mechanism.

16.
Nat Commun ; 12(1): 4673, 2021 08 03.
Article in English | MEDLINE | ID: covidwho-1340997

ABSTRACT

Dynamically adapting the allocation of COVID-19 vaccines to the evolving epidemiological situation could be key to reduce COVID-19 burden. Here we developed a data-driven mechanistic model of SARS-CoV-2 transmission to explore optimal vaccine prioritization strategies in China. We found that a time-varying vaccination program (i.e., allocating vaccines to different target groups as the epidemic evolves) can be highly beneficial as it is capable of simultaneously achieving different objectives (e.g., minimizing the number of deaths and of infections). Our findings suggest that boosting the vaccination capacity up to 2.5 million first doses per day (0.17% rollout speed) or higher could greatly reduce COVID-19 burden, should a new wave start to unfold in China with reproduction number ≤1.5. The highest priority categories are consistent under a broad range of assumptions. Finally, a high vaccination capacity in the early phase of the vaccination campaign is key to achieve large gains of strategic prioritizations.


Subject(s)
COVID-19 Vaccines/administration & dosage , COVID-19/prevention & control , Health Care Rationing/methods , Mass Vaccination/methods , Basic Reproduction Number , COVID-19/epidemiology , COVID-19/transmission , China/epidemiology , Health Priorities , Humans , Incidence , Models, Theoretical , SARS-CoV-2/immunology , Vaccination Coverage
17.
Nat Hum Behav ; 5(8): 1009-1020, 2021 08.
Article in English | MEDLINE | ID: covidwho-1279881

ABSTRACT

COVID-19 vaccination is being conducted in over 200 countries and regions to control SARS-CoV-2 transmission and return to a pre-pandemic lifestyle. However, understanding when non-pharmaceutical interventions (NPIs) can be lifted as immunity builds up remains a key question for policy makers. To address this, we built a data-driven model of SARS-CoV-2 transmission for China. We estimated that, to prevent the escalation of local outbreaks to widespread epidemics, stringent NPIs need to remain in place at least one year after the start of vaccination. Should NPIs alone be capable of keeping the reproduction number (Rt) around 1.3, the synergetic effect of NPIs and vaccination could reduce the COVID-19 burden by up to 99% and bring Rt below the epidemic threshold in about 9 months. Maintaining strict NPIs throughout 2021 is of paramount importance to reduce COVID-19 burden while vaccines are distributed to the population, especially in large populations with little natural immunity.


Subject(s)
COVID-19 Vaccines/administration & dosage , COVID-19/prevention & control , COVID-19/transmission , Vaccination , China , Disease Outbreaks/prevention & control , Humans
18.
Cell Res ; 31(8): 836-846, 2021 08.
Article in English | MEDLINE | ID: covidwho-1275907

ABSTRACT

Severe COVID-19 disease caused by SARS-CoV-2 is frequently accompanied by dysfunction of the lungs and extrapulmonary organs. However, the organotropism of SARS-CoV-2 and the port of virus entry for systemic dissemination remain largely unknown. We profiled 26 COVID-19 autopsy cases from four cohorts in Wuhan, China, and determined the systemic distribution of SARS-CoV-2. SARS-CoV-2 was detected in the lungs and multiple extrapulmonary organs of critically ill COVID-19 patients up to 67 days after symptom onset. Based on organotropism and pathological features of the patients, COVID-19 was divided into viral intrapulmonary and systemic subtypes. In patients with systemic viral distribution, SARS-CoV-2 was detected in monocytes, macrophages, and vascular endothelia at blood-air barrier, blood-testis barrier, and filtration barrier. Critically ill patients with long disease duration showed decreased pulmonary cell proliferation, reduced viral RNA, and marked fibrosis in the lungs. Permanent SARS-CoV-2 presence and tissue injuries in the lungs and extrapulmonary organs suggest direct viral invasion as a mechanism of pathogenicity in critically ill patients. SARS-CoV-2 may hijack monocytes, macrophages, and vascular endothelia at physiological barriers as the ports of entry for systemic dissemination. Our study thus delineates systemic pathological features of SARS-CoV-2 infection, which sheds light on the development of novel COVID-19 treatment.


Subject(s)
COVID-19/pathology , Lung/virology , SARS-CoV-2/isolation & purification , Aged , Aged, 80 and over , Autopsy , COVID-19/virology , China , Cohort Studies , Critical Illness , Female , Fibrosis , Hospitalization , Humans , Kidney/pathology , Kidney/virology , Leukocytes, Mononuclear/pathology , Leukocytes, Mononuclear/virology , Lung/pathology , Male , Middle Aged , RNA, Viral/metabolism , SARS-CoV-2/genetics , Spleen/pathology , Spleen/virology , Trachea/pathology , Trachea/virology
19.
Circ Cardiovasc Qual Outcomes ; 14(5): e007098, 2021 05.
Article in English | MEDLINE | ID: covidwho-1232381

ABSTRACT

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has impacted clinical care worldwide. Evidence of how this health crisis affected common conditions like blood pressure (BP) control is uncertain. METHODS: We used longitudinal BP data from an ongoing randomized clinical trial to examine variations in home BP monitored via a smartphone-based application (app) in a total of 7394 elderly patients with hypertension aged 60 to 80 years stratified by their location in Wuhan (n=283) compared with other provinces of China (n=7111). Change in morning systolic BP (SBP) was analyzed for 5 30-day phases during the pandemic, including preepidemic (October 21 to November 20, 2019), incubation (November 21 to December 20, 2019), developing (December 21, 2019 to January 20, 2020), outbreak (January 21 to February 20, 2020), and plateau (February 21 to March 21, 2020). RESULTS: Compared with non-Wuhan areas of China, average morning SBP (adjusted for age, sex, body mass index) in Wuhan patients was significantly higher during the epidemic growth phases, which returned to normal at the plateau. Between-group differences in ΔSBP were +2.5, +3.0, and +2.1 mm Hg at the incubation, developing, and outbreak phases of COVID-19 (P<0.001), respectively. Sensitivity analysis showed a similar trend in trajectory pattern of SBP in both the intensive and standard BP control groups of the trial. Patients in Wuhan also had an increased regimen change in antihypertensive drugs during the outbreak compared with non-Wuhan patients. Expectedly, Wuhan patients were more likely to check their BP via the app, while doctors were less likely to monitor the app for BP control during the pandemic. CONCLUSIONS: Our data demonstrate that the COVID-19 pandemic was associated with a short-term increase in morning SBP among elderly patients with hypertension in Wuhan but not other parts of China. Further study will be needed to understand if these findings extended to other parts of the world substantially affected by the virus. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03015311.


Subject(s)
Blood Pressure Determination , COVID-19/epidemiology , Hypertension/diagnosis , Hypertension/physiopathology , Smartphone , Aged , Aged, 80 and over , Antihypertensive Agents/therapeutic use , China , Female , Humans , Hypertension/therapy , Longitudinal Studies , Male , Middle Aged , Self Care
20.
Med Sci Monit ; 27: e928837, 2021 Feb 13.
Article in English | MEDLINE | ID: covidwho-1161104

ABSTRACT

BACKGROUND Coronavirus 2 (SARS-CoV-2) was declared a pandemic by the World Health Organization (WHO) in March 2020. To further reveal the pathologic associations between coronavirus and hypoxemia, we report the findings of 4 complete systematic autopsies of severe acute respiratory syndrome coronavirus 2-positive individuals who died of multiple organ failure caused by severe hypoxemia. MATERIAL AND METHODS We examined the donated corpses of 4 deceased patients who had been diagnosed with severe acute respiratory syndrome coronavirus 2. A complete post-mortem examination was carried out on each corpse, and multiple organs were macroscopically examined. RESULTS The 4 corpses were 2 males and 2 females, with an average age of 69 years. Bilateral lungs showed various degrees of atrophy and consolidation, with diffusely tough and solid texture in the sections. A thromboembolism was found in the main pulmonary artery extending into the atrium in 1 corpse, and significant atherosclerotic plaques tagged in the inner wall of the aortic arch were found in 2 corpses. Two corpses were found to have slightly atrophied bilateral renal parenchyma. Atrophic changes in the spleen were found in 2 corpses. Notably, there were significantly expanded alveolar septa and prominent fibroblastic proliferation. CONCLUSIONS The laboratory data of these corpses showed a progressive decrease in blood oxygen saturation, followed by refractory and irreversible hypoxemia. Clinical and laboratory information and autopsy and histologic presentations of multiple organs showed insufficient air exchange due to abnormalities in the respiratory system, and reduced erythropoiesis in bone marrow may play a role.


Subject(s)
Autopsy , COVID-19/pathology , COVID-19/virology , Hypoxia/complications , Hypoxia/pathology , Pneumonia/pathology , Pneumonia/virology , SARS-CoV-2/physiology , Aged , Aged, 80 and over , Alveolar Epithelial Cells/metabolism , Alveolar Epithelial Cells/pathology , COVID-19/complications , Cell Aggregation , Female , Humans , Lung/pathology , Macrophages/pathology , Male , Middle Aged , Mucus/metabolism , Myocardium/pathology , Necrosis , Pneumonia/complications , Thoracic Cavity/pathology
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