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2.
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
3.
Int J Biol Sci ; 18(7): 2703-2713, 2022.
Article in English | MEDLINE | ID: covidwho-1811190

ABSTRACT

Coronavirus disease 2019 (COVID-19), a global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) had resulted in considerable morbidity and mortality. COVID-19 primarily posed a threat to the respiratory system and violated many different organs, including the heart, kidney, liver, and blood vessels with the development of the disease. Severe patients were often accompanied by cardiac injury, and once the heart gets damaged, the mortality of patients will significantly increase. The main clinical manifestations of cardiac injury range from myocarditis, heart failure (HF), arrhythmia, and Takotsubo cardiomyopathy (TCM). A high abundance of angiotensin-converting enzyme II (ACE2) on the membrane of cardiomyocytes makes it possible that the virus can directly attack cardiomyocytes as subsequently evidenced by the detection of spike protein and virus RNA in autopsy cardiac tissues. The secondary myocardial injury through systemic inflammatory and immune response also caused obvious cardiac damage. The pathological manifestations of heart tissue were diverse, varied from mild cardiomyocyte edema, myocardial hypertrophy, cardiomyocyte degeneration, and necrosis to severe myocarditis caused by lymphocyte and macrophage infiltration. However, the mechanism of heart injury was still unclear. Here, we summarized the clinical manifestations and mechanism of SARS-CoV2 mediated cardiac injury, providing a reference for cardiac treatment in critically ill patients.


Subject(s)
COVID-19 , Heart Injuries , Myocarditis , Humans , RNA, Viral , SARS-CoV-2
4.
Clin Immunol ; 239: 109022, 2022 06.
Article in English | MEDLINE | ID: covidwho-1803761

ABSTRACT

In March 2020, when coronavirus disease 2019 (COVID-19) was just beginning to spread around the world, we presented the potential benefits and controversies of anti-inflammatory therapy in COVID-19 patients based on the limited experience and proposed some types of anti-inflammatory drugs with potential therapeutic value, while without evidence-based data. In the past one more year, many clinical trials or real-world studies have been performed, either confirm or deny the efficacy of certain anti-inflammatory drugs in the treatment of COVID-19. In this review we summarize the progress of anti-inflammatory and immune therapy in COVID-19, including glucocorticoids, IL-6 antagonist, IL-1 inhibitor, kinase inhibitors, non-steroidal anti-inflammatory drugs and chloroquine/hydroxychloroquine.


Subject(s)
COVID-19 , Anti-Inflammatory Agents/therapeutic use , COVID-19/drug therapy , Chloroquine/therapeutic use , Humans , Hydroxychloroquine/therapeutic use , SARS-CoV-2
5.
BMJ Open ; 12(3): e055365, 2022 03 28.
Article in English | MEDLINE | ID: covidwho-1769912

ABSTRACT

OBJECTIVES: We aimed to provide an insight into the life of survivors of critical COVID-19 in China. METHODS: We conducted an online survey and qualitative interviews among intensive care unit survivors of critical COVID-19 between November and December 2020 in Wuhan, China. Eligible participants were asked to complete the EQ-5D-5L and the Short Form 36-Item Survey, and invited to participate in a semistructured face-to-face interview. Descriptive analyses and phenomenological approach were adopted to analyse quantitative and qualitative data, respectively. RESULTS: Of 10 survivors who completed the questionnaire, 8 participated in the interview. The mean scores±SD of EuroQol-5 Dimensions-5 Level utility and EuroQol-Visual Analogue Scale were 0.88±0.15 and 80.9±14.2, respectively. The qualitative interview identified four themes, namely poor physical health, post-traumatic stress, social stigma and family support. CONCLUSIONS: COVID-19 survivors continue fighting physical and psychological impacts. Despite strong family support, these patients are struggling with social stigma. It is a long, challenging journey to recovery for patients and society.


Subject(s)
COVID-19 , COVID-19/epidemiology , China/epidemiology , Humans , Intensive Care Units , Qualitative Research , Survivors/psychology
7.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-315658

ABSTRACT

Since early 2020, the coronavirus disease 2019 (COVID-19) has spread rapidly across the world. As at the date of writing this article, the disease has been globally reported in 223 countries and regions, infected over 108 million people and caused over 2.4 million deaths (https://covid19.who.int/, accessed on Feb. 17, 2021). Avoiding person-to-person transmission is an effective approach to control and prevent the pandemic. However, many daily activities, such as transporting goods in our daily life, inevitably involve person-to-person contact. Using an autonomous logistic vehicle to achieve contact-less goods transportation could alleviate this issue. For example, it can reduce the risk of virus transmission between the driver and customers. Moreover, many countries have imposed tough lockdown measures to reduce the virus transmission (e.g., retail, catering) during the pandemic, which causes inconveniences for human daily life. Autonomous vehicle can deliver the goods bought by humans, so that humans can get the goods without going out. These demands motivate us to develop an autonomous vehicle, named as Hercules, for contact-less goods transportation during the COVID-19 pandemic. The vehicle is evaluated through real-world delivering tasks under various traffic conditions.

8.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-308309

ABSTRACT

Background: COVID-19 is a viral respiratory disease caused by the severe acute respiratory syndrome-Coronavirus type 2 (SARS-CoV-2). Patients with this disease may be more prone to venous or arterial thrombosis because of the activation of many factors involved in it, including inflammation, platelet activation and endothelial dysfunction. Interferon gamma inducible protein-10 (IP-10), monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein 1-alpha (MIP1α) are cytokines related to thrombosis. Therefore, this study focused on these three indicators in COVID-19, with the hope to find biomarkers that are associated with patients’ outcome. Methods: This is a retrospective single-center study involving 74 severe and critically ill COVID-19 patients recruited from the ICU department of the Tongji Hospital in Wuhan, China. The patients were divided into two groups: severe patients and critically ill patients. The serum IP-10, MCP-1 and MIP1α level in both groups was detected using the enzyme-linked immunosorbent assay (ELISA) kit. The clinical symptoms, laboratory test results, and the outcome of COVID-19 patients were retrospectively analyzed. Results: The serum IP-10 and MCP-1 level in critically ill patients was significantly higher than that in severe patients ( P <0.001). However, no statistical difference in MIP1α between the two groups was found. The analysis of dynamic changes showed that these indicators remarkably increased in patients with poor prognosis. Since the selected patients were severe or critically ill, no significant difference was observed between survival and death. Conclusions: IP-10 and MCP-1 are biomarkers associated with the severity of COVID-19 disease and can be related to the risk of death in COVID-19 patients.

9.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-325121

ABSTRACT

Early diagnosis and isolation of cases are particularly crucial for coronavirus disease 2019 (COVID-19) in global pandemic. The aim of this study is to determine the diagnostic performance of chest computed tomography (CT) and imaging features for diagnosing COVID-19. Diagnostic accuracy studies of CT and RT-PCR in patients with clinically suspected COVID-19, which were published up to April 25th, 2020 from MEDLINE, EMBASE, and the Cochrane Library. Twelve studies (n=2,204) were included. The pooled sensitivity, specificity, likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) of chest CT for detecting COVID-19 were 94.5% (95% confidence interval (CI) 89.5 to 97.2%) and 41.8% (95% CI 24.2 to 61.6%), 1.6 (95% CI: 1.6-2.3), 0.13 (95% CI: 0.06-0.31), and 12.4 (95% CI: 4.0-38.5), respectively. Initial RT-PCR revealed a better diagnostic performance. Peripheral lesions, bilateral involvement, multiple lesions, and ground-glass opacities (GGO), revealed to be with better diagnostic value than other CT manifestations. Using chest CT for COVID-19 diagnosis has a high sensitivity and a relatively low specificity. Bilateral multiple peripheral lesions and GGO revealed to be with better diagnostic value. For areas with high prevalence, chest CT could be a good screening test to preliminary screen patients with COVID-19 quickly.

10.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-322749

ABSTRACT

Since the outbreak of COVID-19 in China at the end of 2019, the world has experienced a large-scale epidemic caused by the SARS-CoV-2. Epidemiological and clinical course of COVID-19 patients have been reported, but there have been few analyses about the characteristics, predictive risk factors and outcomes of critical patients. In this single-center retrospective case-control study, 90 adult inpatients hospitalized at Tongji Hospital (Wuhan, China) were included. Demographic, clinical, laboratory test and treatment data were obtained and compared between critical and non-critical patients. We found that c ompared with non-critical patients, the critical patients had higher SOFA score and qSOFA scores. Critical patients had lower lymphocyte and platelet count, elevated D-dimer, decreased fibrinogen, and elevated high-sensitivity C-reactive protein (hsCRP) and interleukin-6(IL-6). More critical patients received treatment including antibiotics, anticoagulation, corticosteroid and oxygen therapy than non-critical ones. Multivariable regression showed higher qSOFA score and elevation of IL-6 were related to critical patients. Antibiotic usage and anticoagulation were associated with decreased in-hospital mortality. And critical grouping contributed greatly to in-hospital death. Critical COVID-19 patients have a more severe clinical cours. qSOFA score and elevation of IL-6 are risk factors for critical condition. Non-critical grouping, positive antibiotic application and anticoagulation may be beneficial for patient survival.

12.
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
13.
Adv Sci (Weinh) ; 9(7): e2104192, 2022 03.
Article in English | MEDLINE | ID: covidwho-1589262

ABSTRACT

Coronavirus disease 2019 (COVID-19) patients with impact on skin and hair loss are reported. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is detected in the skin of some patients; however, the detailed pathological features of skin tissues from patients infected with SARS-CoV-2 at a molecular level are limited. Especially, the ability of SARS-CoV-2 to infect skin cells and impact their function is not well understood. A proteome map of COVID-19 skin is established here and the susceptibility of human-induced pluripotent stem cell (hiPSC)-derived skin organoids with hair follicles and nervous system is investigated, to SARS-CoV-2 infection. It is shown that KRT17+ hair follicles can be infected by SARS-CoV-2 and are associated with the impaired development of hair follicles and epidermis. Different types of nervous system cells are also found to be infected, which can lead to neuron death. Findings from the present work provide evidence for the association between COVID-19 and hair loss. hiPSC-derived skin organoids are also presented as an experimental model which can be used to investigate the susceptibility of skin cells to SARS-CoV-2 infection and can help identify various pathological mechanisms and drug screening strategies.


Subject(s)
COVID-19/physiopathology , Induced Pluripotent Stem Cells/cytology , Models, Biological , Organoids/cytology , Skin/cytology , COVID-19/virology , Hair Follicle/virology , Humans , Nervous System/virology , Proteomics , SARS-CoV-2/isolation & purification
14.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-296428

ABSTRACT

Background: The pathological features of severe cardiac injury induced by COVID-19 and relevant clinical features is unknown.<br><br>Methods: This autopsy cohort study, including hearts from 26 deceased patients hospitalized in intensive care unit due to COVID-19, was conducted at four sites in Wuhan, China. Cases were divided into neutrophil-infiltration group and no-neutrophil group according to histopathological identification of neutrophilic infiltrates or not.<br><br>Findings: Among 26 cases, four cases had active myocarditis with histopathological examination. All cases with myocarditis accompanied with extensive neutrophil infiltration, while cases without myocarditis did not. Detection rates of interleukin-6 (100% vs 4.6%) and tumor necrosis factor-α (100% vs 31.8%) in neutrophil-infiltration group were significantly higher compared to no-neutrophil group (p<0.05 for both). At admission, patients with neutrophil infiltration in myocardium had significantly higher baseline values of aspartate aminotransferase, D dimer and high-sensitivity C reactive protein compared to other 22 patients (p<0.05 for all). During hospitalization, patients with neutrophil infiltration had a significantly higher maximum of creatine kinase (CK)-MB (median 280.0 vs 38.7IU/L, p=0.04), and a quantitatively higher top Troponin I (median 1.112 vs 0.220ng/ml, p=0.56) than patients without neutrophil infiltration.<br><br>Interpretation: In hearts from deceased patients with severe COVID-19 , active myocarditis was commonly infiltrated with neutrophils. Cases with neutrophil-infiltrated myocarditis had a series of severe abnormal laboratory tests at admission, and a high maximum of CK-MB during hospitalization. Role of neutrophil on severe heart injury and even systemic condition in COVID-19 should be emphasized.<br><br>Funding Information: : Emergency Key Program of Guangzhou Laboratory, Grant No. EKPG21-32. <br><br>Declaration of Interests: None exist.<br><br>Ethics Approval Statement: Full autopsy was performed after patient death with the approval of the ethics committees and written consent of patient relatives in accordance with regulations issued by the National Health Commission of China and the Helsinki Declaration.

16.
Front Med (Lausanne) ; 8: 659793, 2021.
Article in English | MEDLINE | ID: covidwho-1497084

ABSTRACT

Background: Extracorporeal membrane oxygenation (ECMO) might benefit critically ill COVID-19 patients. But the considerations besides indications guiding ECMO initiation under extreme pressure during the COVID-19 epidemic was not clear. We aimed to analyze the clinical characteristics and in-hospital mortality of severe critically ill COVID-19 patients supported with ECMO and without ECMO, exploring potential parameters for guiding the initiation during the COVID-19 epidemic. Methods: Observational cohort study of all the critically ill patients indicated for ECMO support from January 1 to May 1, 2020, in all 62 authorized hospitals in Wuhan, China. Results: Among the 168 patients enrolled, 74 patients actually received ECMO support and 94 not were analyzed. The in-hospital mortality of the ECMO supported patients was significantly lower than non-ECMO ones (71.6 vs. 85.1%, P = 0.033), but the role of ECMO was affected by patients' age (Logistic regression OR 0.62, P = 0.24). As for the ECMO patients, the median age was 58 (47-66) years old and 62.2% (46/74) were male. The 28-day, 60-day, and 90-day mortality of these ECMO supported patients were 32.4, 68.9, and 74.3% respectively. Patients survived to discharge were younger (49 vs. 62 years, P = 0.042), demonstrated higher lymphocyte count (886 vs. 638 cells/uL, P = 0.022), and better CO2 removal (PaCO2 immediately after ECMO initiation 39.7 vs. 46.9 mmHg, P = 0.041). Age was an independent risk factor for in-hospital mortality of the ECMO supported patients, and a cutoff age of 51 years enabled prediction of in-hospital mortality with a sensitivity of 84.3% and specificity of 55%. The surviving ECMO supported patients had longer ICU and hospital stays (26 vs. 18 days, P = 0.018; 49 vs. 29 days, P = 0.001 respectively), and ECMO procedure was widely carried out after the supplement of medical resources after February 15 (67.6%, 50/74). Conclusions: ECMO might be a benefit for severe critically ill COVID-19 patients at the early stage of epidemic, although the in-hospital mortality was still high. To initiate ECMO therapy under tremendous pressure, patients' age, lymphocyte count, and adequacy of medical resources should be fully considered.

18.
Front Med (Lausanne) ; 8: 678157, 2021.
Article in English | MEDLINE | ID: covidwho-1417107

ABSTRACT

Purpose: This study aimed to describe the clinical and laboratory characteristics and the parameters of the respiratory mechanics of mechanically ventilated patients with confirmed COVID-19 pneumonia and to clarify the risk or protective factors for weaning failure. Methods: Patients diagnosed with COVID-19 pneumonia were selected from the special intensive care unit (ICU) of the Sino-French New City Branch of Tong Ji Hospital, Wuhan, and treated by the National Medical Team Work. They were divided into successful weaning (SW) group (N = 15) and unsuccessful weaning (USW) group (N = 18) according to the prognosis. Information of these patients was analyzed. Results: There were 33 patients included in this study. Patients in the USW group were associated with a poor outcome; the 28-day mortality rate was higher than in the SW group (86.7 vs. 16.7% p < 0.001). By comparison, we found that the initial plateau pressure (Pplat) and driving pressure (DP) of the USW group were higher and that compliance was lower than that of the SW group, but there was no difference between positive end-expiratory pressure (PEEP), partial pressure of carbon dioxide (PCO2), and the ratio of partial pressure arterial oxygen and fraction of inspired oxygen (P/F ratio). Comparing the worst respiratory mechanics parameters of the two groups, the results of the Pplat, DP, compliance, and PEEP were the same as the initial data. The PCO2 of the USW group was higher, while the P/F ratio was lower. A logistic regression analysis suggested that higher Pplat might be an independent risk factor and that higher compliance and lower DP might be protective factors for weaning failure of invasive mechanically ventilated patients with COVID-19 pneumonia. Conclusions: Patients with USW were associated with a poor outcome, higher Pplat might be a risk factor, and a higher compliance and a lower DP might be protective factors for the weaning failure of ventilated COVID-19 patients. Mechanical ventilation settings will affect the patient's prognosis.

19.
Signal Transduct Target Ther ; 6(1): 304, 2021 08 17.
Article in English | MEDLINE | ID: covidwho-1361622

ABSTRACT

A comprehensive analysis of the humoral immune response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential in understanding COVID-19 pathogenesis and developing antibody-based diagnostics and therapy. In this work, we performed a longitudinal analysis of antibody responses to SARS-CoV-2 proteins in 104 serum samples from 49 critical COVID-19 patients using a peptide-based SARS-CoV-2 proteome microarray. Our data show that the binding epitopes of IgM and IgG antibodies differ across SARS-CoV-2 proteins and even within the same protein. Moreover, most IgM and IgG epitopes are located within nonstructural proteins (nsps), which are critical in inactivating the host's innate immune response and enabling SARS-CoV-2 replication, transcription, and polyprotein processing. IgM antibodies are associated with a good prognosis and target nsp3 and nsp5 proteases, whereas IgG antibodies are associated with high mortality and target structural proteins (Nucleocapsid, Spike, ORF3a). The epitopes targeted by antibodies in patients with a high mortality rate were further validated using an independent serum cohort (n = 56) and using global correlation mapping analysis with the clinical variables that are associated with COVID-19 severity. Our data provide fundamental insight into humoral immunity during SARS-CoV-2 infection. SARS-CoV-2 immunogenic epitopes identified in this work could also help direct antibody-based COVID-19 treatment and triage patients.


Subject(s)
Antibodies, Viral/immunology , COVID-19/immunology , Immunity, Humoral , SARS-CoV-2/immunology , Viral Nonstructural Proteins/immunology , COVID-19/mortality , Critical Illness , Disease-Free Survival , Epitopes/immunology , Female , Humans , Immunoglobulin G/immunology , Immunoglobulin M/immunology , Male , Protein Array Analysis , Survival Rate
20.
Front Med (Lausanne) ; 8: 654658, 2021.
Article in English | MEDLINE | ID: covidwho-1325536

ABSTRACT

Purpose: A phenotype of COVID-19 ARDS patients with extremely low compliance and refractory hypercapnia was found in our ICU. In the context of limited number of ECMO machines, feasibility of a low-flow extracorporeal carbon dioxide removal (ECCO2R) based on the renal replacement therapy (RRT) platform in these patients was assessed. Methods: Single-center, prospective study. Refractory hypercapnia patients with COVID-19-associated ARDS were included and divided into the adjusted group and unadjusted group according to the level of PaCO2 after the application of the ECCO2R system. Ventilation parameters [tidal volume (VT), respiratory rate, and PEEP], platform pressure (Pplat) and driving pressure (DP), respiratory system compliance, arterial blood gases, and ECCO2R system characteristics were collected. Results: Twelve patients with refractory hypercapnia were enrolled, and the PaCO2 was 64.5 [56-88.75] mmHg. In the adjusted group, VT was significantly reduced from 5.90 ± 0.16 to 5.08 ± 0.43 ml/kg PBW; DP and Pplat were also significantly reduced from 23.5 ± 2.72 mmHg and 29.88 ± 3.04 mmHg to 18.5 ± 2.62 mmHg and 24.75 ± 3.41 mmHg, respectively. In the unadjusted group, PaCO2 decreased from 94 [86.25, 100.3] mmHg to 80 [67.50, 85.25] mmHg but with no significant difference, and the DP and Pplat were not decreased after weighing the pros and cons. Conclusions: A low-flow ECCO2R system based on the RRT platform enabled CO2 removal and could also decrease the DP and Pplat significantly, which provided a new way to treat these COVID-19 ARDS patients with refractory hypercapnia and extremely low compliance. Clinical Trial Registration: https://www.clinicaltrials.gov/, identifier NCT04340414.

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