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1.
Nat Biomed Eng ; 6(3): 286-297, 2022 03.
Article in English | MEDLINE | ID: covidwho-1751719

ABSTRACT

CRISPR-based assays for the detection of nucleic acids are highly specific, yet they are not fast, sensitive or easy to use. Here we report a one-step fluorescence assay for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in nasopharyngeal samples, with a sample-to-answer time of less than 20 minutes and a sensitivity comparable to that of quantitative real-time PCR with reverse transcription (RT-qPCR). The assay uses suboptimal protospacer adjacent motifs, allowing for flexibility in the design of CRISPR RNAs and slowing down the kinetics of Cas12a-mediated collateral cleavage of fluorescent DNA reporters and cis cleavage of substrates, which leads to stronger fluorescence owing to the accumulation of amplicons generated by isothermal recombinase polymerase amplification. In a set of 204 nasopharyngeal samples with RT-qPCR cycle thresholds ranging from 18.1 to 35.8, the assay detected SARS-CoV-2 with a sensitivity of 94.2% and a specificity of 100%, without the need for RNA extraction. Rapid and sensitive assays for nucleic acid testing in one pot that allow for flexibility in assay design may aid the development of reliable point-of-care nucleic acid testing.


Subject(s)
COVID-19 , RNA, Viral , COVID-19/diagnosis , CRISPR-Cas Systems , Humans , RNA, Viral/genetics , SARS-CoV-2/genetics , Sensitivity and Specificity
3.
Front Med (Lausanne) ; 8: 566609, 2021.
Article in English | MEDLINE | ID: covidwho-1699160

ABSTRACT

Object: To evaluate the clinical efficacy and safety of α-Lipoic acid (ALA) for critically ill patients with coronavirus disease 2019 (COVID-19). Methods: A randomized, single-blind, group sequential, active-controlled trial was performed at JinYinTan Hospital, Wuhan, China. Between February 2020 and March 2020, 17 patients with critically ill COVID-19 were enrolled in our study. Eligible patients were randomly assigned in a 1:1 ratio to receive either ALA (1200 mg/d, intravenous infusion) once daily plus standard care or standard care plus equal volume saline infusion (placebo) for 7 days. All patients were monitored within the 7 days therapy and followed up to day 30 after therapy. The primary outcome of this study was the Sequential Organ Failure Estimate (SOFA) score, and the secondary outcome was the all-cause mortality within 30 days. Result: Nine patients were randomized to placebo group and 8 patients were randomized to ALA group. SOFA score was similar at baseline, increased from 4.3 to 6.0 in the placebo group and increased from 3.8 to 4.0 in the ALA group (P = 0.36) after 7 days. The 30-day all-cause mortality tended to be lower in the ALA group (3/8, 37.5%) compared to that in the placebo group (7/9, 77.8%, P = 0.09). Conclusion: In our study, ALA use is associated with lower SOFA score increase and lower 30-day all-cause mortality as compared with the placebo group. Although the mortality rate was two-folds higher in placebo group than in ALA group, only borderline statistical difference was evidenced due to the limited patient number. Future studies with larger patient cohort are warranted to validate the role of ALA in critically ill patients with COVID-19. Clinical Trial Registration: http://www.chictr.org.cn/showproj.aspx?proj=49534.

4.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-320695

ABSTRACT

Background: Since 2020 COVID-19 pandemic became an emergent public sanitary incident. The epidemiology data and the impact on prognosis of secondary infection in severe and critical COVID-19 patients in China remained largely unclear. Methods: . We retrospectively reviewed medical records of all adult patients with laboratory-confirmed COVID-19 who were admitted to ICUs from January 18 th 2020 to April 26 th 2020 at two hospitals in Wuhan, China and one hospital in Guangzhou, China. We measured the frequency of bacteria and fungi cultured from respiratory tract, blood and other body fluid specimens. The risk factors for and impact of secondary infection on clinical outcomes were also assessed. Results: . Secondary infections were very common (86.6%) when patients were admitted to ICU for >72 hours. The majority of infections were respiratory, with the most common organisms being Klebsiella pneumoniae (24.5%), Acinetobacter baumannii (21.8%), Stenotrophomonas maltophilia (9.9%), Candida albicans (6.8%), and Pseudomonas spp. (4.8%). Furthermore, the proportions of multidrug resistant (MDR) bacteria and carbapenem resistant Enterobacteriaceae (CRE) were high. We also found that age ≥60 years and mechanical ventilation ≥13days independently increased the likelihood of secondary infection. Finally, patients with positive cultures had reduced ventilator free days in 28 days and patients with CRE and/or MDR bacteria positivity showed lower 28 day survival rate. Conclusions: . In a retrospective cohort of severe and critical COVID-19 patients admitted to ICUs in China, the prevalence of secondary infection was high, especially with CRE and MDR bacteria, resulting in poor clinical outcomes.

5.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-320694

ABSTRACT

Background: Since the clinical correlates, prognosis and determinants of AKI in patients with Covid-19 remain largely unclear, we perform a retrospective study to evaluate the incidence, risk factors and prognosis of AKI in severe and critically ill patients with Covid-19. Methods: : We reviewed medical records of all adult patients (>18 years) with laboratory-confirmed Covid-19 who were admitted to the intensive care unit (ICU) between January 23 rd 2020 and April 6 th 2020 at Wuhan JinYinTan Hospital and The First Affiliated Hospital of Guangzhou Medical University. The clinical data, including patient demographics, clinical symptoms and signs, laboratory findings, treatment [including respiratory supports, use of medications and continuous renal replacement therapy (CRRT)] and clinical outcomes, were extracted from the electronic records, and we access the incidence of AKI and the use of CRRT, risk factors for AKI, the outcomes of renal diseases, and the impact of AKI on the clinical outcomes. Results: : Among 210 subjects, 131 were males (62.4%). The median age was 64 years (IQR: 56-71). Of 92 (43.8%) patients who developed AKI during hospitalization, 13 (14.1%), 15 (16.3%) and 64 (69.6%) patients were classified as stage 1, 2 and 3, respectively. 54 cases (58.7%) received CRRT. Age, sepsis, Nephrotoxic drug, IMV and elevated baseline Scr were associated with AKI occurrence. The renal recover during hospitalization among 16 AKI patients (17.4%), who had a significantly shorter time from admission to AKI diagnosis, lower incidence of right heart failure and higher P/F ratio. Of 210 patients, 93 patients deceased within 28 days of ICU admission. AKI stage 3, critical disease, greater age and minimum P/F <150mmHg independently associated with it. Conclusions: : Among patients with Covid-19, the incidence of AKI was high. age , sepsis, nephrotoxic drug, IMV and baseline Scr were strongly associated with the development of AKI. Time from admission to AKI diagnosis, right heart failure and P/F ratio were independently associated with the potential of renal recovery. Finally, AKI KIDGO stage 3 independently predicted the risk of death within 28 days of ICU admission.

6.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-319974

ABSTRACT

Coronavirus Disease 2019 (COVID-19) has caused global pandemic. Here we profiled the humoral response against SARS-CoV-2 by measuring immunoglobulin (Ig) A, IgM and IgG against nucleocapsid, spike proteins and IgM, IgG antibodies against receptor-binding domain (RBD) of the spike protein along with total neutralizing antibodies. We tested 279 plasma samples collected from 176 COVID-19 patients. We demonstrate more severe cases have a late onset in the humoral response compared to mild/moderate infections. All the antibody titers continue to rise in patients with COVID-19 over the disease course. However, these levels are mostly unrelated to the disease severity. The appearance time and titers of neutralizing antibodies showed significant positive correlation to the antibodies against spike protein. Our results suggest late onset of antibody response as a risk factor for disease severity, however there is a limited role of antibody titers in predicting disease severity of COVID-19.

7.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-319973

ABSTRACT

Background: The pandemic of Coronavirus disease 2019 (COVID-19) is ongoing globally, which is a big challenge for public health. Alteration of human microbiota had been observed in COVID-19. However, it is unknown how the microbiota is associated with the fatality in COVID-19.Methods: We conducted metatranscriptome sequencing on 588 longitudinal oropharyngeal swab specimens collected from 192 COVID-19 patients recruited in the LOTUS clinical trial (Registration number: ChiCTR2000029308) (including 39 deceased patients), and 95 healthy controls from the same geographic area.Findings: The upper respiratory tract (URT) microbiota in COVID-19 patients differed from that in healthy controls, while deceased patients possessed a more distinct microbiota. Streptococcus was enriched in recovered patients, whereas potential pathogens, including Candida and Enterococcus, were more abundant in deceased patients. Moreover, the microbiota dominated by Streptococcus was more stable than that dominated by other species. In contrast, the URT microbiota in deceased patients showed a more significant alteration and became more deviated from the norm after admission. The abundance of Streptococcus on admission, particularly that of S. parasanguis, was identified as a strong predictor of fatality by Cox and L1 regularized logistic regression analysis, thus could be used as a potential prognostic biomarker of COVID-19.Interpretation Alteration of the URT microbiota was observed in COVID-19 patients and was associated with the fatality rate. A higher abundance of Streptococcus, especially S. parasanguis, on admission in oropharyngeal swabs predicts a better outcome. The generalization of the results in other populations and underlying mechanisms need further investigations.Trial Registration: Participants were enrolled in ChiCTR2000029308.Funding: This study was funded in part by the National Major Science & Technology Project for Control and Prevention of Major Infectious Diseases in China (2017ZX10103004, 2018ZX10301401), the Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (2019-I2M-2-XX, 2016-I2M-1-014, 2018-I2M-1-003), The Non-profit Central Research Institute Fund of CAMS (2020HY320001, 2019PT310029), Beijing Advanced Innovation Center for Genomics (ICG), and Beijing Advanced Innovation Center for Structural Biology (ICSB).Declaration of Interests: All authors declare no competing interests.Ethics Approval Statement: The study was approved by the Institutional Review Board of Jin Yin-Tan Hospital (KY2020-02.01). Written informed consent was obtained from all patients or their legal representatives if they were too unwell to provide consent.

8.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-319519

ABSTRACT

Multiorgan injuries are a major complication of severe COVID-19;however, its pathogenesis is barely understood. Herein, we profiled the host responses to SARS-CoV-2 infection by performing quantitative proteomics of COVID-19 postmortem samples, and provided a comprehensive proteome map covering the protein alterations in eight different organs/tissues. Our results revealed that lung underwent the most abundant protein alterations mainly enriched in immune-/inflammation-related or morphology-related processes, while surprisingly, other organs/tissues exhibited significant protein alterations mainly enriched in processes related with organ movement, respiration, and metabolism. These results indicate that the major cause of lung injury was excessive inflammatory response, and subsequent intravascular thrombosis and pulmonary architecture/function destruction, while other organs/tissues were mainly injured by hypoxia and functional impairment. Therefore, our findings demonstrate the significant pathophysiological alternations of host proteins/pathways associated with multiorgan injuries of COVID-19, which provides invaluable knowledge about COVID-19-associated host responses and sheds light on the pathogenesis of COVID-19.

9.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-312728

ABSTRACT

Background: The coronavirus disease 2019 (COVID-19) has induced a worldwide pneumonia with a high infectivity and mortality. However, the predicting biomarkers and their potential mechanism in the progression of COVID-19 are not well known. Objective The aim of this study is to identify the candidate predictors of COVID-19 and investigate their underlying mechanism. Methods The retrospective study was conducted to identify the potential laboratory indicators with prognostic values of COVID-19 disease. Then, the prognostic nomogram was constructed to predict the overall survival of COVID-19 patients. Additionally, the scRNA-seq data of BALF and PBMCs from COVID-19 patients were downloaded to investigate the underlying mechanism of the most important prognostic indicators in lungs and peripherals, respectively. Results 304 hospitalized adult COVID-19 patients in Wuhan Jinyintan Hospital were included in the retrospective study. CEA was the only laboratory indicator with significant difference in the univariate (P < 0.001) and multivariate analysis (P = 0.021). The scRNA-seq data of BALF and PBMCs from COVID-19 patients were downloaded to investigate the underlying mechanism of CEA in lungs and peripherals, respectively. The results revealed the potential roles of CEA were significantly distributed in Type II pneumocytes of BALF and developing neutrophils of PBMCs, participating in the progression of COVID-19 by regulating the cell-cell communication. Conclusion This study identifies the prognostic roles of CEA in COVID-19 patients and implies the potential roles of CEACAM8-CEACAM6 in the progression of COVID-19 by regulating the cell-cell communication of developing neutrophils and Type II pneumocyte.

10.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-308257

ABSTRACT

Background: Hospitalized patients with COVID-19 appeared high risk of venous thromboembolism (VTE) defined by some risk assessment models (RAMs), which exhibited the predictor of mortality in patients with non-COVID-19. We aimed to investigate the association between risk of VTE with 30-day mortality in COVID-19 patients.Methods: In this retrospective cohort study, 1030 consecutive hospitalized patients, between January 26, 2020 and March 29, 2020, aged 14–98 years with a confirmed diagnosis of COVID-19-related pneumonia were recruited from Jinyintan Hospital and Union Hosptial, Wuhan, China. We collected baseline data on demographics, SOFA parameters, and VTE RAMs including Padua Prediction Score (PPS), IMPROVE RAM and Caprini RAM. The primary outcome of the study was 30-day mortality. The secondary outcome was the length of stay in hospital. Findings: Thirty-day mortality increased progressively from 2% in patients at low risk of VTE to 63% in those at high risk of VTE defined by PPS ≥ 4. Similar findings were also observed for risk of VTE defined by IMPROVE score ³ 2 and Caprini score ³ 5. Progressive increases in VTE risk also were associated with higher SOFA score. Our findings showed that the presence of high risk of VTE was independently associated with 30-day mortality regardless of adjusted gender, smoking status and some comorbidities with hazard ratios of 29.19 (95% CI 15.76 - 54.05), 37.37 (95% CI 18.43 - 75.78), 20.60 (95% CI 11.41 - 37.19) for PPS, IMPROVE RAM and Caprini RAM, respectively (P < 0.001 for all comparisons). Predictive accuracy of PPS (AUC, 0.900;95% CI 0.881 - 0.919), IMPROVE RAM (AUC, 0.917;95% CI 0.898 - 0.936) or Caprini RAM (AUC, 0.861;95% CI 0.840 - 0.882) as the risk of 30-day mortality was markedly well.Interpretation: The presence of high risk of VTE identifies a group of patients with COVID-19 at higher risk for 30-day mortality. Furthermore, there is higher accuracy of VTE RAMs to predict 30-day mortality in COVID-19 hospitalized patients.Funding Statement: This study is funded by the National Nature Science Foundation of China (81870062 to Jinjun Jiang, 81900038 to Shujing Chen).Declaration of Interests: The authors have no conflict of interest to disclose.Ethics Approval Statement: The study was approved by Jinyintan Hospital Ethics Committee (KY2020-06.01) and Union Hospital Ethics Committee (2020-0039). Written informed consent was waived by the Ethics Commission.

11.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-316032

ABSTRACT

Despite widespread interest in the pathophysiology of COVID-19 in respiratory and cardiovascular systems, little is known about the morphologic and molecular changes in the testis of patients with COVID-19 and the effects of SARS-CoV-2 infection on male fertility. We report here on the pathophysiology and molecular feature of testes obtained at autopsy from six men with COVID-19, as compared with those of testes from three men with age-matched, uninfected SARS-CoV-2. Our histopathological results showed that all COVID-19 patients had severe spermatogenesis damages compared with controls. Importantly, we detected the nuclear acid of the SARS-CoV-2 virus, viral particles, and SARS-CoV-2 spike S1 protein in COVID-19 patient testes, and we also found ACE2 and TMPRSS2 significantly elevated in the testes from COVID-19 patients. Furthermore, we observed a prominent leukocyte infiltration, including CD3+ T lymphocytes, CD20+ B lymphocytes, CD68+ macrophages, HLA-DR+ myeloid cells, and CD38+ plasma cells in the testes of COVID-19 patients. RNA-Seq analyses further revealed SARS-CoV-2 infection could lead to dysfunction of the genes that regulate the spermatogenesis and inflammation response-related pathways. Collectively, our pathological and molecular examination findings indicate that SARS-CoV-2 could directly attack testicular cells, thereby inducing the damage of testicular immune privilege and spermatogenesis defects.

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.
Front Immunol ; 12: 791348, 2021.
Article in English | MEDLINE | ID: covidwho-1608514

ABSTRACT

Background: Striking similarities have been found between coronavirus disease 2019 (COVID-19) and anti-melanoma differentiation-associated gene 5 (MDA5) antibody (Ab)-related dermatomyositis, implying a shared autoinflammatory aberrance. Herein, we aim to investigate whether the anti-MDA5 Ab is present in COVID-19 and correlates with the severity and adverse outcome of COVID-19 patients. Methods and Findings: We retrospectively recruited 274 adult inpatients with COVID-19 in this study, including 48, 164, and 62 cases of deaths, severe, and non-severe patients respectively. The anti-MDA5 Ab was determined by ELISA and verified by Western Blotting, which indicated that the positive rate of anti-MDA5 Ab in COVID-19 patients was 48.2% (132/274). The clinical and laboratory features, as well as outcomes between patients with positive and negative anti-MDA5 Ab were compared and we found that the anti-MDA5 Ab positive patients tended to represent severe disease (88.6% vs 66.9%, P<0.0001). We also demonstrated that the titer of anti-MDA5 Ab was significantly elevated in the non-survivals (5.95 ± 5.16 vs 8.22 ± 6.64, P=0.030) and the positive rate was also higher than that in the survivals (23.5% vs 12.0%, P=0.012). Regarding severe COVID-19 patients, we found that high titer of anti-MDA5 Ab (≥10.0 U/mL) was more prevalent in the non-survivals (31.2% vs 14.0%, P=0.006). Moreover, a dynamic analysis of anti-MDA5 Ab was conducted at different time-points of COVID-19, which revealed that early profiling of anti-MDA5 Ab could distinguish severe patients from those with non-severe ones. Conclusions: Anti-MDA5 Ab was prevalent in the COVID-19 patients and high titer of this antibody is correlated with severe disease and unfavorable outcomes.


Subject(s)
Antibodies/immunology , COVID-19/immunology , Interferon-Induced Helicase, IFIH1/immunology , Severity of Illness Index , Adult , Aged , Antibodies/blood , COVID-19/epidemiology , COVID-19/virology , Disease Progression , Enzyme-Linked Immunosorbent Assay/methods , Female , Humans , Male , Middle Aged , Pandemics , Prognosis , Retrospective Studies , SARS-CoV-2/physiology
14.
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
15.
Front Med (Lausanne) ; 8: 663646, 2021.
Article in English | MEDLINE | ID: covidwho-1394776

ABSTRACT

Background: Pancreatic enzyme elevation has been reported in patients with COVID-19 during the pandemic. However, with the shortage of medical resources and information, several challenges are faced in the examination and treatment of this condition in COVID-19 patients. There is little information on whether such condition is caused by pancreatic injury, and if this is a warning sign of life threatening complications like multiple organ failure in patients. The objective of this study is to explore the relationship between elevated pancreatic enzymes and the underlying risk factors during the management of COVID-19 patients. Method: A total of 55 COVID-19 patients admitted to the intensive care unit (ICU) of Wuhan Jinyintan hospital from January 1 to March 30, 2020 were enrolled in this study. All participants underwent transabdominal ultrasound imaging to assess their pancreas. Results: Out of the 55 patients, three patients had pancreatitis, 29 (52.7%) with elevated pancreatic enzymes, and 23 (41.8%) without. The most common symptoms of patients with COVID-19 were fever and cough. There was no statistical difference in most baseline characteristics except myalgia on admission. Compared with those having normal enzyme levels, patients with elevated pancreatic enzymes had higher rates of mortality (79.3 vs. 52.2%; P = 0.038), and lower rates of discharge (20.7 vs. 47.8%; P = 0.038). Patients with elevated enzymes had higher incidence of mechanical ventilation (P = 0.004) and kidney injury (P = 0.042) than patients without elevated pancreatic enzymes. The results of multivariable logistic analysis showed that the odds ratio were 10.202 (P = 0.002) for mechanical ventilation and 7.673 (P = 0.014) for kidney injury with the elevated enzymes vs. the normal conditions. Conclusions: The findings show that the incidences of pancreatic enzymes elevation are not low in critical COVID-19 patients and only a few of them progressed to acute pancreatitis (AP). Increased pancreatic enzymes levels is associated with poor prognosis in COVID-19 patients. In addition, the kidney injury and oxygenation degradation are associated with the pancreatic enzymes elevation in COVID-19 patients.

17.
Front Med (Lausanne) ; 7: 611460, 2020.
Article in English | MEDLINE | ID: covidwho-1389196

ABSTRACT

Background: The data on long-term outcomes of patients infected by SARS-CoV-2 and treated with extracorporeal membrane oxygenation (ECMO) in China are merely available. Methods: A retrospective study included 73 patients infected by SARS-CoV-2 and treated with ECMO in 21 intensive care units in Hubei, China. Data on demographic information, clinical features, laboratory tests, ECMO durations, complications, and living status were collected. Results: The 73 ECMO-treated patients had a median age of 62 (range 33-78) years and 42 (63.6%) were males. Before ECMO initiation, patients had severe respiratory failure on mechanical ventilation with a median PO2/FiO2 of 71.9 [interquartile range (IQR), 58.6-87.0] mmHg and a median PCO2 of 62 [IQR, 43-84] mmHg on arterial blood analyses. The median duration from symptom onset to invasive mechanical ventilation, and to ECMO initiation was19 [IQR, 15-25] days, and 23 [IQR, 19-31] days. Before and after ECMO initiation, the proportions of patients receiving prone position ventilation were 58.9 and 69.9%, respectively. The median duration of ECMO support was 18.5 [IQR 12-30] days. During the treatments with ECMO, major hemorrhages occurred in 31 (42.5%) patients, and oxygenators were replaced in 21 (28.8%) patients. Since ECMO initiation, the 30-day mortality and 60-day mortality were 63.0 and 80.8%, respectively. Conclusions: In Hubei, China, the ECMO-treated patients infected by SARS-CoV-2 were of a broad age range and with severe hypoxemia. The durations of ECMO support, accompanied with increased complications, were relatively long. The long-term mortality in these patients was considerably high.

18.
Ann Palliat Med ; 10(8): 8557-8570, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1353025

ABSTRACT

BACKGROUND: Since 2020 COVID-19 pandemic became an emergent public sanitary incident. The epidemiology data and the impact on prognosis of secondary infection in severe and critical COVID-19 patients in China remained largely unclear. METHODS: We retrospectively reviewed medical records of all adult patients with laboratory-confirmed COVID-19 who were admitted to ICUs from January 18th 2020 to April 26th 2020 at two hospitals in Wuhan, China and one hospital in Guangzhou, China. We measured the frequency of bacteria and fungi cultured from respiratory tract, blood and other body fluid specimens. The risk factors for and impact of secondary infection on clinical outcomes were also assessed. RESULTS: Secondary infections were very common (86.6%) when patients were admitted to ICU for >72 hours. The majority of infections were respiratory, with the most common organisms being Klebsiella pneumoniae (24.5%), Acinetobacter baumannii (21.8%), Stenotrophomonas maltophilia (9.9%), Candida albicans (6.8%), and Pseudomonas spp. (4.8%). Furthermore, the proportions of multidrug resistant (MDR) bacteria and carbapenem resistant Enterobacteriaceae (CRE) were high. We also found that age ≥60 years and mechanical ventilation ≥13 days independently increased the likelihood of secondary infection. Finally, patients with positive cultures had reduced ventilator free days in 28 days and patients with CRE and/or MDR bacteria positivity showed lower 28-day survival rate. CONCLUSIONS: In a retrospective cohort of severe and critical COVID-19 patients admitted to ICUs in China, the prevalence of secondary infection was high, especially with CRE and MDR bacteria, resulting in poor clinical outcomes.


Subject(s)
COVID-19 , Coinfection , Cross Infection , Adult , Anti-Bacterial Agents/therapeutic use , Coinfection/drug therapy , Cross Infection/drug therapy , Cross Infection/epidemiology , Humans , Middle Aged , Pandemics , Retrospective Studies , SARS-CoV-2
19.
Crit Care ; 25(1): 234, 2021 07 03.
Article in English | MEDLINE | ID: covidwho-1295477

ABSTRACT

BACKGROUND: The coronavirus disease 2019 (COVID-19) has induced a worldwide epidemiological event with a high infectivity and mortality. However, the predicting biomarkers and their potential mechanism in the progression of COVID-19 are not well known. OBJECTIVE: The aim of this study is to identify the candidate predictors of COVID-19 and investigate their underlying mechanism. METHODS: The retrospective study was conducted to identify the potential laboratory indicators with prognostic values of COVID-19 disease. Then, the prognostic nomogram was constructed to predict the overall survival of COVID-19 patients. Additionally, the scRNA-seq data of BALF and PBMCs from COVID-19 patients were downloaded to investigate the underlying mechanism of the most important prognostic indicators in lungs and peripherals, respectively. RESULTS: In total, 304 hospitalized adult COVID-19 patients in Wuhan Jinyintan Hospital were included in the retrospective study. CEA was the only laboratory indicator with significant difference in the univariate (P < 0.001) and multivariate analysis (P = 0.020). The scRNA-seq data of BALF and PBMCs from COVID-19 patients were downloaded to investigate the underlying mechanism of CEA in lungs and peripherals, respectively. The results revealed the potential roles of CEA were significantly distributed in type II pneumocytes of BALF and developing neutrophils of PBMCs, participating in the progression of COVID-19 by regulating the cell-cell communication. CONCLUSION: This study identifies the prognostic roles of CEA in COVID-19 patients and implies the potential roles of CEACAM8-CEACAM6 in the progression of COVID-19 by regulating the cell-cell communication of developing neutrophils and type II pneumocyte.


Subject(s)
COVID-19/metabolism , Carcinoembryonic Antigen/metabolism , Pneumonia, Viral/metabolism , Adult , Aged , Biomarkers/metabolism , Bronchoalveolar Lavage Fluid/chemistry , COVID-19/mortality , Cell Communication , China/epidemiology , Disease Progression , Hospitalization , Humans , Male , Middle Aged , Neutrophils/metabolism , Nomograms , Pneumonia, Viral/mortality , Pneumonia, Viral/virology , Predictive Value of Tests , Prognosis , Retrospective Studies , SARS-CoV-2 , Survival Analysis
20.
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
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