Abnormal Upregulation of Cardiovascular Disease Biomarker PLA2G7 Induced by Proinflammatory Macrophages in COVID-19 patients

BACKGROUND. Coronavirus disease 2019 (COVID-19) triggers distinct patterns of pneumonia progression with multiorgan disease, calling for cell- and/or tissue-type specific host injury markers. METHODS. An integrated hypothesis-free single biomarker analysis framework was performed on nasal swabs (n=484) from patients with COVID-19 in GSE152075. The origin of candidate biomarker was assessed in single-cell RNA data (GSE145926). The candidate biomarker was validated in a cross-sectional cohort (n=564) at both nucletide and protein levels. RESULTS. Phospholipase A2 group VII (PLA2G7) was identified as a candidate biomarker in COVID-19. PLA2G7 was predominantly expressed by proinflammatory macrophages in lungs emerging with progression of COVID-19. In the validation stage, PLA2G7 was found in patients with COVID-19 and pneumonia, especially in severe pneumonia, rather than patients suffered mild H1N1 influenza infection. The positive rates of PLA2G7 ranging from 29.37% to 100.00% were positively correlated with not only viral loads in patients with COVID-19 but also severity of pneumonia in non COVID-19 patients. Although Ct values of PLA2G7 in severe pneumonia was siginificantly lower than that in moderate pneumonia (P=7.2e-11), no differences were observed in moderate pneumonia with COVID-19 between severe pneumonia without COVID-19 (P=0.81). Serum protein levels of PLA2G7, also known as lipoprotein-associated phospholipase A2 (Lp-PLA2), were further found to be elevated and beyond the upper limit of normal in patients with COVID-19, especially among the re-positive patients. CONCLUSIONS. We firstly identified and validated PLA2G7, a biomarker for cardiovascular diseases (CVDs), was abnormally enhanced in COVID-19 patients at both nucletide and protein aspects. These findings provided indications into the prevalence of cardiovascular involvements seen in COVID-19 patients. PLA2G7 could be a hallmark of COVID-19 for monitoring disease progress and therapeutic response.

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Abnormal upregulation of cardiovascular disease biomarker PLA2G7 induced by proinflammatory macrophages in COVID-19 patients

Scientific Reports ◽

10.1038/s41598-021-85848-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Yang Li ◽

Yongzhong Jiang ◽

Yi Zhang ◽

Naizhe Li ◽

Qiangling Yin ◽

...

Keyword(s):

Cardiovascular Disease ◽

Normal Limit ◽

Genomic Analysis ◽

High Rate ◽

Hub Gene ◽

Viral Loads ◽

Protein Levels ◽

Nasal Swabs ◽

Positive Rate ◽

Validation Stage

AbstractHigh rate of cardiovascular disease (CVD) has been reported among patients with coronavirus disease 2019 (COVID-19). Importantly, CVD, as one of the comorbidities, could also increase the risks of the severity of COVID-19. Here we identified phospholipase A2 group VII (PLA2G7), a well-studied CVD biomarker, as a hub gene in COVID-19 though an integrated hypothesis-free genomic analysis on nasal swabs (n = 486) from patients with COVID-19. PLA2G7 was further found to be predominantly expressed by proinflammatory macrophages in lungs emerging with progression of COVID-19. In the validation stage, RNA level of PLA2G7 was identified in nasal swabs from both COVID-19 and pneumonia patients, other than health individuals. The positive rate of PLA2G7 were correlated with not only viral loads but also severity of pneumonia in non-COVID-19 patients. Serum protein levels of PLA2G7 were found to be elevated and beyond the normal limit in COVID-19 patients, especially among those re-positive patients. We identified and validated PLA2G7, a biomarker for CVD, was abnormally enhanced in COVID-19 at both nucleotide and protein aspects. These findings provided indications into the prevalence of cardiovascular involvements seen in patients with COVID-19. PLA2G7 could be a potential prognostic and therapeutic target in COVID-19.

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Lack of group X secreted phospholipase A2 increases survival following pandemic H1N1 influenza infection

Virology ◽

10.1016/j.virol.2014.01.030 ◽

2014 ◽

Vol 454-455 ◽

pp. 78-92 ◽

Cited By ~ 11

Author(s):

Alyson A. Kelvin ◽

Norbert Degousee ◽

David Banner ◽

Eva Stefanski ◽

Alberto J. Leόn ◽

...

Keyword(s):

Phospholipase A2 ◽

Influenza Infection ◽

H1n1 Influenza ◽

Pandemic H1n1 ◽

Pandemic H1n1 Influenza ◽

Secreted Phospholipase A2

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Liposomal Dexamethasone Reduces A/H1N1 Influenza-Associated Morbidity in Mice

10.1101/2021.08.02.454850 ◽

2021 ◽

Author(s):

Seung Hyeok Seok ◽

Yirang Na ◽

Jung Won Kwon ◽

Hailian Quan ◽

Juha Song ◽

...

Keyword(s):

Immune Cells ◽

Death Rate ◽

Influenza A ◽

Cell Damage ◽

Influenza Infection ◽

Severe Pneumonia ◽

H1n1 Influenza ◽

Intranasal Delivery ◽

Necrosis Factor Alpha ◽

Chemokine Ligand

Re-emerging viral threats have continued to challenge the medical and public health systems. It has become clear that a significant number of severe viral infection cases are due to an overreaction of the immune system, which leads to hyperinflammation. In this study, we aimed to demonstrate the therapeutic efficacy of the dexamethasone nanomedicine in controlling the symptoms of influenza infection. We found that the A/Wisconsin/WSLH34939/2009 (H1N1) infection induced severe pneumonia in mice with a death rate of 80%, accompanied by significant epithelial cell damage, infiltration of immune cells, and accumulation of pro-inflammatory cytokines in the airway space. Moreover, the intranasal delivery of liposomal dexamethasone during disease progression reduced the death rate by 20%. It also significantly reduced the protein level of tumor necrosis factor-alpha (TNFα), interleukin1β (IL-1β), IL-6, and the C-X-C motif chemokine ligand 2 (CXCL2) as well as the number of infiltrated immune cells in the bronchoalveolar lavage fluids as compared to the free drug. It was found that the liposomal dexamethasone was mainly distributed into the monocyte/macrophages in the lungs, suggesting its mode of action via the specific delivery of the drug into myeloid cells as a major cell population for inducing the cytokine storm. Taken together, the intranasal delivery of liposomal dexamethasone may serve as a novel promising therapeutic strategy for the treatment of influenza A-induced pneumonia.

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Genetic variants associated with severe pneumonia in A/H1N1 influenza infection

European Respiratory Journal ◽

10.1183/09031936.00020611 ◽

2011 ◽

Vol 39 (3) ◽

pp. 604-610 ◽

Cited By ~ 63

Author(s):

J. Zuniga ◽

I. Buendia-Roldan ◽

Y. Zhao ◽

L. Jimenez ◽

D. Torres ◽

...

Keyword(s):

Genetic Variants ◽

Influenza Infection ◽

Severe Pneumonia ◽

H1n1 Influenza

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Serum C-reactive protein levels in severe and very severe pneumonia in children

Paediatrica Indonesiana ◽

10.14238/pi52.3.2012.161-4 ◽

2012 ◽

Vol 52 (3) ◽

pp. 161

Author(s):

Ni Putu Sucita Wahyu Dewi ◽

Putu Siadi Purniti ◽

Roni Naning

Keyword(s):

Severe Pneumonia ◽

Cross Sectional Study ◽

Sectional Study ◽

C Reactive Protein ◽

Cross Sectional ◽

Pneumonia Severity ◽

Protein Levels ◽

Reactive Protein ◽

Median Serum ◽

Serum Crp

Background Pneumonia is a major cause of death in children fromdeveloping countries. It is difficult to assess pneumonia severity ifclinical symptoms of pneumonia are unclear, co-morbidities occursimultaneously, or there is an absence of consolidation or infiltrateson chest radiograph. Examination of C-reactive protein (CRP)levels can help to determine the severity of pneumonia.Objective To compare serum CRP levels in severe and very severepneumonia cases.Methods This was a cross-sectional study on pediatric patientsaged> 28 days up to 60 months v.ith a diagnosis of severe or verysevere pneumonia. Subjects were hospitalized at the Departmentof Child Health, Udayana University Medical SchooliSanglahHospital, Denpasar from May 2010 to January 2011. There were30 subjects in each group, severe or very severe pneumonia. Datawere analyzed using Mann-Whitney and ANCOVA tests withstatistical significance set at P < 0.05.Results There were significant differences in median serum CRPlevels in the severe and very severe pneumonia groups. The verysevere pneumonia group had a median CRP level of 54.75 mgiL(lQrange 0.22 to 216.00) and the severe pneumonia group had amedian CRP level ofl6.06 mgiL (IQ range 0.97 to 89.35). SerumCRP levels were influenced by the severity of pneumonia (P =0.002) and the timing of the CRP examination (P = 0.001).Conclusion Subjects with very severe pneumonia hadsignificantly higher median CRP level compared to that of subjectswith severe pneumonia. [Paediatr Indones. 2012;52:161A].

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PROTEIN 24 HIV DAN LIMFOSIT T-CD4+ DI INFEKSI HIV TAHAP I

INDONESIAN JOURNAL OF CLINICAL PATHOLOGY AND MEDICAL LABORATORY ◽

10.24293/ijcpml.v21i3.740 ◽

2016 ◽

Vol 21 (3) ◽

pp. 273

Author(s):

I Made Sila Darmana ◽

Endang Retnowati ◽

Erwin Astha Triyono

Keyword(s):

T Lymphocytes ◽

Hiv Infection ◽

T Lymphocyte ◽

Negative Correlation ◽

Stage I ◽

Cross Sectional ◽

Protein Levels ◽

P24 Protein ◽

Persistent Generalized Lymphadenopathy ◽

Spearman Test

Measuring HIV p24 protein is a test which is more practical than determination of CD4+ T-lymphocyte counts and viral load, as it does not require a very sophisticated instrument and requires a lower cost. Independent predictive value of p24 to the decline of CD4+ T-lymphocytes, clinical progression and survival in HIV-infected patients have been reported. In this study, HIV-infected patients were found to have HIV p24 protein levels inversely proportional to CD4+ T-lymphocyte counts by using Spearman test (R2=0.225; p=0.0331). Studies on the correlation between HIV p24 protein levels and CD4+ T-lymphocyte counts in stage I HIV infection have not yet been reported. The aim of this study was to prove the correlation between HIV p24 protein levels and CD4+ T-lymphocytes in stage I HIV infection. Research issue was whether a correlation between HIV p24 protein levels and CD4+ T-lymphocyte counts in stage I HIVinfection existed ? The hypothesis was that a correlation between HIV p24 protein levels and CD4+ T-lymphocyte counts in stage I HIV infection existed. The study design was cross sectional observational. Subjects consisted of 30 stage I HIV-infected patients treated at the Infectious Disease Intermediate Care Unit, Dr. Soetomo Hospital and VCT Clinic of the Dr. Ramelan Naval Hospital, Surabaya from May to July 2014. Stage I HIV infection is an asymptomatic HIV infection or with persistent generalized lymphadenopathy and the patient is able to perform normal activities. Levels of p24 were measured by ELISA method and CD4+ T-lymphocyte counts using flowcytometry(BD FACSCaliburTM). The results were statistically analyzed using Pearson’s correlation test. HIV p24 protein levels in stage I of HIV infection ranged from 1.8 to 10.8 pg/mL, mean of 5.14 pg/mL and a standard deviation of 2.08 pg/mL. CD4+ T-lymphocyte counts decreased with a range of 49-559 cells /uL for absolute values and 4.42–26.02% for percentage values Correlations between blood p24 levels and CD4+ T-lymphocyte counts either absolute (r=–0.392, p=0.032) or percentage (r=–0.363, p=0.049) were found. In stage I HIV-infected patients, a negative correlation was found between p24 levels and CD4+ T-lymphocyte counts, in both CD4+T-lymphocyte counts as absolute and as well as percentage values. This negative correlation showed that the p24 HIV levels were inversely proportional to the CD4+ T-lymphocyte counts. HIV p24 protein levels have a possibility to be used predicting CD4+ T-lymphocyte counts

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Predictors of loss to follow-up in art experienced patients in Nigeria: a 13 year review (2004–2017)

AIDS Research and Therapy ◽

10.1186/s12981-019-0241-3 ◽

2019 ◽

Vol 16 (1) ◽

Author(s):

Ahmad Aliyu ◽

Babatunde Adelekan ◽

Nifarta Andrew ◽

Eunice Ekong ◽

Stephen Dapiap ◽

...

Keyword(s):

Patient Adherence ◽

Cross Sectional Study ◽

Emergency Plan ◽

Cross Sectional ◽

Loss To Follow Up ◽

Viral Loads ◽

Review Period ◽

Lost To Follow Up ◽

Differentiated Care

Abstract Background Expanded access to antiretroviral therapy (ART) leads to improved HIV/AIDS treatment outcomes in Nigeria, however, increasing rates of loss to follow-up among those on ART is threatening optimal standard achievement. Therefore, this retrospective cross-sectional study is aimed at identifying correlates and predictors of loss to follow-up in patients commencing ART in a large HIV program in Nigeria. Methods Records of all patients from 432 US CDC Presidents Emergency Plan for AIDS Relief (PEPFAR) supported facilities across 10 States and FCT who started ART from 2004 to 2017 were used for this study. Bivariate and multivariate analysis of the demographic and clinical parameters of all patients was conducted using STATA version 14 to determine correlates and predictors of loss to follow-up. Results Within the review period, 245,257 patients were ever enrolled on anti-retroviral therapy. 150,191 (61.2%) remained on treatment, 10,960 (4.5%) were transferred out to other facilities, 6926 (2.8%) died, 2139 (0.9%) self-terminated treatment and 75,041 (30.6%) had a loss to follow-up event captured. Males (OR: 1.16), Non-pregnant female (OR: 4.55), Patients on ≥ 3-monthly ARV refills (OR: 1.32), Patients with un-suppressed viral loads on ART (OR: 4.52), patients on adult 2nd line regimen (OR: 1.23) or pediatric on 1st line regimen (OR: 1.70) were significantly more likely to be lost to follow-up. Conclusion Despite increasing access to anti-retroviral therapy, loss to follow-up is still a challenge in the HIV program in Nigeria. Differentiated care approaches that will focus on males, non-pregnant females and paediatrics is encouraged. Reducing months of Anti-retroviral drug refill to less than 3 months is advocated for increased patient adherence.

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Estimating epidemiologic dynamics from cross-sectional viral load distributions

Science ◽

10.1126/science.abh0635 ◽

2021 ◽

pp. eabh0635

Author(s):

James A. Hay ◽

Lee Kennedy-Shaffer ◽

Sanjat Kanjilal ◽

Niall J. Lennon ◽

Stacey B. Gabriel ◽

...

Keyword(s):

Population Distribution ◽

Quantitative Polymerase Chain Reaction ◽

Cross Sectional ◽

Outbreak Management ◽

Viral Loads ◽

Time Estimates ◽

Load Distributions ◽

Random Samples ◽

Combining Data ◽

Polymerase Chain

Estimating an epidemic’s trajectory is crucial for developing public health responses to infectious diseases, but case data used for such estimation are confounded by variable testing practices. We show that the population distribution of viral loads observed under random or symptom-based surveillance, in the form of cycle threshold (Ct) values obtained from reverse-transcription quantitative polymerase chain reaction testing, changes during an epidemic. Thus, Ct values from even limited numbers of random samples can provide improved estimates of an epidemic’s trajectory. Combining data from multiple such samples improves the precision and robustness of such estimation. We apply our methods to Ct values from surveillance conducted during the SARS-CoV-2 pandemic in a variety of settings and offer alternative approaches for real-time estimates of epidemic trajectories for outbreak management and response.

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Higher Viral Load and Prolonged Viral Shedding Period is Associated with Impaired Th17 Cell Response in Patients with H1N1 Influenza A

Infection International ◽

10.1515/ii-2017-0021 ◽

2012 ◽

Vol 1 (3) ◽

pp. 137-145

Author(s):

Gui-lin Yang ◽

Ying-xia Liu ◽

Mu-tong Fang ◽

Wei-long Liu ◽

Xin-chun Chen ◽

...

Keyword(s):

T Cells ◽

Viral Load ◽

Cell Response ◽

Th17 Cell ◽

Influenza A ◽

H1n1 Influenza ◽

Cell Frequency ◽

Viral Loads ◽

Viral Shedding ◽

Ifn Γ

Abstract Objective To explore whether age, disease severity, cytokines and lymphocytes in H1N1 influenza A patients correlate with viral load and clearance. Methods Total of 70 mild and 16 severe patients infected with H1N1 influenza A virus were enrolled in this study. Results It was found that the patients under 14 years old and severe patients displayed significantly higher viral loads and prolonged viral shedding periods compared with the patients over 14 years old and mild patients, respectively (P < 0.05). Moreover, the patients under 14 years old and severe patients displayed significantly lower Th17 cell frequency than the patients over 14 years old and mild patients (P < 0.01). The viral shedding period inversely correlated with the frequency of IL-17+IFN-γ-CD4+ T cells. Additionally, the decreased concentration of serum TGF-β correlated with the decreased frequency of IL-17+IFN-γ-CD4+ T cells. Conclusions Both younger and severe patients are associated with higher viral loads and longer viral shedding periods, which may partially be attributed to the impaired Th17 cell response.

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Đánh giá nồng độ lactate và procalcitonin ở bệnh nhân Covid-19

Journal of Clinical Medicine- Hue Central Hospital ◽

10.38103/jcmhch.2022.75.8 ◽

2022 ◽

Author(s):

Thanh Xuan Nguyen

Keyword(s):

Serum Level ◽

Respiratory Infections ◽

Severe Pneumonia ◽

Cross Sectional Study ◽

Multiple Organ ◽

High Rate ◽

Rt Pcr ◽

Wuhan City ◽

Cross Sectional ◽

The Relationship

TÓM TẮT Đặt vấn đề: Bệnh COVID-19 đa dạng từ không có triệu chứng đến có các triệu chứng nhẹ cho đến viêm phổi nặng, hội chứng suy hô hấp cấp tiến triển (ARDS), nhiễm khuẩn huyết suy đa tạng và tử vong. Người cao tuổi, người có bệnh mạn tính sẽ có nguy cơ diễn biến nặng nhiều hơn. Nghiên cứu này nhằm xác định nồng độ lactate và PCT ở những bệnh nhân Covid-19 và xét mối liên quan giữa lactate và PCT trên bệnh nhân Covid-19. Đối tượng và phương pháp: Nghiên cứu mô tả cắt ngang trên 126 bệnh nhân được chẩn đoán nhiễm Sars-Cov-2 bằng xét nghiệm RT PCR. Kết quả: Tuổi trung bình 55,98 ± 17,1 tuổi (4 - 98 tuổi). Bệnh nhân > 60 tuổi chiếm tỉ lệ cao nhất (42,8%). Trung vị PCT: 3,6 (95%CI:3,21 - 3,75) ng/ml; trung vị lactate 1,5 (95%CI:1,21 - 1,91) mmol/L; lactate có tương quan thuận và yếu với procalcitonin với r = 0,241; p < 0,001. Nồng độ procalcitonin > 0,1 ng/ml; lactate > 2 mmol/l ở bệnh nhân Covid-19 chiếm tỷ lệ cao với 89,7% và 39,7%. Kết luận: Chỉ điểm procalcitonin, lactate tăng cao ở bệnh nhân Covid-19. ABSTRACT ASSESSMENT OF SERUM LEVEL OF LACTATE AND PROCALCITONIN IN COVID-19 PATIENTS Background: Sars-CoV-2 has been identified as the cause of acute respiratory infections in Wuhan city, Hubei province, China, and has since spread worldwide. Sars-CoV-2 is capable of aerosol transmission in enclosed, crowded, and poorly ventilated spaces. COVID-19 illness ranges from asymptomatic to mild symptoms to severe pneumonia, acute respiratory distress syndrome (ARDS), sepsis, multiple organ failure, and death. This study aims to determine lactate and PCT levels in Covid-19 patients and examine the relationship between lactate and PCT in Covid-19 patients. Methods: A cross-sectional study was performed on 126 patients diagnosed with Sars-Cov-2 infection by RT-PCR. Results: Mean age was 55.98 ± 17.1 years (range: 4-98 years). Patients more than 60 years old were accounted for the highest rate (42.8%). Median PCT: 3.6 (95%CI:3.21 - 3.75) ng/ml; median lactate 1.5 (95%CI:1.21 - 1,91) mmol/L; lactate has a positive and weak correlation with procalcitonin with r = 0.241; p < 0.001. Procalcitonin concentration > 0.1 ng/ml; lactate > 2 mmol/l in patients with Covid-19 accounted for a high rate with 89.7% and 39.7%. Conclusion: Serum level of procalcitonin and lactate raise highly in Covid-19 patients. Keywords: Covid-19, procalcitonin, lactate.

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