scholarly journals Seroconversion stages COVID19 into distinct pathophysiological states

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Matthew D Galbraith ◽  
Kohl T Kinning ◽  
Kelly D Sullivan ◽  
Ryan Baxter ◽  
Paula Araya ◽  
...  

COVID19 is a heterogeneous medical condition involving diverse underlying pathophysiological processes including hyperinflammation, endothelial damage, thrombotic microangiopathy, and end-organ damage. Limited knowledge about the molecular mechanisms driving these processes and lack of staging biomarkers hamper the ability to stratify patients for targeted therapeutics. We report here the results of a cross-sectional multi-omics analysis of hospitalized COVID19 patients revealing that seroconversion status associates with distinct underlying pathophysiological states. Low antibody titers associate with hyperactive T cells and NK cells, high levels of IFN alpha, gamma and lambda ligands, markers of systemic complement activation, and depletion of lymphocytes, neutrophils, and platelets. Upon seroconversion, all of these processes are attenuated, observing instead increases in B cell subsets, emergency hematopoiesis, increased D-dimer, and hypoalbuminemia. We propose that seroconversion status could potentially be used as a biosignature to stratify patients for therapeutic intervention and to inform analysis of clinical trial results in heterogenous patient populations.

2020 ◽  
Author(s):  
Matthew D. Galbraith ◽  
Kohl T. Kinning ◽  
Kelly D. Sullivan ◽  
Ryan Baxter ◽  
Paula Araya ◽  
...  

ABSTRACTCOVID19 is a heterogeneous medical condition involving a suite of underlying pathophysiological processes including hyperinflammation, endothelial damage, thrombotic microangiopathy, and end-organ damage. Limited knowledge about the molecular mechanisms driving these processes and lack of staging biomarkers hamper the ability to stratify patients for targeted therapeutics. We report here the results of a cross-sectional multi-omics analysis of hospitalized COVID19 patients revealing that seroconversion status associates with distinct underlying pathophysiological states. Seronegative COVID19 patients harbor hyperactive T cells and NK cells, high levels of IFN alpha, gamma and lambda ligands, markers of systemic complement activation, neutropenia, lymphopenia and thrombocytopenia. In seropositive patients, all of these processes are attenuated, observing instead increases in B cell subsets, emergency hematopoiesis, increased markers of platelet activation, and hypoalbuminemia. We propose that seroconversion status could potentially be used as a biosignature to stratify patients for therapeutic intervention and to inform analysis of clinical trial results in heterogenous patient populations.


2017 ◽  
Vol 1 (3) ◽  
pp. 10-16
Author(s):  
Prakashkumar Kyada ◽  
Kunal Jadhav ◽  
T. K. Biswas ◽  
Varshil Mehta ◽  
Sojib Bin Zaman

Objective: Hypertension is one of the common risk factors for cardiovascular and cerebrovascular diseases/disorders A developing country like India faces the double burden of communicable and non-communicable diseases; of the which, hypertension is the most important treatable cause of mortality and morbidity with loss of functional capacity and decline in the quality of life. Aim: To study the prevalence of end organ damage in the hypertensive geriatric age group. Method: The present study was a cross sectional study, conducted in 150 elderly patients admitted in MGM Hospital, Navi Mumbai, India with the diagnosis of stage I or II hypertension from 2011 to 2013. Results: Data analysis of the present study showed that 68% of elderly population aged between 60 to 69 years were suffering from hypertension. Compared to males, females had a higher rate of target organ damage. This study found that out of all patients with total end organ damage, 54.6 % had CVS complications, 15.7 % had hypertensive retinopathy, 25.9 % and 18.51 had raised creatinine and proteinuria respectively. 19.4 % had cerebrovascular accident (CVA) complications. Among Cardiovascular related complications Coronary artery disease (CAD) was found in 21 patients, out of them 7 had Congestive cardiac Failure (CCF). Left Ventricular Hypertrophy (LVH) was the most common complication and seen in 38 patients. 13.8 % patients had Regional Wall Motion Abnormality (RWMA) Conclusion: The present study concluded that Isolated Systolic Hypertension (ISH) is the commonest type of hypertension in geriatric age group. This study concluded that the most common risk factors of HTN in the elderly are sedentary life style, dyslipidemia and extra salt intake while the most common end organ damage was observed to be Left Ventricular Hypertrophy followed by renal dysfunction. Keywords:  Hypertension,  Isolated Systolic Hypertension, Dyslipidemia.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Simone Canovi ◽  
◽  
Giulia Besutti ◽  
Efrem Bonelli ◽  
Valentina Iotti ◽  
...  

Abstract Background Laboratory data and computed tomography (CT) have been used during the COVID-19 pandemic, mainly to determine patient prognosis and guide clinical management. The aim of this study was to evaluate the association between CT findings and laboratory data in a cohort of COVID-19 patients. Methods This was an observational cross-sectional study including consecutive patients presenting to the Reggio Emilia (Italy) province emergency rooms for suspected COVID-19 for one month during the outbreak peak, who underwent chest CT scan and laboratory testing at presentation and resulted positive for SARS-CoV-2. Results Included were 866 patients. Total leukocytes, neutrophils, C-reactive protein (CRP), creatinine, AST, ALT and LDH increase with worsening parenchymal involvement; an increase in platelets was appreciable with the highest burden of lung involvement. A decrease in lymphocyte counts paralleled worsening parenchymal extension, along with reduced arterial oxygen partial pressure and saturation. After correcting for parenchymal extension, ground-glass opacities were associated with reduced platelets and increased procalcitonin, consolidation with increased CRP and reduced oxygen saturation. Conclusions Pulmonary lesions induced by SARS-CoV-2 infection were associated with raised inflammatory response, impaired gas exchange and end-organ damage. These data suggest that lung lesions probably exert a central role in COVID-19 pathogenesis and clinical presentation.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ameer Kakaje ◽  
Mohammad Marwan Alhalabi ◽  
Ayham Alyousbashi ◽  
Ayham Ghareeb

AbstractAllergic rhinitis (AR) is a common medical condition worldwide. It is an inflammation in the nasal mucosa due to allergen exposure throughout the year. Laryngopharyngeal reflux (LPR) is another medical condition that can overlap with AR. LPR can be considered an extra oesophageal manifestation of gastro-oesophageal reflux disease (GORD) or a different entity. Its diagnosis imposes a real challenge as it has a wide range of unspecific symptoms. Although AR and LPR are not life-threatening, they can severely affect the quality of life for years and cause substantial distress. Moreover, having AR is associated with having asthma which is also in turn associated with GORD. This is a cross-sectional study which used surveys distributed online on Social Media and targeted people across Syria. All participants who responded to the key questions were included. Reflux symptom index (RSI) was used for LPR, and score for allergic rhinitis (SFAR) was used for AR. Demographic questions and whether the participant had asthma were also included in the survey. We found that there was an association between the symptoms of LPR and AR p < 0.0001 (OR, 2.592; 95% CI 1.846–3.639), and their scores were significantly correlated (r = 0.334). Having asthma was associated with LPR symptoms p = 0.0002 (OR 3.096; 95% CI 1.665–5.759) and AR p < 0.0001 (OR 6.772; 95% CI 2.823–16.248). We concluded that there was a significant association between having LPR, AR, and asthma. We need more studies to distinguish between their common symptoms and aetiologies.


BMC Urology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Hui-Yin Yow ◽  
John Jeh Lung Tiong ◽  
Chun-Wai Mai ◽  
Esther van der Werf ◽  
Zulkifli Md Zainuddin ◽  
...  

Abstract Background Nocturia is widely prevalent condition with detrimental effects on quality of life and general health. In Malaysia, there is a lack of up-to-date prevalence study on nocturia. This study aimed to investigate the prevalence of nocturia and awareness pertaining to nocturia among Malaysian adults. Methods A cross-sectional population-based study was conducted among Malaysian adults aged ≥ 18 years old. The data was collected by mixed mode self-administered questionnaire from May 2019 to September 2019. Nocturia was defined as one or more voids at night. Results There were a total of 4616 respondents with 74.5% of response rate. The overall prevalence of nocturia among Malaysian adults was found to be 57.3%. In multivariate analysis, respondents aged 31–40 (1.91 [1.52–2.40]) or > 60 years old (2.03 [1.48–2.71]), and those who presented with hypertension (2.84 [2.28–3.53]), diabetes mellitus (1.78 [1.42–2.25]), renal disease (3.58 [1.93–6.63]) or overactive bladder (1.61 [1.10–2.35]) were associated with higher prevalence of nocturia. A significantly lower disease prevalence (p < 0.05) was noted among those aged 41–50 (0.73 [0.59–0.91]), male (0.78 [0.69–0.88]) and Chinese (0.47 [0.30–0.74]) or Indian (0.34 [0.21–0.54]) ethnicities. A total of 37.3% of respondents with nocturia reported that they faced sleeping difficulty about half the time or more after waking up in the middle of night. Those who had ≥ 2 voids per night experienced significantly higher mean bother score than those who had 1 void per night (p < 0.001). Approximately half (56.7%) of all respondents were not aware that night time urination is a medical condition. Only 25.2% of respondents with nocturia had sought medical attention for their nocturia. Conclusions The prevalence of nocturia among Malaysian adults is high and strongly influenced by age, sex, race and comorbidities. However, the general awareness pertaining to nocturia being a health issue remains low among Malaysians. The findings also highlighted the impact of nocturia on sleep and the need for nocturia education to better address this disease.


2000 ◽  
Vol 89 (2) ◽  
pp. 823-839 ◽  
Author(s):  
Robert H. Fitts ◽  
Danny R. Riley ◽  
Jeffrey J. Widrick

Spaceflight (SF) has been shown to cause skeletal muscle atrophy; a loss in force and power; and, in the first few weeks, a preferential atrophy of extensors over flexors. The atrophy primarily results from a reduced protein synthesis that is likely triggered by the removal of the antigravity load. Contractile proteins are lost out of proportion to other cellular proteins, and the actin thin filament is lost disproportionately to the myosin thick filament. The decline in contractile protein explains the decrease in force per cross-sectional area, whereas the thin-filament loss may explain the observed postflight increase in the maximal velocity of shortening in the type I and IIa fiber types. Importantly, the microgravity-induced decline in peak power is partially offset by the increased fiber velocity. Muscle velocity is further increased by the microgravity-induced expression of fast-type myosin isozymes in slow fibers (hybrid I/II fibers) and by the increased expression of fast type II fiber types. SF increases the susceptibility of skeletal muscle to damage, with the actual damage elicited during postflight reloading. Evidence in rats indicates that SF increases fatigability and reduces the capacity for fat oxidation in skeletal muscles. Future studies will be required to establish the cellular and molecular mechanisms of the SF-induced muscle atrophy and functional loss and to develop effective exercise countermeasures.


2012 ◽  
Vol 24 (9) ◽  
pp. 1409-1418 ◽  
Author(s):  
Senyeong Kao ◽  
Yun-Chang Wang ◽  
Ya-Mei Tzeng ◽  
Chang-Kuo Liang ◽  
Fu-Gong Lin

ABSTRACTBackground: It is well documented that fall risk among elderly people is associated with poor health and depression. In this study, we set out to examine the combined effects of medical condition and depression status on fall incidents among community-dwelling elderly people.Methods: A cross-sectional study was carried out to investigate the fall history of community-dwelling elders involving 360 participants. Those who had experienced at least two falls over the previous year, or one injurious fall, were defined as “fallers.” The Geriatric Depression Scale-15 was used as a screening instrument for depression status.Results: Based on a multivariate logistic regression and stratification analysis, depression was found to interact with various medical conditions on fall risk. In comparison with the non-depressive reference group, a six-fold fall risk was discernible among depressed elders with polypharmacy, while a five-fold risk was found among depressive elders using ancillary devices, along with a four-fold risk among depressive elders with diabetes or cardiovascular disease. Finally, arthritis was found to produce a nine-fold risk of falls among such populations.Conclusions: These findings suggest that greater emphasis should be placed on the integration of depression screening as an element of fall risk assessment in elderly people.


2013 ◽  
Vol 28 (2) ◽  
pp. 145-149 ◽  
Author(s):  
Brett Williams ◽  
Mal Boyle ◽  
Tracy Earl

AbstractIntroductionParamedics rely on establishing a health provider-patient relationship with patients that promotes two-way communication, patient satisfaction, and facilitates appropriate patient assessment and treatment. Paramedics also must have an ability to empathize with patients and their family members in order to develop a successful health provider-patient relationship. The objective of this study was to assess paramedics’ empathy and attitudes toward patients with specific conditions.MethodsThis was a cross-sectional study using a convenience sample of first-, second-, and third-year, Australian undergraduate paramedic students. Student empathy levels were assessed using two standardized self-reporting instruments: the Jefferson Scale of Physician Empathy (JSPE) Health Professional (HP) version and the Medical Condition Regard Scale (MCRS).ResultsA total of 94 paramedic students participated in the study. The JSPE demonstrated that male paramedic students had higher mean empathy scores than did female paramedic students (113.25 and 107.5, respectively; P = .042). The JSPE empathy level scores were lowest among first-year paramedic students (mean = 107.53); age was not found to be a significant variable on empathy scores. The Medical Condition Regard Scale revealed lowest scores in compassion towards substance abuse (mean = 46.42).ConclusionsThe results of this study provide the discipline of paramedic health care with useful data, and provide students, academics, and other educators with important information regarding the improvement of the health provider-patient relationship and paramedic education curriculum development.WilliamsB, BoyleM, EarlT. Measurement of empathy levels in undergraduate paramedic students. Prehosp Disaster Med. 2013;28(2):1-5.


2018 ◽  
Vol 315 (1) ◽  
pp. R104-R112 ◽  
Author(s):  
Kanika Gupta ◽  
Om Jahagirdar ◽  
Kalpna Gupta

Sickle cell disease (SCD) is a genetic disorder associated with hemolytic anemia, end-organ damage, reduced survival, and pain. One of the unique features of SCD is recurrent and unpredictable episodes of acute pain due to vasoocclusive crisis requiring hospitalization. Additionally, patients with SCD often develop chronic persistent pain. Currently, sickle cell pain is treated with opioids, an approach limited by adverse effects. Because pain can start at infancy and continue throughout life, preventing the genesis of pain may be relatively better than treating the pain once it has been evoked. Therefore, we provide insights into the cellular and molecular mechanisms of sickle cell pain that contribute to the activation of the somatosensory system in the peripheral and central nervous systems. These mechanisms include mast cell activation and neurogenic inflammation, peripheral nociceptor sensitization, maladaptation of spinal signals, central sensitization, and modulation of neural circuits in the brain. In this review, we describe potential preventive/therapeutic targets and their targeting with novel pharmacologic and/or integrative approaches to ameliorate sickle cell pain.


2021 ◽  
Vol 18 (1) ◽  
pp. 147916412199252
Author(s):  
Yuwei Yang ◽  
Peng Xu ◽  
Yan Liu ◽  
Xiaohong Chen ◽  
Yiyang He ◽  
...  

Aim: Atherosclerosis involves vascular endothelial damage and lipid metabolism disorder, which is closely related to the occurrence and development of diabetic kidney disease (DKD). However, studies on non-high albuminuria DKD (NHADKD) with an albumin to creatinine ratio (ACR) <30 mg/g are rare. This study is to investigate the relationship between atherogenic factors and the occurrence of NHADKD. Methods: Serum lipid indicators, lipoprotein-associated phospholipase A2 (Lip-PLA2) and homocysteine levels were measured in 1116 subjects to analyze their relationship with NHADKD. Results: Among all subjects, Lip-PLA2 had the closest but relatively weak correlation with ACR ( r = 0.297, p < 0.001) and only homocysteine was moderately correlated with eGFR ( r = −0.465, p < 0.001). However, in patients with NHADKD, these atherosclerotic factors were weakly correlated or uncorrelated with eGFR (max. | r| = 0.247). Stratified risk analysis showed that when ACR was <10 mg/g, homocysteine [OR = 6.97(4.07–11.95)], total cholesterol (total-Chol) [OR = 6.04(3.03–12.04)], and high-density lipoprotein cholesterol (HDL-Chol) [OR = 5.09(2.99–8.64)] were risk factors for NHADKD. There was no significant difference of OR between these three factors ( Z = 0.430–1.044, all p > 0.05). When ACR was ⩾10mg/g, homocysteine [OR = 17.26(9.67–30.82)] and total-Chol [OR = 5.63(2.95–10.76)] were risk factors for NHADKD, and ORhomocysteine was significantly higher than ORtotal-Chol ( Z = 3.023, p < 0.05). Conclusions: The occurrence of NHADKD may be related to the levels of homocysteine, total-Chol, HDL-Chol, and Lip-PLA2 in blood. Among them, homocysteine may be most closely related to NHADKD.


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