scholarly journals SARS-CoV-2 Nucleocapsid Plasma Antigen for Diagnosis and Monitoring of COVID-19

2021 ◽  
Author(s):  
Hannah Wang ◽  
Catherine A Hogan ◽  
Michelle Verghese ◽  
Daniel Solis ◽  
Mamdouh Sibai ◽  
...  

Abstract Background Detection of SARS-CoV-2 nucleocapsid antigen in blood has been described, but the diagnostic and prognostic role of antigenemia is not well understood. This study aimed to determine the frequency, duration, and concentration of nucleocapsid antigen in plasma and its association with COVID-19 severity. Methods We utilized an ultrasensitive electrochemiluminescence immunoassay targeting SARS-CoV-2 nucleocapsid antigen to evaluate 777 plasma samples from 104 individuals with COVID-19. We compared plasma antigen to respiratory nucleic acid amplification testing (NAAT) in 74 individuals with COVID-19 from samples collected ± 1 day of diagnostic respiratory NAAT, and in 52 SARS-CoV-2-negative individuals. We used Kruskal-Wallis tests, multivariable logistic regression, and mixed-effects modeling to evaluate whether plasma antigen concentration was associated with disease severity. Results Plasma antigen had 91.9% (95% CI 83.2-97.0%) clinical sensitivity and 94.2% (84.1-98.8%) clinical specificity. Antigen-negative plasma samples belonged to patients with later respiratory cycle thresholds (Ct) when compared with antigen-positive plasma samples. Median plasma antigen concentration (log10 fg/mL) was 5.4 (IQR 3.9-6.0) in outpatients, 6.0 (5.4-6.5) in inpatients, and 6.6 (6.1-7.2) in intensive care unit (ICU) patients. In models adjusted for age, sex, diabetes, and hypertension, plasma antigen concentration at diagnosis was associated with ICU admission (OR 2.8 [95% CI 1.2-6.2], P=.01), but not with non-ICU hospitalization. Rate of antigen decrease was not associated with disease severity. Conclusions SARS-CoV-2 plasma nucleocapsid antigen exhibited comparable diagnostic performance to upper respiratory NAAT, especially among those with late respiratory Ct. In addition to currently available tools, antigenemia may facilitate patient triage to optimize intensive care utilization.

Author(s):  
Yang Yang ◽  
Chenguang Shen ◽  
Jinxiu Li ◽  
Jing Yuan ◽  
Minghui Yang ◽  
...  

The outbreak of Coronavirus Disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, December 2019, and continuously poses a serious threat to public health. Our previous study has shown that cytokine storm occurred during SARS-CoV-2 infection, while the detailed role of cytokines in the disease severity and progression remained unclear due to the limited case number. In this study, we examined 48 cytokines in the plasma samples from 53 COVID-19 cases, among whom 34 were severe cases, and the others moderate. Results showed that 14 cytokines were significantly elevated upon admission in COVID-19 cases. Moreover, IP-10, MCP-3, and IL-1ra were significantly higher in severe cases, and highly associated with the PaO2/FaO2 and Murray score. Furthermore, the three cytokines were independent predictors for the progression of COVID-19, and the combination of IP-10, MCP-3 and IL-1ra showed the biggest area under the curve (AUC) of the receiver-operating characteristics (ROC) calculations. Serial detection of IP-10, MCP-3 and IL-1ra in 14 severe cases showed that the continuous high levels of these cytokines were associated with disease deterioration and fatal outcome. In conclusion, we report biomarkers that closely associated with disease severity and outcome of COVID-19. These findings add to our understanding of the immunopathologic mechanisms of SARS-CoV-2 infection, providing novel therapeutic targets and strategy.


Author(s):  
Jyot Amrita

Summary   Background: COVID-19 is caused by a novel coronavirus, named severe acute respiratory syndrome coronavirus2 (SARS-CoV-2). The foremost predominant complication of SARS-CoV-2 is arterial hypoxemia thereby disturbing lung compliance, requiring mechanical ventilation. The aim of the current research study is to analyze role of ABG as a valuable assessment tool of disease severity in SARS-CoV-2 patients. Methods: 170 arterial blood samples were collected from patients admitted in Intensive Care Unit (ICU) of Sri Guru Ram Das Charitable Hospital, Amritsar. They were analyzed for arterial blood gas using ABG analyzer. Parameters of ABG such as pH, pCo2, HCO3, O2 saturation, ionized calcium (iCa) and calculated ionized calcium (at pH 7.4) was calculated for all the samples. Results: Continuous variables were described as medians with interquartile ranges (IQRs) and categorical variables as percentages and frequencies. Spearman correlation test was done for calculation of correlation between pH and other ABG parameters. Analysis of arterial blood gas revealed significant negative correlation (p<0.05) between pH and pCO2 and significant positive correlation (p<0.05) between pH and HCO3 and between pH and delta ionized calcium. Low levels (98.2%) of ionized calcium were observed while monitoring the ABG findings though weak negative correlation (p<0.05) was observed between pH and iCa. Conclusion: Our study suggests that ABG analysis acts as a momentous indicator for critically ill patients admitted in Intensive Care Unit (ICU). Estimation of iCa in this critical care setting acts as a distinctive biochemical feature of SARS-CoV-2 disease, as an initial assessment tool, for hypocalcemia. Keywords:  Arterial Blood Gas, SARS-CoV-2, Ionized Calcium, Hypocalcemia


2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S809-S809
Author(s):  
S Kyle Throneberry ◽  
Bert K Lopansri ◽  
Nancy A Grisel

Abstract Background The role of nucleic acid amplification tests (NAAT) for diagnosing Clostridioides difficile (CD) infection remains controversial. Adding CD to multiplex molecular panels (GIPCR) that detects multiple GI pathogens of community origin, has the potential to introduce confusion leading to delayed diagnosis and unnecessary antibiotic use especially if pretest probability is not considered. Methods We conducted a retrospective study to determine the frequency at which clinicians characterize pretest probability and disease severity in adult patients with diarrhea who tested positive for CD by GIPCR (BioFire, Inc.) from July 1, 2017 to October 16, 2018. We excluded immunocompromised patients. Routine testing includes reflex to GDH and toxin A/B detection when GIPCR is positive for CD. Charts were reviewed and clinical suspicion (PTP) was assigned as high, medium, low, or not done. Disease severity was classified as mild, moderate and severe. Exposure to systemic antibiotic within 90 days prior to testing and stool frequency was also captured. Results In total, 447 patients were included in the analysis: 110 (24.6%) were positive for both GDH and Toxin (G+/T+), 158 (35.3%) were G+/T−, 179 (40%) were G−/T−, and 149 (33%) were not classified. Toxin positivity was highest in the setting of high PTP (67%) (figure). In contrast, toxin was negative in most cases when suspicion for CDI was low or not characterized (81%). For medium suspicion, only 36% were T+. Antibiotic exposure prior to testing was observed in 203 (45%) of the cases. More G+/T+ patients received antibiotics (63%) before testing and 66% of G−/T− did not receive antecedent antibiotics. Clinicians did not characterize frequency of diarrhea in 261 (58%) of the patients tested and 95% of cases did not undergo severity classification. When documented, 24% of tested patients had < 3 diarrheal episodes/day (Table 1). Most cases where multiple pathogens were detected were T− (84.5%) and G−/T− (44%) (Table 2). Conclusion Overall, characterization of diarrheal illness was poor and PTP was frequently omitted. A large proportion of GIPCR results positive for CD (40%) were negative for both GDH and Toxin. CD results in molecular testing with syndromic panels should be interpreted with caution. Disclosures All authors: No reported disclosures.


2020 ◽  
Author(s):  
Nikhil Ram-Mohan ◽  
David Kim ◽  
Elizabeth J Zudock ◽  
Marjan M Hashemi ◽  
Kristel C Tjandra ◽  
...  

AbstractBackgroundThe determinants of COVID-19 disease severity and extrapulmonary complications (EPCs) are poorly understood. We characterise the relationships between SARS-CoV-2 RNAaemia and disease severity, clinical deterioration, and specific EPCs.MethodsWe used quantitative (qPCR) and digital (dPCR) PCR to quantify SARS-CoV-2 RNA from nasopharyngeal swabs and plasma in 191 patients presenting to the Emergency Department (ED) with COVID-19. We recorded patient symptoms, laboratory markers, and clinical outcomes, with a focus on oxygen requirements over time. We collected longitudinal plasma samples from a subset of patients. We characterised the role of RNAaemia in predicting clinical severity and EPCs using elastic net regression.Findings23·0% (44/191) of SARS-CoV-2 positive patients had viral RNA detected in plasma by dPCR, compared to 1·4% (2/147) by qPCR. Most patients with serial measurements had undetectable RNAaemia 10 days after onset of symptoms, but took 16 days to reach maximum severity, and 33 days for symptoms to resolve. Initially RNAaemic patients were more likely to manifest severe disease (OR 6·72 [95% CI, 2·45 – 19·79]), worsening of disease severity (OR 2·43 [95% CI, 1·07 - 5·38]), and EPCs (OR 2·81 [95% CI, 1·26 – 6·36]). RNA load correlated with maximum severity (r = 0·47 [95% CI, 0·20 - 0·67]).InterpretationdPCR is more sensitive than qPCR for the detection of SARS-CoV-2 RNAaemia, which is a robust predictor of eventual COVID-19 severity and oxygen requirements, as well as EPCs. Since many COVID-19 therapies are initiated on the basis of oxygen requirements, RNAaemia on presentation might serve to direct early initiation of appropriate therapies for the patients most likely to deteriorate.FundingNIH/NIAID (Grants R01A153133, R01AI137272, and 3U19AI057229 – 17W1 COVID SUPP #2) and a donation from Eva Grove.Research in contextEvidence before this studyThe varied clinical manifestations of COVID-19 have directed attention to the distribution of SARS-CoV-2 in the body. Although most concentrated and tested for in the nasopharynx, SARS-CoV-2 RNA has been found in blood, stool, and numerous tissues, raising questions about dissemination of viral RNA throughout the body, and the role of this process in disease severity and extrapulmonary complications. Recent studies have detected low levels of SARS-CoV-2 RNA in blood using either quantitative reverse transcriptase real-time PCR (qPCR) or droplet digital PCR (dPCR), and have associated RNAaemia with disease severity and biomarkers of dysregulated immune response.Added value of this studyWe quantified SARS-CoV-2 RNA in the nasopharynx and plasma of patients presenting to the Emergency Department with COVID-19, and found an array-based dPCR platform to be markedly more sensitive than qPCR for detection of SARS-CoV-2 RNA, with a simplified workflow well-suited to clinical adoption. We collected serial plasma samples during patients’ course of illness, and showed that SARS-CoV-2 RNAaemia peaks early, while clinical condition often continues to worsen. Our findings confirm the association between RNAaemia and disease severity, and additionally demonstrate a role for RNAaemia in predicting future deterioration and specific extrapulmonary complications.Implications of all the available evidenceVariation in SARS-CoV-2 RNAaemia may help explain disparities in disease severity and extrapulmonary complications from COVID-19. Testing for RNAaemia with dPCR early in the course of illness may help guide patient triage and management.


2020 ◽  
Vol 19 (1) ◽  
pp. 3
Author(s):  
Giulliano Gardenghi

Introduction: Patients in the intensive care unit (ICU) have several deleterious effects of immobilization, including weakness acquired in the ICU. Exercise appears as an alternative for early mobilization in these patients. Objective: This work aims to highlight the hemodynamic repercussions and the applicability of exercise in the ICU. Methods: An integrative literature review was carried out, with articles published between 2010 and 2018, in the Lilacs, PubMed and Scielo databases, using the following search terms: exercise, cycle ergometer, intensive care units, early mobilization, mechanical ventilation, artificial respiration. Results: 13 articles were included, addressing hemodynamic monitoring and the role of exercise as early mobilization, with or without ventilatory support. The exercise sessions were feasible and safe within the ICU environment. Conclusion: Physical exercise can be performed safely in an ICU environment, if respecting a series of criteria such as those presented here. It is important that the assistant professional seeks to prescribe interventions based on Exercise Physiology that can positively intervene in the functional prognosis in critically ill patients.Keywords: exercise, intensive care units, patient safety.


2020 ◽  
Vol 35 (2) ◽  
pp. 100-104
Author(s):  
Maksudur Rahman ◽  
Mohammad Abdullah Al Mamun ◽  
MAK Azad Chowdhury ◽  
Abu Sayeed Munsi

Background: Recently it has been apprehended that sildenafil, a drug which has been successfully using in the treatment of PPHN and erectile dysfunction in adult, is going to be withdrawn from the market of Bangladesh due to threat of its misuses. Objective: The aim of this study was to see the extent of uses of sildenafil in the treatment of PPHN and importance of availability of this drugs in the market inspite of its probable misuses. Methods: This cross sectional study was conducted in neonatal intensive care unit (NICU), special baby care unit (SCABU) and cardiac intensive care unit (CICU) of Dhaka Shishu (Children) Hospital from June, 2017 to May 2018. Neonates with PPHN were enrolled in the study. All cases were treated with oral sildenefil for PPHN along with others management according to hospital protocol. Data along with other parameters were collected and analyzed. Results: Total 320 patients with suspected PPHN were admitted during the study period. Among them 92 (29%) cases had PPHN. Male were 49(53 %) cases and female were 43(47%) cases. Mean age at hospital admission was 29.7±13.4 hours. Based on echocardiography,13(14%) cases had mild, 38 (41%) cases moderate and 41(45%) cases severe PPHN. Mean duration of sildenafil therapy was 11.9±7.1 days. Improved from PPHN were 83 (90%) cases. Mortality was 10% (9). Conclusion: In this study it was found that the incidence of PPHN is 29% among the suspected newborns. Sildenafil is successfull in improving the oxygenation of PPHN and to decrease the mortality of neonates. DS (Child) H J 2019; 35(2) : 100-104


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