scholarly journals Misinterpretation of viral load in COVID-19

Author(s):  
Renan Lyra Miranda ◽  
Alexandro Guterres ◽  
Carlos Henrique de Azeredo Lima ◽  
Paulo Niemeyer Filho ◽  
Mônica R. Gadelha

AbstractKnowledge of viral load is essential for formulating strategies for antiviral treatment, vaccination, and epidemiological control of COVID-19. Moreover, patients identification with high viral load could also be useful to understand risk factors such as age, comorbidities, severity of symptoms and hypoxia to decide the need for hospitalization. Several studies are evaluating the importance of analyzing viral load in different types of samples, clinical outcomes and viral transmission pathways. However, in a great number of emerging studies cycle threshold (Ct) values by itself is often used as a viral load indicator, which may be a mistake. In this study, we compared tracheal aspirate with nasopharyngeal samples obtained from critically ill COVID-19 patients and demonstrate how the raw Ct could lead to misinterpretation of results. Further, we analyzed nasopharyngeal swabs positive samples and propose a method to reduce evaluation error that could occur from using raw Ct. Based on these findings, we show the impact that normalization of Ct values has on interpretation of viral load data from different biological samples from patients with COVID-19, transmission and lastly in relations with clinical outcomes.ImportanceIn a pandemic, prevention of disease transmission is key. Reliable data for profiles of viral load are needed and important to guide antiviral treatment, infection control and vaccination. The differential expression of SARS-CoV-2 viral RNA among patient groups is a current topic of interest and viral load has been associated with a diversity of outcomes. However, in a great number of emerging studies cycle threshold (Ct) values by itself is often used as a viral load indicator, which may be a mistake. In this study, we compared tracheal aspirate with nasopharyngeal samples obtained from critically ill COVID-19 patients and demonstrate how the raw Ct could lead to misinterpretation of results. Based on these findings, we show the impact that normalization of Ct values has on interpretation of viral load data from different biological samples from patients with COVID-19, transmission and lastly in relations with clinical outcomes.

2019 ◽  
Vol 35 (7) ◽  
pp. 615-626 ◽  
Author(s):  
Angel Joel Cadena ◽  
Sara Habib ◽  
Fred Rincon ◽  
Stephanie Dobak

Malnutrition is frequently seen among patients in the intensive care unit. Evidence shows that optimal nutritional support can lead to better clinical outcomes. Recent clinical trials debate over the efficacy of enteral nutrition (EN) over parenteral nutrition (PN). Multiple trials have studied the impact of EN versus PN in terms of health-care cost and clinical outcomes (including functional status, cost, infectious complications, mortality risk, length of hospital and intensive care unit stay, and mechanical ventilation duration). The aim of this review is to address the question: In critically ill adult patients requiring nutrition support, does EN compared to PN favorably impact clinical outcomes and health-care costs?


2018 ◽  
Vol 54 (2) ◽  
pp. 119-124
Author(s):  
Melissa Heim ◽  
Ryan Draheim ◽  
Anna Krupp ◽  
Paula Breihan ◽  
Ann O’Rourke ◽  
...  

Background: A multidisciplinary team updated an institution-specific pain, agitation, and delirium (PAD) guideline based on the recommendations from the Society of Critical Care Medicine (SCCM) PAD guidelines. This institution-specific guideline emphasized protocolized sedation with increased as needed boluses, and nonbenzodiazepine infusions, daily sedation interruption, and pairing of spontaneous awakening (SAT) and breathing trials (SBT). Objective: The purpose of this study was to evaluate the impact of implementation of a PAD guideline on clinical outcomes and medication utilization in an academic medical center intensive care unit (ICU). It was hypothesized that implementation of an updated guideline would improve clinical outcomes and decrease usage of benzodiazepine infusions. Methods: Pre-post retrospective chart review of 2417 (1147 pre, 1270 post) critically ill, mechanically ventilated adults in a medical/surgical ICU over a 2-year period (1 year pre and post guideline implementation). Results: After guideline implementation, average ventilation days was reduced (3.98 vs 3.43 days, P = .0021), as well as ICU and hospital length of stay (LOS) (4.79 vs 4.34 days, P = .048 and 13.96 vs 12.97 days, P = .045, respectively). Hospital mortality (19 vs 19%, P = .96) and acute physiology and chronic health evaluation (APACHE) IV scores (77.28 vs 78.75, P = .27) were similar. After guideline implementation, the percentage of patients receiving midazolam infusions decreased (422/1147 [37%] vs 363/1270 patients [29%], P = .0001). The percentage of patients receiving continuous infusion propofol (679/1147 [59%] vs 896/1270 [70%], P = .0001) and dexmedetomidine (78/1147 [7%] vs 147/1270 [12%], P = .0001) increased. Conclusions: Implementing a multidisciplinary PAD guideline utilizing protocolized sedation and daily sedation interruption decreased ventilation days and ICU and hospital LOS while decreasing midazolam drip usage.


Author(s):  
Olof Elvstam ◽  
Gaetano Marrone ◽  
Patrik Medstrand ◽  
Carl Johan Treutiger ◽  
Anders Sönnerborg ◽  
...  

Abstract Background The impact of low levels of human immunodeficiency virus (HIV) RNA (low-level viremia [LLV]) during combination antiretroviral therapy (cART) on clinical outcomes is unclear. We explored the associations between LLV and all-cause mortality, AIDS, and serious non-AIDS events (SNAEs). Methods We grouped individuals starting cART 1996–2017 (identified from the Swedish InfCare HIV register) as virologic suppression (VS; <50 copies/mL), LLV (repeated viral load, 50–999 copies/mL), and nonsuppressed viremia (NSV; ≥1000 copies/mL). Separately, LLV was subdivided into 50–199 and 200–999 copies/mL (reflecting different definitions of virologic failure). Proportional-hazard models (including sex, age, pre-ART CD4 count and viral load, country of birth, injection drug use, treatment experience and interruptions, and an interaction term between viremia and time) were fitted for the study outcomes. Results A total of 6956 participants were followed for a median of 5.7 years. At the end of follow-up, 60% were categorized as VS, 9% as LLV, and 31% as NSV. Compared with VS, LLV was associated with increased mortality (adjusted hazard ratio [aHR], 2.2; 95% confidence interval [CI], 1.3–3.6). This association was also observed for LLV 50–199 copies/mL (aHR, 2.2; 95% CI, 1.3–3.8), but was not statistically significant for LLV 200–999 copies/mL (aHR, 2.1; 95% CI, .96–4.7). LLV 50–999 copies/mL was not linked to increased risk of AIDS or SNAEs, but in subanalysis, LLV 200–999 copies/mL was associated with SNAEs (aHR, 2.0; 95% CI, 1.2–3.6). Conclusions In this population-based cohort, LLV during cART was associated with adverse clinical outcomes.


Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3851-3851
Author(s):  
Irina B. Pateva ◽  
Steven L Shein ◽  
MaryAnn O'Riordan ◽  
Sanjay P Ahuja

Abstract Introduction: The association of packed Red Blood Cell (pRBC) transfusions with worse outcomes in critically ill adults is well documented. The impact of pRBC transfusions on clinical outcomes in critically ill children, however, has not been well studied. Associations of pRBCs with outcomes such as mortality and length of stay need to be studied in large clinical databases. This will lead to improvement of our knowledge and generation of guidelines for transfusions in children hospitalized in the Pediatric Intensive Care Units (PICU). Methods: With IRB approval, the Pediatric Health Information System (PHIS) database was queried for children ≤ 18 years admitted to the PICU, receiving pRBC transfusions between January 2011 and December 2015. The PHIS is a database that captures de-identified patient information from 45 pediatric hospitals in the US. The patients of this study were stratified by age groups: less than 1 month of age; 1 month to < 3years; 3 to <10 years; 10 to < 15 years and 15 to 18 years. Patients with underlying hematological or oncological diagnoses and who had undergone HSCT were excluded from the study. Information regarding major comorbidities such as mechanical ventilation, sepsis, use of vasoactive agents, acute kidney injury (AKI) and post-operative state were extracted. Patients who received pRBCs and who did not receive pRBCs were included in the analyses. The primary outcomes were Length of Stay (LOS) and mortality. Multiple linear and logistic regression analyses were performed to define the association between pRBC transfusions and outcomes and to control for sepsis, mechanical ventilation, vasoactive medications, post-operative state and AKI. Data are shown as median (IQR). Results: Of the 393,384 patients who met the inclusion criteria, 43,569 (11%) had transfusions, with 97.2% of the patients receiving only 1 transfusion. The median (IQR) overall length of stay was 5.0 days (2, 10) and the overall mortality was 3.1%. The median (IQR) LOS for those who received pRBCs was 13 days (6, 29) compared to 4.0 days (2, 8) for those who did not. Mortality for those who received pRBCs was 10.1% compared to 2.2% for those who did not. The highest rate of pRBC transfusion was noted in the patients less than 1 month old (22%). The highest unadjusted mortality for patients who received pRBCs was also in the same age group- 7%. The associations between transfusion of pRBCs and outcomes are summarized in Table 1. Of the 393,384 patients, 19,686 (5.0 %) had sepsis; 143,085 (36.4%) were on mechanical ventilation; 141,123 (35.9%) were on vasoactive agents and 14,243 (3.6%) had AKI. After adjusting for sepsis, mechanical ventilation, use of vasoactive agents, post-op state and AKI, pRBC transfusions were associated with significantly increased LOS for all age groups. The highest increase in LOS was noted for the infants younger than 1 month of age - by 11.6 days (p<0.001). The mortality was also increased in patients who received PRBCs, when adjusted for other comorbidites, the highest risk was for patients in the age group of 15 to 18 years old: OR 2.50 (95% CI 2.14- 2.93). Conclusions: In this large, multicenter database study, we identified an association of increased mortality and LOS in critically ill children who received pRBC transfusions. More studies are needed to further investigate the impact of blood transfusions on clinical outcomes in the pediatric population. Disclosures No relevant conflicts of interest to declare.


Author(s):  
Tracy R Glass ◽  
Huldrych F Günthard ◽  
Alexandra Calmy ◽  
Enos Bernasconi ◽  
Alexandra U Scherrer ◽  
...  

Abstract Background Since the advent of universal test-and-treat , more people living with human immunodeficiency virus (PLHIV) initiating antiretroviral therapy (ART) are asymptomatic with a preserved immune system. We explored the impact of asymptomatic status on adherence and clinical outcomes. Methods PLHIV registered in the Swiss HIV Cohort Study (SHCS) between 2003 and 2018 were included. We defined asymptomatic as Centers for Disease Control and Prevention stage A within 30 days of starting ART, non-adherence as any self-reported missed doses and viral failure as two consecutive viral load&gt;50 copies/mL after &gt;24 weeks on ART. Using logistic regression models, we measured variables associated with asymptomatic status and adherence and Cox proportional hazard models to assess association between symptom status and viral failure. Results Of 7131 PLHIV, 76% started ART when asymptomatic and 1478 (22%) experienced viral failure after a median of 1.9 years (interquartile range, 1.1–4.2). In multivariable models, asymptomatic PLHIV were more likely to be younger, men who have sex with men, better educated, have unprotected sex, have a HIV-positive partner, have a lower viral load, and have started ART more recently. Asymptomatic status was not associated with nonadherence (odds ratio, 1.03 [95% confidence interval {CI}, .93–1.15]). Asymptomatic PLHIV were at a decreased risk of viral failure (adjusted hazard ratio, 0.87 [95% CI, .76–1.00]) and less likely to develop resistance (14% vs 27%, P &lt; .001) than symptomatic PLHIV. Conclusions Despite concerns regarding lack of readiness, our study found no evidence of adherence issues or worse clinical outcomes in asymptomatic PLHIV starting ART.


Author(s):  
Kwang Su Kim ◽  
Keisuke Ejima ◽  
Yusuke Ito ◽  
Shoya Iwanami ◽  
Hirofumi Ohashi ◽  
...  

The scientific community is focussed on developing antiviral therapies to mitigate the impacts of the ongoing novel coronavirus disease (COVID-19) outbreak. This will be facilitated by improved understanding of viral dynamics within infected hosts. Here, using a mathematical model in combination with published viral load data collected from the same specimen (throat / nasal swabs or nasopharyngeal / sputum / tracheal aspirate), we compare within-host dynamics for patients infected in the current outbreak with analogous dynamics for MERS-CoV and SARS-CoV infections. Our quantitative analyses revealed that SARS-CoV-2 infection dynamics are more severe than those for mild cases of MERS-CoV, but are similar to severe cases, and that the viral dynamics of SARS-CoV infection are similar to those of MERS-CoV in mild cases but not in severe case. Consequently, SARS-CoV-2 generates infection dynamics that are more severe than SARS-CoV. Furthermore, we used our viral dynamics model to predict the effectiveness of unlicensed drugs that have different methods of action. The effectiveness was measured by AUC of viral load. Our results indicated that therapies that block de novo infections or virus production are most likely to be effective if initiated before the peak viral load (which occurs around three days after symptom onset on average), but therapies that promote cytotoxicity are likely to have only limited effects. Our unique mathematical approach provides insights into the pathogenesis of SARS-CoV-2 in humans, which are useful for development of antiviral therapies.


2021 ◽  
Vol 8 ◽  
pp. 204993612110059
Author(s):  
Alexander H. Flannery ◽  
Katie L. Wallace ◽  
Christian N. Rhudy ◽  
Allison S. Olmsted ◽  
Rachel C. Minrath ◽  
...  

Background: While vancomycin loading doses may facilitate earlier pharmacokinetic–pharmacodynamic target attainment, the impact of loading doses on clinical outcomes remains understudied. Critically ill patients are at highest risk of morbidity and mortality from methicillin resistant Staphylococcus aureus (MRSA) infection and hypothesized to most likely benefit from a loading dose. We sought to determine the association between receipt of a vancomycin loading dose and clinical outcomes in a cohort of critically ill adults. Methods: Four hundred and forty-nine critically ill patients with MRSA cultures isolated from blood or respiratory specimens were eligible for the study. Cohorts were established by receipt of a loading dose (⩾20 mg/kg actual body weight) or not. The primary outcome was clinical failure, a composite outcome of death within 30 days of first MRSA culture, blood cultures positive ⩾7 days, white blood cell count up to 5 days from vancomycin initiation, temperature up to 5 days from vancomycin initiation, or substitution (or addition) of another MRSA agent. Results: There was no difference in the percentage of patients experiencing clinical failure between the loading dose and no loading dose groups (74.8% versus 72.8%; p = 0.698). Secondary outcomes were also similar between groups, including mortality and acute kidney injury, as was subgroup analysis based on site of infection. Exploratory analyses, including assessment of loading dose based on quartiles and a multivariable logistic regression model showed no differences. Conclusion: Use of vancomycin loading doses was not associated with improved clinical outcomes in critically ill patients with MRSA infection.


2020 ◽  
Vol 3 ◽  
pp. 21-21
Author(s):  
Luise V. Marino ◽  
Clémence Moullet ◽  
Corinne Jotterand Chaparro

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