scholarly journals COVID-19 infection with asymptomatic or mild disease severity in young patients: Clinical course and association between prevalence of pneumonia and viral load

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0250358
Author(s):  
Cherry Kim ◽  
Wooil Kim ◽  
Ji Hoon Jeon ◽  
Hyeri Seok ◽  
Sun Bean Kim ◽  
...  
Keyword(s):  
Viral Load ◽  
Retrospective Study ◽  
Disease Severity ◽  
Clinical Characteristics ◽  
Clinical Course ◽  
Young Patients ◽  
Viral Loads ◽  
Mild Disease ◽  
Recovery Times ◽  
The Mean

Few studies have focused on clinical courses or viral loads in young asymptomatic or mild patients with COVID-19 infection. We sought to better understand the clinical course and association between viral load and prevalence of pneumonia in young COVID-19 patients with asymptomatic or mild disease severity. In this retrospective study, 106 COVID-19 young patients with asymptomatic or mild disease severity were analyzed for clinical characteristics, clinical course, prevalence of radiologically proven pneumonia and viral load. The cut-off value of viral load for presence of pneumonia was also investigated. The mean age was 28.0±9.3 years. Eleven patients (10.4%) experienced viral remission within one week of diagnosis, but one (0.9%) transferred to the hospital due to aggravation of pneumonia. Patients with pneumonia had significantly higher viral load than those without, and the cut-off value of the Ct value for presence of pneumonia were 31.38. The patients with pneumonia had significantly slower recovery times than those without. Diarrhea was significantly more common in patients with pneumonia than patients without pneumonia. In conclusion, most young asymptomatic and mildly symptomatic patients showed stable clinical course. There were significant differences in viral load and recovery times between patients with and without pneumonia.

scholarly journals SARS-CoV-2 viral load is associated with increased disease severity and mortality

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Jesse Fajnzylber ◽  
◽  
James Regan ◽  
Kendyll Coxen ◽  
Heather Corry ◽  
...  
Keyword(s):  
Viral Load ◽  
Disease Severity ◽  
Diverse Range ◽  
Viral Loads ◽  
Mild Disease ◽  
Reactive Protein ◽  
Markers Of Inflammation ◽  
Increased Risk ◽  
Risk Of Disease ◽  
Absolute Lymphocyte Counts

Abstract The relationship between SARS-CoV-2 viral load and risk of disease progression remains largely undefined in coronavirus disease 2019 (COVID-19). Here, we quantify SARS-CoV-2 viral load from participants with a diverse range of COVID-19 disease severity, including those requiring hospitalization, outpatients with mild disease, and individuals with resolved infection. We detected SARS-CoV-2 plasma RNA in 27% of hospitalized participants, and 13% of outpatients diagnosed with COVID-19. Amongst the participants hospitalized with COVID-19, we report that a higher prevalence of detectable SARS-CoV-2 plasma viral load is associated with worse respiratory disease severity, lower absolute lymphocyte counts, and increased markers of inflammation, including C-reactive protein and IL-6. SARS-CoV-2 viral loads, especially plasma viremia, are associated with increased risk of mortality. Our data show that SARS-CoV-2 viral loads may aid in the risk stratification of patients with COVID-19, and therefore its role in disease pathogenesis should be further explored.

scholarly journals SARS-CoV-2 Viral Load is Associated with Increased Disease Severity and Mortality

2020 ◽  
Author(s):  
Jesse Fajnzylber ◽  
James Regan ◽  
Kendyll Coxen ◽  
Heather Corry ◽  
Colline Wong ◽  
...  
Keyword(s):  
Viral Load ◽  
Disease Severity ◽  
Diverse Range ◽  
Viral Loads ◽  
Mild Disease ◽  
Reactive Protein ◽  
Markers Of Inflammation ◽  
Increased Risk ◽  
Risk Of Disease ◽  
Absolute Lymphocyte Counts

Abstract The relationship between SARS-CoV-2 viral load and risk of disease progression remains largely undefined in coronavirus disease 2019 (COVID-19). We quantified SARS-CoV-2 viral load from participants with a diverse range of COVID-19 severity, including those requiring hospitalization, outpatients with mild disease, and individuals with resolved infection. SARS-CoV-2 plasma RNA was detected in 27% of hospitalized participants and 13% of outpatients diagnosed with COVID-19. Amongst the participants hospitalized with COVID-19, higher prevalence of detectable SARS-CoV-2 plasma viral load was associated with worse respiratory disease severity, lower absolute lymphocyte counts, and increased markers of inflammation, including C-reactive protein and IL-6. SARS-CoV-2 viral loads, especially plasma viremia, were associated with increased risk of mortality. SARS-CoV-2 viral load may aid in the risk stratification of patients with COVID-19 and its role in disease pathogenesis should be further explored.

scholarly journals SARS-CoV-2 Viral Load is Associated with Increased Disease Severity and Mortality

2020 ◽  
Author(s):  
Jesse M Fajnzylber ◽  
James Regan ◽  
Kendyll Coxen ◽  
Heather Corry ◽  
Colline Wong ◽  
...  
Keyword(s):  
Viral Load ◽  
Disease Severity ◽  
Diverse Range ◽  
Viral Loads ◽  
Mild Disease ◽  
Reactive Protein ◽  
Markers Of Inflammation ◽  
Increased Risk ◽  
Risk Of Disease ◽  
Absolute Lymphocyte Counts

The relationship between SARS-CoV-2 viral load and risk of disease progression remains largely undefined in coronavirus disease 2019 (COVID-19). We quantified SARS-CoV-2 viral load from participants with a diverse range of COVID-19 severity, including those requiring hospitalization, outpatients with mild disease, and individuals with resolved infection. SARS-CoV-2 plasma RNA was detected in 27% of hospitalized participants and 13% of outpatients diagnosed with COVID-19. Amongst the participants hospitalized with COVID-19, higher prevalence of detectable SARS-CoV-2 plasma viral load was associated with worse respiratory disease severity, lower absolute lymphocyte counts, and increased markers of inflammation, including C-reactive protein and IL-6. SARS-CoV-2 viral loads, especially plasma viremia, were associated with increased risk of mortality. SARS-CoV-2 viral load may aid in the risk stratification of patients with COVID-19 and its role in disease pathogenesis should be further explored.

scholarly journals SARS-CoV-2 Persistence in Immunocompromised Children

2021 ◽  
Author(s):  
Susan Dolan ◽  
Jean Mulcahy Levy ◽  
Angla Moss ◽  
Kelly Pearce ◽  
Samuel Dominguez ◽  
...  
Keyword(s):  
Viral Load ◽  
Median Time ◽  
Immunosuppressive Treatment ◽  
Viral Persistence ◽  
High Viral Load ◽  
Viral Loads ◽  
Mild Disease ◽  
Kaplan Meier ◽  
Diagnostic Panel ◽  
Event Times

Introduction/Objectives: We evaluated the length of time immunocompromised children (ICC) remain positive for SARS-CoV-2, identified factors associated with viral persistence and determined cycle threshold (CT) values of children with viral persistence as a surrogate of viral load. Methods: We conducted a retrospective cohort study of ICC at a pediatric hospital from March 2020-2021. Immunocompromised status was defined as primary, secondary or acquired due to medical comorbidities/immunosuppressive treatment. The primary outcome was time to first-of-two consecutive negative SARS-CoV-2 Polymerase chain reaction (PCR) tests at least 24 hours apart. Testing of sequential clinical specimens from the same subject was conducted using the Centers for Disease Control (CDC) 2019-nCoV Real-Time RT-PCR Diagnostic Panel assay. Descriptive statistics, Kaplan-Meier curve median event times and log-rank-sum tests were used to compare outcomes between groups. Results: Ninety-one children met inclusion criteria. Median age was 15.5 years (IQR 8-18 yrs), 64% were male, 58% were white, and 43% were Hispanic/Latinx. Most (67%) were tested in outpatient settings and 58% were asymptomatic. The median time to two negative tests was 42 days (IQR 25.0,55.0), with no differences in median time by illness presentation or level of immunosuppression. Seven children had >1 sample available for repeat testing, and 5/7 (71%) children had initial CT values of <30, (moderate to high viral load); 4 children had CT values of <30 3-4 weeks later, suggesting persistent moderate to high viral loads. Conclusions: Most ICC with SARS-CoV-2 infection had mild disease, with prolonged viral persistence >6 weeks and moderate to high viral load.

scholarly journals The Characterization of Disease Severity Associated IgG Subclasses Response in COVID-19 Patients

2021 ◽  
Vol 12 ◽  
Author(s):  
Huanle Luo ◽  
Tingting Jia ◽  
Jiamin Chen ◽  
Shike Zeng ◽  
Zengzhao Qiu ◽  
...  
Keyword(s):  
Viral Load ◽  
Disease Severity ◽  
Young Patients ◽  
Neutralizing Antibody ◽  
Igg Subclasses ◽  
Nasopharyngeal Swab ◽  
Obvious Effect ◽  
Old Patients ◽  
Biological Sex ◽  
Specific Igg

Increasing evidence suggests that dysregulated immune responses are associated with the clinical outcome of coronavirus disease 2019 (COVID-19). Nucleocapsid protein (NP)-, spike (S)-, receptor binding domain (RBD)- specific immunoglobulin (Ig) isotypes, IgG subclasses and neutralizing antibody (NAb) were analyzed in 123 serum from 63 hospitalized patients with severe, moderate, mild or asymptomatic COVID-19. Mild to modest correlations were found between disease severity and antigen specific IgG subclasses in serum, of which IgG1 and IgG3 were negatively associated with viral load in nasopharyngeal swab. Multiple cytokines were significantly related with antigen-specific Ig isotypes and IgG subclasses, and IL-1β was positively correlated with most antibodies. Furthermore, the old patients (≥ 60 years old) had higher levels of chemokines, increased NAb activities and SARS-CoV-2 specific IgG1, and IgG3 responses and compromised T cell responses compared to the young patients (≤ 18 years old), which are related with more severe cases. Higher IgG1 and IgG3 were found in COVID-19 patients with comorbidities while biological sex had no effect on IgG subclasses. Overall, we have identified diseases severity was related to higher antibodies, of which IgG subclasses had weakly negative correlation with viral load, and cytokines were significantly associated with antibody response. Further, advancing age and comorbidities had obvious effect on IgG1 and IgG3.

scholarly journals Saliva viral load is a dynamic unifying correlate of COVID-19 severity and mortality

2021 ◽  
Author(s):  
Julio Silva ◽  
Carolina Lucas ◽  
Maria Sundaram ◽  
Benjamin Israelow ◽  
Patrick Wong ◽  
...  
Keyword(s):  
Viral Load ◽  
Disease Severity ◽  
T Cell Subsets ◽  
Temporal Association ◽  
Strongly Correlated ◽  
Immunological Parameters ◽  
Viral Loads ◽  
Patient Demographics ◽  
Over Time

While several clinical and immunological parameters correlate with disease severity and mortality in SARS-CoV-2 infection, work remains in identifying unifying correlates of coronavirus disease 2019 (COVID-19) that can be used to guide clinical practice. Here, we examine saliva and nasopharyngeal (NP) viral load over time and correlate them with patient demographics, and cellular and immune profiling. We found that saliva viral load was significantly higher in those with COVID-19 risk factors; that it correlated with increasing levels of disease severity and showed a superior ability over nasopharyngeal viral load as a predictor of mortality over time (AUC=0.90). A comprehensive analysis of immune factors and cell subsets revealed strong predictors of high and low saliva viral load, which were associated with increased disease severity or better overall outcomes, respectively. Saliva viral load was positively associated with many known COVID-19 inflammatory markers such as IL-6, IL-18, IL-10, and CXCL10, as well as type 1 immune response cytokines. Higher saliva viral loads strongly correlated with the progressive depletion of platelets, lymphocytes, and effector T cell subsets including circulating follicular CD4 T cells (cTfh). Anti-spike (S) and anti-receptor binding domain (RBD) IgG levels were negatively correlated with saliva viral load showing a strong temporal association that could help distinguish severity and mortality in COVID-19. Finally, patients with fatal COVID-19 exhibited higher viral loads, which correlated with the depletion of cTfh cells, and lower production of anti-RBD and anti-S IgG levels. Together these results demonstrated that viral load – as measured by saliva but not nasopharyngeal — is a dynamic unifying correlate of disease presentation, severity, and mortality over time.

“EPIDEMIOLOGICAL AND CLINICAL CHARACTERIZATION OF COVID19 PATIENTS: A RETROSPECTIVE OBSERVATIONAL STUDY OF 245 CASES IN A GOVERNMENT TEACHING INSTITUTE OF NORTH INDIA.”

2021 ◽  
pp. 50-53
Author(s):  
Divya Jain ◽  
Umesh Shukla ◽  
Jyotsna Madan ◽  
Bhanu K Bhakri ◽  
Devendra Kumar Gupta ◽  
...  
Keyword(s):  
Clinical Characteristics ◽  
North India ◽  
Contact Tracing ◽  
Mild Disease ◽  
Source Of Infection ◽  
Asymptomatic Patients ◽  
Care Workers ◽  
Study Population ◽  
The Mean ◽  
Novel Coronavirus

Background and objectives: Worldwide literature on presentation of patients infected with novel coronavirus shows huge variability in terms of severity and outcome depending on the demographic characteristics of the affected population. We aim to present epidemiological and clinical characteristics of COVID-19 patients admitted at our facility. Methods: Retrospective analysis of epidemiological, and clinical characteristics of patients admitted at a dedicated COVID hospital in North India. Results: Records of 245 patients were analyzed. The mean (SD) age was 32 (17.87) years ranging from 1 day to 81 years. Children <18 years of age constituted around 18% of the study population of which only about a fourth (23%) were symptomatic. About 52.4% of patients were males. Almost 40% cases were detected through contact tracing of known infected patients and in about 56% cases the source of infection was indeterminate. About 67% were asymptomatic and most of the symptomatic patients had mild disease. Among the symptomatic patients cough (19.9%) and fever (17.1%) were most common symptoms followed by throat irritation. Comorbidities were present in 32 (13.06%) patients, of which hypertension in 6.12% was the most common. There were 22 (8.97%) health care workers (HCW) among the patients. Majority of the affected HCW were working in areas with relatively low infection risk. Six (2.44%) patients required oxygen supplementation. The mean duration of stay in hospital was 9.6 ±.57 days. Interpretations & Conclusions: Our observations indicate a relatively younger age of affected population and high proportion of asymptomatic patients. Children are usually asymptomatic with relatively better prognosis.

scholarly journals A41 Deep sequencing of respiratory syncytial virus links viral diversity to disease severity

2019 ◽  
Vol 5 (Supplement_1) ◽  
Author(s):  
Inne Nauwelaers ◽  
Tiina Talts ◽  
Monica Galiano ◽  
Peter Openshaw
Keyword(s):  
Viral Load ◽  
Respiratory Syncytial Virus ◽  
Disease Severity ◽  
Illumina Sequencing ◽  
Likelihood Method ◽  
Evolutionary Analysis ◽  
Viral Loads ◽  
Ct Value ◽  
A Genome ◽  
Syncytial Virus

Abstract Respiratory syncytial virus (RSV) is a common virus that can cause bronchiolitis in infants and pneumonia in immunocompromised and elderly people. RSV belongs to the Pneumoviridae family and consists of a genome of 15 kb. Its genome contains ten genes that code for eleven proteins, with M2 coding for two different proteins in overlapping open reading frames. It is unclear why some infected children have severe disease and others have mild or asymptomatic disease. In this project, methods for complete genome sequencing of RSV via Sanger and Illumina MiSeq platforms were optimized. One hundred and twenty-four community samples (59 RSV A and 65 RSV B) from 2014 to 2018 were collected (in collaboration with the Royal College of General Practitioners) and sequenced. Samples were selected based on viral load (e.g. Ct values had to be < 30). The genotype of each sample was determined by constructing phylogenetic trees with reference sequences from all genotypes. Trees were reconstructed using the maximum likelihood method. Furthermore, Illumina sequencing was used to deep sequence seven community samples and four hospital samples that were spatiotemporally matched (obtained via Imperial College NHS Trust hospitals). Variants were studied to investigate if certain variants influence disease severity (e.g. cause mild (community samples) or severe infection (hospital samples)). Analysis so far showed that ON1 (with a seventy-two nucleotide duplication in attachment protein G) is the most common genotype in both community and hospitalized samples (90% and 75% of samples, respectively), with GA2 (without duplication) as the next most common genotype for RSV A subtypes (7% and 25%). Three per cent of community samples were of the GA5 genotype. Samples from the RSV B subgroup all belong to the BA genotypes with a 60-nucleotide duplication in G. Samples that were selected for Illumina sequencing had a Ct value between 19.0 and 29.1, while hospital samples had a Ct value of 18.3 to 29.1. Viral load, therefore, did not explain disease severity in these selected samples. The Shannon entropy from Illumina sequenced samples averaged at 22.78 in community samples (ranges from 15 to 28) and 38.78 in hospitalized samples (ranges from 31 to 57). This indicated that diversity of the virus pool might influence disease severity; however, more samples need to be analyzed. There are no specific variants that could explain disease severity. Diversity of the virus pool could explain the link between higher viral loads and disease severity, which is sometimes found but cannot always be confirmed. Higher viral loads can harbor more diverse viral particles compared to lower viral loads. Future work will focus on more in-depth variation and diversity analysis and on evolutionary analysis of both community and hospital samples. We will also investigate intra-host evolution of RSV in acute infections using consecutive samples and its possible implications on the host response.

scholarly journals Viral load dynamics and disease severity in patients infected with SARS-CoV-2 in Zhejiang province, China, January-March 2020: retrospective cohort study

BMJ ◽  
2020 ◽  
pp. m1443 ◽  
Author(s):  
Shufa Zheng ◽  
Jian Fan ◽  
Fei Yu ◽  
Baihuan Feng ◽  
Bin Lou ◽  
...  
Keyword(s):  
Viral Load ◽  
Retrospective Cohort ◽  
Severe Disease ◽  
Zhejiang Province ◽  
Serum Samples ◽  
Viral Loads ◽  
Mild Disease ◽  
Stool Samples ◽  
Serum And Urine ◽  
Serum And Urine Samples

AbstractObjectiveTo evaluate viral loads at different stages of disease progression in patients infected with the 2019 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the first four months of the epidemic in Zhejiang province, China.DesignRetrospective cohort study.SettingA designated hospital for patients with covid-19 in Zhejiang province, China.Participants96 consecutively admitted patients with laboratory confirmed SARS-CoV-2 infection: 22 with mild disease and 74 with severe disease. Data were collected from 19 January 2020 to 20 March 2020.Main outcome measuresRibonucleic acid (RNA) viral load measured in respiratory, stool, serum, and urine samples. Cycle threshold values, a measure of nucleic acid concentration, were plotted onto the standard curve constructed on the basis of the standard product. Epidemiological, clinical, and laboratory characteristics and treatment and outcomes data were obtained through data collection forms from electronic medical records, and the relation between clinical data and disease severity was analysed.Results3497 respiratory, stool, serum, and urine samples were collected from patients after admission and evaluated for SARS-CoV-2 RNA viral load. Infection was confirmed in all patients by testing sputum and saliva samples. RNA was detected in the stool of 55 (59%) patients and in the serum of 39 (41%) patients. The urine sample from one patient was positive for SARS-CoV-2. The median duration of virus in stool (22 days, interquartile range 17-31 days) was significantly longer than in respiratory (18 days, 13-29 days; P=0.02) and serum samples (16 days, 11-21 days; P<0.001). The median duration of virus in the respiratory samples of patients with severe disease (21 days, 14-30 days) was significantly longer than in patients with mild disease (14 days, 10-21 days; P=0.04). In the mild group, the viral loads peaked in respiratory samples in the second week from disease onset, whereas viral load continued to be high during the third week in the severe group. Virus duration was longer in patients older than 60 years and in male patients.ConclusionThe duration of SARS-CoV-2 is significantly longer in stool samples than in respiratory and serum samples, highlighting the need to strengthen the management of stool samples in the prevention and control of the epidemic, and the virus persists longer with higher load and peaks later in the respiratory tissue of patients with severe disease.

Off label targeted therapy use in adolescents and young adults with sarcoma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e21504-e21504
Author(s):  
Lisa M. Kopp ◽  
Kathylynn Saboda ◽  
Bhuvana Setty ◽  
Mary Frances Wedekind ◽  
Daniel Weiser ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Targeted Therapy ◽  
Clinical Characteristics ◽  
Kinase Inhibitors ◽  
Young Patients ◽  
Complete Response ◽  
Off Label ◽  
Chi Squared ◽  
The Mean ◽  
Early Phase Clinical Trials

e21504 Background: Outcomes for patients with metastatic or recurrent sarcomas remains dismal with < 20% overall survival. Due to the rarity of sarcomas, the development, testing, and approval of new therapies takes years. Most early phase clinical trials are restricted to adults leaving young patients with limited options. Little is known about the prevalence and clinical characteristics of patients receiving off-label targeted therapy (OLTT). In this multi-institutional retrospective review we evaluated OLTT use in this population. Methods: Patients with recurrent sarcoma diagnosed between the years of 2008 – 2016 were identified at six institutions. Charts were reviewed for OLTT use and additional clinical characteristics. ANOVA [Analysis of Variance] and Kruskal Wallis Rank sum tests were used for normally and non-normally distributed continuous data. Categorical data was analyzed using chi-squared tests or fisher exact tests. Results: The prevalence of OLTT use was 29% for the patients included in our analysis. Of the 99 cases, the mean age for OLTT was 18 years, ranging 3 – 34 years. Nearly half had recurrent tumor in multiple sites at the time of OLTT use, and 64% did not undergo resection prior to OLTT. Lack of clinical trial availability was the most common reason for OLTT use (31% of cases). The most common OLTT drug class used were tyrosine kinase inhibitors. Progression in 81% of cases was the primary reason for stopping OLTT and toxicity limited use in 12% of cases. One case had a complete response, 5 cases had a partial response and 4 cases had stable disease per RECIST. Conclusions: OLTT use is exceedingly prevalent in patients with recurrent sarcoma. Clinical trials for children and adolescents with recurrent sarcoma will identify optimal agents to improve outcomes in this understudied population.

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