Viral load dynamics in adult patients with A(H1N1)pdm09 influenza

2013 ◽  
Vol 142 (4) ◽  
pp. 753-758 ◽  
Author(s):  
J. Y. NOH ◽  
J. Y. SONG ◽  
S. Y. HWANG ◽  
W. S. CHOI ◽  
J. Y. HEO ◽  
...  
Keyword(s):  
Viral Load ◽  
Symptom Onset ◽  
Influenza A ◽  
Onset Time ◽  
Clinical Findings ◽  
Viral Clearance ◽  
Virus Infections ◽  
Hospital Visit ◽  
Viral Shedding ◽  
Respiratory Specimens

SUMMARYThe dynamics of influenza A viral load in respiratory samples collected from adult A(H1N1)pdm09 influenza patients were investigated. Three respiratory specimens were obtained every 2–4 days and clinical findings were recorded at the time each specimen was collected. A total of 105 serial specimens were collected from 35 patients. Viral clearance was more rapid in patients aged 15–29 years than patients aged 30–49 years (P < 0·01) or ⩾50 years (P < 0·01). Hospitalized patients showed slow viral clearance compared to outpatients (P < 0·01). Resolution of cough and headache was correlated with viral load reduction in respiratory specimens. Viral shedding was found in 17 patients (48·6%) 5 days after symptom onset. Time to hospital visit after symptom onset was significantly correlated with prolonged viral shedding (odds ratio 9·0, 95% confidence interval 1·56–51·87, P = 0·01). These findings will contribute to infection control aspects with respect to managing patients with influenza virus infections.

scholarly journals Clinical and Virologic Characteristics and Outcomes of Coronavirus Disease 2019 at a Cancer Center

2021 ◽  
Author(s):  
Leah H Yoke ◽  
Juhye M Lee ◽  
Elizabeth M Krantz ◽  
Jessica Morris ◽  
Sara Marquis ◽  
...  
Keyword(s):  
Viral Load ◽  
Cancer Patients ◽  
Symptom Onset ◽  
Treatment Strategies ◽  
Viral Clearance ◽  
Cancer Center ◽  
High Morbidity ◽  
Antimicrobial Use ◽  
Viral Shedding ◽  
Increased Risk

Abstract Background High morbidity and mortality have been observed in cancer patients with COVID-19 infection; however, there are limited data on antimicrobial use, co-infections, and viral shedding. Methods We conducted a retrospective cohort study of adult patients at the Seattle Cancer Care Alliance diagnosed with COVID-19 infection between 2/28/2020 and 6/15/2020 to characterize antimicrobial use, coinfections, viral shedding and outcomes within 30 days after diagnosis. Cycle threshold values were used as a proxy for viral load. We determined viral clearance, defined as two consecutive negative PCR results using SARS-CoV-2 RT-PCR results through 7/30/2020. Results Seventy-one patients were included with a median age of 61 years; 59% had a solid tumor. Only 3 patients had documented respiratory bacterial co-infection. Empiric antibiotics for pneumonia were prescribed more frequently early in the study period (2/29/20-3/28/20;12/34) compared to the later period (3/29/20-6/15/20; 2/36) (P = .002). The median number of days from symptom onset to viral clearance was 37 days with viral load rapidly declining in the first 7-10 days after symptom onset. Within 30 days of diagnosis, 29 (41%) patients were hospitalized and 12 (17%) died. Each additional comorbidity was associated with 45% lower odds of days alive and out of hospital in the month following diagnosis in adjusted models. Conclusions Patients at a cancer center, particularly those with multiple comorbidities, are at increased risk of poor outcomes from COVID-19 disease. Prolonged viral shedding is frequently observed among cancer patients and its implications on transmission and treatment strategies warrant further study.

scholarly journals Infectivity of healthcare workers diagnosed with coronavirus disease 2019 (COVID-19) approximately 2 weeks after onset of symptoms: A cross-sectional study

2021 ◽  
pp. 1-3
Author(s):  
Yves Longtin ◽  
Hugues Charest ◽  
Caroline Quach ◽  
Patrice Savard ◽  
Mariana Baz ◽  
...  
Keyword(s):  
Symptom Onset ◽  
Healthcare Workers ◽  
Positive Culture ◽  
Cross Sectional Study ◽  
Sectional Study ◽  
Cross Sectional ◽  
Viral Shedding ◽  
Viral Culture ◽  
Respiratory Coronavirus ◽  
Respiratory Specimens

Abstract We performed viral culture of respiratory specimens in 118 severe acute respiratory coronavirus virus 2 (SARS-CoV-2)–infected healthcare workers (HCWs), ∼2 weeks after symptom onset. Only 1 HCW (0.8%) had a positive culture. No factors for prolonged viral shedding were identified. Infectivity is resolved in nearly all HCWs ∼2 weeks after symptom onset.

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

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.

scholarly journals Viral Kinetics and Resistance Development in Children Treated with Neuraminidase Inhibitors: The Influenza Resistance Information Study (IRIS)

2019 ◽  
Vol 71 (5) ◽  
pp. 1186-1194 ◽  
Author(s):  
Rueshandra Roosenhoff ◽  
Vaughan Reed ◽  
Andy Kenwright ◽  
Martin Schutten ◽  
Charles A Boucher ◽  
...  
Keyword(s):  
Viral Load ◽  
Influenza A ◽  
Antiviral Treatment ◽  
Vaccination Status ◽  
Viral Clearance ◽  
Viral Rna ◽  
Baseline Viral Load ◽  
Influenza B ◽  
Resistance Mutations ◽  
Viral Burden

Abstract Background We studied the effect of age, baseline viral load, vaccination status, antiviral therapy, and emergence of drug resistance on viral shedding in children infected with influenza A or B virus. Methods Samples from children (aged ≤13 years) enrolled during the 7 years of the prospective Influenza Resistance Information Study were analyzed using polymerase chain reaction to determine the influenza virus (sub-)type, viral load, and resistance mutations. Disease severity was assessed; clinical symptoms were recorded. The association of age with viral load and viral clearance was examined by determining the area under the curve for viral RNA shedding using logistic regression and Kaplan-Meier analyses. Results A total of 2131 children infected with influenza (683, A/H1N1pdm09; 825, A/H3N2; 623, influenza B) were investigated. Age did not affect the mean baseline viral load. Children aged 1−5 years had prolonged viral RNA shedding (±1–2 days) compared with older children and up to 1.2-fold higher total viral burden. Besides, in older age (odds ratio [OR], 1.08; confidence interval [CI], 1.05–1.12), prior vaccination status (OR, 1.72; CI, 1.22–2.43) and antiviral treatment (OR, 1.74; CI, 1.43–2.12) increased the rate of viral clearance. Resistance mutations were detected in 49 children infected with influenza A virus (34, A/H1N1pdm09; 15, A/H3N2) treated with oseltamivir, most of whom were aged &lt;5 years (n = 39). Conclusions Children aged 1−5 years had a higher total viral burden with prolonged virus shedding and had an increased risk of acquiring resistance mutations following antiviral treatment. Clinical Trials Registration NCT00884117.

scholarly journals Factors Associated With Viral Load Kinetics of Middle East Respiratory Syndrome Coronavirus During the 2015 Outbreak in South Korea

2020 ◽  
Author(s):  
Jeong-Sun Yang ◽  
Min-Gyu Yoo ◽  
Hye-Ja Lee ◽  
Han Byul Jang ◽  
Hee-Dong Jung ◽  
...  
Keyword(s):  
Viral Load ◽  
Middle East ◽  
Symptom Onset ◽  
Healthcare Workers ◽  
Middle East Respiratory Syndrome ◽  
Viral Loads ◽  
Hospitalization Period ◽  
Using Data ◽  
Kinetics Of ◽  
Respiratory Specimens

Abstract We conducted a retrospective study of Middle East respiratory syndrome coronavirus (MERS-CoV) viral load kinetics using data from patients hospitalized with MERS-CoV infection between 19 May and 20 August 2015. Viral load trajectories were considered over the hospitalization period using 1714 viral load results measured in serial respiratory specimens of 185 patients. The viral load levels were significantly higher among nonsurvivors than among survivors (P = .003). Healthcare workers (P = .001) and nonspreaders (P &lt; .001) had significantly lower viral loads. Viral RNA was present on the day of symptom onset and peaked 4–10 days after symptom onset.

scholarly journals Temporal dynamics in viral shedding and transmissibility of COVID-19

2020 ◽  
Author(s):  
Xi He ◽  
Eric HY Lau ◽  
Peng Wu ◽  
Xilong Deng ◽  
Jian Wang ◽  
...  
Keyword(s):  
Viral Load ◽  
Disease Control ◽  
Symptom Onset ◽  
Temporal Dynamics ◽  
Temporal Patterns ◽  
Control Measures ◽  
Separate Sample ◽  
Viral Shedding ◽  
Index Disease

ABSTRACTWe report temporal patterns of viral shedding in 94 laboratory-confirmed COVID-19 patients and modelled COVID-19 infectiousness profile from a separate sample of 77 infector-infectee transmission pairs. We observed the highest viral load in throat swabs at the time of symptom onset, and inferred that infectiousness peaked on or before symptom onset. We estimated that 44% of transmission could occur before first symptoms of the index. Disease control measures should be adjusted to account for probable substantial pre-symptomatic transmission.

scholarly journals Viral Kinetics and Antibody Responses in Patients with COVID-19

2020 ◽  
Author(s):  
Wenting Tan ◽  
Yanqiu Lu ◽  
Juan Zhang ◽  
Jing Wang ◽  
Yunjie Dan ◽  
...  
Keyword(s):  
Antibody Response ◽  
Incubation Period ◽  
Disease Severity ◽  
Prospective Cohort ◽  
Clinical Manifestations ◽  
Viral Clearance ◽  
Prolonged Incubation ◽  
Clinical Specimens ◽  
Viral Shedding ◽  
Respiratory Specimens

AbstractBackgroundA pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been spreading over the world. However, the viral dynamics, host serologic responses, and their associations with clinical manifestations, have not been well described in prospective cohort.MethodsWe conducted a prospective cohort and enrolled 67 COVID-19 patients admitting between Jan 26 and Feb 5, 2020. Clinical specimens including nasopharyngeal swab, sputum, blood, urine and stool were tested periodically according to standardized case report form with final follow-up on February 27. The routes and duration of viral shedding, antibody response, and their associations with disease severity and clinical manifestations were systematically evaluated. Coronaviral particles in clinical specimens were observed by transmission electron microscopy (TEM).ResultsThe median duration of SARS-CoV-2 RNA shedding were 12 (3-38), 19 (5-37), and 18 (7-26) days in nasopharyngeal swabs, sputum and stools, respectively. Only 13 urines (5.6%) and 12 plasmas (5.7%) were viral positive. Prolonged viral shedding was observed in severe patients than that of non-severe patients. Cough but not fever, aligned with viral shedding in clinical respiratory specimens, meanwhile the positive stool-RNA appeared to align with the proportion who concurrently had cough and sputum production, but not diarrhea. Typical coronaviral particles could be found directly in sputum by TEM. The anti-nucleocapsid-protein IgM started on day 7 and positive rate peaked on day 28, while that of IgG was on day 10 and day 49 after illness onset. IgM and IgG appear earlier, and their titers are significantly higher in severe patients than non-severe patients (p<0.05). The weak responders for IgG had a significantly higher viral clearance rate than that of strong responders (p= 0.011).ConclusionsNasopharyngeal, sputum and stools rather than blood and urine, were the major shedding routes for SARS-CoV-2, and meanwhile sputum had a prolonged viral shedding. Symptom cough seems to be aligned with viral shedding in clinical respiratory and fecal specimens. Stronger antibody response was associated with delayed viral clearance and disease severity.Summary boxesWhat is already known on this topicAs a newly appearing infectious disease, early efforts have focused on virus identification, describing the epidemiologic characteristics, clinical course, prognostics for critically illed cases and mortality. Among COVID-19 cases reported in mainland China (72 314 cases, updated through February 11, 2020), 81% are mild, 14% are severe, and 5% are critical. The estimated overall case fatality rate (CFR) is 2.3%.Some case series reported had shown that SARS-CoV-2 could shed in upper/lower respiratory specimens, stools, blood and urines of patients. However, important knowledge gaps remain, particularly regarding full kinetics of viral shedding and host serologic responses in association with clinical manifestations and host factors.What this study addsThe incubation period has no change after spreading out of Wuhan, and has no sex or age differences, however, children had prolonged incubation period. Due to early recognition and intervention, COVID-19 illness of Chongqing cohort is milder than that of Wuhan patients reported.This prospective cohort study on SARS-CoV-2 infection shows clearly that the viral and serological kinetics were related in duration of infection, disease severity, and clinical manifestations of COVID-19. Our data demonstrate that nasopharyngeal, sputum and stools are major shedding routes for SARS-CoV-2, and stronger NP antibody response is associated with delayed viral clearance and disease severity.

scholarly journals SARS-CoV-2, SARS-CoV-1 and MERS-CoV viral load dynamics, duration of viral shedding and infectiousness: a living systematic review and meta-analysis

2020 ◽  
Author(s):  
Muge Cevik ◽  
Matthew Tate ◽  
Oliver Lloyd ◽  
Alberto Enrico Maraolo ◽  
Jenna Schafers ◽  
...  
Keyword(s):  
Viral Load ◽  
Respiratory Tract ◽  
Symptom Onset ◽  
Grey Literature ◽  
Viral Rna ◽  
Viral Dynamics ◽  
Upper Respiratory Tract ◽  
Live Virus ◽  
Viral Shedding ◽  
Upper Respiratory

Background Viral load kinetics and the duration of viral shedding are important determinants for disease transmission. We aim i) to characterise viral load dynamics, duration of viral RNA, and viable virus shedding of SARS-CoV-2 in various body fluids and ii) to compare SARS-CoV-2 viral dynamics with SARS-CoV-1 and MERS-CoV. Methods: Medline, EMBASE, Europe PMC, preprint servers and grey literature were searched to retrieve all articles reporting viral dynamics and duration of SARS-CoV-2, SARS-CoV-1 and MERS-CoV shedding. We excluded case reports and case series with < 5 patients, or studies that did not report shedding duration from symptom onset. PROSPERO registration: CRD42020181914. Findings: Seventy-nine studies on SARS-CoV-2, 8 on SARS-CoV-1, and 11 on MERS-CoV were included. Mean SARS-CoV-2 RNA shedding duration in upper respiratory tract, lower respiratory tract, stool and serum were 17.0, 14.6, 17.2 and 16.6 days, respectively. Maximum duration of SARS-CoV-2 RNA shedding reported in URT, LRT, stool and serum was 83, 59, 35 and 60 days, respectively. Pooled mean duration of SARS-CoV-2 RNA shedding was positively associated with age (p=0.002), but not gender (p = 0.277). No study to date has detected live virus beyond day nine of illness despite persistently high viral loads. SARS-CoV-2 viral load in the upper respiratory tract appears to peak in the first week of illness, while SARS-CoV-1 and MERS-CoV peak later. Conclusion: Although SARS-CoV-2 RNA shedding in respiratory and stool can be prolonged, duration of viable virus is relatively short-lived. Thus, detection of viral RNA cannot be used to infer infectiousness. High SARS-CoV-2 titres are detectable in the first week of illness with an early peak observed at symptom onset to day 5 of illness. This review underscores the importance of early case finding and isolation, as well as public education on the spectrum of illness. However, given potential delays in the isolation of patients, effective containment of SARS-CoV-2 may be challenging even with an early detection and isolation strategy. Funding: No funding was received.

scholarly journals Peginterferon-lambda for the treatment of COVID-19 in outpatients

2020 ◽  
Author(s):  
Jordan J. Feld ◽  
Christopher Kandel ◽  
Mia J. Biondi ◽  
Robert A. Kozak ◽  
Muhammad Atif Zahoor ◽  
...  
Keyword(s):  
Public Health ◽  
Viral Load ◽  
Adverse Events ◽  
Outpatient Setting ◽  
Viral Clearance ◽  
Clinical Deterioration ◽  
Baseline Viral Load ◽  
High Baseline ◽  
Viral Loads ◽  
Viral Shedding

SummaryBackgroundThere are currently no effective treatments for outpatients with coronavirus disease 2019 (COVID-19). Interferon-lambda-1 is a Type III interferon involved in the innate antiviral response with activity against respiratory pathogens.MethodsIn this double-blind, placebo-controlled trial, outpatients with laboratory-confirmed COVID-19 were randomized to a single subcutaneous injection of peginterferon-lambda 180μg or placebo within 7 days of symptom onset or first positive swab if asymptomatic. The primary endpoint was proportion negative for SARS-CoV-2 RNA on Day 7 post-injection.FindingsThere were 30 patients per arm, with median baseline SARS-CoV-2 viral load of 6.71 (IQR 1.3-8.0) log copies/mL. The decline in SARS-CoV-2 RNA was greater in those treated with peginterferon-lambda than placebo (p=0.04). On Day 7, 24 participants (80%) in the peginterferon-lambda group had an undetectable viral load compared to 19 (63%) in the placebo arm (p=0.15). After controlling for baseline viral load, peginterferon lambda treatment resulted in a 4.12-fold (95CI 1.15-16.7, p=0.029) higher likelihood of viral clearance by Day 7. Of those with baseline viral load above 10E6 copies/mL, 15/19 (79%) in the peginterferon-lambda group were undetectable on Day 7 compared to 6/16 (38%) in the placebo group (p=0.012). Adverse events were similar between groups with only mild reversible transaminase elevations more frequently observed in the peginterferon-lambda group.InterpretationPeginterferon-lambda accelerated viral decline in outpatients with COVID-19 resulting in a greater proportion with viral clearance by Day 7, particularly in those with high baseline viral load. Peginterferon-lambda may have potential to prevent clinical deterioration and shorten duration of viral shedding.(NCT04354259)FundingThis study was supported by the Toronto COVID-19 Action Initiative, University of Toronto and the Ontario First COVID-19 Rapid Research Fund. Medication was supplied by Eiger BioPharma.Research in ContextTreatment trials for COVID-19 have largely focused on hospitalized patients and no treatments are approved for people with mild to moderate disease in the outpatient setting. A number of studies in ambulatory populations have been registered but no controlled studies in the outpatient setting have been reported to date (Pubmed Search October 20, 2020, COVID-19 treatment; controlled trials). Uncontrolled case series of hydroxychloroquine with or without azithromycin have been reported with mixed results but no clear signal of efficacy and some concerns raised about cardiac toxicity. Treamtent in the outpatient setting has potential to prevent infected individuals from deteriorating and perhaps more importantly, may shorten the duration of viral shedding, reducing the risk of transmission and the duration required for self-isolation, with significant public health and societal impact.Added value of this studyThis is the first study to show an antiviral effect in outpatients with COVID-19. After controlling for baseline viral load, those treated with peginterferon-lambda had a 4.12-fold (95%CI 1.15-16.7, p=0.029) higher odds of viral clearance by Day 7 compared to those who received placebo. The viral load decline was faster with pegterferon-lambda and the effect was most pronounced in those with high viral loads. In individuals with a baseline viral load of 10E6 copies/mL or higher, 15/19 (79%) in the peginterferon-lambda arm cleared by Day 7 compared to 6/16 (38%) (p=0.012) in the placebo arm (OR 6.25, 95%CI 1.49-31.1, p=0.012), translating to a median time to viral clearance of 7 days (95%CI 6.2-7.8 days) with peginterferon-lambda compared to 10 days (95%CI 7.8-12.2 days) with placebo (p=0.038). Those with low viral loads (<10E6 copies/mL) cleared quickly in both groups. Peginterferon-lambda was well-tolerated with a similar side effect profile to placebo and no concerning laboratory adverse events.Implications of all available evidenceThere is no currently approved therapy for outpatients with COVID-19. This study showed that peginterferon-lambda accelerated viral clearance, particularly in those with high baseline viral loads, highlighting the importance of quantitative viral load testing in the evaluation of antiviral agents for COVID-19. Treatment early in the course of disease may prevent clinical deterioration and shorenting of the duration of viral shedding may have important public health impact by limiting transmission and reducing the duration required for self-isolation. Additional trials of peginterferon-lambda and other antiviral strategies in the outpatient setting are required.

scholarly journals Modeling SARS-CoV-2 viral kinetics and association with mortality in hospitalized patients from the French COVID cohort

2021 ◽  
Vol 118 (8) ◽  
pp. e2017962118
Author(s):  
Nadège Néant ◽  
Guillaume Lingas ◽  
Quentin Le Hingrat ◽  
Jade Ghosn ◽  
Ilka Engelmann ◽  
...  
Keyword(s):  
Risk Factors ◽  
Viral Load ◽  
Hospital Admission ◽  
Symptom Onset ◽  
Hospitalized Patients ◽  
Viral Clearance ◽  
Viral Dynamics ◽  
Viral Kinetics ◽  
Peak Viral Load ◽  
Reduction Of Mortality

The characterization of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral kinetics in hospitalized patients and its association with mortality is unknown. We analyzed death and nasopharyngeal viral kinetics in 655 hospitalized patients from the prospective French COVID cohort. The model predicted a median peak viral load that coincided with symptom onset. Patients with age ≥65 y had a smaller loss rate of infected cells, leading to a delayed median time to viral clearance occurring 16 d after symptom onset as compared to 13 d in younger patients (P < 10−4). In multivariate analysis, the risk factors associated with mortality were age ≥65 y, male gender, and presence of chronic pulmonary disease (hazard ratio [HR] > 2.0). Using a joint model, viral dynamics after hospital admission was an independent predictor of mortality (HR = 1.31, P < 10−3). Finally, we used our model to simulate the effects of effective pharmacological interventions on time to viral clearance and mortality. A treatment able to reduce viral production by 90% upon hospital admission would shorten the time to viral clearance by 2.0 and 2.9 d in patients of age <65 y and ≥65 y, respectively. Assuming that the association between viral dynamics and mortality would remain similar to that observed in our population, this could translate into a reduction of mortality from 19 to 14% in patients of age ≥65 y with risk factors. Our results show that viral dynamics is associated with mortality in hospitalized patients. Strategies aiming to reduce viral load could have an effect on mortality rate in this population.

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