scholarly journals Virologic features of SARS-CoV-2 infection in children

Author(s):  
Lael M. Yonker ◽  
Julie Boucau ◽  
James Regan ◽  
Manish Chandra Choudhary ◽  
Madeleine D. Burns ◽  
...  

Background: Data on viral factors causing pediatric disease and guidance for pediatric-specific considerations have lagged behind adults throughout the COVID-19 pandemic. As COVID-19 infections and deaths increase in the pediatric population, characterization of SARS-CoV-2 viral dynamics in children would enable data-driven public health guidance. Methods: Nasal swabs collected from children with COVID-19 were analyzed. Viral load was quantified by RT-PCR; viral culture was assessed by direct observation of cytopathic effects and semiquantitative viral titers. Correlations with age or symptom duration were analyzed. SARS-CoV-2 whole genome amplification was compared with contemporaneous Massachusetts sequences to assess for clustering patterns. Results: Ninety-seven children with COVID-19 (median age 10 years, range 2 weeks-22 years) were included in this study. Age did not impact SARS-CoV-2 viral load in nasal secretions: children of all ages were equally likely to carry live, replicating virus. Children within the first five days of illness had higher viral loads and rates of culture positivity, and viral load in hospitalized children (n=30) did not differ from hospitalized adults (n=21) with similar duration of symptoms. While pediatric SARS-CoV-2 sequences were representative of those in the community, novel variants were identified. Conclusions: Children can carry high quantities of live, replicating virus, creating a potential reservoir for transmission and evolution of genetic variants. As guidance around social distancing and masking evolves following vaccine uptake in older populations, a clear understanding of SARS-CoV-2 infection dynamics in children is critical for rational development of public health policies and vaccination strategies to mitigate the impact of COVID-19.  

Author(s):  
Emily Happy Miller ◽  
Jason Zucker ◽  
Delivette Castor ◽  
Medini K Annavajhala ◽  
Jorge L Sepulveda ◽  
...  

Abstract Background The relationship between SARS-CoV-2 viral load and patient symptom duration in both in- and outpatients, and the impact of these factors on patient outcomes, are currently unknown. Understanding these associations is important to clinicians caring for patients with COVID-19. Methods We conducted an observational study between March 10–May 30, 2020 at a large quaternary academic medical center in New York City. Patient characteristics, laboratory values, and clinical outcomes were abstracted from the electronic medical records. Of all patients tested for SARS-CoV-2 during this time (N=16,384), there were 5,467 patients with positive tests, of which 4,254 had available Ct values and were included in further analysis. Univariable and multivariable logistic regression models were used to test associations between Ct values, duration of symptoms prior to testing, patient characteristics and mortality. The primary outcome is defined as death or discharge to hospice. Results Lower Ct values at diagnosis (i.e. higher viral load) were associated with significantly higher mortality among both in- and out-patients. Interestingly, patients with a shorter time since the onset of symptoms to testing had a worse prognosis, with those presenting less than three days from symptom onset having 2-fold increased odds of death. After adjusting for time since symptom onset and other clinical covariates, Ct values remained a strong predictor of mortality. Conclusions SARS-CoV-2 RT-PCR Ct value and duration of symptoms are strongly associated with mortality. These two factors add useful information for clinicians to risk stratify patients presenting with COVID-19.


2018 ◽  
Vol 36 (3) ◽  
pp. 297-324
Author(s):  
Bruno Buonomo ◽  
Rossella Della Marca ◽  
Alberto d’Onofrio

AbstractHesitancy and refusal of vaccines preventing childhood diseases are spreading due to ‘pseudo-rational’ behaviours: parents overweigh real and imaginary side effects of vaccines. Nonetheless, the ‘Public Health System’ (PHS) may enact public campaigns to favour vaccine uptake. To determine the optimal time profiles for such campaigns, we apply the optimal control theory to an extension of the susceptible-infectious-removed (SIR)-based behavioural vaccination model by d’Onofrio et al. (2012, PLoS ONE, 7, e45653). The new model is of susceptible-exposed-infectious-removed (SEIR) type under seasonal fluctuations of the transmission rate. Our objective is to minimize the total costs of the disease: the disease burden, the vaccination costs and a less usual cost: the economic burden to enact the PHS campaigns. We apply the Pontryagin minimum principle and numerically explore the impact of seasonality, human behaviour and latency rate on the control and spread of the target disease. We focus on two noteworthy case studies: the low (resp. intermediate) relative perceived risk of vaccine side effects and relatively low (resp. very low) speed of imitation. One general result is that seasonality may produce a remarkable impact on PHS campaigns aimed at controlling, via an increase of the vaccination uptake, the spread of a target infectious disease. In particular, a higher amplitude of the seasonal variation produces a higher effort and this, in turn, beneficially impacts the induced vaccine uptake since the larger is the strength of seasonality, the longer the vaccine propensity remains large. However, such increased effort is not able to fully compensate the action of seasonality on the prevalence.


2020 ◽  
Vol 71 (10) ◽  
pp. 2663-2666 ◽  
Author(s):  
Jared Bullard ◽  
Kerry Dust ◽  
Duane Funk ◽  
James E Strong ◽  
David Alexander ◽  
...  

Abstract Background Reverse-transcription polymerase chain reaction (RT-PCR) has become the primary method to diagnose viral diseases, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). RT-PCR detects RNA, not infectious virus; thus, its ability to determine duration of infectivity of patients is limited. Infectivity is a critical determinant in informing public health guidelines/interventions. Our goal was to determine the relationship between E gene SARS-CoV-2 RT-PCR cycle threshold (Ct) values from respiratory samples, symptom onset to test (STT), and infectivity in cell culture. Methods In this retrospective cross-sectional study, we took SARS-CoV-2 RT-PCR–confirmed positive samples and determined their ability to infect Vero cell lines. Results Ninety RT-PCR SARS-CoV-2–positive samples were incubated on Vero cells. Twenty-six samples (28.9%) demonstrated viral growth. Median tissue culture infectious dose/mL was 1780 (interquartile range, 282–8511). There was no growth in samples with a Ct > 24 or STT > 8 days. Multivariate logistic regression using positive viral culture as a binary predictor variable, STT, and Ct demonstrated an odds ratio (OR) for positive viral culture of 0.64 (95% confidence interval [CI], .49–.84; P < .001) for every 1-unit increase in Ct. Area under the receiver operating characteristic curve for Ct vs positive culture was OR, 0.91 (95% CI, .85–.97; P < .001), with 97% specificity obtained at a Ct of > 24. Conclusions SARS-CoV-2 Vero cell infectivity was only observed for RT-PCR Ct < 24 and STT < 8 days. Infectivity of patients with Ct > 24 and duration of symptoms > 8 days may be low. This information can inform public health policy and guide clinical, infection control, and occupational health decisions. Further studies of larger size are needed.


2020 ◽  
Vol 30 (Supplement_5) ◽  
Author(s):  
A Odone ◽  
V Gianfredi ◽  
B Frascella ◽  
F Balzarini ◽  
A Oradini Alacreu ◽  
...  

Abstract The second and final phase of the EUVIS (EUrope Vaccines ICT Strategies) project, coordinated by the School of Public Health of the University Vita-Salute San Raffaele in Milan (Italy), aims at collecting best practices on the use and impact of Information and Communication Technologies (ICT) and digital tools to increase vaccine uptake and ultimately vaccination coverage in Europe. The field of ICT has flourished in recent years revolutionizing the processes of gathering, spreading and utilizing health information among healthcare providers, citizens and mass media. In particular, we are interested in any digital technology that can improve vaccine uptake supporting actions aimed at both increasing the demand of vaccines (i.e provide access to information through telecommunications, networks, the Internet, wireless, mobile devices), and the supply of effective and efficient life-course immunization services (i.e ICT-based interventions to support immunization programmes delivery and their monitoring). Within EUVIS we have previously conducted a series of systematic reviews to pool available evidence from experimental studies on the impact of selected ICT-based intervention (i.e. e-mail reminders, personal health records, among others) to improve vaccine uptake and other associated outcomes. In the current study, second and final phase of the EUVIS project, we are conducting a survey at the European level to gather original data on the use and impact of ICT and digital tools within immunization programmes in selected countries. The survey tool was developed on the basis of findings from EUVIS phase one and experts' consultation; it consisted on a 55-item questionnaire, distributed to public health professionals working in health agencies, institutions and the academia to build “ICT and immunization” countries' profile, as well as to gather, pool and critically appraise data on perceived potential and challenges of immunization programmes' digitalization in Europe.


Vaccines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 659
Author(s):  
Luca Coppeta ◽  
Ottavia Balbi ◽  
Zaira Grattagliano ◽  
Grazia Genga Mina ◽  
Antonio Pietroiusti ◽  
...  

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected more than one hundred million people since the beginning of the worldwide pandemic. In this study, data from a large hospital in central Italy was used to evaluate the impact of the first dose of the BNT162b2 mRNA vaccine on SARS-CoV-2 infections in terms of the prevalence of symptomatic cases, symptom duration, and viral clearance timing. All vaccinated Healthcare Workers (HCWs) with positive RT-PCR by nasopharyngeal (NP) swabs were divided into two cohorts (positive RT-PCR within day 12 and positive RT-PCR between day 13 and day 21 after first dose administration) and compared for the presence and duration of symptoms and the timing of viral clearance. The same variables were evaluated across HCWs with positive RT-PCR within 6 days after first dose administration and non-vaccinated HCWs with positive RT-PCR between 1 October 2020 and 28 February 2021. Eighteen HCWs tested positive on RT-PCR by NP swab from day 1 to day 12 after the 1st dose administration (incidence rate 6.2 × 10−4) and 5 HCWs from day 13 to day 21 (incidence rate 2.3 × 10−4). Symptom duration and viral clearance timing are significantly shorter in the cohort of HCWs with positive RT-PCR 12 days after the first dose of the BNT162b2 mRNA vaccine. The administration of the first dose proved effective in reducing presence, symptom duration, and viral clearance even in HCWs vaccinated for less than 6 days. These results could have implications on public health and post-exposure prophylaxis.


PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0257979
Author(s):  
Michael J. Satlin ◽  
Jason Zucker ◽  
Benjamin R. Baer ◽  
Mangala Rajan ◽  
Nathaniel Hupert ◽  
...  

Public health interventions such as social distancing and mask wearing decrease the incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but it is unclear whether they decrease the viral load of infected patients and whether changes in viral load impact mortality from coronavirus disease 2019 (COVID-19). We evaluated 6923 patients with COVID-19 at six New York City hospitals from March 15-May 14, 2020, corresponding with the implementation of public health interventions in March. We assessed changes in cycle threshold (CT) values from reverse transcription-polymerase chain reaction tests and in-hospital mortality and modeled the impact of viral load on mortality. Mean CT values increased between March and May, with the proportion of patients with high viral load decreasing from 47.7% to 7.8%. In-hospital mortality increased from 14.9% in March to 28.4% in early April, and then decreased to 8.7% by May. Patients with high viral loads had increased mortality compared to those with low viral loads (adjusted odds ratio 2.34). If viral load had not declined, an estimated 69 additional deaths would have occurred (5.8% higher mortality). SARS-CoV-2 viral load steadily declined among hospitalized patients in the setting of public health interventions, and this correlated with decreases in mortality.


2022 ◽  
Author(s):  
Miquel Oliu-Barton ◽  
Bary SR Pradel ◽  
Nicolas Woloszko ◽  
Lionel Guetta-Jeanrenaud ◽  
Philippe Aghion ◽  
...  

Abstract In the COVID-19 pandemic, governments have used various interventions,1,2 including COVID certificates as proof of vaccination, recovery, or a recent negative test, required for individuals to access shops, restaurants, and education or workplaces.3 While arguments for and against COVID certificates have focused on reducing transmission and ethical concerns,4,5 the effect of the certificates on vaccine uptake, public health, and the economy requires investigation. We construct counterfactuals based on innovation diffusion theory6 and validate them with econometric methods7 to evaluate the impact of incentives created by COVID certificates in France, Germany, and Italy. We estimate that from their announcement during summer 2021 to the end of the year, the intervention led to increased vaccine uptake in France of 13.0 (95% CI 9.7–14.9) percentage points (p.p.) of the total population, in Germany 6.2 (2.6–6.9) p.p., and in Italy 9.7 (5.4–12.3) p.p.; averted an additional 3,979 (3,453–4,298) deaths in France (i.e., 31.7%), 1,133 (-312–1,358) in Germany (5.6%), and 1,331 (502–1,794) in Italy (14.0%); and prevented gross domestic product (GDP) losses of €6.0 (5.9–6.1) billion in France, €1.4 (1.3–1.5) billion in Germany, and €2.1 (2.0–2.2) billion in Italy. Notably, the application of COVID certificates substantially reduced the pressure on intensive care units (ICUs) and, in France, averted surpassing the occupancy levels where prior lockdowns were instated. Overall, our findings are more substantial than predicted8 and may help to inform decisions about when and how to employ COVID certificates to increase vaccination and thus avoid stringent interventions, such as closures, curfews, and lockdowns, with large social and economic consequences.


2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S314-S314
Author(s):  
Lillian B Brown ◽  
Lisa Gail Winston ◽  
Barbara Haller ◽  
Phong Pham ◽  
Beatrice Marcelo ◽  
...  

Abstract Background Most diagnostic tests for SARS-CoV-2, the causative agent of COVID-19, are RT-PCR based. This method is sensitive but cannot distinguish replicating from non-replicating virus. RT-PCR cycle threshold (Ct) values are inversely correlated with viral load, and higher Ct values have been correlated with lower in vitro viral infectivity. However, relatively few data exist on the association between Ct values and patients’ duration of symptoms remains unclear. We thus evaluated Ct values and symptom duration in a cohort of patients hospitalized with COVID-19. Methods We assessed all patients admitted to San Francisco General Hospital between April 1 and May 18, 2020 with confirmed COVID-19 infection based on RT-PCR testing (Abbott m2000 platform). We included patients having diagnostic testing for suspected COVID-19 and patients having asymptomatic testing per hospital policy. For symptomatic patients, date of symptom onset was abstracted from hospital records, and time from symptom onset to test date was calculated. RT-PCR Ct values were manually extracted. Median Ct and IQR were calculated for patients with < 10 days of symptoms, ≥10 days of symptoms, and asymptomatic disease. Between-group comparisons were performed using the Kruskal-Wallis test. Results Among 61 patients with positive RT-PCR tests, 40 patients reported < 10 days of symptoms at the time of testing, 15 reported ≥10 days of symptoms, and 6 were asymptomatic. The median Ct value was 14.2 cycles (IQR, 10.2, 18.3) among patients reporting < 10 days of symptoms, 19.7 cycles (IQR, 15.3, 23.9) among patients reporting ≥10 days of symptoms, and 26.3 (IQR, 25.0, 29.1) among asymptomatic patients. Ct values were significantly lower among patients with < 10 days of symptoms compared to patients with >=10 days of symptoms (p=0.01) and when compared to asymptomatic patients (p=0.0002) [Figure]. Cycle threshold (Ct) by days of symptoms at time of testing Conclusion SARS-CoV-2 RT-PCR cycle threshold values were higher (indicating lower viral load) in patients with longer symptom duration and were highest in asymptomatic patients. These results add to emerging data suggesting that strategies for optimal isolation of patients in both community and hospital settings could be informed by a combination of symptom duration and RT-PCR Ct values. Disclosures All Authors: No reported disclosures


Author(s):  
Kyueun Lee ◽  
Hawre Jalal ◽  
Jonathan M. Raviotta ◽  
Mary G. Krauland ◽  
Richard K. Zimmerman ◽  
...  

AbstractBackgroundsThe influenza season of 2020-21 was remarkably low, likely due to implementation of public health preventive measures such as social distancing, mask-wearing, and school closure and due to decreased international travel. This leads to a key public health question: what will happen in the 2021-22 influenza season? To answer this, we developed a multi-season influenza model that accounted for residual immunity from prior infection.MethodWe built a multi-strain, non-age structured compartmental model that captures immunity over multiple influenza seasons. By the end of the influenza season, we sorted the population based on their experience of natural infection and/or vaccination, which determines the susceptibility to influenza infection in the following season. Because the exact parameters of transmission rates and immunity are unknown, we implemented Bayesian calibration against the observed influenza epidemics (influenza hospitalization rates from 2012 to 2020 in the US) to estimate those parameters. In forward projections, we simulated low influenza activity in 2020-21 season by lowering transmission rate by 20%. Compared to the counterfactual case, in which influenza activity remained at the normal level in 2020-21, we estimated the change in the number of hospitalizations in the following seasons with varying level of vaccine uptake and effectiveness. We measured the change in population immunity over time by varying the number of seasons with low influenza activity.ResultWith the low influenza activity in 2020-21, the model estimated 102,000 [95% CI: 57,000-152,000] additional hospitalizations in 2021-22, without change in vaccine uptake and effectiveness. The expected change in hospitalization varied depending on the level of vaccine uptake and effectiveness in the following year. Achieving 50% increase in one of two measures (1.5X vaccine uptake with 1X vaccine efficacy or 1.5X vaccine efficacy with 1X vaccine uptake) was necessary to avert the expected increase in hospitalization in the next influenza season. Otherwise, increases in both measures by 25% averted the expected increase in influenza-hospitalization. If the low influenza activity seasons continue, population immunity would remain low during those seasons, with 48% the population susceptible to influneza infection.ConclusionWe predicted a large compensatory influenza season in 2021-2 due to a light season in 2020-21. However, higher influenza vaccine uptake would reduce this projected increase in influenza.


2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S653-S653
Author(s):  
Katy Shaw-Saliba ◽  
Yu-Hsiang Hsieh ◽  
Richard E Rothman

Abstract Background The factors that influence influenza viral load are poorly understood, but may have important implications for viral transmission and disease severity. We explored the relationship between patient and virus factors on influenza viral load across 4 consecutive influenza seasons. Methods Adult influenza-positive patients presenting to emergency departments in Baltimore, MD and Taipei, Taiwan between 2014 and 2018 were consented and enrolled. Nasopharyngeal (NP) samples and detailed paired data on symptom duration, demographics, and vaccination were collected. Viral load was inferred using the cycle threshold (Ct) values from quantitative real-time RT–PCR assays for 299 samples and influenza subtype was determined. Bivariate and multivariate analyses were conducted. Results Viral load was impacted by both patient and virus characteristics. Older age and shorter duration of symptoms was associated with a higher viral load (age: Ct difference -0.04, P = 0.022. symptoms: each increasing day, Ct difference +1.02, P < 0.001). Seasonal variability was observed, with the highest viral load associated with the 2014–2015 predominant H3N2 subtype (Ct 21.69, P < 0.001), where there was also a vaccine mismatch. Across seasons, H1N1 was associated with a lower viral load than H3N2 (Ct value + 2.66, P < 0.001). There was not association between gender and immunosuppression on viral load. Conclusion Our study demonstrates that both host and virus factors that can affect Ct values and inferred viral loads. As anticipated, higher viral load, were found to be associated with older age and shorter duration of symptoms; interestingly infection with the H3N2 subtype, traditionally associated with more severe disease was also associated with higher viral loads. Future-focused studies are required to better characterize these relationships, and directly evaluate relevance to both transmission and disease severity. Disclosures All authors: No reported disclosures.


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