Burden of SARS-CoV-2 and protection from symptomatic second infection in children

AbstractImportanceThe impact of the SARS-CoV-2 pandemic on children remains unclear. Better understanding of the burden of COVID-19 among children and their protection against re-infection is crucial as they will be among the last groups vaccinated.ObjectiveTo characterize the burden of COVID-19 and assess how protection from symptomatic re-infection among children may vary by age.DesignA prospective, community-based pediatric cohort study conducted from March 1, 2020 through October 15, 2021.SettingThe Nicaraguan Pediatric Influenza Cohort is a community-based cohort in District 2 of Managua, Nicaragua.ParticipantsA total of 1964 children aged 0-14 years participated in the cohort. Non-immunocompromised children were enrolled by random selection from a previous pediatric influenza cohort. Additional newborn infants aged ≤4 weeks were randomly selected and enrolled monthly, via home visits.ExposuresPrior COVID-19 infection as confirmed by positive anti SARS-CoV-2 antibodies (receptor binding domain [RBD] and spike protein) or real time RT-PCR confirmed COVID-19 infection ≥60 days prior to current COVID-19.Main Outcomes and MeasuresSymptomatic COVID-19 cases confirmed by real time RT-PCR and hospitalization within 28 days of symptom onset of confirmed COVID-19 case.ResultsOverall, 49.8% of children tested were seropositive over the course of the study. There were also 207 PCR-confirmed COVID-19 cases, 12 (6.4%) of which were severe enough to require hospitalization. Incidence of COVID-19 was highest among children aged <2 years—16.1 per 100 person-years (95% Confidence Interval [CI]: 12.5, 20.5)—approximately three times that of children in any other age group assessed. Additionally, 41 (19.8%) symptomatic SARS-CoV-2 episodes were re-infections, with younger children slightly more protected against symptomatic reinfection. Among children aged 6-59 months, protection was 61% (Rate Ratio [RR]:0.39, 95% CI:0.2,0.8), while protection among children aged 5-9 and 10-14 years was 64% (RR:0.36,0.2,0.7), and 49% (RR:0.51,0.3-0.9), respectively.Conclusions and RelevanceIn this prospective community-based pediatric cohort rates of symptomatic and severe COVID-19 were highest among the youngest participants, with rates stabilizing around age 5. Reinfections represent a large proportion of PCR-positive cases, with children <10 years displaying greater protection from symptomatic reinfection. A vaccine for children <5 years is urgently needed.Key PointsQuestionWhat is the burden of COVID-19 among young children and how does protection from re-infection vary with age?FindingsIn this study of 1964 children aged 0-14 years children <5 years had the highest rates of symptomatic and severe COVID-19 while also displaying greater protection against re-infection compared to children ≥10 years.MeaningGiven their greater risk of infection and severe disease compared to older children, effective vaccines against COVID-19 are urgently needed for children under 5.

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Epidemiological Analysis of COVID-19 Patients detected by Real-Time Reverse Transcription - Polymerase Chain reaction in a Tertiary Care Biosafety Level III Laboratory, Rawalpindi

Journal of Rawalpindi Medical College ◽

10.37939/jrmc.v25i1.1576 ◽

2021 ◽

Vol 25 (1) ◽

pp. 128-133

Author(s):

Rabia Anjum ◽

Nadeem Ikram ◽

Asma Nafisa ◽

Naeem Akhtar

Keyword(s):

Polymerase Chain Reaction ◽

Real Time ◽

Reverse Transcription ◽

Severe Disease ◽

Tertiary Care ◽

Positive Test ◽

Age Group ◽

Rt Pcr ◽

Chain Reaction ◽

Polymerase Chain

Introduction: Unexpected eruption and global dissemination of Coronavirus disease (COVID-19) has tested the healthcare systems of both developed and developing countries.Objective: To analyze the spectrum of novel coronavirus infection in a tertiary care setup.Materials and Methods: All oropharyngeal and nasopharyngeal samples (n=7057) were collected in a viral transport medium (VTM) for qualitative analysis by a real-time reverse transcription-polymerase chain reaction (RT-PCR) machine. Positive and negative controls were applied with each batch. Positive cases were stratified into mild, moderate, severe, and asymptomatic, according to the guidelines of the National Institute of Health, Pakistan. Descriptive statistical tests were applied including percentage, chi-square tests, mean, median, and mode. P < 0.05 was counted as statistically significant.Results: Average positive test rate was 18.97% (n=1339). The maximum positivity rate (26%) of COVID-19 infection was observed in June 2020. Most of the cases (60%) belonged to Rawalpindi District, were male (n=844, 63.03%), and belonged to age group (20-40 years) and mean of 36 and age range from 2-85 years. Forty-nine percent of COVID-19 infected patients were asymptomatic and only 9.8% progressed to severe disease. Overall, the mortality rate was 159(11.87%) in RT-PCR confirmed cases.Conclusion: Average positive test rate was 18.97%. The majority of the participants belonged to the young age group (20-40 yrs.) with a range from 2 to 85 years. Forty-nine percent positive COVID-19 infected patients were asymptomatic while 9.8% had severe disease.

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Designing the landscape for technological development in neonatal neurocritical care

BMJ Innovations ◽

10.1136/bmjinnov-2018-000288 ◽

2018 ◽

Vol 4 (4) ◽

pp. 163-171

Author(s):

Colin Hamilton ◽

Robert Phaal ◽

Mita Brahmbhatt ◽

Peter Jarritt ◽

Topun Austin

Keyword(s):

Real Time ◽

Neurocritical Care ◽

Brain Injuries ◽

Unmet Needs ◽

Technology Development ◽

Clinical Skills ◽

Technological Development ◽

Newborn Infants ◽

Patient Pathway ◽

The Impact

ObjectivesTo identify current ‘gaps’ in clinical practice or therapeutic knowledge of the care of neonatal neurointensive care patients and to determine the impact healthcare technologies can have on improving outcomes.DesignThe Cambridge Institute for Manufacturing’s (IfM) roadmapping methodology.SettingCambridge, UK.Participants16 delegates were selected through professional networks. They provided coverage of academia and clinical skills, as well as expertise in neonatology, engineering and technology development.Main outcome measuresA ‘strategic landscape’ has been developed with ‘landmarks’ identified as ‘trends or drivers’, ‘patient pathway experience and unmet needs’ and ‘enabling project or resources’. Priorities were voted on by delegates.Results26 strategic ‘landmarks’ were identified, and of these 8 were considered ‘trends or drivers’, 8 ‘patient pathway experience and unmet needs’ and 10 as ‘enabling project or resources’. Of these, five priorities for the future of neonatal neurocritical care were identified by a voting process: real-time video monitoring for parents; individualised management of preterm infants in neonatal neurocritical care based on real-time multimodal monitoring; continuous electroencephalogram monitoring for early seizure diagnosis; neuroprotection: understanding basic mechanisms; and sleep measurement.ConclusionsThrough the use of the IfM methodology, a list of priorities has been developed for future work into improving the experience and possible outcomes of newborn infants with brain injuries and their families. While not an exhaustive list, it provides the beginning for a national conversation on the topic.

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Assessing the burden of Covid-19 in the slums of Bangalore city: Results of Rapid Community Survey

Indian Journal of Community Health ◽

10.47203/ijch.2021.v33i03.012 ◽

2021 ◽

Vol 33 (3) ◽

pp. 475-479

Author(s):

Ranganath Thimnahalli Sobagaiah ◽

Ramesh Nugehally Raju Masthi ◽

Lalitha Krishnappa ◽

Ambika Rangaiah ◽

Girish Nagaraja Rao ◽

...

Keyword(s):

Inner Core ◽

Venous Blood ◽

Sampling Technique ◽

Community Survey ◽

Age Group ◽

Rt Pcr ◽

Community Based ◽

Cross Sectional ◽

Bangalore City ◽

Cluster Random Sampling

Background: Karnataka, more so Bangalore, reported an increase in number of COVID-19 cases in early April 2021. Objective: To assess the burden of COVID-19 in the slums of Bengaluru city. Materials and Methods: A cross-sectional multi centre community-based study was done in the 2nd and 3rd week of April 2021 in 24 different slums in Bangalore city. WHO cluster random sampling technique was followed. Swabs for RTPCR test and 4 ml of venous blood was collected from 728 subjects more than 18 years of age. Results: A total of 51 (7%) subjects were positive for COVID-19 through RT-PCR. Majority 33 (56.9%) were in the age group of 18-44 years. 148 (20.3%) subjects were sero-positive on blood examination and 18-44 years was the (59.4%) preponderant age group. Overall seropositivity was 20.3% (95%CI; 17.4-23.2) and RT-PCR positivity is 7% (95%CI; 5.2-8.8%) among the subjects surveyed. In the inner core area of Bangalore, seropositivity was 24.2% (95%CI; 21.0 – 27.3) and RT-PCR positivity was 8% (95%CI; 6.1-9.9). Two doses of COVID-19 vaccine were taken only by 1.55% subjects during the study period. Conclusion: The study showed that one in 5 subjects were sero-positive to SARS-CoV-2 and one in 15 individuals had active COVID-19 infection.

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A homozygous telomerase T-motif variant resulting in markedly reduced repeat addition processivity in siblings with Hoyeraal Hreidarsson syndrome

Blood ◽

10.1182/blood-2012-08-447755 ◽

2013 ◽

Vol 121 (18) ◽

pp. 3586-3593 ◽

Cited By ~ 18

Author(s):

Maria M. Gramatges ◽

Xiaodong Qi ◽

Ghadir S. Sasa ◽

Julian J.-L. Chen ◽

Alison A. Bertuch

Keyword(s):

Protein Function ◽

Severe Disease ◽

Computational Algorithms ◽

Key Points ◽

The Impact ◽

Motif Variant ◽

Limited Sensitivity

Key Points Biallelic inheritance of a telomerase T-motif mutation selectively impairs repeat addition processivity and results in severe disease. Computational algorithms commonly used to predict the impact of variants on protein function have limited sensitivity with regard to hTERT.

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Comparison of relative mRNA quantification models and the impact of RNA integrity in quantitative real-time RT-PCR

Biotechnology Letters ◽

10.1007/s10529-006-9127-2 ◽

2006 ◽

Vol 28 (19) ◽

pp. 1601-1613 ◽

Cited By ~ 366

Author(s):

Simone Fleige ◽

Vanessa Walf ◽

Silvia Huch ◽

Christian Prgomet ◽

Julia Sehm ◽

...

Keyword(s):

Real Time ◽

Rt Pcr ◽

Mrna Quantification ◽

Rna Integrity ◽

The Impact

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The impact of primer and probe-template mismatches on the sensitivity of pandemic influenza A/H1N1/2009 virus detection by real-time RT-PCR

Journal of Clinical Virology ◽

10.1016/j.jcv.2010.03.012 ◽

2010 ◽

Vol 48 (2) ◽

pp. 91-95 ◽

Cited By ~ 41

Author(s):

Chonticha Klungthong ◽

Piyawan Chinnawirotpisan ◽

Kittinun Hussem ◽

Thipwipha Phonpakobsin ◽

Wudtichai Manasatienkij ◽

...

Keyword(s):

Real Time ◽

Pandemic Influenza ◽

Influenza A ◽

Virus Detection ◽

Rt Pcr ◽

Influenza A H1n1 ◽

The Impact

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Epidemiology of invasiveHaemophilus influenzaeinfections in England and Wales in the pre-vaccination era (1990–2)

Epidemiology and Infection ◽

10.1017/s0950268800058155 ◽

1995 ◽

Vol 115 (1) ◽

pp. 89-100 ◽

Cited By ~ 24

Author(s):

E. C. Anderson ◽

N. T. Begg ◽

S. C. Crawshaw ◽

R. M. Hargreaves ◽

A. J. Howard ◽

...

Keyword(s):

Haemophilus Influenzae ◽

Diagnostic Category ◽

Case Fatality ◽

The Elderly ◽

Age Group ◽

Type B ◽

Older Children ◽

Survey Period ◽

England And Wales ◽

Children Under 5

SummaryThis survey defined the pattern of invasiveHaemophilus influenzaeinfections during 1990–2 in six regions in England and Wales during the pre-vaccination era providing a baseline against which any changes in patterns of disease due to the introduction of theHaemophilus influenzaetype b vaccination programme can be monitored. A total of 946 cases of invasiveHaemophilus influenzaewere recorded during the survey period of which almost 90 % were due to type b and most of the remainder were non-typeable. Type b infections occurred predominantly in children less than 5 years of age (88%) with the highest attack rate in male infants in the 6–11 month age group. Diagnostic category varied with both age and serotype; meningitis was the commonest presentation overall but pneumonia and bacteraemia were more common in adults and non-typeable isolates. Mortality was highest in neonates and the elderly (over 65 years of age) who were more likely to have an underlying predisposing condition than older children and adults. Children under 5 years of age had a higher case fatality rate for non-typeable than for type b infections. Ampicillin resistance was 15% and there were no cefotaxime resistant type b isolates.

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NF-κB and pSTAT3 synergistically drive G6PD overexpression and facilitate sensitivity to G6PD inhibition in ccRCC

10.21203/rs.3.rs-27362/v3 ◽

2020 ◽

Author(s):

Qiao Zhang ◽

Zhe Yang ◽

Yueli Ni ◽

Honggang Bai ◽

Qiaoqiao Han ◽

...

Keyword(s):

Western Blot ◽

Real Time ◽

Signaling Pathway ◽

Protein Interaction ◽

Xenograft Model ◽

Metabolic Reprogramming ◽

Regulatory Function ◽

Rt Pcr ◽

Repressive Effect ◽

The Impact

Abstract Background: Glucose 6-phosphate dehydrogenase (G6PD) serves key roles in cancer cell metabolic reprogramming, and has been reported to be involved in certain carcinogenesis. Previous results from our laboratory demonstrated that overexpressed G6PD was a potential prognostic biomarker in clear cell renal cell carcinoma (ccRCC), the most common subtype of kidney cancer. G6PD could stimulate ccRCC growth and invasion through facilitating reactive oxygen species (ROS)-phosphorylated signal transducer and activator of transcription 3 (pSTAT3) activation and ROS-MAPK-MMP2 axis pathway, respectively. However, the reasons for ectopic G6PD overexpression and the proliferation repressive effect of G6PD inhibition in ccRCC are still unclear. Methods: The impact of ROS accumulation on NF-κB signaling pathway and G6PD expression was determined by real-time RT-PCR and Western blot in ccRCC cells following treatment with ROS stimulator or scavenger. The regulatory function of NF-κB signaling pathway in G6PD transcription was analyzed by real-time RT-PCR, Western blot, luciferase and ChIP assay in ccRCC cells following treatment with NF-κB signaling activator/inhibitor or lentivirus infection. ChIP and Co-IP assay was performed to demonstrate protein-DNA and protein-protein interaction of NF-κB and pSTAT3, respectively. MTS assay, human tissue detection and xenograft model were conducted to characterize the association between NF-κB, pSTAT3, G6PD expression level and proliferation functions. Results: ROS-stimulated NF-κB and pSTAT3 signaling over-activation could activate each other, and exhibit cross-talks in G6PD aberrant transcriptional regulation. The underlying mechanism was that NF-κB signaling pathway facilitated G6PD transcription via direct DNA–protein interaction with p65 instead of p50. p65 and pSTAT3 formed a p65/pSTAT3 complex, occupied the pSTAT3-binding site on G6PD promoter, and contributed to ccRCC proliferation following facilitated G6PD overexpression. G6PD, pSTAT3, and p65 were highly expressed and positively correlated with each other in ccRCC tissues, confirming that NF-κB and pSTAT3 synergistically promote G6PD overexpression. Moreover, G6PD inhibitor exhibited tumor-suppressor activities in ccRCC and attenuated the growth of ccRCC cells both in vitro and in vivo . Conclusion: ROS-stimulated aberrations of NF-κB and pSTAT3 signaling pathway synergistically drive G6PD transcription through forming a p65/pSTAT3 complex. Moreover, G6PD activity inhibition may be a promising therapeutic strategy for ccRCC treatment.

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An Integrated Diagnostic Approach for Citrus Exocortis Viroid

10.21203/rs.3.rs-768766/v1 ◽

2021 ◽

Author(s):

Chih-Hsu Lin ◽

Ting-Hsuan Hung ◽

I Hu ◽

Ta-Hsin Ku ◽

Chun-Yi Lin ◽

...

Keyword(s):

Real Time ◽

Reverse Transcription ◽

Severe Disease ◽

Blot Hybridization ◽

Rt Pcr ◽

Dot Blot ◽

Tomato Cultivar ◽

Dot Blot Hybridization ◽

Reverse Transcription Pcr ◽

One Step

Abstract BackgroundCitrus exocortis viroid (CEVd) is a circular single-stranded RNA pathogen consists of around 370 nucleotides and leads to a severe disease showing bark scaling symptom on citrus crops, which leads to yield decrease and economic loss. Since the absence of viroid-encoded proteins, methods for CEVd detection mainly counts on bioassays or nucleic acid-base approaches. In order to validate the CEVd disease, here we developed an integrated diagnostic protocol. MethodsCEVd transcripts were inoculated onto two susceptible cultivars of Solanum lycopersicum L., cv. Rutgers and cv. Double-Fortune, seedings. After inoculation, total RNAs of the two tomato cultivars were extracted to detect CEVd infection by dot blot hybridization, one-step reverse transcription PCR (one-step RT-PCR) and real-time reverse transcription PCR (real-time RT-PCR). In addition, the symptom development of both cultivars was recorded weekly. ResultsThe tomato cultivar Rutgers rather than Double-Fortune or others was selected as a suitable CEVd-indicator plant and the bio-index score was established based on epinasty, vein necrosis, leaf size reduction and stunting symptoms. In addition, the isolate of CEVd that collected from citrus field could rapidly and consistently cause the index symptoms on Rutgers. As expected, CEVd could be specifically and sensitively detected in both tomato and citrus plants by dot-blot hybridization and RT-PCR technologies, including one-step RT-PCR and real-time RT-PCR. Furthermore, we found that the levels of CEVd genomic RNA or CEVd derived small RNAs are correlated to symptom severity. ConclusionsIn this study, we developed an integrated detection method for CEVd and revealed potential underlying viroid-host interactions.

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