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Sarah Wulf Hanson; Cristiana Abbafati; Joachim G Aerts; Ziyad Al-Aly; Charlie Ashbaugh; Tala Ballouz; Oleg Blyuss; Polina Bobkova; Gouke Bonsel; Svetlana Borzakova; Danilo Buonsenso; Denis Butnaru; Austin Carter; Helen Chu; Cristina De Rose; Mohamed Mustafa Diab; Emil Ekbom; Maha El Tantawi; Victor Fomin; Robert Frithiof; Aysylu Gamirova; Petr V Glybochko; Juanita A. Haagsma; Shaghayegh Haghjooy Javanmard; Erin B Hamilton; Gabrielle Harris; Majanka H Heijenbrok-Kal; Raimund Helbok; Merel E Hellemons; David Hillus; Susanne M Huijts; Michael Hultstrom; Waasila Jassat; Florian Kurth; Ing-Marie Larsson; Miklos Lipcsey; Chelsea Liu; Callan D Loflin; Andrei Malinovschi; Wenhui Mao; Lyudmila Mazankova; Denise McCulloch; Dominik Menges; Noushin Mohammadifard; Daniel Munblit; Nikita A Nekliudov; Osondu Ogbuoji; Ismail M Osmanov; Jose L. Penalvo; Maria Skaalum Petersen; Milo A Puhan; Mujibur Rahman; Verena Rass; Nickolas Reinig; Gerard M Ribbers; Antonia Ricchiuto; Sten Rubertsson; Elmira Samitova; Nizal Sarrafzadegan; Anastasia Shikhaleva; Kyle E Simpson; Dario Sinatti; Joan B Soriano; Ekaterina Spiridonova; Fridolin Steinbeis; Andrey A Svistunov; Piero Valentini; Brittney J van de Water; Rita van den Berg-Emons; Ewa Wallin; Martin Witzenrath; Yifan Wu; Hanzhang Xu; Thomas Zoller; Christopher Adolph; James Albright; Joanne O Amlag; Aleksandr Y Aravkin; Bree L Bang-Jensen; Catherine Bisignano; Rachel Castellano; Emma Castro; Suman Chakrabarti; James K Collins; Xiaochen Dai; Farah Daoud; Carolyn Dapper; Amanda Deen; Bruce B Duncan; Megan Erickson; Samuel B Ewald; Alize J Ferrari; Abraham D. Flaxman; Nancy Fullman; Amiran Gamkrelidze; John R Giles; Gaorui Guo; Simon I Hay; Jiawei He; Monika Helak; Erin N Hulland; Maia Kereselidze; Kris J Krohn; Alice Lazzar-Atwood; Akiaja Lindstrom; Rafael Lozano; Beatrice Magistro; Deborah Carvalho Malta; Johan Mansson; Ana M Mantilla Herrera; Ali H Mokdad; Lorenzo Monasta; Shuhei Nomura; Maja Pasovic; David M Pigott; Robert C Reiner Jr.; Grace Reinke; Antonio Luiz P Ribeiro; Damian Francesco Santomauro; Aleksei Sholokhov; Emma Elizabeth Spurlock; Rebecca Walcott; Ally Walker; Charles Shey Wiysonge; Peng Zheng; Janet Prvu Bettger; Christopher JL Murray; Theo Vos.
Preprint in English | medRxiv | ID: ppmedrxiv-22275532

ABSTRACT

ImportanceWhile much of the attention on the COVID-19 pandemic was directed at the daily counts of cases and those with serious disease overwhelming health services, increasingly, reports have appeared of people who experience debilitating symptoms after the initial infection. This is popularly known as long COVID. ObjectiveTo estimate by country and territory of the number of patients affected by long COVID in 2020 and 2021, the severity of their symptoms and expected pattern of recovery DesignWe jointly analyzed ten ongoing cohort studies in ten countries for the occurrence of three major symptom clusters of long COVID among representative COVID cases. The defining symptoms of the three clusters (fatigue, cognitive problems, and shortness of breath) are explicitly mentioned in the WHO clinical case definition. For incidence of long COVID, we adopted the minimum duration after infection of three months from the WHO case definition. We pooled data from the contributing studies, two large medical record databases in the United States, and findings from 44 published studies using a Bayesian meta-regression tool. We separately estimated occurrence and pattern of recovery in patients with milder acute infections and those hospitalized. We estimated the incidence and prevalence of long COVID globally and by country in 2020 and 2021 as well as the severity-weighted prevalence using disability weights from the Global Burden of Disease study. ResultsAnalyses are based on detailed information for 1906 community infections and 10526 hospitalized patients from the ten collaborating cohorts, three of which included children. We added published data on 37262 community infections and 9540 hospitalized patients as well as ICD-coded medical record data concerning 1.3 million infections. Globally, in 2020 and 2021, 144.7 million (95% uncertainty interval [UI] 54.8-312.9) people suffered from any of the three symptom clusters of long COVID. This corresponds to 3.69% (1.38-7.96) of all infections. The fatigue, respiratory, and cognitive clusters occurred in 51.0% (16.9-92.4), 60.4% (18.9-89.1), and 35.4% (9.4-75.1) of long COVID cases, respectively. Those with milder acute COVID-19 cases had a quicker estimated recovery (median duration 3.99 months [IQR 3.84-4.20]) than those admitted for the acute infection (median duration 8.84 months [IQR 8.10-9.78]). At twelve months, 15.1% (10.3-21.1) continued to experience long COVID symptoms. Conclusions and relevanceThe occurrence of debilitating ongoing symptoms of COVID-19 is common. Knowing how many people are affected, and for how long, is important to plan for rehabilitative services and support to return to social activities, places of learning, and the workplace when symptoms start to wane. Key PointsO_ST_ABSQuestionC_ST_ABSWhat are the extent and nature of the most common long COVID symptoms by country in 2020 and 2021? FindingsGlobally, 144.7 million people experienced one or more of three symptom clusters (fatigue; cognitive problems; and ongoing respiratory problems) of long COVID three months after infection, in 2020 and 2021. Most cases arose from milder infections. At 12 months after infection, 15.1% of these cases had not yet recovered. MeaningThe substantial number of people with long COVID are in need of rehabilitative care and support to transition back into the workplace or education when symptoms start to wane.

2.
Preprint in English | medRxiv | ID: ppmedrxiv-22272926

ABSTRACT

BackgroundTo investigate the impact of the COVID-19 pandemic and infection prevention measures on children visiting emergency departments across Europe. MethodsRoutine health data were extracted retrospectively from electronic patient records of children aged <16 years, presenting to 38 emergency departments (ED) in 16 European countries for the period January 2018 - May 2020, using predefined and standardized data domains. Observed and predicted numbers of ED attendances were calculated for the period February 2020 to May 2020. Poisson models and incidence rate ratios (IRR) were used to compare age groups, diagnoses and outcomes. FindingsReductions in pediatric ED attendances, hospital admissions and high triage urgencies were seen in all participating sites. ED attendances were relatively higher in countries with lower SARS-CoV-2 prevalence (incidence rate ratio (IRR) 2{middle dot}62, 95% CI 2{middle dot}19 to 3{middle dot}13) and in children aged >12 months (12-<24 months IRR 0{middle dot}89, 95% CI 0{middle dot}86 to 0{middle dot}92; 2-<5years IRR 0{middle dot}84, 95% CI 0{middle dot}82 to 0{middle dot}87; 5-<12 years IRR 0{middle dot}74, 95% CI 0{middle dot}72 to 0{middle dot}76; 12-<16 years IRR 0{middle dot}74, 95% CI 0{middle dot}71 to 0{middle dot}77; vs. age <12 months as reference group). The impact on pediatric intensive care admissions (IRR 1{middle dot}30, 95% CI 1{middle dot}16 to 1{middle dot}45) was not as great as the impact on general admissions. Lower triage urgencies were reduced more than higher triage urgencies (urgent triage IRR 1{middle dot}10, 95% CI 1{middle dot}08 to 1{middle dot}12; emergent and very urgent triage IRR 1{middle dot}53, 95% CI 1{middle dot}49 to 1{middle dot}57; vs. non-urgent triage category). Reductions were highest and sustained throughout the study period for children with communicable infectious diseases. InterpretationReductions in ED attendances were seen across Europe during the first COVID-19 lockdown period. More severely ill children continued to attend hospital more frequently compared to those with minor injuries and illnesses, although absolute numbers fell. FundingRGN was supported by National Institute of Health Research, award number ACL-2018-021-007. Trial registryISRCTN91495258

3.
Preprint in English | medRxiv | ID: ppmedrxiv-21256539

ABSTRACT

There is increasing reporting by patients organization and researchers of long covid (or post-acute sequelae of SARS-CoV-2 - PASC), characterized by symptoms such as fatigue, dyspnea, chest pain, cognitive and sleeping disturbances, arthralgia and decline in quality of life. Immune system dysregulation with a hyperinflammatory state, direct viral toxicity, endothelial damage and microvascular injury have been proposed as pathologenic mechanisms. Recently, cohorts of children with PASC have been reported in Italy, Sweden and Russia. However, immunological studies of children with PASC have never been performed. In this study, we documented significant immunologic differences between children that completely recovered from acute infection and those with PASC, providing the first objective laboratory sign of the existence of PASC in children.

4.
Preprint in English | medRxiv | ID: ppmedrxiv-21256110

ABSTRACT

BackgroundThe long-term sequelae of coronavirus disease 2019 (Covid-19) in children remain poorly characterised. This study aimed to assess long-term outcomes in children previously hospitalised with Covid-19 and associated risk factors. MethodsThis is a prospective cohort study of children ([≤]18 years old) admitted with confirmed Covid-19 to Z.A. Bashlyaeva Childrens Municipal Clinical Hospital in Moscow, Russia. Children admitted to the hospital during the first wave of the pandemic, between April 2, 2020 and August 26, 2020, were included. Telephone interview using the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) Covid-19 Health and Wellbeing paediatric follow up survey. Persistent symptoms (>5 months) were further categorised by system(s) involved. FindingsOverall, 518 of 853 (61%) of eligible children were available for the follow-up assessment and included in the study. Median age was 10.4 years (IQR, 3-15.2) and 270 (52.1%) were girls; median follow-up since hospital discharge was 256 (223-271) days. At the time of the follow-up interview 126 (24.3%) participants reported persistent symptoms among which fatigue (53, 10.7%), sleep disturbance (36, 6.9%,) and sensory problems (29, 5.6%) were the most common. Multiple symptoms were experienced by 44 (8.4%) participants. Risk factors for persistent symptoms were: age "6-11 years" (odds ratio 2.74 (95% confidence interval 1.37 to 5.75) and "12-18 years" (2.68, 1.41 to 5.4), and a history of allergic diseases (1.67, 1.04 to 2.67). InterpretationA quarter of children experienced persistent symptoms months after hospitalization with acute covid-19 infection, with almost one in ten experiencing multi-system involvement. Older age and allergic diseases were associated with higher risk of persistent symptoms at follow-up. Our findings highlight the need for replication and further investigation of potential mechanisms as well as clinical support to improve long term outcomes in children. FundingNone. O_TEXTBOXResearch in contextO_ST_ABSEvidence before this studyC_ST_ABSEvidence suggests that Covid-19 may result in short- and long-term consequences to health. Studies in children and adolescents are limited and available evidence is scarce. We searched Embase for publications from inception to April, 25, 2021, using the following phrases or combinations of phrases "post-covid condition" or "post-covid syndrome" or "covid sequalae" or "post-acute covid" or "long covid" or "long hauler" with "pediatric*" or "paediatric*" or "child*" or "infant*" or "newborn*" or "toddler*" or "neonate*" or "neonatal" or "adolescent*" or "teen*". We found small case series and small cohort studies looking at Covid-19 consequences in children. No large cohort studies of previously hospitalised children, assessing symptom duration, categorisation or attempting multivariable analyses to identify independent risk factors for long Covid development were identified. Added value of this studyTo our knowledge, this is the largest cohort study with the longest follow-up since hospital discharge of previously hospitalised children. We found that even months after discharge from the hospital, approximately a quarter of children experience persistent symptoms with one in ten having multi-system involvement. Older age and allergic diseases are associated with Covid-19 consequences. Parents of some children report emotional and behavioural changes in their children after Covid-19. Implications of all the available evidenceOur findings highlight the need for continued global research of Covid-19 consequences in the paediatric population. Older children admitted to the hospital should be carefully monitored upon discharge. Large, controlled studies aiming to identify risk groups and potential intervention strategies are required to fill knowledge gaps. C_TEXTBOX

5.
Preprint in English | medRxiv | ID: ppmedrxiv-21251212

ABSTRACT

Data from adult studies how that COVID-19 is more severe in men than women. However, no data are available for the pediatric population. For this reason, we performed this study aiming to understand if sex influenced disease severity and outcomes in a large cohort of latin-american children with COVID-19 and Multisystem Inflammatory Syndrome (MIS-C). We found that a higher percentage of male children developed MIS-C (8.9% vs 5% in females) and died (1.2% and 0.4% in females), although on multivariate adjusted analyses the only statistically significant difference was found in need of hospitalization, with females less frequently admitted compared with boys (25.6% vs 35.4%). This data are preliminary and need further independent studies to better assess the role of sex.

6.
Preprint in English | medRxiv | ID: ppmedrxiv-21250375

ABSTRACT

There is increasing evidence that adult patients diagnosed with acute COVID-19 suffer from Long COVID initially described in Italy. To date, data on Long COVID in children are lacking. We assessed persistent symptoms in pediatric patients previously diagnosed with COVID-19. More than a half reported at least one persisting symptom even after 120 days since COVID-19, with 42.6% being impaired by these symptoms during daily activities. Symptoms like fatigue, muscle and joint pain, headache, insomnia, respiratory problems and palpitations were particularly frequent, as also described in adults. The evidence that COVID-19 can have long-term impact children as well, including those with asymptomatic/paucisymptomatic COVID-19, highlight the need for pediatricians, mental health experts and policy makers of implementing measures to reduce impact of the pandemic on childs health.

7.
Preprint in English | medRxiv | ID: ppmedrxiv-20243568

ABSTRACT

BackgroundTo date, there are no comprehensive data on antibiotic use in children with COVID-19 and Multisystem Inflammatory Syndrome (MIS-C). MethodsMulticenter cohort study from 5 Latin American countries. Children 17 years of age or younger with microbiologically confirmed SARS-CoV-2 infection or fulfilling MIS-C definition were included. Antibiotic prescriptions were collected and factors associated with their use were calculated. Findings990 children were included, with a median age of 3 years (interquartile range 1-9). Of these, 69 (7.0%) were diagnosed with MIS-C. The prevalence of antibiotic use was 24.5% (n = 243). MIS-C with (OR = 45.48) or without (OR = 10.35) cardiac involvement, provision of intensive care (OR = 9.60), need for hospital care (OR = 6.87), pneumonia and/or ARDS detected through chest X-rays (OR = 4.40), administration of systemic corticosteroids (OR = 4.39), oxygen support, mechanical ventilation or CPAP (OR = 2.21), pyrexia (OR = 1.84), and female sex (OR = 1.50) were independently associated with increased use of antibiotics. On the contrary, lower respiratory tract infections without radiologic evidence of pneumonia/ARDS and not requiring respiratory support (OR = 0.34) were independently associated with decreased use of antibiotics. There was significant variation in antibiotic use across the hospitals. ConclusionsOur study showed a relatively high rate of antibiotic prescriptions in children with COVID-19 and in particular in those with severe disease or MIS-C. Importantly, we found a significant variation in reasons for prescriptions of antibiotics and type of chosen therapies, as well in hospital practices, highlighting current uncertainties and lack of guidelines for the recognition of bacterial infections in children with COVID-19. Prospective studies are needed to provide better evidence on the recognition and management of bacterial infections in COVID-19 children. What is knownCOVID-19 may worsen antibiotic prescription practices What this newCOVID-19 and MIS-C children frequently received antibiotics There was a wide variation in antibiotic prescriptions among institutions, highlighting the lack of practicle guidelines in the use of antibiotics in children with COVID-19

8.
Preprint in English | medRxiv | ID: ppmedrxiv-20225714

ABSTRACT

Growing evidences are showing the potential indirect effects of COVID-19 on the health systems of low-resource settings, where diseases such as Tuberculosis, HIV and Malaria represent major killers. Therefore, we performed a retrospective study aimed to evaluate the impact of COVID-19 on Malaria programs in a peripheral region of Sierra Leone, previously involved by the Ebola outbreak in 2015, when malaria care have been impaired since local health systems were overwhelmed by Ebola cases. During COVID-19 in Sierra Leone, we did not notice a drop in malaria diagnosis in children, suggesting that a proactive approach in the management of malaria in endemic countries during COVID-19 may have had a positive impact. A comprehensive approach that include also educational activities to sensitize the local population, was useful to guarantee successful malaria diagnosis and treatment, and prevents excess of malaria deaths due to potential disruption of the local health systems related to the SARS-CoV-2 pandemic. Contribution to the fieldwe performed a retrospective study aimed to evaluate the impact of COVID-19 on Malaria programs in a peripheral region of Sierra Leone, previously involved by the Ebola outbreak in 2015, when malaria care have been impaired since local health systems were overwhelmed by Ebola cases. During COVID-19 in Sierra Leone, we did not notice a significant change in the middle term period in malaria diagnosis in children, suggesting that a proactive approach in the management of malaria in endemic countries during COVID-19 may have had a positive impact. A comprehensive approach that include also educational activities to sensitize the local population, was useful to guarantee successful malaria diagnosis and treatment, and prevents excess of malaria deaths due to potential disruption of the local health systems related to the SARS-CoV-2 pandemic. Funding statementnothing to declare Ethics statementsO_ST_ABSStudies involving animal subjectsC_ST_ABSGenerated Statement: No animal studies are presented in this manuscript. Studies involving human subjectsGenerated Statement: The studies involving human participants were reviewed and approved by Bureh Town Community Hospital. Written informed consent to participate in this study was provided by the participants legal guardian/next of kin. Inclusion of identifiable human dataGenerated Statement: No potentially identifiable human images or data is presented in this study. Data availability statementGenerated Statement: The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

9.
Preprint in English | medRxiv | ID: ppmedrxiv-20210328

ABSTRACT

IntroductionThe impact of school opening on the SARS-CoV-2 pandemic is still unknown. This study aims to provide preliminary information about the number of SARS-CoV-2 cases among students attending Italian schools. MethodsData are extracted and analysed from an open access, online dataset that monitor, on a daily basis, media news about SARS-CoV-2 infections of students attending Italian schools ResultsAs of 5 October 2020, a total of 1350 cases of SARS-CoV-2 infections have been registered in the Italian territory schools (involving 1059 students, 145 teachers and 146 other school members), for a total of 1212 out of 65104 (1.8%) Italian schools involved. National schools reported only 1 case of SARS-CoV-2 infection in more than 90% of cases, and only in one high school a cluster of more than 10 cases have been described (P 0.015). The detection of one or more SARS-CoV-2 infections leaded to the closure of 192 (14.2%) entire schools, more frequently nursery/kindergartens (P<0.0005). DiscussionOur preliminary data support low transmission of SARS-CoV-2 within schools, at least among younger students. However, entire schools are frequently closed in the fear of larger outbreaks. Continuous monitoring of school settings, hopefully through daily updated open access datasets, are needed to better understand the impact of schools on the pandemic, and provide guidelines that better consider different risks within different age groups.

10.
Preprint in English | medRxiv | ID: ppmedrxiv-20184242

ABSTRACT

BackgroundTo date, there are no comprehensive data on pediatric COVID-19 from Latin America. This study aims to assess COVID-19 and Multisystem Inflammatory Syndrome (MIS-C) in Latin American children, in order to appropriately plan and allocate resources to face the pandemic on a local and International lever MethodsAmbispective multicentre cohort study from five Latin American countries. Children aged 18 years or younger with microbiologically confirmed SARS-CoV-2 infection were included. Findings409 children were included, with a median age of 53.0 years (IQR 0.6-9.0). Of these, 95 191 (23.2%) were diagnosed with MIS-C. 191 (46.7%) children were admitted to hospital and 52 (12.7%) required admission to a Pediatric Intensive Care Unite (PICU). 92 (22.5%) patients required oxygen support: 8 (2%) were started on continuous positive airway pressure (CPAP) and 29 (7%) on mechanical ventilation. 35 (8.5%) patients required inotropic support. The following factors were associated with PICU admission: pre-existing medical condition (P < 0.0001), immunodeficiency (P = 0.01), lower respiratory tract infection (P< 0.0001), gastrointestinal symptoms (P = 0.006), radiological changes suggestive of pneumonia and acute respiratory distress syndrome (P< 0.0001), low socioeconomic conditions (P 0.009). ConclusionsThis study shows a generally more severe form of COVID-19 and a high number of MIS-C in Latin American children, compared with studies from China, Europe and North America, and support current evidence of a more severe disease in Latin/Hyspanic children or in people of lower socioeconomic level. The findings highlight an urgent need of more data of COVID-19 in South America.

11.
Preprint in English | medRxiv | ID: ppmedrxiv-20169912

ABSTRACT

Wheather children are easily susceptible to SARS-CoV-2 infection is still a debated question and a currently a hot topic, particularly in view of important decisions on school opening. For this reason, we decide to describe preliminary data showing the prevalence of anti-SARS-CoV-2 IgG in children with known household exposure to SARS-CoV-2. Our report shows that household transmission of SARS-CoV-2 is high in both adults and children, with similar rates of SARS-CoV-2 IgG in all age groups, including the younger children. A total of 44 out of 80 household contacts (55%) of index patients had anti SARS-CoV-2 IgG. In particular, 16 (59,26%) adult partners had IgG antibodies compared with 28 (52,83%) of pediatric contacts (P > 0.05). Among the pediatric population, children [≥] 5 years of age had similar probability of having SARS-CoV-2 IgG (21/39, 53.8%) compared with those < 5 years (7/14, 50%) (P > 0.05). Adult partners and children also had a probability of having SARS-CoV-2 IgG. Interestingly, 35.7% of children and 33.3% of adults with SARS-CoV-2 IgG were previously diagnosed as COVID-19 cases. Since this evidence of high rate of IgG in children exposed to SARS-CoV-2 has public health implication, with this comment we highlight the need of establishing appropriate guidelines for school opening and other social activities related to childhood.

12.
Preprint in English | medRxiv | ID: ppmedrxiv-20075481

ABSTRACT

Study objectiveWe aimed to describe the preparedness and response to the COVID-19 pandemic in referral EDs caring for children across Europe. MethodsWe did a cross-sectional point prevalence survey, which was developed and disseminated through the pediatric emergency medicine research networks for Europe (REPEM) and the United Kingdom and Ireland (PERUKI). We included a pre-determined number of centers based on each country population: five to ten EDs for countries with > 20 million inhabitants and one to five EDs for the other countries. ED directors or named delegates completed the survey between March 20th and 21st to report practice in use one month after the outbreak in Northern Italy. We used descriptive statistics to analyse data. ResultsOverall 102 centers from 18 countries completed the survey: 34% did not have an ED contingency plan for pandemics and 36% had never had simulations for such events. Wide variation on PPE items was shown for recommended PPE use at pre-triage and for patient assessment, with 62% of centers experiencing shortage in one or more PPE items. COVID-19 positive ED staff was reported in 25% of centers. Only 17% of EDs had negative pressure isolation rooms. ConclusionWe identified variability and gaps in preparedness and response to the COVID-19 epidemic across European referral EDs for children. Early availability of a documented contingency plan, provision of simulation training, appropriate use of PPE, and appropriate isolation facilities emerged as key factors that should be optimized to improve preparedness and inform responses to future pandemics.

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