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Mass drug administration (MDA) with monthly dihydroartemisinin-piperaquine (DHA-PQP) appears useful in malaria control and elimination strategies. Determining the relationship between consecutive piperaquine phosphate (PQP) exposure and its impact on QT interval prolongation is a key safety consideration for MDA campaigns. Healthy volunteers from Papua New Guinea received a 3-day course of DHA-PQP (2.1/17.1 mg/kg) monthly for 3 consecutive months in a single arm longitudinal study. Plasma PQP concentrations were measured after the third dose of each course (at 52-54 h) and at 0 h of course 3. Twelve-lead electrocardiographic readings were conducted at 0 h, 48 h, 52 h, and day 7 of each course. QT interval corrected by Fridericia's formula (QTcF) was measured at each time point. A pharmacokinetic-pharmacodynamic model using nonlinear mixed effects models was developed to correlate PQP concentrations with QTcF. Ten thousand female and 10,000 male individuals were simulated at each treatment course. Eighty-two participants were included; mean age was 28.3 years (standard deviation [SD] +/- 12.3 years), and 36 (44%) were female. Pharmacokinetic-pharmacodynamic models were determined with 290 PQP concentrations and 868 QTcF observations. The average baseline QTcF was 392 ms with a between-subject variability SD +/- 14.4 ms and between-occasion variability SD +/- 3.64 ms. From the population modeled, only 0.08% of males and 0.45% of females would be at risk of an absolute QTcF of >500 ms. DHA-PQP is safe at standard doses in consecutive months, and the likelihood of severe cardiac events occurring during an MDA campaign is very low. This study has been registered at ClinicalTrials.gov under identifier NCT02605720.

COVID-19 affects children to a lesser extent than adults but they can still get infected and transmit SARS-CoV-2 to their contacts. Field deployable non-invasive sensitive diagnostic techniques are needed to evaluate the infectivity dynamics of SARS-CoV-2 in pediatric populations and guide public health interventions, particularly if this population is not fully vaccinated. We evaluated the utility of high-throughput Luminex assays to quantify saliva IgM, IgA and IgG antibodies against five SARS-CoV-2 spike (S) and nucleocapsid (N) antigens in a contacts and infectivity longitudinal study in 122 individuals (52 children and 70 adults). We compared saliva versus serum/plasma samples in infected children and adults diagnosed by weekly RT-PCR over 35 days (n=62), and those who consistently tested negative over the same follow up period (n=60), in the Summer of 2020 in Barcelona, Spain. Saliva antibody levels in SARS-CoV-2 RT-PCR positive individuals were significantly higher than in negative individuals and correlated with those measured in sera/plasmas. Asymptomatic infected individuals had higher levels of anti-S IgG than symptomatic individuals, suggesting a protective anti-disease role for antibodies. Higher anti-S IgG and IgM levels in serum/plasma and saliva, respectively, in infected children compared to infected adults could also be related to stronger clinical immunity in them. Among infected children, males had higher levels of saliva IgG to N and RBD than females. Despite overall correlation, individual clustering analysis suggested that responses that may not be detected in blood could be patent in saliva, and vice versa. In conclusion, measurement of SARS-CoV-2-specific saliva antibodies should be considered as a complementary non-invasive assay to serum/plasma to determine COVID-19 prevalence and transmission in pediatric populations before and after vaccination campaigns. The project has been funded by Stavros Niarchos Foundation (SNF), Banco Santander and other private donors of KidsCorona, and Fundació Privada Daniel Bravo Andreu. RR had the support of the Health Department, Catalan Government (PERIS SLT017/20/000224). Development of SARS-CoV-2 reagents was partially supported by the NIAID Centers of Excellence for Influenza Research and Surveillance (CEIRS) contract HHSN272201400008C. ISGlobal receives support from the Spanish Ministry of Science and Innovation through the “Centro de Excelencia Severo Ochoa 2019-2023” Program (CEX2018-000806-S), and support from the Generalitat de Catalunya through the CERCA Program. CISM is supported by the Government of Mozambique and the Spanish Agency for International Development (AECID). Peer Reviewed Article signat per 20 autors/es: Carlota Dobaño (1,2), Selena Alonso (1), Marta Vidal (1), Alfons Jiménez (1,3), Rocío Rubio (1), Rebeca Santano (1), Diana Barrios (1), Gemma Pons Tomas (4), María Melé Casas (4), María Hernández García (4), Mònica Girona-Alarcón (5,6), Laura Puyol (1), Barbara Baro (1), Pere Millat-Martínez (1), Sara Ajanovic (1), Núria Balanza (1), Sara Arias (1), Natalia Rodrigo Melero (7), Carlo Carolis (7), Aleix García-Miquel (8), Elisenda Bonet-Carné (8,9,10), Joana Claverol (5,11), Marta Cubells (5,11), Claudia Fortuny (5,12), Victoria Fumadó (5,12), Anna Codina (13), Quique Bassat (1,3,4,14,15), Carmen Muñoz-Almagro (3,5,16,17), Mariona Fernández de Sevilla (3,4,5), Eduard Gratacós (8,9,18), Luis Izquierdo (1,2), Juan José García-García (3,4,5), Ruth Aguilar (1), Iolanda Jordan (3,5,6) and Gemma Moncunill (1,2) // (1) ISGlobal, Hospital Clínic - Universitat de Barcelona, Barcelona, Spain, (2) Consorcio de Investigación Biomédica en Red (CIBER) de Enfermedades Infecciosas, Madrid, Spain, (3) Consorcio de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain, (4) Pediatrics Department, Hospital Sant Joan de Déu, Universitat de Barcelona, Esplugues, Spain, (5) Institut de Recerca Sant Joan de Déu, Esplugues, Spain, (6) Paediatric Intensive Care Unit, Hospital Sant Joan de Déu, Universitat de Barcelona, Barcelona, Spain, (7) Biomolecular Screening and Protein Technologies Unit, Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, Spain, (8) Fetal Medicine Research Center (Hospital Clínic and Hospital Sant Joan de Déu), Universitat de Barcelona, Barcelona, Spain, (9) Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain, (10) Universitat Politècnica de Catalunya, BarcelonaTech, Barcelona, Spain, (11) Fundació Sant Joan de Déu, Barcelona, Spain, (12) Infectious Diseases Department, Hospital Sant Joan de Déu, Barcelona, Spain, (13) Biobank Hospital Sant Joan de Déu, Barcelona, Spain, (14) Centro de Investigação em Saúde de Manhiça (CISM), Maputo, Mozambique, (15) Catalan Institution for Research and Advanced Studies (ICREA), Barcelona, Spain, (16) Department of Medicine, Universitat Internacional de Catalunya, Barcelona, Spain, (17) Molecular Microbiology Department, Hospital Sant Joan de Déu, Esplugues, Spain, (18) Center for Biomedical Research on Rare Diseases (CIBER-ER), Madrid, Spain

Background: During the COVID-19 pandemic, lockdown strategies have been widely used to contain SARS-CoV-2 virus spread. Children and adolescents are especially vulnerable to suffering psychological effects as result of such measures. In Spain, children were enforced to a strict home lockdown for 42 days during the first wave. Here, we studied the effects of lockdown in children and adolescents through an online questionnaire.Methods: A cross-sectional study was conducted in Spain using an open online survey from July (after the lockdown resulting from the first pandemic wave) to November 2020 (second wave). We included families with children under 16 years-old living in Spain. Parents answered a survey regarding the lockdown effects on their children and were instructed to invite their children from 7 to 16 years-old (mandatory scholar age in Spain) to respond a specific set of questions. Answers were collected through an application programming interface system, and data analysis was performed using R.Results: We included 1,957 families who completed the questionnaires, covering a total of 3,347 children. The specific children's questionnaire was completed by 167 kids (7–11 years-old), and 100 adolescents (12–16 years-old). Children, in general, showed high resilience and capability to adapt to new situations. Sleeping problems were reported in more than half of the children (54%) and adolescents (59%), and these were strongly associated with less time doing sports and spending more than 5 h per day using electronic devices. Parents perceived their children to gain weight (41%), be more irritable and anxious (63%) and sadder (46%). Parents and children differed significantly when evaluating children's sleeping disturbances.Conclusions: Enforced lockdown measures and isolation can have a negative impact on children and adolescent's mental health and well-being. In future waves of the current pandemic, or in the light of potential epidemics of new emerging infections, lockdown measures targeting children, and adolescents should be reconsidered taking into account their infectiousness potential and their age-specific needs, especially to facilitate physical activity and to limit time spent on electronic devices.