COVID-19 in patients with rheumatic diseases in northern Italy: a single-centre observational and case–control study

Abstract: BACKGROUND: The highest number of COVID-19 cases in Italy have been reported in Lombardy, a region in northern Italy. We aimed to analyse the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients with rheumatic and musculoskeletal diseases living in a district of Lombardy with a high prevalence of COVID-19. METHODS: We did a single-centre observational study at the Azienda Socio Sanitaria Territoriale (ASST) Spedali Civili of Brescia, Italy. We collected data from patients with rheumatic and musculoskeletal diseases enrolled in our outpatient clinic to identify confirmed or possible cases of SARS-CoV-2 infection. Data were collected through a survey that was administered via telephone or in the outpatient clinic by rheumatologists. We also did a case–control study of all patients with confirmed COVID-19 pneumonia and rheumatic and musculoskeletal diseases who were admitted to the ASST Spedali Civili of Brescia during the study period. Cases were matched by age, sex, and month of hospital admission to at least two controls admitted to the same hospital for COVID-19 pneumonia during the study period. FINDINGS: Between Feb 24 and May 1, 2020, we collected data from 1525 patients with rheumatic and musculoskeletal diseases: 117 (8%) presented with symptoms that were compatible with COVID-19. 65 patients had a swab confirmation of SARS-CoV-2 infection, whereas 52 presented with a spectrum of symptoms indicative of COVID-19 but were not swab tested. Patients with confirmed COVID-19 were older than those with suspected COVID-19 (median age 68 [IQR 55–76] years vs 57 [49–67] years; p=0·0010) and more likely to have arterial hypertension (33 [51%] vs 14 [27%] patients; odds ratio [OR] 2·8 [95% CI 1·3–6·1]; p=0·031) and obesity (11 [17%] vs 1 [2%]; OR 11·0 [1·3–83·4]; p=0·0059). We found no differences in rheumatological disease or background therapy between confirmed and suspected COVID-19 cases. 47 (72%) of the 65 patients with confirmed COVID-19 developed pneumonia that required admission to hospital. 12 (10%) deaths occurred among the 117 patients with confirmed or suspected COVID-19 (ten in those with confirmed COVID-19 and two in those with suspected COVID-19). Deceased patients with confirmed COVID-19 were older than survivors (median age 78·8 years [IQR 75·3–81·3] vs 65·5 years [53·3–74·0]; p=0·0002). We observed no differences in sex, comorbidities, or therapies between the deceased patients and survivors. The case–control study comprised 26 patients with rheumatic and musculoskeletal diseases and COVID-19 pneumonia and 62 matched controls. We found no significant differences between cases and controls in duration of COVID-19 symptoms before admission, duration of stay in hospital, or the local chest X-ray scoring system. Glucocorticoids were used for severe respiratory manifestations related to lung involvement in 17 (65%) of 26 cases and tocilizumab in six (23%) of 26; thrombotic events occurred in four (15%) of 26 cases. Four (15%) of 26 cases and six (10%) of 62 controls died during the study period. INTERPRETATION: In this cohort of patients with rheumatic and musculoskeletal diseases in a geographical region with a high prevalence of COVID-19, a poor outcome from COVID-19 seems to be associated with older age and the presence of comorbidities rather than the type of rheumatic disease or the degree of pharmacological immunosuppression. FUNDING: None.


Systemic steroids in patients with COVID-19: pros and contras, an endocrinological point of view


Response to letter Steroids: a therapeutic option for COVID-19 pneumonia patients with end stage-stage renal disease


Clinical Management of Adult Coronavirus Infection Disease 2019 (COVID-19) Positive in the Setting of Low and Medium Intensity of Care: a Short Practical Review

Abstract: Coronavirus disease 2019 (COVID-2019) is a viral infection which is rapidly spreading on a global scale and causing a severe acute respiratory syndrome that affects today about four and a half million registered cases of people around the world. The aim of this narrative review is to provide an urgent guidance for the doctors who take care of these patients. Recommendations contained in this protocol are based on limited, non-definitive, evidence and experience-based opinions about patients with low and medium intensity of care. A short guidance on the management of COVID-19 is provided for an extensive use in different hospital settings. The evidence-based knowledge of COVID-19 is rapidly evolving, and we hope that, in the near future, a definitive and most efficacious treatment will be available including a specific vaccine for SARS-CoV-2.


Adjuvant corticosteroid therapy for critically ill patients with COVID-19


Role of corticosteroid in the management of COVID-19: A systemic review and a Clinician’s perspective

Abstract: BACKGROUND AND AIMS: Interest in corticosteroid therapy in COVID-19 has been rekindled after the results from Randomized Evaluation of COVid-19 thERapY (RECOVERY) Trial. However, the World health Organization has not recommended corticosteroid in the treatment of COVID-19. We sought to conduct a systematic review on the role of corticosteroid in the management of patients of COVID-19. METHODS: A systematic electronic search of PubMed, Cochrane and MedRxiv database using specific keywords was made up till June 17, 2020. Full text of all the original articles with supplementary appendix that fulfilled the inclusion criteria were retrieved and a detailed analysis of results were represented. RESULTS: Of the 5 studies (4 retrospective studies and 1 quasi-prospective study) conducted for evaluating the role of corticosteroids, 3 studies have shown benefit, while 2 studies shown no benefit and there was a suggestion of significant harm in critical cases in one sub-study. RECOVERY trial is the only randomized controlled trial that has shown a significant reduction of death by 35% in ventilated patients and by 20% amongst patients on supplemental oxygen therapy with the dexamethasone, although no benefit was observed in mild cases. CONCLUSIONS: While the results from retrospective studies are heterogenous and difficult to infer of a definitive protective benefit with corticosteroids, RECOVERY trial found a significantly better outcome with dexamethasone, mostly in severe cases. Nonetheless, more studies are needed to replicate the outcome shown in RECOVERY trial for a substantial conclusion.


The use of dexamethasone in the treatment of COVID-19


The curious case of COVID-19 in children


The intriguing features of COVID-19 in children and its impact on the pandemic


Children in Coronaviruses’ Wonderland: What Clinicians Need to Know

Abstract: Human coronaviruses (HCoVs) commonly cause mild upper-respiratory tract illnesses but can lead to more severe and diffusive diseases. A variety of signs and symptoms may be present, and infections can range in severity from the common cold and sore throat to more serious laryngeal or tracheal infections, bronchitis, and pneumonia. Among the seven coronaviruses that affect humans (SARS)-CoV, the Middle East respiratory syndrome (MERS)-CoV, and the most recent coronavirus disease 2019 (COVID-19) represent potential life-threatening diseases worldwide. In adults, they may cause severe pneumonia that evolves in respiratory distress syndrome and multiorgan failure with a high mortality rate. Children appear to be less susceptible to develop severe clinical disease and present usually with mild and aspecific symptoms similar to other respiratory infections typical of childhood. However, some children, such as infants, adolescents, or those with underlying diseases may be more at-risk categories and require greater caution from clinicians. Available data on pediatric coronavirus infections are rare and scattered in the literature. The purpose of this review is to provide to clinicians a complete and updated panel useful to recognize and characterize the broad spectrum of clinical manifestations of coronavirus infections in the pediatric age.


Covid-19 in children: A brief overview after three months experience.

Abstract: Severe Acute Respiratory Syndrome - Coronavirus - 2 (SARS-CoV-2) and its related Coronavirus Disease - 19 (COVID-19) has become a health emergency worldwide. The medical community has been concerned since the beginning of the outbreak about the potential impact of COVID-19 in children, especially in those with underlying chronic diseases. Fortunately, COVID-19 has been reported to be less severe in children than in adults. However, epidemiologic and clinical data are scarce. Children show unique features of SARS-CoV-2 involvement that may account for the low rate of infection and death in this age group. The purpose of this review is to summarize the most relevant evidence of COVID-19 in children highlighting similarities and differences with adults.


Coronavirus Disease 2019 (COVID-19) in adolescents: An update on current clinical and diagnostic characteristics.

Abstract: The current outbreak of infections with SARS-CoV-2 is defined as Coronavirus Disease 2019 (COVID-19). The clinical symptoms of COVID-19 include fever, fatigue, cough, breathing difficulty that may lead to respiratory distress; a small population of patients may have diarrhea, nausea or vomiting. The highest infection rate occurs in adults; however, neonates, children, and adolescents can also be infected. As the outbreak continues to spread worldwide, attention has switched toward determinants of clinical manifes- tations and disease severity. The situation surrounding the outbreak is rapidly evolving and the information and recommendations are changing as new information becomes available. This paper summarises the cur- rent findings (April 3,2020) from a systematic literature review on the current knowledge of COVID-19 in adolescents (10-19 years according to the WHO definition) and reports the preliminary epidemiological data stated by the Italian National Institute of Health.


Pediatric Acute Lung Injury Epidemiology and Natural History study: Incidence and outcome of the acute respiratory distress syndrome in children.

Abstract: OBJECTIVES The incidence and outcome of the acute respiratory distress syndrome in children are not well-known, especially under current ventilatory practices. The goal of this study was to determine the incidence, etiology, and outcome of acute respiratory distress syndrome in the pediatric population in the setting of lung protective ventilation. DESIGN A 1-yr, prospective, multicenter, observational study in 12 geographical areas of Spain (serving a population of 3.77 million ≤ 15 yrs of age) covered by 21 pediatric intensive care units. SUBJECTS All consecutive pediatric patients receiving invasive mechanical ventilation and meeting American-European Consensus Criteria for acute respiratory distress syndrome. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Data on ventilatory management, gas exchange, hemodynamics, and organ dysfunction were collected. A total of 146 mechanically ventilated patients fulfilled the acute respiratory distress syndrome definition, representing a incidence of 3.9/100,000 population ≤ 15 yrs of age/yr. Pneumonia and sepsis were the most common causes of acute respiratory distress syndrome. At the time of meeting acute respiratory distress syndrome criteria, mean PaO2/FIO2 was 99 mm Hg ± 41 mm Hg, mean tidal volume was 7.6 mL/kg ± 1.8 mL/kg predicted body weight, mean plateau pressure was 27 cm H2O ± 6 cm H2O, and mean positive end-expiratory pressure was 8.9 cm ± 2.9 cm H2O. Overall pediatric intensive care unit and hospital mortality were 26% (95% confidence interval 19.6-33.7) and 27.4% (95% confidence interval 20.8-35.1), respectively. At 24 hrs, after the assessment of oxygenation under standard ventilatory settings, 118 (80.8%) patients continued to meet acute respiratory distress syndrome criteria (PaO2/FIO2 104 mm Hg ± 36 mm Hg; pediatric intensive care units mortality 30.5%), whereas 28 patients (19.2%) had a PaO2/FIO2 >200 mm Hg (pediatric intensive care units mortality 7.1%) (p = .014). CONCLUSIONS This is the largest study to estimate prospectively the pediatric population-based acute respiratory distress syndrome incidence and the first incidence study performed during the routine application of lung protective ventilation in children. Our findings support a lower acute respiratory distress syndrome incidence and mortality than those reported for adults. PaO2/FIO2 ratios at acute respiratory distress syndrome onset and at 24 hrs after onset were helpful in defining groups at greater risk of dying (clinical trials registered with http://www.clinicaltrials.gov; NCT 01142544).


COVID-19 in Children, Pregnancy and Neonates: A Review of Epidemiologic and Clinical Features.

Abstract: The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has spread rapidly across the globe. In contrast to initial reports, recent studies suggest that children are just as likely as adults to become infected with the virus but have fewer symptoms and less severe disease. In this review, we summarize the epidemiologic and clinical features of children infected with SARS-CoV-2 reported in pediatric case series to date. We also summarize the perinatal outcomes of neonates born to women infected with SARS-CoV-2 in pregnancy. We found 11 case series including a total of 333 infants and children. Overall, 83% of the children had a positive contact history, mostly with family members. The incubation period varied between 2 and 25 days with a mean of 7 days. The virus could be isolated from nasopharyngeal secretions for up to 22 days and from stool for more than 30 days. Co-infections were reported in up to 79% of children (mainly mycoplasma and influenza). Up to 35% of children were asymptomatic. The most common symptoms were cough (48%; range 19%-100%), fever (42%; 11%-100%) and pharyngitis (30%; 11%-100%). Further symptoms were nasal congestion, rhinorrhea, tachypnoea, wheezing, diarrhea, vomiting, headache and fatigue. Laboratory test parameters were only minimally altered. Radiologic findings were unspecific and included unilateral or bilateral infiltrates with, in some cases, ground-glass opacities or consolidation with a surrounding halo sign. Children rarely needed admission to intensive care units (3%), and to date, only a small number of deaths have been reported in children globally. Nine case series and 2 case reports described outcomes of maternal SARS-CoV-2 infection during pregnancy in 65 women and 67 neonates. Two mothers (3%) were admitted to intensive care unit. Fetal distress was reported in 30% of pregnancies. Thirty-seven percent of women delivered preterm. Neonatal complications included respiratory distress or pneumonia (18%), disseminated intravascular coagulation (3%), asphyxia (2%) and 2 perinatal deaths. Four neonates (3 with pneumonia) have been reported to be SARS-CoV-2 positive despite strict infection control and prevention procedures during delivery and separation of mother and neonates, meaning vertical transmission could not be excluded.


Clinical and epidemiological characteristics of children with COVID-19.


Pediatric COVID-19: Systematic review of the literature.

Abstract: OBJECTIVES There is limited data regarding the demographics and clinical features of SARS-CoV-2 infection in children. This information is especially important as pneumonia is the single leading cause of death in children worldwide. This Systematic Review aims to elucidate a better understanding of the global impact of COVID-19 on the pediatric population. METHODS A systematic review of the literature was performed in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines to gain insight into pediatric COVID-19 epidemiology. Specifically, Pubmed and Google Scholar databases were searched to identify any relevant article with a focus on Pediatric Covid 19, Pediatric Covid-19, Pediatric SARS-COV-2, and Pediatric Coronavirus 19. References within the included articles were reviewed. All articles that met criteria where analyzed for demographics, clinical, laboratory, radiographic, treatment and outcomes data. RESULTS Ten studies including two case series and 8 retrospective chart reviews, altogether describing a total of 2914 pediatric patients with COVID-19 were included in this systematic review. Of the patients whose data was available, 56% were male, the age range was 1 day to 17 years, 79% were reported to have no comorbidities, and of the 21% with comorbidities, the most common were asthma, immunosupression, and cardiovascular disease. Of pediatric patients that were tested and positive for an infection with SARS-CoV-2, patients were asymptomatic, 14.9% of the time. Patients presented with cough (48%), fever (47%) and sore throat/pharyngitis (28.6%), more commonly than with upper respiratory symptoms/rhinorrhea/sneezing/nasal congestion (13.7%), vomiting/nausea (7.8%) and diarrhea (10.1%). Median lab values including those for WBC, lymphocyte count and CRP, were within the reference ranges with the exception of procalcitonin levels, which were slightly elevated in children with COVID-19 (median procalcitonin levels ranged from 0.07 to 0.5 ng/mL. Computed tomography (CT) results suggest that unilateral CT imaging findings are present 36% of cases while 64% of pediatric patients with COVID-19 had bilateral findings. Of the studies with age specific hospitalization data available, 27.0% of patients hospitalized were infants under 1 year of age. Various treatment regimens including interferon, antivirals, and hydroxychloroquine therapies have been trialed on the pediatric population but there are currently no studies showing efficacy of one regimen over the other. The mortality rate of children that were hospitalized with COVID-19 was 0.0018%. CONCLUSION In contrast to adults, most infected children appear to have a milder course and have better outcomes overall. Additional care may be needed for children with comorbidities and younger children. This review also suggests that unilateral CT chest imaging findings were seen in 36.4% pediatric COVID-19 patients. This is particularly concerning as the work-up of pediatric patients with cough may warrant a bronchoscopy to evaluate for airway foreign bodies. Extra precautions need to be taken with personal protective equipment for these cases, as aerosolizing procedures may be a method of viral transmission. LEVEL OF EVIDENCE 4 (Systematic Review).


Coronavirus disease 2019 (COVID-19) in children and/or adolescents: a meta-analysis.

Abstract: BACKGROUND To assess the overall prevalence of clinical signs, symptoms, and radiological findings in children and/or adolescents with COVID-19. METHODS We systematically researched in PubMed, Scopus and Web of Science databases observational studies describing COVID-19 in children and/or adolescents until April 11, 2020. Data regarding clinical and radiological features were extracted from eligible studies and meta-analysis was performed using random-effects modeling. RESULTS We examined 19 eligible studies for a total of 2855 children and/or adolescents with COVID-19. Approximately 47% of subjects had fever (95% confidence interval [CI] 22-72%; I2 = 98.6%), 37% cough (95%CI 15-63%; I2 = 98.6%), 4% diarrhea (95%CI 0-12%; I2 = 92.2%), 2% nasal congestion (95%CI 0-7%; I2 = 87.7%), 1% dyspnea (95%CI 0-7%; I2 = 91.5%) and 0% abdominal pain (95%CI 0-1%; I2 = 76.3%). Subjects presented mild symptoms in 79% (95%CI 65-91%; I2 = 93.5%) of cases, whereas only 4% (95%CI 1-9%; I2 = 76.4%) were critical. Among those with pneumonia on computed tomography, 26.4% (95%CI 13-41%; I2 = 80.8%) presented a unilateral involvement, 16% (95%CI 5-29%, I2 = 81.2%) had bilateral involvement and 9% (95%CI 0-24%; I2 = 88.7%) had interstitial pneumonia. CONCLUSIONS Children and/or adolescents tend to have a mild COVID-19 course with a good prognosis. IMPACT Compared to adults, children and/or adolescents tend to have a mild COVID-19 course with a good prognosis. This study provides new and consistence information on the clinical and radiological characteristics of COVID-19 in pediatrics. This study may help to fight COVID-19 in pediatric population.


Epidemiology, Clinical Features, and Disease Severity in Patients With Coronavirus Disease 2019 (COVID-19) in a Children's Hospital in New York City, New York.

Abstract: Importance Descriptions of the coronavirus disease 2019 (COVID-19) experience in pediatrics will help inform clinical practices and infection prevention and control for pediatric facilities. Objective To describe the epidemiology, clinical, and laboratory features of patients with COVID-19 hospitalized at a children's hospital and to compare these parameters between patients hospitalized with and without severe disease. Design, Setting, and Participants This retrospective review of electronic medical records from a tertiary care academically affiliated children's hospital in New York City, New York, included hospitalized children and adolescents (≤21 years) who were tested based on suspicion for COVID-19 between March 1 to April 15, 2020, and had positive results for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Exposures Detection of SARS-CoV-2 from a nasopharyngeal specimen using a reverse transcription-polymerase chain reaction assay. Main Outcomes and Measures Severe disease as defined by the requirement for mechanical ventilation. Results Among 50 patients, 27 (54%) were boys and 25 (50%) were Hispanic. The median days from onset of symptoms to admission was 2 days (interquartile range, 1-5 days). Most patients (40 [80%]) had fever or respiratory symptoms (32 [64%]), but 3 patients (6%) with only gastrointestinal tract presentations were identified. Obesity (11 [22%]) was the most prevalent comorbidity. Respiratory support was required for 16 patients (32%), including 9 patients (18%) who required mechanical ventilation. One patient (2%) died. None of 14 infants and 1 of 8 immunocompromised patients had severe disease. Obesity was significantly associated with mechanical ventilation in children 2 years or older (6 of 9 [67%] vs 5 of 25 [20%]; P = .03). Lymphopenia was commonly observed at admission (36 [72%]) but did not differ significantly between those with and without severe disease. Those with severe disease had significantly higher C-reactive protein (median, 8.978 mg/dL [to convert to milligrams per liter, multiply by 10] vs 0.64 mg/dL) and procalcitonin levels (median, 0.31 ng/mL vs 0.17 ng/mL) at admission (P < .001), as well as elevated peak interleukin 6, ferritin, and D-dimer levels during hospitalization. Hydroxychloroquine was administered to 15 patients (30%) but could not be completed for 3. Prolonged test positivity (maximum of 27 days) was observed in 4 patients (8%). Conclusions and Relevance In this case series study of children and adolescents hospitalized with COVID-19, the disease had diverse manifestations. Infants and immunocompromised patients were not at increased risk of severe disease. Obesity was significantly associated with disease severity. Elevated inflammatory markers were seen in those with severe disease.


Risks to children during the covid-19 pandemic: some essential epidemiology.


Longitudinal symptom dynamics of COVID-19 infection in primary care

Abstract: Importance: Data regarding the clinical characteristics of COVID-19 infection is rapidly accumulating. However, most studies thus far are based on hospitalized patients and lack longitudinal follow up. As the majority of COVID-19 cases are not hospitalized, prospective studies of symptoms in the population presenting to primary care are needed. Objective: To assess the longitudinal dynamic of clinical symptoms in non-hospitalized individuals prior to and throughout the diagnosis of SARS-CoV-2 infection. Design, Setting, and Participants: From 1/3/2020 to 07/06/2020, information on symptoms from either surveys or primary care visits was available for 206,377 individuals, including 2,471 who tested positive for COVID-19. Data were extracted from electronic health records (EHR) of the second largest Health Maintenance Organization in Israel, consisting of both results of PCR tests and symptoms recorded by primary care physicians, and linked longitudinal self reported symptoms. Exposures: Diagnosis of COVID-19 disease was made by PCR testing for SARS-CoV-2 from nasopharyngeal swabs. Main Outcomes and Measures: Longitudinal prevalence of clinical symptoms Results: In adults, the most prevalent symptoms recorded in EHR were cough (11.6%), fever (10.3%), and myalgia (7.7%) and the most prevalent self-reported symptoms were cough (21%), fatigue (19%) and rhinorrhea and/or nasal congestion (17%). In children, the most prevalent symptoms recorded in the EHR were fever (7%), cough (5.5%) and abdominal pain (2.4%). Emotional disturbances were documented in 15.9% of the positive adults and 4.2% of the children. Loss of taste and smell, either self-reported or documented by a physician, 3 weeks prior to testing, were the most discriminative symptoms in adults (OR =11.18 and OR=5.47 respectively). Additional symptoms included self reported confusion (OR =4.02), and fatigue (OR = 1.73) and a documentation of syncope, rhinorrhea (OR = 2.09 for both ) and fever (OR= 1.62 ) by a physician. Mean time to recovery was 23.5 +- 9.9 days. Children had a significantly shorter disease duration (21.7 +- 8.8 days, p-value=0.01). Several symptoms, including fatigue, myalgia, runny nose and shortness of breath were reported weeks after recovery. Conclusions and Relevance: As the COVID-19 pandemic progresses rapidly worldwide, obtaining accurate information on symptoms and their progression is of essence. Our study shed light on the full clinical spectrum of symptoms experienced by infected individuals in primary care, and may alert physicians for the possibility of COVID-19 infection.


Clinical features of covid-19 in children

Abstract: In early December, pneumonia cases of unknown origin started to appear and, on the 7thof January 2020, these cases were declared to be caused by a novel beta-coronavirus according to viral genome sequencing on the 11thof February, 2020. Coronaviruses are enveloped, single strand RNA viruses that have been known to have the ability to mutate rapidly, alter tissue tropism and adjust to different epidemiological situations. As of the end of April 2020, 122,392 laboratory-confirmed cases of COVID-19 had been detected in Turkey, of whom 3,258 died. From the beginning of the COVID-19 epidemic, children seem to be less affected than adults. Therefore, there are limited data regarding the clinical features of COVID-19 in children. The majority of children with confirmed COVID-19 had a history of household contact. The most common symptoms were fever and cough. Previous data suggest that nearly half of patients are afebrile at the onset of the disease. Hospitalization and PICU admission rates for children were lower than for adults. However, PICU admission can be necessitated in children with severe disease. Infants, particularly under the age of 12 months, were more likely to develop severe disease. In children, milder and asymptomatic cases can be challenging and can play a role in transmission. In particular, clinicians should test those children who have a history of family cluster even though they are asymptomatic or present with mild symptoms.


Pay attention to SARS-CoV-2 infection in children


Guidelines for coronavirus disease 2019 response in children and adolescents

Abstract: The Korean Society of Pediatric Infectious Diseases and the Korea Centers for Disease Control and Prevention issued the guidelines about coronavirus disease 2019 (COVID-19) for children and adolescents. Case definitions and management of COVID-19 in neonates, infants, children and adolescents are presented in this guideline. In addition, guidelines for caregiver management are also provided. In this review, we introduce the contents of the current guidelines for COVID-19 in children and adolescents in Korea.


COVID-19 Disease in Children: Clinical Course, Diagnosis and Treatment Overview and Literature Data Compilation

Abstract: The novel Coronavirus is named as SARS-CoV-2 is a highly contagious infection agent compared to the previous human coronaviruses Each previous outbreak had distinctive danger The high potential of infectiousness is the primary danger of novel coronavirus While MERS-CoV infection is known to have higher mortality rate, SARS-CoV-2 has spread to many people all over the world in a concise time SARS-CoV-2 (like SARS-CoV and MERS) infects fewer children and results in milder clinical symptoms than in adults The primary pathogenesis of it is not known;the difference in children's immunities, less likelihood of exposure to the agent may be the reasons Nevertheless, along with being mostly asymptomatic, the child population is a potential source for infection spread


Clinical Features and Outcome of SARS-CoV-2 Infection in Children: A Systematic Review and Meta-analysis.

Abstract: BACKGROUND AND OBJECTIVE Knowledge about COVID-19 in children is limited due to the paucity of reported data. The pediatric age group comprises only less than 5% of total COVID-19 worldwide, therefore, large studies in this population are unlikely in the immediate future. Hence, we planned to synthesize the current data that will help in a better understanding of COVID-19 in children. METHODS Four different electronic databases (MEDLINE, EMBASE, Web of Science, and CENTRAL) were searched for articles related to COVID-19 in the pediatric population. We included studies reporting disease characteristics and outcomes of COVID-19 in patients aged less than 19 years. We performed a random-effect meta-analysis to provide pooled estimates of various disease characteristics. RESULTS 27 studies (4857 patients) fulfilling the eligibility criteria were included in this systematic review, from a total of 883 records. About half of the patients had each of fever and cough, 11% (6-17%) had fast breathing, and 6-13% had gastrointestinal manifestations. Most of the patients had mild to moderate disease, and only 4% had a severe or critical illness. Leukopenia was the commonest reported laboratory abnormality. CONCLUSION Even among the symptomatic COVID-19 cases, severe manifestations are seen in very few children. Though fever and respiratory symptoms are most common, many children also have gastrointestinal manifestations.


Covid-19 in children: A brief overview after three months experience


Covid-19 and pregnancy

Abstract: Guideline: Coronavirus (COVID-19) Infection in pregnancyPublished by the Royal College of Obstetricians and Gynaecologists (RCOG), with input from the Royal College of Midwives, the Royal College of Paediatrics and Child Health (RCPH), the Royal College of Anaesthetists, and the Obstetric Anaesthetists' Association.This summary is based on version 8 of the guideline, published on 17 April 2020 (https://www.rcog.org.uk/globalassets/documents/guidelines/2020-04-17-coronavirus-covid-19-infection-in-pregnancy.pdf).


Coronavirus Disease (COVID-19) in Children - What We Know So Far and What We Do Not?

Abstract: Pediatric coronavirus disease - 19 (COVID-19) infection is relatively mild when compared to adults, and children are reported to have a better prognosis Mortality in children appears rare Clinical features of COVID-19 in children include fever and cough, but a large proportion of infected children appears to be asymptomatic and may contribute to transmission It remains unclear why children and young adults are less severely affected than older individuals, but this might involve differences in immune system function in the elderly and/or differences in the expression/function of the cellular receptor for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) - Angiotensin converting enzyme 2 (ACE2) Laboratory findings and chest imaging may not be specific in children with COVID-19 Diagnosis is by Reverse transcriptase-Polymerase chain reaction (RT-PCR) testing of upper or lower respiratory tract secretions This review additionally considers COVID-19 in immunosuppressed children, and also suggests a management algorithm for the few children who appear to present with life threatening infection, including the potential use of antiviral and immunomodulatory treatment The most significant threat to global child health from SARS-CoV-2 is unlikely to be related to COVID 19 in children, but rather the socio-economic consequences of a prolonged pandemic


Characteristics of Hospitalized Pediatric COVID-19 Cases - Chicago, Illinois, March - April 2020

Abstract: BACKGROUND: To date, no report on COVID-19 pediatric patients in a large urban center with data on underlying comorbidities and co-infection for hospitalized cases has been published. METHODS: Case series of Chicago COVID-19 patients aged 0-17 years reported to Chicago Department of Public Health (CDPH) from 3/5/20-4/8/20. Enhanced case investigation performed. Chi-square and Wilcoxon two-sample tests to compare characteristics among hospitalized and non-hospitalized cases. RESULTS: During March 5-April 8, 2020, 6369 lab-confirmed cases of COVID-19 were reported to CDPH; 64 (1.0%) were among children 0-17 years. Ten patients (16%) were hospitalized, seven (70%) required intensive care (ICU); median length of hospitalization 4 days (range: 1-14). Reported fever and dyspnea were significantly higher in hospitalized patients compared to non-hospitalized patients (9/10 vs. 28/54, p = 0.04 and 7/10 vs. 10/54, p = 0.002, respectively). Hospitalized patients were significantly younger than non-hospitalized patients (median, 3.5 years vs. 12 years; p = 0.03) and all either had an underlying comorbidity or co-infection. Among the 34 unique households with multiple laboratory-confirmed infections, median number of laboratory-confirmed infections was 2 (range: 2-5), and 31 (91%) households had at least one COVID-19 infected adult. For 15 households with available data to assess transmission, 11 (73%) were adult-to-child, 2 (13%) child-to-child, and 2 (13%) child-to-adult. CONCLUSIONS: Enhanced case investigation of hospitalized patients revealed that underlying comorbidities and co-infection might have contributed to severe disease. Given frequency of household transmission, healthcare providers should consider alternative dispositional planning for affected families of children living with comorbidities.


Coronavirus disease (COVID-19) and neonate: What neonatologist need to know

Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cause china epidemics with high morbidity and mortality, the infection has been transmitted to other countries. About three neonates and more than 230 children cases are reported. The disease condition of the main children was mild. There is currently no evidence that SARS-CoV-2 can be transmitted transplacentally from mother to the newborn. The treatment strategy for children with Coronavirus disease (COVID-19) is based on adult experience. Thus far, no deaths have been reported in the pediatric age group. This review describes the current understanding of COVID-19 infection in newborns and children.


SARS-CoV-2 testing and outcomes in the first 30 days after the first case of COVID-19 at an Australian children's hospital

Abstract: OBJECTIVE: International studies describing COVID-19 in children have shown low proportions of paediatric cases and generally a mild clinical course. We aimed to present early data on children tested for SARS-CoV-2 at a large Australian tertiary children's hospital according to the state health department guidelines, which varied over time. METHODS: We conducted a retrospective cohort study at The Royal Children's Hospital, Melbourne, Australia. It included all paediatric patients (aged 0-18 years) who presented to the ED or the Respiratory Infection Clinic (RIC) and were tested for SARS-CoV-2. The 30-day study period commenced after the first confirmed positive case was detected at the hospital on 21 March 2020, until 19 April 2020. We recorded epidemiological and clinical data. RESULTS: There were 433 patients in whom SARS-CoV-2 testing was performed in ED (331 [76%]) or RIC (102 [24%]). There were four (0.9%) who had positive SARS-CoV-2 detected, none of whom were admitted to hospital or developed severe disease. Of these SARS-CoV-2 positive patients, 1/4 (25%) had a comorbidity, which was asthma. Of the SARS-CoV-2 negative patients, 196/429 (46%) had comorbidities. Risk factors for COVID-19 were identified in 4/4 SARS-CoV-2 positive patients and 47/429 (11%) SARS-CoV-2 negative patients. CONCLUSION: Our study identified a very low rate of SARS-CoV-2 positive cases in children presenting to a tertiary ED or RIC, none of whom were admitted to hospital. A high proportion of patients who were SARS-CoV-2 negative had comorbidities.


Managing COVID-19 disease in pediatric patients

Abstract: Children are less likely to be infected with SARS-CoV-2 than adults and often have a milder course of COVID-19 disease and a lower case fatality rate. Children account for an estimated 1% to 5% of those diagnosed with COVID-19. Even so, preschool-aged children, infants, and children with underlying health conditions may still be at risk for severe disease and complications. Unique aspects of COVID-19 presentation and disease course in children and possible vertical transmission to newborns from COVID-19-positive mothers are discussed.


Novel coronavirus infection (COVID-19) in children younger than one year: A systematic review of symptoms, management and outcomes

Abstract: AIM: The aim of this systematic review was to evaluate the clinical characteristics of COVID-19 in neonates and children under one year of age. METHODS: A systematic literature review of the MEDLINE, PubMed, CINAHL, Embase and EBSCO databases was carried out for studies from January 1, 2020, to April 7, 2020. We included all papers that addressed clinical manifestations, laboratory results, imaging findings and outcomes in infants and neonates. RESULTS: Our search identified 77 peer-reviewed papers, and 18 papers covering 160 infants were reviewed. One paper was from Vietnam, and the other 17 were from China: eight were cross-sectional studies, eight were case reports, one was a case series, and one was a prospective cohort study. The most common clinical symptoms were fever (54%) and cough (33%). Most infants were treated symptomatically, with frequent use of various empirical medications. Infants and neonates tended to have more severe COVID-19 disease than older children: 11 (7%) were admitted to intensive care and one infant died. The mortality rate was 0.006%, with favourable outcomes in most cases. CONCLUSION: Infants and neonates were more vulnerable to more severe COVID-19 disease than older children, but morbidity and mortality were low.


[Pediatric impact of COVID-19]

Abstract: Children infected with SARS-CoV-2 are underrepresented during the current COVID-19 outbreak Unlike other respiratory viruses, SARS-CoV-2 rather infects adults who subsequently infect their children From recent Chinese and Italian data, children commonly present mild to moderate disease, a large proportion of them being asymptomatic In particular, children present significantly less fever, cough and pneumonia compared to adults However, more cases of pneumonia were reported from children infected with SARS-CoV-2 compared to those infected with H1N1 No vertical transmission of SARS-CoV-2 has been described so far


SARS-CoV-2 infection in infants under 1 year of age in Wuhan City, China

Abstract: BACKGROUND: The clinical characteristics and outcome of COVID-19 in children are different from those in adults. We aimed to describe the characteristics of infants under 1 year of age (excluding newborns) with COVID-19. METHODS: We retrospectively retrieved data of 36 infants with SARS-CoV-2 infection in Wuhan Children's Hospital from January 26 to March 22, 2020. Clinical features, chest imaging findings, laboratory tests results, treatments and clinical outcomes were analyzed. RESULTS: The mean age of the infected infants was 6.43 months, with a range of 2-12 months. 61.11% of the patients were males and 38.89% females. 86.11% of the infants were infected due to family clustering. Cough (77.78%) and fever (47.22%) were the most common clinical manifestations. Chest CT scan revealed 61.11% bilateral pneumonia and 36.11% unilateral pneumonia. 47.22% of the infants developed complications. Increased leucocytes, neutrophils, lymphocytes, and thrombocytes were observed in 11.11, 8.33, 36.11 and 44.44% of infants, respectively. Decreased leucocytes, neutrophils, thrombocyte and hemoglobin were observed in 8.33, 19.44, 2.78 and 36.11% of infants, respectively. Increased C-reactive protein, procalcitonin, lactate dehydrogenase, alanine aminotransferase, creatine kinase and D-dimer were observed in 19.44, 67.74, 47.22, 19.44, 22.22 and 20.69% of infants, respectively. Only one infant had a high level of creatinine. Co-infections with other respiratory pathogens were observed in 62.86% of infants. CD3 (20.69%), CD4 (68.97%), CD19 (31.03%) and Th/Ts (44.83%) were elevated; CD8 (6.9%) and CD16+CD56 (48.28%) was reduced. IL-4 (7.69%), IL-6 (19.23%), IL-10 (50%), TNF-α (11.54%) and IFN-Î³ (19.23%) were elevated. Up to March 22, 97.22% of infants recovered, while a critical ill infant died. When the infant's condition deteriorates rapidly, lymphocytopenia was discovered. Meanwhile, C-reactive protein, D-dimer, alanine aminotransferase, creatine kinase, creatinine, IL-6 and IL-10 increased significantly. CONCLUSIONS: In the cohort, we discovered that lymphocytosis, elevated CD4 and IL-10, and co-infections were common in infants with COVID-19, which were different from adults with COVID-19. Most infants with COVID-19 have mild clinical symptoms and good prognosis.


[Clinical features of coronavirus disease 2019 in children aged <18 years in Jiangxi, China: an analysis of 23 cases]

Abstract: OBJECTIVE: To study the clinical features of coronavirus disease 2019 (COVID-19) in children aged <18 years. METHODS: A retrospective analysis was performed from the medical data of 23 children, aged from 3 months to 17 years and 8 months, who were diagnosed with COVID-19 in Jiangxi, China from January 21 to February 29, 2020. RESULTS: Of the 23 children with COVID-19, 17 had family aggregation. Three children (13%) had asymptomatic infection, 6 (26%) had mild type, and 14 (61%) had common type. Among these 23 children, 16 (70%) had fever, 11 (48%) had cough, 8 (35%) had fever and cough, and 8 (35%) had wet rales in the lungs. The period from disease onset or the first nucleic acid-positive detection of SARS-CoV-2 to the virus nucleic acid negative conversion was 6-24 days (median 12 days). Of the 23 children, 3 had a reduction in total leukocyte count, 2 had a reduction in lymphocytes, 2 had an increase in C-reactive protein, and 2 had an increase in D-dimer. Abnormal pulmonary CT findings were observed in 12 children, among whom 9 had patchy ground-glass opacities in both lungs. All 23 children received antiviral therapy and were recovered. CONCLUSIONS: COVID-19 in children aged <18 years often occurs with family aggregation, with no specific clinical manifestation and laboratory examination results. Most of these children have mild symptoms and a good prognosis. Epidemiological history is of particular importance in the diagnosis of COVID-19 in children aged <18 years.


Clinical Features and Outcome of SARS-CoV-2 Infection in Children: A Systematic Review and Meta-analysis

Abstract: BACKGROUND AND OBJECTIVE: Knowledge about COVID-19 in children is limited due to the paucity of reported data. The pediatric age group comprises only less than 5% of total COVID-19 worldwide, therefore, large studies in this population are unlikely in the immediate future. Hence, we planned to synthesize the current data that will help in a better understanding of COVID-19 in children. METHODS: Four different electronic databases (MEDLINE, EMBASE, Web of Science, and CENTRAL) were searched for articles related to COVID-19 in the pediatric population. We included studies reporting disease characteristics and outcomes of COVID-19 in patients aged less than 19 years. We performed a random-effect meta-analysis to provide pooled estimates of various disease characteristics. RESULTS: 27 studies (4857 patients) fulfilling the eligibility criteria were included in this systematic review, from a total of 883 records. About half of the patients had each of fever and cough, 11% (6-17%) had fast breathing, and 6-13% had gastrointestinal manifestations. Most of the patients had mild to moderate disease, and only 4% had a severe or critical illness. Leukopenia was the commonest reported laboratory abnormality. CONCLUSION: Even among the symptomatic COVID-19 cases, severe manifestations are seen in very few children. Though fever and respiratory symptoms are most common, many children also have gastrointestinal manifestations.


COVID-19 and Neonatal Respiratory Care: Current Evidence and Practical Approach

Abstract: The novel coronavirus disease 2019 (COVID-19) pandemic has urged the development and implementation of guidelines and protocols on diagnosis, management, infection control strategies, and discharge planning. However, very little is currently known about neonatal COVID-19 and severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infections. Thus, many questions arise with regard to respiratory care after birth, necessary protection to health care workers (HCW) in the delivery room and neonatal intensive care unit (NICU), and safety of bag and mask ventilation, noninvasive respiratory support, deep suctioning, endotracheal intubation, and mechanical ventilation. Indeed, these questions have created tremendous confusion amongst neonatal HCW. In this manuscript, we comprehensively reviewed the current evidence regarding COVID-19 perinatal transmission, respiratory outcomes of neonates born to mothers with COVID-19 and infants with documented SARS-CoV-2 infection, and the evidence for using different respiratory support modalities and aerosol-generating procedures in this specific population. The results demonstrated that to date, neonatal COVID-19 infection is uncommon, generally acquired postnatally, and associated with favorable respiratory outcomes. The reason why infants display a milder spectrum of disease remains unclear. Nonetheless, the risk of severe or critical illness in young patients exists. Currently, the recommended respiratory approach for infants with suspected or confirmed infection is not evidence based but should include all routinely used types of support, with the addition of viral filters, proper personal protective equipment, and placement of infants in isolation rooms, ideally with negative pressure. As information is changing rapidly, clinicians should frequently watch out for updates on the subject. KEY POINTS: · Novel coronavirus disease 2019 (COVID-19) pandemic urged development of guidelines.. · Neonatal COVID-19 disease is uncommon.. · Respiratory outcomes in neonates seems favorable.. · Current neonatal respiratory care should continue.. · Clinicians should watch frequently for updates..


[Retracted: Clinical and epidemiological characteristics of 34 children with 2019 novel coronavirus infection in Shenzhen]

Abstract: Objective: To describe the characteristics of clinical manifestations and epidemiology of children with 2019 novel coronavirus (2019-nCoV) infection. Methods: All 34 children with laboratory-confirmed 2019-nCoV infection by quantitative real-time reverse transcription-PCR through nasopharyngeal swab specimens were admitted to the Third People's Hospital of Shenzhen from January 19 to Febuary 7, 2020. Clinical data and epidemiological history of these patients were retrospectively collected and analyzed. Results: Among the 34 cases, 14 were males, and 20 were females. The median age was 8 years and 11 months. No patients had underlying diseases. There were 28 children (82%) related with a family cluster outbreak. There were 26 children (76%) with a travel or residence history in Hubei Province. These patients could be categorized into different clinical types, including 22 (65%) common cases, 9 (26%) mild cases and 3 (8.8%) asymptomatic cases. No severe or critical cases were identified. The most common symptoms were fever (17 cases, 50%) and cough (13 cases, 38% ). In the 34 cases, the white blood cell counts of 28 cases (82%) were normal. Five cases had white blood cell counts more than 10×10(9)/L. One case had white blood cell counts less than 4×10(9)/L. Neutropenia and lymphopenia was found in one case, respectively. C-reactive protein levels and erythrocyte sedimentation rates were elevated in 1 and 5 case, respectively. Elevated procalcitonin was found in 1 case and D-Dimer in 3 cases. The levels of lactic dehydrogenase (LDH) were more than 400 U/L in 10 cases. The CT images of these patients showed bilateral multiple patchy or nodular ground-glass opacities and/or infiltrating shadows in middle and outer zone of the lung or under the pleura. Twenty patients were treated with lopinavir and ritonavir. Glucocorticoids and immunoglobulin were not used in any cases. All the cases improved and were discharged from hospital. Further following up was need. Conclusions: The clinical manifestations in children with 2019-nCoV infection are non-specific and are milder than that in adults. Chest CT scanning is heplful for early diagnosis. Children's infection is mainly caused by family cluster outbreak and imported cases. Family daily prevention is the main way to prevent 2019-nCoV infection.


The role of children in the transmission of mild SARS-CoV-2 infection


COVID-19 in children: Epidemiology, presentation, diagnosis and management

Abstract: The new pandemic coronavirus disease (COVID-19) has affected children, including neonates, who mostly comprise of approximately 2% of total confirmed cases. Most children are asymptomatic or have mild disease and much lower mortality compared to adults for yet unknown reasons. Recovery from illness has largely been universal and <2% have severe disease requiring intensive care. Standardised guidelines from initial studies are now available for diagnosis, treatment, and prevention. Treatment is mostly supportive with no recommendations for any specific drugs so far. As the pandemic evolves, it is expected that more children will be diagnosed and treated with evolving newer regimens. Research should now focus on early diagnosis, better drugs for children, intensive care modalities, and a universal vaccine. New developments will help in better prevention asides from the other precautionary measures already being practiced.


A wake-up call: COVID-19 and its impact on children's health and wellbeing


Novel coronavirus disease (COVID-19) in children

Abstract: Coronavirus disease (COVID-19) was firstly reported at the end of 2019. The disease rapidly spread all around the world in a few months and was declared a worldwide pandemic by WHO in March 2020. By April 9, there were 1,436,198 confirmed COVID-19 cases in the world, nearly with 6% mortality rate. This novel infectious disease causes respiratory tract illness that may generally occur as mild upper respiratory tract disease or pneumonia. In older patients and/or patients with underlying conditions, it may result in acute respiratory distress syndrome, multi organ failure and even death. According to the current literature, children account approximately for 1%5% of diagnosed COVID-19 cases. Generally, COVID-19 seems to be a less severe disease for children than adults. Approximately 90% of pediatric patients are diagnosed as asymptomatic, mild, or moderate disease. However, up to 6.7% of cases may be severe. Severe illness is generally seen in patients smaller than 1 year of age and patients who have underlying disesases. The epidemiological and clinical patterns of COVID-19 and treatment approaches in pediatric patients still remain unclear although many pediatric reports are published. This review aims to summarize the current epidemics, clinical presentations, diagnosis, and treatment of COVID-19 in pediatric patients.


Coronavirus disease 2019 in children: Current status

Abstract: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged from China in December 2019. The outbreak further exploded in Europe and America in mid-March 2020 to become a global health emergency. We reviewed recent published articles and on-line open messages on SARS-CoV-2-positive infants and children younger than 20 years of age. Symptoms are usually less severe in children than in adults. Twelve critically or mortally ill children were found in the published or news reports before April 6, 2020. Vertical transmission from the mother to her fetus or neonate has not been proven definitively. However, six early-onset (<7 days) and 3 late-onset neonatal SARS-CoV-2 infections were found in the literature. We also summarized the presentations and contact information of 24 SARS-CoV-2-positive children announced by the Taiwan Centers for Disease Control. Early identification and isolation, adequate management, prevention, and vaccine development are the keys to controlling the disease spread. Clinical physicians should be alert to asymptomatic children with COVID-19. Multidirectional investigations are crucial in the global fight against COVID-19.


The different clinical characteristics of corona virus disease cases between children and their families in China - the character of children with COVID-19

Abstract: This study aims to analyze the different clinical characteristics between children and their families infected with severe acute respiratory syndrome coronavirus 2. Clinical data from nine children and their 14 families were collected, including general status, clinical, laboratory test, and imaging characteristics. All the children were detected positive result after their families onset. Three children had fever (22.2%) or cough (11.2%) symptoms and six (66.7%) children had no symptom. Among the 14 adult patients, the major symptoms included fever (57.1%), cough (35.7%), chest tightness/pain (21.4%), fatigue (21.4%) and sore throat (7.1%). Nearly 70% of the patients had normal (71.4%) or decreased (28.6%) white blood cell counts, and 50% (7/14) had lymphocytopenia. There were 10 adults (71.4%) showed abnormal imaging. The main manifestations were pulmonary consolidation (70%), nodular shadow (50%), and ground glass opacity (50%). Five discharged children were admitted again because their stool showed positive result in SARS-CoV-2 PCR. COVID-19 in children is mainly caused by family transmission, and their symptoms are mild and prognosis is better than adult. However, their PCR result in stool showed longer time than their families. Because of the mild or asymptomatic clinical process, it is difficult to recognize early for pediatrician and public health staff.


COVID-19 multisystem inflammatory syndrome in three teenagers with confirmed SARS-CoV-2 infection

Abstract: Coronavirus disease 2019 (COVID-19) is generally a relatively mild illness in children. An emerging disease entity coined as pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) has been reported recently, but is very rare and only affects a very small minority of children. Here we describe the clinical presentations and outcomes of three teenagers with serologically-confirmed SARS-CoV-2 infection admitted to a pediatric intensive care unit for PIMS-TS. Although their initial presentations were very similar, their COVID-19-related disease varied in severity.


Epidemiology and Clinical Features of Coronavirus Disease 2019 in Moroccan Children

Abstract: OBJECTIVES: This study aims to analyze the epidemiological and clinical features of coronavirus disease 19 (COVID-19) in a Moroccan pediatric population METHODS: A retrospective study of a cohort of 74 children with RT-PCR confirmed COVID-19 We collected information on clinical and laboratory features of all children (age <18 years) admitted between 2 March, 2020 and 1 April, 2020 RESULTS: The mean (SD) age of the 74 children (40 girls) was 7 (1 5) years The mean (SD) time from illness onset to diagnosis was 2 (1) days 54 children were asymptomatic, while eight had fever, and five cases had cough Recovery was after a mean (SD) of 12 (1) days CONCLUSION: COVID-19 was mostly mild in the pediatric population in Morocco


Children with Coronavirus Disease 2019 (COVID-19): A Review of Demographic, Clinical, Laboratory and Imaging Features in 2,597 Pediatric Patients

Abstract: An epidemic of coronavirus disease 2019 (COVID-19) has been spreading worldwide. With the rapid increase in the number of infections, children with COVID-19 appear to be rising. Most research findings regarding adult cases, which are not always transferrable to children. Evidence-based studies are still expected to formulate clinical decisions for pediatric patients. In this review, we evaluated the demographic, clinical, laboratory and imaging features from 2,597 pediatric patients of COVID-19 that reported recently. We found that even lymphopenia was the most common lab finding in adults, it infrequently occurred in children (9.8%). Moreover, elevated creatine kinase MB isoenzyme (CK-MB) was much more commonly observed in children (27.0%) than that in adults, suggesting that heart injury would be more likely to happen in pediatric patients. Our analysis may contribute to determine the spectrum of disease in children, as well as to develop strategies to control the disease transmission. This article is protected by copyright. All rights reserved.


Clinical characteristics and outcome of SARS-CoV-2 infection in Italian pediatric oncology patients: a study from the Infectious Diseases Working Group of the AIEOP

Abstract: BACKGROUND: Little is known as yet about the outcome of SARS-CoV-2 infection in children being treated for cancer. METHODS: We collected information on the clinical characteristics and outcomes of a cohort of 29 children (16 females and 13 males, median age 7 years, range [0-16]) diagnosed with SARS-CoV-2 infection while on chemotherapy/immunotherapy (N=26), or after stem cell transplantation (N=3) during the peak of the epidemic in Italy. These patients suffered from leukemia (N=16), lymphoma (N=3), solid tumors (N=10), and Langerhans cell histiocytosis (N=1). RESULTS: The course of the disease was mild in all cases, with only 12 children developing symptoms (pneumonia in 3 cases), and none needing intensive care. Fifteen patients were hospitalized, including 7 asymptomatic patients. Nine patients (including 5 with no symptoms) were given hydroxychloroquine, and 3 of them were also given lopinavir/ritonavir. CONCLUSIONS: SARS-CoV-2 infection seems to take a milder clinical course in children than in adults with cancer. Specific SARS-CoV-2 treatment seems unnecessary for most children. In the light of our findings, and albeit with the necessary caution, we suggest avoiding major changes to planned anticancer treatments in pediatric patients acquiring COVID-19.


Lessons from COVID-19 in children: Key hypotheses to guide preventative and therapeutic strategies

Abstract: The current pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), reveals a peculiar trend of milder disease and lower case fatality in children compared to adults. Consistent epidemiologic evidence of reduced severity of infection in children across different populations and countries suggests there are underlying biologic differences between children and adults that mediate differential disease pathogenesis. This presents a unique opportunity to learn about disease modifying host factors from pediatric populations. Our review summarizes the current knowledge of pediatric clinical disease, role in transmission, risks for severe disease, protective immunity, as well as novel therapies and vaccine trials for children. We then define key hypotheses and areas for future research that can use the pediatric model of disease, transmission, and immunity to develop preventive and therapeutic strategies for people of all age groups.


SARS-CoV-2: The Path of Prevention and Control

Abstract: The 2019 coronavirus pandemic (COVID-19) continues to expand worldwide. Although the number of cases and the death rate among children and adolescents are reported to be low compared to adults, limited data have been reported. We urgently need to find treatment and vaccine to stop the epidemic. Vaccine development is in progress, but any approved and effective vaccine for COVID-19 is at least 12 to 18 months. The World Health Organization (WHO), the Center for Disease Control and Prevention (CDC), and the Food and Agriculture Organization (FAO) have issued instructions and strategies for containing COVID-19 outbreak to the general public, physicians, travelers and injured patients to follow so that the transmission to a healthy population can be prevented. In this review, we summarize demographic data, clinical characteristics, complications and outcomes and finally prevention and control of this serious pandemic.


Coronavirus Disease 2019 in Children Cared for at Texas Children's Hospital: Initial Clinical Characteristics and Outcomes

Abstract: We describe the clinical course of 57 children with coronavirus disease 2019 (COVID-19) cared for through a single hospital system. Most children were mildly symptomatic, and only a few patients with underlying medical conditions required hospitalization. System-wide patient evaluation processes allowed for prompt identification and management of COVID-19 patients.


Spectrum of COVID-19 in Children

Abstract: The prevalence of coronavirus disease 2019 (COVID-19) is lower in children compared to adults. Children contribute to 1-5% of all COVID-19 cases (1) . A recent study from China reported that 171(12.3%) of 1391 children with suspected disease had confirmed COVID-19 infection (2) . As of May 15, 2020, there are 33,241 children with COVID-19 in the United States (3) . The most common symptoms in children with confirmed and suspected COVID-19 include fever and cough followed by diarrhea, and abdominal pain.


COVID-19 virus and children: What do we know?


Clinical characteristics of COVID-19 in children compared with adults in Shandong Province, China

Abstract: AIMS AND BACKGROUND: The COVID-19 outbreak spread in China and is a threat to the world. We reported on the epidemiological, clinical, laboratory, and radiological characteristics of children cases to help health workers better understand and provide timely diagnosis and treatment. METHODS: Retrospectively, two research centers' case series of 67 consecutive hospitalized cases including 53 adult and 14 children cases with COVID-19 between 23 Jan 2020 and 15 Feb 2020 from Jinan and Rizhao were enrolled in this study. Epidemiological, clinical, laboratory, and radiological characteristics of children and adults were analyzed and compared. RESULTS: Most cases in children were mild (21.4%) and conventional cases (78.6%), with mild clinical signs and symptoms, and all cases were of family clusters. Fever (35.7%) and dry cough (21.4%) were described as clinical manifestations in children cases. Dry cough and phlegm were not the most common symptoms in children compared with adults (p = 0.03). In the early stages of the disease, lymphocyte counts did not significantly decline but neutrophils count did in children compared with adults (p = 0.02). There was a lower level of CRP (p = 0.00) in children compared with adults. There were 8 (57.1%) asymptomatic cases and 6 (42.9%) symptomatic cases among the 14 children cases. The age of asymptomatic patients was younger than that of symptomatic patients (p = 0.03). Even among asymptomatic patients, 5 (62.5%) cases had lung injuries including 3 (60%) cases with bilateral involvement, which was not different compared with that of symptomatic cases (p = 0.58, p = 0.74). CONCLUSIONS: The clinical symptoms of children are mild, there is substantial lung injury even among children, but that there is less clinical disease, perhaps because of a less pronounced inflammatory response, and that the occurrence of this pattern appears to inversely correlate with age.


Epidemiology, Clinical Features, and Disease Severity in Patients With Coronavirus Disease 2019 (COVID-19) in a Children's Hospital in New York City, New York

Abstract: Importance: Descriptions of the coronavirus disease 2019 (COVID-19) experience in pediatrics will help inform clinical practices and infection prevention and control for pediatric facilities. Objective: To describe the epidemiology, clinical, and laboratory features of patients with COVID-19 hospitalized at a children's hospital and to compare these parameters between patients hospitalized with and without severe disease. Design, Setting, and Participants: This retrospective review of electronic medical records from a tertiary care academically affiliated children's hospital in New York City, New York, included hospitalized children and adolescents (≤21 years) who were tested based on suspicion for COVID-19 between March 1 to April 15, 2020, and had positive results for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Exposures: Detection of SARS-CoV-2 from a nasopharyngeal specimen using a reverse transcription-polymerase chain reaction assay. Main Outcomes and Measures: Severe disease as defined by the requirement for mechanical ventilation. Results: Among 50 patients, 27 (54%) were boys and 25 (50%) were Hispanic. The median days from onset of symptoms to admission was 2 days (interquartile range, 1-5 days). Most patients (40 [80%]) had fever or respiratory symptoms (32 [64%]), but 3 patients (6%) with only gastrointestinal tract presentations were identified. Obesity (11 [22%]) was the most prevalent comorbidity. Respiratory support was required for 16 patients (32%), including 9 patients (18%) who required mechanical ventilation. One patient (2%) died. None of 14 infants and 1 of 8 immunocompromised patients had severe disease. Obesity was significantly associated with mechanical ventilation in children 2 years or older (6 of 9 [67%] vs 5 of 25 [20%]; P = .03). Lymphopenia was commonly observed at admission (36 [72%]) but did not differ significantly between those with and without severe disease. Those with severe disease had significantly higher C-reactive protein (median, 8.978 mg/dL [to convert to milligrams per liter, multiply by 10] vs 0.64 mg/dL) and procalcitonin levels (median, 0.31 ng/mL vs 0.17 ng/mL) at admission (P < .001), as well as elevated peak interleukin 6, ferritin, and D-dimer levels during hospitalization. Hydroxychloroquine was administered to 15 patients (30%) but could not be completed for 3. Prolonged test positivity (maximum of 27 days) was observed in 4 patients (8%). Conclusions and Relevance: In this case series study of children and adolescents hospitalized with COVID-19, the disease had diverse manifestations. Infants and immunocompromised patients were not at increased risk of severe disease. Obesity was significantly associated with disease severity. Elevated inflammatory markers were seen in those with severe disease.


Neurologic and Radiographic Findings Associated With COVID-19 Infection in Children

Abstract: Importance: Neurological manifestations have been reported in adults with coronavirus disease 2019 (COVID-19), which is caused by the highly pathogenic virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Objective: To report the neurological manifestations of children with COVID-19. Design, Setting, and Participants: In this case-series study, patients younger than 18 years who presented with SARS-CoV-2 infection and neurological symptoms to Great Ormond Street Hospital for Children (London, UK) between March 1, 2020, and May 8, 2020, were included after infection was confirmed by either a quantitative reverse transcription-polymerase chain reaction assay by nasopharyngeal swab or a positive test result for IgG antibodies against SARS-CoV-2 in serum. Main Outcomes and Measures: Clinical and paraclinical features were retrieved from electronic patient records. Results: Of the 27 children with COVID-19 pediatric multisystem inflammatory syndrome, 4 patients (14.8%) who were previously healthy had new-onset neurological symptoms. Symptoms included encephalopathy, headaches, brainstem and cerebellar signs, muscle weakness, and reduced reflexes. All 4 patients required intensive care unit admission for the treatment of COVID-19 pediatric multisystem inflammatory syndrome. Splenium signal changes were seen in all 4 patients on magnetic resonance imaging of the brain. In the 2 patients whose cerebrospinal fluid was tested, samples were acellular, with no evidence of infection on polymerase chain reaction or culture (including negative SARS-CoV-2 polymerase chain reaction results) and negative oligoclonal band test results. In all 3 patients who underwent electroencephalography, a mild excess of slow activity was found. Tests for N-methyl-d-aspartate receptor, myelin oligodendrocyte glycoprotein, and aquaporin-4 autoantibodies had negative results in all patients. In all 3 patients who underwent nerve conduction studies and electromyography, mild myopathic and neuropathic changes were seen. Neurological improvement was seen in all patients, with 2 making a complete recovery by the end of the study. Conclusions and Relevance: In this case-series study, children with COVID-19 presented with new neurological symptoms involving both the central and peripheral nervous systems and splenial changes on imaging, in the absence of respiratory symptoms. Additional research is needed to assess the association of neurological symptoms with immune-mediated changes among children with COVID-19.


Pandemic school closures: risks and opportunities


Feasibility of Social Distancing Practices in US Schools to Reduce Influenza Transmission During a Pandemic

Abstract: Schools are socially dense environments, and school-based outbreaks often predate and fuel community-wide transmission of seasonal and pandemic influenza. While preemptive school closures can effectively reduce influenza transmission, they are disruptive and currently recommended only for pandemics. We assessed the feasibility of implementing other social distancing practices in K-12 schools as a first step in seeking an alternative to preemptive school closures. METHODS: We conducted 36 focus groups with education and public health officials across the United States. We identified and characterized themes and compared feasibility of practices by primary versus secondary school and region of the United States. RESULTS: Participants discussed 29 school practices (25 within-school practices implemented as part of the school day and 4 reduced-schedule practices that impact school hours). Participants reported that elementary schools commonly implement several within-school practices as part of routine operations such as homeroom stay, restriction of hall movement, and staggering of recess times. Because of routine implementation and limited use of individualized schedules within elementary schools, within-school practices were generally felt to be more feasible for elementary schools than secondary schools. Of reduced-schedule practices, shortening the school week and the school day was considered the most feasible; however, reduced-schedule practices were generally perceived to be less feasible than within-school practices for all grade levels. CONCLUSIONS: Our findings suggest that schools have many options to increase social distance other than closing. Future research should evaluate which of these seemingly feasible practices are effective in reducing influenza transmission in schools and surrounding communities.


How COVID-19 has exposed inequalities in the UK food system: The case of UK food and poverty

Abstract: This article draws upon our perspective as academic-practitioners working in the fields of food insecurity, food systems, and inequality to comment, in the early stages of the pandemic and associated lockdown, on the empirical and ethical implications of COVID-19 for socio-economic inequalities in access to food in the UK. The COVID-19 pandemic has sharpened the profound insecurity of large segments of the UK population, an insecurity itself the product of a decade of ‘austerity’ policies. Increased unemployment, reduced hours, and enforced self-isolation for multiple vulnerable groups is likely to lead to an increase in UK food insecurity, exacerbating diet-related health inequalities. The social and economic crisis associated with the pandemic has exposed the fragility of the system of food charity which, at present, is a key response to growing poverty. A vulnerable food system, with just-in-time supply chains, has been challenged by stockpiling. Resultant food supply issues at food banks, alongside rapidly increasing demand and reduced volunteer numbers, has undermined many food charities, especially independent food banks. In the light of this analysis, we make a series of recommendations. We call for an immediate end to the five week wait for Universal Credit and cash grants for low income households. We ask central and local government to recognise that many food aid providers are already at capacity and unable to adopt additional responsibilities. The government’s - significant - response to the economic crisis associated with COVID-19 has underscored a key principle: it is the government’s responsibility to protect population health, to guarantee household incomes, and to safeguard the economy. Millions of households were in poverty before the pandemic, and millions more will be so unless the government continues to protect household incomes through policy change.


Threats and opportunities in remote learning of mathematics: implication for the return to the classroom

Abstract: Australian schools, like schools elsewhere, have been through a period of closure. The closure creates both threats and opportunities for teachers and students. In the context of a project exploring approaches to teaching in early years, we outline some considerations and offer advice to teachers and educators on strategies for welcoming students back to school.


Impact of the Covid-19 Pandemic on Early Childhood Care and Education


Returning to School: Separation Problems and Anxiety in the Age of Pandemics

Abstract: The shift to the postpandemic school environment will cause dramatic changes and is likely to increase separation problems. In this article, we look at the anxiety problems that some parents and their children might experience when school reopens after the COVID-19 lockdown. Using a behavioral theory of development, we provide suggestions for how to handle the departure and separation problems that may emerge as parents drop their children off at school. Many parents are unsure about how to handle anxiety or fear as their children return to school or have to visit other environments outside their homes. Social distancing has caused families to develop stronger dependencies at home and to create new routines that vary, in many instances greatly, from their prepandemic routines. Families are adjusting to the new “normal.” They are keeping their children busy with schoolwork as best they can. In particular, families have likely developed close attachment relationships. Families have been struggling with an unprecedented lockdown, and for many parents and their children, this extended period of family confinement and severe restrictions has been especially stressful, and the timing for returning to school is uncertain. We emphasize here that parents can be responsive to their children’s needs, plan ahead, provide reassurance, and depart firmly without vacillating, and we provide other tips to avoid inadvertently shaping children’s negative or anxiety behaviors as they go back to school. We offer some specific advice for parents and teachers to follow to prevent the departure and separation problems that typically develop during challenging behavioral interactions in school settings.


Covid-19: US cases soar as Trump pushes for schools to open.


Children and the COVID-19 pandemic.

Abstract: As a result of the COVID-19 pandemic, many school districts have closed for the remainder of the academic year. These closures are unfortunate because, for many students, schools are their only source of trauma-informed care and supports. When schools reopen, they must develop a comprehensive plan to address the potential mental health needs of their students. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


Covid-19: Delaying school reopening by two weeks would halve risks to children, says iSAGE.


Covid-19: Government must plan for schools to reopen, say paediatricians.


Debate: COVID-19 and psychological well-being of children and adolescents in Italy.

Abstract: Italy was the first country in Europe to deal with COVID-19. Measures taken by the government to contain the spread of the virus were based mainly on quarantine and social distancing, with dramatic economic, social and psychological consequences. Since March, Italian children and adolescents are facing school closures, which have caused a disruption in the daily lives of millions of young people and their families. To date, despite the slow reopening, the government has decided to maintain school closures for the entire academic year, leaving the future of young people in uncertainty. There is already some evidence that quarantine and social isolation are having negative impact on children's and adolescents' psychological well-being. Moreover, this situation will mainly affect those children and adolescents with pre-existing vulnerabilities and those suffering of mental disorders. It is imperative to keep young people's needs at the core of reconstruction plans, allowing them to return to school safely, and providing them with some strategies to heal and dealing with this stressful and potentially traumatic situation.


Covid-19: Push to reopen schools risks new wave of infections, says Independent SAGE.


Covid-19: Papers justifying government's plans to reopen schools are "inconclusive," say union bosses.


Back to school: Safe for children with underlying medical conditions.

Abstract: As schools reopen as a result of low community transmission rates of COVID-19, parents and teachers will have understandable concerns about the risks to students and staff.


COVID-19 screening strategies that permit the safe re-opening of college campuses

Abstract: Importance: The COVID-19 pandemic poses an existential threat to many US residential colleges: either they open their doors to students in September or they risk serious financial consequences. Objective: To define SARS-CoV-2 screening performance standards that would permit the safe return of students to campus for the Fall 2020 semester. Design: Decision and cost-effectiveness analysis linked to a compartmental epidemic model to evaluate campus screening using tests of varying frequency (daily-weekly), sensitivity (70%-99%), specificity (98%-99.7%), and cost ($10-$50/test). Reproductive numbers Rt = {1.5, 2.5, 3.5} defined three epidemic scenarios, with additional infections imported via exogenous shocks. We generally adhered to US government guidance for parameterization data. Participants: A hypothetical cohort of 5000 college-age, uninfected students. Main Outcome(s) and Measure(s): Cumulative tests, infections, and costs; daily isolation dormitory census; incremental cost-effectiveness; and budget impact. All measured over an 80-day, abbreviated semester. Results: With Rt = 2.5, daily screening with a 70% sensitive, 98% specific test produces 85 cumulative student infections and isolation dormitory daily census averaging 108 (88% false positives). Screening every 2 (7) days nets 135 (3662) cumulative infections and daily isolation census 66 (252) with 73% (4%) false positives. Across all scenarios, test frequency exerts more influence on outcomes than test sensitivity. Cost-effectiveness analysis selects screening every {2, 1, 7} days with a 70% sensitive test as the preferred strategy for Rt = {2.5, 3.5, 1.5}, implying a screening cost of {$470, $920, $120} per student per semester. Conclusions & Relevance: Rapid, inexpensive and frequently conducted screening (even if only 70% sensitive) would be cost-effective and produce a modest number of COVID-19 infections. While the optimal screening frequency hinges on the success of behavioral interventions to reduce the base severity of transmission (Rt), this could permit the safe return of student to campus.


Distinctive trajectories of COVID-19 epidemic by age and gender: a retrospective modeling of the epidemic in South Korea

Abstract: Objectives: Elderly people had suffered disproportional burden of COVID-19. We hypothesized that males and females in different age groups might have different epidemic trajectories. Methods: Using publicly available data from South Korea, daily new COVID-19 cases were fitted with generalized additive models, assuming Poisson and negative binomial distributions. Epidemic dynamics by age and gender groups were explored with interactions between smoothed time terms and age and gender. Results: A negative binomial distribution fitted the daily case counts best. Interaction between the dynamic patterns of daily new cases and age groups was statistically significant (p<0.001), but not with gender group. People aged 20-39 years led the epidemic processes in the society with two peaks: one major peak around March 1 and a smaller peak around April 7, 2020. The epidemic process among people aged 60 or above was trailing behind that of younger people with smaller magnitude. After March 15, there was a consistent decline of daily new cases among elderly people, despite large fluctuations of case counts among young adults. Conclusions: Although young people drove the COVID-19 epidemic in the whole society with multiple rebounds, elderly people could still be protected from virus infection after the peak of epidemic.


Trust, threats, and consequences of the COVID-19 pandemic in Norway and Sweden: A comparative survey

Abstract: Objectives: Norway and Sweden, two neighboring countries with similar populations, health care systems and socioeconomics, have reacted differently to the COVID-19 pandemic. Norway closed all kindergartens, schools and universities, and banned sports and cultural activities, while Sweden kept most institutions and trainings facilities open. We aimed to compare peoples' attitudes towards authorities and control measures, and effects on life in Norway and Sweden. Design: Anonymous web-based surveys for individuals age 15 or older distributed through Facebook using the snowball method. Setting: Norway and Sweden, mid-March to mid-April, 2020. Participants: Altogether, 3,508 individuals participated in the survey; 3000 in Norway and 508 in Sweden. 79% of the participants were women, 60% of the Norwegians and 47% of the Swedes were between 30-49 years, and around 45% of the participants in both countries had more than 4 years of higher education. Outcome measures: Perceived threat of the pandemic, views on infection control measures, and impact on daily life. We performed descriptive analyses of the responses and compared the two countries. Results: People had high trust in the health services in both countries, but differed in the degree of trust in their government (17% had high trust in Norway and 37% in Sweden). More Norwegians than Swedes agreed that school closure was a good measure (66% Norway and 18% in Sweden), and that countries with open schools were irresponsible (65% in Norway and 23% in Sweden). About the same amount responded that COVID-19 was a large to very large threat to the population (53% in Norway and 58% in Sweden), whereas more Norwegians than Swedes responded that the threat from repercussions of the mitigation measures were large or very large (71% in Norway and 56% in Sweden). Compliance with infection preventive measures was high and similar in the two countries (more than 98%). In Norway, 69% lived a more sedentary life during the pandemic versus 50% in Sweden; and Norwegians reported they ate more than Swedes (44% in Norway and 33% in Sweden). Conclusion: Sweden, with less restrictive measures against the COVID-19 pandemic, had a higher level of trust in the authorities, while Norwegians reported a more negative lifestyle during the pandemic. The level of trust in the health care system and self-reported compliance with preventive measures was high in both countries.


Geospatially Referenced Demographic Agent-Based Modeling of SARS-CoV-2-Infection (COVID-19) Dynamics and Mitigation Effects in a Real-world Community

Abstract: Re-opening societies and economies across the globe following the initial wave of the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) pandemic requires scientifically-guided decision processes and policy development. Public health authorities now consider it highly likely that transmission of SARS-CoV-2 and COVID-19 will follow a pattern of seasonal circulation globally. To guide mitigation strategies and tactics in a location-specific manner, accurate simulation of prolonged or intermittent patterns of social/physical distancing is required in order to prevent healthcare systems and communities from collapsing. It is equally important to capture the stochastic appearance of individual transmission events. Traditional epidemiological/statistical models cannot make predictions in a geospatial temporal manner based on human individuals in a community. Thus, the challenge is to conduct spatio-temporal simulations of transmission chains with real-world geospatial and georeferenced information of the dynamics of the disease and the effect of different mitigation strategies such as isolation of infected individuals or location closures. Here, we present a stochastic, geospatially referenced and demography-specific agent-based model with agents representing human beings and include information on age, household composition, daily occupation and schedule, risk factors, and other relevant properties. Physical encounters between humans are modeled in a time-dependent georeferenced network of the population. The model (GERDA-1) can predict infection dynamics under normal conditions and test the effect of different mitigation scenarios such as school closures, reduced social contacts as well as closure or reopening of public/work spaces. Specifically, it also includes the fate and influence of health care workers and their access to protective gear. Key predictions so far entail: (i) the effect of specific groups on the spreading, specifically that children in school contribute substantially to distribution. (ii) the result of reopening society depends crucially on how strict the measures have been during lock-down. (iii) the outcome of reopening is a stochastic process - in the majority of cases, we must expect a second wave, in some cases not. To the best of our best knowledge, the GERDA-1 model is the first model able to predict a bimodal behavior of SARS-Cov-2 infection dynamics. Given the criticality of the global situation, informing the scientific community, decision makers and the general public seems prudent. Therefore, we here provide a pre-print of the GERDA-1 model together with a first set of predictions and analyses as work in progress.


Assessing the nationwide impact of COVID-19 mitigation policies on the transmission rate of SARS-CoV-2 in Brazil

Abstract: COVID-19 is now identified in almost all countries in the world, with poorer regions being particularly more disadvantaged to efficiently mitigate the impacts of the pandemic. In the absence of efficient therapeutics or vaccines, control strategies are currently based on non-pharmaceutical interventions, comprising changes in population behavior and governmental interventions, among which the prohibition of mass gatherings, closure of non-essential establishments, quarantine and movement restrictions. In this work we analyzed the effects of 547 published governmental interventions, and population adherence thereof, on the dynamics of COVID-19 cases across all 27 Brazilian states, with emphasis on state capitals and remaining inland cities. A generalized SEIR model with a time-varying transmission rate (TR), that considers transmission by asymptomatic individuals, is presented. Confirmed COVID-19 cases were used to calibrate the model parameters using non-linear least squares methods. We analyze the changes on the TR and effective reproduction number as a function of both the extent of enforced measures across Brazilian states as well as population movement. The social mobility reduction index, a measure of population movement, together with the stringency index, adapted to incorporate the degree of restrictions imposed by governmental regulations, were used in conjunction to quantify and compare the effects of varying degrees of policy strictness across Brazilian states. Our results show that population adherence to social distance recommendations plays an important role for the effectiveness of interventions, and represents a major challenge to the control of COVID-19 in low- and middle-income countries.


Relaxing lockdown measures in epidemic outbreaks using selective socio-economic containment with uncertainty

Abstract: After an initial phase characterized by the introduction of timely and drastic containment measures aimed at stopping the epidemic contagion from SARS-CoV2, many governments are preparing to relax such measures in the face of a severe economic crisis caused by lockdowns. Assessing the impact of such openings in relation to the risk of a resumption of the spread of the disease is an extremely difficult problem due to the many unknowns concerning the actual number of people infected, the actual reproduction number and infection fatality rate of the disease. In this work, starting from a compartmental model with a social structure, we derive models with multiple feedback controls depending on the social activities that allow to assess the impact of a selective relaxation of the containment measures in the presence of uncertain data. Specific contact patterns in the home, work, school and other locations for all countries considered have been used. Results from different scenarios in some of the major countries where the epidemic is ongoing, including Germany, France, Italy, Spain, the United Kingdom and the United States, are presented and discussed.


Shut and re-open: the role of schools in the spread of COVID-19 in Europe

Abstract: We investigate the effect of school closure and subsequent reopening on the transmission of COVID-19, by considering Denmark, Norway, Sweden, and German states as case studies. By comparing the growth rates in daily hospitalisations or confirmed cases under different interventions, we provide evidence that the effect of school closure is visible as a reduction in the growth rate approximately 9 days after implementation. Limited school attendance, such as older students sitting exams or the partial return of younger year groups, does not appear to significantly affect community transmission. A large-scale reopening of schools while controlling or suppressing the epidemic appears feasible in countries such as Denmark or Norway, where community transmission is generally low. However, school reopening can contribute to significant increases in the growth rate in countries like Germany, where community transmission is relatively high. Our findings underscore the need for a cautious evaluation of reopening strategies that ensure low classroom occupancy and a solid infrastructure to quickly identify and isolate new infections.


An analysis of SARS-CoV-2 viral load by patient age

Abstract: As children are under-represented in current studies aiming to analyse transmission of SARS-coronavirus 2 (SARS-CoV-2), their contribution to transmission is unclear. Viral load, as measured by RT-PCR, can inform considerations regarding transmission, especially if existing knowledge of viral load in other respiratory diseases is taken into account. RT-PCR threshold cycle data from 3303 patients who tested positive for SARS-CoV-2 (out of 77,996 persons tested in total, drawn from across Germany) were analysed to examine the relationship between patient age and estimated viral load. Two PCR systems were used. In data from the PCR system predominantly used for community and cluster screening during the early phase of the epidemic (Roche LightCycler 480 II), when such screening was frequent practice, viral loads do not differ significantly in three comparisons between young and old age groups (differences in log10 viral loads between young and old estimated from raw viral load data and a Bayesian mixture model of gamma distributions collectively range between -0.11 and -0.43). Data from a second type of PCR system (Roche cobas 6800/8800), introduced into diagnostic testing on March 16, 2020 and used during the time when household and other contact testing was reduced, show a credible but small difference in the three comparisons between young and old age groups (differences, measured as above, collectively range between -0.43 and -0.83). This small difference may be due to differential patterns of PCR instrument utilization rather than to an actual difference in viral load. Considering household transmission data on influenza, which has a similar viral load kinetic to SARS-CoV-2, the viral load differences between age groups observed in this study are likely to be of limited relevance. Combined data from both PCR instruments show that viral loads of at least 250,000 copies, a threshold we previously established for the isolation of infectious virus in cell culture at more than 5% probability, were present across the study period in 29.0% of kindergarten-aged patients 0-6 years old (n=38), 37.3% of those aged 0-19 (n=150), and in 51.4% of those aged 20 and above (n=3153). The differences in these fractions may also be due to differences in test utilization. We conclude that a considerable percentage of infected people in all age groups, including those who are pre- or mild-symptomatic, carry viral loads likely to represent infectivity. Based on these results and uncertainty about the remaining incidence, we recommend caution and careful monitoring during gradual lifting of non-pharmaceutical interventions. In particular, there is little evidence from the present study to support suggestions that children may not be as infectious as adults.


Stepping out of lockdown should start with school re-openings while maintaining distancing measures. Insights from mixing matrices and mathematical models.

Abstract: Australia is one of a few countries which has managed to control COVID-19 epidemic before a major epidemic took place. Currently with just under 7000 cases and 100 deaths, Australia is seeing less than 20 new cases per day. This is a positive outcome, but makes estimation of current effective reproduction numbers difficult to estimate. Australia, like much of the world is poised to step out of lockdown and looking at which measures to relax first. We use age-based contact matrices, calibrated to Chinese data on reproduction numbers and difference in infectiousness and susceptibility of children to generate next generation matrices (NGMs) for Australia. These matrices have a spectral radius of 2.49, which is hence our estimated basic reproduction number for Australia. The effective reproduction number (Reff) for Australia during the April/May lockdown period is estimated by other means to be around 0.8. We simulate the impact of lockdown on the NGM by first applying observations through Google Mobility Report for Australia at 3 locations: home (increased contacts by 18%), work (reduced contacts by 34%) and other (reduced contacts by 40%), and we reduce schools to 3% reflecting attendance rates during lockdown. Applying macro-distancing to the NGM leads to a spectral radius of 1.76. We estimate that the further reduction of the reproduction number to current levels of Reff = 0.8 is achieved by a micro-distancing factor of 0.26. That is, in a given location, people are 26% as likely as usual to have an effective contact with another person. We apply both macro and micro-distancing to the NGMs to examine the impact of different exit strategies. We find that reopening schools is estimated to reduce Reff from 0.8 to 0.78. This is because increase in school contact is offset by decrease in home contact. The NGMs all estimate that adults aged 30-50 are responsible for the majority of transmission. We also find that micro-distancing is critically important to maintain Reff <1. There is considerable uncertainty in these estimates and a sensitivity and uncertainty analysis is presented.