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Literature

General Pediatric Epidemiology

Editorial on children as limited transmitters of COVID-19

Editorial piece highlighting recent papers on the low likelihood of children to be the index case of COVID-19 clusters among families and communities. Majority of children has been infected by an adult; there is no evidence to suggest that children are the drivers of this pandemic, per the authors. The authors acknowledge that school closures happened early. The relatively mild or asymptomatic cases in children may mean they cough less, thereby producing fewer infective particles. School closure has been shown to have minimal effect on slowing viral spread in models.


40 children with COVID-19 and the infection dynamics in their families in Switzerland

A look at the household contacts of 40 children with COVID-19 in Switzerland. Most of the children presented as mild or atypical cases. Of the household contacts, 79% were adults who were suspected or confirmed COVID-19 cases; only in 8% of cases did the child develop symptoms before an adult. The authors conclude that children are not often the index case in a house (<10% of the time).


Contact survey study in China

Study using contact surveys to compare effects of social distancing and school closure on COVID-19 outbreak in Shanghai and Wuhan, China. Found that social distancing (much stricter policy in China than in the US) was enough to control the outbreak. School closure did not interrupt transmission in this model but delayed the peak and reduced it by 40-60%. Primary school children make up less of the population in these cities than US (10% in Shanghai vs 20% in the US).


No difference in respiratory specimen viral loads of SARS-CoV-2 according to age

Analysis of 3,712 cases positive for SARS CoV-2 RT-PCR by various respiratory swabs of all ages, stratified by decades and school stages. No statistical difference found between age groups. Authors caution against opening schools since children may be as infective as adults despite a higher rate of asymptomatic infection.


Report of nosocomial COVID-19 outbreak on a pediatric dialysis unit in Germany

Report of a COVID-19 outbreak on a pediatric dialysis unit in Germany, resulting in 12 positive cases among 48 total exposed (28 health care workers, 13 patients, and 7 visitors). Index case was a healthcare worker. Of the pediatric patients, all with CKD on dialysis, 2 were asymptomatic, the rest had mild to moderate disease. Test in this group was more likely to be positive in patients with symptoms, but symptoms did not predict risk if there was a known exposure. Contact tracing and infection control stopped the outbreak.


Evidence of presymptomatic transmission of COVID-19 in Singapore

A look at 7 clusters of 2–5 patients with COVID-19 in Singapore, each cluster suggesting presymptomatic transmission. At time of writing, these clusters were 6.4% of Singapore’s cases. These clusters occurred in church, singing class, and from travel. These data support other findings that singing (including church) may have higher transmissibility than talking; environmental contamination is and alternate explanation. These findings underline the importance of physical distancing.


CDC Weekly Report describes COVID-19 in US children up to April 2

US CDC report on the epidemiology of COVID-19 through April 2, 2020. There were 2,572 cases of COVID-19 in children. One third (32%) occurred in ages 15-17 years. Known exposure to household or community contact with COVID-19 in 91%. Half reported fever (56%) and/or cough (54%) as a symptom (which is less common than reported by adults). Hospitalization status is known for 745 of these children, 20% of whom were hospitalized (but 5.7% of the total cases including those with incomplete information). Children under 1 year had the highest rates of hospitalization (15–62%). Underlying condition information known in 345 children; of those 23% had one underlying condition, most commonly chronic lung (including asthma). There have been 3 pediatric deaths in the US.


Efficacy of surgical face masks to prevent spread of seasonal coronavirus

Randomized study looking at the effect of surgical face masks on detection of seasonal coronavirus, influenza, and rhinoviruses in respiratory droplets and aerosols from exhaled breaths and coughing over 30 mins in 111 participants. Without a mask, 3 of 10 infected with seasonal coronavirus had positive respiratory droplets and aerosols detected; with a mask none of the 11 participants had positive droplets or aerosols. This supports the use of face masks to prevent spreading infection when worn by infected individuals. This paper does not demonstrate the efficacy of facemasks to prevent well people from getting infected with respiratory viruses, including coronaviruses and did not study SARS-CoV-2.


Early description of SARS CoV-2

Early paper in Nature describing a novel coronavirus (now called SARS-CoV-2) and its genetic similarity to a bat coronavirus  and to SARS-CoV, the virus that caused SARS.


Report of 72,314 COVID-19 cases in China

Summary report of 72,314 cases in China of COVID-19. Of these, 62% were confirmed by throat swab PCR. Prevalence highest (87%) in older age groups (30–79 years), who also suffered more severe disease, although next highest prevalence (8%) was in 20–29 year olds. Children under 19 years make up only 2%. Disease is mild in 81% of cases; case fatality overall is 2.3% among these reported cases. These numbers do not account for the likely large group of asymptomatic people who are likely transmitters of SARS-CoV-2, including children.


Detection of SARS CoV-2 in different specimens

Study examining SARS-CoV-2 detection in various specimens in patients with PCR confirmed COVID-19 via nasopharyngeal swab. Looked at 1070 specimens from 205 patients (age 5–67 years), 19% had severe illness. Bronchoalveolar lavage (BAL) fluid had highest positive rates (93%), then sputum (72%), then nasal swab (63%), pharyngeal swab (32%), feces (29%), and blood (1%); none found in urine. COVID-19 transmission via respiratory process is clear, but whether it can be transmitted by feces (fecal-oral) or blood requires further research.


Incubation estimation for COVID-19 from adult data in China

Analysis of 181 adult COVID-19 cases from areas without known community transmission. Median incubation period 5.1 days, and 97% of patients will develop symptoms within 11.5 days of exposure. This report is based on confirmed cases, which are more likely to be hospitalized. This does not reflect the high number of mild or undiagnosed cases; also does not include data from children.


Study showing multifaceted public health interventions slowed Wuhan transmission

Cohort study of 32,583 confirmed COVID-19 cases in Wuhan looking at effect of various public health interventions on reproduction number (mean secondary infections from a primary source). Multiple interventions associated with decreased reproduction number although cases did not decline until the strictest measures were taken (separate COVID-19 hospital wards with appropriate protective equipment for healthcare staff, public spaces closed and compulsory facemasks and stay-at-home orders, self-monitoring of temperature and symptoms). Data suggest that social distancing and home quarantine measures alone did not reduce transmission. The addition of rapid testing and door-to-door and individual symptom surveys to identify presumptive community cases seemed to be components of reduced transmission.


Conjunctivitis and ocular findings of COVID-19 in adult case series

Case series of 38 adult patients clinically diagnosed with COVID-19 (28 of whom had positive nasopharyngeal swab PCR). Of those, 12 (31.6%) had conjunctivitis and 2 (5.2%) had positive conjunctival swab as well as nasopharyngeal swab for SARS CoV-2 by PCR. Conjunctivitis could be a presenting symptom though in this case series it appeared in the most critical patients. Tears could contribute to transmission.


Review of Wu et al.

Review of Wu et al. with discussion of whether ocular findings could contribute to transmission of COVID-19.


CDC weekly report on COVID-19 in children up to April 2, 2020

US CDC report on the epidemiology of COVID-19 through April 2, 2020. There were 2,572 cases of COVID-19 in children. One third (32%) occurred in ages 15-17 years. Known exposure to household or community contact with COVID-19 in 91%. Half reported fever (56%) and/or cough (54%) as a symptom, less frequent than in adults. Hospitalization status is known for only 745 of these children, 20% of which were hospitalized (which is 5.7% of the total cases, including those with incomplete information). Children under 1 year had the highest rates of hospitalization (15–62%). Underlying condition information known in 345 children; of those 23% had one underlying condition, most commonly chronic lung disease (including asthma). There have been 3 known pediatric deaths in the US in children infected with SARS-CoV-2.


Efficacy of surgical face masks to prevent spread of seasonal coronavirus

Randomized study evaluating the effect of surgical face masks on detection of seasonal coronavirus, influenza, and rhinoviruses in respiratory droplets and aerosols from exhaled breaths and coughing over 30 mins in 111 participants. Without a mask, 3 of 10 infected with seasonal coronavirus had positive respiratory droplets and aerosols detected; with a mask none of the 11 participants had positive droplets or aerosols. This supports the use of face masks to prevent spreading infection when worn by infected individuals. This paper did not demonstrate the efficacy of facemasks to prevent well people from getting infected (not studied). It also did not evaluate SARS-CoV-2.


Epidemiology of COVID-19 among children in China

Retrospective study of 2143 pediatric patients in China with COVID-19 (34% lab-confirmed, 66% suspected). Of the confirmed cases, 13% were asymptomatic, 84% were mild or moderate, fewer than 3% were severe, and fewer than 1% were critical. Only one child, a 14-year-old, died.


CDC weekly report on COVID-19 cases in children in the US

US CDC report on the epidemiology of COVID-19 through March 16, 2020. There were 123 cases of COVID-19 in children; none were hospitalized or died. These cases account for just 1.6-2.5% of the cases in the US. For the country as a whole, there were at the time a total of 2,449 cases of whom about 25% had been hospitalized, 8% admitted to an ICU, and 2.5% who had died. 


Early cohort study of person-to-person transmission of COVID-19 in China

Single cluster study documenting first known person-to-person transmission of COVID-19 in one family. Enrolled 6 family members age 10 to 66 years old who travelled to Wuhan, China from Dec. 29 to Jan. 4 and back to Guongdong province. The 5 adults were all symptomatic; the pediatric patient was asymptomatic. All patients had ground-glass opacities on CT. A family member who had not visited Wuhan also developed symptoms and was confirmed positive for SARS-CoV-2 4 days after the other family members returned home. Genome sequence of each patient’s virus is presented. 


Case series of epidemiological and clinical features in 36 children with COVID-19 in China

Observational cohort of 36 children (ages 1 to 16 years) with confirmed COVID-19 infection. Of these, 89% had positive household contact, prompting testing in the child. Moderate disease in 53%, asymptomatic in 28%, URI in 19%. Fever or cough with pneumonia seen in 30%; pneumonia only (evidenced by imaging: x-ray and/or CT) seen in 22%. Authors posit that lack of symptoms in children contributes to community spread of COVID-19.

Pregnancy and Neonates

Case series of 7 infants 2 months and younger with COVID-19 in New York

McLaren SH, Dayan PS, Fenster DB, et al. Novel coronavirus infection in febrile infants aged 60 days and youngerPediatrics. 2020:e20201550. doi:10.1542/peds.2020-1550

Case series of 7 infants 2 months and younger who presented with fever and confirmed positive for SARS CoV-2 by RT-PCR. Age range 11–56 days. No maternal or delivery data available. Fever was the only presenting symptom for 3 infants; none appeared ill or had respiratory distress. Two had bacterial UTIs, none had severe disease requiring oxygen or ventilation. All were discharged within 7 days. One returned at 14 days febrile, still positive for SARS CoV-2 and did not have signs of other infections.


Guidelines for neonatal resuscitation born to mothers with suspected or confirmed COVID-19

Chandrasekharan P, Vento M, Trevisanuto D, et al. Neonatal resuscitation and postresuscitation care of infants born to mothers with suspected or confirmed SARS-CoV-2 infection. Am J Perinatol. 2020;14203. doi:10.1055/s-0040-1709688

Guidelines in the event of neonatal resuscitation for infants born to mothers with suspected or confirmed COVID-19. Authors acknowledge the limited and inconclusive data on vertical transmission or transmission during delivery. Three options are offered in detail: A) minimal risk of COVID-19 transmission, no mother-infant bonding, ample healthcare resources B) limited risk of transmission, some bonding, declining resources, or C) accept the risk of transmission, encourage bonding, resources/space limited. Emphasis on shared decision making with parents given lack of robust evidence.


Case series of 9 pregnant women with COVID-19 and their neonates in China

Retrospective review of 9 pregnant women with confirmed COVID-19, gestational ages 36–39 weeks, all delivered via Cesarean. No severe maternal pneumonia. In 6 patients amniotic fluid, cord blood, and neonatal throat swabs were obtained, all negative for SARS-CoV-2 except one positive neonatal throat swab at 30 hours. This study did not find convincing evidence of vertical transmission. Placentas were not tested.


Discussion of COVID-19 effect on pregnancy outcomes based on SARS and MERS

Review of the limited literature on SARS and MERS in pregnancy. Both can cause severe complications or maternal death. In China, 1 case of COVID-19 reported in a neonate born to a positive mother; transmission mechanism is unknown but likely via contact and not vertical. Neonate had moderate disease.


Case report of COVID-19 in a neonate in China

Case report of neonate found positive for COVID-19 at 36 hours of life, after mother tested positive. Born via Cesarean delivery with no contact between mother and child post-delivery. Cord blood, placenta, and breastmilk samples were negative for SARS-CoV-2. The neonate had no fever, but CT showed ground-glass opacities. Unclear if this was vertical or horizontal transmission.


Case series of 10 neonates born to mothers with COVID-19 in China

Retrospective analysis of 10 neonates born to mothers with confirmed COVID-19. Of the 9 mothers, 4 had symptoms (fever and cough) prior to delivery and 5 developed symptoms within 6 days postpartum. Intrauterine fetal distress found in fetus of 6 mothers, Cesarean delivery in 7 mothers, only comorbidities were scarred uterus and vaginal bleeding in the 3rd trimester. None of the neonates tested positive for COVID-19; however, 6 were born premature, 6 had “shortness of breath”, 1 died on DOL 9 (respiratory distress, shock, multiple organ failure, and DIC), 4 remained hospitalized at time of publishing. No evidence of vertical transmission, but there is concern for adverse events in the newborn due to perinatal COVID-19 infection.


Is there evidence of vertical transmission of COVID-19?

The following 4 papers present preliminary evidence supporting, but not definitively proving, the possibility of vertical transmission of SARS CoV-2: two papers present cases of neonates with positive IgG and IgM for SARS CoV-2, but negative PCR tests, and one presents neonates with evidence of early-onset COVID-19 disease. The fourth paper is an editorial that cautions diagnosing congenital infections, including COVID-19, using IgM. Infants were either asymptomatic or had mild to moderate disease. Further evidence is needed to understand whether SARS CoV-2 can be transmitted vertically.

1. Case study of neonate with positive SARS CoV-2 IgM in China

Case study of a COVID-19 positive mother who presented with respiratory symptoms and fever together with ground-glass opacities on chest CT; she was admitted and delivered 20 days later. There was no contact between mother and infant post-delivery. Infant had no symptoms and was quarantined in NICU until discharge about a month later. The infant’s IgG and IgM were elevated for SARS CoV-2 at 2 hours of life (IgM sensitivity cited at 70%, specificity 96%) and continued to be elevated at discharge. The infant’s nasopharyngeal swab was negative for SARS CoV-2 throughout her course and she remained asymptomatic with normal chest CT; white count and cytokines were elevated. As IgM cannot cross the placenta, this suggests the possibility, if the test is a true positive, of earlier fetal infection; the IgG level could reflect infant or maternal infection. Mother’s vaginal swab was negative by PCR for SARS CoV-2; placenta and amniotic fluid were not tested.

2. Cohort of 33 neonates born to COVID-19 positive mothers, 3 with early disease.

Cohort of 33 neonates born to SARS CoV-2 positive mothers, 3 of whom were positive for SARS CoV-2; all 3 had pneumonia with respiratory distress by DOL 2, despite cesarean delivery and strict infection control measures. Patient 1: full-term neonate with fever, lethargy, and abnormal chest x-ray; normal labs. Patient 2: full-term neonate with fever, lethargy, and emesis; leukocytosis and abnormal chest x-ray. Patient 3: born at 31 weeks EGA with low initial Apgars, requiring NIPPV and antibiotics for confirmed bacterial sepsis. All 3 neonates were SARS CoV-2 positive on nasopharyngeal swab by DOL 2 and the first two had negative swabs by day 6, the third by day 7. Vertical transmission cannot be ruled out given early disease and PCR positivity, despite cesarean delivery and infection prevention measures. 

3. SARS CoV-2 antibodies present in 6 infants of mothers with COVID-19 in China

Retrospective review of 6 mothers in Wuhan diagnosed with COVID-19, and their infants, all of whom were born via cesarean delivery with mother-infant separation post-delivery. All neonates had negative throat and blood samples; all were asymptomatic. Five neonates had elevated IgG, two had elevated IgM. Cited sensitivity and specificity for IgG 98% and 98%, and for IgM 88% and 99% respectively. No data available for cord blood, placenta, amniotic fluid, or breastmilk. 

4. Editorial on the evidence of possible vertical transmission of COVID-19 in China

Editorial on Dong L et al., 2020 and Zeng L et al., 2020. This editorial cautions against conclusions of vertical transmission given that IgM levels fell quickly in the case presented by Dong et al. and IgM testing is inherently prone to false positives. Also notes that IgM levels are not used for most other congenital diagnosis of other viral infections such as CMV, Zika, or rubella.

Clinical Features - Infants

Case series of 7 infants 2 months and younger with COVID-19 in New York

McLaren SH, Dayan PS, Fenster DB, et al. Novel coronavirus infection in febrile infants aged 60 days and younger. Pediatrics. 2020:e20201550. doi:10.1542/peds.2020-1550

Case series of 7 infants 2 months and younger who presented with fever and confirmed positive for SARS CoV-2 by RT-PCR. Age range 11–56 days. No maternal or delivery data available. Fever was the only presenting symptom for 3 infants; none appeared ill or had respiratory distress. Two had bacterial UTIs, none had severe disease requiring oxygen or ventilation. All were discharged within 7 days. One returned at 14 days febrile, still positive for SARS CoV-2 and did not have signs of other infections.


Infant positive for SARS-CoV-2 PCR 16 hours after birth, concerning for vertical transmission

Case report of the earliest known infection of COVID-19 in a neonate. Mother (history of diabetes, obesity, and previous cesarean delivery) delivered at 33 weeks via cesarean due to maternal respiratory compromise. No delayed cord clamping; baby immediately separated, baby required initial intubation and found positive for SARS-CoV-2 by PCR on nasopharyngeal swab at 16 hours of life (when mother also tested positive). Imaging normal. After extubation, baby developed respiratory symptoms by day 6 requiring nasal cannula. IgG and IgM for SARS-CoV-2 were negative in infant; initially negative in mother but positive by day 4 postpartum (9 days after symptom onset). This case is concerning for vertical transmission given the early positivity and low risk of transmission during delivery or postpartum. Placenta, amniotic fluid, and maternal blood were not tested for SARS-CoV-2.


Two case studies of febrile infants with COVID-19 in New York city

Two case studies of febrile infants (25-day-old and 2-month-old) who had no respiratory symptoms, only fever. Both infants were well appearing, neither infant had known COVID-19 contacts. Infectious evaluations were negative except both were positive for SARS-CoV-2 by PCR on nasopharyngeal swab. The infants were discharged after stopping empiric antibiotics when cultures were negative. These cases highlight the risk of possible introduction of COVID-19 into hospitals when admitting infants for bacterial infection evaluations. Authors encourage routine testing of febrile infants for COVID-19 even in the absence of respiratory symptoms.


Case study of asymptomatic 6-month-old with COVID-19

A case study of a 6-month-old infant exposed to COVID-19 from caregivers and found to have a high viral load of SARS CoV-2 on nasopharyngeal swab. He had no well caregivers and was admitted to the hospital without symptoms. On day 2 of admission, he had viremia with one fever to 38.5°C which resolved within 1 hour; otherwise he was asymptomatic the entire duration. His daily nasopharyngeal PCR tests remained positive until day 17 of admission. SARS CoV-2 was also detected in his stool. Highlights the fact that children may be asymptomatic or only mildly ill and still shed for prolonged periods. Also brings up the need for a pediatric-specific case definition.


Case series of 9 infants under 1 year with COVID-19 in China

Retrospective case series of 9 infants age 28 days to 1 year admitted to the hospital with confirmed COVID-19. Symptoms were fever in 4 children, mild URIs in 2, no symptoms in 1, and no information on the remaining 2. All infants had at least 1 infected family member. None had severe complications requiring ventilation or intensive care.


Case study of 2-month-old with severe COVID-19

Case study of a 55-day old female with confirmed COVID-19 after her caregivers were found positive. On admission, she had rhinorrhea and dry cough; her chest CT showed patchy shadows with ground-glass opacity on the right. White count was normal, but she had elevated LFTs. Her respiratory status progressed to thick sputum with oxygen requirement. Pneumonia was treated empirically with interferon and amoxicillin-clavulanate. By day 7 of illness, her imaging and labs indicated worsening pneumonia and myocardial injury, although she was still eating and stable. By day 12 of illness, she started to recover. By day 15, her nasopharyngeal swabs were negative; anal swabs continued to be positive for SARS CoV-2 until after she was transferred for observation.


Case series of infants born to mothers with SARS in Hong Kong

Case series of 5 neonates born to mothers diagnosed with SARS in 2003 (this is SARS-CoV, not the current virus SARS CoV-2. Two were born extremely preterm (28 and 26 weeks), delivered via Cesarean delivery during the mothers’ acute illness, and required ventilatory support at birth but were eventually weaned off. One born at 32 weeks via Cesarean had a fever but no evidence of respiratory infection. The remaining two had uneventful neonatal courses and were born after the mothers recovered from SARS. None of the infants tested positive for SARS nor showed signs or symptoms; there was no evidence of vertical transmission.

Clinical Features - All Ages

Cohort study of 582 children with COVID-19 in Europe

This cohort study looks at 582 children from 82 health care institutions across 25 European countries all with confirmed SARS CoV-2 infection by PCR. Median age is 5 years, slightly more males than females. Just over half were known to be infected by a parent, but in 40% the source was outside the family or unknown. Two thirds presented with fever. A quarter had pre-existing medical conditions and two-thirds were admitted to the hospital—only 8% required ICU, 4% mechanical ventilation, 3% inotropic support, <1% on ECMO. Risk factors for ICU admission were younger than 1 month old, preexisting conditions, male, and lower respiratory infection at time of presentation. Medications rarely used, the most was hydroxychloroquine in 7%, remdesivir in 3%. Four patients (all over 10 years) died, two with preexisting conditions, two without.


Recommendations for people with epilepsy regarding COVID-19

Recommendations for providers to guide care for patients with epilepsy during the COVID-19 pandemic. Emphasis on limiting hospital and health care facility exposure using telehealth as appropriate, ensuring adequate medication supply, emergency planning, delaying tests or imaging that are non-emergent, and encouraging families to seek care only when necessary. Providers should emphasize the importance of establishing routine and taking care of mental health issues to avoid further exacerbation of seizure disorder. Includes epilepsy resources.


Case report of 10-year-old with new ITP following COVID-19 exposure

Case report of a 10-year-old female who presented with immune thrombocytopenia (ITP). Two and a half weeks earlier, she had had a mild cough and fever after known COVID-19 exposure but had since recovered and been well before the rash appeared. At time of presentation, she was SARS CoV-2 positive by RT-PCR but no longer had respiratory symptoms or fever; she was also positive for rhino/enterovirus. She was admitted for IVIG and discharged with full recovery by 2 weeks. One other adult case of ITP following COVID-19 disease is described. This paper suggests the possibility that SARS CoV-2 may trigger ITP in pediatrics.


Case series of 4 COVID-19 positive children in Malaysia

Case series of 4 children with COVID-19 in Malaysia. Ages 20 months to 11 years. All likely contracted in China. All 4 had mild cases.


Case series of 74 pediatric COVID-19 patients in China

Retrospective case series of 74 pediatric COVID-19 patients in Qingdao and Wuhan, China. None of the children had comorbidities/underlying conditions. About 90% were infected by household contacts; no evidence of transmission from the children to others. Of the 74, only 1 (13-year-old) had severe pneumonia. About a third each were asymptomatic, had acute URI, or had mild LRI. Only a third had cough and/or fever, the most common symptoms. Lab results varied: 18% had elevated CRP, 25% had leukocytosis, abnormal lymphocyte in 13%. About half were screened for other respiratory viruses and half of those were positive. Fecal samples positive for SARS CoV-2 in 13%, shedding time average 11 days. Half the children had radiologic abnormalities and majority were nonspecific for COVID-19 (i.e. no ground glass opacities). Most were not treated; none required mechanical ventilation; all were discharged to quarantine at home.


How does coronavirus kill? Clinicians trace a ferocious rampage through the body, from brain to toes


Data on severity of COVID-19 in children in Spain

Retrospective review of COVID-19 pediatric patients in Madrid, Spain. Between March 2–16, 365 kids were tested with 41 (11%) positive for SARS-CoV-2. Of those 41, median age was 1 year, 60% were hospitalized, ~10% admitted to a PICU needing respiratory support. At this time, testing was reserved for patients likely needing hospitalization or with comorbidities, which probably accounts for the higher proportion of hospitalized patients than found in other studies. This study is consistent with other reports that suggest disease is worse in patients under 1 year. No deaths. Of note, 67% of the 41 positive patients did not have underlying conditions.


Description of COVID-19 clinical manifestations in children

Editorial of pediatric case series from China by Dong et al., 2020. Pediatric cases are less severe than adults, but those with accompanying other respiratory tract infection had more significant illness. Preschool age and infants are more likely to have severe manifestation than older children. Children may play role in community transmission due asymptomatic presentation and prolonged shedding.


Expert opinion on COVID-19 in children based on data from China

Expert opinion statement based on 28 children (age 1.5 months to 17 years) infected with SARS-CoV-2 in China. Most children were exposed by close contact or part of family outbreaks. Patients had a range of symptoms from fever and dry cough, to symptoms consistent with an LRI, but most were asymptomatic. Early phase of disease shows white counts normal or low; LFTs, CRP, and ESR elevated. Authors recommend chest x-ray in suspected cases; chest CT when necessary. Supportive care including hospitalization, oxygen, ventilation, and ECMO when warranted. Includes advice on medication and traditional Chinese medicine that were used but that are not evidence-based. Encourages social isolation as prevention.


Case series of 10 children with COVID-19 in China

Case series of 10 children with confirmed COVID-19, aged 3 months to 11 years. Seven had infected household contacts and 3 had contact with people from Wuhan. Symptom onset between 1 and 10 days from exposure, mean 6.5 days. Clinical manifestations: 8 had fever (resolved 24 hours within onset), 6 had cough, 4 had sore throat. Four had chest x-rays with patchy infiltrates. All received supportive care, none required oxygen. SARS CoV-2 detectable on nasopharyngeal or throat swab within 4-48 hours of symptom onset and undetectable within 6-22 days. Detection by PCR in feces performed in 6 children, 5 of whom were still detectable at time of publishing (a month after symptoms). All children were discharged.


Report of pediatric cases of COVID-19 in China

This report shows that about 1% of 72,000 cases in China occurred in children. About 16% had no symptoms and 65% had pneumonia. Only 3 children of the 171 reported required intensive care/mechanical ventilation, all of whom had co-morbidities (hydronephrosis, leukemia, and intussusception). One death: a 10-month-old with intussusception one month after admission. 


Overview of COVID-19 and other Coronavirus Infections in Children

This is a review article in coronaviruses in children. Epidemiology, clinical course, and management of children with common coronaviruses, SARS, MERS, and current knowledge of COVID-19. In children with COVID-19, about 50% have fever, 38% have cough, 85% have normal white blood count; there have been isolated reports of asymptomatic children with positive chest CTs. Children may be silent transmitters; however most pediatric cases have occurred in household outbreaks. Provides detailed case definition for COVID-19. Treatment is supportive pending future trials.


Case series of epidemiological and clinical features in 36 children with COVID-19 in China

Observational cohort of 36 children (ages 1 to 16 years) with confirmed COVID-19 infection. Of these, 89% had positive household contact, prompting testing in the child. Moderate disease in 53%, asymptomatic in 28%, URI in 19%. Fever or cough with pneumonia seen in 30%; pneumonia only (evidenced by imaging: x-ray and/or CT) seen in 22%. Authors posit that lack of symptoms in children contributes to community spread of COVID-19.

Diagnostics and Imaging

Case series supporting lung ultrasound for management of children with COVID-19 in Italy

Denina M, Scolfaro C, Silvestro E, et al. Lung ultrasound in children with COVID-19. Pediatrics. 2020. doi:10.1542/peds.2020-1157

Case series of 8 pediatric patients hospitalized in Italy, two each with severe, moderate, and mild disease. In 7 of the cases, ultrasound findings correlated with radiographic findings, including showing improvement/resolution on discharge. Though small, these data support the use of bedside ultrasound in COVID-19 management due to reduced radiation exposure and less patient movement around the hospital (thereby likely limiting transmission).


Conjunctivitis and ocular findings of COVID-19 in adult case series

Case series of 38 adult patients clinically diagnosed with COVID-19 (28 of whom had positive nasopharyngeal swab PCR). Of those, 12 (31.6%) had conjunctivitis and 2 (5.2%) had positive conjunctival swab as well as nasopharyngeal swab for SARS CoV-2 by PCR. Conjunctivitis could be a presenting symptom though in this case series it appeared in the most critical patients. Tears could contribute to transmission.


Review of Wu et al.

Review of Wu et al. with discussion of whether ocular findings could contribute to transmission of COVID-19.


Viral loads of SARS CoV-2 in oropharyngeal samples in adults

To KK-W, Tsang OT-Y, Leung W-S, et al. Temporal profiles of viral load in posterior oropharyngeal saliva samples and serum antibody responses during infection by SARS-CoV-2: an observational cohort study. Lancet Infect Dis. 2020;3099(20):1-10. doi:10.1016/S1473-3099(20)30196-1

Cohort study of 23 adult patients with COVID-19 in Hong Kong measuring daily morning viral loads by PCR of posterior oropharynx saliva (expectorated sputum) or endotracheal aspirate samples. Viral loads were highest at presentation and within the first week of symptoms, which may contribute to the high person-to-person transmission rates. SARS CoV-2 remained detectable in a third of patients up to 20 days; persistence did not correlate with clinical course and some patients continued to have detectable viral loads despite symptom recovery. Serum samples were also collected; IgG and IgM were elevated about 10 days after symptom onset. The implications for children are that morning saliva could prove a sensitive means of diagnosis (if proven in children), and transmission may occur both before and after the symptomatic period.


CT findings in children with COVID-19 in China

Case series of 20 pediatric patients (age 1–14 years) with confirmed COVID-19 in China. Clinical manifestations included fever in 60% and cough in 65%. Some children co-infected with RSV or influenza. Lung lesions were found in the early stage on CT in 80% of patients (50% bilaterally, 30% unilaterally); none in the neonates. Subpleural lesions seen in all patients with ground-glass opacities in 60% and consolidation with halo sign in 50%. Of note, 35% of this cohort had “congenital or acquired” diseases.

Treatment

Case series from China looking at ACEI/ARB medications in COVID-19 patients

Case series of 362 adult hospitalized patients with hypertension and COVID-19 (72% older than 60 years, 32% on ACE-inhibitors or ARBs). No differences found in disease severity or risk of death, regardless of type of hypertensive medication. This paper supports current guidelines to continue hypertension treatment in COVID-19 patients.


AHA guidelines on providing CPR to suspected or confirmed COVID-19 patients

American Heart Association and others created guidelines for performing CPR on suspected or confirmed COVID-19 patients. Main recommendations: to reduce provider exposure by donning airborne and droplet PPE and minimizing staff in resuscitation, to prioritize oxygenation and ventilation with lower aerosolization risk including engaging intubation staff with the highest likelihood of success, and to consider the appropriateness of the resuscitation. Also includes algorithm-specific recommendations.


Editorial cautioning against unproven treatments (HCQ and CQ) for COVID-19

Editorial noting limitations of the two human studies on hydroxychloroquine (HCQ) and chloroquine (CQ) in COVID-19 patients (weak methodology, uncontrolled or poorly controlled, no follow up). Misplaced promotion of these drugs as treatments for COVID-19 has led to shortages, which puts patients with certain rheumatological diseases at risk of life-threatening adverse effects from withdrawal. Unregulated use of these drugs as prophylaxis has also led to poisonings and one death. Currently, 10 clinical trials are underway to test whether these drugs are a legitimate form of prophylaxis or treatment for COVID-19.


Two articles on chloroquine’s activity against influenza: effective in vitro but not in humans

OOi et al. show that chloroquine was effective against influenza virus in vitro at concentrations predicted to be lower than found in plasma when the drug is used for malaria treatment. Paton et al., show in a randomized, double-blind, placebo-controlled trial of about 1500 patients without lab-confirmed influenza (that is, the drug was used as chemoprophylaxis) that chloroquine at malaria dosing did not prevent influenza. While chloroquine has been shown to have in vitro efficacy against SARS-CoV-2, it is unknown at this time whether it will be effective in human trials.


IDSA Guidelines for adults with COVID-19

Infectious Disease Society of America’s guidelines for COVID-19. Guidance for antimicrobial medications, tocilizumab, and convalescent plasma acknowledge the “knowledge gap” and encourage enrolling patients in a clinical trial whenever possible prior to use. For facilities without the ability to enroll patients in trials, local registries for similar patients encouraged. Conditional recommendation against use of steroids in pneumonia cases, based on low certainty of evidence; recommend steroid use in ARDS patients in context of a clinical trial. No recommendations are made for a specific treatment course. No pediatric-specific recommendations.


Virologic data on hydroxychloroquine and azithromycin in France

Open label, non-randomized trial evaluating viral load of SARS CoV-2 after treatment with hydroxychloroquine with and without azithromycin compared to controls. Results from 36 adults in France: 20 treated with hydroxychloroquine 200 mg TID for 10 days (6 additionally received azithromycin to prevent bacterial super-infection) versus 16 controls. By day 6 post inclusion, 100% from combination group and 70% of hydroxychloroquine alone group showed viral clearance from nasopharyngeal swab versus 12.5% in controls. Note that this paper did not look at clinical outcomes and it was open-label without randomization.


How CQ and HCQ are plausible treatments for COVID-19

In 2003, in the era of the first SARS epidemic, this article was published. It is a cogent review of the mechanisms of action that antimalarials, such as chloroquine and hydroxychloroquine, might use to inhibit viral infections, such as those caused by SARS-CoV-1, and SARS-CoV-2.

Reviews

Review of pediatric COVID-19 literature

Review of current pediatric literature on COVID-19. Includes articles reviewed for this site.


Expert opinion on COVID-19 in children based on data from China

Expert opinion statement based on 28 children (age 1.5 months to 17 years) infected with SARS-CoV-2 in China. Most children were exposed by close contact or part of family outbreaks. Patients had a range of symptoms from fever and dry cough, to symptoms consistent with an LRI, but most were asymptomatic. Early phase of disease shows white counts normal or low; LFTs, CRP, and ESR elevated. Authors recommend chest x-ray in suspected cases; chest CT when necessary. Supportive care including hospitalization, oxygen, ventilation, and ECMO when warranted. Includes advice on medication and traditional Chinese medicine that were used but that are not evidence-based. Encourages social isolation as prevention.  


Description of COVID-19 clinical manifestations in children

Editorial of pediatric case series from China by Dong et al., 2020. Pediatric cases are less severe than adults, but those with accompanying other respiratory tract infection had more significant illness. Preschool age and infants are more likely to have severe manifestation than older children. Children may play role in community transmission due asymptomatic presentation and prolonged shedding.


Report of pediatric cases of COVID-19 in China

This report shows that about 1% of 72,000 cases in China occurred in children. About 16% had no symptoms and 65% had pneumonia. Only 3 children of the 171 reported required intensive care/mechanical ventilation, all of whom had co-morbidities (hydronephrosis, leukemia, and intussusception). One death: a 10-month-old with intussusception one month after admission. 

Mental Health

Mental health effects of social isolation on primary school children in China

Survey of 1,784 primary school students in China, who had been at home just over a month on average, shows that prevalence of depressive symptoms (23%) and anxiety symptoms (19%) were increased from normal rates. Children worried about COVID-19 had an increased risk of having depressive or anxiety symptoms; no demographic associations. This cohort will continue to be followed.

Multisystem Inflammatory Syndrome-Children (MIS-C)

Case series of 58 children with MIS-C in England

Case series of 58 children with MIS-C (referred to as PIMS-TS for Pediatric Inflammatory Multisystem Syndrome Temporally Associated with SARS CoV-2) in England. Median age 9 years. Of the 58, 45 (78%) had evidence of current or past infections with SARS CoV-2 (15 PCR positive, 40 positive IgG). All presented with persistent fever, half had abdominal pain and erythematous rash; other symptoms varied. Half required intensive care and had shock requiring inotropic support; mechanical ventilation required in 43%. Three patterns of disease were identified: 23 patients had persistent fever and inflammatory markers without organ failure, Kawasaki Disease (KD), or shock; 29 patients had shock and 4 of those had arrhythmias; 7 fulfilled KD criteria. Treatments included IVIG and steroids in two-thirds. One-fifth recovered with just supportive care. Lab work and clinical course not predictive of coronary artery dilatation or aneurysm.


Case series of 44 MIS-C patients in the US

Case Series of 44 patients with multisystem inflammatory syndrome-children (ages <21 years old). All patients had either known exposure to COVID-19 patient with clinical symptoms, confirmed PCR for SARS CoV-2, or positive antibody testing. Gastrointestinal symptoms were present in 84%, fever in 100%, rash in 70.5%. Almost a third had presented within the week prior to admission for mild GI symptoms. Most patients received steroids, IVIG, and anticoagulation. None of the patients required mechanical ventilation.


Case series of 17 children with MIS-C in New York

Case series of 17 pediatric patients with multisystem inflammatory syndrome-children at a single hospital in New York City. All were previously healthy (mild asthma in 3 was the only comorbidity). Median age 8 years. All tested positive for SARS CoV-2 (8 by PCR, 9 by serology). All had fever, 14 had gastrointestinal symptoms, most had mucocutaneous symptoms. Three were hypoxic at presentation and 14 had signs of shock. Inflammatory markers elevated in all patients. Eight patients met Kawasaki criteria. Sixteen patients had abnormal echocardiograms. Fourteen received steroids; 13 received IVIG; all discharged home.


Call to ENTs to consider Kawasaki Disease (or MIS-C) in COVID-19 patients

Recognizing the increased incidence of Kawasaki Disease in children with COVID-19, this paper encourages otolaryngologists to be vigilant for Kawasaki Disease (and MIS-C) as many presentations start with one or more otolaryngologic symptom. Early diagnosis is key. KD and MIS-C can develop during or after recovery from COVID-19.


Editorial on MIS-C and COVID-19

Editorial published prior to naming the MIS-C disease syndrome; cautions practitioners on the unestablished association between Kawasaki Disease and COVID-19. Notes the low documentation of MIS-C in China and the West Coast, although relatively low numbers of pediatric cases may explain the lack of data. The possible causal association between COVID-19 and cases of KD or MIS-C may be overstated given the lower transmission of other childhood viruses from school and daycare closures and parental reluctance to seek medical care in non-emergent situations.


Study from 2005 linking a new coronavirus to Kawasaki Disease

Case-control study conducted in 2005 following the SARS outbreak. Of 11 case children with Kawasaki Disease, 8 were found positive for a then-novel coronavirus versus 1 of the 22 controls. This raises the question of whether coronaviruses can trigger Kawasaki Disease.


Cohort study of children with Kawasaki-like disease in Italy

Comparison of patients with Kawasaki-like disease diagnosis before and since start of the COVID-19 pandemic. In the 5 years before the COVID-19 pandemic, there were 19 cases over 5 years versus 10 cases in the one month after the start of the pandemic—a 30-fold increase. Of the 10 cases since the start of COVID-19, 8 were positive for SARS CoV-2 antibodies and 2 positive by PCR (one serology-negative patient was tested soon after receiving IVIG). Five met Kawasaki Disease Shock Syndrome criteria. All 10 patients recovered with treatment according to the Kawasaki algorithm and were discharged.  (Note, this disease syndrome is now being called MIS-C or Multisystem Inflammatory Syndrome- Children)


Case report of MIS-C in a 6-year-old in Michigan

Previously healthy 6-year-old, initially diagnosed with streptococcal pharyngitis, who developed respiratory distress and hypotension requiring inotropic medications and PICU admission. She met atypical Kawasaki criteria and was treated with IVIG. Her ECHO revealed myocarditis and she required ECMO for 6 days after which she clinically improved.  This same hospital had two other (less severe) cases of MIS-C in COVID-19 positive pediatric patients.


Case series of patients with MIS-C in France and Switzerland

Case series of 35 pediatric patients (mean age 10 years) in pediatric intensive care units in France and Switzerland who developed febrile cardiogenic shock or left ventricular dysfunction—31 of these patients had evidence of current or recent infection with SARS CoV-2 by either nasopharyngeal PCR, fecal PCR, or antibody testing. None had underlying cardiac disease. All were febrile at presentation, 80% had GI symptoms, 17% with chest pain, other symptoms similar to Kawasaki Disease. Median 6 days from symptom onset to heart failure. All patients ended up in PICU; 80% on inotropic drugs for cardiogenic shock, 28% required ECMO (all weaned), two-thirds required mechanical respiratory support. Treated primarily with IVIG; overall clinical outcomes favorable.


Guidance for MIS-C and COVID-19

Clinical guidelines for MIS-C including case definition, clinical management, and treatment principles. Based on expert reviews of cases.

Case report of a 6-month-old with Kawasaki Disease and COVID-19

Case report of a 6-month-old who presented with classic Kawasaki Disease (KD) following 5 days of fever and rash. Patient was admitted and treated according to KD algorithm. COVID-19 testing performed before admission due to x-ray findings and possible congestion and found positive. Patient did well and was discharged to quarantine at home. Relationship between KD and COVID-19 is still unclear.


Statement noting increased MIS-C, many of whom have COVID-19, in the UK

Statement reporting an increase in the number of MIS-C cases in the UK, primarily children presenting with toxic shock-like disease or an illness meeting criteria for atypical Kawasaki Disease. Lab findings: inflammatory markers elevated (ESR, CRP, and ferritin); elevated troponin and proBNP have been noted in these patients when they have myocarditis.

School, Camp, Day Care Re-opening

Amounts of SARS CoV-2 found in nasopharynx stratified by age

Analysis of 145 nasopharyngeal swabs from patients with mild or moderate symptomatic COVID-19 (aged 0–65 years) comparing levels of viral RNA among 3 age groups: younger than 5 years, 5–17 years, and 18–65 years. All swabs were obtained within a week of symptom onset. Found that children under 5 have higher levels of viral RNA than the older age groups. There is evidence of correlation between viral levels and infectivity. This should be considered when planning school or daycare reopening.


Response to Viner et al. rapid systematic review, recommends restarting schools

Editorial response to Viner et al. rapid systematic review for school closure’s effect on COVID-19 pandemic. Agrees the evidence presented may not be generalizable to COVID-19. Given the weak evidence for continued closures and the effect of social isolation on the mental health of children and adolescents, recommends restarting schools as soon as possible.


Modelling study estimates school closures have limited effect on transmission of COVID-19

Modelling study that uses an age-structured mathematical model using data from China, Italy, Japan, Singapore, Canada, and South Korea. Their models estimate that those under age 20 are half as susceptible to infection from COVID-19 than those over 20 years. Also estimate that 79% of infections in ages 10 to 19-year-olds is subclinical (asymptomatic or paucisymptomatic) versus 31% in those over 70 years. They suggest that school closures have a limited effect on controlling the COVID-19 pandemic.


Modelling study weighs benefit of school closures against increased childcare needs by US health care workers

Using US population data and focusing on school closures for children age 3–12 years, this paper estimates that 15% of all health care workers have childcare obligations for this age range that are not met by another non-working adult or older sibling. Nurses and nurse practitioners are the most affected group. A slight rise in the COVID-19 case mortality fraction to 2.3% following school closures (due to the 15% reduction in health care workers) would undo the benefit of the closures. This is likely an underestimate as children younger than age 3 were not included in the projections. Significant variation exists across states and there are several limitations to the model. The small benefit of school closures should be weighed against increasing childcare needs of healthcare workers, exposing grandparents who may become the caregivers, and the longer term economic and developmental losses to the children.


COVID-19 deaths in children are 0.092% of all-cause mortality in 7 countries

This paper compares the death rates among children from COVID-19 compared to all-cause deaths in seven countries, including the United States. Of the 42,846 COVID-19 cases in children, 44 have died, representing 0.092% of all-cause mortality. This mortality rate is equal to or less than that of influenza in these countries.


Guidelines from 5 countries who reopened schools and have no outbreaks of COVID-19

This paper describes the school reopening policies and practices in five countries: China, Demark, Norway, Singapore, Taiwan. These countries have restarted schools and at the time of publishing have not had any COVID-19 cases arising from schools. Each country’s school practices regarding screening, testing, hygiene, etc. are included.


Rapid systematic review of the effect school closures have on disease control

Sixteen articles included in the analysis, including papers analyzing school closures during the 2003 SARS epidemic, preprint articles on COVID-19 school closures, and modelling studies on effect of school closure on transmission of SARS. The overall quality of available evidence is low. There is no strong evidence that school closures interrupted disease transmission in the SARS outbreak or would be predicted to do so in modelling studies. In the COVID-19 pandemic, household contacts have been the origin of the vast majority of cases in children. Differences in transmission dynamics between influenza and COVID-19 make comparisons difficult. Evidence for or against the closure or re-opening of schools and the public health impacts with COVID-19 epidemiology remain equivocal at this point.

LitCOVD, National Library of Medicine complete and up-to-date, searchable COVID-19 database.