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
- Dong L, Tian J, He S, et al. Possible vertical transmission of SARS-CoV-2 from an infected mother to her newborn. JAMA. 2020:E1-E3. doi:10.1001/jama.2020.4621
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.
- Zeng L, Xia S, Yuan W, et al. Neonatal early-onset infection with SARS-CoV-2 in 33 neonates born to mothers with COVID-19 in Wuhan, China. JAMA Pediatr. 2020;23(77):26-28. doi:10.1001/jamapediatrics.2020.0878
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
- Zeng H, Xu C, Fan J, et al. Antibodies in infants born to mothers with COVID-19 pneumonia. JAMA. 2020:E1-E2. doi:10.1001/jama.202.4861
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
- Kimberlin D, Stagno S. Can SARS-CoV-2 infection be acquired in utero? More definitive evidence is needed. JAMA. 2020:E1-E2. doi:10.1001/jama.2020.4868
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.
Early cohort study of person-to-person transmission of COVID-19 in China
- Chan, J.F., et al., A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster. Lancet, 2020. 24: p. 24.
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.
Expert opinion on COVID-19 in children based on data from China
- Shen, K., et al., Diagnosis, treatment, and prevention of 2019 novel coronavirus infection in children: experts’ consensus statement. World J Pediatr, 2020.
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 epidemiological and clinical features in 36 children with COVID-19 in China
- Qiu H, Wu J, Hong L, Luo Y, Song Q, Chen D. Clinical and epidemiological features of 36 children with coronavirus disease 2019 (COVID-19) in Zhejiang, China: an observational cohort study. Lancet. 2020;(20):1-8. doi: https://doi.org/10.1016/ S1473-3099(20)30198-5
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.
Case study of asymptomatic 6-month-old with COVID-19
- Kam KQ, Yung CF, Cui L, Lin Tzer Pin R, Mak TM, Maiwald M, et al. A well infant with coronavirus disease 2019 (COVID-19) with high viral load. Clin Infect Dis. 2020.
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
- Wei M, Yuan J, Liu Y, Fu T, Yu X, Zhang ZJ. Novel coronavirus infection in hospitalized infants under 1 year of age in China. JAMA. 2020.
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
- Cui Y, Tian M, Huang D, Wang X, Huang Y, Fan L, et al. A 55-day-old female infant infected with COVID 19: presenting with pneumonia, liver injury, and heart damage. J Infect Dis. 2020.
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.
Virologic data on hydroxychloroquine and azithromycin in France
- Gautret P, Lagier J, Parola P, et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents. 2020: 1-24.
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.
Case series of 10 children with COVID-19 in China
- Cai J, et al. A case series of children with 2019 novel coronavirus infection: clinical and epidemiological features. Clin Infect Dis. 2020. doi: 10.1093/cid/ciaa198
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.
Case series of infants born to mothers with SARS in Hong Kong
- Shek CC, Ng PC, Fung GPG, et al. Infants born to mothers with severe acute respiratory syndrome. Pediatrics. 2003;112(4). doi:10.1542/peds.112.4.e254
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.
Epidemiology of COVID-19 among children in China
- Dong Y, Mo X, Hu Y, Qi X, Jiang F, Jiang Z, et al. Epidemiological characteristics of 2143 pediatric patients with 2019 coronavirus disease in China. Pediatrics. 2020. doi: 10.1542/peds.2020-0702
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.
CT findings in children with COVID-19 in China
- Xia W, Shao J, Guo Y, Peng X, Li Z, Hu D. Clinical and CT features in pediatric patients with COVID-19 infection: Different points from adults. Pediatr Pulmonol. 2020:1–6.
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.
Description of COVID-19 clinical manifestations in children
- Cruz A, Zeichner S. COVID-19 in children: initial characterization of the pediatric disease. Pediatrics. 2020. doi: 10.1542/peds.2020-0834
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
- Lu X, Liquiong Z, Du H, et al. SARS-CoV-2 infection in children. N Engl J Med. 2020:1-3.
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.
CDC weekly report on COVID-19 cases in children in the US
- Centers for Disease Control and Prevention. Severe outcomes among patients with coronavirus disease 2019 (COVID-19)—United States, February 12-March 15, 2020. Morb Mortal Wkly Rep. 2020;69(March 18, 2020).
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.
Discussion of COVID-19 effect on pregnancy outcomes based on SARS and MERS
- Schwartz DA, Graham AL. Potential maternal and infant outcomes from (Wuhan) coronavirus 2019-nCoV infecting pregnant women: Lessons from SARS, MERS, and other human coronavirus infections. Viruses. 2020;12(2):1-16. doi:10.3390/v12020194
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
- Wang S, Guo L, Chen L, et al. A case report of neonatal COVID-19 infection in China. Clin Infect Dis. 2020:ciaa225. doi:10.1093/cid/ciaa225
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.
Comparison of SARS CoV-2 to SARS CoV-1 stability on surfaces
- van Doremalen N, Bushmaker T, Morris DH, et al. Aerosol and surface stability of HCoV-19 (SARS-CoV-2) compared to SARS-CoV-1. J Chem Inf Model. 2020;53(9):1689-1699. doi:10.1017/CBO9781107415324.004
SARS-CoV-2 found on plastic up to 72 hours, stainless steel up to 48 hours, and on cardboard up to 24 hours. It is viable in aerosols at least 3 hours. This is a laboratory experiment and it is not clear how it translates to infectivity, but points out that fomites are likely playing a role in transmission.
Overview of COVID-19 and other Coronavirus Infections in Children
- Zimmerman P, Curtis N. Coronavirus infections in children including COVID-19. Pediatr Infect Dis J. 2020:1-14. doi:10.1097/INF.0000000000002660
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 10 neonates born to mothers with COVID-19 in China
- Zhu H, Wang L, Fang C, et al. Clinical analysis of 10 neonates born to mothers with 2019-nCoV pneumonia. Transl Pediatr. 2020;1(9):51-60. doi:10.21037/tp.2020.02.06
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.