MANUSCRIPT CITATION 

Gale C, Quigley MA, Placzek A, Knight M, Ladhani S, Draper ES, et al. Characteristics and outcomes of neonatal SARS-CoV-2 infection in the UK: a prospective national cohort study using active surveillance. Lancet Child Adolesc Health. 2020; doi:10.1016/S2352-4642(20)30342-4. PMID: 33181124 

TYPE OF INVESTIGATION 

Prospective cohort study

QUESTION

What are the incidence, characteristics, modes of transmission and outcomes of SARS-CoV-2 infection in neonates hospitalised in the United Kingdom (UK)?

METHODS

• Design: Prospective cohort study of infants with confirmed SARS-CoV-2 infection in the first 28 days of life who were receiving inpatient care in a UK hospital between March 1 and April 30, 2020
• Allocation: No allocation
• Blinding: Unblinded
• Follow up: All infants were followed to hospital discharge, death or ongoing hospital admission as at July 28 2020
• Setting: The study gathered data through the British Paediatric Surveillance Unit (BPSU), which is responsible for collating disease reports from 155 hospital trusts and health boards and 190 associated neonatal units in the UK. Additionally, cases reported to Public Health England, Health Protection Scotland, Paediatric Intensive Care Audit Network (PICANet) and the UK Obstetric Surveillance System (UKOSS) were also reviewed
• Patients: Eligible patients included neonates with a diagnosis of SARS-CoV-2 confirmed via analysis of a sample taken in the first 28 days of life, and who were receiving or had received inpatient care in a hospital in the UK during this time. The population included infants of varied gestations and ethnic backgrounds
• Interventions: Not applicable
• Outcomes: The incidence of SARS-Cov-2 infection, and identification of cases of vertical and nosocomial transmission. Case severity was determined by pre-set criteria based on one of the first cohort studies of SARS-Cov-2 infection in children (Dong Y, Mo X, Hu Y., et al. Epidemiology of COVID-19 among children in China. Pediatrics. 2020 145:e20200702). Severe disease was defined as having at least two of the following:
  1. Any of hyperthermia (>37.5^oC), apnoea, cough, tachypnoea, respiratory distress or recession, supplemental oxygen requirement, poor feeding or vomiting or diarrhoea
  2. Any of low white blood cell count (<5×10⁹/L), low lymphocyte count (<1×10⁹/L), or raised C-reactive protein concentration (>5mg/L)
  3. Abnormal chest Xray.
• Analysis and sample size: Descriptive statistics and estimation of incidence at a population level using historical UK data for the birth denominator.

MAIN RESULTS

66 neonates were identified, the majority (73%, n=48) of whom were born >37 weeks, with a fairly even split between males and females. A range of ethnicities were represented with 55% (n=36) of neonates identified as white, 21% (n=14) as Asian or Asian-British, 12% (n=8) as Black, African, Caribbean or Black-British and 11% (N=7) as Mixed or Other. Overall, 42% (n=28) of infants were identified as having severe disease.

Amongst babies who were born to mothers with confirmed SARS-CoV-2 infection (26%, n=17), 11% (n=7) were separated immediately after birth. Only 3% of infants overall were suspected of having a vertically acquired infection and 12% suspected of having a nosocomially acquired infection. The remainder of cases were believed to be due to close contact with a family member or other individual with SARS-CoV-2 infection.

The majority of neonates (70%, n=46) received antibiotics. Several cases also received one or more of antivirals, corticosteroids, immunoglobulins or anti-arrhythmics (each n=<3). 33% of neonates (n=22) required one or more types of respiratory support including invasive ventilation, non-invasive ventilatory support and supplemental oxygen.

At the time of analysis, the majority of infants (88%, n=58) had been discharged home (some with follow up community nursing) whilst the remainder were either still admitted, had been transferred to another hospital or had died (n=3, 4 and 1 respectively). The authors note that the single death was considered to be unrelated to SARS-CoV-2 infection.

Patient presentation (see figure 3 in original paper)

*Percentages are calculated on non-missing data

CONCLUSION

The surveillance data collected showed that SARS-Cov-2 infection in neonatal inpatients in UK hospitals occurred rarely, with an incidence of 5.6/10,000 live births. While uncommon, SARS-CoV-2 infection appears to cause more severe disease in neonates than older children. Most cases were acquired either after exposure to a close contact (mother included), or via nosocomial transmission. Possible vertical transmission occurred rarely (2 of 66: (3% of cases) and disease severity for these infants was mild. This finding supports current WHO guidance that babies born to mothers who test positive to SARS-CoV-2 should not be separated from their mothers, and breastfeeding should be encouraged.  Infections in infants from Black, Asian or other minority ethnic backgrounds amongst this study’s population were disproportionately high, a finding which warrants further investigation.

COMMENTARY 

The impact of the SARS-Cov-2 pandemic has transformed the means by which healthcare is delivered, including for perinatal care. Given neonates have unique vulnerabilities to acquiring infections (1), determining optimal practices to prevent and respond to neonatal SARS-CoV-2 infections has been an area of much discussion and debate amongst perinatal healthcare providers.

Published information on the clinical characteristics and mode of acquisition for neonatal SARS-CoV-2 infection was scarce earlier in the pandemic, largely limited to case reports. An early cohort study from China revealed higher disease severity in young infants than older children, by criteria which defined severe and critical cases as including early respiratory and in some cases gastrointestinal symptoms, or progression to severe respiratory or systemic illness, respectively (2). Gale et al’s paper presents data from a peak period of SARS-CoV-2 infection in the United Kingdom (UK), and is an important contribution to our understanding of the incidence, disease severity and transmission modes for neonatal SARS-Cov-2 infection.  This study found that COVID-19 disease severe enough to require hospitalisation was rare in neonates, at 5.6 per 1000 livebirths. While many infections were mild, the study confirms a higher propensity to severe disease in neonates than older children (2,3). 42% of cases were defined as severe, albeit using criteria which may include neonates who, while unwell, would not necessarily require intensive care (2).

Data on transmission modes for neonatal SARS-CoV-2 infection has been limited and conflicting. World Health Organisation (WHO) guidelines endorse keeping mother and baby together in cases of maternal SARS-CoV-2 infection (4). However, confusion as to the likelihood of viral transmission may have influenced adherence to these guidelines, with a number of cases where separation of mothers and babies occurred, including in this cohort. This study confirms that vertical transmission is rare, and that transmission by close contact is unlikely to occur with maternal SARS-CoV-2 infection, even where a mother with active infection co-rooms with her baby. This finding supports ongoing implementation of WHO guidelines to keep mothers and babies together, a practice important for bonding, establishment of feeding, and newborn survival (5). Nosocomial transmission did occur, underscoring a need for stringent infection control procedures for all centres which provide care for patients with SARS-CoV-2 infection.

This paper also highlights inequality in disease incidence for SARS-Cov-2 for babies of Black, Asian and Minority Ethnic (BAME) groups, with an incidence three to four-fold that of individuals classified as having white ethnicity. This finding is not isolated to neonates, with a disproportionately high disease incidence amongst individuals of BAME groups among pregnant women and the wider adult populations (6,7). This observation is a substantial public health concern which likely speaks to the influence of social determinants of health.

Providers of perinatal healthcare still have much to learn about SARS-CoV-2. Ongoing collection and analysis of comprehensive perinatal epidemiologic data will remain paramount for our capacity respond to this pandemic in a manner which is well informed, evidence-based, and effective in optimizing the health and wellbeing of all mothers and babies affected.

REFERENCES

1. Raymond S, Stortz J, Mira JC, Larson SD, Wynn JL, Moldawer. L. Immunological Defects in Neonatal Sepsis and Potential Therapeutic Approaches. Front Pediatr. 2017; 5:14. doi: 10.3389/fped.2017.00014.
2. Dong Y, Mo Z, Hu Y, Qi X, Jiang F, Jiang Z, Tong S. Epidemiology of COVID-19 Among Children in China. 2020; 145(6):e20200702
3. Swann OV, Holden KA, Turtle L, Pollock L, Fairfield CJ, Drake TM, et al. Clinical characteristics of children and young people admitted to hospital with covid-19 in United Kingdom: prospective multicenter observational cohort study. BMJ 2020; 370:m3249. doi: 10.1136/bmj.m3246.
4. World Health Organization. Breastfeeding and COVID-19: Scientific brief. 2020 World Health Organization. Ref: WHO/2019-nCoV/Sci_Brief/Breastfeeding/2020.1. Online: https://www.who.int/publications/i/item/WHO-2019-nCoV-Sci_Brief-Breastfeeding-2020.1 Accessed 1 February 2021.
5. Minckas N, Medvedev MM, Adejuyigbe EA, Brotherton H, Chellani H, et al. Preterm care during the COVID-19 pandemic: A comparative risk analysis of neonatal deaths averted by kangaroo mother care versus mortality due to SARS-CoV-2 infection. EClinicalMedicine 2021; 33: 100733. doi: 1016/j.eclinm.2021.100733.
6. Knight M, Bunch K, Vousden N, Morris E, Simpson N, Gale C, et al. Characteristics and outcomes of pregnant women admitted to hospital with confirmed SARS-CoV-2 infection in UK: national population based cohort study. BMJ 2020; m2107. doi: 10.1136/bmj.m2107.
7. Vahidy FS, Nicholas JC, Meeks, JR, Khan O, Pan A, Jones SL, et al. Racial and ethnic disparities in SARS-CoV-2 pandemic: analysis of a COVID-19 observational registry for a diverse US metropolitan population. BMJ Open;10:e039849. doi: 10.1136/bmjopen-2020-039849.