Virus World

Neonatal Monkeypox Virus Infection In this report, peripartum transmission of monkeypox virus to a newborn infant is described. The ongoing monkeypox outbreak was recently declared to be a Public Health Emergency of International Concern by the World Health Organization.1 Young children are at risk for severe disease; therefore, early recognition and prompt treatment are important. We report a case of perinatally acquired monkeypox virus infection and adenovirus coinfection in a 10-day-old infant. After the infant’s uneventful birth in late April 2022, a rash developed on day 9 of life. The rash was initially vesicular, starting on the palms and soles and subsequently spreading to the face and trunk, and gradually became pustular (Figure 1). Nine days before the birth, the infant’s father had had a febrile illness, followed by a widespread rash; the rash resolved before the infant’s birth. Four days after the infant’s delivery, a similar rash developed in the mother. The family lived in the United Kingdom, and there was no history of travel to Africa or of contact with any travelers. The infant was transferred to the regional pediatric intensive care unit on day 15 of life owing to evolving hypoxemic respiratory failure (Fig. S1 in the Supplementary Appendix, available with the full text of this letter at NEJM.org). A number of diagnoses (neonatal varicella, herpes simplex virus infection, coxsackievirus or enterovirus infection, staphylococcal skin infection, scabies, syphilis, and gonorrhea) were considered.

The presence of axillary lymphadenopathy, the nature of the skin lesions, and the atypical timeline of intrafamilial infection aroused concern regarding human monkeypox. Polymerase-chain-reaction testing of blood, urine, vesicular-fluid, and throat-swab samples obtained from the infant and mother led to a diagnosis of monkeypox virus infection (clade IIb). Adenovirus was also identified in the infant’s respiratory secretions and blood. The infant’s condition worsened, and invasive ventilation was initiated. A 2-week course of enteral tecovirimat (at a dose of 50 mg twice a day) was commenced in combination with intravenous cidofovir. After 4 weeks in intensive care, including 14 days of invasive ventilation, the infant recovered and was discharged home. The timeline of intrafamilial infection and test results is shown in Figure S2.  Reports of neonatal monkeypox virus infection are rare.3 This was a case of neonatal monkeypox virus infection after peripartum transmission within a family cluster; transplacental transmission could not be ruled out.4 Because this was a single case, it is not possible to attribute the clinical illness to either pathogen (monkeypox virus or adenovirus) directly, nor is it possible to attribute the improvement in the infant’s clinical condition to the use of tecovirimat or cidofovir.5 Monkeypox virus infection should be considered in the differential diagnosis of a neonatal vesicular rash.

Published in NEJM (Oct. 12, 2022):

https://doi.org/10.1056/NEJMc2210828 

A neonate born to a mother infected with SARS-CoV-2 at a hospital in Wuhan, China, had elevated levels of immunoglobuin M, or IgM, and immunoglobulin G, or IgG, antibodies and abnormal cytokine test results 2 hours after birth, suggesting that the newborn was infected in utero, researchers reported in JAMA.

At 2 hours of age, the neonate’s SARS-CoV-2 IgG level was 140.32 AU/mL, and their IgM level was 45.83 AU/mL, the researchers wrote. Cytokines were elevated (interleukin-6, 28.26 pg/mL; interleukin-10, 153.60 pg/mL), and white blood cell count was 18.08 x 109/L. A chest CT was normal. According to the paper, results from five real-time RT-PCR reaction tests on nasopharyngeal swabs taken between 2 hours and 16 days of age were all negative. At 16 days, the infant’s IgM and IgG levels were still elevated. “Although infection at delivery cannot be ruled out, IgM antibodies usually do not appear until 3 to 7 days after infection and the elevated IgM in the neonate was evident in a blood sample drawn 2 hours after birth,” the researchers wrote.

IgG antibodies, unlike IgM antibodies, can be transmitted to the fetus through the placenta and appear later than IgM antibodies. The elevated IgG level may reflect maternal or infant infection. The mother’s vaginal secretions tested negative for SARS-CoV-2, the researchers reported. According to a second letter in JAMA, neonatal throat swabs and blood samples from newborns born from six pregnant women with confirmed COVID-19 at another hospital in Wuhan all tested negative via RT-PCR, but all six infants had antibodies against SARS-CoV-2 in neonatal blood sera samples.

Original Study Published in Jama (March 26, 2020):

https://doi.org//doi:10.1001/jama.2020.4621

It remains unclear whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can be shed into breastmilk and transmitted to a child through breastfeeding. Recent investigations have found no evidence of SARS-CoV-2 in human breastmilk, but sample sizes were small.

We examined milk from two nursing mothers infected with SARS-CoV-2. Both mothers were informed about the study and gave informed consent. Ethical approval for this case study was waived by the Ethics Committee of Ulm University and all samples were anonymised. Clinical data and the timecourse of infection in the two mothers is shown in figure 1. After feeding and nipple disinfection, milk was collected with pumps and stored in sterile containers at 4°C or −20°C until further analysis. We determined viral loads using RT-qPCR for SARS-CoV-2 N and ORF1b-nsp14 genes, in both whole and skimmed milk (obtained after removal of the lipid fraction). 

We detected SARS-CoV-2 RNA in milk samples from Mother 2 for 4 consecutive days. Detection of viral RNA in milk from Mother 2 coincided with mild COVID-19 symptoms and a SARS-CoV-2 positive diagnostic test of the newborn (Newborn 2). Mother 2 had been wearing a surgical mask since the onset of symptoms and followed safety precautions when handling or feeding the neonate (including proper hand and breast disinfection, strict washing, and sterilisation of milk pumps and tubes). However, whether Newborn 2 was infected by breastfeeding or other modes of transmission remains unclear. Further studies of milk samples from lactating women and possible virus transmission via breastfeeding are needed to develop recommendations on whether mothers with COVID-19 should breastfeed.

Published in The Lancet (May 21, 2020):

https://doi.org/10.1016/S0140-6736(20)31181-8

A newborn immune system responds to HIV infection less effectively than a more mature one, so an HIV-positive baby should be started on antiretroviral therapy as soon after birth as possible, new research suggests. Although treatment early in life was known to be advantageous, the study, published Wednesday in Science Translational Medicine, shows the immune system’s response in detail for the first time. The study could energize efforts to treat newborns with HIV, several experts say, and it may help pave the way for an eventual long-lasting treatment or even a cure. In the study, 10 HIV-positive newborns in Botswana were started on antiretroviral therapy—the gold-standard treatment for HIV—within hours or days of birth instead of the more typical four months. If an HIV-positive pregnant woman is receiving treatment, and the amount of virus in her body is well controlled, she will not pass the disease on to her baby, although the infant will have antibodies to HIV in his or her bloodstream. If the mother’s disease is not well controlled, the baby may be born with HIV.

To look for HIV-positive babies, the team screened more than 10,000 newborns using very small amounts of blood. The researchers identified 40 who were HIV-positive and began treating them with a three-drug cocktail within days of birth. The study reported on 10 of those babies, who are now almost two years old, and compared them with HIV-positive babies who did not receive treatment until four months of age.  The early treated babies fared much better in measures of viral levels in their bloodstream and lower levels of immune activity, which predicts the course of the disease, according to the study, which was conducted by a research team at the Ragon Institute of Massachusetts General Hospital, the Massachusetts Institute of Technology and Harvard University, Brigham and Women’s Hospital, and the Botswana Harvard AIDS Institute Partnership in Botswana. The babies coped well with the drug regimen, with only one having to discontinue therapy because of side effects, said Roger Shapiro, a senior author of the paper and an immunologist at the Harvard T. H. Chan School of Public Health, in a news conference on Tuesday. 

The stakes are high for getting tScientists have known since a study published in 2008 that treating HIV-positive babies as early as possible leads to better outcomes, but the new paper provides a “very comprehensive scientific rationale for why that is the case,” says Sten Vermund, dean of the Yale School of Public Health and a pediatrician and infectious disease epidemiologist, who was not involved in the new research. “As soon as possible might be too late. We really would be better treating right at birth.”hese babies treated, says Pat Flynn, an infectious disease specialist at St. Jude Children’s Research Hospital in Memphis, Tenn., who was not involved in the new study. HIV infection can have devastating neurological consequences, likely because of ongoing inflammation in the brain. Every day, between 300 and 500 babies in sub-Saharan Africa are infected with HIV, according to the study’s authors, who cite data from the Joint United Nations Program on HIV/AIDS (UNAIDS).  Up to half of them will die by age two if they do not receive antiretroviral therapy. Infants infected in utero face even worse outcomes than those infected during birth or breastfeeding, said Mathias Lichterfeld, a co-author and an infectious disease specialist at the Ragon Institute and Brigham and Women’s in the news conference. Putting all HIV-positive pregnant women on antiretroviral therapy is the best way to prevent them passing the virus to their babies, but many such women face barriers to accessing treatment, Shapiro said....

Published in Science Translational Medicine (27 Nov. 2019):

https://doi.org/10.1126/scitranslmed.aax7350