Virus World

A new COVID-19 study reveals children with coronavirus, even those who are asymptomatic, can shed the virus for up to three weeks following infection. New research suggests that children can shed SARS-CoV-2, the virus that causes COVID-19, even if they never develop symptoms or for long after symptoms have cleared. But many questions remain about the significance of the pediatric population as vectors for this sometimes deadly disease, according to an invited commentary by Children’s National Hospital doctors that accompanies this new study published online Aug. 28, 2020 in JAMA Pediatrics. The commissioned editorial, written by Roberta L. DeBiasi, M.D., M.S., chief of the Division of Pediatric Diseases, and Meghan Delaney, D.O., M.P.H., chief of the Division of Pathology and Lab Medicine, provides important insight on the role children might play in the spread of COVID-19 as communities continue to develop public health strategies to reign in this disease.

The study that sparked this commentary focused on 91 pediatric patients followed at 22 hospitals throughout South Korea. “Unlike in the American health system, those who test positive for COVID-19 in South Korea stay at the hospital until they clear their infections even if they aren’t symptomatic,” explains Dr. DeBiasi. The patients here were identified for testing through contact tracing or developing symptoms. About 22% never developed symptoms, 20% were initially asymptomatic but developed symptoms later, and 58% were symptomatic at their initial test. Over the course of the study, the hospitals where these children stayed continued to test them every three days on average, providing a picture of how long viral shedding continues over time. The study’s findings show that the duration of symptoms varied widely, from three days to nearly three weeks. There was also a significant spread in how long children continued to shed virus and could be potentially infectious. While the virus was detectable for an average of about two-and-a-half weeks in the entire group, a significant portion of the children—about a fifth of the asymptomatic patients and about half of the symptomatic ones—were still shedding virus at the three week mark.  Drs. DeBiasi and Delaney write in their commentary that the study makes several important points that add to the knowledge base about COVID-19 in children. One of these is the large number of asymptomatic patients—about a fifth of the group followed in this study. Another is that children, a group widely thought to develop mostly mild disease that quickly passes, can retain symptoms for weeks. A third and important point, they say, is the duration of viral shedding. Even asymptomatic children continued to shed virus for a long time after initial testing, making them potential key vectors.

However, the commentary authors say, despite these important findings, the study raises several questions. One concerns the link between testing and transmission. A qualitative “positive” or “negative” on testing platforms may not necessarily reflect infectivity, with some positives reflecting bits of genetic material that may not be able to make someone sick or negatives reflecting low levels of virus that may still be infectious.  Testing reliability may be further limited by the testers themselves, with sampling along different portions of the respiratory tract or even by different staff members leading to different laboratory results. It’s also unknown whether asymptomatic individuals are shedding different quantities of virus than those with symptoms, a drawback of the qualitative testing performed by most labs. Further, testing only for active virus instead of antibodies ignores the vast number of individuals who may have had and cleared an asymptomatic or mild infection, an important factor for understanding herd immunity. Lastly, Drs. DeBiasi and Delaney point out, the study only tested for viral shedding from the respiratory tract even though multiple studies have detected the virus in other bodily fluids, including stool. It’s unknown what role these other sources might play in the spread of this disease...

Original study published in JAMA (August 21, 2020):

https://doi.org/10.1001/jamapediatrics.2020.3988 

See also editorial (August 28, 2020)

https://doi.org/10.1001/jamapediatrics.2020.3996

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