Novemember 20, 2023
RSV
Respiratory Syncytial Virus
RSV is a 150 nanometer RNA virus that comes from a human orthopneumovirus that circulates in the winter primarily. Young children and infants infected with RSV mostly have upper respiratory tract symptoms where a subset develop lower respiratory tract disease known as bronchiolitis with the primary infection.
It is the most common reason for hospitalization in infants between 0 and 6 months of age. Bronchiolitis appears as a wheezy, cough centric illness that rarely may progress to increased respiratory effort noted by wheezing, rales (lung crackles - sounds like stepping on leaves), chest wall rib retractions, grunting, fast breathing, nasal flaring and eventually respiratory hypoxia. If it persists, the event can rarely lead to respiratory collapse and death. Annually, 150 children under 5 years of age die from RSV in the US. Most of these children are premature births and have cardiopulmonary disease issues. Term healthy children rarely succumb to RSV in a serious way. A recent study of German infants and children hospitalized with RSV identified these risk factors: age <6 months, birth at 28–37 weeks gestational age, congenital defects, perinatal respiratory and cardiovascular disorders, and various other comorbidities as significant risk factors for ICU admission and death. ( Cai et. al. 2020)
We see tons of cases of RSV annually and rarely see a severe outcome beyond hospitalization and recovery. A real consequence of RSV exposure is the increased incidence of asthma in children significantly infected with RSV. Thus, it is a virus with significant consequence for some part of the population.
The immunobiology of RSV susceptibility is becoming more clear as the years pass. Individuals with an immune polarity toward innate/adaptive T helper cell type 2 (parasite fighting T cell type skewed which is now primarily caused by diets, endocrine disrupting chemicals, pollution and microbiome alterations) are at much higher risk of disease. The lung and the intestinal microbiome of an infant is primarily driven by maternal health, delivery route, feeding route, age at delivery and chemical exposures including peri and postnatal antibiotics. Therefore, as always we have to go upstream and ask ourselves the question, how do we really prevent RSV from affecting so many children. My answers: prevent preterm birth first and foremost and prevent maternal TH2 skewing of immune health. These are not simple realities and they are certainly not being discussed in primary obstetrical care and medical science news.
Prevention is always the key. If we cannot convince society to focus on prevention naturally, then things invariably default to medicine. Thus, in the absence of home based prevention, we shift to pharmaceutical based prevention for the child as a measure of help.
See below for a primer in avoidance of risk through TH2 modulation and maternal health.
Now we have a new medicine on the market called Nirsevimab. It is a human monoclonal antibody that has one change in the YTE motif of the RSV antibody that is not naturally found in humans. The antibody circulates in the body for 4-6 months allowing it to bind, target and kill the RSV virus preventing disease. Efficacy appears to be strong based on trial data.
The company, Sanofi, received FDA approval for this drug after completing clinical trials in children. The data is available to review, so I did. The studies were completed in classic double blind placebo controlled methodology. The MELODY Study has a primary cohort enrolling 1490 healthy late preterm and term infants with 994 participants assigned to receive a single dose of nirsevimab and 496 participants assigned to receive placebo. The second study is the MEDLEY study: The MEDLEY trial evaluated the safety and pharmacokinetics of nirsevimab in infants with congenital heart disease, chronic lung disease, and prematurity in preterm infants. This was a Phase 2/3 randomized, double-blind, palivizumab-controlled study that enrolled 925 infants. There were 310 participants assigned in the CHD–CLD cohort and 615 participants assigned in the preterm cohort. In the other study called HARMONIE, a randomized, open-label, parallel 2-arm study that compared a single dose of nirseviamb to no intervention (standard of care), for the prevention of hospitalizations due to RSV-related lower respiratory tract infection (LRTI) in infants born >29 weeks gestational age entering their first RSV season. 8058 infants were randomized, 4037 received one intramuscular injection of nirsevimab while the remaining 4021 received no intervention.
The studies note equal side effects between placebo and active intervention arms, however, the companies Pharm D representative that I have been conversing with has not answered the main question on drug associated antibodies that were found in 6% of the actively treated patients. What this means is that for every 100 infants given the monoclonal antibody drug, 6 will develop an antibody against the drug. What is the significance of this? They have no idea. My concern is molecular mimicry. Is this protein structure of this drug similar in any way to any human protein structure of the body? If so, could this lead to an issue down the road? No idea yet as the studies were short lived. The second concern that I am waiting for an answer on is this: does this drug have an anaphylaxis risk like many of the monoclonal antibody drugs? The risk of anaphylaxis is 1-2 per 1000 patients for humanized mAb drugs. This has to weighed against the risk of death from RSV which is 1 per 100,000 infected for all infants. This drug has one alteration making it less likely to cause an effect per the company. Anaphylaxis is due to the immunogenic properties of the mAbs protein component. Fully human mAbs, which consist of 99% human components, are associated with a lower risk of anaphylaxis compared to humanized mAbs which carry up to 10% of non human elements. (Badini-Martinez et. al. 2023) Every dose contains: 50 mg of nirsevimab in 0.5 mL (100 mg/mL). Excipients: L-histidine, L-histidine hydrochloride, L-arginine hydrochloride, sucrose, polysorbate 80, water. Polysorbate 80 is a preservative and (rarely) potential trigger on allergy. Let us say, that when they really roll out this medicine in 100,000 babies that 2 anaphylax and get sick or die from the treatment. Which is worse the disease or the treatment? This remains to be seen as the volume treated is a fraction of the amount needed to be certain of safety.
Lots of questions and not enough answers for me to be comfortable yet with this therapy unless the patient in question is higher risk as defined by the CDC. The hypothetical risk may be worth it for children with known risk factors as above.
As always, this is my opinion, the science and not a recommendation for readers.
The to do in avoiding preterm delivery and TH2 skewing reducing total RSV risk for any infant:
1) Avoid c section deliveries where possible
2) Breastfeed for a year
3) Eat a whole 30 style diet while pregnant - no processed foods. Especially, avoid high fructose corn syrup and fructose based beverages and food. This is a huge risk for preeclampsia and preterm birth. Listen to podcast #50 with Rick Johnson discussing the causes of preeclampsia and premature birth
4) Avoid all chemicals while pregnant including and especially maternal skin and hair products that have EDC's in them. Visit www.EWG.org for more on this topic. EDC Information While on the website - if you agree, sign the petition to ban roundup from our food sources!
5) Pregnant women should consult a provider about the right prenatal supplements to take to support optimal health - listen to the podcast #48 with Dr. Leslie Stone for more on this topic
6) Exercise mildly daily while pregnant for enhanced glycemic control
7) Meditate, pray and stay positive in your thoughts as this reduces cortisol and stress chemistry that drives poor immune activity
Dr. M
