Respiratory syncytial virus seropositivity at birth is associated with adverse neonatal respiratory outcomes

Abstract

Background: More than 60 years since the discovery of the respiratory syncytial virus (RSV), the effects of prenatal exposure to this virus remain largely unknown. In this investigation, we sought to find evidence of RSV seroconversion in cord blood and explore its clinical implications for the newborn. Methods: Offspring from 22 pregnant women with a history of viral respiratory infection during the third trimester of pregnancy (respiratory viral illness [RVI] group) and 40 controls were enrolled in this study between 1 September 2016 and 31 March 2019. Cord blood sera were tested for anti-RSV antibodies by indirect fluorescent antibody assay. RSV seropositivity was defined as the presence of anti-RSV immunoglobulin M (IgM) or immunoglobulin A (IgA), in addition to IgG in cord blood serum at ≥1:20 dilution. Results: Anti-RSV IgG was present in all cord blood serum samples from infants born to RVI mothers (95% confidence interval [CI] = 82%-100%), with 16 samples also having elevated titers for either anti-RSV IgA or IgM (73%; 95% CI = 52%-87%). No controls had evidence of anti-RSV antibodies. Eight (50%) seropositive newborns developed at least one respiratory tract finding, including respiratory distress syndrome (N = 8), respiratory failure (N = 3), and pneumonia (N = 1). RSV seropositive newborns also required more days on oxygen, had leukocytosis and elevated C-reactive protein (P = .025, P = .047, and P < .001, respectively). Conclusion: This study provides evidence of acute seropositivity against RSV in cord blood of newborns delivered from mothers with a history of upper respiratory tract illness in the third trimester. Cord blood seropositivity for anti-RSV IgA or IgM was associated with adverse clinical and laboratory outcomes in newborns.

Potential Neurocognitive Symptoms Due to Respiratory Syncytial Virus Infection

“…Interestingly, the serological analysis performed on the mother of the patient showed an elevated titer of antibodies against hRSV, suggesting the possibility of vertical transmission of the virus [40]. Accordingly, a study performed in neonates at birth in which mothers who had a history of respiratory illness during the pregnancy showed anti-hRSV IgA, IgM, and IgG titers in cord blood samples [41]. In these cases, half of the neonates showed respiratory problems that included apnea, respiratory failure, and pneumonia, where 56% of them needed supplemental oxygen [41].…”

“…Accordingly, a study performed in neonates at birth in which mothers who had a history of respiratory illness during the pregnancy showed anti-hRSV IgA, IgM, and IgG titers in cord blood samples [41]. In these cases, half of the neonates showed respiratory problems that included apnea, respiratory failure, and pneumonia, where 56% of them needed supplemental oxygen [41].…”

“…Pathogens 2021, 10, x FOR PEER REVIEW 3 of 12 respiratory failure, and pneumonia, where 56% of them needed supplemental oxygen [41]. Additionally, other important parameters such as white blood cells and C-reactive protein in serum were high in the neonates with anti-hRSV antibodies compared to controls [41].…”

“…Pathogens 2021, 10, x FOR PEER REVIEW 3 of 12 respiratory failure, and pneumonia, where 56% of them needed supplemental oxygen [41]. Additionally, other important parameters such as white blood cells and C-reactive protein in serum were high in the neonates with anti-hRSV antibodies compared to controls [41]. These observations led to studies using the BeWoo cell line (human choriocarcinoma cells), where the peak of the viral load detected was at 24 hrs post-infection applying MOI 5 [18].…”

RSV-induced changes in a 3-dimensional organoid model of human fetal lungs

“…We have previously shown in animal models transplacental transmission of RSV from the lungs of pregnant rats to the developing lungs of their offspring [ 2 ]. More recent studies have confirmed the existence of vertical RSV transmission in humans by: (a) real-time PCR detection of RSV RNA in peripheral blood at birth [ 3 ]; (b) RSV replication in human placenta, where it can be accumulated and then transferred to fetal lung tissues by migrating Hofbauer cells [ 4 ]; and (c) anti-RSV IgA and IgM in the cord blood of newborns delivered from mothers with a history of upper respiratory tract illness in the third trimester [ 5 ]. Also, an independent study confirmed RSV RNA detection in mononuclear cells by droplet digital (dd)PCR in 58% of human cord blood samples tested, with a positivity rate increased up to 80% during winter months [ 6 ].…”