Browsing by Author "Alenquer, M"
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- Balance Between Maternal Antiviral Response and Placental Transfer of Protection in Gestational SARS-CoV-2 InfectionPublication . Gonçalves, J; Melro, M; Alenquer, M; Araújo, C; Castro-Neves, J; Amaral-Silva, D; Ferreira, F; Ramalho, JS; Charepe, N; Serrano, F; Pontinha, C; Amorim, MJ; Soares, HThe intricate interplay between maternal immune response to SARS-CoV-2 and the transfer of protective factors to the fetus remains unclear. By analyzing mother-neonate dyads from second and third trimester SARS-CoV-2 infections, our study shows that neutralizing antibodies (NAbs) are infrequently detected in cord blood. We uncovered that this is due to impaired IgG-NAb placental transfer in symptomatic infection and to the predominance of maternal SARS-CoV-2 NAbs of the IgA and IgM isotypes, which are prevented from crossing the placenta. Crucially, the balance between maternal antiviral response and transplacental transfer of IgG-NAbs appears to hinge on IL-6 and IL-10 produced in response to SARS-CoV-2 infection. In addition, asymptomatic maternal infection was associated with expansion of anti-SARS-CoV-2 IgM and NK cell frequency. Our findings identify a protective role for IgA/IgM-NAbs in gestational SARS-CoV-2 infection and open the possibility that the maternal immune response to SARS-CoV-2 infection might benefit the neonate in 2 ways, first by skewing maternal immune response toward immediate viral clearance, and second by endowing the neonate with protective mechanisms to curtail horizontal viral transmission in the critical postnatal period, via the priming of IgA/IgM-NAbs to be transferred by the breast milk and via NK cell expansion in the neonate.
- Saliva Molecular Testing Bypassing RNA Extraction is Suitable for Monitoring and Diagnosing SARS-CoV-2 Infection in ChildrenPublication . Alenquer, M; Milheiro Silva, T; Akpogheneta, O; Ferreira, F; Vale-Costa, S; Medina-Lopes, M; Batista, F; Garcia, AM; Barreto, VM; Paulino, C; Costa, J; Sobral, J; Diniz-da-Costa, M; Ladeiro, S; Corte-Real, R; Delgado Alves, J; Leite, RB; Demengeot, J; Brito, MJ; Amorim, MJBackground: Adults are being vaccinated against SARS-CoV-2 worldwide, but the longitudinal protection of these vaccines is uncertain, given the ongoing appearance of SARS-CoV-2 variants. Children remain largely unvaccinated and are susceptible to infection, with studies reporting that they actively transmit the virus even when asymptomatic, thus affecting the community. Methods: We investigated if saliva is an effective sample for detecting SARS-CoV-2 RNA and antibodies in children, and associated viral RNA levels to infectivity. For that, we used a saliva-based SARS-CoV-2 RT-qPCR test, preceded or not by RNA extraction, in 85 children aged 10 years and under, admitted to the hospital regardless of COVID-19 symptomatology. Amongst these, 29 (63.0%) presented at least one COVID-19 symptom, 46 (54.1%) were positive for SARS-CoV-2 infection, 28 (32.9%) were under the age of 1, and the mean (SD) age was 3.8 (3.4) years. Saliva samples were collected up to 48 h after a nasopharyngeal swab-RT-qPCR test. Results: In children aged 10 years and under, the sensitivity, specificity, and accuracy of saliva-RT-qPCR tests compared to NP swab-RT-qPCR were, respectively, 84.8% (71.8%-92.4%), 100% (91.0%-100%), and 91.8% (84.0%-96.6%) with RNA extraction, and 81.8% (68.0%-90.5%), 100% (91.0%-100%), and 90.4% (82.1%-95.0%) without RNA extraction. Rescue of infectious particles from saliva was limited to CT values below 26. In addition, we found significant IgM positive responses to SARS-CoV-2 in children positive for SARS-CoV-2 by NP swab and negative by saliva compared to other groups, indicating late infection onset (>7-10 days). Conclusions: Saliva is a suitable sample type for diagnosing children aged 10 years and under, including infants aged <1 year, even bypassing RNA extraction methods. Importantly, the detected viral RNA levels were significantly above the infectivity threshold in several samples. Further investigation is required to correlate SARS-CoV-2 RNA levels to viral transmission.
- Secretory IgA and T Cells Targeting SARS-CoV-2 Spike Protein Are Transferred to the Breastmilk Upon mRNA VaccinationPublication . Gonçalves, J; Juliano, AM; Charepe, N; Alenquer, M; Athayde, D; Ferreira, F; Archer, M; Amorim, MJ; Serrano, F; Soares, HIn view of the scarcity of data to guide decision making, we evaluated how BNT162b2 and mRNA-1273 vaccines affect the immune response in lactating women and the protective profile of breastmilk. Compared with controls, lactating women had a higher frequency of circulating RBD memory B cells and higher anti-RBD antibody titers but similar neutralizing capacity. We show that upon vaccination, immune transfer to breastmilk occurs through a combination of anti-spike secretory IgA (SIgA) antibodies and spike-reactive T cells. Although we found that the concentration of anti-spike IgA in breastmilk might not be sufficient to directly neutralize SARS-CoV-2, our data suggest that cumulative transfer of IgA might provide the infant with effective neutralization capacity. Our findings put forward the possibility that breastmilk might convey both immediate (through anti-spike SIgA) and long-lived (via spike-reactive T cells) immune protection to the infant. Further studies are needed to address this possibility and to determine the functional profile of spike T cells.