Detectable antibodies against SARS-CoV-2 in newborns from mothers infected with COVID-19 at different gestational ages

Abstract

Maternal antibodies may partially confer protection to neonates from some viral infections1Chu H.Y. Englund J.A. Maternal immunization.Clin Infect Dis. 2014; 59: 560-568Crossref PubMed Scopus (99) Google Scholar; however, understanding the nature and durability of perinatal humoral immune responses to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is limited.2Gudbjartsson D.F. Norddahl G.L. Melsted P. Gunnarsdottir K. Holm H. Eythorsson E. et al.Humoral immune response to SARS-CoV-2 in Iceland.N Engl J Med. 2020; 383: 1724-1734Crossref PubMed Scopus (607) Google Scholar In this study, dynamic changes of antibody levels of six newborns born to mothers with corona virus disease-2019 (COVID-19) were investigated. Out of six pregnant women with laboratory-confirmed COVID-19, three were in the second trimester of pregnancy, with gestational ages of 28 weeks and 4 days, 29 weeks and 5 days, and 17 weeks and 5 days, and the other three were in the third trimester of pregnancy, with gestational ages of 36 weeks and 1 day, 37 weeks and 2 days, and 34 weeks and 1 day. Throat swab and blood samples were collected from all pregnant women at delivery and from their newborns at birth. After delivery, all six mothers with their newborns were followed-up for six months and were re-tested for viral nucleic acid and serum antibodies every month (±1 week). Antibody testing was conducted using qualitative (colloidal gold) antibody-detection kits or quantitative chemiluminescence immunoassay. Characteristics and chest computed tomography findings of six pregnant women are summarized in Supplementary Table 1 and in Supplementary Figs. 1 and 2, respectively. Three women with COVID-19 were in the third trimester of pregnancy and their three newborns were delivered at the acute phase of infection. Another three women with COVID-19 were in the second trimester of pregnancy and delivered three newborns at 37, 56, and 111 days after recovery from COVID-19. Neonatal characteristics at birth are presented in Supplementary Table 2. All six newborns were full-term infants with gestational ages between 37 weeks and 5 days and 40 weeks and 5 days. All six pregnant women had positive nucleic acid test results when hospitalized, with median duration of viral shedding after admission of 29.0 (range, 18.8–42.3) days; 20, 26, and 39 days in the three infected pregnant women during the third trimester and 52, 25, and 32 days in the three infected women during the second trimester. After delivery, neither of the mothers nor their infants had positive polymerase chain reaction (PCR) results, symptoms, or evidence of COVID-19. Levels of IgG and IgM antibody are shown in Table 1. All women in the third trimester of pregnancy had detectable levels of specific IgM and IgG at delivery, and their newborns at birth had apparent IgG and one had IgM. After delivery, one mother had detectable IgM for 60 days, another for 90 days, and the third had it <30 days. However, those three mothers had recognizable IgG for four or five months. Of their three newborns, two had duration of detectable IgG of 120 days and one had duration of 60 days. One had duration of IgM above 10 AU/mL for 30 days. Upon delivery, three infected women in the second trimester with their newborns were asymptomatic having negative PCR results; however, were positive for IgG but negative for IgM. Six months later, these mothers still had high titers of IgG reaching a >4-fold increase above the cut-off value. Detectable levels of IgG in three newborns lasted for 150, 180, and 180 days, respectively.Table 1SARS Cov-2 specific antibodies in six infants and their mothers with COVID-19.aNo. 1-3 were women in the second trimester of pregnancy and No. 4-6 were women in the third trimester of pregnancy.No.IgM/IgG titers, AU/mLbThe cut-off value is 10.0 AU/ml., by age of infantD 1D 30D 60D 90D 120D 150D 1801Mother8.15/166.988.68/169.307.18/169.705.39/71.994.75/45.463.61/34.823.53/40.52Infant4.52/68.824.12/45.385.24/38.263.45/26.372.86/22.472.03/12.211.65/8.722Mother9.41/753.708.72/291.677.12/273.38(−)/(+)cAntibody testing was conducted using qualitative (Colloidal Gold) antibody-detection kits.(−)/(+)cAntibody testing was conducted using qualitative (Colloidal Gold) antibody-detection kits.(−)/(+)cAntibody testing was conducted using qualitative (Colloidal Gold) antibody-detection kits.4.61/249.99Infant7.27/132.756.82/114.266.53/103.58(−)/(+)cAntibody testing was conducted using qualitative (Colloidal Gold) antibody-detection kits.(−)/(+)cAntibody testing was conducted using qualitative (Colloidal Gold) antibody-detection kits.(−)/(+)cAntibody testing was conducted using qualitative (Colloidal Gold) antibody-detection kits.2.05/51.543Mother8.91/122.158.64/180.037.53/166.545.18/152.70(−)/(+)cAntibody testing was conducted using qualitative (Colloidal Gold) antibody-detection kits.(−)/(+)cAntibody testing was conducted using qualitative (Colloidal Gold) antibody-detection kits.5.34/92.78Infant6.49/63.265.37/53.325.54/44.834.35/38.63(−)/(+)cAntibody testing was conducted using qualitative (Colloidal Gold) antibody-detection kits.(−)/(+)cAntibody testing was conducted using qualitative (Colloidal Gold) antibody-detection kits.2.31/21.434Mother(+)/(+)cAntibody testing was conducted using qualitative (Colloidal Gold) antibody-detection kits.8.24/73.10(−)/(+)cAntibody testing was conducted using qualitative (Colloidal Gold) antibody-detection kits.(−)/(+)cAntibody testing was conducted using qualitative (Colloidal Gold) antibody-detection kits.(−)/(+)cAntibody testing was conducted using qualitative (Colloidal Gold) antibody-detection kits.(−)/(−)cAntibody testing was conducted using qualitative (Colloidal Gold) antibody-detection kits.(−)/(−)cAntibody testing was conducted using qualitative (Colloidal Gold) antibody-detection kits.Infant(−)/(+)cAntibody testing was conducted using qualitative (Colloidal Gold) antibody-detection kits.4.53/48.51(−)/(+)cAntibody testing was conducted using qualitative (Colloidal Gold) antibody-detection kits.(−)/(+)cAntibody testing was conducted using qualitative (Colloidal Gold) antibody-detection kits.(−)/(+)cAntibody testing was conducted using qualitative (Colloidal Gold) antibody-detection kits.(−)/(−)cAntibody testing was conducted using qualitative (Colloidal Gold) antibody-detection kits.(−)/(−)cAntibody testing was conducted using qualitative (Colloidal Gold) antibody-detection kits.5Mother(+)/(+)cAntibody testing was conducted using qualitative (Colloidal Gold) antibody-detection kits.18.16/72.2810.46/44.528.96/33.27(−)/(+)cAntibody testing was conducted using qualitative (Colloidal Gold) antibody-detection kits.(−)/(−)cAntibody testing was conducted using qualitative (Colloidal Gold) antibody-detection kits.(−)/(−)cAntibody testing was conducted using qualitative (Colloidal Gold) antibody-detection kits.Infant(−)/(+)cAntibody testing was conducted using qualitative (Colloidal Gold) antibody-detection kits.6.53/35.262.07/16.390.37/0.60(−)/(−)(−)/(−)(−)/(−)6Mother279.72/107.89112.66/116.30108.01/98.37(+)/(+)cAntibody testing was conducted using qualitative (Colloidal Gold) antibody-detection kits.(−)/(+)cAntibody testing was conducted using qualitative (Colloidal Gold) antibody-detection kits.(−)/(+)cAntibody testing was conducted using qualitative (Colloidal Gold) antibody-detection kits.(−)/(−)cAntibody testing was conducted using qualitative (Colloidal Gold) antibody-detection kits.Infant45.83/140.3211.75/69.94(−)/(+)cAntibody testing was conducted using qualitative (Colloidal Gold) antibody-detection kits.(−)/(+)cAntibody testing was conducted using qualitative (Colloidal Gold) antibody-detection kits.(−)/(+)cAntibody testing was conducted using qualitative (Colloidal Gold) antibody-detection kits.(−)/(−)cAntibody testing was conducted using qualitative (Colloidal Gold) antibody-detection kits.(−)/(−)cAntibody testing was conducted using qualitative (Colloidal Gold) antibody-detection kits.a No. 1-3 were women in the second trimester of pregnancy and No. 4-6 were women in the third trimester of pregnancy.b The cut-off value is 10.0 AU/ml.c Antibody testing was conducted using qualitative (Colloidal Gold) antibody-detection kits. Open table in a new tab In this study, levels of SARS-CoV-2 specific antibodies in infants from mothers infected with COVID-19 at different gestational ages were monitored. Of six pregnant infected women in January, 2020, three were in their third trimester and the other three at their second trimester. However, they had different responses of immunity. Three infected women in the third trimester had positive reverse transcription (RT)-PCR results and detectable levels of IgG and IgM upon delivery. Their three newborns did not have positive RT-PCR results but had detectable IgG at birth and one had IgM. SARS-CoV-2 nucleic acid was not detected in three infected women in their second trimester of pregnancy at delivery and in their newborns at birth. Nevertheless, both mothers and their babies were positive for virus-specific IgG but were negative for IgM. After delivery, women in the second trimester of pregnancy and their babies had a longer duration of detectable IgG than women in the third trimester of pregnancy and their babies (6, 6, and 6 vs. 4, 4, and 5 months in mothers and 5, 6, and 6 vs. 4, 4, and 2 months in infants, respectively). Maternal antibodies may protect the fetus from maternal in utero transmission.1Chu H.Y. Englund J.A. Maternal immunization.Clin Infect Dis. 2014; 59: 560-568Crossref PubMed Scopus (99) Google Scholar However, antibody persistence in infants born to infected women with COVID-19 is very unclear. Thus, this study focused on the potential duration of neonatal antibody IgG. Regarding the duration of passive immunity from gestational maternal SARS-CoV-2 specific IgG in neonates, our findings are in agreement with published results.2Gudbjartsson D.F. Norddahl G.L. Melsted P. Gunnarsdottir K. Holm H. Eythorsson E. et al.Humoral immune response to SARS-CoV-2 in Iceland.N Engl J Med. 2020; 383: 1724-1734Crossref PubMed Scopus (607) Google Scholar, 3Gao J. Li W. Hu X. Wei Y. Wu J. Luo X. et al.Disappearance of SARS-CoV-2 antibodies in infants born to women with COVID-19, Wuhan, China.Emerg Infect Dis. 2020; 26: 2491-2494Crossref PubMed Scopus (12) Google Scholar, 4Li K. Huang B. Wu M. Zhong A. Li L. Cai Y. et al.Dynamic changes in anti-SARS-CoV-2 antibodies during SARS-CoV-2 infection and recovery from COVID-19.Nat Commun. 2020; 11: 6044Crossref PubMed Scopus (120) Google Scholar These results also demonstrated that asymptomatic infants had a strong immune response from their COVID-19 mothers infected in the second trimester of pregnancy. This may be related to the characteristics of antibodies, since IgG may be passively transferred from the mother to the fetus through the placenta, which begins at the end of the second trimester and reaches high levels at the time of birth.5Kohler P.F. Farr R.S. Elevation of cord over maternal IgG immunoglobulin: evidence for an active placental IgG transport.Nature. 1966; 210: 1070-1071Crossref PubMed Scopus (244) Google Scholar Maternal IgM usually does not pass through an intact placental barrier due to its larger macromolecular structure. Our data might have implications for understanding the duration of protective effect from maternal to infants, and for potential vaccination efforts. However, more work is needed to understand SARS-CoV-2 immunity in infants, because it is unclear what level of antibody titers in infants are considered protective against infection.6Alter G. Seder R. The power of antibody-based surveillance.N Engl J Med. 2020; 383: 1782-1784Crossref PubMed Scopus (59) Google Scholar