Maternal–foetal transfer of severe acute respiratory syndrome coronavirus 2 antibodies among women with and those without HIV infection : AIDS

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Maternal–foetal transfer of severe acute respiratory syndrome coronavirus 2 antibodies among women with and those without HIV infection

Nunes, Marta C.a,b; Jones, Stephaniea,b; Ditse, Zanelea,b; da Silva, Kellya,b; Serafin, Natalia,b; Strehlau, Renatec; Wise, Amyd; Burke, Meganc; Baba, Vuyelwae; Baillie, Vicky L.a,b; Nzimande, Ayandaa; Jafta, Nwabisaa; Adam, Marye; Mlandu, Philiswae; Melamu, Mpolokenge; Phelp, Juliettee; Feldman, Charlesf; Adam, Yasmine; Madhi, Shabir A.a,b,g,∗; Kwatra, Gaurava,b,g,h,∗

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AIDS 36(13):p 1777-1782, November 1, 2022. | DOI: 10.1097/QAD.0000000000003345
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South Africa has the highest rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in Africa, with more than 3,7 million laboratory-confirmed cases and 99 890 confirmed deaths by 20 March 2022 ( South Africa also has among the highest prevalence of HIV infection globally, with an estimated 8.2 million (14% of population) people with HIV of whom approximately 72% are on antiretroviral treatment (ART) (; It is unclear whether SARS-CoV-2 infection impacts negatively on pregnant women with HIV as compared with those without HIV infection, as well as on pregnancy-related conditions [1–3].

A few studies have reported on the immunological responses after coronavirus disease (COVID-19) in adults living with HIV, unrelated to pregnancy, and have generally shown similar antibody responses compared with individuals without HIV [4–6]. Studies among pregnant women have also demonstrated that this population mount robust humoral immune responses to SARS-CoV-2 infection, in particular to SARS-CoV-2 nucleocapsid protein, spike full-length protein, and spike receptor-binding domain [7]; and that anti-SARS-CoV-2 immunoglobulin G (IgG) are transferred via the placenta to the foetus [7–11]. We are, however, unaware of any studies comparing the levels of anti-SARS-CoV-2 IgG between pregnant women living with HIV (WLWHIV) and pregnant women without HIV and the transplacental transfer of antibodies to their infants.

In this work, we measured SARS-CoV-2 full-length antispike protein IgG in blood samples collected from WLWHIV and without HIV when presenting in labour, and from paired cord-blood samples, independently of previous SARS-CoV-2 confirmed infection.


We conducted two parallel, observational studies from April 2020 to March 2021, in South Africa, to assess the association of SARS-CoV-2 infection, diagnosed on nasal swabs, and birth outcomes: study A, enrolled women at any stage during pregnancy and they were followed up until delivery; study B enrolled women upon presentation in labour. At the time of enrolment in either study, nasal swabs were collected for investigation for SARS-CoV-2 infection by nucleic acid amplification test (NAAT) [12]. At the time of delivery, maternal venous blood and cord-blood were collected whenever possible and were analysed for SARS-CoV-2 full-length antispike protein IgG by a quantitative assay on the Luminex platform as described [13,14]. Thirty-two binding antibody units (BAU)/ml were established as the assay threshold indicative of antibody detection, that is, seropositivity, for details please see [13]. Only seropositive women were included in the current analysis.

Samples included in the current analysis were collected between May 2020 and January 2021 when no COVID-19 vaccine was available in South Africa.

Participants’ characteristics were described as percentages or means with standard deviations (SD) and were compared between WLWHIV and without HIV by chi-square or Fisher's exact-tests and Student's t test. Geometric mean concentrations (GMCs) and the corresponding 95% confidence interval (CI) were estimated using logarithmic transformation and compared between the two HIV groups by univariate and multivariate linear regression. A stratification by maternal age was performed and the mean age of the entire cohort was used to create two age groups. The ratio of cord-blood to maternal blood antibody levels was calculated to estimate the transplacental transfer of antibodies. Spearman's rank correlation coefficient (rho) was used to correlate maternal and cord-blood antibody levels.

The study was approved by the University of the Witwatersrand Human Research Ethics Committee (181110 and 20313). All participating women provided written informed consent for themselves and their infants.


A total of 184 maternal cord-blood pairs were used in the current study, including 47 WLWHIV and 137 without HIV. Table 1 shows the demographics and clinical characteristics of the study participants. Information regarding ART was available for 45 of the WLWHIV, all of whom were on ART; most commonly on tenofovir disoproxil fumarate–emtricitabine–efavirenz (30 women). Eleven women were enrolled and tested for SARS-CoV-2 infection during pregnancy at 86 mean days (SD: 58) before delivery, with 3 (27%) having a positive NAAT result. One-hundred and seventy-three women were enrolled at time of labour, five (3%) had positive NAAT results, 163 (94%) negative and 5 (3%) inclusive results. Women living with HIV were significantly older (mean age: 30 vs. 28 years; P = 0.017) and had less pregnancy-related complications (57% vs. 77%; P = 0.006) compared with those without HIV (Table 1).

Table 1 - Demographic and clinical characteristics of study participants and antispike IgG levels at delivery and in cord-blood.
Women living with HIV Women without HIV
Demographic and clinical characteristics N = 47 N = 137 P value
Time of enrolment 0.48
 Pregnancy 4 (9) 7 (5)
 Delivery 43 (91) 130 (95)
SARS-CoV-2 result 0.049
 Positive 0 (0) 8 (6)
 Negative 44 (94) 127 (93)
 Inconclusive 3 (6) 2 (1)
SARS-CoV-2 reactive result during pregnancy 0 (0) 3/7 (43) 0.21
SARS-CoV-2 reactive result at delivery 0 (0) 5/130 (4) 0.08
Mean age in years at enrolment, SD 30 (6) 28 (7) 0.029
Age in years at enrolment 0.022
 ≤30 22 (47) 90 (66)
 >30 25 (53) 47 (34)
Race 0.99
 Black African 46 (98) 134 (98)
 Coloured 1 (2) 3 (2)
Comorbid conditiona 5 (11) 15 (11) 0.94
Pregnancy-related complicationsb 26 (57) 106 (77) 0.006
Multiple gestation pregnancyc 1 (2) 4 (3) 0.99
Infant gender 0.20
 Female 21 (45) 75 (56)
 Male 26 (55) 60 (44)
Mode of delivery 0.82
 Vaginal 29 (62) 82 (60)
 Caesarean 18 (38) 55 (40)
Gestational age in weeks at delivery 0.15
 ≥37 33 (70) 110 (80)
 <37 14 (30) 27 (20)
Birthweight in grams 0.13
 ≥2500 36 (77) 118 (86)
 <2500 11 (23) 19 (14)
Women living with HIV Women without HIV Unadjusted P value
Serology results for antispike IgG N = 47 N = 137 Adjusted P valued
Seropositive cord-blood samples 39 (83) 116 (85) 0.78
Maternal antispike geometric mean concentrations in BAU/ml (95% CI) 157 (122–204) 187 (161–218) 0.250.17
 Mothers ≤30 years old 124 (96–160) 179 (148–216) 0.070.049 e
 Mothers >30 years old 194 (126–299) 204 (157–267) 0.82
Cord-blood antispike geometric mean concentrations in BAU/ml (95% CI) 143 (100–203) 205 (168–250) 0.070.033
 Mothers ≤30 years old 94 (65–137) 186 (145–239) 0.0140.007 e
 Mothers >30 years old 194 (113–335)f 244 (176–339) 0.440.67e
Cord-blood: maternal blood antispike units (95% CI) 0.94 (0.80–1.11) 1.04 (0.93–1.16) 0.370.20
 Mothers ≤30 years old 0.75 (0.54–1.04) 1.00 (0.45–1.16) 0.130.12e
 Mothers >30 years old 1.10 (0.94–1.28)f 1.12 (0.96–1.30) 0.87
Results are n (%) unless stated otherwise. Bold P values represent significant differences between women living with HIV and women without HIV. BAU, binding antibody units; CI, confidence interval; severe acute respiratory syndrome coronavirus 2; SD, standard deviation.
aComorbid conditions include: asthma, tuberculosis, chronic obstructive pulmonary disease/emphysema, other chronic lung disease, hypertension, cardiovascular disease, stroke, diabetes, anaemia, epilepsy, thyroid disease, cancer, malnutrition, obesity, renal failure, other organ failure.
bPregnancy-related complication include: pregnancy-induced hypertension, preeclampsia, eclampsia, HELLP (haemolysis, elevated liver enzymes, low platelet count), gestational diabetes, hyperemesis, trauma, pregnancy-related infection, vaginal discharge, chorioamnionitis, maternal sepsis, maternal tachycardia, embolic disease, antepartum haemorrhage, postpartum haemorrhage, placenta previa/accrete/increta, placental abruption, premature contractions, premature rupture of the membranes, oligohydramnios, polyhydramnios.
cIf multiple births information relates to the first born.
dCalculated by logistic or linear regression. Adjusted for age (≤30 years or >30 years) and pregnancy-related complications, unless stated otherwise.
eAdjusted for pregnancy-related complications only.
fComparison between mothers 30 years old or less vs. mothers older than 30 years P 0.04 or less.

Overall, 155 (84%) cord-blood samples were seropositive (Fig. 1). No difference was observed in the frequency of seropositivity between the HIV groups (83% living with HIV vs. 85% without HIV, P = 0.36) (Table 1). Of the 29 seronegative cord-blood samples, two of the corresponding mothers had negative NAAT results during pregnancy (one living with HIV and one without HIV), three women were SARS-CoV-2-positive at delivery (all of whom were without HIV), 21 women had negative NAAT results at delivery (six living with HIV and 15 without HIV) and three women had inconclusive NAAT results at delivery (one living with HIV and two without HIV) (Fig. 1).

Fig. 1:
Diagram of participants enrolled into the study by nucleic acid amplification test (NAAT) reactivity and antispike IgG positivity.

Antispike GMCs were not statistically significantly different between WLWHIV [157 BAU/ml (95% CI: 122–204)] and without HIV [187 BAU/ml (95% CI: 161–218); P = 0.17]. However, restricting the analysis to women 30 years old or less, those WLWHIV [124 BAU/ml (95% CI: 96–116)] had lower GMCs compared with those without HIV [179 BAU/ml (95% CI: 148–216); P = 0.049] (Table 1). Cord-blood samples from newborns of WLWHIV had lower GMCs [143 BAU/ml ( 95% CI: 100–203)] compared with the HIV-uninfected group [205 BAU/ml (95% CI: 168–250); P = 0.033]; particularly in women 30 years old or less [94 BAU/ml (95% CI: 65–137) vs. 186 BAU/ml (95% CI: 145–239); P = 0.007] (Table 1). Either overall or stratified by HIV status, there was good correlation between the antibody levels in the maternal and cord-blood samples (overall rho = 0.83; living with HIV group rho = 0.88; without HIV group rho = 0.81; P < 0.0001 for all). The cord-to-maternal blood antibody ratio was 1.0 (95% CI: 0.92–1.11), and this was similar between the two HIV groups. Among the group living with HIV, the cord-blood GMCs and the cord-to-maternal blood antibody ratio were lower in women 30 years old or less compared with the older women, Table 1.


In the current analysis, we demonstrated that independently of maternal HIV infection status, there was efficient transplacental transfer of antispike IgG antibodies produced after natural infection. In previous studies, this highly efficient transplacental transfer of maternal IgG has also been demonstrated for antinucleocapsid IgG [7]. In our study, as WLWHIV had, however, slightly lower GMCs and lower cord-to-maternal blood antibody ratio, the GMC in cord-blood samples from newborns of WLWHIV were lower than those in HIV-unexposed newborns. Data from randomized COVID-19 vaccine efficacy trials have shown that neutralizing and binding antibodies against spike proteins, correlated with protection against SARS-CoV-2 infection afforded by vaccination [15,16]. Therefore, the clinical significance of our findings should be carefully monitored.

There were some differences between the WLWHIV and those without HIV. As the enrolment was done at secondary and tertiary care hospitals, where pregnancies with complications normally deliver, there was a very high rate of pregnancy-related complications, especially in women without HIV. Furthermore, WLWHIV were older than those without HIV, and we detected that older women had slightly higher GMCs and better transplacental transfer of antibodies, particularly if living with HIV. This is different to what has been observed previously in a study of maternal influenza vaccination and a recent study of a mRNA COVID-19 vaccine during pregnancy, where an inverse relationship was observed between vaccine-induced antibody levels in newborns and mother's age [17,18]. We need, however, to consider that immune responses to SARS-CoV-2 infections among this cohort of women have probably been mainly primary immune responses, rather than anamnestic responses following previous infections, as it is the case for immune responses to influenza infection and vaccination in adults.

Although women were tested for SARS-CoV-2 infection by NAAT, this occurred at a single time point, either during pregnancy or when presenting for labour, and so we were unable to delineate the exact timing of infection in the majority of women; however, we detected a high seropositivity rate over the course of these first two waves of COVID-19 in South Africa. Out of the eight women with SARS-CoV-2 infections detected at delivery, three had no antibodies in cord-blood, which may be because of the infections being recent. Another limitation of our study was that we were unable to adjust for level of HIV control among the WLWHIV, as no CD4+ cell counts neither viral loads were available at the time of swabbing.

Our results warrant further studies in WLWHIV and the evaluation of the possible impact on protection against SARS-CoV-2 infection of lower antibodies in HIV-exposed young infants. Additionally, vaccination of pregnant women with COVID-19 vaccines has been shown to induce a good immune response, with efficient transplacental transfer of antibody; it will be, however, crucial to evaluate the transfer of vaccine-induced antibodies in WLWHIV as no studies have reported on that [19].


The authors would like to thank the study participants, all the healthcare workers at Chris Hani Baragwanath Academic Hospital and Rahima Moosa Mother and Child Hospital and the Wits VIDA staff.

Funding: this study was supported by the Bill & Melinda Gates Foundation (grant number INV-017282). There was also partial support from the Department of Science and Technology and National Research Foundation: South African Research Chair Initiative in Vaccine Preventable Diseases.

Authors’ role: M.C.N., conceptualization of the study and the analysis, data interpretation, writing of the manuscript. S.J., overall supervision of the project. Z.D., K.S., N.S., R.S., A.W., M.B., V.B., M.A., P.M., M.M., and J.P., participant recruitment and management. V.L.B., A.N., and N.J., sample analysis, data analysis. C.F., data interpretation, writing of the first draft of the manuscript. Y.A., overall supervision of the project. S.A.M., conceptualization of the study. G.K., conceptualization of the study and the analysis. All the authors, manuscript revision.

Conflicts of interest

M.C.N. reports grants from the Bill & Melinda Gates Foundation, European & Developing Countries Clinical Trials Partnership, Pfizer, AstraZeneca, and Sanofi-Pasteur; and personal fees from Pfizer and Sanofi-Pasteur. S.A.M. reports grants and personal fees from the Bill & Melinda Gates Foundation, and grants from the South African Medical Research Council, Novavax, Pfizer, Minervax, and European & Developing Countries Clinical Trials Partnership. G.K. reports grants from the Bill & Melinda Gates Foundation.


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S.A.M. and G.K. equally contributed to the writing of this article.


antibodies; coronavirus disease 2019; placental transfer; severe acute respiratory syndrome coronavirus 2

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