The report by Montejano et al.[1] on efficacy of sotrovimab for persistent coronavirus disease 2019 in a severely immunocompromised patient highlighted the value of neutralizing monoclonal antibodies (mAbs) against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) for patients with HIV.

Here, we report mAbs treatment in two pregnant woman, one HIV-positive and one HIV-negative, who both tested SARS-CoV-2 positive shortly before delivery. The first case is an asymptomatic, nonvirologically suppressed HIV-positive pregnant woman (viral load 1210 copies/ml; CD4+ 74 cells/μl, nadir 33 cells/μl) who tested SARS-CoV-2-positive 1 day before planned elective cesarean section (nasopharyngeal swap PCR 18 000 copies/ml; variant not determined). She received two doses of BNT162b2 more than 6 months prior but missed out on booster vaccination. Unfortunately, she was nonadherent to antiretroviral therapy (ART) during her current pregnancy with high risk for MTCT. In this situation and with the surge of the SARS-CoV-2-Omicron variant, the mother and her newborn were also regarded at risk for severe COVID-19 and adverse pregnancy outcomes. As recommended by CDC, mAbs should not be withheld from pregnant women, and safe and successful use has been reported [2–4]. Therefore, this woman received 500 mg Sotrovimab around 44 h before cesarean section of a healthy girl (weight 2510 g, length 47 cm, APGAR 9/9/10). The infant received postexposure prophylaxis against HIV as recommended per national guideline (AZT, 3TC, NVP), and was repeatedly tested HIV and SARS-CoV-2 negative.

Our second case is an HIV-negative, nonvaccinated 31 years old primigravida who presented in her 33rd week of pregnancy with fever and dyspnea because of COVID-19 pneumonia after onset of symptoms 5 days before [nasopharyngeal swap PCR 330 000 copies/ml; EDTA PCR-positive; variant of concern (VOC) Delta B.1.617.2]. Gynecological and obstetrical assessment demonstrated fetal well being by CTG and ultrasound. She received Casirivimab plus Imdevimab 4000 mg each (REGEN-COV, Roche Pharma AG, Grenzach-Wyhlen, Germany) according to the RECOVERY protocol [5]. However, with increasing oxygen dependency, she was transferred to the ICU for high-flow respiratory support later that day. On the following day, an interdisciplinary decision was made to deliver (33+1 gestational weeks, weight 2165 g, length 45 cm, APGAR 8/9/10) by cesarean section to avoid mechanical ventilation. The preterm boy had mild respiratory distress and needed CPAP with 30–40% oxygen for several hours. Formula was fed before breastfeeding could be initiated 3 days later after the mother recovered. Both mothers and infants had favorable outcomes.

We used routine serum samples (and pumped breast milk) to measure mAb transfer from mothers to children by Roche Elecsys anti-SARS-CoV-2 S Ig ElectroChemiLuminescent ImmunoAssay (sensitivity, 93.9%; specificity, 99.6%; cutoff, 0.8 U/ml) with a receptor-binding domain protein (RBD) sandwich assay design (anti-S RBD) [6]. A significant vertical antibody transfer decreased over the following weeks (Table 1).

Table 1 - SARS-CoV-2 serology in mother‘s serum, breast milk, and infant serum. A – timeline Case 1 Day -2c Day of birth Day 18 Day 32 Day 53 Mother HIV +  SARS CoV2 N Iga Negative Negative  SARS CoV2 S RBDb 5830 24 335.0 Infant HIV-exposed  SARS CoV2 N Iga – Negative Negative Negative Negative  SARS CoV2 S RBDb – 2287.0 952.0 729.6 442.7 B – timeline Case 2 Day -1c Day 3 Day 6 Day 20 Day 47 Mother  SARS CoV2 N Iga Negative – 23.57 –  SARS CoV2 S RBDb Negative – >25 000 – Infant  SARS CoV2 N Iga – No material – No material Negative  SARS CoV2 S RBDb – 712.4 – 227.5 151.7 Breastmilkd  SARS CoV2 N Iga – 2.61 –  SARS CoV2 S RBDb – 123.2 –

a(S/NO).

bReceptor-binding site (RBD) Ig (AU/ml).

cMonoclonal antibodies (mAbs) Sotrovimab (case 1), Casirivimab plus Imdevimab (case 2) were given same day after blood samples for serology had been taken.

dBreast milk was expressed by using an electric breast pump.

Pregnant women are at high risk for severe COVID-19, and, unfortunately, vaccine hesitancy and misinformation are still prominent in this at-risk population [7,8]. Studies showed a significant reduction of hospitalization or death after early mAb treatment [9,10]. Survival benefits were also observed in hospitalized seronegative patients with moderate-to-severe COVID-19 after high-dose Casirivimab with Imdevimab in the RECOVERY trial [5], which also included pregnant participants.

To our best knowledge, these cases show vertical mAb transfer from mother to child for the first time in vivo. Limitations are that, for ethical reasons, routine blood samples were used that were not optimized for pharmacokinetic evaluation. Additionally, onset of intrinsic humoral immune response may have influenced serologic testing.

Infants receive maternal transplacental passive immunity against many pathogens, including SARS-CoV-2 after COVID-19 disease or vaccination in pregnancy [11–13]. Anti-SARS-CoV-2 IgG and IgA antibodies can be detected in breastmilk of convalescent and vaccinated mothers [13–16] but will not benefit HIV-exposed infants exclusively receiving formula feeding. Vaccination in pregnancy is superior to natural infection for providing antibody transfer, and maternal vaccination protects infants aged less than 6 months from COVID-19 hospitalization [17,18]. Although there is debate about the risk of SARS-CoV-2 infection and severe illness in neonates, we and others experienced severe neonatal COVID-19 cases [19,20]. In addition, HIV-exposed uninfected infants live with increased risk of morbidity and hospitalization, maybe also for severe COVID-19 [21,22]. However, sufficient data in HIV-exposed infants are lacking.

Our cases indicate the well tolerated and effective use of mAbs as an antiviral prophylaxis or treatment option for unvaccinated or immunocompromised pregnant women. At the same time, mAbs could provide valuable exposure prophylaxis for a short period after delivery, protecting a vulnerable population, including HIV-exposed infants. Unfortunately, immune escape from neutralizing antibodies of new SARS-CoV-2 lineages is of great concern [23].

Acknowledgements

We thank the patients and parents for consenting to the case presentation. In addition, we are grateful to all staff members of the University Medical Center Hamburg-Eppendorf for supporting the diagnosis and management of the patients.

Ethics approval and consent to participation: ethical approval was waived in accordance to state law. Written informed consent to participate was obtained by the parents.

Consent for publication: written consent for publication was obtained from the patients’ parents. There are no identifying images or other personal or clinical details of the patients that compromise anonymity in this manuscript.

Availability of data and material: additional data and information can be obtained from the corresponding author.

Funding: The authors received no external funding for conduction of the research or publication of the manuscript.

Author contributions: R.K. and S.S. designed the analysis, R.K. drafted the manuscript. U.S.S., P.K., C.R., A.C.T., S.J. coordinated the patients management. R.K., P.K., M.L. and S.S. contributed in writing the manuscript. M.L. was responsible for diagnostic microbiology and data interpretation, R.K., U.S.S., M.L., S.S. confirmed the accuracy and originality of the data. All authors read, revised and approved the final manuscript and agreed on contributions and ensured the accuracy and integrity of this work.

Conflicts of interest

There are no conflicts of interest.

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