Stronger type I interferon responses in females compared to males, starting from intrauterine life, underpin the sex differences observed in HIV-1 cure/remission outcomes in children and adults. In adults these innate immune sex differences favour females achieving HIV-1 cure/remission over males. Recent studies of the adult viral reservoir reflect the ability of innate immune responses in females, including natural killer (NK) cell activity, to remove cells harbouring intact proviral DNA more effectively than males. In children, the situation is more complex. Initially, in the first years of life, males have a higher propensity to achieve HIV-1 cure/remission, at this stage benefiting from the effects of having weaker interferon (IFN)-I responses, including low baseline HIV-1 DNA loads and being recipients of an IFN-I sensitive transmitted founder virus. By mid-childhood, the picture is mixed, with the impact of stronger innate immunity in females combined with the development of more effective HIV-specific CD8 + T-cell response via immune ontogeny tending to favour females beyond the age of 5-10 years. In children, therefore, the double-edged sword effects of IFN-I in the setting of vertical transmission and immune ontogeny results in distinct, dynamic sex advantages through childhood.

Introduction: despite the success of antiretroviral therapy (ART), the emergence of HIV drug resistance (HIVDR) remains a major threat in sub-Saharan Africa, where therapeutic options remain limited. With the goal of supporting ART response, we sought to monitor viral load (VL) response and acquired HIVDR emergence among patients initiating ART in the Cameroonian setting. Methods: a facility-based cohort study was conducted from March 2016 to May 2021 in urban (Yaoundé) and rural (Obala) settings in the centre region of Cameroon. Included were recently diagnosed HIV individuals initiating ART at the level of the health facilities. VL was measured at three different time points. For those with unsuppressed viremia (>1000 copies/mL), genotyping for HIVDR was performed in the protease, reverse-transcriptase, and integrase gene regions, and interpreted using HIVdb.v9.1. Data were analyzed with p<0.05 considered significant. Time-to-event analysis (Kaplan-Meier and Cox regression) was used to identify determinants of virological failure. Results: overall, 87 newly diagnosed participants (50.6% from urban and 49.4% from rural) were enrolled. Median (interquartile range, IQR) age was 42 (34.0-50.5) years, sex ratio (F/M) was 3/2, and all participants initiated treatment with non-nucleoside reverse transcriptase inhibitor (NNRTI)-based ART regimen. At initiation, median VL was 34,000 (13,963-122,000) copies/mL; at T1 (~3 years after initiation), median VL dropped to 9,800 (4,700-30,500) copies/mL, and 17.2% (15/87) switched to protease inhibitor-based ART. At the end of the study (T2), 58.6% (51/87) had achieved undetectable VL (<40copies/mL), 3.4% had VL between 40-999 copies/mL, and 37.9% VL >1000 copies/mL. The proportion with virological failure was 9.1% (4/44) in the urban setting versus 67.4% (29/43) in the rural setting. Time-to-event analysis revealed that patients in the rural setting had a 4.6-fold higher risk of virological failure (hazard ratio (HR) = 4.60, 95% CI: 2.29-9.27). Among those with unsuppressed VL, overall rate of HIVDR was 62.5% (20/32), driven by the mutations: M184V (31.25%) for NRTI, K103N (18.75%) for NNRTI and M46I (9.30%) for PI/r, and 0% major resistance mutations to integrase strand transfer inhibitors (INSTI), without any significant disparity between urban and rural. Conclusion: viral load monitoring reveals poor ART response in rural settings, which prompts the need for improving access to ART. Among those with unsuppressed VL, the burden and patterns of HIVDR are similar in both settings, likely due to the wide use of NNRTI-based ART. Viral susceptibility to INSTIs supports a possible switch to dolutegravir-based ART for optimal response.

People living with HIV treated during acute infection are the group for whom achieving functional cure appears most viable. Follicular CD8+ T cells could contribute to HIV reservoir clearance by accessing B cell follicles through CXCR5 expression. This study examines peripheral follicular CD8+ T cells using flow cytometry, transcriptome analyses, and functional assays in people treated during acute (n = 37) and chronic (n = 18) infection, as well as in individuals naturally controlling HIV (n = 20) and living without HIV (n = 10). Our results reveal that early, as opposed to late, treatment initiation preserves antiviral effector functions of follicular CD8+ T cells, which are further enhanced by PD1 inhibition. We also identify a correlation between follicular CD8+ T cells and intact proviral HIV DNA levels in acute, but not chronic, infection. Longitudinal transcriptomic analysis of peripheral effector cells after 48 weeks of suppressive therapy indicated traits of recent antigen exposure, suggesting potential recirculation into lymphoid tissue. These findings underscore the pivotal role of follicular CD8+ T cells in anti-HIV responses and support investigating targeted cure strategies, such as antiPD1 therapy, especially in individuals initiating treatment during acute infection.

Under-reporting of COVID-19 and the limited information about circulating SARS-CoV-2 variants remain major challenges for many African countries. We analyzed SARS-CoV-2 infection dynamics in Addis Ababa and Jimma, Ethiopia, focusing on reinfection, immunity, and vaccination effects. We conducted an antibody serology study spanning August 2020 to July 2022 with five rounds of data collection across a population of 4723, sequenced PCR-test positive samples, used available test positivity rates, and constructed two mathematical models integrating this data. A multivariant model explores variant dynamics identifying wildtype, alpha, delta, and omicron BA.4/5 as key variants in the study population, and cross-immunity between variants, revealing risk reductions between 24% and 69%. An antibody-level model predicts slow decay leading to sustained high antibody levels. Retrospectively, increased early vaccination might have substantially reduced infections during the delta and omicron waves in the considered group of individuals, though further vaccination now seems less impactful. Detailed data on SARS-CoV-2 dynamics in Africa remain limited. Here, the authors use longitudinal serology and SARS-CoV-2 sequencing data from Ethiopia between August 2020 and July 2022 to characterise circulating variants, identify infection pathways, and explore cross-immunity properties.

Zusammenfassung In der frühen Phase der COVID-19-Pandemie wurden in Deutschland viele lokale Sammlungen klinischer Daten mit SARS-CoV-2 infizierter Patient:innen initiiert. Im Rahmen des Nationalen Pandemie-Kohorten-Netzes (NAPKON) des Netzwerkes Universitätsmedizin wurde der „Integrationskern“ etabliert, um die rechtlichen, technischen und organisatorischen Voraussetzungen für eine Integration von Bestandsdaten in laufende prospektive Datensammlungen zu konzipieren und die Machbarkeit der entwickelten Lösungen mittels Use Cases (UCs) zu prüfen. Detaillierte Studienunterlagen der Datensammlungen wurden eingeholt. Nach strukturierter Dokumentenanalyse, bewertete ein Review Board, gemäß definierter Kriterien die Integrierbarkeit der Daten in NAPKON. Von 30 kontaktierten Universitätskliniken hatten 20 auf die Anfrage geantwortet. Die Patient:inneninformationen und Einwilligungen zeigten ein heterogenes Bild bezüglich der pseudonymen Weitergabe der Daten an Dritte und des Re-Kontakts. Ein Großteil der Datensammlungen (n=13) erfüllte die Kriterien für eine Integration in NAPKON, bei vier Studien wären Anpassungen der regulatorischen Dokumente erforderlich. Drei Kohorten waren nicht für einen Einschluss in NAPKON geeignet. Die rechtlichen Rahmenbedingungen einer retrospektiven Datenintegration und einer einwilligungsfreien Datennutzung über Forschungsklauseln (§27 BDSG) wurde durch ein Rechtsgutachten der TMF – Technologie- und Methodenplattform, für die vernetzte medizinische Forschung e. V., Berlin erarbeitet. Anhand zweier vom NAPKON-Lenkungsausschuss ausgewählter UCs(CORKUM, LMU München; Pa-COVID-19, Charité- Universitätsmedizin Berlin) wurde die Machbarkeit einer Datenintegration bis Ende 2021 in NAPKON gezeigt. Es erfolgte gemäß den Vorgaben die Qualitätssicherung und die aufwandsgenaue Abrechnung der übertragenen Fälle. Basierend auf den Ergebnissen können Empfehlungen für verschiedene Kontexte formuliert werden, um technisch-operative Voraussetzungen wie Interoperabilität, Schnittstellen und Datenmodelle für die Datenintegration zu schaffen sowie regulatorische Anforderungen an Ethik, Datenschutz, ärztliche Schweigepflichtsentbindung und den Datenzugang bei der Integration bestehender Kohortendaten zu erfüllen. Die mögliche Integration von Daten in Forschungsnetzwerke und deren Sekundärnutzung sollte bereits in der Planungsphase einer Studie – insbesondere beim Informed Consent – berücksichtigt werden, um den größtmöglichen Nutzen aus den erhobenen Daten zu ziehen.

In the early phase of the COVID-19 pandemic, many local collections of clinical data on patients infected with SARS- CoV-2 were initiated in Germany. As part of the National Pandemic Cohort Network (NAPKON) of the University Medicine Network, the "Integration Core" was established to design the legal, technical and organisational requirements for the integration of inventory data into ongoing prospective data collections and to test the feasibility of the newly developed solutions using use cases (UCs). Detailed study documents of the data collections were obtained. After structured document analysis, a review board evaluated the integrability of the data in NAPKON according to defined criteria. Of 30 university hospitals contacted, 20 responded to the request. Patient information and consent showed a heterogeneous picture with regard to the pseudonymised transfer of data to third parties and re-contact. The majority of the data collections (n = 13) met the criteria for integration into NAPKON; four studies would require adjustments to the regulatory documents. Three cohorts were not suitable for inclusion in NAPKON. The legal framework for retrospective data integration and consent-free data use via research clauses ( 27 BDSG) was elaborated by a legal opinion by TMF - Technology, Methods and Infrastructure for Networked Medical Research, Berlin. Two UCs selected by the NAPKON steering committee (CORKUM, LMU Munich; Pa-COVID-19, Charite-Universitatsmedizin Berlin) were used to demonstrate the feasibility of data integration in NAPKON by the end of 2021. Quality assurance and performance-based reimbursement of the cases were carried out according to the specifications. Based on the results, recommendations can be formulated for various contexts in order to create technical-operational prerequisites such as interoperability, interfaces and data models for data integration and to fulfil regulatory requirements on ethics, data protection, medical confidentiality and data access when integrating existing cohort data. The possible integration of data into research networks and their secondary use should be taken into account as early as the planning phase of a study - particularly with regard to informed consent - in order to maximise the benefits of the data collected.

Human immunodeficiency virus type 1 (HIV-1) disease manifestations differ between cisgender women and men, including better control of viral replication during primary infection and less frequent residual HIV-1 replication on antiretroviral therapy (ART) in cisgender women with HIV-1 (WWH). Investigating plasmacytoid dendritic cell (pDC) functions and HIV-1 reservoir sizes in 20 WWH on stable ART, we observed inverse correlations between interferon-α and tumor necrosis factor responses of pDCs to Toll-like receptor 7/8 stimulation and intact/total proviral HIV-1 DNA levels. Additionally, ISG15 mRNA levels in peripheral blood mononuclear cells correlated with cytokine responses of pDCs. These findings demonstrate an association between higher type I interferon responses and lower HIV-1 reservoir sizes in WWH on ART, warranting studies to identify the underlying mechanisms.

Immune cell phenotyping frequently detects lineage-unrelated receptors. Here, we report that surface receptors can be transferred from primary macrophages to CD4 T cells and identify the Fcγ receptor CD32 as driver and cargo of this trogocytotic transfer. Filamentous CD32+ nanoprotrusions deposit distinct plasma membrane patches onto target T cells. Transferred receptors confer cell migration and adhesion properties, and macrophage-derived membrane patches render resting CD4 T cells susceptible to infection by serving as hotspots for HIV-1 binding. Antibodies that recognize T cell epitopes enhance CD32-mediated trogocytosis. Such autoreactive anti-HIV-1 envelope antibodies can be found in the blood of HIV-1 patients and, consistently, the percentage of CD32+ CD4 T cells is increased in their blood. This CD32-mediated, antigen-independent cell communication mode transiently expands the receptor repertoire and functionality of immune cells. HIV-1 hijacks this mechanism by triggering the generation of trogocytosis-promoting autoantibodies to gain access to immune cells critical to its persistence.

The SARS-CoV-2 pandemic has highlighted the need to better define in-hospital transmissions, a need that extends to all other common infectious diseases encountered in clinical settings. To evaluate how whole viral genome sequencing can contribute to deciphering nosocomial SARS-CoV-2 transmission 926 SARS-CoV-2 viral genomes from 622 staff members and patients were collected between February 2020 and January 2021 at a university hospital in Munich, Germany, and analysed along with the place of work, duration of hospital stay, and ward transfers. Bioinformatically defined transmission clusters inferred from viral genome sequencing were compared to those inferred from interview-based contact tracing. An additional dataset collected at the same time at another university hospital in the same city was used to account for multiple independent introductions. Clustering analysis of 619 viral genomes generated 19 clusters ranging from 3 to 31 individuals. Sequencing-based transmission clusters showed little overlap with those based on contact tracing data. The viral genomes were significantly more closely related to each other than comparable genomes collected simultaneously at other hospitals in the same city (n = 829), suggesting nosocomial transmission. Longitudinal sampling from individual patients suggested possible cross-infection events during the hospital stay in 19.2% of individuals (14 of 73 individuals). Clustering analysis of SARS-CoV-2 whole genome sequences can reveal cryptic transmission events missed by classical, interview-based contact tracing, helping to decipher in-hospital transmissions. These results, in line with other studies, advocate for viral genome sequencing as a pathogen transmission surveillance tool in hospitals.

With SARS-CoV-2 evolving, disease severity and presentation have changed due to changes in mechanisms of entry and effector site as well as due to effects of vaccination- and/or infection-acquired immunity. We re-assessed fetal lung pathology in pregnancies with uncomplicated SARS-CoV-2 infections during the late, omicron-dominated pandemic phase to inform disease understanding and pregnancy consultation. In this case-control study, fetal lung volumes were assessed by fetal MRI in 24 pregnancies affected by mild maternal SARS-CoV-2 infection during the omicron-dominated pandemic phase with prevailing immunity through vaccination and/or prior SARS-CoV-2 infection. Fetal lung volumes (normalized to estimated fetal weight) in 24 pregnancies (GA 33.3 ± 3.8, 12 female fetuses) following mild, uncomplicated SARS-CoV-2 infection did not differ significantly from both, published reference values (96.3

Courses of SARS-CoV-2 infections are highly variable, ranging from asymptomatic to lethal COVID-19. Though research has shown that host genetic factors contribute to this variability, cohort-based joint analyses of variants from the entire allelic spectrum in individuals with confirmed SARS-CoV-2 infections are still lacking. Here, we present the results of whole genome sequencing in 1,220 mainly vaccine-naïve individuals with confirmed SARS-CoV-2 infection, including 827 hospitalized COVID-19 cases. We observed the presence of autosomal-recessive or likely compound heterozygous monogenic disorders in six individuals, all of which were hospitalized and significantly younger than the rest of the cohort. We did not observe any suggestive causal variants in or around the established risk gene TLR7. Burden testing in the largest population subgroup (i.e., Europeans) suggested nominal enrichments of rare variants in coding and non-coding regions of interferon immune response genes in the overall analysis and male subgroup. Case-control analyses of more common variants confirmed associations with previously reported risk loci, with the key locus at 3p21 reaching genome-wide significance. Polygenic scores accurately captured risk in an age-dependent manner. By enabling joint analyses of different types of variation across the entire frequency spectrum, this data will continue to contribute to the elucidation of COVID-19 etiology.

Next to its classical role in MHC II-mediated antigen presentation, CD74 was identified as a high-affinity receptor for macrophage migration inhibitory factor (MIF), a pleiotropic cytokine and major determinant of various acute and chronic inflammatory conditions, cardiovascular diseases and cancer. Recent evidence suggests that CD74 is expressed in T cells, but the functional relevance of this observation is poorly understood. Here, we characterized the regulation of CD74 expression and that of the MIF chemokine receptors during activation of human CD4+ T cells and studied links to MIF-induced T-cell migration, function, and COVID-19 disease stage. MIF receptor profiling of resting primary human CD4+ T cells via flow cytometry revealed high surface expression of CXCR4, while CD74, CXCR2 and ACKR3/CXCR7 were not measurably expressed. However, CD4+ T cells constitutively expressed CD74 intracellularly, which upon T-cell activation was significantly upregulated, post-translationally modified by chondroitin sulfate and could be detected on the cell surface, as determined by flow cytometry, Western blot, immunohistochemistry, and re-analysis of available RNA-sequencing and proteomic data sets. Applying 3D-matrix-based live cell-imaging and receptor pathway-specific inhibitors, we determined a causal involvement of CD74 and CXCR4 in MIF-induced CD4+ T-cell migration. Mechanistically, proximity ligation assay visualized CD74/CXCR4 heterocomplexes on activated CD4+ T cells, which were significantly diminished after MIF treatment, pointing towards a MIF-mediated internalization process. Lastly, in a cohort of 30 COVID-19 patients, CD74 surface expression was found to be significantly upregulated on CD4+ and CD8+ T cells in patients with severe compared to patients with only mild disease course. Together, our study characterizes the MIF receptor network in the course of T-cell activation and reveals CD74 as a novel functional MIF receptor and MHC II-independent activation marker of primary human CD4+ T cells.

Background The severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) pandemic causes a high burden of acute and long-term morbidity and mortality worldwide despite global efforts in containment, prophylaxis, and therapy. With unprecedented speed, the global scientific community has generated pivotal insights into the pathogen and the host response evoked by the infection. However, deeper characterization of the pathophysiology and pathology remains a high priority to reduce morbidity and mortality of coronavirus disease 2019 (COVID-19). Methods NAPKON-HAP is a multi‐centered prospective observational study with a long‐term follow‐up phase of up to 36 months post-SARS-CoV-2 infection. It constitutes a central platform for harmonized data and biospecimen for interdisciplinary characterization of acute SARS-CoV-2 infection and long-term outcomes of diverging disease severities of hospitalized patients. Results Primary outcome measures include clinical scores and quality of life assessment captured during hospitalization and at outpatient follow-up visits to assess acute and chronic morbidity. Secondary measures include results of biomolecular and immunological investigations and assessment of organ-specific involvement during and post-COVID-19 infection. NAPKON-HAP constitutes a national platform to provide accessibility and usability of the comprehensive data and biospecimen collection to global research. Conclusion NAPKON-HAP establishes a platform with standardized high-resolution data and biospecimen collection of hospitalized COVID-19 patients of different disease severities in Germany. With this study, we will add significant scientific insights and provide high-quality data to aid researchers to investigate COVID-19 pathophysiology, pathology, and chronic morbidity.

Currently, SARS-CoV-2 Omicron BA.5 subvariants BF.7 and BQ.1.1 are rapidly emerging worldwide. To evaluate the SARS-CoV-2-neutralizing capacity of sera and saliva from triple vaccinated individuals, either boosted with an adapted bivalent COVID-19 vaccine or recovered from BA.4/BA.5 infection, we analyzed the sensitivity of replication-competent SARS-CoV-2 Omicron subvariants BA.4/5, BQ.1.1 and BF.7 to neutralization. Analysis of SARS-CoV-2-specific IgGs and IgAs showed increased serum IgG titers in the vaccinated group, while the serum and salivary IgA levels were comparable. Similar and efficient serum neutralization against the ancestral strain of SARS-CoV-2 and Omicron BA.4/BA.5 was detected in both cohorts, but critically reduced for BQ.1.1 and BF.7. In contrast, salivary neutralization against BA.4/BA.5 was increased in the convalescent compared to the vaccinated group, while salivary neutralizing capacity against BQ.1.1 and BF.7 was comparable in these groups. Further, personalized protective effects studied in a human 3D respiratory model revealed the importance of salivary protection against different Omicron subvariants.IMPORTANCEIn BA.4/BA.5-convalescent versus vaccinated groups, salivary neutralization capacity increased against SARS-CoV-2 Omicron BA.4/BA.5. In contrast, it neutralized novel Omicron subvariants BQ.1.1 and BF.7 similarly. Salivary protection against various Omicron subvariants was even more evident when tested in a personalized approach using highly differentiated respiratory human 3D models.

Dysregulation of the myeloid cell compartment is a feature of severe disease in hospitalized COVID-19 patients. Here, we investigated the response of circulating dendritic cell (DC) and monocyte subpopulations in SARS-CoV-2 infected outpatients with mild disease and compared it to the response of healthy individuals to yellow fever vaccine virus YF17D as a model of a well-coordinated response to viral infection. In SARS-CoV-2-infected outpatients circulating DCs were persistently reduced for several weeks whereas after YF17D vaccination DC numbers were decreased temporarily and rapidly replenished by increased proliferation until 14 days after vaccination. The majority of COVID-19 outpatients showed high expression of CD86 and PD-L1 in monocytes and DCs early on, resembling the dynamic after YF17D vaccination. In a subgroup of patients, low CD86 and high PD-L1 expression were detected in monocytes and DCs coinciding with symptoms, higher age, and lower lymphocyte counts. This phenotype was similar to that observed in severely ill COVID-19 patients, but less pronounced. Thus, prolonged reduction and dysregulated activation of blood DCs and monocytes were seen in a subgroup of symptomatic non-hospitalized COVID-19 patients while a transient coordinated activation was characteristic for the majority of patients with mild COVID-19 and the response to YF17D vaccination.

IntroductionTo explore whether the reported lower pathogenicity in infected individuals of variant of concern (VoC) Omicron and its current subvariants compared to VoC Delta may be related to fundamental differences in the initial virus-tissue interaction, we assessed their ability to penetrate, replicate and cause damage in a human 3D respiratory model.MethodsFor this, we used TEER measurements, real-time PCR, LDH, cytokine and complex confocal imaging analyses.Results and discussionWe observed that Delta readily penetrated deep into the respiratory epithelium and this was associated with major tissue destruction, high LDH activity, high viral loads and pronounced innate immune activation as observed by intrinsic C3 activation and IL-6 release at infection sites. In contrast, Omicron subvariants BA.5, BQ.1.1 and BF7 remained superficially in the mucosal layer resulting merely in outward-directed destruction of cells, maintenance of epithelial integrity, minimal LDH activity and low basolateral release of virus at infection sites, as well as significantly smaller areas of complement activation and lower IL-6 secretion. Interestingly, also within Omicron subvariants differences were observed with newer Omicron subvariants BQ.1.1 and BF.7 illustrating significantly reduced viral loads, IL-6 release and LDH activity compared to BA.5. Our data indicate that earliest interaction events after SARS-CoV-2 transmission may have a role in shaping disease severity.

Lung transplant recipients are at increased risk of severe disease following infection with severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) due to high-dose immunosuppressive drugs and the lung is the main organ affected by Coronavirus disease 2019 (COVID-19). Several studies have confirmed increased SARS-CoV-2-related mortality and morbidity in patients living with lung allografts; however, detailed immunological studies of patients with SARS-CoV-2 infection in the early phase following transplantation remain scarce. We investigated patients who were infected with SARS-CoV-2 in the early phase (18–103 days) after receiving double-lung allografts (n = 4, LuTx) in comparison to immunocompetent patients who had not received solid organ transplants (n = 88, noTx). We analyzed SARS-CoV-2-specific antibody responses against the SARS-CoV-2 spike and nucleocapsid proteins using enzyme-linked immunosorbent assays (ELISA), chemiluminescence immunoassays (CLIA), and immunoblot assays. T cell responses were investigated using Elispot assays. One LuTx patient suffered from persistent infection with fatal outcome 122 days post-infection despite multiple interventions including remdesivir, convalescent plasma, and the monoclonal antibody bamlanivimab. Two patients experienced clinically mild disease with prolonged viral shedding (47 and 79 days), and one patient remained asymptomatic. Antibody and T cell responses were significantly reduced or undetectable in all LuTx patients compared to noTx patients. Patients in the early phase following lung allograft transplantation are vulnerable to infection with SARS-CoV-2 due to impaired immune responses. This patient population should be vaccinated before LuTx, protected from infection post–LuTx, and in case of infection treated generously with currently available interventions.

The COVID-19 pandemic has resulted in severe acute and long-term effects for the respiratory system. With SARS-CoV-2 evolving, the latest omicron variant was described as showing less severe involvement of the lower respiratory tract in adults. Effects in the vulnerable cohort of the unborn, however, remain unknown.We therefore investigated pregnancies with mild SARS-CoV-2 omicron infection using fetal MRI to assess lung volume as a measure of pulmonary growth. In n=24 cases, fetal lung volumes were normalized by estimated fetal weight and described as the percentage of the respective 50th percentile reference values, as well as compared to a site-specific non-COVID control group (n=15).In fetuses exposed to the SARS-CoV-2 omicron variant, lung volume did not differ significantly from both, published reference values (96·3% ± 22·5% of 50th percentile reference values, p=0·430), or fetal lung volumes of a site-specific, non-COVID control group (94·2% ± 18·5% of 50th percentile reference values, p=0·762). When stratifying the results by trimester of infection (first/second and third trimester infection), no significant differences in lung volumes were observed when compared to the site-specific non-COVID control group. This finding is in stark contrast to our previously published data for the alpha variant of the virus, which revealed reduced lung growth with third trimester infection in the pre-vaccination era.Demonstrating preserved lung growth with omicron variant exposure, our findings might reflect tropism-related effects as well as the impact of vaccination, thereby informing counseling and surveillance of affected pregnancies.Funding: The work was supported by grants from the following organizations: Young Investigator Grant by the Helmholtz Association and the Helmholtz Zentrum München, Germany (NWG VH-NG-829: A.H., K.F.), “Physician Scientists for Groundbreaking Projects” at Helmholtz Zentrum München, Munich, Germany (A.H., S.S.), German Center for Lung Research (DZL, Federal Ministry of Education and Research, Germany (BMBF: A.H.)), German Research Fund (DFG, Research Training Group GRK2338: A.H.), Bavarian Ministry for Science and Art (Corona Forschungsprogramm 2021/22: A.H., S.S), as well as the Chan Zuckerberg Initiative 'Mapping the Pediatric Inhalation Interface: Nose, Mouth, and Airways'. Additional financial support was provided by the Stiftung AtemWeg (LSS AIRR: A.H.).Declaration of Interest: All authors declare no conflict of interest.Ethical Approval: The study was approved by the local institutional review board (ethical approval #LMU-207–33).