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Open research questions in COVID-19 Impact on Reproduction

62 unresolved questions extracted from the limitations and future-work sections of 499 COVID-19 Impact on Reproduction papers in our library. Each links back to the study that raised it.

What the literature leaves open

  • Background Real-world COVID-19 risk and COVID-19 vaccine effectiveness (VE) data in children with obesity, as measured by body mass index (BMI), remain scarce.

    Association of body mass index with COVID-19 risk and vaccine effectiveness in children · 2026 · DOI

  • However, there is limited evidence on the impact of mild SARS-CoV-2 infection during pregnancy in sub-Saharan Africa, particularly among women living with HIV (WLWH), who may face heightened risk of adverse effects due to immune dysregulation and elevated obstetric risks.

    Adverse Birth Outcomes Associated with SARS-CoV-2 Infection Among Pregnant Women with and without HIV: A Longitudinal Cohort Study · 2026 · DOI

  • Page 15 First, we focused on a single state where child welfare administration and COVID-19-related policies did not vary substantially within the state, enabling our examination of changes in child maltreatment and service by COVID-19 phases. However, this approach also limits the generalizability of our findings to other state contexts. Second, the time windows for the pre-COVID-19, COVID-19, and post-COVID-19 periods were not fully balanced due to the availability of administrative data when the quantitative phase was conducted. Although our models adjusted for seasonal patterns, this limitation may influence interpretation of the observed changes. Third, we used a broad definition of child maltreatment, including all types of abuse and neglect to assess reporting. We recognize that the pandemic may have affected different types of child maltreatment, including neglect, in different ways. Fourth, because child maltreatment is a sensitive topic and COVID-19 created recruitment barriers, our qualitative sample was drawn through a community partner whose network included statewide service providers and parents primarily in the St. Louis area. As a result, the sample was not fully representative. For example, we were unable to recruit substance use treatment providers, and participants did not reflect the full range of rural, poor, or African American communities across Missouri. However, the qualitative phase was not to generalize county-level patterns, but to provide context for the quantitative findings. Even with a limited sample, participants offered meaningful insights into service disparities across counties, which added important nuance to the administrative data. Relatedly, neighborhood- level data would offer a clearer view of community factors such as local resources, civil society strength, and concentrated disadvantage that may shape child maltreatment outcomes. Because the administrative data include only county-level identifiers, we could not examine these neighborhood dynamics.

    County variations in child maltreatment risk and service responses during and post the COVID-19 pandemic: a mixed-methods study · 2026 · DOI

  • The study’s timing and setting amid the COVID-19 pandemic added specific boundaries to the recruitment of participants and the methodologies that could be employed. As we note in the inclusivity statement concluding this paper, including participants representing more diverse perspectives in terms of gender identity and family constitution could have enriched our findings. Alternatively, the relative homogeneity among current participants, of whom all but two were in heterosexual cisgender relationships, made it specifically interesting to zoom in on the discourses shaping paternal involvement in society’s most mainstream relationship form. Regarding fathers’ participation specifically, the project itself uncovered interesting mechanisms through which they excluded themselves. While we explicitly invited all parents to participate, self-selection initially resulted in minimal response from partners. To address this disparity, we then set up a campaign specifically targeting their involvement, culminating in the participants in this 267 study. Also, when interviewing parent-couples, mothers tended to lead the conversation, while fathers more often waited until they were explicitly addressed. Gendered family dynamics, explicit or implicit, may have affected the data thus collected. Striving to diversify our insights, we organized two additional online focus groups tailored specifically for fathers to demonstrate our interest in their viewpoints, but no participants applied. Overall, the fact that recruitment and interviews were conducted via telephone and digital media (except for one couple) is a known barrier to inclusivity, for which new solutions still need to be found (Goedhart et al., 2022). Finally, we value making explicit that this work was performed by a group of white, middle-class women from a Western European welfare state. This undeniably shapes our worldview, approach to study participants, and sensitivity to (gendered) discourse, limiting the generalizability of our analyses to other contexts and cultures (Shi-xu, 2023).

    Nice but not essential: discourses on Dutch fathers’ involvement in maternity care and parenting during the COVID-19 pandemic · 2026 · DOI

  • The prospective design, inclusion of a control group, and use of standardized imaging devices constitute key strengths of this study [19, 20]. However, sev- eral limitations should be acknowledged. The single- center design and relatively small sample size may limit the generalizability of our findings. In addition, a priori power analysis was not performed; therefore, the study may have been underpowered to detect small or subtle differences. Accordingly, the findings should be interpreted with caution, and larger stud- ies are warranted. Only non-severe COVID-19 cases were included, which may partly explain the absence of observed retinal microvascular changes. Given that systemic inflammation is more pronounced in patients with severe and critical COVID-19, the results derived from this cohort cannot be extrapo- lated to more severely affected populations. Further- more, the lack of stratification by disease severity or treatment modalities (e.g., anticoagulant or steroid use), the absence of systemic inflammatory marker assessment, and the exclusive focus on thickness- based parameters represent additional limitations. Additionally, OCT angiography was not performed, as it is an advanced imaging modality and there was no clinical indication for OCT angiography based on OCT macular scans and fundoscopic examinations. Finally, the observational nature of the study pre- cludes causal inference.

    The effects of COVID-19 infection on ophthalmologic findings in pregnant women: a prospective controlled observational study · 2026 · DOI

  • This study had several limitations. First, menstrual cycle data were self-reported by participants during telephone interviews, which may be subject to recall, individual perception, and reporting biases, as interpretations of menstrual irregularities may vary among patients. Additionally, the retrospective observational design inherently limits the ability to establish temporal and causal relationships between vaccination and menstrual changes. Second, lifestyle factors such as physical activity, diet, psychological stress, and other pandemic-related influences were not controlled for and may have affected menstrual patterns independently of vaccination status. Third, although the study included a large sample within Dubai Health, it may not be fully generalizable to the entire UAE population, as many individuals received vaccinations through other healthcare sectors or were temporary visitors to the country. Furthermore, the study population consisted solely of women registered with the Dubai Health system, which may introduce selection bias and limit the representation of women who did not access formal healthcare services. Finally, the relatively short study period may not have captured the longer-term effects of vaccination on menstrual health. Another limitation of this study is the absence of a control group. Additionally, comparisons between Pfizer and Sinopharm recipients should be interpreted cautiously, as baseline population differences may have influenced the observed findings.

    Effect of COVID-19 Vaccination on the Menstrual Cycle Among Women in Dubai · 2026 · DOI

  • Several limitations should be acknowledged. As a cross-sectional study design, temporal relationships between age, psychological factors, education, relationship status, and contraceptive use cannot be established, limiting causal infer- ence. Although multivariable modeling was used to adjust for measured confounders, residual confounding from unmea- sured or imprecisely measured variables including fertility intentions, sexual activity, or access barriers remains possible. Some covariates contained missing data and were addressed using multiple imputation by chained equations under a missing-at-random assumption prior to multivariable logistic regression. While this approach preserves sample size and is generally preferable to complete-case analysis, the validity of the estimates depends on the adequacy of the imputation model and the plausibility of the missing-at-random assumption; therefore, some bias may persist if missingness was not fully explained by observed variables. In addition, key variables were modeled in ways that may not fully capture their underlying complexity. Age was exam- ined both categorically and continuously, and while broadly consistent patterns were observed, the continuous specifica- tion assumes a linear relationship that may obscure non-linear differences across reproductive age groups. Psychological distress was assessed using separate anxiety and depression scores, and although anxiety showed a modest, borderline association with contraceptive use while depression did not, these relationships may be sensitive to model specification and residual confounding. Similarly, education and relationship status were included as categorical variables, but these may not fully reflect underlying socioeconomic position, partnership dynamics, or access to resources that influence con- traceptive behavior. These findings should therefore be interpreted with caution in light of both the cross-sectional design and the imputation process. Finally, data were collected during the early phase of the pandemic and may not capture subsequent adaptations in service delivery. PLOS Global Public Health | https://doi.org/10.1371/journal.pgph.0006049 May 22, 2026 10 / 13 Implications for policy and future research Despite these limitations, the findings highlight actionable priorities for SRH policy in small developing states, especially in times of continual funding and policy changes of large donors [41]. Emergency response planning should prioritize con- tinuity of contraceptive services, expand access to self-managed and long-acting methods where feasible, and integrate mental health considerations into SRH programming. Future research should employ longitudinal designs and multi- variable analyses to better understand pathways linking psychosocial distress and reproductive decision-making during crises, particularly among adolescents and young adults in SIDS contexts.

    Factors associated with contraceptive use among reproductive-age women during a pandemic: Evidence from a small developing state · 2026 · DOI

  • This study has some limitations. First of all, the smallness of the subjects’ cohort, although healthy and COVID-19 subjects were GA-matched. Moreover, women affected by SARS-CoV-2 showed a heterogeneity in symptoms, hence they might also show different placental lesions. Another constraint of this study is the absence of pathological subjects’ clinical outcome data and the impossibility of conducting histological analyses due to the legislation in force during the pandemic. Nevertheless, the findings here reported showed promising results and opened the way for future research on viral infection in the human placenta. Magnetic Resonance Materials in Physics, Biology and Medicine Fig. 5 a ROC curve; b bar-plot of the IVIM features’ importance for the classification.

    The MRI two-perfusion IVIM model improves understanding of SARS-CoV-2 virus impact on placental tissue · 2026 · DOI

  • Clinical surveillance protocols need to be developed and validated to identify neurodevelopmental deficits and latent or subclinical anomalies in newborns, toddlers, and children exposed to SARS-CoV-2 in utero, particularly in ectodermal derivatives including neural and cutaneous tissues.

    SARS-CoV-2 pseudoparticles preferentially infect ectoderm in human embryonic tissues · 2026 · DOI

  • The hESC-derived germ layer model lacks the protective placental barrier and maternal immune system present in vivo; safety and tissue-specific delivery efficacy of protease and endocytosis inhibitors (Ambroxol, Camostat, Dyngo4a) in pregnant individuals and embryos/fetuses must be established in appropriate in vivo models.

    SARS-CoV-2 pseudoparticles preferentially infect ectoderm in human embryonic tissues · 2026 · DOI

  • Although aprotinin and Dyngo4a showed variable efficacy across different cell types tested, future studies must test drug combinations over a range of doses to assess synergy, additivity, and antagonism while establishing in vivo pharmacokinetics and placental transfer rates of these endocytosis and serine protease inhibitors in the context of preventing SARS-CoV-2 vertical transmission.

    SARS-CoV-2 pseudoparticles preferentially infect ectoderm in human embryonic tissues · 2026 · DOI

  • The fluorescent peptide substrate used to measure TMPRSS2 protease activity lacks full specificity for its intended target; future studies should employ more specific assays or alternative protease measurement approaches to accurately quantify TMPRSS2 activity differences between ectodermal and non-ectodermal germ layers.

    SARS-CoV-2 pseudoparticles preferentially infect ectoderm in human embryonic tissues · 2026 · DOI

  • The study tested only a single MOI in hESC-derived germ layers, whereas in vivo viral particle exposure varies among pregnant patients; future studies should test multiple MOIs to determine how variable viral loads influence infection outcomes and tropism patterns across ectodermal cell types.

    SARS-CoV-2 pseudoparticles preferentially infect ectoderm in human embryonic tissues · 2026 · DOI

  • Future studies must investigate whether the increased susceptibility of ectodermal tissues observed in hESC-derived germ layer models is recapitulated in differentiated adult neural and epithelial systems to mechanistically explain the diverse neurological outcomes of COVID-19 including Guillain-Barré syndrome and encephalopathy.

    SARS-CoV-2 pseudoparticles preferentially infect ectoderm in human embryonic tissues · 2026 · DOI

  • Longitudinal monitoring of children born to mothers with COVID-19 is needed to determine whether delayed neurological deficits or developmental abnormalities in ectodermal derivatives emerge during childhood, as the study only examined early prenatal susceptibility in vitro.

    SARS-CoV-2 pseudoparticles preferentially infect ectoderm in human embryonic tissues · 2026 · DOI

  • 8 million PTB annually worldwide, the modest reductions observed during early pandemic lockdowns translate into large numbers of PTB averted globally and warrant further research into causal pathways.

    Changes in preterm birth and stillbirth during COVID-19 lockdowns in 26 countries · 2023 · DOI

  • The sparse literature on this topic attributes the 1919 bust to individuals postponing conceptions during the peak of the 1918-20 influenza pandemic and the 1920 boom to recuperation of those conceptions.

    Did the 1918 influenza pandemic cause a 1920 baby boom? Demographic evidence from neutral Europe · 2023 · DOI

  • However, little is known about the efficiency of transplacental transfer of RSV-specific antibodies in a setting with a high burden of malaria and HIV, to guide the implementation of such a vaccination program.

    Efficiency of transplacental transfer of respiratory syncytial virus (RSV) specific antibodies among pregnant women in Kenya · 2022 · DOI

  • INTRODUCTION: Conflicting reports of increases and decreases in rates of preterm birth (PTB) and stillbirth in the general population during the coronavirus disease 2019 (COVID-19) pandemic have surfaced.

    COVID‐19 pandemic and population‐level pregnancy and neonatal outcomes in general population: A living systematic review and meta‐analysis (Update#2: November 20, 2021) · 2022 · DOI

  • Despite the increasing number of published studies on COVID-19 in pregnancy, there are insufficient good-quality data to draw unbiased conclusions with regard to the severity of the disease or specific complications of COVID-19 with reference to the mode of delivery, vertical/peripartum transmission, and complications in neonates, born by infected pregnant women.

    COVID-19 Pandemic and Birth Experience. The Monopoly of Caesarean Sections. A Critical Realist Review · 2021 · DOI

  • INTRODUCTION: Conflicting reports of increases and decreases in rates of preterm birth (PTB) and stillbirth in the general population during the COVID-19 pandemic have surfaced.

    COVID‐19 pandemic and population‐level pregnancy and neonatal outcomes: a living systematic review and meta‐analysis · 2021 · DOI

  • The constantly increasing number of publications regarding the course of COVID-19 infection in pregnant women has been published, however, the available data remains limited and many questions remain unanswered.

    COVID-19 during pregnancy, delivery and postpartum period based on EBM · 2020 · DOI

  • Robust estimates of disease severity are still lacking, and the proportionate risk of severe maternal morbidity and mortality related to COVID-19 cannot be determined without analyzing large-scale population-based data from several countries adjusting for several confounding factors and outcome modifiers.

    Severe maternal morbidity and mortality associated with COVID‐19: The risk should not be downplayed · 2020 · DOI

  • However, there is no evidence suggesting transplacental transmission based on very limited data, as the analysis of amniotic fluid, cord blood, neonatal throat swab, and breast milk samples available from six of the nine patients were found to be negative for SARS-COV-2.

    Novel corona virus disease (COVID‐19) in pregnancy: What clinical recommendations to follow? · 2020 · DOI

  • Because the full clinical spectrum of congenital Zika virus infection is not yet known, all infants born to women with laboratory evidence of possible recent Zika virus infection during pregnancy should receive postnatal neuroimaging and Zika virus testing in addition to a comprehensive newborn physical exam and hearing screen.

    Vital Signs: Update on Zika Virus–Associated Birth Defects and Evaluation of All U.S. Infants with Congenital Zika Virus Exposure — U.S. Zika Pregnancy Registry, 2016 · 2017 · DOI

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62 open questions have been extracted from the limitations and future-work passages of 499 COVID-19 Impact on Reproduction papers in our library. Each one below links back to the study that raised it, so you can read the original claim in context.

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