Pandemic left measurable changes in teen brains, hormones, and immunity

New research reveals how the COVID-19 pandemic reshaped teens’ stress biology, altering hormones, inflammation, and brain activity in ways that could shape their health for years to come.

Study: The effects of the COVID-19 pandemic on neurobiological functioning in adolescents. Image Credit: Prostock-studio / Shutterstock

In a recent article published in the journal Translational Psychiatry, researchers in the United States compared stress-related data collected from adolescents before and after the coronavirus disease 2019 (COVID-19) pandemic lockdowns to investigate how these unprecedented changes affected stress-sensitive biological systems.

They found that post-lockdown, adolescents showed significantly lower levels of daily cortisol production, higher levels of systemic inflammation, and reduced activation in the prefrontal cortex (PFC) during affective processing (on average assessed approximately one year after lockdown onset, range 0.43–2.06 years).

Background

Chronic stress affects physical and mental health by disrupting the HPA axis, immune response, and brain function. The HPA axis produces cortisol, which regulates inflammation, metabolism, and blood pressure. Chronic stress disrupts this system, increasing inflammation and altering brain function in areas like the amygdala, PFC, and hippocampus.

Adolescence is a sensitive period with hormonal changes, immune shifts, and rapid brain maturation, especially in the PFC, creating heightened vulnerability to stress and increasing mental health risk. The COVID-19 pandemic introduced unprecedented stress, with rates of depression and anxiety doubling among adolescents.

While research has documented pandemic-related altered stress hormone levels and structural brain changes, little is known about the combined effects of these changes on neural, endocrine, and immune systems in youth.

No prior study has examined these systems simultaneously in a single adolescent sample. In this study, researchers addressed that gap by comparing pre- and post-lockdown adolescents on systemic inflammation, cortisol secretion patterns, and PFC activation during emotional processing.

About the Study

Participants were 154 adolescents between the ages of 13.9 and 19.4 years from a longitudinal study on early life stress in the San Francisco Bay Area. Two matched groups were assessed either before the COVID-19 pandemic (n=76) or after lockdown restrictions ended (n=78), matched on early life stress exposure, socioeconomic status, pubertal stage, age, sex, and race.

The only significant demographic difference was that post-COVID adolescents had a higher body mass index (BMI; p=0.025), which was statistically controlled for in analyses.

Only one participant in the post-COVID group reported prior COVID-19 infection, and sensitivity analyses excluding this individual yielded the same pattern of results. Exclusion criteria included major medical, neurological, or psychiatric illness. Data collection included biological samples, neuroimaging, and psychosocial measures.

Endocrine function was measured via saliva samples collected at four times across two weekdays to calculate cortisol awakening response (CAR) and total daily cortisol output. Immune function was assessed from dried blood spot samples measuring C-reactive protein levels.

Neural function was examined during two tasks: a Monetary Incentive Delay (MID) task assessing medial PFC and nucleus accumbens activation during reward processing, and an affect labeling task measuring ventrolateral PFC activation during implicit emotion regulation. Statistical analyses used nonparametric methods due to non-normal data distributions.

Group differences in neurobiological measures were tested while controlling for body mass index (BMI), assay batch, waking time, and early life stress. An overall multivariate analysis (pseudo-F(1,3250)=7.43, p=0.006) confirmed significant group effects across systems.

Key Findings

The pre- and post-COVID adolescent groups were similar in all demographic characteristics except BMI, which was higher in the post-COVID group. Multivariate analysis revealed a significant overall effect of pandemic group on endocrine, immune, and neural measures.

For HPA-axis function, post-COVID adolescents had lower total daily cortisol output compared to their pre-COVID peers, while the cortisol awakening response did not differ. The authors interpret this as evidence of a dysregulated HPA-axis response with differential effects on components of the cortisol profile.

Regarding immune function, the post-COVID group displayed higher levels of C-reactive protein, indicating increased systemic inflammation. In terms of neural activity, post-COVID adolescents showed reduced medial PFC activation when receiving monetary rewards and reduced ventrolateral PFC activation during implicit regulation of negative emotions. No group differences were found in nucleus accumbens activation during reward anticipation.

Collectively, these results indicate widespread differences in stress-related biological systems following the pandemic, with lower basal cortisol output, heightened inflammation, and diminished prefrontal engagement during key affective processes.

Conclusions

This study provides evidence that the COVID-19 pandemic and associated lockdowns coincided with measurable changes across multiple stress-sensitive systems in adolescents. Reduced cortisol production, elevated inflammation, and decreased prefrontal activation suggest heightened allostatic load, a marker of cumulative physiological “wear and tear.” Such changes resemble those seen after prolonged early-life stress, which in prior research has been linked to higher risks for cancer, diabetes, stroke, depression, and poorer socioeconomic outcomes.

Strengths include the use of matched pre- and post-pandemic samples from a longitudinal study and the simultaneous assessment of endocrine, immune, and neural function. However, limitations include reliance on multiple imputation for missing data, a predominantly White and higher-income sample that may not generalize to minority or lower-SES populations disproportionately affected by the pandemic, and a modest sample size for neuroimaging analyses that the authors caution should be replicated in larger cohorts.

These findings imply that pandemic-related stress may have altered normative developmental trajectories, increasing adolescents’ risk for physical and mental health problems. Understanding and addressing these biological disruptions is essential for supporting youth resilience in the post-pandemic era.