How COVID-19 shaped mental health: from infection to pandemic effects

Abstract

The Coronavirus Disease 2019 (COVID-19) pandemic has threatened global mental health, both indirectly via disruptive societal changes and directly via neuropsychiatric sequelae after SARS-CoV-2 infection. Despite a small increase in self-reported mental health problems, this has (so far) not translated into objectively measurable increased rates of mental disorders, self-harm or suicide rates at the population level. This could suggest effective resilience and adaptation, but there is substantial heterogeneity among subgroups, and time-lag effects may also exist. With regard to COVID-19 itself, both acute and post-acute neuropsychiatric sequelae have become apparent, with high prevalence of fatigue, cognitive impairments and anxiety and depressive symptoms, even months after infection. To understand how COVID-19 continues to shape mental health in the longer term, fine-grained, well-controlled longitudinal data at the (neuro)biological, individual and societal levels remain essential. For future pandemics, policymakers and clinicians should prioritize mental health from the outset to identify and protect those at risk and promote long-term resilience.

Fig. 1 |. Mental health symptom scores before and during the first COVID-19 pandemic year in Dutch people with or without lifetime depressive and/or anxiety disorders.

Trajectories of mean depressive symptoms (QIDS score), anxiety symptoms (BAI score), loneliness (De Jong questionnaire score) and Fear of COVID-19 score before and during the first year of the COVID-19 pandemic in healthy controls (blue line, n = 378) and in patients with depressive and/or anxiety disorders (red line, n = 908). The x-axis indicates time with one pre-COVID assessment (averaged over up to five earlier assessments conducted between 2006 and 2019) and 11 online assessments during April 2020 through February 2021. Symbols indicate the mean score during the assessment with 95% CIs. As compared to pre-COVID assessment scores, the figure shows a statistically significant increase of depression and loneliness symptoms during the first pandemic peak (April 2020) in healthy controls but not in patients (for more details, see refs. ^,). Asterisks indicate where subsequent wave scores differ from the prior wave scores (P < 0.05). The figure also illustrates the stability of depressive and anxiety symptoms during the first COVID year, a significant increase in loneliness during this period and fluctuations of Fear of COVID-19 score that positively correlate with infection rates in the Netherlands. Raw data are from the Netherlands Study of Depression and Anxiety (NESDA), which were re-analyzed for the current plots to illustrate differences between two groups (healthy controls versus patients). BAI, Beck Anxiety Inventory; QIDS, Quick Inventory of Depressive Symptoms.

Fig. 2 |. Possible mechanisms of SARS-CoV-2-mediated neuroinflammation.

(1) Elevation of BBB-destabilizing cytokines (IL-1β and TNF) within the serum due to CRS or local interactions of mononuclear and endothelial cells. (2) Virus-induced endotheliitis increases susceptibility to microthrombus formation due to platelet activation, elevation of vWF and fibrin deposition. (3) Cytokine, mononuclear and endothelial cell interactions promote disruption of the BBB, which may allow entry of leukocytes expressing IFNg into the CNS (4), leading to microglial activation (5). (6) Activated microglia may eliminate synapses and/or express cytokines that promote neuronal injury. (7) Injured neurons express IL-6 which, together with IL-1β, promote a ‘gliogenic switch’ in NSCs (8), decreasing adult neurogenesis. (9) The combination of microglial (and possibly astrocyte) activation, neuronal injury and synapse loss may lead to dysregulation of NTs and neuronal circuitry. IFNg, interferon-g; NSC, neural stem cell; NT, neurotransmitter; TJ, tight junction; TNF, tumor necrosis factor; vWF, von Willebrand factor.