Researchers have reported that people who survived the acute phase of COVID-19 are at an increased risk of an array of incident mental health disorders. They concluded that tackling mental health disorders among survivors of the disease should be a priority.

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The researchers from the US Department of Veterans Affairs, Saint Louis University and Washington University were involved in the study. The British Medical Journal published the study on 16 February 2022. Mental health studies on COVID-19 patients carried out earlier were limited to short follow-up (<6 months) and the selection of mental health outcomes was narrow.

They showed that people with COVID-19 might be at increased risk of anxiety and depression. They suggested a more comprehensive assessment of the mental health manifestations in people with COVID-19 at one year as important.

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Present study

Researchers extracted data from the US Department of Veterans Affairs national healthcare databases to estimate the risks of incident mental health outcomes in people who survived the acute phase of COVID-19. 

From the data, the researchers constructed a cohort of 153,848 US veterans who survived the first 30 days of SARS-CoV-2 infection and two control groups-a contemporary group consisting of 56,37,840 users of the US Department of Veterans Health Care System (Veterans Health Administration) with no evidence of SARS-CoV-2 infection, and a historical control (predating the COVID-19 pandemic) consisting of 58,59,251 users of the healthcare system during 2017.

They followed these cohorts to estimate the risks of a set of pre-specified incident mental health outcomes in the overall cohort and according to care setting during the acute phase of the infection that is, whether people were or were not admitted to the hospital during the first 30 days of COVID-19.

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What did the study suggest

In this study, the researchers found that the COVID-19 group of patients had the following symptoms: an increased risk of incident anxiety disorders, depressive disorders, stress and adjustment disorders and use of antidepressants and benzodiazepines. The risk of incident opioid prescriptions, opioid use disorders, and other (non-opioid) substance use disorders also increased. The COVID-19 group showed an increased risk of incident neurocognitive decline and sleep disorders.

The researchers noted that the risk of any incident mental health diagnosis or prescription was increased. The risks of examined outcomes were increased even among people who were not admitted to the hospital and were highest among those who were admitted to the hospital during the acute phase of COVID-19. Results were consistent with those in the historical control group.

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Risk higher in COVID-19 group

The risk of incident mental health disorders was consistently higher in the COVID-19 group in comparison to the people with COVID-19 not admitted to the hospital.

The data were compared to those not admitted to hospital for seasonal influenza, admitted to hospital with COVID-19 versus admitted to hospital with seasonal influenza and admitted to hospital with COVID-19 versus admitted to hospital for any other cause. Extensive data enabled the researchers to quantify risks in these disorders.

"Given the large and growing number of people with COVID-19 (to date >70 million people in the US, >15 million people in the UK, and about 350 million people globally), the absolute risks of incident mental health disorders might translate into large numbers of potentially affected people around the world," the researchers said.

The researchers added:

"Our results should be used to promote awareness of the increased risk of mental health disorders among survivors of acute COVID-19 and call for the integration of mental healthcare as a core component of post-acute COVID-19 care strategies. International bodies, national governments, and health systems must develop and implement strategies for early identification and treatment of affected individuals."

The mechanism/s of the increased risks of mental health disorders in people with COVID-19 are not entirely clear. According to the researchers, the putative mechanisms under examination include:

• Peripheral T cell infiltration of brain parenchyma
• Dysregulated microglia and astrocytes
• Disturbances in synaptic signalling of upper layer excitatory neurons

All these features generally overlap with disease phenotypes of genetic variants associated with impaired cognition, depression, and other neuropsychiatric disorders.

"Other likely mechanisms include a potential role of angiotensin-converting enzyme 2 mediated neuroinflammation and the indirect effect of a dysregulated immune response on the central nervous system. Non-biologic mechanisms (eg, changes in employment, financial problems, social isolation, trauma, grief, and changes in diet and physical activity), which could have differentially impacted people with COVID-19 compared with their contemporaries, might also have contributed to the increased burden of mental health disorders in people with COVID-19," the researchers said.

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Strengths and limitations of this study

The study has several strengths. The researchers selected a large national cohort of people with COVID-19 to estimate risks of a comprehensive set of pre-specified incident mental health outcomes compared with two controls (a contemporary group with no evidence of SARS-CoV-2 infection and a historical group that predated the pandemic). In the COVID-19 group, they provided risk estimates for those who were and were not admitted to the hospital, facilitating a better understanding of the magnitude of risk in these populations.

The researchers compared the risk of mental health outcomes in people with COVID-19 versus seasonal influenza and separately for people admitted to hospital for COVID-19 compared with those admitted to hospital for any other cause. They used advanced statistical methodologies

The researchers admitted:

"We used the vast national electronic healthcare databases of the US Department of Veterans Affairs to select our cohorts, and although we used validated outcome definitions (including diagnostic codes and prescription records) and advanced statistical methodologies to balance the study arms for a battery of predefined and algorithmically selected high dimensional variables across several data domains, we cannot completely rule out misclassification bias and residual confounding." 

They categorised the COVID-19 group into those who were and those who were not admitted to hospital for COVID-19 during the first 30 days of a positive SARS-CoV-2 test result; This approach does not account for the spectrum of disease severity among participants who were not admitted to hospital (eg, with or without symptoms of COVID-19). Researchers did not examine the severity of the mental health outcomes.

In spite of careful handling of data, the researchers cannot completely rule out the possibility that increased attention to people with COVID-19 might have resulted in greater ascertainment of mental health conditions compared with both the contemporary and historical control groups.

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Comments from the experts

In an accompanying editorial Professor Scott Weich, Mental Health Research Unit, School of Health and Related Research, University of Sheffield, UK asserted that the risks are clear; it is now time to learn and respond.

"A clear picture has emerged of the mental health impacts of the early waves of the COVID-19 pandemic in England when hospital admissions and mortality were common and lockdowns particularly restrictive. Longitudinal population-based studies show that symptoms of anxiety and depression were marked but often transient, increasing during lockdowns and subsiding afterwards to pre-pandemic levels. Nevertheless, around 10% of the population experienced persistent distress, with women, 18-30 years old, people with pre-existing mental or physical health problems, those living in deprived areas, and ethnic minority communities most affected." he noted.

His response to: What have we learnt?

He clarified:

"The worst of the pandemic might be behind us in terms of mortality and social restrictions. Taking stock, it could be argued that much of the research concerned with the mental health impacts of COVID-19 represents more hindsight than insight. Looking back at what happened is arguably less important than reflecting on what we have learnt, what we need to do next, and what we still do not know. Our attachment to syndromal phenotypes means that we have learnt remarkably little about the causes of mental ill health—in this case psychopathology associated with a viral pandemic. We continue to generate more heat than light as we reflect on the usual biopsychosocial suspects without cutting through to conclusive insights or effective interventions."

He highlighted many issues, thus: "We do not yet know the true incidence and consequences of long COVID, and we are still witnessing the unfolding toll of the pandemic on healthcare staff. In addition, we do not have an effective response to the devastating disruption to health, social care, and voluntary sector services on the lives of people with serious mental illness. In addition, while epidemiological research has flourished, at least in terms of scientific publications, we are guilty of failing to prioritise evaluations of mental healthcare interventions, including clinical trials, just when these are most needed. "

In an accompanying opinion piece, a senior author of the BMJ paper, Dr Ziyad Al-Aly, Director, Clinical Epidemiology Center, Research and Development Service, Saint Louis, MO, USA cautioned, "Some may use their findings to gaslight or dismiss long COVID as a psychosomatic condition or explain the myriad manifestations of long COVID as the result of mental illness."

He asserted:

"This dismissal is contrary to scientific evidence and is harmful to patients and communities. Mental health disorders represent one part of the multifaceted nature of long COVID, which can affect nearly every organ system (including the brain, heart, and kidneys). Our results should be used to promote awareness of this risk among people with COVID-19 and to guide efforts for the early identification and treatment of affected individuals. The body of evidence on long COVID—from our work and others—suggests the need to reframe our thinking about SARS-CoV-2. It is not only a respiratory virus; it is a systemic virus that may provoke damage and clinical consequences in nearly every organ system—including mental health disorders and neurocognitive decline."

"Long COVID demands greater attention now to better understand it, prevent it, and treat affected individuals. International bodies, governments, and other stakeholders must pay attention. Failure to attend to the risks of long COVID risks amplifying the profound losses we have experienced in this global pandemic," he added.

In a press release issued on 16 February 2022 from the Science Media Centre, London, Julia Faulconbridge, the British Psychological Society’s Division of Clinical Psychology, while accepting that these are interesting findings, wondered how applicable they are to other contexts.

She argued:

"There is limited information on potential causal mechanisms for the correlations that were found. The lack of diversity in the study is an issue, with all the group being American veterans, and the majority being older white men. It is likely this group were already more predisposed to higher levels of mental health difficulties and socioeconomic and relationship difficulties." 

“The study is limited to what is in medical records and so does not give any picture of the wider context of the people’s lives and so does not help us to understand the impact of the illness and how changes in their circumstances may have led to the mental health problems," she added.

She cautioned:

"As an example, the interplay between socioeconomic factors and mental health issues as a possible factor is only mentioned in passing as they are mainly considering possible medical causes for the mental health difficulties. The study states that the relationship between mental health problems and COVID may not be unidirectional, as those with mental health problems are more at risk of getting COVID."

“We know that those living in poverty, in insecure work and living in poor housing are also more at risk both of getting COVID and are more at risk of mental health problems There is no data on the impact that having COVID has had on their lives, for example, their ability to work, and the subsequent impact on their mental health," she stated.

She suggested that there needs to be further research and consideration of the wider context of people’s lives – for example, living conditions, employment and relationships, on their likelihood to experience mental health difficulties, as well as possible longer-term physiological and neurological changes, in order to understand the mental health impacts of COVID-19.

Disclaimer- The views and opinions expressed in this article are those of the author's and do not necessarily reflect the official policy or position of M3 India.

Dr K S Parthasarathy is a former Secretary of the Atomic Energy Regulatory Board and a former Raja Ramanna Fellow, Department of Atomic Energy. A Ph. D. from the University of Leeds, UK, he is a medical physicist with a specialisation in radiation safety and regulatory matters. He was a Research Associate at the University of Virginia Medical Centre, Charlottesville, USA. He served the International Atomic Energy Agency as an expert and member in its Technical and Advisory Committees.