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Hospitalized COVID-19 survivors showed greater cognitive impairment 6 months later, compared with patients hospitalized for other causes, but the overall disease burden was similar, based on data from 85 adults with COVID-19.
Previous studies have shown that cognitive and neuropsychiatric symptoms can occur from 2-6 months after COVID-19 recovery, and such symptoms are known to be associated with hospitalization for other severe medical conditions, Vardan Nersesjan, MD, of Copenhagen University Hospital, and colleagues wrote.
However, it remains unknown if COVID-19 is associated with a unique pattern of cognitive and mental impairment compared with other similarly severe medical conditions, they said.
In a study published in JAMA Psychiatry (2022 Mar 23. doi: 10.1001/jamapsychiatry.2022.0284), the researchers identified 85 adult COVID-19 survivors and 61 controls with non-COVID medical conditions who were treated and released between July 2020 and July 2021. The COVID-19 patients and controls were matched for age, sex, and ICU status. Cognitive impairment was assessed using the Mini-International Neuropsychiatric Interview, the Montreal Cognitive Assessment (MoCA), neurologic examination, and a semistructured interview to determine subjective symptoms.
The primary outcomes were the total scores on the MoCA and any new-onset psychiatric diagnoses. Secondary outcomes included specific psychiatric diagnoses such as depression, neurologic examination findings, and self-reported neuropsychiatric and cognitive symptoms. The mean age of the COVID-19 patients was 56.8 years, and 42% were women.
At 6 months’ follow-up, cognitive status was significantly lower in COVID-19 survivors, compared with controls, based on total geometric mean MoCA scores (26.7 vs. 27.5, P = .01). However, cognitive status improved significantly from 19.2 at hospital discharge to 26.1 at 6 months in 15 of the COVID-19 patients (P = .004), the researchers noted.
New-onset psychiatric diagnoses occurred in 16 COVID-19 patients and 12 of the controls (19% vs. 20%); this difference was not significant.
Secondary outcomes were not significantly different at 6 months between the groups, with the exception of anosmia, which was significantly more common in the COVID-19 patients; however, the significance disappeared in adjusted analysis, the researchers said.
The study findings were limited by several factors including the inability to prove causality because of the case-control feature and by the inability to detect small differences in neuropsychiatric outcomes, the researchers noted.
However, the results were strengthened by the use of a prospectively matched control group with similar disease severity admitted to the same hospital in the same time frame. Although the overall burden of neuropsychiatric and neurologic symptoms and diagnoses appeared similar in COVID-19 patients and those with other medical conditions, more research in larger populations is needed to determine smaller differences in neuropsychiatric profiles, the researchers noted.
Study fills research gap
The study is important at this time because, although prolonged neuropsychiatric and cognitive symptoms have been reported after COVID-19, the field lacked prospective case-control studies with well-matched controls to investigate whether these outcomes differed from those seen in other critical illnesses that had also required hospitalization, corresponding author Michael E. Benros, MD, of the Mental Health Center, Copenhagen, said in an interview.
“I was surprised that there was a significant worse cognitive functioning among COVID-19 patients 6 months after symptom onset also when compared to this well-matched control group that had been hospitalized for non–COVID-19 illness, although the absolute difference between the groups in cognition score were small,” said Dr. Benros. “Another notable finding is the large improvement in cognitive functioning from discharge to follow-up,” he added on behalf of himself and fellow corresponding author Daniel Kondziella, MD.
The study results show that cognitive function affected by COVID-19 and critical illness as observed at discharge showed a substantial improvement at 6 months after symptom onset, said Dr. Benros. “However, the cognitive function was significantly worse among severely ill COVID-19 patients 6 months after symptom onset when compared to a matched control group of individuals hospitalized for non–COVID-19 illness, although this difference in cognitive function was rather small in absolute numbers, and smaller than what had been suggested by other studies that lacked control groups. Strikingly, neuropsychiatric disorders were similar across the two groups, which was also the case when looking at neuropsychiatric symptoms.
“Larger prospective case-control studies of neuropsychiatric and cognitive functioning after COVID-19, compared with matched controls are still needed to detect smaller differences, and more detailed cognitive domains, and with longer follow-up time, which we are currently conducting,” Dr. Benros said.
Controlled studies will help planning
“Lingering neuropsychiatric complications are common after COVID-19, but only controlled studies can tell us whether these complications are specific to COVID-19, rather than a general effect of having been medically ill,” Alasdair G. Rooney, MRCPsych MD PhD, of the University of Edinburgh, said in an interview. “The answer matters ultimately because COVID-19 is a new disease; societies and health care services need to be able to plan for its specific consequences.”
The health status of the control group is important as well. “Most previous studies had compared COVID-19 survivors against healthy controls or patients from a historical database. This new study compared COVID-19 survivors against those hospitalized for other medical causes over the same period,” Dr. Rooney said. “This is a more stringent test of whether COVID-19 has specific neurocognitive and neuropsychiatric consequences.
“The study found that new-onset neuropsychiatric diagnoses and symptoms were no more likely to occur after COVID-19 than after similarly severe medical illnesses,” Dr. Rooney said. “This negative finding runs counter to some earlier studies and may surprise some.” The findings need to be replicated in larger samples, but the current study shows the importance of prospectively recruiting active controls.
“In a subgroup analysis, some patients showed good improvement in cognitive scores between discharge and follow-up. While unsurprising, this is encouraging and suggests that the early postdischarge months are an important time for neurocognitive recovery,” Dr. Rooney noted.
“The findings suggest that COVID-19 may impair attention more selectively than other medical causes of hospitalization. COVID-19 survivors may also be at higher risk of significant overall cognitive impairment than survivors of similarly severe medical illnesses, after a similar duration,” said Dr. Rooney. “If the results are replicated by other prospective studies, they would suggest that there is something about COVID-19 that causes clinically significant neurocognitive difficulties in a minority of survivors.
“Larger well-controlled studies are required, with longer follow-up and more detailed neurocognitive testing,” as the duration of impairment and scope for further recovery are not known, Dr. Rooney added. Also unknown is whether COVID-19 affects attention permanently, or whether recovery is simply slower after COVID-19 compared to other medical illnesses.
“Knowing who is at the greatest risk of severe cognitive impairment after COVID-19 is important and likely to allow tailoring of more effective shielding strategies,” said Dr. Rooney. “This study was conducted before the widespread availability of vaccines for COVID-19. Long-term neuropsychiatric outcomes in vaccinated patients remain largely unknown. Arguably, these are now more important to understand, as future COVID-19 waves will occur mainly among vaccinated individuals.”
The study was supported by the Lundbeck Foundation and the Novo Nordisk Foundation. Lead author Dr. Nersesjan had no financial conflicts to disclose. Dr. Benros reported grants from Lundbeck Foundation and Novo Nordisk Foundation during the conduct of the study. Dr. Rooney had no financial conflicts to disclose.
This article was updated 3/25/22.
Hospitalized COVID-19 survivors showed greater cognitive impairment 6 months later, compared with patients hospitalized for other causes, but the overall disease burden was similar, based on data from 85 adults with COVID-19.
Previous studies have shown that cognitive and neuropsychiatric symptoms can occur from 2-6 months after COVID-19 recovery, and such symptoms are known to be associated with hospitalization for other severe medical conditions, Vardan Nersesjan, MD, of Copenhagen University Hospital, and colleagues wrote.
However, it remains unknown if COVID-19 is associated with a unique pattern of cognitive and mental impairment compared with other similarly severe medical conditions, they said.
In a study published in JAMA Psychiatry (2022 Mar 23. doi: 10.1001/jamapsychiatry.2022.0284), the researchers identified 85 adult COVID-19 survivors and 61 controls with non-COVID medical conditions who were treated and released between July 2020 and July 2021. The COVID-19 patients and controls were matched for age, sex, and ICU status. Cognitive impairment was assessed using the Mini-International Neuropsychiatric Interview, the Montreal Cognitive Assessment (MoCA), neurologic examination, and a semistructured interview to determine subjective symptoms.
The primary outcomes were the total scores on the MoCA and any new-onset psychiatric diagnoses. Secondary outcomes included specific psychiatric diagnoses such as depression, neurologic examination findings, and self-reported neuropsychiatric and cognitive symptoms. The mean age of the COVID-19 patients was 56.8 years, and 42% were women.
At 6 months’ follow-up, cognitive status was significantly lower in COVID-19 survivors, compared with controls, based on total geometric mean MoCA scores (26.7 vs. 27.5, P = .01). However, cognitive status improved significantly from 19.2 at hospital discharge to 26.1 at 6 months in 15 of the COVID-19 patients (P = .004), the researchers noted.
New-onset psychiatric diagnoses occurred in 16 COVID-19 patients and 12 of the controls (19% vs. 20%); this difference was not significant.
Secondary outcomes were not significantly different at 6 months between the groups, with the exception of anosmia, which was significantly more common in the COVID-19 patients; however, the significance disappeared in adjusted analysis, the researchers said.
The study findings were limited by several factors including the inability to prove causality because of the case-control feature and by the inability to detect small differences in neuropsychiatric outcomes, the researchers noted.
However, the results were strengthened by the use of a prospectively matched control group with similar disease severity admitted to the same hospital in the same time frame. Although the overall burden of neuropsychiatric and neurologic symptoms and diagnoses appeared similar in COVID-19 patients and those with other medical conditions, more research in larger populations is needed to determine smaller differences in neuropsychiatric profiles, the researchers noted.
Study fills research gap
The study is important at this time because, although prolonged neuropsychiatric and cognitive symptoms have been reported after COVID-19, the field lacked prospective case-control studies with well-matched controls to investigate whether these outcomes differed from those seen in other critical illnesses that had also required hospitalization, corresponding author Michael E. Benros, MD, of the Mental Health Center, Copenhagen, said in an interview.
“I was surprised that there was a significant worse cognitive functioning among COVID-19 patients 6 months after symptom onset also when compared to this well-matched control group that had been hospitalized for non–COVID-19 illness, although the absolute difference between the groups in cognition score were small,” said Dr. Benros. “Another notable finding is the large improvement in cognitive functioning from discharge to follow-up,” he added on behalf of himself and fellow corresponding author Daniel Kondziella, MD.
The study results show that cognitive function affected by COVID-19 and critical illness as observed at discharge showed a substantial improvement at 6 months after symptom onset, said Dr. Benros. “However, the cognitive function was significantly worse among severely ill COVID-19 patients 6 months after symptom onset when compared to a matched control group of individuals hospitalized for non–COVID-19 illness, although this difference in cognitive function was rather small in absolute numbers, and smaller than what had been suggested by other studies that lacked control groups. Strikingly, neuropsychiatric disorders were similar across the two groups, which was also the case when looking at neuropsychiatric symptoms.
“Larger prospective case-control studies of neuropsychiatric and cognitive functioning after COVID-19, compared with matched controls are still needed to detect smaller differences, and more detailed cognitive domains, and with longer follow-up time, which we are currently conducting,” Dr. Benros said.
Controlled studies will help planning
“Lingering neuropsychiatric complications are common after COVID-19, but only controlled studies can tell us whether these complications are specific to COVID-19, rather than a general effect of having been medically ill,” Alasdair G. Rooney, MRCPsych MD PhD, of the University of Edinburgh, said in an interview. “The answer matters ultimately because COVID-19 is a new disease; societies and health care services need to be able to plan for its specific consequences.”
The health status of the control group is important as well. “Most previous studies had compared COVID-19 survivors against healthy controls or patients from a historical database. This new study compared COVID-19 survivors against those hospitalized for other medical causes over the same period,” Dr. Rooney said. “This is a more stringent test of whether COVID-19 has specific neurocognitive and neuropsychiatric consequences.
“The study found that new-onset neuropsychiatric diagnoses and symptoms were no more likely to occur after COVID-19 than after similarly severe medical illnesses,” Dr. Rooney said. “This negative finding runs counter to some earlier studies and may surprise some.” The findings need to be replicated in larger samples, but the current study shows the importance of prospectively recruiting active controls.
“In a subgroup analysis, some patients showed good improvement in cognitive scores between discharge and follow-up. While unsurprising, this is encouraging and suggests that the early postdischarge months are an important time for neurocognitive recovery,” Dr. Rooney noted.
“The findings suggest that COVID-19 may impair attention more selectively than other medical causes of hospitalization. COVID-19 survivors may also be at higher risk of significant overall cognitive impairment than survivors of similarly severe medical illnesses, after a similar duration,” said Dr. Rooney. “If the results are replicated by other prospective studies, they would suggest that there is something about COVID-19 that causes clinically significant neurocognitive difficulties in a minority of survivors.
“Larger well-controlled studies are required, with longer follow-up and more detailed neurocognitive testing,” as the duration of impairment and scope for further recovery are not known, Dr. Rooney added. Also unknown is whether COVID-19 affects attention permanently, or whether recovery is simply slower after COVID-19 compared to other medical illnesses.
“Knowing who is at the greatest risk of severe cognitive impairment after COVID-19 is important and likely to allow tailoring of more effective shielding strategies,” said Dr. Rooney. “This study was conducted before the widespread availability of vaccines for COVID-19. Long-term neuropsychiatric outcomes in vaccinated patients remain largely unknown. Arguably, these are now more important to understand, as future COVID-19 waves will occur mainly among vaccinated individuals.”
The study was supported by the Lundbeck Foundation and the Novo Nordisk Foundation. Lead author Dr. Nersesjan had no financial conflicts to disclose. Dr. Benros reported grants from Lundbeck Foundation and Novo Nordisk Foundation during the conduct of the study. Dr. Rooney had no financial conflicts to disclose.
This article was updated 3/25/22.
Hospitalized COVID-19 survivors showed greater cognitive impairment 6 months later, compared with patients hospitalized for other causes, but the overall disease burden was similar, based on data from 85 adults with COVID-19.
Previous studies have shown that cognitive and neuropsychiatric symptoms can occur from 2-6 months after COVID-19 recovery, and such symptoms are known to be associated with hospitalization for other severe medical conditions, Vardan Nersesjan, MD, of Copenhagen University Hospital, and colleagues wrote.
However, it remains unknown if COVID-19 is associated with a unique pattern of cognitive and mental impairment compared with other similarly severe medical conditions, they said.
In a study published in JAMA Psychiatry (2022 Mar 23. doi: 10.1001/jamapsychiatry.2022.0284), the researchers identified 85 adult COVID-19 survivors and 61 controls with non-COVID medical conditions who were treated and released between July 2020 and July 2021. The COVID-19 patients and controls were matched for age, sex, and ICU status. Cognitive impairment was assessed using the Mini-International Neuropsychiatric Interview, the Montreal Cognitive Assessment (MoCA), neurologic examination, and a semistructured interview to determine subjective symptoms.
The primary outcomes were the total scores on the MoCA and any new-onset psychiatric diagnoses. Secondary outcomes included specific psychiatric diagnoses such as depression, neurologic examination findings, and self-reported neuropsychiatric and cognitive symptoms. The mean age of the COVID-19 patients was 56.8 years, and 42% were women.
At 6 months’ follow-up, cognitive status was significantly lower in COVID-19 survivors, compared with controls, based on total geometric mean MoCA scores (26.7 vs. 27.5, P = .01). However, cognitive status improved significantly from 19.2 at hospital discharge to 26.1 at 6 months in 15 of the COVID-19 patients (P = .004), the researchers noted.
New-onset psychiatric diagnoses occurred in 16 COVID-19 patients and 12 of the controls (19% vs. 20%); this difference was not significant.
Secondary outcomes were not significantly different at 6 months between the groups, with the exception of anosmia, which was significantly more common in the COVID-19 patients; however, the significance disappeared in adjusted analysis, the researchers said.
The study findings were limited by several factors including the inability to prove causality because of the case-control feature and by the inability to detect small differences in neuropsychiatric outcomes, the researchers noted.
However, the results were strengthened by the use of a prospectively matched control group with similar disease severity admitted to the same hospital in the same time frame. Although the overall burden of neuropsychiatric and neurologic symptoms and diagnoses appeared similar in COVID-19 patients and those with other medical conditions, more research in larger populations is needed to determine smaller differences in neuropsychiatric profiles, the researchers noted.
Study fills research gap
The study is important at this time because, although prolonged neuropsychiatric and cognitive symptoms have been reported after COVID-19, the field lacked prospective case-control studies with well-matched controls to investigate whether these outcomes differed from those seen in other critical illnesses that had also required hospitalization, corresponding author Michael E. Benros, MD, of the Mental Health Center, Copenhagen, said in an interview.
“I was surprised that there was a significant worse cognitive functioning among COVID-19 patients 6 months after symptom onset also when compared to this well-matched control group that had been hospitalized for non–COVID-19 illness, although the absolute difference between the groups in cognition score were small,” said Dr. Benros. “Another notable finding is the large improvement in cognitive functioning from discharge to follow-up,” he added on behalf of himself and fellow corresponding author Daniel Kondziella, MD.
The study results show that cognitive function affected by COVID-19 and critical illness as observed at discharge showed a substantial improvement at 6 months after symptom onset, said Dr. Benros. “However, the cognitive function was significantly worse among severely ill COVID-19 patients 6 months after symptom onset when compared to a matched control group of individuals hospitalized for non–COVID-19 illness, although this difference in cognitive function was rather small in absolute numbers, and smaller than what had been suggested by other studies that lacked control groups. Strikingly, neuropsychiatric disorders were similar across the two groups, which was also the case when looking at neuropsychiatric symptoms.
“Larger prospective case-control studies of neuropsychiatric and cognitive functioning after COVID-19, compared with matched controls are still needed to detect smaller differences, and more detailed cognitive domains, and with longer follow-up time, which we are currently conducting,” Dr. Benros said.
Controlled studies will help planning
“Lingering neuropsychiatric complications are common after COVID-19, but only controlled studies can tell us whether these complications are specific to COVID-19, rather than a general effect of having been medically ill,” Alasdair G. Rooney, MRCPsych MD PhD, of the University of Edinburgh, said in an interview. “The answer matters ultimately because COVID-19 is a new disease; societies and health care services need to be able to plan for its specific consequences.”
The health status of the control group is important as well. “Most previous studies had compared COVID-19 survivors against healthy controls or patients from a historical database. This new study compared COVID-19 survivors against those hospitalized for other medical causes over the same period,” Dr. Rooney said. “This is a more stringent test of whether COVID-19 has specific neurocognitive and neuropsychiatric consequences.
“The study found that new-onset neuropsychiatric diagnoses and symptoms were no more likely to occur after COVID-19 than after similarly severe medical illnesses,” Dr. Rooney said. “This negative finding runs counter to some earlier studies and may surprise some.” The findings need to be replicated in larger samples, but the current study shows the importance of prospectively recruiting active controls.
“In a subgroup analysis, some patients showed good improvement in cognitive scores between discharge and follow-up. While unsurprising, this is encouraging and suggests that the early postdischarge months are an important time for neurocognitive recovery,” Dr. Rooney noted.
“The findings suggest that COVID-19 may impair attention more selectively than other medical causes of hospitalization. COVID-19 survivors may also be at higher risk of significant overall cognitive impairment than survivors of similarly severe medical illnesses, after a similar duration,” said Dr. Rooney. “If the results are replicated by other prospective studies, they would suggest that there is something about COVID-19 that causes clinically significant neurocognitive difficulties in a minority of survivors.
“Larger well-controlled studies are required, with longer follow-up and more detailed neurocognitive testing,” as the duration of impairment and scope for further recovery are not known, Dr. Rooney added. Also unknown is whether COVID-19 affects attention permanently, or whether recovery is simply slower after COVID-19 compared to other medical illnesses.
“Knowing who is at the greatest risk of severe cognitive impairment after COVID-19 is important and likely to allow tailoring of more effective shielding strategies,” said Dr. Rooney. “This study was conducted before the widespread availability of vaccines for COVID-19. Long-term neuropsychiatric outcomes in vaccinated patients remain largely unknown. Arguably, these are now more important to understand, as future COVID-19 waves will occur mainly among vaccinated individuals.”
The study was supported by the Lundbeck Foundation and the Novo Nordisk Foundation. Lead author Dr. Nersesjan had no financial conflicts to disclose. Dr. Benros reported grants from Lundbeck Foundation and Novo Nordisk Foundation during the conduct of the study. Dr. Rooney had no financial conflicts to disclose.
This article was updated 3/25/22.
FROM JAMA PSYCHIATRY