Throughout most of the COVID-19 pandemic, the primary research focus has been on the respiratory and inflammatory symptoms present during the illness’s acute phase. However, increasing evidence is emerging that cognitive symptoms persist well beyond the acute phase and well after patients have cleared the virus. These cognitive symptoms, such as problems with memory, attention, and reasoning, lead us to a number of questions about the connection between COVID-19 and cognition. What causes cognitive symptoms in COVID-19 patients and patients recovering from COVID-19? Which patients are at greatest risk of cognitive symptoms? What is the best way to assess cognition in COVID-19 patients? How long will the cognitive changes last, and are they permanent? Here we will look at what we currently know and discuss how to conduct future research effectively, including suggesting cognitive assessments that may help answer important questions about cognitive decline and COVID-19.

Causes of Cognitive Symptoms in COVID-19 Patients

Based on animal models and human studies, there are good reasons to expect that a virus like COVID-19 could have harmful cognitive effects. Some of the risk factors for severe COVID-19, such as advanced age, hypertension, diabetes, obesity, and COPD, make people more susceptible to cognitive complications during and after inflammatory states. This increased risk, or cognitive frailty, means that individuals most likely to suffer from severe COVID-19 are also the most susceptible to cognitive decline based on inflammation from the disease.

Lung damage from COVID-19 can result in hypoxemia, a below-normal level of oxygen in the blood. Cognitive decline has been observed in patients with conditions like COPD and sleep apnea who also experience chronic hypoxemia. Vascular inflammation may also contribute to cognitive decline in COVID-19 patients. Severe COVID-19 is associated with hyperinflammatory states, which in turn increase the risk of delirium. The resulting delirium can cause both long-term and short-term cognitive deficits. It is also likely that the virus has a direct neurological effect resulting from the breakdown of the blood brain barrier, vasogenic edema, oxidative stress, and microglial activation.

Additionally, because of the transmissibility of the disease, COVID-19 patients have not been afforded some of the measures frequently taken with ICU patients to minimize the potential of cognitive decline, such as the presence of family members to talk to sedated patients.

Identifying Patients at Greatest Risk

Patients who suffered from moderate to severe cases appear to be at higher risk for cognitive symptoms along with “long haulers,” patients who have cleared the virus but continue to have chronic symptoms. Some comorbidities make cognitive decline following COVID-19 more likely. These include hypertension, diabetes, obesity, and COPD. Advanced age also increases the risk.

Some treatments used during the acute phase of the illness are associated with an increased risk of cognitive decline. This risk is particularly apparent for mechanical ventilation and prolonged sedation. Patients with lung scarring regardless of illness severity during the acute phase appear to be at higher risk, possibly due to chronic hypoxemia.

Although many of the studies focused on moderate to severe cases or cases of long haulers, one of the largest studies examining more than 84,000 patients in the UK found that even patients with mild cases that did not report breathing difficulty exhibited cognitive deficits. The study did, however, show that the magnitude of the cognitive deficits scaled with symptom severity.

Future Research in COVID-19 and Cognition

Because of this disease’s relative newness, we do not know whether the cognitive deficits associated with COVID-19 are long-term, although they clearly last beyond the acute phase of the disease. Longitudinal studies examining cognitive and psychiatric changes will be important in understanding the potential impact. Some of the studies showed that executive function is one of the areas affected, but a clear picture of which cognitive domains are impacted has not emerged. Additionally, most published research did not incorporate performance-based cognitive tasks that could improve our understanding of the impact on activities of daily living (ADLs). While there is an emerging consensus that COVID-19 can cause cognitive decline, additional work with refined research tools such as cognitive tests is needed.

VeraSci offers two tools that can provide a clearer picture of cognition in COVID-19 and patients that have recovered from COVID-19. The Brief Assessment of Cognition (BAC) assesses several different domains of cognition and is sensitive to cognitive impairment in a wide range of clinical conditions, including cancer, heart disease, Alzheimer’s disease, depression, and schizophrenia. The BAC can be administered remotely, an important consideration for assessing COVID-19 patients. The Virtual Reality Functional Capacity Assessment Tool (VRFCAT) simulates key instrumental activities of daily living (iADLs) and detects meaningful changes in patients’ lives. As we move towards the development of treatments to improve cognitive performance for COVID patients, iADLs have an important role to play in demonstrating that a given treatment provides clinically meaningful improvement.

As experts in cognition, we have the expertise you need to move your research forward, from cognitive assessments to rater training to trial design. Contact us to learn more.

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