Chris Robinson, University of FloridaOne in three survivors of COVID-19, those more commonly referred to as COVID-19 long-haulers, suffered from neurologic or psychiatric disability six months after infection, a recent landmark study of more than 200,000 post-COVID-19 patients showed.
Researchers looked at 236,379 British patients diagnosed with COVID-19 over six months, analyzing neurologic and psychiatric complications during that time period. They compared those individuals to others who had experienced similar respiratory illnesses that were not COVID-19.
They found a significant increase in several medical conditions among the COVID-19 group, including memory loss, nerve disorders, anxiety, depression, substance abuse and insomnia. Additionally, the symptoms were present among all age groups and in patients who were asymptomatic, isolating in home quarantine, and those admitted to hospitals.
The results of this study speak to the seriousness of long-term consequences of COVID-19 infection. Numerous reports of brain fog, post-traumatic stress disorder, heart disease, lung disease and gastrointestinal disease have peppered the media and puzzled scientists over the past 12 months, begging the question: What effect does COVID-19 have on the body long after the acute symptoms have resolved?
I am an assistant professor of neurology and neurosurgery and can’t help but wonder what we have learned from past experience with other viruses. One thing in particular stands out: COVID-19 consequences will be with us for quite some time.
Learning from history
Past virus outbreaks, such as the 1918 flu pandemic and the SARS epidemic of 2003, have provided examples of the challenges to expect with COVID-19. And, the long-term effects of other viral infections help provide insight.
Several other viruses, including a large majority of those that cause common upper and lower respiratory infections, have been shown to produce such chronic symptoms as anxiety, depression, memory problems and fatigue. Experts believe that these symptoms are likely due to long-term effects on the immune system. Viruses trick the body into producing a persistent inflammatory response resistant to treatment.
Myalgic encephalomyelitis, also known as chronic fatigue syndrome, is one such illness. Researchers believe this condition results from continuous activation of the immune system long after the initial infection has resolved.
In contrast to other viral infections, the COVID-19 survivors in the study reported persistent symptoms lasting more than six months, with no significant improvement over time. The abundance of psychiatric symptoms was also notable and likely attributable to both infection and pandemic-related experience.
These findings are leading researchers to hypothesize several mechanisms following acute COVID-19 infection that may lead to long-haul COVID-19. With the known historical context of chronic symptoms following other viruses, doctors and researchers may have a glimpse into the future of COVID-19 with the potential to create therapies to alleviate patients’ persistent symptoms.
When does COVID-19 really end?
COVID-19 is now known to be a disease that affects all organ systems, including the brain, lungs, heart, kidneys and intestines.
Several theories exist as to the cause of chronic, lingering symptoms. Hypotheses include direct organ damage from the virus, continual activation of the immune system after acute infection and persistent lasting virus particles that find safe harbor within the body.
To date, autopsy studies have not confirmed the presence or overabundance of COVID-19 particles in the brain, making the immune theories the most likely cause of brain dysfunction.
Some recovered COVID-19 patients detail significant improvement or resolution of long symptoms following inoculation with the COVID-19 vaccine. Others report improvement following a short course of steroids. The most plausible explanation for the direct effects of long COVID-19 on the brain are due to its body-wide connections and the fact that COVID-19 is a multi-organ disease.
These findings may point to a direct immune related cause of long COVID-19, though no real answers yet exist to define the true cause and duration of the disease.
The post-COVID-19 world
In February, the National Institutes of Health announced a new initiative to study long COVID-19, now collectively defined as Post-Acute Sequelae of SARS-CoV-2. The NIH created a fund of US$1.15 billion to study this new disease. The aims of the study include the cause of long-term symptoms, the number of people affected by the disease and vulnerabilities leading to long COVID-19.
In my view, public health officials should continue to be open and transparent when discussing the short- and long-term effects of COVID-19. Society as a whole needs the best information possible to understand its effects and resolve the problem.
COVID-19 remains and will continue to be one of the largest socioeconomic problems across the world as we begin to recognize the true long-term impacts of the disease. Both the scientific and research communities should continue to be diligent in the fight long after the acute infections are gone. It appears that the chronic effects of the disease will be with us for some time to come.
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As well as our physical health, the quality of our diet matters for our mental and brain health. Observational studies across countries, cultures and age groups show that better-quality diets – those high in vegetables, fruits, other plant foods (such as nuts and legumes), as well as good-quality proteins (such as fish and lean meat) – are consistently associated with reduced depression.
Importantly, these relationships are independent of one another. Lack of nutritious food seems to be a problem even when junk food intake is low, while junk and processed foods seem to be problematic even in those who also eat vegetables, legumes and other nutrient-dense foods. We’ve documented these relationships in adolescents, adults and older adults.
Diet has an impact early in life
The diet-mental health relationship is evident right at the start of life. A study of more than 20,000 mothers and their children showed the children of mothers who ate an unhealthier diet during pregnancy had a higher level of behaviours linked to later mental disorders.
We also saw the children’s diets during the first years of life were associated with these behaviours. This suggests mothers’ diets during pregnancy and early life are both important in influencing the risk for mental health problems in children as they grow.
This is consistent with what we see in animal experiments. Unhealthy diets fed to pregnant animals results in many changes to the brain and behaviour in offspring. This is very important to understand if we want to think about preventing mental disorders in the first place.
Teasing out the cause from the correlation
It’s important to note that, at this stage, most of the existing data in this field come from observational studies, where it is difficult to tease apart cause and effect. Of course, the possibility that mental ill health promoting a change in diet explains the associations, rather than the other way around, is an important one to consider.
Many studies have investigated this and largely ruled it out as the explanation for the associations we see between diet quality and depression. In fact, we published a study suggesting that a past experience of depression was associated with better diets over time.
But the relatively young field of nutritional psychiatry is still lacking data from intervention studies (where study participants are given an intervention that aims to improve their diet in an attempt to affect their mental health). These sorts of studies are important in determining causality and for changing clinical practice.
Our recent trial was the first intervention study to examine the common question of whether diet will improve depression.
We recruited adults with major depressive disorder and randomly assigned them to receive either social support (which is known to be helpful for people with depression), or support from a clinical dietitian, over a three-month period.
The dietary group received information and assistance to improve the quality of their current diets. The focus was on increasing the consumption of vegetables, fruits, wholegrains, legumes, fish, lean red meats, olive oil and nuts, while reducing their consumption of unhealthy “extra” foods, such as sweets, refined cereals, fried food, fast food, processed meats and sugary drinks.
The results of the study showed that participants in the dietary intervention group had a much greater reduction in their depressive symptoms over the three months, compared to those in the social support group.
At the end of the trial, 32% of those in the dietary support group, compared to 8% of those in the social support group, met criteria for remission of major depression.
These results were not explained by changes in physical activity or body weight, but were closely related to the extent of dietary change. Those who adhered more closely to the dietary program experienced the greatest benefit to their depression symptoms.
While this study now needs to be replicated, it provides preliminary evidence that dietary improvement may be a useful strategy for treating depression.
Depression is a whole-body disorder
It’s important to understand researchers now believe depression is not just a brain disorder, but rather a whole-body disorder, with chronic inflammation being an important risk factor. This inflammation is the result of many environmental stressors common in our lives: poor diet, lack of exercise, smoking, overweight and obesity, lack of sleep, lack of vitamin D, as well as stress.
Many of these factors influence gut microbiota (the bacteria and other microorganisms that live in your bowel, also referred to as your “microbiome”), which in turn influence the immune system and – we believe – mood and behaviour.
In fact, gut microbiota affect more than the immune system. New evidence in this field suggests they are important to almost every aspect of health including our metabolism and body weight, and brain function and health. Each of these factors is relevant to depression risk, reinforcing the idea of depression as a whole-body disorder.
If we do not consume enough nutrient-dense foods such as fruits, vegetables, fish and lean meats, this can lead to insufficiencies in nutrients, antioxidants and fibre. This has a detrimental impact on our immune system, gut microbiota and other aspects of physical and mental health.
Gut microbiota are particularly reliant on an adequate intake of dietary fibre, while the health of the gut may be compromised by added sugars, fats, emulsifiers and artificial sugars found in processed foods.
A diet high in added fats and refined sugars also has a potent negative impact on brain proteins that we know are important in depression: proteins called neurotrophins. These protect the brain against oxidative stress and promote the growth of new brain cells in our hippocampus (a part of the brain critical for learning and memory, and important to mental health). In older adults we have shown that diet quality is related to the size of the hippocampus.
Now we know diet is important to mental and brain health as well as physical health, we need to make healthy eating the easiest, cheapest and most socially acceptable option for people, no matter where they live.