Could a specialized diet alleviate long COVID?

Nuria Pastor-Soler, MD, PhD, is the principal investigator of the long COVID clinical trial and an associate professor of medicine at the Keck School of Medicine of USC.

Nuria Pastor-Soler, MD, PhD, is the principal investigator of the long COVID clinical trial and an associate professor of medicine at the Keck School of Medicine of USC.  CREDIT Ricardo Carrasco III

Approximately 7% of Americans have had long COVID, a range of ongoing health problems experienced after infection and recovery from COVID-19. Symptoms can include fatigue, brain fog, headaches, chest pain, heart palpitations and more.  

To date, there is no proven treatment for the syndrome, and the mechanisms that cause it are not fully understood.  

Now, a new clinical trial from Keck Medicine of USC is investigating if a diet designed to lower inflammation may play a role in easing this often debilitating condition.  

The premise of the trial revolves around recent research indicating that long COVID may be caused by a hyper inflammatory response that becomes activated during COVID-19 as the body fights off the virus but, in some people, does not recede even after the infection has passed. High inflammation levels in the body can lead to organ damage and other health problems.  

“We are examining if food choice can quiet the body’s inflammatory response and in doing so, effectively minimize or curtail long COVID symptoms,” said Adupa Rao, MD, an investigator of the clinical trial and medical director of the Keck Medicine Covid Recovery Clinic.  

The study will examine the anti-inflammatory effect of a low-carbohydrate diet to lower blood glucose (sugar) levels in combination with a medical food that raises blood ketone levels. Ketones, including beta-hydroxybutyrate, the active ketone in this food, are chemicals the body produces to provide energy when the body is low on carbohydrates and sugars. A low-carb diet and ketones have both been associated with reduced inflammation in the body.  

Researchers plan to enroll 50 long COVID patients being treated by Keck Medicine’s Covid Recovery Clinic. Half the individuals will receive a 30-day dietary intervention and half will not. At the end of the month, researchers will determine how patients tolerated the regimen as well as compare inflammatory markers and long COVID symptoms between the two groups of patients. 

If the nutritional intervention is tolerated well by patients and improves their health issues, researchers plan to expand the clinical trial to a larger population.  

“Research like ours is vital to expand our understanding of long COVID and ultimately help identify effective treatments to improve patients’ quality of life,” said principal investigator of the clinical trial, Nuria Pastor-Soler, MD, PhD, who is also an associate professor of medicine at the Keck School of Medicine of USC. “The results of this trial will hopefully move us closer to potential solutions.” 

Raising awareness of Long Covid ‘blue legs’ symptom

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Patient standing at 0 minutes CREDIT University of Leeds

An unusual case of a Long Covid patient’s legs turning blue after 10 minutes of standing highlights the need for greater awareness of this symptom among people with the condition, according to new research published in the Lancet

The paper, authored by Dr Manoj Sivan at the University of Leeds, focuses on the case of one 33-year man who developed with acrocyanosis – venous pooling of blood in the legs. 

A minute after standing, the patient’s legs began to redden and became increasingly blue over time, with veins becoming more prominent. After 10 minutes the colour was much more pronounced, with the patient describing a heavy, itchy sensation in his legs. His original colour returned two minutes after he returned to a non-standing position. 

The patient said he had started to experience the discolouration since his COVID-19 infection. He was diagnosed with postural orthostatic tachycardia syndrome (POTS), a condition that causes an abnormal increase in heart rate on standing.  

Dr Sivan, Associate Clinical Professor and Honorary Consultant in Rehabilitation Medicine in the University of Leeds’ School of Medicine, said: “This was a striking case of acrocyanosis in a patient who had not experienced it before his COVID-19 infection.  

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Patient standing at 2 minutes

“Patients experiencing this may not be aware that it can be a symptom of Long Covid and dysautonomia and may feel concerned about what they are seeing. Similarly, clinicians may not be aware of the link between acrocyanosis and Long Covid. 

“We need to ensure that there is more awareness of dysautonomia in Long Covid so that clinicians have the tools they need to manage patients appropriately.” 

Long Covid affects multiple systems in the body and has an array of symptoms, affecting patients’ ability to perform daily activities. The condition also affects the autonomic nervous system, which is responsible for regulating blood pressure and heart rate.  

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Patient standing at 10 minutes

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Acrocyanosis has previously been observed in children with dysfunction of the autonomic nervous system (dysautonomia), a common symptom of post-viral syndromes. 

Previous research by Dr Sivan’s team has shown that both dysautonomia and POTS frequently develop in people with Long Covid. 

Dysautonomia is also seen in a number of other long-term conditions such as Fibromyalgia and Myalgic Encephalomyelitis, also known as Chronic Fatigue Syndrome or ME.  

Dr Sivan said: “We need more awareness about dysautonomia in long term conditions; more effective assessment and management approaches, and further research into the syndrome. This will enable both patients and clinicians to better manage these conditions.” 

Low levels of vitamin D linked to long COVID

Vitamin D
Vitamin D

Long COVID risk has been found to increase with low levels of vitamin D, according to research presented at the 25th European Congress of Endocrinology in Istanbul. The findings suggest that individuals should have their vitamin D levels checked after COVID-19.

Also known as post COVID-19 syndrome, long COVID is a new condition in which the effects of COVID-19 last for more than 12 weeks after contracting the initial infection. Studies have shown that it affects 50-70% of patients previously hospitalised for COVID-19, yet very little is known about the condition. One risk factor for worse outcomes for hospitalised COVID-19 patients, such as intubation and mechanical ventilation or death, is low vitamin D levels, but its role in long COVID has not been adequately investigated.

For this study, supported by Abiogen Pharma SpA, researchers from the Vita-Salute San Raffaele University and IRCCS San Raffaele Hospital in Milan examined 100 patients aged 51-70 years, with and without long COVID. They measured their vitamin D levels when first admitted to hospital for COVID-19 and six months after being discharged, and found lower vitamin D levels in patients with long COVID compared to those without. This result was more evident in patients who experienced ‘brain fog’ symptoms, such as confusion, forgetfulness and poor concentration, at the six-month follow-up.

The researchers included patients without any bone conditions and only those who went to hospital for COVID-19, without ending up in the intensive care units (ICUs). They matched the two groups, with and without long COVID, in terms of age, sex, pre-existing chronic diseases and COVID-19 severity. “Previous studies on the role of vitamin D in long COVID were not conclusive mainly due to many confounding factors,” said lead investigator Professor Andrea Giustina. “The highly-controlled nature of our study helps us better understand the role of vitamin D deficiency in long COVID, and establish that there is likely a link between vitamin D deficiency and long COVID.”

While Professor Giustina acknowledges that larger studies are needed to confirm this link, he and his team are now focussed on finding out whether vitamin D supplements can reduce the risk of long COVID. “Our study shows that COVID-19 patients with low vitamin D levels are more likely to develop long COVID but it is not yet known whether vitamin D supplements could improve the symptoms or reduce this risk altogether.”

More than a thousand studies on coronaviruses summarized by researchers at Eötvös Loránd University

Researchers at Eötvös Loránd University (ELTE) have processed the scientific findings on COVID-19 disease severity, which reveal the risk factors and possible causes of the differential course of the disease.

The web of risk factors of severe COVID-19

Researchers at Eötvös Loránd University (ELTE) have processed the scientific findings on COVID-19 disease severity, which reveal the risk factors and possible causes of the differential course of the disease. Their study was published in Viruses. CREDIT Photo: Müller Viktor, Zsichla Levente / Eötvös Loránd University

Researchers at Eötvös Loránd University (ELTE) have processed the scientific findings on COVID-19 disease severity, which reveal the risk factors and possible causes of the differential course of the disease. Their study was published in Viruses.

The COVID-19 pandemic has affected the whole world, but the number of cases and deaths is very unevenly distributed between geographical regions and individual risk has been significantly influenced by the infected individual, the infectious virus strain and some characteristics of the environment.

The clinical course and outcome of COVID-19 is highly variable.

Understanding why some people become asymptomatic while others lose their lives is essential both to cure the disease and to control the epidemic.

Levente Zsichla, a student of the Institute of Biology at ELTE and his supervisor, Dr. Viktor Müller, Associate Professor at the Institute of Biology at ELTE, analysed more than a thousand studies to provide a comprehensive picture of how processes influence the severity of COVID-19 at the individual level.

In their study, they examined in detail the role of demographic factors (age and biological sex, and related pregnancy), the interactions of the disease with other infectious and non-communicable comorbidities, and the influence of genetic polymorphisms, lifestyle, microbiota and established immune memory. In addition, the impact of genetic variation in the coronavirus (SARS-CoV-2) and environmental factors such as air pollution and socioeconomic status were reviewed.

For each factor, the evidence, sometimes conflicting, for the association with COVID-19 outcomes was examined and possible mechanisms of action were outlined. They also reviewed the complex interactions between different risk factors and the feedback effects of epidemic closures on these factors. We review some examples from their study.

WHAT IS ALREADY KNOWN – AGE AND UNDERLYING DISEASES

Advanced age is among the strongest risk factors for COVID-19 mortality. This effect was first reported in early 2020 and has since been confirmed by numerous studies. These findings show that

the risk of death in adults doubles approximately every 6-7 years of life,

and (in the case of the first major wave of the pandemic) has already exceeded 1% in the 65-75 age group. Ageing of lung tissue and the immune system, and the age-related increase in sterile systemic inflammation levels may also be responsible for this phenomenon.

Some chronic diseases also increase the risk of severe COVID-19, but there are exceptions and controversial cases. While obesity, diabetes, hypertension, chronic kidney disease and cardiovascular disease are certainly risk factors, the results for several immunological, neurological and mental diseases are still inconclusive. There is also such controversy within lung diseases. While chronic obstructive pulmonary disease seems to have a clear aggravating effect, in the majority of studies allergic asthma has been found to be a neutral or even risk-reducing underlying condition. This may be because, although both conditions are associated with shortness of breath, chest tightness, wheezing and coughing, the causes and mechanisms of the two conditions are largely different.

MEN ARE MORE VULNERABLE, WOMEN HAVE MORE COMPLICATIONS

Data show that men are at about twice the risk of serious COVID-19 infection, not only among older people but also regardless of age. Similar associations have also been shown for other viral respiratory diseases (e.g. influenza) and infectious pneumonia, so the mechanism is probably not unique to COVID-19. The role of several X-linked genes and the differential expression of other genes that play a key role in the immune system may underlie this phenomenon. In addition, men with severe COVID-19 often have immunological problems involving a family of immune molecules produced against viruses, interferons. In a significant proportion of patients, the production of these interferons is disturbed or the body starts to produce antibodies against them, inactivating the otherwise protective proteins.

Women have a lower risk of severe COVID-19 disease, but a higher rate of post-COVID-19 syndrome. Pregnancy is a particular risk factor for the course of the infection, with pregnant infected women more likely to develop gestational hypertension, more often being admitted to intensive care and the consequences for the foetus/infant.

INDIRECT EFFECTS OF THE ENVIRONMENT

Poor socioeconomic status, including poverty, poor housing conditions or belonging to an ethnic minority, has been shown to be a risk factor in many countries. It also affects people’s lifestyle, nutrition, exposure to air pollution and infectious respiratory diseases, and the availability and quality of health care. Unsurprisingly, and supported by research evidence, regular physical activity and a healthy diet are beneficial for overall health and COVID-19 outcomes, while excessive alcohol consumption increases the risk of serious disease. Even more surprisingly, the impact of smoking, which significantly impairs respiratory function, on the clinical outcome of SARS-CoV-2 infection remains undetermined. In contrast, a growing body of research links long-term exposure to high concentrations of particulate matter with severe coronavirus disease.

SIGNIFICANCE OF THE REVIEW

There have been several summaries of factors influencing the outcome of COVID-19, but these have either covered a small area or provided only a sketchy summary of a wider range of risk factors. The new study provides the most comprehensive overview of risk factors,

highlighting the dominant role of age, biological sex, certain chronic underlying diseases, previously acquired specific immunity, and the infectious virus strain in the course of the disease.

If you take the time to read it – and we recommend it to our brave and persistent readers – you will see how complex the science is and how often it is difficult to draw clear conclusions. It also reveals the amazing scientific collaboration that has taken place over the past few years as the international scientific community has joined forces to find answers and solutions to the pandemic threatening the world. Fortunately, with the development of effective vaccines and the immunity of those who have been affected, the pandemic has gradually been pushed into the background. Nevertheless, as the virus is expected to be with us for a long time to come, the conclusions of this study will be needed well into the future.

Most long covid effects resolve within a year after a mild infection

The mild disease does not lead to substantial long-term illness in most infected individuals, say researchers.

Most symptoms or conditions that develop after mild covid-19 infection linger for several months but return to normal within a year finds a large study from Israel published by The BMJ today.

In particular, vaccinated people were at lower risk of breathing difficulties – the most common effect to develop after mild infection – than unvaccinated people.

These findings suggest that, although the long covid phenomenon has been feared and discussed since the beginning of the pandemic, the vast majority of mild disease cases do not suffer serious or chronic long term illness, say the researchers.

Long covid is defined as symptoms persisting or new symptoms appearing more than four weeks after initial infection. In March 2022, an estimated 1.5 million people in the UK (2.4% of the population) reported long covid symptoms, mainly fatigue, shortness of breath, loss of smell, loss of taste, and difficulty concentrating.

But the clinical effects of long covid one year after mild infection and their association with age, sex, covid-19 variants, and vaccination status are still unclear.

To address this, researchers compared the health of uninfected individuals with those who had recovered from mild covid-19 for a year after infection.

They used electronic records of a large public healthcare organisation in Israel, in which almost 2 million members were tested for covid-19 between 1 March 2020 and 1 October 2021. Over 70 long covid conditions were analysed in a group of infected and matched uninfected members (average age 25 years; 51% female).

They compared conditions in unvaccinated people, with and without covid-19 infection, controlling for age, sex and covid-19 variants, during early (30-180 days) and late (180-360 days) time periods after infection. Conditions in vaccinated versus unvaccinated people with covid-19 were also compared over the same time periods.

To ensure only mild disease was assessed, they excluded patients admitted to hospital with more serious illness. Other potentially influential factors, such as alcohol intake, smoking status, socioeconomic level, and a range of pre-existing chronic conditions were also taken into account.

Covid-19 infection was significantly associated with increased risks of several conditions including loss of smell and taste, concentration and memory impairment, breathing difficulties, weakness, palpitations, streptococcal tonsillitis and dizziness in both early and late time periods, while hair loss, chest pain, cough, muscle aches and pains and respiratory disorders resolved in the late period.

For example, compared with non-infected people, mild covid-19 infection was associated with a 4.5-fold higher risk of smell and taste loss (an additional 20 people per 10,000) in the early period and an almost 3-fold higher risk (11 per 10,000 people) in the late period. 

The overall burden of conditions after infection across the 12-month study period was highest for weakness (an additional 136 people per 10,000) and breathing difficulties (107 per 10,000).

When conditions were assessed by age, breathing difficulties were the most common, appearing in five of the six age groups but remaining persistent throughout the first year post-infection in the 19-40, 41-60, and over 60 years age groups. 

Weakness appeared in four of the six age groups and remained persistent in the late phase only in the 19-40 and 41-60 age groups.

Male and female patients showed minor differences, and children had fewer outcomes than adults during the early phase of covid-19, which mostly resolved in the late period. Findings were similar across the wild-type, Alpha and Delta covid-19 variants.

Vaccinated people who became infected had a lower risk of breathing difficulties and similar risk for other conditions compared with unvaccinated infected patients.

The researchers point to some limitations, such as incomplete measurement within medical records, so data might not fully reflect diagnoses and outcomes reported. And they can’t rule out the possibility that covid-19 patients may use healthcare services more frequently, resulting in higher reporting and increased screening for potential covid-related outcomes in these patients.

Nevertheless, this was a large detailed analysis of health records across a diverse population, representing one of the longest follow-up studies in patients with mild covid-19 to date. And findings should apply to similar western populations worldwide.

“Our study suggests that mild covid-19 patients are at risk for a small number of health outcomes and most of them are resolved within a year from diagnosis,” say the researchers.

“Importantly, the risk for lingering dyspnoea was reduced in vaccinated patients with breakthrough infection compared with unvaccinated people, while risks of all other outcomes were comparable,” they add.