Infectious Diseases

Posted on Diabetes, Infectious Diseases

The century-old vaccine protects type 1 diabetics from infectious diseases including COVID-19.

Researchers identified immune cells as a potential key factor for protection against MS disease

–In new research, investigators at Massachusetts General Hospital (MGH) show that the 100-year-old Bacillus Calmette-Guérin (BCG) vaccine, originally developed to prevent tuberculosis, protects individuals with type 1 diabetes from severe COVID-19 disease and other infectious diseases.

Two back-to-back randomized double-blinded placebo-controlled trials found that the BCG vaccine provided continuous protection for nearly the entire COVID-19 pandemic in the US, regardless of the viral variant.

“Individuals with type 1 diabetes are highly susceptible to infectious diseases and had worse outcomes when they were infected with the SARS-CoV-2 virus,” said senior author Denise Faustman, MD, PhD, director of the Immunobiology Laboratory at MGH and an Associate Professor of Medicine at Harvard Medical School. “Published data from other investigators show mRNA COVID-19 vaccines are ineffective in this group of vulnerable patients. But we’ve shown that BCG can protect type 1 diabetics from COVID-19 and other infectious diseases.”  

The 18-month Phase III trial, published in iScience, was conducted late in the US pandemic when the highly transmissible Omicron variant was circulating. A 15-month Phase II trial was conducted early in the pandemic; the results of that trial were published in Cell Reports Medicine.

During the COVID-19 pandemic, several international trials tested whether BCG, given as a single shot or booster to previously BCG-vaccinated adults, protected them from infection and COVID-19. This research expanded the large global clinical trial database, showing that BCG administered to newborns is a platform for all infectious diseases, maybe for decades. However, results from these COVID-19 booster trials in people previously vaccinated with BCG were mixed, with five randomized trials showing efficacy and seven trials showing no benefit. 

The MGH Phase II and Phase III clinical trials testing BCG differed from other BCG trials in important ways. Instead of receiving one dose of BCG, participants received five or six doses of a particularly potent strain of BCG vaccine. The US participants were followed for a total of 36 months instead of weeks or months. “We know that in people who are naïve to BCG vaccine, the off-target effects can take at least two years to achieve full protection,” said Faustman. “Giving multiple doses of the vaccine may speed up that process.”

And importantly, the US population had never received BCG vaccines, so these clinical trials were not booster trials. “The Phase II and Phase III trials conducted at MGH were unique in that they were the only COVID trials in the world in which the study population had never received a BCG vaccine and was never exposed to TB,” said Faustman. “Trials conducted in countries where participants had previously received BCG vaccine as newborns or who had previous exposure to tuberculosis may have obscured any benefit from a BCG booster.”

The MGH trials enrolled 141 participants with type 1 diabetes; 93 people in the treatment group received five or six doses of BCG vaccine, and the 48 individuals in the placebo group received sham vaccine and were followed for 36 months to capture diverse COVID-19 genetic variants and many infectious disease exposures.

During the earlier Phase II trial (January 2020 to April 2021), when the virus was more lethal but less transmissible, the BCG vaccine’s efficacy was 92%, comparable to the efficacy of the Pfizer and Moderna COVID-19 vaccines in healthy adults.

Over the full 34 months of the US COVID-19 pandemic, the BCG vaccine had a significant efficacy of 54.3%. The investigators also found that the BCG-treated participants had lower rates of viral, bacterial, and fungal infections as well as COVID-19 disease itself.

The BCG vaccine confers an immunity that likely lasts decades, a clear advantage to the COVID-19 vaccine and vaccines against other infectious diseases, such as influenza, where the duration of effectiveness is only two or three months. “The BCG vaccine offers the prospect of near-lifelong protection against every variant of COVID-19, the flu, respiratory syncytial virus, and other infectious diseases,” said Faustman.

Some of the BCG-treated participants also received the commercially available COVID-19 vaccines during the Phase III trial. The investigators observed that the Pfizer, Moderna, and Johnson & Johnson vaccines did not protect people with type 1 diabetes against COVID-19. “Our study showed that the BCG vaccine neither increased the efficacy of the COVID-19 vaccine, nor was it harmful to those who received the COVID-19 vaccine,” said Faustman.  “As the pandemic continues to evolve, it will be interesting to see if we can work with the FDA to allow access to BCG vaccine for type 1 diabetics, who appear to be particularly at risk for all infectious diseases.”

Posted on Infectious Diseases, Multiple Sclerosis

PLEASE DO NOT IGNORE!!! Individuals with multiple sclerosis face a substantially greater risk of hospitalisation and death from COVID-19, despite high rates of vaccination.

UK study in almost 12 million people during the Omicron wave finds that even after repeated doses of COVID-19 vaccines, individuals with multiple sclerosis had a seven times greater risk of hospitalisation and a four-fold increased risk of dying from CO

New real-world research being presented at this year’s European Congress of Clinical Microbiology and Infectious Diseases (ECCMID 2024) in Barcelona, Spain (27-30 April) reveals that people living with multiple sclerosis (MS) face a much higher risk of being hospitalised and dying from COVID-19 than the general population. The risk persists in individuals who received 3 or more vaccine doses.

These findings indicate that vaccination alone may not adequately protect individuals with MS from severe COVID-19 outcomes and underscore the urgent need for additional preventive measures against COVID-19 in this vulnerable population, say researchers.
Lead author Professor Jennifer Quint from Imperial College London, UK explains, “Having multiple sclerosis in itself doesn’t increase the risk of getting COVID-19, rather it’s the taking of immune modifying medicine such as B-cell depletion therapies that can reduce the effectiveness of vaccines by preventing the immune system from mounting a robust protective response. Some MS-specific factors, such as having underlying conditions or higher levels of disability, can contribute to poor outcomes. As a result, even after repeated doses of COVID-19 vaccines, some individuals with MS remain at high risk of serious outcomes from COVID-19.”
The new analyses are part of the INFORM (INvestigation of Covid-19 Risk among iMmunocompromised populations) study, which analysed data of nearly 12 million people aged 12 years and older in England to assess COVID-19’s impact, risk, and healthcare resource use (HCRU) among immunocompromised populations compared with the general population during the Omicron wave.
Previous results from INFORM found that immunocompromised individuals face disproportionate burdens from COVID-19, with a substantially higher risk of developing severe COVID-19 outcomes than the general population [1]. However, the specific burden faced by individuals with MS, which was not categorised as immunocompromised, was not assessed previously.
To find out more, researchers compared the risk of COVID-19 hospitalisation and death in vaccinated individuals with MS and the general population in England from 1st January to 31st December, 2022.
They analysed routinely collected national primary and secondary care electronic data from a random sample of 25% of all individuals aged 12 years or older in England registered with the National Health Service (NHS). Subgroup analysis was conducted among individuals vaccinated with three or more doses of COVID-19 by Jan 1st, 2022.
Of 11,990,730 individuals included in the study, 16,350 (0.1%) individuals with MS were identified. Over half (6,060,635) of those in the general population and more than three-quarters (12,905) of patients with MS had been fully vaccinated (received at least three doses of a COVID-19 vaccine by Jan 1st, 2022).
During the study, the general population recorded 20,910 COVID-19 hospitalisations and 4,810 COVID-19 deaths, corresponding to crude overall incidence rates of 0.24 and 0.06 per 100 person-years, respectively.
Among individuals with MS, there were 215 COVID-19 hospitalisations and 25 COVID-19 deaths, corresponding to substantially higher overall incidence rates of 1.28 and 0.14 per 100 person-years, respectively.
After adjusting for age and sex, having MS was associated with a seven times greater risk of COVID-19 hospitalisation and fourfold increased risk of dying from COVID-19 compared to the general population.
“We hope that these findings raise awareness that the threat of COVID-19 is still very real for many, and that vaccine boosters are inadequate to protect this clinically vulnerable group”, says Professor Quint. “With new variants constantly emerging, people living with MS should be considered an important high-risk group for COVID-19 hospitalisation and death for which additional preventive measures and multi-layered public health protections are urgently needed.”
Despite the important findings, the authors point to several limitations, including that they can’t rule out the possibility that other unmeasured factors such as underling illness and level of MS disability might have influenced the results. They also note that they did not examine the effect of use of disease modifying therapies, time since last vaccination, type of vaccination, and prior infection.

Posted on Infectious Diseases

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.” 

Posted on Fatigue, Fibromyalgia, Infectious Diseases

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

CREDIT

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.” 

Posted on Infectious Diseases

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.