Certain live attenuated vaccines can prevent serious complications from COVID-19

COVID-19 continues to wreak havoc around the world, with over a million deaths to date. What if an existing vaccine could make COVID-19 less deadly? A recently published study put the theory to the test with promising results.

A research team led by Dr. Larenas-Linnemann of Medica Sur, Mexico City, reported on her clinical observations on 255 subjects who have been vaccinated with the mumps-measles-rubella (MMR) vaccine since the onset of coronavirus disease 2019 (COVID-). 19) pandemic.

Many vaccinated patients were family members or caregivers of patients who had already contracted COVID-19 and were therefore at extremely high risk. Thirty-six of the patients have now contracted COVID-19, but all with a remarkably mild course, with less severe symptoms than would be expected based on their health and age.

The paper published in the September issue of Allergy, the European Journal of Allergy and Immunology, is now available for free download.

MMR vaccination as part of COVID-19 taking advantage of a measles outbreak

At the onset of the COVID-19 pandemic, taking into account the highly contagious and virulent nature of the virus and the lack of preventive measures available, researchers looked for methods to improve innate immunity – which actually gives the immune system a boost to prepare for a wide variety of attacks .

Because COVID-19 was new to humans, there was no treatment or vaccination to specifically combat it. But Dr. Larenas-Linnemann, who was Dutch and had completed her basic training in the Netherlands, watched with admiration a compatriot’s work on a little-known concept called “trained immunity”.

Technically speaking, trained immunity refers to the increased immune response to a particular pathogen after exposure (through vaccination or natural disease) to another unrelated pathogen; The immune response to subsequent exposure to an unrelated pathogen is more rapid and is associated with increased production of certain cytokines.

This means that surprisingly, some vaccinations not only prevent the target disease (like measles), but can also help people fight other diseases.

Trained immunity is a form of non-specific immunity. It was controversial at first, but after decades of groundbreaking fieldwork by a Danish team studying the tuberculosis vaccine and live polio vaccine in Northern Europe and Africa, followed by years of authoritative laboratory work by Dr. Larenas-Linnemann’s compatriot Mihai Netea and others it is now believed that certain live attenuated vaccines may better prepare the body to fight a range of pathogens.

The team of Dr. Larenas-Linnemann wondered: Could a live attenuated vaccine protect her patients from this completely new disease, COVID-19? Taking advantage of the fact that the Mexico pandemic coincided with a surge in measles cases, which had motivated the Department of Health to recommend re-vaccination against measles, the team decided to put the concept of trained immunity to the test.

Therefore, starting in March 2020, the researchers recommended the MMR vaccination to their patients, especially for family members of COVID-19 cases.

Observational study on MMR for COVID-19 prevention

In a prospective observational study at Hospital Médica Sur, named Mexico City’s Best Hospital since 2011, the team gave its patients boosters for a standard vaccine for children, measles-mumps-rubella (MMR), which is considered safe worldwide (a Booster) is even required in many places to start college or military service).

Patients were closely watched for COVID-19 infection. Patients were classified as high risk for COVID infection as many cared for sick family members and were vulnerable due to their age or other risk factors.

The COVID-19 infection was considered confirmed with a positive result of a SARS-CoV-2 antigen test, the detection of specific antibodies or the combined presence of direct contact with a confirmed case plus anosmia / ageusia and at least two classic COVID infections. 19 symptoms. Direct contact with a confirmed case, accompanied by classic symptoms but without changes in smell or taste, was considered to be the most likely case.

The clinical severity of COVID-19 was rated on a simplified scale from zero for asymptomatic cases, through 1 for mild, 2 for moderate, 3 for non-oxygenated lower respiratory symptoms, up to 6 for death. In-house measurements of pulse oximetry and the peak expiratory flow rate (PEFR) were also used to determine the severity.

Results: None of the 36 cases required supplemental oxygen

Among the 255 subjects vaccinated, there were 24 confirmed and 12 (high) probable COVID-19 cases, thirteen with risk factors that can often make COVID-19 more severe (high blood pressure, diabetes, obesity, smoking, or uncontrolled asthma).

In their publication, the authors describe the risk factors for each patient. All received general supportive measures; Some received high-dose off-label ivermectin for the first two days. In general, the cases were less severe than expected.

All of them had at most mild respiratory symptoms. Only one patient with uncontrolled asthma had low blood oxygen for a day. No patient had respiratory failure that required oxygen.

We were relieved that MMR, commonly viewed as a vaccine for children, seemed to help our older adult patients weather the storm as well. ”

Dr. Larenas-Linnemann

reaction

“We wouldn’t be surprised if MMR could offer some protection against severe COVID-19,” said researcher Peter Aaby of the Bandim Health Project in Guinea-Bissau and the Vitamins and Vaccine Research Center (CVIVA) of the Statens Serum Institute, a government public Health and research facility of the Danish Ministry of Health in Copenhagen, Denmark and a pioneer in this field.

“Together with my partner Dr. Christine Stabell Benn, we have been reporting on mortality reductions through attenuated live vaccines such as polio, BCG and measles vaccine / MMR for several decades and advocate optimized vaccination plans. With the COVID in view of the urgency of the crisis, it is good to see that the potential of unspecific immune effects is being taken seriously. ”

Global research on the application of trained immunity to COVID-19 prevention

Researchers around the world are studying the ability of existing live attenuated vaccines to prevent serious complications from COVID-19.

Several clinical studies are currently underway on tuberculosis (BCG) vaccination of SARS-CoV-2 exposed health care workers to reduce the severity of a possible infection.

However, one of the effects described in experiments with BCG-trained immunity was an increase in interleukin-6 cytokine (IL-6), which the Médica Sur team was reluctant to use this method because of high levels of IL-related immune overactivation. 6 levels described in severe COVID-19 cases.

In addition, BCG vaccines and live polio vaccines are not used in the United States or Canada, making BCG and polio vaccines difficult to use across North America. Existing BCG supplies are also badly needed to save infant lives around the world.

The team of Dr. Larenas-Linnemann chose the MMR vaccine instead because of its safety profile, as well as previous studies describing trained immunity to MMR in newborns from hepatitis infected mothers, and retrospective studies showing a 26-49% decrease in all-cause mortality rates. showed measles vaccination programs.

What’s next

These first observation data from Dr. Larenas-Linnemann and her group in Mexico City, who show a milder course of COVID-19 in people recently vaccinated with MMR, are promising.

The researchers are continuing their strategy of recommending MMR vaccinations to household contacts of COVID-19 patients and plan to continue collecting data on additional clinical cases.

They are also looking to work with basic immunologists to investigate the immunological background of their observations. Dr. Larenas-Linnemann said: “We are grateful that we were able to offer this to our patients and hope that these first data from real life will spark interest in the approach.”

Conclusive evidence of the value of an MMR vaccine in reducing COVID-19 complications requires a prospective, randomized study. This is exactly what the microbiologist Dr. Paul Fidel of Louisiana State University recently launched.

He hypothesized that live attenuated vaccines induce myeloid suppressor cells (MDSCs), another form of trained innate immunity, to suppress the fatal sepsis that often occurs in severe COVID-19 cases, as stated in an opinion / hypothesis in mBio outlined.

Funding from the Parsemus Foundation and Fast Grants will enroll first responders and healthcare workers in the hardest-hit New Orleans area in the MMR randomized controlled trial. The team of Dr. Fidel is still looking for means to test whether MMR can offer protection to nursing home residents who are particularly prone to the disease.