So what hampers immunity?
Compromised immunity exists in two broad categories. There are those with medical conditions that directly affect the immune response, causing it to underperform. And there are also those whose medical conditions are managed using immunosuppressive drugs.
The former group of conditions are called immunodeficiencies. These can exist from birth as a result of genetic alterations, though they are very rare. They can also be acquired later in life through many different causes. These include malnutrition, obesity, diabetes and HIV infection.
The ways in which some of these factors negatively affect the immune system are well known. For example, HIV infects white blood cells know as helper T cells. As a result, patients have fewer of these cells available to fight off other infections.
But in many cases we don’t fully understand why a condition leads to immunodeficiency. For example, diabetes is a risk factor not just for COVID-19 but also other viral and bacterial infections, including hepatitis B and tuberculosis. However, studies are beginning to reveal how uncontrolled blood sugar in diabetic patients makes their immune systems less effective. Signalling between immune cells is impaired, as is their ability to kill disease-causing microorganisms.
Then, there are immunosuppressive drugs, which patients receive for many different reasons. These range from having organ transplants to asthma to blood cancers or autoimmune conditions. There are many types of these drugs, with different ones used for different conditions. The extent to which a drug may affect the COVID-19 vaccine response will vary depending on how the drug works.
Antimetabolites, for instance, are drugs that interfere with some of the most basic aspects of cell function. To take an example, one such drug – mycophenolate – affects the ability of immune cells to create new DNA and divide properly. Antimetabolites have wide-ranging effects – being used in chemotherapy and to stop the body rejecting organ transplants – and are associated with poorer COVID-19 vaccine responses.
Another class of immunosuppressive drug are what are known as “targeted biologics”. These can block specific parts of the immune system while leaving others unaffected. For example, drugs that block an immune-signalling molecule called TNF work in a very focused way, and so have been shown to have less of an effect on the COVID-19 vaccine response compared to antimetabolites.
However, other targeted biologics – for example rituximab, a type of artificially created (or “monoclonal”) antibody – affect COVID-19 vaccine responses more significantly. Rituximab targets a specific molecule on the surface of immune cells that produce antibodies, reducing their productive ability. For this reason, patients should avoid receiving rituximab for a period before and after COVID-19 vaccination.
At the moment, much of what we know about how well COVID-19 vaccines work in immunocompromised groups comes from smaller studies. It’s vital that data is gathered from larger groups to help us fully understand the barriers to getting people to create effective vaccine responses. In the meantime, people with conditions or taking medications that are known to lower the effectiveness of the immune system should be aware that their level of vaccine protection could be below average.