Does Estrogen Affect the Coronavirus?

The Coronavirus pandemic has impacted all of us. We wake up every morning and hear the latest grim statistics and deleterious effect this disease is having on our healthcare system, economy, and, well, just about every aspect of modern life.

Each day we learn more about the nuances of this new disease and speculation about some of the unknowns.

Why do some people get so much sicker than others?

Why do children seem to be spared from some of the serious complications?

And, pertinent to this blog, why do women appear to fare better than men?

Increasingly, it appears that more men than women are being admitted to ICUs and have lower chances of surviving Covid-19.  In China, Europe, and the US more men than women have died from the Coronavirus.

Why would this be? Is it possible that there is something about estrogen that may be protective? Does estrogen affect the immune system in a positive fashion? The answers to these questions may interest you.

We have known for many years that women tend to fight infections better than men. This is particularly true in the case of bacteria such as the ones that cause tuberculosis (TB) and Salmonella.  Women are also less likely to have complications from many viral infections, such as Hepatitis B. The white blood cells in women tend to produce a stronger antibody response to these organisms. And, while research indicates that having two X chromosomes boosts a woman’s immune response, it is known that estrogen, per se, has powerful anti-inflammatory effects. The benefit of this is that once an invading organism is detected, the body can quickly and efficiently mount a defense.

To understand how estrogen plays a beneficial role, let me provide a brief overview of the immune system. It is a very complex system and is comprised of organs such as our spleen and lymph nodes, a bevy of specialized cells (such as white cells and macrophages), and hundreds of protein elements such as immunoglobulins and cytokines.

When a foreign substance (meaning anything the body doesn’t recognize as itself) enters your system, your immune army comes into play.  Specialized white blood cells – the B and T lymphocytes – latch onto the invader and take imprints of its shape.  The B cells start producing immunoglobulins based on the imprints taken.  These scavenger proteins circulate in the blood stream and latch onto particles that match the imprint, essentially putting “targets” on them to flag them so that other components of the immune system can attack them.  The T cells are direct fighters, engulfing the intruders and destroying them  The T cells also produce and release cytokines.  Cytokines are chemicals that can cause many effects in the body, such as generating a fever, stimulating blood vessels to dilate, irritating nerve endings to cause pain, or signaling cells to proliferate – all elements that are part of the inflammatory response.

We generally think that the main job of the immune system is to fight infections. However, our immune system is also involved in quelling complications from other mishaps that damage our tissues, such as a cut or other injury. Cells that are injured release substances that activate the immune system. The ensuing inflammation facilitates the healing process. Fluid accumulates to wall off the damaged tissue (thus causing swelling), blood vessels expand to deliver more supplies to the area (causing redness and warmth), and white cells congregate to chew up the debris (causing pus). Collectively, all this activity results in destroying noxious agents, removing dead cells, and promoting the healing process. Unfortunately, in some cases, too much inflammation can also damage surrounding healthy tissue. The process is a complicated balancing act.

So how does menopause fit into this discussion?

After menopause, studies show that women’s immune systems are not as robust. There are lower numbers of disease-fighting white cells present and they don’t function as efficiently.  This would lead to a greater chance of getting an infection as well as a higher likelihood the infection would be more severe.

The question to be answered is whether postmenopausal estrogen replacement would bolster the immune system.  A considerable amount of research suggests that it does.  Estrogen has been shown to promote the function of the B cells that make antibodies as well as the T cells that help capture and engulf infectious particles.

In addition, estrogen plays a major role in cytokine production.  Cytokines cause many effects, some which tend to be beneficial and some which can have negative effects.  We know that estrogen suppresses inflammation in the joints, blood vessels, and other areas.  This is why HRT has been shown to decrease joint pain and protect the lining of the arteries from damage, thus decreasing the risk of heart attacks and strokes. These benefits are thought to occur secondary to the way estrogen regulates cytokines – promoting the production of “good cytokines” and limiting the production of the ones that may cause “bad” effects.

.So what may be the role of estrogen when it comes to Covid-19, the disease caused by the novel Coronavirus?  The presence of estrogen may help women fight the virus in multiple ways.  Research shows that estrogen appears to decrease the number of receptors that the virus can find once it enters the body.  In addition, women taking estrogen may have a more rapid and aggressive white cell response, blocking the virus from replicating and infecting more cells.

It also appears that estrogen can moderate the cytokine response caused by a Covid infection.  One of the reasons people get so sick from this virus is that when it settles in the lungs it can trigger a “cytokine storm,” a massive inflammatory response that causes so much lung damage that ICU treatment and ventilator support is needed.  It is not known if administering estrogen would be beneficial in this situation, but there are several studies in the works to look at this.

We know that older age is a risk factor for a more severe Covid infection.  Based on what we know about estrogen, it is possible that menopausal and postmenopausal women on HRT may fare better than women not on HRT. The good news is that there is no reason to suspect that taking estrogen would be detrimental.