The Possible Role of Oxytocin in Long COVID

The Centers for Disease Control and Prevention (CDC) defines post-COVID conditions as a wide range of new, returning, or ongoing health problems people can struggle with four or more weeks after first being infected with the coronavirus. (You might have also heard the terms "long COVID," "long-haul COVID," "post-acute COVID-19," "long-term effects of COVID," or "chronic COVID," which can all be subsumed under the newer term “post-COVID conditions.”) As of July 2021, “long COVID,” as its perhaps most commonly known, can be considered a disability under the Americans with Disabilities Act (ADA).

Even patients who appeared to be asymptomatic can develop post-COVID conditions. This presents a conundrum, then, since it appears as if these symptoms can happen to anyone who had COVID-19—regardless of severity.

What Do Post-COVID Conditions Look Like?

People who were infected with the coronavirus may report a variety of symptoms weeks and months after the infection because the virus may affect many organs such as the lungs, heart, or brain. Possible symptoms include, but are not limited to, the following:

• Headaches
• Depression and/or anxiety
• Changes in smell and/or taste
• Pins-and-needles feeling
• Brain fog, or difficulty thinking, focusing, and paying attention
• Memory problems
• Fast or pounding heartbeat
• Fatigue
• Joint and/or muscle pain
• Sleep problems
• Dizziness when standing; feeling lightheaded
• Skin rashes
• Changes in menstrual cycles
• Digestive issues such as diarrhea
• Cough
• Difficulty breathing or shortness of breath
• Symptoms that get worse after physical or mental activities

Why Do Some Patients Develop Long-Term COVID?

According to a recent Mayo Clinic Study, women are more likely to suffer from long-term COVID effects than men. Other recent studies, published across different domains, have shed some additional light on the question of why some people, but not others, develop long COVID.

One possible explanation for the progression of the infection into long-term conditions is the overwhelmed immune system response to viruses in some patients. When challenged, some people's immune systems can become unbalanced and secrete many more pro-inflammatory cytokines (causing inflammation) instead of balancing them with anti-inflammatory ones (molecules fighting and protecting against overactive immune system damage).

The excessive release of these pro-inflammatory cells can lead to what's known as a “cytokine storm,” which in turn may contribute to increased morbidity and mortality. This explains why severely ill COVID patients tend to have a high concentration of pro-inflammatory cytokines as compared with moderately sick patients.

Can Oxytocin Help Prevent Long COVID Symptoms?

Scientists have so far struggled to connect the dots across the different findings. However, I argue that one small chemical may connect the dots: the hormone oxytocin. The location of oxytocin's receptors, its mode of action, and its role at the intersection of the immune, endocrine, and nervous systems make it a credible biological target against the progression of COVID infection.

What can help restore the balance in the immune system (i.e., lead to the release of more anti- than pro-inflammatory molecules)? Oxytocin. Although most famous for its roles in reproduction and lactation, oxytocin has a regulatory role in the immune system as well. It is anti-inflammatory instead of pro-inflammatory, which helps calm the cytokine storm.

In one experiment, for example, scientists deleted the oxytocin receptor gene in human skin cells exposed to UV irradiation. The result was exacerbated oxidative stress and the release of inflammatory cytokines (1). This suggests that oxytocin plays an important protective role.

The heart, too, has oxytocin receptors, and oxytocin plays a protective role in the heart and lungs (2). In one experiment, giving oxytocin infusions to rats who had had heart attacks suppressed inflammation by reducing the number of pro-inflammatory molecules (3).

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Another potential avenue for reducing the severity of post-COVID symptoms is to reduce pre-existing conditions related to COVID mortality and morbidity. These include cardiovascular disease, diabetes, and obesity (2). Oxytocin plays a protective role in all these conditions; for example, patients with Type 2 diabetes tend to show low levels of oxytocin. It is also cardio-protective and is anti-hypertensive.

What Reduces Oxytocin in Our Bodies?

Hypothalamic-pituitary-adrenal (HPA) activation inhibits oxytocin brain cells from doing their job. Thus, anything that over-activates the HPA axis can reduce the protective roles of oxytocin.

High on the list of things that turn on the HPA axis is social stress. In one experiment, socially isolated mice with nerve injury showed high levels of pro-inflammatory gene expression in the frontal cortex seven days post-injury. But when the mice were treated with oxytocin, the inflammation in the frontal cortex was extinguished and the animals stopped showing depressive behaviors (4).

Blocking oxytocin even in healthy, non-isolated animals has been found to lead to depressive behavior and inflammation in the frontal cortex. Together, these findings indicate that socialization’s protective effects occur via the release of oxytocin.

Why Fostering Social Connection Might Help

If social isolation reduces oxytocin and leads to exacerbation of inflammation, then socialization should have the opposite effects. Indeed, social connections are necessary for our health and well-being partly because they promote oxytocin release.

Social connections are even more needed during times of high uncertainty and distress, such as pandemics. Oxytocin systems in both human and animal studies have been shown to encourage stress-reducing, pro-social behaviors as well as anti-inflammatory effects. In fact, oxytocin is the link between the stress-buffering and anti-inflammatory effects of social support (5 ).

Lockdown mandates and social distancing may have contributed to secondary somatic and psychological diseases because they challenged the oxytocin protective system. In turn, social distancing could convert an acute COVID infection into a chronic condition because of the debilitating effects of isolation on our oxytocin levels. It may be that we need the oxytocin at the beginning of the infection to recruit a surplus of anti-inflammatory soldiers to fight against COVID.

Studies have shown that the flu vaccine tends to be less effective after a period of social isolation. It may be reasonable to extend these findings to the COVID vaccine as well. Perhaps some combination of oxytocin (or oxytocin-promoting behaviors, such as hugging loved ones or praying) and the vaccine is a more effective solution than the vaccine alone.

What's more, I argue that elevating oxytocin during the early stages of infection may help prevent the progression into long-term COVID disabilities. Thus, oxytocin may remedy some of the psychosocial stress endured by the pandemic.

The COVID pandemic overwhelmed our immune system, induced social stress, and increased financial burdens. It is imperative that we find an adjunct to the protective measures already in place in order to prevent long-term problems. Oxytocin is safe and can be released by many everyday behaviors—even something as simple as a hug.