The ‘positives’ of feeling bad in a pandemic
“ … the prospect of fatigue and headache after vaccination for COVID-19 should be viewed positively, as a necessary prelude to an effective immune response”.
STREETWISE came across this article in Science Immunology (https://immunology.sciencemag.org), which states the development of multiple vaccines against SARS-CoV-2 virus, the cause of coronavirus disease (COVID-19), within one year of the epidemic is, “unprecedented and an immense accomplishment”.
It says the efficacy of many developed vaccines exceeded expectations, “and there are high hopes that the epidemic will soon be in the past. Yet several challenges remain”.
The authors explain because vaccinations are far from complete and have barely begun in many developing nations, it is feared global herd immunity against the virus may take several years. Nearly four million people have died from COVID-19, with 182,254,551 confirmed cases in 220 countries and territories as of June 28.
“There is also the growing problem of vaccine hesitancy, especially in the young who generally cope well with COVID-19, with minimal or even no symptoms,” according to Australian immunologists Jonathan Sprent and Cecile King. “In addition, it is well documented COVID-19 vaccines can have substantial side effects; indeed, fear of these side effects may approach that of SARS-CoV-2 infection itself in some populations. Therefore, what are the side effects of COVID-19 vaccines – and could they paradoxically be beneficial?”
The Pfizer and Moderna vaccines have received the most attention in regard to side effects: “As with other vaccines, these effects can on rare occasion be the result of delayed-onset, local allergic reactions. In the vast majority of cases, however, the major complaint is a combination of fever, headache, myalgia and general malaise, affecting about 60 per cent of recipients after the second dose of the vaccines. These symptoms can be troubling and have been the subject of comment in the press and in top scientific journals. Yet, other than vague reference to an ongoing immune response, the actual cause of the side effects has received almost no attention. So what is the cause of these effects? As discussed here, most of the symptoms can likely be attributed simply to exuberant production of a cytokine that plays a vital role in potentiating early stages of the immune response, namely type I interferon (IFN-I).
“To date, we have been unable to locate direct evidence on IFN-I production after vaccination against SARS-CoV-2 infection. This is more than likely, however, given that other mRNA vaccines are known to be powerful inducers of IFN-I. Therefore, the key question arises whether strong IFN-I production accounts for the side effects of COVID-19 vaccines? In considering this question, it should be noted that IFN-I has been used therapeutically for many years, currently for treating hepatitis B and C and multiple sclerosis. In these contexts, IFN-I injection elicits the same prominent pattern of fever, headaches and fatigue as the current COVID-19 vaccines. Moreover, when used repeatedly, therapeutic IFN-I administration can also lead to depression and cognitive slowing and thereby closely mimic the still-poorly understood clinical condition of chronic fatigue syndrome. Given that IFN-I stimulates synthesis of many different cytokines and chemokines, which of these downstream effects account for the symptoms of IFN-I administration is still unclear.”
Importantly, the authors note that effective immune responses to SARS-CoV-2 and other pathogens are IFN-I-dependent which, “begs the question of how vaccines induce immunity”. They said it is highly likely, albeit not proven, that the side effects of COVID-19 vaccines are simply a by-product of, “a short burst of IFN-I generation concomitant with induction of an effective immune response”.
They added side effects vary considerably according to the recipient’s age and sex, with more severe effects in females than males and in younger people than the elderly: “The point to emphasise here is the striking correlation with IFN-I production. Thus, closely paralleling the intensity of typical immune responses, IFN–I generation is substantially stronger in females than males and in younger than older people.”
Additionally, for SARS-CoV-2 infection, “it was mentioned earlier that IFN-I levels are low, reflecting antagonism by the virus. By contrast, IFN-I levels are generally high in influenza infection. This difference may explain why ‘flu-like’ symptoms are prominent for influenza but usually mild during SARS-CoV-2 infection. It is worth noting, however, that current COVID-19 vaccines lead to selective expression of just the spike protein, which fails to antagonise IFN-I. Hence, IFN-I production by the vaccines might be appreciably higher than following SARS-CoV-2 infection itself, which could then explain why young people tend to have significant side effects to COVID-19 vaccines yet can be asymptomatic during SARS-CoV-2 infection”.
In light of the above, the prospect of fatigue and headache after vaccination for COVID-19 should be viewed positively: as a necessary prelude to an effective immune response. The side effects of vaccination will nearly always be mild and transient, and indicate merely that the vaccine is doing its job of stimulating production of interferon, the body’s in-built immune stimulator.
* Featured image courtesy of the US Centers for Disease Control and Prevention (CDC).
