Fitzpatrick Translational Science

COVID-19 Resistance and Why Does it Matter Anymore?

There is a wide interest in finding an explanation as to why some people are resistant to getting COVID-19. Wired published an interesting article on this mystery. Early in the Pandemic, scientists from around the world set up the COVID Human Genetic Effort to understand why some people became very sick and others did not. 15,000 people from around the world applied to be screened (usually a healthy spouse of someone who got very sick or healthcare worker). However, a wrench was thrown in the works when the Omicron variant came on the scene and half of the people whose DNA had been sent off to be sequenced ended up getting infected with the variant.

Back in September, 2020, the Fitzpatrick team published data that supported the hypothesis that some people do not contract COVID-19 because they appear to have cross-reactive antibodies that protect them from developing the infection. There may also be something to the theory that certain people are predisposed to getting less severe COVID-19 symptoms than others. However, it may not be due to the same cross-reactive antibodies.

An October, 2022 Henry Ford Health publication states that as many as 1 in 10 individuals may have a gene mutation that allows antibodies and T cells to fend off COVID-19. Evidence suggests that a person’s genetic background can also have a significant impact on COVID-19 severity. Each of us carry specific HLA (human leukocyte antigens) genes called “alleles” which have proven to be important factors in the host response to foreign pathogens. A 2021 European study proves that certain HLA alleles may interact with patient factors to influence the development of severe COVID-19 complications. A 2023 study by Lehman, et al from Germany also thoroughly examined HLA alleles and blood groups for COVID-19 correlation. They found that certain HLA alleles in people were indeed associated with lesser symptoms.

COVID-19 severity may also vary by country or geographic area. HLA alleles associated with asymptomatic carriage of the disease are common in populations of European descent based at higher latitudes. Genetic associations tend to be stronger in areas with more homogenous ethnic groups as well. Populations are also not equally stratified by the same set of confounding variables. Several factors have been associated with COVID-19 mortality rates experienced by country, including UV exposure, temperature, humidity, life expectancy and rates of obesity and cancer. A meta-analysis by Thakur, et al. in 2021 found geographic differences in COVID-19 severity and mortality. It found that COVID-19 severity and mortality are variable based on medical conditions specific to geographic regions. The highest disease severity was found in Asian regions, while the highest mortality was found in European and Latin American regions.

Having protective HLA alleles implies cross-protective immunity; however, while some alleles may be associated with a decrease in COVID-19 severity, other variations of these alleles may be associated with an increase in disease severity. Alleles may also interact with age, sex and BMI to determine clinical outcomes following COVID exposure.

Seroprevalence – The COVID-19 SeroHub
The NIH has an outstanding online tool called “the COVID-19 SeroHub”. It contains nearly all of the US-based published COVID-19 seroprevalence data. It shows us what percent of people in a certain cohort (ethnicity, age, gender and antigen target - nucleocapsid, spike, spike & nucleocapsid, or not specified) tested positive at a certain point in time for COVID-19. As one can see, COVID-19 seroprevalence was nearly 100% for all ethnicities as far back as the 4th quarter in 2021. Each of the studies describes the location, specifics and seroprevalence percent. The US started hitting over 90% by June, 2021 in many of the studies. As of June, 2022, the NIH estimated that 97.4% of the US population has shown COVID-19 seropositivity. So lately, when someone says they just got COVID for the first time, we can likely tell them it’s the first time they KNOW they have it, but it’s very likely they had it at least once earlier. Note that the NIH seroprevalence data will not be able to tell us if a person had multiple infections.

With COVID-19 seroprevalence hovering close to 100%, it seems appropriate that vaccine mandates (such as the Pentagon’s) have ceased, or will soon end, even though the Health Care Worker vaccine mandate is still in effect. Fewer severe cases of COVID-19 are being reported, health care staffing shortages due to vaccine mandates are still an issue, and the expiration of a national public health emergency that has been in place since January 2020 is set to expire May 11. As we posted in December, 2020, C19 vaccines have helped get the US to our current immunity status.

Why Does COVID-19 Resistance Matter?

If seroprevalence is near 100%, then why does COVID-19 resistance matter anymore? One reason stems from the fact that if you can figure out why somebody cannot get infected, then you can potentially figure out how to prevent others from getting infected and contribute to future treatments. This would apply not only to the current COVID-19 situation, but hopefully to future epidemics and pandemics as well. There are genetic mutations that give natural immunity to other diseases like HIV, norovirus, and a parasite that causes recurring malaria. In fact, an HIV drug was inspired by the discovery of a gene mutation that prohibits the virus from latching onto cells, and more recently, two patients have received stem cell transplants from a donor carrying the mutation and became HIV free. The concept of inborn resistance against infection is still a fairly new one for scientists though.

In the last 20 years, there have been two other novel coronavirus epidemics: SARS in 2003 and MERS in 2012. The 229E common cold coronavirus was estimated to come into existence in the mid 1960’s (along with 3 other common cold coronaviruses). Our “Why is it Bats Again?” post in January, 2020 describes these coronaviruses. SARS and MERS were fairly limited, as they were only transmitted by people who were symptomatic. Thus, it was easier to identify and isolate those patients (as opposed to the asymptomatic spread of COVID-19). We predict that the world will most certainly encounter yet another coronavirus within the next couple decades.

Scientists estimate that only 1% of viruses found in mammals have been identified. Since recent pandemics were caused by zoonotic transmission (75% of emerging diseases are zoonotic), there is a large void in being able to predict what, when and how the next one will be. Historically, an influenza pandemic occurs every 15-30 years. Experts predict the next pandemic will either be a new strain of bird flu or another new coronavirus. The Fitzpatrick team would like to think that public health agencies (and their communications department), politicians, physicians and thought-leaders will all be better prepared and more ethical in their recommendations the next time around.

Kevin Fitzpatrick