Immunological Ghosts: (Epi)Genetic Racialization in the COVID-19 Pandemic

Recently, a research article was published in JAMA that found that Black Americans had greater expression of a gene, TMPRSS2, in their nasal passages1. Because that gene codes for a membrane protein that COVID-19 is able to use to enter cells, the study authors argued that such ‘racial and ethnic genetic differences’ might underlie the dramatic inequality in COVID-19 mortality borne by Black people who, along with Latinx people, are dying of the virus at six times the rate of age-matched Whites2. I found the paper unsettling and therefore shared it with my students. I wanted to discuss it in the course I teach on the early life origins of health. I hoped to use the paper as a demonstration of how genomic tools continue to be used to erroneously naturalize or justify racial biological difference and inferiority.

I told the students that we would apply what we were learning about developmental plasticity and scientific racism to critique the paper together. The class was powerful: students correctly identified flaws in the paper’s claims and assumptions. First, we noted, self-identification as Black is an insufficient proxy for genetic variation 3. Second, although levels of gene expression may be under genetic control, they also likely reflect cellular adaptation to daily and long-term environmental exposures.  Finally, although gene expression levels of TMPSRSS2 were higher in Black individuals— who indeed suffer high rates of COVID-19 mortality— they were relatively low in Latinx identified participants, who also suffer a disproportionately negative impact from COVID-19.

During that class, I told the students that I wanted to arm them with tools that can be used to dismantle the notions of White genetic superiority, which are not far removed from White supremacy, that are deeply embedded in genomic science and population health. Those tools involve a knowledge of the intergenerational impacts of developmental exposure to chronic stress,  dispossession, and discrimination, which are unfairly normalized within a racialized discourse of genetic ‘risk’. This fosters cognitive biases supporting our national tolerance and acceptance of this the narrative that Black and Brown death and illness is the “natural consequence” of “poor genes” and “poor choices”. 4 Researchers on health inequality, like myself, must counter this fallacy with evidence for the ways our bodies materially incorporate, reflect, and transmit the social environment.5

Several of my students have asked me if racism might make one more susceptible to COVID-19. I find this question profoundly troubling. On the one hand, it is important to account for the bodily impact of racism. On the other hand, focusing on the proximal ways discrimination shapes immune function can re-inscribe ideas of racial biological inferiority, masquerading as the seemingly neutral language of ‘plasticity’ and ‘epigenetics.’ In my brief review of the literature here, I find evidence suggesting that immune changes due to early life stress may have cross-talk with the immune dysregulation seen in severe COVID-19. A more pressing question, for me, is whether that evidence does anything to change the damning narrative that Black and Brown deaths as inevitable— whether it is a sufficient indictment of the fundamental social causes of COVID-19 inequality, or rather a new articulation of (epi)genetic determinism.

Our immune system broadly consists of two arms: The first is the innate system, which handles nonspecific inflammatory processes at the onset of a viral or bacterial infection. The second is the adaptive system, which people may be more aware of, due to its typical activation upon their vaccination. We would not survive long without either arm; because our body depends on their careful balance and integration. However, research has shown that early life stress results in a tendency for the body to overemphasize the innate system 6. This reflects deep phylogenetic histories that drive stress-related immunological shifts allowing the body to privilege immediate survival when one is under threat. It enables one to attend to the need to produce a hormonal and inflammatory cascade that will trigger the release of energy for immediate use, find and mark wounds for repair, and attack damaged cells or pathogens. This is a powerful process that becomes destructive when frequently activated under conditions of chronic and unrelenting stress. Consequently, under constant adversity, the body seems  to weather and erode from within 7.

The modification of immune functioning can be observed intergenerationally due to a child’s enmeshment in their maternal and familial environment. Chronic inflammation changes maternal physiology in ways that can impact the developing fetus, who’s development relies on its mother’s immunological tolerance of the placenta. Compounding such alterations in the in-utero environment, children also inherit the oppressive social and environmental conditions that contemporary racial capitalism demands for the maintenance of White supremacy. We see these effects borne out in long-standing racial inequalities in the hypertensive disorders of pregnancy, low birthweight, pre-term birth, and adult chronic and autoimmune diseases 8–10.

An extensive literature links early childhood adversity with inflammatory biomarkers; but these studies tend to conceptualize adversity as individual rather than racialized experiences. 11,12 In fact, for Americans, racial disparities in inflammation are already evident in early childhood. By the age of ten, Black and Latinx children have higher odds of chronic low-grade inflammation than their White peers. For the children of immigrants, odds for elevated inflammation are more than twice as high.13 As a result of the cumulative nature of developmental conditions, even small differences in inflammation occurring during early life can result in the dramatic downstream racial disparities in metabolic and cardiovascular health seen by adulthood. No studies have specifically examined the role of racism in the relative bodily investment or emphasis on the previously mentioned innate and adaptive immune systems. Nevertheless, some evidence suggests that childhood adversity weakens adaptive responses in a fashion resembling premature aging of adaptive immunity or “immunosenescence14,15.”

There is still much to learn about why the severity of COVID-19  is so variable. Emerging evidence suggests the possibility of insufficient coordination between the innate and adaptive arms of immunity. While early work focused on overactivation of the innate, inflammatory immune response— known somewhat imprecisely as ‘cytokine storms’-- newer evidence suggests, the failure of the immune system to activate a persistent adaptive response may be significant.16,17 Immunosenescence has been implicated in age-related COVID-19 mortalities among the elderly.

To date, little research has been done to examine how structural racism, heightened inflammation, and weakened adaptive immunity together contribute to an increased risk of morbidity and COVID-19 mortality for communities of color.18

When my students asked whether racism might make one more susceptible to COVID-19, I answered “yes”. As a result  of racism, Black and Brown people experience outsized exposure to the virus because they are denied work opportunities that allow them to socially distance. These same diminished opportunities also result in lower incomes and concomitant reduction in their access to personal protective equipment (PPE, such as face-masks) or primary healthcare. When Black and Brown people have access to healthcare, they are more likely to encounter racial-bias among healthcare providers, which could delay effective treatments and thus prove lethal.

When students ask me whether racism might make one more susceptible to COVID-19, they are also asking a different, related question. My students— especially the Black, Indigenous and people of color (BIPOC) with whom I am in community and solidarity—want to know whether there is something essential in their bodies, in their nasal passages, or in their blood that renders them and their loved ones at risk. Studies examining the proximal processes of embodiment can answer that in the affirmative. I, however, wonder what is the political nature of their ‘proof’ for the essential differences that make BIPOC more vulnerable to COVID-19? What reparations can be demanded with it? How might we wield it as a protective shield? “It is in our blood”, I say, “but it need not be”. “It is induced, not inherent”, I add. But these words are of no comfort.

References

1.    Bunyavanich, S., Grant, C. & Vicencio, A. Racial/Ethnic Variation in Nasal Gene Expression of Transmembrane Serine Protease 2 (TMPRSS2). JAMA (2020) https://jamanetwork.com/journals/jama/fullarticle/2770682

2.    Centers for Disease Control. COVID-19 Provisional Counts - Health Disparities.  (2020)https://www.cdc.gov/nchs/nvss/vsrr/covid19/health_disparities.htm.

3.    Non, A. L. & Gravlee, C. C. Biology and Culture Beyond the Genome: Race, Racism, and Health. Am. Anthropol. 117, 737–738 (2015). https://doi.org/10.1111/aman.12365

4.    McClure, E. S., Vasudevan, P., Bailey, Z., Patel, S. & Robinson, W. R. Racial Capitalism within Public Health: How Occupational Settings Drive COVID-19 Disparities. Am. J. Epidemiol. (2020)  https://doi.org/10.1093/aje/kwaa126

5.    Krieger, N. Living and Dying at the Crossroads: Racism, Embodiment, and Why Theory Is Essential for a Public Health of Consequence. Am. J. Public Health 106, 832–833 (2016). https://dx.doi.org/10.2105%2FAJPH.2016.303100

6.    Georgiev, A. V., Kuzawa, C. W. & McDade, T. W. Early developmental exposures shape trade-offs between acquired and innate immunity in humans. Evol Med Public Health 2016, 256–269 (2016). https://dx.doi.org/10.1093%2Femph%2Feow022

7.    Geronimus, A. T. Understanding and eliminating racial inequalities in women’s health in the United States: the role of the weathering conceptual framework. J. Am. Med. Womens. Assoc. 56, 133–6, 149–50 (2001). https://pubmed.ncbi.nlm.nih.gov/11759779/

8.    Lee, H., Okunev, I., Tranby, E. & Monopoli, M. Different levels of associations between medical co-morbidities and preterm birth outcomes among racial/ethnic women enrolled in Medicaid 2014–2015: retrospective analysis. BMC Pregnancy Childbirth 20, 33 (2020). https://doi.org/10.1186/s12884-020-2722-8

9.    Tanaka, M. et al. Racial disparity in hypertensive disorders of pregnancy in New York State: a 10-year longitudinal population-based study. Am. J. Public Health 97, 163–170 (2007). https://dx.doi.org/10.2105%2FAJPH.2005.068577

10.  Miller, G. E. et al. Maternal socioeconomic disadvantage is associated with transcriptional indications of greater immune activation and slower tissue maturation in placental biopsies and newborn cord blood. Brain Behav. Immun. 64, 276–284 (2017). https://dx.doi.org/10.1016%2Fj.bbi.2017.04.014

11.  Murphy, M. O., Cohn, D. M. & Loria, A. S. Developmental origins of cardiovascular disease: Impact of early life stress in humans and rodents. Neurosci. Biobehav. Rev. 74, 453–465 (2017). https://dx.doi.org/10.1016%2Fj.neubiorev.2016.07.018

12.  Fagundes, C. P., Glaser, R. & Kiecolt-Glaser, J. K. Stressful early life experiences and immune dysregulation across the lifespan. Brain Behav. Immun. 27, 8–12 (2013). https://dx.doi.org/10.1016%2Fj.bbi.2012.06.014

13.  Schmeer, K. K. & Tarrence, J. Racial-ethnic Disparities in Inflammation: Evidence of Weathering in Childhood? J. Health Soc. Behav. 59, 411–428 (2018). https://psycnet.apa.org/doi/10.1177/0022146518784592

14.  Franceschi, C. et al. Inflamm-aging: an evolutionary perspective on immunosenescence. Ann. N. Y. Acad. Sci. 908, 244–254 (2000). https://doi.org/10.1111/j.1749-6632.2000.tb06651.x

15.  Elwenspoek, M. M. C. et al. T Cell Immunosenescence after Early Life Adversity: Association with Cytomegalovirus Infection. Front. Immunol. 8, 1263 (2017). https://dx.doi.org/10.3389%2Ffimmu.2017.01263

16.  Du, S. Q. & Yuan, W. Mathematical modeling of interaction between innate and adaptive immune responses in COVID-19 and implications for viral pathogenesis. J. Med. Virol. (2020)  https://doi.org/10.1002/jmv.25866

17.  Vardhana, S. A. & Wolchok, J. D. The many faces of the anti-COVID immune response. J. Exp. Med. 217, (2020). https://dx.doi.org/10.1084%2Fjem.20200678

18.       Napoli, C., Tritto, I., Mansueto, G., Coscioni, E. & Ambrosio, G. Immunosenescence exacerbates the COVID-19. Arch. Gerontol. Geriatr. 90, 104174 (2020). https://dx.doi.org/10.1016%2Fj.archger.2020.104174

Luisa Maria Rivera, MPH is a PhD candidate in the department of Anthropology at Emory University. Her research examines embodiment, intergenerational trauma, and epigenetic discourses of self and society. She pairs research on the biological embedding of stress with in-depth ethnography in Latinx and scientific communities. 

(c) 2020 Luisa Maria Rivera