The COVID-19 Pandemic: Does Our Early Life Environment, Life Trajectory and Socioeconomic Status Determine Disease Susceptibility and Severity?

Abstract

A poor socioeconomic environment and social adversity are fundamental determinants of human life span, well-being and health. Previous influenza pandemics showed that socioeconomic factors may determine both disease detection rates and overall outcomes, and preliminary data from the ongoing coronavirus disease (COVID-19) pandemic suggests that this is still true. Over the past years it has become clear that early-life adversity (ELA) plays a critical role biasing the immune system towards a pro-inflammatory and senescent phenotype many years later. Cytotoxic T-lymphocytes (CTL) appear to be particularly sensitive to the early life social environment. As we understand more about the immune response to SARS-CoV-2 it appears that a functional CTL (CD8+) response is required to clear the infection and COVID-19 severity is increased as the CD8+ response becomes somehow diminished or exhausted. This raises the hypothesis that the ELA-induced pro-inflammatory and senescent phenotype may play a role in determining the clinical course of COVID-19, and the convergence of ELA-induced senescence and COVID-19 induced exhaustion represents the worst-case scenario with the least effective T-cell response. If the correct data is collected, it may be possible to separate the early life elements that have made people particularly vulnerable to COVID-19 many years later. This will, naturally, then help us identify those that are most at risk from developing the severest forms of COVID-19. In order to do this, we need to recognize socioeconomic and early-life factors as genuine medically and clinically relevant data that urgently need to be collected. Finally, many biological samples have been collected in the ongoing studies. The mechanisms linking the early life environment with a defined later-life phenotype are starting to be elucidated, and perhaps hold the key to understanding inequalities and differences in the severity of COVID-19.

Socioeconomic inequalities in the spread of coronavirus-19 in the United States: A examination of the emergence of social inequalities

“…However, there is growing concern about the potential for post-COVID-19 syndrome ( Davido, Seang, Tubiana, & de Truchis, 2020 ). This syndrome is likely to impact those who were already most disadvantaged thereby amplifying the impacts of a lifetime of exposures ( Holuka et al, 2020 ). Future work is needed to follow individuals with the post-COVID syndrome and determine the longer-term consequences of the infection.…”

Macrolevel association of COVID-19 with non-communicable disease risk factors in India

“…Multiple studies from across the globe have reported that individuals with established coronary heart disease, heart failure, chronic respiratory, renal or liver disease and cancers or their risk factors such as diabetes, hypertension, obesity, and other vascular risk factors are at greater risk of acquiring infection and developing complications and deaths from COVID-19 [ [2] , [3] , [4] , [5] , [6] , [7] , [8] , [9] , [10] ]. Environmental factors such as urbanization, crowding, ambient and indoor air pollution, poor sanitation and low socioeconomic status are also important in increasing the risk of disease incidence and deaths [ 5 , [11] , [12] , [13] ].…”

Is Early Life Adversity a Trigger towards Inflammageing?

“…Furthermore, exposure to ELA is a major risk factor for T2D, as well as cardiovascular disease and "a significant proportion of the cardio-metabolic and diabetic disease burden may be attributable to maltreatment" (Chandan et al, 2020). As reviewed in (Holuka et al, 2020), it would appear that low SES transcriptionally programs inflammatory pathways shared with T2D including genes such as: F8, CCL1, CD1D, KLRG1, NLRP12, and TLR3 as well as AVP, FKBP5, and OXTR (Holuka et al, 2020). This transcriptional inflammatory link is further re-enforced by the observation that elements of the ELA immunophenotype described below such as the accumulation of senescent CD8+ CTLs with increased levels of systemic inflammatory markers (Lau et al, 2019, Yi et al, 2019.…”

“…As we and others have recently highlighted (Holuka et al, 2020), we need to start considering both socioeconomic and early life environment data as genuinely important medical information that should be routinely collected. It is important that the retrospective life-trajectory data is collected, even under the risk of recall bias.…”

“…Here the prior ELA has been characterised, and a wide variety of cross-sectional studies can be conceived that would investigate the effect of this exposure to ELA many decades ago on the relative morbidity and mortality of COVID-19 in these population. It has already been highlighted (Holuka et al, 2020) that the ELA immunophenotype may play a significant role in determining the outcome of COVID-19 disease. In summary, exposure to early life adversity would appear to not only produce a specific immunophenotype, but to accelerate the overall immune-ageing and inflammageing processes.…”