The novel coronavirus severe acute respiratory syndrome coronavirus 2 causing the Coronavirus disease (COVID-19) pandemic has ravaged the world with over 72 million total cases and over 1.6 million deaths worldwide as of early December 2020. An overwhelming preponderance of cases and deaths is observed within the elderly population, and especially in those with pre-existing conditions and comorbidities. Aging causes numerous biological changes in the immune system, which are linked to age-related illnesses and susceptibility to infectious diseases. Age-related changes influence the host immune response and therefore not only weaken the ability to fight respiratory infections but also to mount effective responses to vaccines. Immunosenescence and inflamm-aging are considered key features of the aging immune system wherein accumulation of senescent immune cells contribute to its decline and simultaneously increased inflammatory phenotypes cause immune dysfunction. Age-related quantitative and qualitative changes in the immune system affect cells and soluble mediators of both the innate and adaptive immune responses within lymphoid and non-lymphoid peripheral tissues. These changes determine not only the susceptibility to infections, but also disease progression and clinical outcomes thereafter. Furthermore, the response to therapeutics and the immune response to vaccines are influenced by age-related changes within the immune system. Therefore, better understanding of the pathophysiology of aging and the immune response will not only help understand age-related diseases but also guide targeted management strategies for deadly infectious diseases like COVID-19.

The novel severe acute respiratory syndrome coronavirus 2, the cause of the coronavirus disease 2019 (COVID-19) pandemic, has ravaged the world, with over 22 million total cases and over 770,000 deaths worldwide as of August 18, 2020. While the elderly are most severely affected, implicating an age bias, a striking factor in the demographics of this deadly disease is the gender bias, with higher numbers of cases, greater disease severity, and higher death rates among men than women across the lifespan. While pre-existing comorbidities and social, behavioral, and lifestyle factors contribute to this bias, biological factors underlying the host immune response may be crucial contributors. Women mount stronger immune responses to infections and vaccinations and outlive men. Sex-based biological factors underlying the immune response are therefore important determinants of susceptibility to infections, disease outcomes, and mortality. Despite this, gender is a profoundly understudied and often overlooked variable in research related to the immune response and infectious diseases, and it is largely ignored in drug and vaccine clinical trials. Understanding these factors will not only help better understand the pathogenesis of COVID-19, but it will also guide the design of effective therapies and vaccine strategies for gender-based personalized medicine. This review focuses on sex-based differences in genes, sex hormones, and the microbiome underlying the host immune response and their relevance to infections with a focus on coronaviruses.

The SARS-CoV-2 novel coronavirus has caused the COVID-19 pandemic with over 35 million cases and over a million deaths worldwide as of early October 2020. The populations most affected are the elderly and especially those with underlying comorbidities. In terms of race and ethnicity, black and hispanic populations are affected at disproportionately higher rates. Individuals with underlying conditions that cause an immune-compromised state are considered vulnerable to this infection. The immune response is an important determinant in viral infections including coronaviruses, not only in the antiviral defense but also in the disease progression, severity, and clinical outcomes of COVID-19. Systemic lupus erythematosus is a chronic autoimmune disease which also disproportionately afflicts black and hispanic populations. In lupus patients, an aberrant immune response is characterized by the presence of circulating autoantibodies, lymphopenia, aberrant T cells, and proinflammatory cytokines along with defective regulatory mechanisms, leading to immune-mediated damage to tissues. Lupus patients are often treated with immune-suppressants and therefore are immunecompromised and more susceptible to infections and may be vulnerable to coronavirus infection. While the anti-viral immune response is important to protect from coronavirus infection, an uncontrolled proinflammatory cytokine response can lead to cytokine storm which causes damage to the lungs and other organs, causing significant morbidity and mortality. Better understanding of the underlying immune response and therapeutic strategies in lupus and COVID-19 is important to guide management of this deadly infectious disease in the context of lupus and vice-versa.