Does chronic swelling in older PLWH increase susceptibility of PLWH to more severe results with COVID-19? Does chronic swelling accelerate raises in SARS-CoV-2 viral burden once PLWH are infected? Does chronic swelling influence disease severity and progression, as well as subsequent time to resolution of SARS-CoV-2 illness? Because biological ageing is definitely associated with mechanistic changes in innate and adaptive immune signaling and immune response, 106 and chronic swelling drives dysregulation between biological and chronological ageing,107 there is a need to better understand whether people ageing with HIV-1 illness differ from the general population in their coordination of immune response, leukocyte composition, timing and dynamics of response, and cell signaling upon SARS-CoV-2 illness

Does chronic swelling in older PLWH increase susceptibility of PLWH to more severe results with COVID-19? Does chronic swelling accelerate raises in SARS-CoV-2 viral burden once PLWH are infected? Does chronic swelling influence disease severity and progression, as well as subsequent time to resolution of SARS-CoV-2 illness? Because biological ageing is definitely associated with mechanistic changes in innate and adaptive immune signaling and immune response, 106 and chronic swelling drives dysregulation between biological and chronological ageing,107 there is a need to better understand whether people ageing with HIV-1 illness differ from the general population in their coordination of immune response, leukocyte composition, timing and dynamics of response, and cell signaling upon SARS-CoV-2 illness. Clinical research efforts to effectively control COVID-19 will need a better understanding of risk factors for infection and, once infected, a more exact alignment between severity of disease and underlying immunophenotypes. identified in the United States (WA1 in Seattle, Washington; UC4 in San Francisco Bay Area, California; NY1-PVC8001 in New York City) and in Europe (BavPat1 in Munich, Germany).2,3 Within the span of a few months (December 2019 to April 2020), several 1,000 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) coronavirus isolates were identified, all posting genetic relatedness to SARS-CoV, 1st identified in 2011, but distinct enough to form their personal evolutionary cluster. Over this first yr (December 2019 HG6-64-1 to December 2020) of the SARS-CoV-2 pandemic, 80 million people worldwide were infected, with global mortality totaling 2 million deaths.4 By comparison, the HIV-1 pandemic offers taken nearly 35 years (1984C2019) to infect an comparative 80 million people worldwide, offers sustained 30 million deaths in total, and 700,000 deaths in this past year alone.5 Thus, at present, there is a syndemic of 40 million people living with HIV-1 infection (PLWH) and 100 million with SARS-CoV-2 infection worldwide.4 In contrast with HIV-1 infection, which is nearly always fatal in the absence of potent antiretroviral therapy (ART), outcomes from SARS-CoV-2 infection are more heterogeneous, with 10%C20% of infections leading to severe clinical conditions and 1%C10% resulting in death within 2C3 weeks of infection. Although SARS-CoV-2 outcomes remain unpredictable for an individual, emerging research has recognized populations at higher risk for severe disease outcomes once infected, including older age ( 65 years old),6,7 male sex,8,9 and persons with preexisting conditions like cardiovascular disease and obesity.6,10 Whereas combination antiretroviral therapy (cART) has had HG6-64-1 a positive impact on PLWH life expectancy, it is not curative and importantly does not restore full immunocompetence.11,12 The extent to which PLWH experience adverse outcomes upon coinfection with SARS-CoV-2 is an active area of investigation. Initial results based on smaller cohort studies were inconclusive, but more recent and larger cohort studies suggest HG6-64-1 that COVID-19 mortality is usually higher in PLWH than in the general population. For example, a meta-analysis of five cohort studies13C17 indicated that overall COVID-19-related deaths in PLWH were nearly double that of persons without HIV-1 contamination.18 A study of 24,000 persons in South Africa reported that mortality rates were doubled in PLWH.14 Similarly, a study of 17 million persons in the United Kingdom, including 27,000 PLWH, also showed a higher mortality rate in PLWH, especially among Black persons.13 Explanatory factors may include biological and sociological factors such as restricted access to health care resources (needle HG6-64-1 exchange, counseling, and mental health services) and health delivery infrastructure (transit, continuity of care, adherence to antiretroviral therapy [ARV], and pre-exposure prophylaxis [PrEP] distribution) that resulted from public measures in response to COVID-19.19,20 What follows is a conversation of difficulties in the HIV-1 and SARS-CoV-2 syndemic, including (i) the role of age, sex, and race as drivers or risk factors for COVID-19; (ii) whether chronic inflammation common in PLWH influences response; (iii) whether models for severity and trajectory of COVID-19 may differ in PLWH; (iv) vaccine considerations; and finally, (v) long-term health outcomes in PLWH that are further burdened by coinfection with SARS-CoV-2 (Table 1). Table 1. Pressing Questions and Difficulties in HIV-1 and SARS-CoV-2 Syndemic Question 1: Are biological aging, sex and race drivers of COVID-19 severity? br / Difficulties: br / ??Identifying specific age-related mechanisms dysregulated in PLWH with and without SARS-CoV-2 infection br / ???Creating sex-specific immune profiles in PLWH with SARS-CoV-2 coinfection br / ???Determining role for sex hormones in infection risk, disease outcomes, UPA and response to immunomodulatory treatment br / ???Removing racially based structural inequities and community/workplace exposure to reduce risk for infection, hospitalization, and mortality br / ???Inclusion of race in prioritizing populations for treatment, prophylaxis, and vaccination.