Interaction of Biopsychosocial Stress, Alcohol Misuse, and Neurobehavioral Sequelae of COVID-19

摘要 2019年SARS-CoV-2冠状病毒（COVID-19）大流行继续影响世界，第四波疫情正在蔓延。 路易斯安那州和新奥尔良市在人均病例和住院治疗方面处于领先地位。那里 目前迫切需要确定COVID-19的无症状病例、治疗和健康影响。 这场大流行造成了数周的不确定性、焦虑和令人震惊的感染率所造成的社会孤立 以及社交距离、自我隔离和就地避难措施的授权。饮酒会 在胁迫和不确定的时候增加，经常被滥用来科普压力，焦虑， 萧条少数群体和艾滋病毒携带者是弱势群体，他们的艾滋病毒感染率过高， 暴露于慢性和终身的社会压力源，与心理健康状况较差的比率升高有关，包括 抑郁症、酒精使用障碍（AUD）和创伤后应激障碍。认知和 与AUD相关的行为缺陷通常归因于持续的神经适应， 目前的AUD患者表现出认知障碍，包括工作记忆、执行能力、 功能性和冲动性，所有这些都导致了适应不良的决策。过量的酒精暴露也 损害周围神经系统的元件以产生特征性小纤维神经病， 由此产生的痛觉过敏（或增加的疼痛敏感性）被假设为促成饮酒的动机因素。 我们的初步数据确定了PLWH相对于HIV的痛觉过敏状态（疼痛敏感性增加）。 消极的个人。神经功能缺陷，如认知能力下降和疼痛，与术后疼痛有关。 COVID-19急性后遗症（PASC）。我们的初步数据还表明， 在政府发布限制措施以控制COVID-19后，使用、吸烟和心理社会压力因素在一个队列中 艾滋病毒携带者和艾滋病毒阴性者。我们的首要假设是，酒精滥用会增加风险， PACS的严重性。为了验证这一假设，我们的研究小组准备进行一项双向研究 利用新奥尔良酒精使用和艾滋病毒（NOAH）纵向研究队列，包括PLWH和 艾滋病毒阴性个体。利用现有的NOAH队列，我们可以及时做出反应， 确定无症状病例的启动时间，并增加持续报告健康状况不佳者获得护理的机会 对弱势群体的关注。来自我们提议的NOAH-PACS研究的数据将描述完整的 PACS谱和新出现的疾病表型，并识别其发展的风险因素。结果 将推进合并症、酒精使用和护理相关结果的社会决定因素背后的科学 在艾滋病毒携带者和艾滋病毒阴性者中。该提案的结果将告知PACS的管理层 并将为未来的研究项目提供信息，以开发行为和药物干预的目标， 减少创伤性社会事件后的适应不良应激反应和酒精滥用。

ABSTRACT The SARS-CoV-2 coronavirus 2019 (COVID-19) pandemic continues to impact the world and the fourth wave of the pandemic has Louisiana and the city of New Orleans leading in per capita cases and hospitalizations. There is an urgent and ongoing need to determine asymptomatic cases, treatment and health impacts of COVID-19. The pandemic has caused weeks of uncertainly, anxiety, and social isolation imposed by alarming infection rates and mandates for social distancing, self-quarantine, and shelter-in-place measures. Alcohol consumption can increase during times of duress and uncertainty and is often misused to cope with stress, anxiety, and depression. Minority populations and PLWH are vulnerable populations who have an excessively high rate of exposure to chronic and lifetime social stressors, linked to elevated rates of poorer mental health including depressive disorders, alcohol use disorders (AUDs), and post-traumatic stress disorder. Cognitive and behavioral deficits associated with AUD are commonly attributed to persistent neuro adaptations, as both former and current AUD patients demonstrate cognitive impairments including deficits in working memory, executive functioning, and impulsivity, all contributing to maladaptive decision-making. Excessive alcohol exposure also damages elements of the peripheral nervous system to produce a characteristic small fiber neuropathy, and the resulting hyperalgesia (or increased pain sensitivity) is hypothesized to contribute to motivational factors to drink. Our preliminary data identifies a state of hyperalgesia (increased pain sensitivity) in PLWH relative to HIV- negative individuals. Neurological deficits, such as cognitive decline and pain, have been associated with post- acute sequelae of COVID-19 (PASC). Our preliminary data also demonstrates a significant increase in alcohol use, smoking, and psychosocial stressors post government-issued restrictions to control COVID-19 in a cohort of PLWH and HIV-negative individuals. Our overarching hypothesis is that alcohol misuse increases the risk and severity of PACS. To test this hypothesis, our research team is prepared to conduct an ambidirectional study leveraging the New Orleans Alcohol Use and HIV (NOAH) longitudinal study cohort including both PLWH and HIV-negative individuals. Utilizing the existing NOAH cohort, we can respond in a timely manner with minimal start up time identifying asymptomatic cases and increasing access to care for on-going under reported health concerns in a vulnerable population. Data from our proposed NOAH-PACS study will characterize the full spectrum of PACS and emerging phenotypes of disease and identify risk factors for their development. Results will advance the science behind social determinants of comorbidities, alcohol use, and care-related outcomes among PLWH and those that are HIV-negative. Results of this proposal will inform the management of PACS and will inform future research projects to develop targets for behavioral and pharmacological intervention to decrease maladaptive stress responses and alcohol misuse following traumatic societal events.