Features of acute COVID-19 associated with Post-Acute Sequelae of SARS-CoV-2 phenotypes: results from the IMPACC study

Post-acute sequelae of SARS-CoV-2 (PASC) is a significant public health concern. We describe Patient Reported Outcomes (PROs) on 590 participants prospectively assessed from hospital admission for COVID-19 through one year after discharge. Modeling identified 4 PRO clusters based on reported deficits (minimal, physical, mental/cognitive, and multidomain), supporting heterogenous clinical presentations in PASC, with sub-phenotypes associated with female sex and distinctive comorbidities. During the acute phase of disease, a higher respiratory SARS-CoV-2 viral burden and lower Receptor Binding Domain and Spike antibody titers were associated with both the physical predominant and the multidomain deficit clusters. A lower frequency of circulating B lymphocytes by mass cytometry (CyTOF) was observed in the multidomain deficit cluster. Circulating fibroblast growth factor 21 (FGF21) was significantly elevated in the mental/cognitive predominant and the multidomain clusters. Future efforts to link PASC to acute anti-viral host responses may help to better target treatment and prevention of PASC.严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染后急性后遗症（PASC）是一项重大公共卫生关切。本研究描述了590名参与者的患者报告结局（PROs），这些参与者从新冠病毒感染入院开始，被前瞻性随访评估至出院后1年。建模分析基于报告的功能缺损，鉴定出4类患者报告结局簇（轻度、躯体、精神/认知及多领域缺损簇），证实了PASC存在异质性临床表现，且其亚表型与女性性别及特异性合并症相关。在疾病急性期，较高的呼吸道新冠病毒载量以及较低的受体结合域（RBD）和刺突蛋白抗体滴度，与躯体主导型和多领域缺损型簇均存在关联。多领域缺损簇患者的循环B淋巴细胞频率经质谱流式细胞术（CyTOF）检测显著降低。精神/认知主导型及多领域簇患者的循环成纤维细胞生长因子21（FGF21）水平显著升高。未来将PASC与急性期抗病毒宿主应答相关联的研究，或有助于更精准地靶向PASC的治疗与预防。