■急性感染期间SARS-CoV-2病毒动力学与长期COVID发展之间的关系在很大程度上是未知的。
■在2021年10月至2022年2月之间,共有7361名无症状社区居民参加了“在家测试我们”父母研究。参与者自我收集前鼻拭子,每24-48小时进行SARS-CoV-2RT-PCR检测,共10-14天,无论症状或感染状态。在招募时没有COVID-19病史,随后在父母研究中发现SARS-CoV-2RT-PCR检测≥1阳性的参与者于2023年8月重新联系,并询问他们是否经历了长时间的COVID,定义为SARS-CoV-2感染后持续3个月或更长时间的新症状的发展。参与者的周期阈值被转换成病毒载量,使用最低点后的病毒载量对病毒清除的斜率进行建模。使用对数二项式模型,将建模的斜率作为曝光,我们计算了随后发展为1-2种症状的长期COVID的相对风险,3-4症状,或5+症状,调整年龄,症状的数量,和SARS-CoV-2变种。还计算了基于病毒清除的个体长期COVID症状的调整后相对风险(aRR)。
■172名参与者有资格进行分析,59人(34.3%)报告经历长期COVID。具有3-4个症状和5个症状的长期COVID的风险增加了2.44倍(aRR:2.44;95%CI:0.88-6.82)和4.97倍(aRR:4.97;95%CI:1.90-13.0),每增加一个病毒载量斜率单位,分别。与从未发展为长COVID的参与者相比,发展为长COVID的参与者在急性疾病期间从病毒载量峰值到病毒清除的时间明显更长(8.65[95%CI:8.28-9.01]与10.0[95%CI:9.25-10.8])。病毒清除斜率与疲劳的长期COVID症状呈显著正相关(aRR:2.86;95%CI:1.22-6.69),脑雾(ARR:4.94;95%CI:2.21-11.0),呼吸短促(RR:5.05;95%CI:1.24-20.6),胃肠道症状(aRR:5.46;95%CI:1.54-19.3)。
■我们观察到,在急性COVID-19期间,从病毒载量峰值到病毒RNA清除的时间更长与发展为长COVID的风险增加有关。Further,较慢的清除率与较多的长型COVID症状相关。这些发现表明,早期病毒宿主动力学在随后长COVID的发展中具有重要的机械意义。
UNASSIGNED: The relationship between SARS-CoV-2 viral dynamics during acute infection and the development of long COVID is largely unknown.
UNASSIGNED: A total of 7361 asymptomatic community-dwelling people enrolled in the Test Us at Home parent study between October 2021 and February 2022. Participants self-collected anterior nasal swabs for SARS-CoV-2 RT-PCR testing every 24-48 hours for 10-14 days, regardless of symptom or infection status. Participants who had no history of COVID-19 at enrollment and who were subsequently found to have ≥1 positive SARS-CoV-2 RT-PCR test during the parent study were recontacted in August 2023 and asked whether they had experienced long COVID, defined as the development of new symptoms lasting 3 months or longer following SARS-CoV-2 infection. Participant\'s cycle threshold values were converted into viral loads, and slopes of viral clearance were modeled using post-nadir viral loads. Using a log binomial model with the modeled slopes as the exposure, we calculated the relative risk of subsequently developing long COVID with 1-2 symptoms, 3-4 symptoms, or 5+ symptoms, adjusting for age, number of symptoms, and SARS-CoV-2 variant. Adjusted relative risk (aRR) of individual long COVID symptoms based on viral clearance was also calculated.
UNASSIGNED: 172 participants were eligible for analyses, and 59 (34.3%) reported experiencing long COVID. The risk of long COVID with 3-4 symptoms and 5+ symptoms increased by 2.44 times (aRR: 2.44; 95% CI: 0.88-6.82) and 4.97 times (aRR: 4.97; 95% CI: 1.90-13.0) per viral load slope-unit increase, respectively. Participants who developed long COVID had significantly longer times from peak viral load to viral clearance during acute disease than those who never developed long COVID (8.65 [95% CI: 8.28-9.01] vs. 10.0 [95% CI: 9.25-10.8]). The slope of viral clearance was significantly positively associated with long COVID symptoms of fatigue (aRR: 2.86; 95% CI: 1.22-6.69), brain fog (aRR: 4.94; 95% CI: 2.21-11.0), shortness of breath (aRR: 5.05; 95% CI: 1.24-20.6), and gastrointestinal symptoms (aRR: 5.46; 95% CI: 1.54-19.3).
UNASSIGNED: We observed that longer time from peak viral load to viral RNA clearance during acute COVID-19 was associated with an increased risk of developing long COVID. Further, slower clearance rates were associated with greater number of symptoms of long COVID. These findings suggest that early viral-host dynamics are mechanistically important in the subsequent development of long COVID.