Herbert Carly, Antar Annukka A R, Broach John, Wright Colton, Stamegna Pamela, Luzuriaga Katherine, Hafer Nathaniel, McManus David D, Manabe Yukari C, Soni Apurv
Program in Digital Medicine, Department of Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA.
University of Massachusetts Center for Clinical and Translational Science, University of Massachusetts Chan Medical School, Worcester, MA, USA.
medRxiv. 2024 Jul 5:2024.07.04.24309953. doi: 10.1101/2024.07.04.24309953.
The relationship between SARS-CoV-2 viral dynamics during acute infection and the development of long COVID is largely unknown.
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.
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).
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.
急性感染期间严重急性呼吸综合征冠状病毒2（SARS-CoV-2）病毒动力学与长期新冠的发展之间的关系很大程度上尚不清楚。
2021年10月至2022年2月期间，共有7361名无症状社区居民参加了“在家检测我们”的母研究。参与者每24 - 48小时自行采集前鼻拭子进行SARS-CoV-2逆转录聚合酶链反应（RT-PCR）检测，持续10 - 14天，无论症状或感染状态如何。在母研究中，对入组时无新冠病毒病病史且随后被发现SARS-CoV-2 RT-PCR检测结果≥1次呈阳性的参与者，于2023年8月再次联系，询问他们是否经历过长期新冠，长期新冠定义为SARS-CoV-2感染后出现持续3个月或更长时间的新症状。将参与者的循环阈值转换为病毒载量，并使用最低点后病毒载量对病毒清除斜率进行建模。使用以建模斜率为暴露因素的对数二项模型，我们计算了随后出现1 - 2种症状、3 - 4种症状或5种及以上症状的长期新冠的相对风险，并对年龄、症状数量和SARS-CoV-2变异株进行了调整。还计算了基于病毒清除情况的个体长期新冠症状的调整后相对风险（aRR）。
172名参与者符合分析条件，59名（34.3%）报告经历过长期新冠。每病毒载量斜率单位增加，出现3 - 4种症状和5种及以上症状的长期新冠风险分别增加2.44倍（aRR：2.44；95%置信区间：0.88 - 6.82）和4.97倍（aRR：4.97；95%置信区间：1.90 - 13.0）。出现长期新冠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显著长于未出现长期新冠的参与者（8.65 [95%置信区间：8.28 - 9.01] 天对10.0 [95%置信区间：9.25 - 10.8] 天）。病毒清除斜率与长期新冠的疲劳症状（aRR：2.86；95%置信区间：1.22 - 6.69）、脑雾（aRR：4.94；95%置信区间：2.21 - 11.0）、呼吸急促（aRR：5.05；95%置信区间：1.24 - 20.6）和胃肠道症状（aRR：5.46；95%置信区间：1.54 - 19.3）显著正相关。
我们观察到，在急性新冠期间从病毒载量峰值到病毒RNA清除的时间越长，出现长期新冠的风险越高。此外，清除率越慢，长期新冠的症状数量越多。这些发现表明，早期病毒 - 宿主动力学在长期新冠的后续发展中具有重要机制意义。
