Department of Pulmonary and Infectious Diseases, Copenhagen University Hospital, North Zealand, Hillerød, Denmark.
Statens Serum Institut, Copenhagen, Denmark.
Virol J. 2023 Jan 25;20(1):14. doi: 10.1186/s12985-023-01974-8.
Viral shedding and neutralizing antibody (NAb) dynamics among patients hospitalized with severe coronavirus disease 2019 (COVID-19) and immune correlates of protection have been key questions throughout the pandemic. We investigated the duration of reverse transcriptase-polymerase chain reaction (RT-PCR) positivity, infectious viral shedding and NAb titers as well as the association between NAb titers and disease severity in hospitalized COVID-19 patients in Denmark 2020-2021.
Prospective single-center observational cohort study of 47 hospitalized COVID-19 patients. Oropharyngeal swabs were collected at eight time points during the initial 30 days of inclusion. Serum samples were collected after a median time of 7 (IQR 5 - 10), 37 (IQR 35 - 38), 97 (IQR 95 - 100), and 187 (IQR 185 - 190) days after symptom onset. NAb titers were determined by an in-house live virus microneutralization assay. Viral culturing was performed in Vero E6 cells.
Patients with high disease severity had higher mean log NAb titers at day 37 (1.58, 95% CI [0.34 -2.81]), 97 (2.07, 95% CI [0.53-3.62]) and 187 (2.49, 95% CI [0.20- 4.78]) after symptom onset, compared to patients with low disease severity. Peak viral load (0.072, 95% CI [- 0.627 - 0.728]), expressed as log SARS-CoV-2 copies/ml, was not associated with disease severity. Virus cultivation attempts were unsuccessful in almost all (60/61) oropharyngeal samples collected shortly after hospital admission.
We document an association between high disease severity and high mean NAb titers at days 37, 97 and 187 after symptom onset. However, peak viral load during admission was not associated with disease severity.
The study is registered at https://clinicaltrials.gov/ (NCT05274373).
在患有严重 2019 年冠状病毒病（COVID-19）的住院患者中，病毒脱落和中和抗体（NAb）动力学以及保护的免疫相关性一直是整个大流行期间的关键问题。我们研究了丹麦 2020-2021 年期间住院 COVID-19 患者的逆转录酶-聚合酶链反应（RT-PCR）阳性、传染性病毒脱落和 NAb 滴度的持续时间，以及 NAb 滴度与疾病严重程度之间的关系。
对 47 例住院 COVID-19 患者进行前瞻性单中心观察队列研究。在纳入的最初 30 天内，在 8 个时间点采集口咽拭子。血清样本在症状出现后中位数时间为 7（IQR 5-10）、37（IQR 35-38）、97（IQR 95-100）和 187（IQR 185-190）天采集。NAb 滴度通过内部活病毒微量中和测定法确定。病毒培养在 Vero E6 细胞中进行。
疾病严重程度高的患者在症状出现后第 37（1.58，95%置信区间[0.34-2.81]）、97（2.07，95%置信区间[0.53-3.62]）和 187（2.49，95%置信区间[0.20-4.78]）天的平均 NAb 滴度较高，与疾病严重程度低的患者相比。峰值病毒载量（0.072，95%置信区间[-0.627-0.728]），表示为 SARS-CoV-2 拷贝/ml 的对数，与疾病严重程度无关。几乎所有（60/61）在入院后不久采集的口咽样本中，病毒培养尝试均未成功。
我们记录了疾病严重程度高与症状出现后第 37、97 和 187 天平均 NAb 滴度高之间的关联。然而，住院期间的峰值病毒载量与疾病严重程度无关。
