背景：串行间隔是原发性病例的症状发作与继发性病例的症状发作之间的时间段。了解序列间隔对于确定COVID-19等传染病的传播动态非常重要，包括繁殖次数和二次发作率，这可能会影响控制措施。COVID-19的早期荟萃分析报告，原始野生型变体的系列间隔为5.2天（95%CI：4.9-5.5），Alpha变体的系列间隔为5.2天（95%CI：4.87-5.47）。在其他呼吸道疾病的流行过程中，连续间隔已被证明会减少，这可能是由于累积的病毒突变和实施更有效的非药物干预措施。因此，我们汇总了文献，以估计Delta和Omicron变体的序列间隔。
方法：本研究遵循系统评价和荟萃分析指南的首选报告项目。对PubMed进行了系统的文献检索，Scopus,科克伦图书馆,ScienceDirect,和预打印服务器medRxiv，用于2021年4月4日至2023年5月23日发表的文章。搜索词为：（“串行间隔”或“生成时间”），(\"Omicron\"或\"Delta\"),和（“SARS-CoV-2”或“COVID-19”）。使用限制性最大似然估计模型对Delta和Omicron变体进行荟萃分析，每个研究都具有随机效应。报告汇总平均估计值和95%置信区间(95%CI)。
结果：Delta的荟萃分析包括46,648个主要/次要病例对，Omicron包括18,324。纳入研究的平均连续间隔为Delta的2.3-5.8天，Omicron的2.1-4.8天。Delta的合并平均序列间隔为3.9天（95％CI：3.4-4.3）（20项研究），Omicron为3.2天（95％CI：2.9-3.5）（20项研究）。BA.1的平均估计序列间隔为3.3天（95％CI：2.8-3.7）（11项研究），BA.2为2.9天（95％CI：2.7-3.1）（六项研究），BA.5为2.3天(95%CI:1.6-3.1)(三项研究)。
结论：Delta和Omicron的序列间隔估计比祖先的SARS-CoV-2变体短。最近的Omicron亚变体的串行间隔甚至更短，这表明串行间隔可能会随着时间的推移而缩短。这表明从一代病例到下一代病例的传播更快，与它们的祖先相比，这些变异体观察到的更快的生长动态一致。随着SARS-CoV-2继续循环和发展，串行间隔可能会发生其他变化。人群免疫力的变化（由于感染和/或疫苗接种）可能会进一步改变它。
BACKGROUND: The serial interval is the period of time between symptom onset in the primary case and symptom onset in the secondary case. Understanding the serial interval is important for determining transmission dynamics of infectious diseases like COVID-19, including the reproduction number and secondary attack rates, which could influence control measures. Early meta-analyses of COVID-19 reported serial intervals of 5.2 days (95% CI: 4.9-5.5) for the original wild-type variant and 5.2 days (95% CI: 4.87-5.47) for Alpha variant. The serial interval has been shown to decrease over the course of an epidemic for other respiratory diseases, which may be due to accumulating viral mutations and implementation of more effective nonpharmaceutical interventions. We therefore aggregated the literature to estimate serial intervals for Delta and Omicron variants.
METHODS: This study followed Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. A systematic literature search was conducted of PubMed, Scopus, Cochrane Library, ScienceDirect, and preprint server medRxiv for articles published from April 4, 2021, through May 23, 2023. Search terms were: (\"serial interval\" or \"generation time\"), (\"Omicron\" or \"Delta\"), and (\"SARS-CoV-2\" or \"COVID-19\"). Meta-analyses were done for Delta and Omicron variants using a restricted maximum-likelihood estimator model with a random effect for each study. Pooled average estimates and 95% confidence intervals (95% CI) are reported.
RESULTS: There were 46,648 primary/secondary case pairs included for the meta-analysis of Delta and 18,324 for Omicron. Mean serial interval for included studies ranged from 2.3-5.8 days for Delta and 2.1-4.8 days for Omicron. The pooled mean serial interval for Delta was 3.9 days (95% CI: 3.4-4.3) (20 studies) and Omicron was 3.2 days (95% CI: 2.9-3.5) (20 studies). Mean estimated serial interval for BA.1 was 3.3 days (95% CI: 2.8-3.7) (11 studies), BA.2 was 2.9 days (95% CI: 2.7-3.1) (six studies), and BA.5 was 2.3 days (95% CI: 1.6-3.1) (three studies).
CONCLUSIONS: Serial interval estimates for Delta and Omicron were shorter than ancestral SARS-CoV-2 variants. More recent Omicron subvariants had even shorter serial intervals suggesting serial intervals may be shortening over time. This suggests more rapid transmission from one generation of cases to the next, consistent with the observed faster growth dynamic of these variants compared to their ancestors. Additional changes to the serial interval may occur as SARS-CoV-2 continues to circulate and evolve. Changes to population immunity (due to infection and/or vaccination) may further modify it.
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