Risk of reinfection, vaccine protection, and severity of infection with the BA.5 omicron subvariant: a nation-wide population-based study in Denmark.
Risk of reinfection, vaccine protection, and severity of infection with the BA.5 omicron subvariant: a nation-wide population-based study in Denmark.
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DOI：
10.1016/s1473-3099(22)00595-3
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发表时间：
2023-02
影响因子：
56.3
通讯作者：
Valentiner-Branth, Palle
中科院分区：
文献类型：
--
作者：
Hansen, Christian Holm;Friis, Nikolaj Ulrik;Bager, Peter;Stegger, Marc;Fonager, Jannik;Fomsgaard, Anders;Gram, Mie Agermose;Christiansen, Lasse Engbo;Ethelberg, Steen;Legarth, Rebecca;Krause, Tyra Grove;Ullum, Henrik;Valentiner-Branth, Palle
对SARS-CoV-2 Omicron亚型BA.5的免疫力和严重性的估计对于评估其尽管接种了疫苗但在全球迅速传播所产生的公共卫生影响是重要的。在丹麦，我们评估了BA.5相对于BA.2的自然和疫苗免疫以及严重程度，丹麦是一个拥有高mRNA疫苗接种覆盖率和免费RT-PCR检测的国家。这项在丹麦进行的全国性人群研究包括在2022年4月10日至6月30日(即结果期)期间进行过RTPCR检测的18岁或以上的居民，以及自2020年2月以来国家新冠肺炎监测系统确定为拥有RTPCR检测阳性的信息、全基因组测序、疫苗接种和住院信息的居民，主要诊断为新冠肺炎。首先，我们采用病例对照设计，病例是在结果期感染BA.5或BA.2的人，对照组是在结果期检测为SARS-CoV-2感染阴性的人。我们计算了之前经PCR确认的Omicron感染对BA.5和BA.2感染的保护作用，以及在三次接种疫苗的个人中住院的情况。其次，我们比较了感染BA.5和BA.2的人的疫苗接种状况，并估计了针对每个亚型的相对疫苗保护。第三，我们比较了BA.5感染者和BA.2感染者使用新冠肺炎的住院率。我们使用Logistic回归对性别、年龄、地区、聚合酶链式反应检测日期、合并症以及疫苗接种和既往感染状况进行了调整，以评估效果。在8678例BA5病例、29例 292病例中192例(0.7%)和178例 669阴性对照中33例 972(19.0%)有OMICRON感染，经校正分析估计其对BA5感染的保护率为92.7%(95%可信区间91·6~93.7)，对BA2感染的保护率为97.1%(96·6~97.5)。我们发现，由于感染BA.5(96.4%[95%CI 74·2-99.5])和BA.2(91.2%[76.3-96.7])，对住院的保护作用同样很高。疫苗接种率(3mRNA量与无)分别为9878例和32 272例中的9307例(94.2%)和30 581(94.8%)，尽管在校正分析中，BA5例的疫苗接种率略高于BA.2例(OR 1·18[95%CI 0·99-1·42]；p=0.064)，这可能表明对BA.5的疫苗保护作用略差。尽管在研究期间因新冠肺炎住院的人数较少且稳定，但BA 5患者因新冠肺炎住院的比率(2 10例[1.9%])高于BA 2患者(5 14例[1.4%]36 80 5)，OR值为1·34(95%CI 1·14-1·57)，调整后OR为1·69(95%CI 1·22-2·33)。这项研究提供的证据表明，在接种了三次疫苗的个人中，以前感染过Omicron的人对BA.5和BA.2感染提供了高度的保护。然而，如果有既往感染史的人比没有感染史的人更有可能因为怀疑新冠肺炎以外的原因而站出来进行检测，那么超过90%的保护率估计可能太高了。我们的分析还表明，疫苗对BA.5感染的保护类似于或略弱于对BA.2感染的保护。最后，有证据表明，与BA.2感染相比，BA.5感染与住院风险增加有关。这项研究没有资金来源。
Estimates of immunity and severity for the SARS-CoV-2 omicron subvariant BA.5 are important to assess the public health impact associated with its rapid global spread despite vaccination. We estimated natural and vaccine immunity and severity of BA.5 relative to BA.2 in Denmark, a country with high mRNA-vaccination coverage and free-of-charge RT-PCR testing. This nation-wide population-based study in Denmark included residents aged 18 years or older who had taken an RT-PCR test between 10 April and 30 June, 2022 (ie, the outcome period), and who the national COVID-19 surveillance system identified as having information since February 2020 on RT-PCR tests, whole-genome sequencing, vaccinations, and hospitalisation with a positive RT-PCR test and COVID-19 as the main diagnosis. First, we used a case–control design, in which cases were people infected with BA.5 or BA.2 during the outcome period and controls were people who tested negative for SARS-CoV-2 infection during the outcome period. We calculated the protection provided by a previous PCR-confirmed omicron infection against BA.5 and BA.2 infection and hospitalisation among triple-vaccinated individuals. Second, we compared vaccination status in people infected with BA.5 versus BA.2 and estimated relative vaccine protection against each subvariant. Third, we compared rates of hospitalisation for COVID-19 among people infected with BA.5 versus BA.2. We estimated effects using logistic regression with adjustment for sex, age, region, PCR-test date, comorbidity and, as appropriate, vaccination and previous infection status. A total of 210 (2·4%) of 8678 of BA.5 cases, 192 (0·7%) of 29 292 of BA.2 cases, and 33 972 (19·0%) of 178 669 PCR-negative controls previously had an omicron infection, which was estimated in the adjusted analyses to offer 92·7% (95% CI 91·6–93·7) protection against BA.5 infection and 97·1% (96·6–97·5) protection against BA.2 infection. We found similarly high amounts of protection against hospitalisation owing to infection with BA.5 (96·4% [95% CI 74·2–99·5]) and BA.2 (91·2% [76·3–96·7]). Vaccine coverage (three mRNA doses vs none) was 9307 (94·2%) of 9878 among BA.5 cases and 30 581 (94·8%) of 32 272 among BA.2 cases, although in the adjusted analysis, there was a trend towards slightly higher vaccination coverage among BA.5 cases than BA.2 cases (OR 1·18 [95% CI 0·99–1·42]; p=0·064), possibly suggesting marginally poorer vaccine protection against BA.5. The rate of hospitalisation due to COVID-19 was higher among the BA.5 cases (210 [1·9%] of 11 314) than among the BA.2 cases (514 [1·4%] of 36 805), with an OR of 1·34 (95% CI 1·14–1·57) and an adjusted OR of 1·69 (95% CI 1·22–2·33), despite low and stable COVID-19 hospitalisation numbers during the study period. The study provides evidence that a previous omicron infection in triple-vaccinated individuals provides high amounts of protection against BA.5 and BA.2 infections. However, protection estimates greater than 90% might be too high if individuals with a previous infection were more likely than those without one to come forward for a test for reasons other than suspicion of COVID-19. Our analysis also showed that vaccine protection against BA.5 infection was similar to, or slightly weaker than, protection against BA.2 infection. Finally, there was evidence that BA.5 infections were associated with an increased risk of hospitalisation compared with BA.2 infections. There was no funding source for this study.