Egger Thomas, Dörr Tamara, Thoma Reto, Nigg Susanne, Risch Lorenz, Cremonesi Alessio, Vernazza Pietro, Kohler Philipp, Kahlert Christian R
Cantonal Hospital St. Gallen, Clinic for infectious diseases and hospital hygiene, Switzerland.
Labormedizinisches Zentrum Dr Risch Ostschweiz AG, Buchs, Switzerland.
J Immunol Methods. 2025 Jan;536:113800. doi: 10.1016/j.jim.2024.113800. Epub 2025 Jan 4.
Dried blood spots (DBS) have been proposed as a cost-effective surveillance method for population-wide screening of SARS-CoV-2 immunity but sensitivity of DBS based on self-collected DBS samples is unknown. To evaluate the success of vaccination strategies, it is necessary to differentiate vaccination from natural infection. Therefore, a test for antibodies against the viral nucleocapsid protein (anti-N) is desirable.
In our prospectively followed cohort of healthcare workers (HCW) in eastern Switzerland, we assessed SARS-CoV-2-anti-N-seroprevalence using DBS on a biweekly basis from March to September 2020. Phlebotomy samples were collected in March and September and tested for anti-N-seropositivity, as well as SARS-CoV-2 spike antibodies for quantitative validation. Venous antibody testing was compared with DBS results for anti-N using the Roche Elecsys electro-chemiluminescence immunoassay.
792 HCW (median age 38.3 years) were included, 35 (4.4 %) were SARS-CoV-2-anti-N-seropositive. Of 43 matching DBS, 25 tested positive for anti-N, accounting for a sensitivity of 58.1 % (95 %CI 43.3-71.6 %). We found a significant correlation of anti-N from DBS with results from phlebotomy samples (r = 0.77;p < 0.0001), with higher levels being associated with a higher true-positive rate. Anti-N in DBS correlated significantly with quantitatively validated anti-S obtained from serum (r = 0.67;p < 0.0001).
Although home DBS collection was feasible in a larger cohort and we found a high correlation between anti-N detection in DBS and phlebotomy samples, the sensitivity of self-collected DBS samples was significantly impaired for the Roche Elecsys anti-N assay. Therefore, we cannot recommend this method for DBS when testing from venous blood is possible.
干血斑（DBS）已被提议作为一种具有成本效益的监测方法，用于全人群的SARS-CoV-2免疫筛查，但基于自我采集的DBS样本的检测灵敏度尚不清楚。为了评估疫苗接种策略的成效，有必要区分疫苗接种与自然感染。因此，需要一种针对病毒核衣壳蛋白抗体（抗N）的检测方法。
在我们对瑞士东部医护人员（HCW）进行前瞻性随访的队列研究中，我们在2020年3月至9月期间每两周使用DBS评估一次SARS-CoV-2抗N血清阳性率。在3月和9月采集静脉血样本，并检测抗N血清阳性情况以及SARS-CoV-2刺突抗体以进行定量验证。使用罗氏电化学发光免疫分析法将静脉抗体检测结果与DBS抗N检测结果进行比较。
纳入了792名医护人员（中位年龄38.3岁），其中35人（4.4%）SARS-CoV-2抗N血清呈阳性。在43份匹配的DBS样本中，25份抗N检测呈阳性，灵敏度为58.1%（95%CI 43.3 - 71.6%）。我们发现DBS抗N检测结果与静脉血样本结果之间存在显著相关性（r = 0.77；p < 0.0001），水平越高，真阳性率越高。DBS中的抗N与从血清中定量验证的抗S显著相关（r = 0.67；p < 0.0001）。
尽管在更大的队列中进行家庭DBS采集是可行的，并且我们发现DBS抗N检测与静脉血样本之间存在高度相关性，但对于罗氏电化学发光抗N检测法，自我采集的DBS样本的灵敏度显著受损。因此，当可以进行静脉血检测时，我们不推荐使用这种DBS检测方法。
