Evidence of previous SARS-CoV-2 infection in seronegative patients with long COVID.

Evidence of previous SARS-CoV-2 infection in seronegative patients with long COVID.
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DOI:
10.1016/j.ebiom.2022.104129
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发表时间:
2022-07
期刊:
影响因子:
11.1
通讯作者:
Sithole, Nyaradzai
Sithole, Nyaradzai
中科院分区:
医学1区
文献类型:
--
作者:
Krishna, Benjamin A.;Lim, Eleanor Y.;Mactavous, Lenette;Lyons, Paul A.;Doffinger, Rainer;Bradley, John R.;Smith, Kenneth G. C.;Sinclair, John;Matheson, Nicholas J.;Lehner, Paul J.;Wills, Mark R.;Sithole, Nyaradzai

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目前,对于新冠肺炎的诊断、定义、症状或病程还没有达成共识。在许多感染或可能感染SARS-CoV-2但在急性疾病期间未进行检测和/或SARS-CoV-2抗体阴性的患者中,Long CoVID的诊断复杂性变得复杂。鉴于长期冠状病毒感染的诊断难题,我们开始研究确诊为SARS-CoV-2感染和/或长期冠状病毒感染的患者的SARS-CoV-2特异性T细胞反应,这些患者大多是非住院患者。我们发现在γ检测阳性6个月后,T细胞对SARS-CoV-2多肽的反应释放IL-2(但不释放干扰素-−)对既往SARS-CoV-2感染和GT;既敏感(75%+/−13%),又特异(88%+/PCR7%)。我们发现,42-53%的慢性冠状病毒感染患者,但没有可检测到的SARS-CoV-2抗体,仍有可检测到的SARS-CoV-2特异性T细胞反应。我们的研究揭示了(可检测到的T细胞介导的IL-2释放)在血清阴性的长期COVID患者中既往感染SARS-CoV-2的证据。这项工作由阿登布鲁克慈善信托基金(900276给NS)、NIHR奖(G112259给NS)资助,并得到NIHR剑桥生物医学研究中心的支持。NJM由MRC(TSF MR/T032413/1)和NHSBT(WPA15-02)支持。PJL由惠康信托基金(PRF 210688/Z/18/Z,084957/Z/08/Z)、医学研究理事会研究补助金MR/V011561/1和联合王国研究和创新COVID免疫联盟赠款(MR/V028448/1)支持。
There is currently no consensus on the diagnosis, definition, symptoms, or duration of COVID-19 illness. The diagnostic complexity of Long COVID is compounded in many patients who were or might have been infected with SARS-CoV-2 but not tested during the acute illness and/or are SARS-CoV-2 antibody negative. Given the diagnostic conundrum of Long COVID, we set out to investigate SARS-CoV-2-specific T cell responses in patients with confirmed SARS-CoV-2 infection and/or Long COVID from a cohort of mostly non-hospitalised patients. We discovered that IL-2 release (but not IFN-γ release) from T cells in response to SARS-CoV-2 peptides is both sensitive (75% +/−13%) and specific (88%+/−7%) for previous SARS-CoV-2 infection >6 months after a positive PCR test. We identified that 42–53% of patients with Long COVID, but without detectable SARS-CoV-2 antibodies, nonetheless have detectable SARS-CoV-2 specific T cell responses. Our study reveals evidence (detectable T cell mediated IL-2 release) of previous SARS-CoV-2 infection in seronegative patients with Long COVID. This work was funded by the Addenbrooke's Charitable Trust (900276 to NS), NIHR award (G112259 to NS) and supported by the NIHR Cambridge Biomedical Research Centre. NJM is supported by the MRC (TSF MR/T032413/1) and NHSBT (WPA15-02). PJL is supported by the Wellcome Trust (PRF 210688/Z/18/Z, 084957/Z/08/Z), a Medical Research Council research grant MR/V011561/1 and the United Kingdom Research and a Innovation COVID Immunology Consortium grant (MR/V028448/1).
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