Viral Shedding and Antibody Response in 37 Patients With Middle East Respiratory Syndrome Coronavirus Infection
Viral Shedding and Antibody Response in 37 Patients With Middle East Respiratory Syndrome Coronavirus Infection
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DOI：
10.1093/cid/civ951
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发表时间：
2016-02-15
影响因子：
11.8
通讯作者：
Memish, Ziad A.
中科院分区：
文献类型：
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作者：
Corman, Victor M.;Albarrak, Ali M.;Memish, Ziad A.
背景中东呼吸综合征（MERS）冠状病毒引起孤立病例和严重呼吸道疾病的爆发。疾病的自然史的基本特征知之甚少。我们研究了37例感染MERS冠状病毒的成人患者的下呼吸道和上呼吸道（分别为LRT和URT）、血液、粪便和尿液中的病毒载量。抗体和血清中和活性在整个疾病过程中进行了测定。在诊断后的3周内收集的199份LRT样本在93%的检测中产生了病毒RNA。平均（最大）病毒载量为5 x 10（6）（6 x 10（10））拷贝/mL。84份URT样本中的病毒载量（阳性检测频率）为1.9 x 10（4）拷贝/mL（47.6%）。在检测的108份血清样本中，有33%的样本产生了病毒RNA。只有14.6%的粪便样本和2.4%的尿液样本产生病毒RNA。所有的血清转化都发生在诊断后的前2周，这对应于症状发作后的第二周和第三周。免疫球蛋白M检测在灵敏度方面与免疫球蛋白G（IgG）检测相比没有优势。所有存活的患者，但只有略多于一半的致命病例，产生IgG和中和抗体。IgG和中和抗体水平与LRT病毒载量呈弱负相关。抗体的存在并不导致病毒从LRT中消除。MERS患者呼吸道病毒脱落的时间和强度与严重急性呼吸道综合征患者非常相似。血液病毒RNA似乎没有传染性。肺外的病毒复制位点似乎是可能的。中和抗体不足以清除感染。
Background. The Middle East respiratory syndrome (MERS) coronavirus causes isolated cases and outbreaks of severe respiratory disease. Essential features of the natural history of disease are poorly understood.Methods. We studied 37 adult patients infected with MERS coronavirus for viral load in the lower and upper respiratory tracts (LRT and URT, respectively), blood, stool, and urine. Antibodies and serum neutralizing activities were determined over the course of disease.Results. One hundred ninety-nine LRT samples collected during the 3 weeks following diagnosis yielded virus RNA in 93% of tests. Average (maximum) viral loads were 5 x 10(6) (6 x 10(10)) copies/mL. Viral loads (positive detection frequencies) in 84 URT samples were 1.9 x 10(4) copies/mL (47.6%). Thirty-three percent of all 108 serum samples tested yielded viral RNA. Only 14.6% of stool and 2.4% of urine samples yielded viral RNA. All seroconversions occurred during the first 2 weeks after diagnosis, which corresponds to the second and third week after symptom onset. Immunoglobulin M detection provided no advantage in sensitivity over immunoglobulin G (IgG) detection. All surviving patients, but only slightly more than half of all fatal cases, produced IgG and neutralizing antibodies. The levels of IgG and neutralizing antibodies were weakly and inversely correlated with LRT viral loads. Presence of antibodies did not lead to the elimination of virus from LRT.Conclusions. The timing and intensity of respiratory viral shedding in patients with MERS closely matches that of those with severe acute respiratory syndrome. Blood viral RNA does not seem to be infectious. Extrapulmonary loci of virus replication seem possible. Neutralizing antibodies do not suffice to clear the infection.