Systemic and mucosal antibody responses specific to SARS-CoV-2 during mild versus severe COVID-19,Journal of Allergy and Clinical Immunology

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Systemic and mucosal antibody responses specific to SARS-CoV-2 during mild versus severe COVID-19
Journal of Allergy and Clinical Immunology ( IF 11.4 ) Pub Date : 2020-11-20 , DOI: 10.1016/j.jaci.2020.10.040
Carlo Cervia ₁ , Jakob Nilsson ₁ , Yves Zurbuchen ₁ , Alan Valaperti ₁ , Jens Schreiner ₁ , Aline Wolfensberger ₂ , Miro E Raeber ₁ , Sarah Adamo ₁ , Sebastian Weigang ₃ , Marc Emmenegger ₄ , Sara Hasler ₁ , Philipp P Bosshard ₅ , Elena De Cecco ₄ , Esther Bächli ₆ , Alain Rudiger ₇ , Melina Stüssi-Helbling ₈ , Lars C Huber ₈ , Annelies S Zinkernagel ₂ , Dominik J Schaer ₉ , Adriano Aguzzi ₄ , Georg Kochs ₁₀ , Ulrike Held ₁₁ , Elsbeth Probst-Müller ₁ , Silvana K Rampini ₉ , Onur Boyman ₁₂

Affiliation

Department of Immunology, University Hospital Zurich, Zurich, Switzerland.
Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland.
Institute of Virology, Medical Center, University of Freiburg, Freiburg, Germany.
Institute of Neuropathology, University Hospital Zurich, Zurich, Switzerland.
Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.
Clinic for Internal Medicine, Uster Hospital, Uster, Switzerland.
Department of Medicine, Limmattal Hospital, Schlieren, Switzerland.
Clinic for Internal Medicine, City Hospital Triemli Zurich, Zurich, Switzerland.
Department of Internal Medicine, University Hospital Zurich, Zurich, Switzerland.
Institute of Virology, Medical Center, University of Freiburg, Freiburg, Germany; Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Department of Biostatistics, at Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Zurich, Switzerland.
Department of Immunology, University Hospital Zurich, Zurich, Switzerland; Faculty of Medicine, University of Zurich, Zurich, Switzerland.

Background

Whereas severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibody tests are increasingly being used to estimate the prevalence of SARS-CoV-2 infection, the determinants of these antibody responses remain unclear.

Objectives

Our aim was to evaluate systemic and mucosal antibody responses toward SARS-CoV-2 in mild versus severe coronavirus disease 2019 (COVID-19) cases.

Methods

Using immunoassays specific for SARS-CoV-2 spike proteins, we determined SARS-CoV-2–specific IgA and IgG in sera and mucosal fluids of 2 cohorts, including SARS-CoV-2 PCR-positive patients (n = 64) and PCR-positive and PCR-negtive health care workers (n = 109).

Results

SARS-CoV-2–specific serum IgA titers in patients with mild COVID-19 were often transiently positive, whereas serum IgG titers remained negative or became positive 12 to 14 days after symptom onset. Conversely, patients with severe COVID-19 showed a highly significant increase of SARS-CoV-2–specific serum IgA and IgG titers after symptom onset. Very high titers of SARS-CoV-2–specific serum IgA were correlated with severe acute respiratory distress syndrome. Interestingly, some health care workers with negative SARS-CoV-2–specific serum antibody titers showed SARS-CoV-2–specific IgA in mucosal fluids with virus-neutralizing capacity in some cases. SARS-CoV-2–specific IgA titers in nasal fluids were inversely correlated with age.

Conclusions

Systemic antibody production against SARS-CoV-2 develops mainly in patients with severe COVID-19, with very high IgA titers seen in patients with severe acute respiratory distress syndrome, whereas mild disease may be associated with transient production of SARS-CoV-2–specific antibodies but may stimulate mucosal SARS-CoV-2–specific IgA secretion.

中文翻译：

轻度与重度 COVID-19 期间针对 SARS-CoV-2 的全身和粘膜抗体反应

背景

尽管严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 特异性抗体检测越来越多地用于估计 SARS-CoV-2 感染的流行率，但这些抗体反应的决定因素仍不清楚。

目标

我们的目的是评估轻度与重度 2019 冠状病毒病 (COVID-19) 病例中针对 SARS-CoV-2 的全身和粘膜抗体反应。

方法

使用针对 SARS-CoV-2 刺突蛋白的特异性免疫测定，我们确定了 2 个队列的血清和粘膜液中的 SARS-CoV-2 特异性 IgA 和 IgG，其中包括 SARS-CoV-2 PCR 阳性患者 (n = 64) 和 PCR 患者- PCR 阳性和阴性的医护人员 (n = 109)。

结果

轻度 COVID-19 患者的 SARS-CoV-2 特异性血清 IgA 滴度通常呈短暂阳性，而血清 IgG 滴度在症状出现后 12 至 14 天保持阴性或变为阳性。相反，重症 COVID-19 患者在症状出现后，SARS-CoV-2 特异性血清 IgA 和 IgG 滴度显着增加。非常高滴度的 SARS-CoV-2 特异性血清 IgA 与严重急性呼吸窘迫综合征相关。有趣的是，一些 SARS-CoV-2 特异性血清抗体滴度为阴性的医护人员在某些情况下显示粘膜液中的 SARS-CoV-2 特异性 IgA 具有病毒中和能力。鼻液中 SARS-CoV-2 特异性 IgA 滴度与年龄呈负相关。