Di Stefano Mariantonietta, Mirabella Lucia, Cotoia Antonella, Faleo Giuseppina, Rauseo Michela, Rizzo Anna Chiara, Fiore Josè Ramon, Cinnella Gilda, Serviddio Gaetano
Department of Surgical and Medical Science, Section of Infectious Diseases, University of Foggia, 71122 Foggia, Italy.
Anesthesia and Intensive Care Unit, Department of Surgical and Medical Science, Policlinico Riuniti di Foggia, University of Foggia, 71122 Foggia, Italy.
Viruses. 2024 Nov 28;16(12):1851. doi: 10.3390/v16121851.
SARS-CoV-2 infection induces a humoral immune response, producing virus-specific antibodies such as IgM, IgG, and IgA. IgA antibodies are present at mucosal sites, protecting against respiratory and other mucosal infections, including SARS-CoV-2, by neutralizing viruses or impeding attachment to epithelial cells. Since SARS-CoV-2 spreads through the nasopharynx, the specific IgAs of SARS-CoV-2 are produced quickly after infection, effectively contributing to virus neutralization. Dimeric IgA has been reported to be 10 to 15 times more potent than its equivalent IgG, suggesting that this isotype may be particularly interesting in developing new monoclonal antibodies and/or new vaccines efficiently neutralizing the virus at the mucosal sites. It is still unclear whether IgA antibodies in BAL might play a role in the disease course and if their presence may have a prognostic significance. However, a harmful effect on diseases with high IgA titers has been reported. This study evaluated mucosal-specific IgA and IgG profiles in BAL of patients with COVID-19 acute respiratory failure admitted to the ICU. We included 57 patients (41 males and 16 females), admitted to the ICU of the University of Foggia. We used a commercially available ELISA assay to evaluate the presence of SARS-CoV-2 IgG and IgA antibodies in plasma and BAL of the 57 hospitalized patients with severe COVID-19 respiratory failure. However, 40/57 BAL and plasma from infected patients were available for the ELISA test; the remaining specimens were unsuitable. IgG and IgA antibodies against SARS-CoV-2 were detectable in 37 (92.5%) and 40 (100%) plasma specimens, respectively. IgG antibodies were found in a single sample, while IgAs were detected in 19 of 40 BAL samples analyzed. Correlations between these parameters and patient outcomes reveal a signature associated with survival. Interestingly, a statistically significant inverse correlation was found between the mortality rate and the presence of IgA to SARS-CoV-2 in BAL specimens. None of the 19 patients with a positive IgA died, compared to 7 out of 12 patients with a negative IgA-BAL (: <0.0004). Despite being limited in size, this study suggests a significant protective effect of mucosal immunity in COVID-19 patients, even in advanced disease stages, and a role of IgA in the defense against the virus, as well as the possible use of effective vaccines and therapeutic strategies based on IgA antibodies.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染会引发体液免疫反应，产生病毒特异性抗体，如IgM、IgG和IgA。IgA抗体存在于黏膜部位，通过中和病毒或阻止其附着于上皮细胞，预防包括SARS-CoV-2在内的呼吸道及其他黏膜感染。由于SARS-CoV-2通过鼻咽部传播，感染后会迅速产生SARS-CoV-2特异性IgA，有效促进病毒中和。据报道，二聚体IgA的效力比其等效的IgG高10至15倍，这表明该同种型在开发能有效在黏膜部位中和病毒的新型单克隆抗体和/或新型疫苗方面可能特别有意义。目前尚不清楚支气管肺泡灌洗（BAL）中的IgA抗体是否会在疾病进程中发挥作用，以及其存在是否具有预后意义。然而，已有报道称高IgA滴度对疾病有有害影响。本研究评估了入住重症监护病房（ICU）的新型冠状病毒肺炎（COVID-19）急性呼吸衰竭患者BAL中的黏膜特异性IgA和IgG谱。我们纳入了57例患者（41例男性和16例女性），他们均入住福贾大学的ICU。我们使用市售酶联免疫吸附测定（ELISA）法评估57例住院的重症COVID-19呼吸衰竭患者血浆和BAL中SARS-CoV-2 IgG和IgA抗体的存在情况。然而，40/57例感染患者的BAL和血浆可用于ELISA检测；其余标本不适合检测。在37例（92.5%）和40例（100%）血浆标本中分别检测到针对SARS-CoV-2的IgG和IgA抗体。在单个样本中发现了IgG抗体，而在分析的40例BAL样本中的19例中检测到了IgA。这些参数与患者预后之间的相关性揭示了一种与生存相关的特征。有趣的是，在BAL标本中，死亡率与SARS-CoV-2 IgA的存在之间存在统计学上显著的负相关。19例IgA阳性患者均未死亡，相比之下，12例IgA-BAL阴性患者中有7例死亡（P<0.0004）。尽管本研究规模有限，但它表明黏膜免疫在COVID-19患者中具有显著的保护作用，即使在疾病晚期也是如此，同时表明IgA在抵御病毒方面发挥作用，以及基于IgA抗体的有效疫苗和治疗策略的可能用途。
