The COVID-19 pandemic, caused by SARS-CoV-2, has had a devastating global impact. Effective immune responses are crucial to controlling the pathogenesis of COVID-19, with humoral immunity playing a vital role. Antibodies, produced by B lymphocytes, are key players in this response; they can be categorized as neutralizing antibodies (NAbs) or non-neutralizing antibodies (nNAbs). nNAbs bind to the virus without directly neutralizing it, alerting the immune system to its presence. NAbs, however, directly neutralize the virus by blocking its entry into cells. These antibodies, whether induced by infection or vaccination, are critical for protection against SARS-CoV-2. Currently, COVID-19 vaccines, mAb therapies, and convalescent plasma all rely on NAbs to prevent infection. However, challenges exist, including adverse effects associated with mAbs and vaccines, as well as the emergence of immune-evading SARS-CoV-2 variants. This necessitates a thorough understanding of NAb-mediated immune responses to guide the development of more effective vaccines and treatments. This review summarizes current knowledge on the role of NAbs in SARS-CoV-2 protection and their potential clinical implications, highlighting the challenges in antibody-based prophylaxis, therapy, and vaccination.

The review extensively cites existing literature to support its claims. Studies demonstrating the protective role of NAbs against primary SARS-CoV-2 infection are highlighted, including those showing a correlation between NAb titers and protection. Research on the various immunoglobulin types involved in protection (IgG, IgM, IgA) and their persistence over time is summarized. The mechanisms of action of NAbs are explained through references to studies focusing on neutralization of viral entry, interaction with host cell coreceptors, and effector functions. The literature review also incorporates studies on the clinical use of antibodies in COVID-19 diagnostics, assessment of immunity, and prognosis, as well as their role in the development and efficacy of COVID-19 vaccines and therapies. Additionally, the review extensively cites research concerning the challenges associated with convalescent plasma, mAbs, and vaccines, particularly the emergence of antibody-resistant variants and the potential for antibody-dependent enhancement (ADE).

This review article uses a systematic approach to gather and synthesize information from the existing scientific literature. The authors performed a comprehensive search of relevant databases, including PubMed and other relevant sources to identify studies that investigated the role of neutralizing antibodies in SARS-CoV-2 infection, their protective mechanisms, and their clinical applications. Specific keywords were likely used, such as "SARS-CoV-2," "neutralizing antibodies," "COVID-19," "vaccine," "monoclonal antibodies," "convalescent plasma," "immune response," and "antibody-dependent enhancement." Inclusion criteria likely focused on peer-reviewed studies published in reputable journals. The selected studies were critically appraised to assess their methodological rigor and the validity of their findings. The authors extracted relevant data from the included studies, focusing on the protective roles of NAbs, their mechanisms of action, clinical implications, and associated challenges. This data was then synthesized to create a narrative overview of the current understanding of the role of neutralizing antibodies in COVID-19.

Several key findings are presented in this review. NAbs, particularly those targeting the receptor-binding domain (RBD) of the spike (S) protein, are highly predictive of protection against SARS-CoV-2 infection. High-affinity NAbs, mainly IgG, but also IgM and IgA, contribute to viral clearance during acute infection. The duration of NAb persistence varies; while some studies report a decline after a few months, others show their persistence for much longer periods. NAbs protect against reinfection, although the level of protection depends on the quantity and quality of antibodies. Different COVID-19 vaccines elicit varying NAb responses, with some displaying superior neutralization against certain SARS-CoV-2 variants. NAbs mediate their protective effects by directly blocking viral entry (neutralization) and by engaging in effector mechanisms (ADCC, ADCP, CDC). Anti-N protein antibodies, while abundant, lack significant neutralizing capability compared to anti-S protein antibodies. Clinically, NAbs are valuable diagnostic tools, biomarkers for disease severity and prognosis, and crucial for therapeutic applications (convalescent plasma, mAbs). Challenges exist, including the emergence of antibody-resistant variants, ADE, and adverse reactions associated with certain therapies and vaccines. Booster doses of vaccines have been shown to enhance NAb levels and protection against new variants, though the duration of this protection remains a concern. The neutralization potency index is identified as a superior predictor of disease severity and patient outcomes compared to antibody levels alone. Convalescent plasma therapy shows inconsistent results, with some studies showing benefits and others showing no significant effect. Similarly, monoclonal antibody therapy has been effective in some patients but loses efficacy against certain variants. The review highlights that further research is crucial to address these challenges and improve the effectiveness and safety of antibody-based COVID-19 prevention and treatment strategies.

This review's findings address the critical need for a deeper understanding of NAbs in COVID-19. The strong correlation between NAb levels and protection against infection emphasizes the importance of these antibodies in both natural immunity and vaccine-induced immunity. The variability in NAb persistence underscores the need for continued monitoring and potentially the development of longer-lasting vaccines or booster strategies. The discussion of various immunoglobulin types involved in protection expands our understanding of the complexity of the humoral immune response to SARS-CoV-2. The mechanisms of NAb action and their clinical applications provide valuable insights for diagnostics, therapeutic development, and vaccine design. The discussion of challenges—ADE and variant emergence—highlights the crucial need for ongoing research focused on vaccine improvement and the development of broadly neutralizing antibodies (bNAbs). The varying effectiveness of convalescent plasma and mAb therapies further supports this need. The identification of the neutralization potency index as a robust marker of disease severity offers a valuable tool for risk stratification and treatment optimization. In summary, this review underscores the importance of NAbs in fighting SARS-CoV-2 and identifies several key areas that require further research to enhance prevention and treatment strategies.

Neutralizing antibodies are central to protection against SARS-CoV-2 infection. This review emphasizes their role in preventing primary infection and reinfection, their diverse mechanisms of action, and their various clinical applications in diagnostics, prognosis, and therapy. However, challenges remain, particularly the emergence of variants and the potential for ADE. Future research should focus on developing broadly neutralizing antibodies and vaccines that elicit durable and effective immune responses against emerging SARS-CoV-2 variants. Further studies evaluating the long-term efficacy of current vaccines and therapies, along with strategies to minimize ADE, are crucial. The neutralization potency index holds promise as a valuable tool for guiding clinical decision-making in COVID-19.

As a review article, this paper is limited by the scope of the included literature. The findings are based on the available evidence at the time of writing, and future research may modify or expand upon the current understanding. The quality and methodology of the cited studies are not uniformly assessed, which could introduce some bias. The review mainly focuses on the humoral immune response and does not delve deeply into other components of the immune system that may contribute to overall protection against SARS-CoV-2. Furthermore, the review acknowledges the inconsistencies in the clinical data on convalescent plasma therapy; this highlights the need for larger, more robust clinical trials to fully understand its potential benefits and limitations.