Protective roles and protective mechanisms of neutralizing antibodies against SARS-CoV-2 infection and their potential clinical implications

Neutralizing antibodies (NAbs) are central players in the humoral immunity that defends the body from SARS-CoV-2 infection by blocking viral entry into host cells and neutralizing their biological effects. Even though NAbs primarily work by neutralizing viral antigens, on some occasions, they may also combat the SARS-CoV-2 virus escaping neutralization by employing several effector mechanisms in collaboration with immune cells like natural killer (NK) cells and phagocytes. Besides their prophylactic and therapeutic roles, antibodies can be used for COVID-19 diagnosis, severity evaluation, and prognosis assessment in clinical practice. Furthermore, the measurement of NAbs could have key implications in determining individual or herd immunity against SARS-CoV-2, vaccine effectiveness, and duration of the humoral protective response, as well as aiding in the selection of suitable individuals who can donate convalescent plasma to treat infected people. Despite all these clinical applications of NAbs, using them in clinical settings can present some challenges. This review discusses the protective functions, possible protective mechanisms against SARS-CoV-2, and potential clinical applications of NAbs in COVID-19. This article also highlights the possible challenges and solutions associated with COVID-19 antibody-based prophylaxis, therapy, and vaccination.

[1]  Lindsay N. Carpp,et al.  Immune correlates analysis of the PREVENT-19 COVID-19 vaccine efficacy clinical trial , 2022, Nature Communications.

[2]  D. Follmann,et al.  A Covid-19 Milestone Attained - A Correlate of Protection for Vaccines. , 2022, The New England journal of medicine.

[3]  S. Pittaluga,et al.  SARS-CoV-2 infection and persistence in the human body and brain at autopsy , 2022, Nature.

[4]  Lindsay N. Carpp,et al.  Immune correlates analysis of the ENSEMBLE single Ad26.COV2.S dose vaccine efficacy clinical trial , 2022, Nature Microbiology.

[5]  A. Palese,et al.  Evaluation of qualitative and semi-quantitative cut offs for rapid diagnostic lateral flow test in relation to serology for the detection of SARS-CoV-2 antibodies: findings of a prospective study , 2022, BMC Infectious Diseases.

[6]  A. McCulloch,et al.  Performance Evaluation of the Microfluidic Antigen LumiraDx SARS-CoV-2 and Flu A/B Test in Diagnosing COVID-19 and Influenza in Patients with Respiratory Symptoms , 2022, Infectious Diseases and Therapy.

[7]  T. Shioda,et al.  Reevaluation of antibody-dependent enhancement of infection in anti-SARS-CoV-2 therapeutic antibodies and mRNA-vaccine antisera using FcR- and ACE2-positive cells , 2022, Scientific Reports.

[8]  N. Lee,et al.  Quantitative Analysis of Anti-N and Anti-S Antibody Titers of SARS-CoV-2 Infection after the Third Dose of COVID-19 Vaccination , 2022, Vaccines.

[9]  A. Pollard,et al.  Safety and immunogenicity of the ChAdOx1 nCoV-19 (AZD1222) vaccine in children aged 6–17 years: a preliminary report of COV006, a phase 2 single-blind, randomised, controlled trial , 2022, The Lancet.

[10]  L. Estcourt,et al.  Convalescent Plasma for Covid-19 — Making Sense of the Inconsistencies , 2022, The New England journal of medicine.

[11]  M. Hernán,et al.  Fourth Dose of BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Setting , 2022, The New England journal of medicine.

[12]  Cunbao Liu,et al.  Th2-Oriented Immune Serum After SARS-CoV-2 Vaccination Does Not Enhance Infection In Vitro , 2022, Frontiers in Immunology.

[13]  Endeshaw Chekol Abebe,et al.  Mutational Pattern, Impacts and Potential Preventive Strategies of Omicron SARS-CoV-2 Variant Infection , 2022, Infection and drug resistance.

[14]  F. Rey,et al.  Potent human broadly SARS-CoV-2–neutralizing IgA and IgG antibodies effective against Omicron BA.1 and BA.2 , 2022, bioRxiv.

[15]  A. Casadevall,et al.  Early Outpatient Treatment for Covid-19 with Convalescent Plasma , 2022, The New England journal of medicine.

[16]  D. Volke,et al.  Sensitive and specific serological ELISA for the detection of SARS-CoV-2 infections , 2022, Virology Journal.

[17]  D. Harats,et al.  Efficacy of a Fourth Dose of Covid-19 mRNA Vaccine against Omicron , 2022, The New England journal of medicine.

[18]  Gheyath K Nasrallah,et al.  Effect of mRNA Vaccine Boosters against SARS-CoV-2 Omicron Infection in Qatar , 2022, The New England journal of medicine.

[19]  S. Gharbia,et al.  Covid-19 Vaccine Effectiveness against the Omicron (B.1.1.529) Variant , 2022, The New England journal of medicine.

[20]  L. Lopalco,et al.  SARS-CoV-2 vaccination elicits unconventional IgM specific responses in naïve and previously COVID-19-infected individuals , 2022, EBioMedicine.

[21]  T. Hillig,et al.  Long-Term Comparison of 7 SARS-CoV-2 Antibody Assays in the North Zealand Covid-19 Cohort , 2022, The journal of applied laboratory medicine.

[22]  M. Van Ranst,et al.  Lower persistence of anti-nucleocapsid compared to anti-spike antibodies up to one year after SARS-CoV-2 infection , 2022, Diagnostic Microbiology and Infectious Disease.

[23]  C. Mussini,et al.  Another piece in the COVID-19 treatment puzzle , 2022, The Lancet.

[24]  Q. Bassat,et al.  High-titre methylene blue-treated convalescent plasma as an early treatment for outpatients with COVID-19: a randomised, placebo-controlled trial , 2022, The Lancet Respiratory Medicine.

[25]  Chih-Cheng Lai,et al.  The impact of neutralizing monoclonal antibodies on the outcomes of COVID‐19 outpatients: A systematic review and meta‐analysis of randomized controlled trials , 2022, Journal of medical virology.

[26]  A. Casadevall,et al.  Mucosal Vaccines, Sterilizing Immunity, and the Future of SARS-CoV-2 Virulence , 2022, Viruses.

[27]  Christina C. Chang,et al.  mRNA-based COVID-19 vaccine boosters induce neutralizing immunity against SARS-CoV-2 Omicron variant , 2022, Cell.

[28]  P. Schommers,et al.  mRNA booster immunization elicits potent neutralizing serum activity against the SARS-CoV-2 Omicron variant , 2021, Nature Medicine.

[29]  Stanley Xu,et al.  Guillain-Barre Syndrome after COVID-19 Vaccination in the Vaccine Safety Datalink , 2021, medRxiv.

[30]  D. Easton,et al.  Covid-19 Vaccine Effectiveness in New York State , 2021, The New England journal of medicine.

[31]  J. Muñóz-Valle,et al.  Overview of Neutralizing Antibodies and Their Potential in COVID-19 , 2021, Vaccines.

[32]  Lindsay N. Carpp,et al.  Immune correlates analysis of the mRNA-1273 COVID-19 vaccine efficacy clinical trial , 2021, Science.

[33]  P. Pang,et al.  Early Treatment for Covid-19 with SARS-CoV-2 Neutralizing Antibody Sotrovimab. , 2021, The New England journal of medicine.

[34]  L. Corey,et al.  Efficacy and Safety of NVX-CoV2373 in Adults in the United States and Mexico , 2021, medRxiv.

[35]  S. Bernardini,et al.  Serological anti-SARS-CoV-2 neutralizing antibodies association to live virus neutralizing test titers in COVID-19 paucisymptomatic/symptomatic patients and vaccinated subjects , 2021, International Immunopharmacology.

[36]  O. A. Ogun,et al.  Effectiveness of mRNA BNT162b2 COVID-19 vaccine up to 6 months in a large integrated health system in the USA: a retrospective cohort study , 2021, The Lancet.

[37]  K. Stiasny,et al.  Highly active engineered IgG3 antibodies against SARS-CoV-2 , 2021, Proceedings of the National Academy of Sciences.

[38]  Q. Sattentau,et al.  Immunological and pathological outcomes of SARS-CoV-2 challenge following formalin-inactivated vaccine in ferrets and rhesus macaques , 2021, Science advances.

[39]  B. Mustanski,et al.  Durability of antibody response to vaccination and surrogate neutralization of emerging variants based on SARS-CoV-2 exposure history , 2021, Scientific Reports.

[40]  J. Mascola,et al.  Durability of mRNA-1273 vaccine–induced antibodies against SARS-CoV-2 variants , 2021, Science.

[41]  A. Garcia-Basteiro,et al.  Seven-month kinetics of SARS-CoV-2 antibodies and role of pre-existing antibodies to human coronaviruses , 2021, Nature Communications.

[42]  Haya Altawalah Antibody Responses to Natural SARS-CoV-2 Infection or after COVID-19 Vaccination , 2021, Vaccines.

[43]  M. Lipsitch,et al.  Covid-19 Breakthrough Infections in Vaccinated Health Care Workers , 2021, The New England journal of medicine.

[44]  J. Jardine,et al.  SARS-CoV-2 Neutralizing Antibody Responses towards Full-Length Spike Protein and the Receptor-Binding Domain , 2021, The Journal of Immunology.

[45]  A. Ruello,et al.  Serum Neutralizing Activity against B.1.1.7, B.1.351, and P.1 SARS-CoV-2 Variants of Concern in Hospitalized COVID-19 Patients , 2021, Viruses.

[46]  F. Krammer A correlate of protection for SARS-CoV-2 vaccines is urgently needed , 2021, Nature Medicine.

[47]  M. Wener,et al.  Anti-SARS-CoV-2 Antibody Levels Measured by the AdviseDx SARS-CoV-2 Assay Are Concordant with Previously Available Serologic Assays but Are Not Fully Predictive of Sterilizing Immunity , 2021, Journal of clinical microbiology.

[48]  J. Vekemans,et al.  Correlates of protection against symptomatic and asymptomatic SARS-CoV-2 infection , 2021, Nature Medicine.

[49]  J. Blackburn,et al.  Performance of the EUROIMMUN Anti-SARS-CoV-2 ELISA Assay for detection of IgA and IgG antibodies in South Africa , 2021, PloS one.

[50]  C. Woods,et al.  In vitro and in vivo functions of SARS-CoV-2 infection-enhancing and neutralizing antibodies , 2021, Cell.

[51]  C. Rice,et al.  Naturally enhanced neutralizing breadth against SARS-CoV-2 one year after infection , 2021, Nature.

[52]  W. Niu,et al.  ACE2 can act as the secondary receptor in the FcγR-dependent ADE of SARS-CoV-2 infection , 2021, iScience.

[53]  T. Miura,et al.  Is SARS-CoV-2 Neutralized More Effectively by IgM and IgA than IgG Having the Same Fab Region? , 2021, Pathogens.

[54]  S. Rhatomy,et al.  Convalescent plasma as a treatment modality for Coronavirus Disease 2019 in Indonesia: A case reports , 2021, Annals of Medicine and Surgery.

[55]  M. Hassany,et al.  Effect of 2 Inactivated SARS-CoV-2 Vaccines on Symptomatic COVID-19 Infection in Adults: A Randomized Clinical Trial. , 2021, JAMA.

[56]  P. Tang,et al.  Impacts of COVID-19 Pandemic on Psychological Well-Being of Older Chronic Kidney Disease Patients , 2021, Frontiers in Medicine.

[57]  D. Standley,et al.  An infectivity-enhancing site on the SARS-CoV-2 spike protein targeted by antibodies , 2021, Cell.

[58]  E. Wood,et al.  Convalescent plasma or hyperimmune immunoglobulin for people with COVID-19: a living systematic review. , 2021, The Cochrane database of systematic reviews.

[59]  M. Davenport,et al.  Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection , 2021, Nature Medicine.

[60]  Endeshaw Chekol Abebe,et al.  Neuropilin 1: A Novel Entry Factor for SARS-CoV-2 Infection and a Potential Therapeutic Target , 2021, Biologics : targets & therapy.

[61]  F. Dèng,et al.  SARS-CoV-2 interacts with platelets and megakaryocytes via ACE2-independent mechanism , 2021, Journal of Hematology & Oncology.

[62]  Elisabeth Mahase Covid-19: Unusual blood clots are “very rare side effect” of Janssen vaccine, says EMA , 2021, BMJ.

[63]  D. Ho,et al.  Increased resistance of SARS-CoV-2 variant P.1 to antibody neutralization , 2021, Cell Host & Microbe.

[64]  M. Schull,et al.  Vaccine Induced Prothrombotic Immune Thrombocytopenia (VIPIT) Following AstraZeneca COVID-19 Vaccination , 2021 .

[65]  Elisabeth Mahase Covid-19: WHO says rollout of AstraZeneca vaccine should continue, as Europe divides over safety , 2021, BMJ.

[66]  A. Kelleher,et al.  Long-term persistence of RBD+ memory B cells encoding neutralizing antibodies in SARS-CoV-2 infection , 2021, Cell Reports Medicine.

[67]  E. Chu,et al.  Evaluation of the automated LIAISON® SARS-CoV-2 TrimericS IgG assay for the detection of circulating antibodies , 2021, Clinical chemistry and laboratory medicine.

[68]  A. Iafrate,et al.  Multiple SARS-CoV-2 variants escape neutralization by vaccine-induced humoral immunity , 2021, Cell.

[69]  M. Sajadi,et al.  Binding and Neutralization Antibody Titers After a Single Vaccine Dose in Health Care Workers Previously Infected With SARS-CoV-2. , 2021, JAMA.

[70]  Junjiang Fu,et al.  Evaluation and characterization of HSPA5 (GRP78) expression profiles in normal individuals and cancer patients with COVID-19 , 2021, International journal of biological sciences.

[71]  M. Nussenzweig,et al.  mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants , 2021, Nature.

[72]  V. Calvez,et al.  Rapid decline of neutralizing antibodies against SARS-CoV-2 among infected healthcare workers , 2021, Nature Communications.

[73]  M. Mulligan,et al.  Neutralization of viruses with European, South African, and United States SARS-CoV-2 variant spike proteins by convalescent sera and BNT162b2 mRNA vaccine-elicited antibodies , 2021, bioRxiv.

[74]  P. Espinosa,et al.  Neurological Complications of COVID-19: Guillain-Barre Syndrome Following Pfizer COVID-19 Vaccine , 2021, Cureus.

[75]  Y. Kawaoka,et al.  Antibody titers against SARS-CoV-2 decline, but do not disappear for several months , 2021, EClinicalMedicine.

[76]  P. Roy,et al.  Sputnik V COVID-19 vaccine candidate appears safe and effective , 2021, The Lancet.

[77]  Kenneth G. C. Smith,et al.  SARS-CoV-2 B.1.1.7 escape from mRNA vaccine-elicited neutralizing antibodies , 2021 .

[78]  V. Kulasingam,et al.  Quantitative Measurement of Anti-SARS-CoV-2 Antibodies: Analytical and Clinical Evaluation , 2021, Journal of Clinical Microbiology.

[79]  S. Yerly,et al.  Antibody persistence in the first 6 months following SARS-CoV-2 infection among hospital workers: a prospective longitudinal study , 2021, Clinical Microbiology and Infection.

[80]  M. Nussenzweig,et al.  mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants , 2021, bioRxiv.

[81]  K. Kupferschmidt New coronavirus variants could cause more reinfections, require updated vaccines , 2021 .

[82]  S. Mallapaty,et al.  China COVID vaccine reports mixed results - what does that mean for the pandemic? , 2021, Nature.

[83]  L. Katz (A Little) Clarity on Convalescent Plasma for Covid-19 , 2021, The New England journal of medicine.

[84]  D. Qu,et al.  Enhancement versus neutralization by SARS-CoV-2 antibodies from a convalescent donor associates with distinct epitopes on the RBD , 2021, Cell Reports.

[85]  Y. Bi,et al.  COVID-19 reinfection in the presence of neutralizing antibodies , 2021, National science review.

[86]  Qiang Zhou,et al.  AXL is a candidate receptor for SARS-CoV-2 that promotes infection of pulmonary and bronchial epithelial cells , 2021, Cell Research.

[87]  F. Cosset,et al.  A longitudinal study of SARS-CoV-2-infected patients reveals a high correlation between neutralizing antibodies and COVID-19 severity , 2021, Cellular & Molecular Immunology.

[88]  Bjoern Peters,et al.  Immunological memory to SARS-CoV-2 assessed for up to 8 months after infection , 2021, Science.

[89]  F. Polack,et al.  Prevention of severe COVID-19 in the elderly by early high-titer plasma therapy , 2021, The New England Journal of Medicine.

[90]  Huachen Zhu,et al.  SARS-CoV-2 infection and disease outcomes in non-human primate models: advances and implications , 2021, Emerging microbes & infections.

[91]  Jelena S. Bezbradica,et al.  The role and uses of antibodies in COVID-19 infections: a living review , 2021, Oxford open immunology.

[92]  A. Iafrate,et al.  COVID-19-neutralizing antibodies predict disease severity and survival , 2020, Cell.

[93]  Nguyen H. Tran,et al.  Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK , 2020, Lancet.

[94]  C. Rice,et al.  Enhanced SARS-CoV-2 neutralization by dimeric IgA , 2020, Science Translational Medicine.

[95]  L. Carter,et al.  Airway antibodies emerge according to COVID-19 severity and wane rapidly but reappear after SARS-CoV-2 vaccination , 2020, JCI insight.

[96]  M. Nussenzweig,et al.  Antibody potency, effector function, and combinations in protection and therapy for SARS-CoV-2 infection in vivo , 2020, The Journal of experimental medicine.

[97]  Nguyen H. Tran,et al.  Safety and immunogenicity of ChAdOx1 nCoV-19 vaccine administered in a prime-boost regimen in young and old adults (COV002): a single-blind, randomised, controlled, phase 2/3 trial. , 2020, Lancet.

[98]  A. Fontanet,et al.  Asymptomatic and symptomatic SARS-CoV-2 infections elicit polyfunctional antibodies , 2020, Cell Reports Medicine.

[99]  D. Lauffenburger,et al.  Single-Shot Ad26 Vaccine Protects Against SARS-CoV-2 in Rhesus Macaques , 2020, Nature.

[100]  Caizheng Yu,et al.  Linear epitope landscape of the SARS-CoV-2 Spike protein constructed from 1,051 COVID-19 patients , 2020, Cell Reports.

[101]  O. Schwartz,et al.  IgA dominates the early neutralizing antibody response to SARS-CoV-2 , 2020, Science Translational Medicine.

[102]  OUP accepted manuscript , 2021, The Journal of Applied Laboratory Medicine.

[103]  J. Mascola,et al.  Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine , 2020, The New England journal of medicine.

[104]  Sergei L. Kosakovsky Pond,et al.  Emergence and rapid spread of a new severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) lineage with multiple spike mutations in South Africa , 2020, medRxiv.

[105]  William T. Harvey,et al.  Recurrent emergence and transmission of a SARS-CoV-2 spike deletion H69/V70 , 2020, bioRxiv.

[106]  P. Dormitzer,et al.  Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine , 2020, The New England journal of medicine.

[107]  P. Hotez,et al.  Neutralizing antibodies for the treatment of COVID-19 , 2020, Nature Biomedical Engineering.

[108]  Nguyen H. Tran,et al.  T cell and antibody responses induced by a single dose of ChAdOx1 nCoV-19 (AZD1222) vaccine in a phase 1/2 clinical trial , 2020, Nature Medicine.

[109]  L. Carter,et al.  Functional SARS-CoV-2-Specific Immune Memory Persists after Mild COVID-19 , 2020, Cell.

[110]  C. Cordon-Cardo,et al.  Robust neutralizing antibodies to SARS-CoV-2 infection persist for months , 2020, Science.

[111]  M. Beer,et al.  SARS-CoV-2 spike D614G variant confers enhanced replication and transmissibility , 2020, bioRxiv.

[112]  A. Helenius,et al.  Neuropilin-1 facilitates SARS-CoV-2 cell entry and infectivity , 2020, Science.

[113]  B. Haynes,et al.  Prospects for a safe COVID-19 vaccine , 2020, Science Translational Medicine.

[114]  J. Dubuisson,et al.  Anti-spike, Anti-nucleocapsid and Neutralizing Antibodies in SARS-CoV-2 Inpatients and Asymptomatic Individuals , 2020, Frontiers in Microbiology.

[115]  C. Rice,et al.  Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants , 2020, bioRxiv.

[116]  E. Walsh,et al.  Safety and Immunogenicity of Two RNA-Based Covid-19 Vaccine Candidates , 2020, The New England journal of medicine.

[117]  A. Gingras,et al.  Persistence of serum and saliva antibody responses to SARS-CoV-2 spike antigens in COVID-19 patients , 2020, Science Immunology.

[118]  William T. Hu,et al.  Extrafollicular B cell responses correlate with neutralizing antibodies and morbidity in COVID-19 , 2020, Nature Immunology.

[119]  A. Zangrillo,et al.  COVID-19 survival associates with the immunoglobulin response to the SARS-CoV-2 spike Receptor Binding Domain. , 2020, The Journal of clinical investigation.

[120]  N. Hacohen,et al.  Viral epitope profiling of COVID-19 patients reveals cross-reactivity and correlates of severity , 2020, Science.

[121]  Chiman Karami,et al.  The immune response and immune evasion characteristics in SARS-CoV, MERS-CoV, and SARS-CoV-2: Vaccine design strategies , 2020, International Immunopharmacology.

[122]  C. Coopersmith,et al.  Convalescent Plasma for the Treatment of COVID-19: Perspectives of the National Institutes of Health COVID-19 Treatment Guidelines Panel , 2020, Annals of Internal Medicine.

[123]  A. Pain,et al.  Early Humoral Response Correlates with Disease Severity and Outcomes in COVID-19 Patients , 2020, medRxiv.

[124]  M. Beltramello,et al.  Mapping Neutralizing and Immunodominant Sites on the SARS-CoV-2 Spike Receptor-Binding Domain by Structure-Guided High-Resolution Serology , 2020, Cell.

[125]  K. Lynch,et al.  Kinetics of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Antibody Avidity Maturation and Association with Disease Severity , 2020, Clinical Infectious Diseases.

[126]  M. H. Nicknam,et al.  COVID-19: Significance of antibodies. , 2020, Human antibodies.

[127]  Yifan Cheng,et al.  Antibody-dependent enhancement of coronavirus , 2020, International Journal of Infectious Diseases.

[128]  S. Kent,et al.  Antibody-dependent enhancement and SARS-CoV-2 vaccines and therapies , 2020, Nature Microbiology.

[129]  D. Lauffenburger,et al.  Ad26 vaccine protects against SARS-CoV-2 severe clinical disease in hamsters , 2020, Nature Medicine.

[130]  V. Shinde,et al.  Phase 1–2 Trial of a SARS-CoV-2 Recombinant Spike Protein Nanoparticle Vaccine , 2020, The New England journal of medicine.

[131]  P. Kellam,et al.  Antibody response to SARS-CoV-2 infection in humans: A systematic review , 2020, medRxiv.

[132]  S. Caddy Russian SARS-CoV-2 vaccine , 2020, BMJ.

[133]  J. Bloom,et al.  Neutralizing Antibodies Correlate with Protection from SARS-CoV-2 in Humans during a Fishery Vessel Outbreak with a High Attack Rate , 2020, Journal of Clinical Microbiology.

[134]  L. Carter,et al.  Functional SARS-CoV-2-specific immune memory persists after mild COVID-19 , 2020, medRxiv.

[135]  Yongxiang Yi,et al.  SARS-CoV-2 neutralizing antibody levels are correlated with severity of COVID-19 pneumonia , 2020, Biomedicine & Pharmacotherapy.

[136]  E. Walsh,et al.  Phase I/II study of COVID-19 RNA vaccine BNT162b1 in adults , 2020, Nature.

[137]  Shibo Jiang,et al.  Effect of Low-Pathogenic Human Coronavirus-Specific Antibodies on SARS-CoV-2 , 2020, Trends in Immunology.

[138]  M. Sajadi,et al.  Specificity and Performance of Nucleocapsid and Spike-based SARS-CoV-2 Serologic Assays , 2020, medRxiv.

[139]  K. Lynch,et al.  Kinetics of SARS-CoV-2 Antibody Avidity Maturation and Association with Disease Severity , 2020, medRxiv.

[140]  Rebecca J. Loomis,et al.  SARS-CoV-2 mRNA Vaccine Design Enabled by Prototype Pathogen Preparedness , 2020, Nature.

[141]  M. Hall,et al.  Fruitful Neutralizing Antibody Pipeline Brings Hope To Defeat SARS-Cov-2 , 2020, Trends in Pharmacological Sciences.

[142]  J. Sodroski,et al.  Potent neutralizing antibodies against multiple epitopes on SARS-CoV-2 spike , 2020, Nature.

[143]  Nguyen H. Tran,et al.  Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial , 2020, The Lancet.

[144]  T. Malik,et al.  The newly emerged COVID-19 disease: a systemic review , 2020, Virology Journal.

[145]  Mei San Tang,et al.  Association between SARS-CoV-2 neutralizing antibodies and commercial serological assays , 2020, bioRxiv.

[146]  Chuan Qin,et al.  Primary exposure to SARS-CoV-2 protects against reinfection in rhesus macaques , 2020, Science.

[147]  X. Tang,et al.  Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections , 2020, Nature Medicine.

[148]  M. Bachmann,et al.  Strategies to Prevent SARS-CoV-2-Mediated Eosinophilic Disease in Association with COVID-19 Vaccination and Infection , 2020, International Archives of Allergy and Immunology.

[149]  D. Burton,et al.  Isolation of potent SARS-CoV-2 neutralizing antibodies and protection from disease in a small animal model , 2020, Science.

[150]  Patrick W. Johnson,et al.  Early safety indicators of COVID-19 convalescent plasma in 5,000 patients. , 2020, The Journal of clinical investigation.

[151]  L. Poon,et al.  Antibody profiles in mild and severe cases of COVID-19 , 2020, Clinical chemistry.

[152]  Larissa B. Thackray,et al.  A SARS-CoV-2 Infection Model in Mice Demonstrates Protection by Neutralizing Antibodies , 2020, Cell.

[153]  Kari C. Nadeau,et al.  Distribution of ACE2, CD147, CD26, and other SARS‐CoV‐2 associated molecules in tissues and immune cells in health and in asthma, COPD, obesity, hypertension, and COVID‐19 risk factors , 2020, Allergy.

[154]  A. Casadevall,et al.  A Randomized Trial of Convalescent Plasma for COVID-19-Potentially Hopeful Signals. , 2020, JAMA.

[155]  M. Drebot,et al.  Two Detailed Plaque Assay Protocols for the Quantification of Infectious SARS‐CoV‐2 , 2020, Current protocols in microbiology.

[156]  Yajuan Li,et al.  Serum IgA, IgM, and IgG responses in COVID-19 , 2020, Cellular & Molecular Immunology.

[157]  Linqi Zhang,et al.  Human neutralizing antibodies elicited by SARS-CoV-2 infection , 2020, Nature.

[158]  K. Kadkhoda COVID‐19: are neutralizing antibodies neutralizing enough? , 2020, Transfusion.

[159]  P. Sorger,et al.  SARS-CoV-2 infection protects against rechallenge in rhesus macaques , 2020, Science.

[160]  R. Baric,et al.  DNA vaccine protection against SARS-CoV-2 in rhesus macaques , 2020, Science.

[161]  F. Yu,et al.  Serology characteristics of SARS-CoV-2 infection since exposure and post symptom onset , 2020, European Respiratory Journal.

[162]  L. Lopalco,et al.  Humoral Immune Responses in COVID-19 Patients: A Window on the State of the Art , 2020, Frontiers in Immunology.

[163]  M. V. van Breemen,et al.  Potent neutralizing antibodies from COVID-19 patients define multiple targets of vulnerability , 2020, Science.

[164]  Stéphane Hallegatte,et al.  Socio-Economic Impacts of COVID-19 on Household Consumption and Poverty , 2020, Economics of Disasters and Climate Change.

[165]  M. Wener,et al.  Performance Characteristics of the Abbott Architect SARS-CoV-2 IgG Assay and Seroprevalence in Boise, Idaho , 2020, Journal of Clinical Microbiology.

[166]  F. Gao,et al.  A noncompeting pair of human neutralizing antibodies block COVID-19 virus binding to its receptor ACE2 , 2020, Science.

[167]  Wayne T. Nicholson,et al.  Deployment of convalescent plasma for the prevention and treatment of COVID-19. , 2020, The Journal of clinical investigation.

[168]  Yan Peng,et al.  Effectiveness of convalescent plasma therapy in severe COVID-19 patients , 2020, Proceedings of the National Academy of Sciences.

[169]  W. Dietz,et al.  Obesity and its Implications for COVID‐19 Mortality , 2020, Obesity.

[170]  Bin Zhang,et al.  Treatment With Convalescent Plasma for Critically Ill Patients With Severe Acute Respiratory Syndrome Coronavirus 2 Infection , 2020, Chest.

[171]  Jing Yuan,et al.  Treatment of 5 Critically Ill Patients With COVID-19 With Convalescent Plasma. , 2020, JAMA.

[172]  Y. Yazdanpanah,et al.  SARS-CoV-2 specific antibody responses in COVID-19 patients , 2020, medRxiv.

[173]  Qi Zhao,et al.  Perspectives on therapeutic neutralizing antibodies against the Novel Coronavirus SARS-CoV-2 , 2020, International journal of biological sciences.

[174]  Qiang Zhou,et al.  Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2 , 2020, Science.

[175]  Yuan Shi,et al.  Convalescent plasma as a potential therapy for COVID-19 , 2020, The Lancet Infectious Diseases.

[176]  M. Letko,et al.  Functional assessment of cell entry and receptor usage for SARS-CoV-2 and other lineage B betacoronaviruses , 2020, Nature Microbiology.

[177]  B. Graham,et al.  Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation , 2020, Science.

[178]  Su Hwan Lee,et al.  Use of Convalescent Plasma Therapy in Two COVID-19 Patients with Acute Respiratory Distress Syndrome in Korea , 2020, Journal of Korean medical science.

[179]  B. Graham,et al.  Cryo-EM Structure of the 2019-nCoV Spike in the Prefusion Conformation , 2020, bioRxiv.

[180]  C. Blandizzi,et al.  Anti-SARS-CoV-2 neutralizing monoclonal antibodies: clinical pipeline , 2020, mAbs.

[181]  S. Yerly,et al.  Validation and clinical evaluation of a SARS-CoV-2 surrogate virus neutralisation test (sVNT) , 2020, Emerging microbes & infections.

[182]  J. Sodroski,et al.  SARS-CoV-2 neutralizing antibody responses are more robust in patients with severe disease , 2020, bioRxiv.

[183]  Yaokai Chen,et al.  Patterns of IgG and IgM antibody response in COVID-19 patients , 2020, Emerging microbes & infections.

[184]  Naveen Vankadari,et al.  Emerging COVID-19 coronavirus: glycan shield and structure prediction of spike glycoprotein and its interaction with human CD26 , 2020, Emerging microbes & infections.

[185]  Kari C. Nadeau,et al.  in a prospective longitudinal study , 2020 .

[186]  E. Sedova,et al.  Non-neutralizing Antibodies Directed at Conservative Influenza Antigens , 2019, Acta naturae.

[187]  Qinjian Zhao,et al.  Viral neutralization by antibody-imposed physical disruption , 2019, Proceedings of the National Academy of Sciences.

[188]  I. Wilson,et al.  Antibody responses to viral infections: a structural perspective across three different enveloped viruses , 2019, Nature Microbiology.

[189]  L. Hanna,et al.  Functional and Protective Role of Neutralizing Antibodies (NAbs) Against Viral Infections , 2019, Recent Developments in Applied Microbiology and Biochemistry.

[190]  S. Fortune,et al.  Beyond binding: antibody effector functions in infectious diseases , 2017, Nature Reviews Immunology.

[191]  S. Payne Viruses: From Understanding to Investigation , 2017 .

[192]  Tse-Ching Chen,et al.  Sterilizing immunity to influenza virus infection requires local antigen-specific T cell response in the lungs , 2016, Scientific Reports.

[193]  P. Horby,et al.  Evaluation of Convalescent Plasma for Ebola Virus Disease in Guinea. , 2016, The New England journal of medicine.

[194]  P. Klasse,et al.  Neutralization of Virus Infectivity by Antibodies: Old Problems in New Perspectives. , 2014, Advances in biology.

[195]  Michael Reth,et al.  Matching cellular dimensions with molecular sizes , 2013, Nature Immunology.

[196]  A. Schmaljohn Protective antiviral antibodies that lack neutralizing activity: precedents and evolution of concepts. , 2013, Current HIV research.

[197]  E. Mohammadi,et al.  Barriers and facilitators related to the implementation of a physiological track and trigger system: A systematic review of the qualitative evidence , 2017, International journal for quality in health care : journal of the International Society for Quality in Health Care.

[198]  S. Plotkin Correlates of Protection Induced by Vaccination , 2010, Clinical and Vaccine Immunology.

[199]  Shibo Jiang,et al.  The spike protein of SARS-CoV — a target for vaccine and therapeutic development , 2009, Nature Reviews Microbiology.

[200]  Y. Guan,et al.  Treatment with convalescent plasma for influenza A (H5N1) infection. , 2007, The New England journal of medicine.

[201]  D. Dimitrov,et al.  Potent cross-reactive neutralization of SARS coronavirus isolates by human monoclonal antibodies , 2007, Proceedings of the National Academy of Sciences.

[202]  H. Doerr,et al.  Molecular and Biological Characterization of Human Monoclonal Antibodies Binding to the Spike and Nucleocapsid Proteins of Severe Acute Respiratory Syndrome Coronavirus , 2005, Journal of Virology.

[203]  Wenhui Li,et al.  Potent neutralization of severe acute respiratory syndrome (SARS) coronavirus by a human mAb to S1 protein that blocks receptor association. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[204]  M. Radosevich,et al.  Treatment of severe acute respiratory syndrome with convalescent plasma. , 2003, Hong Kong medical journal = Xianggang yi xue za zhi.

[205]  P. Stone,et al.  What is a systemic review? , 2002, Applied nursing research : ANR.

[206]  M. Krausz Old Problems–New Perspectives , 1996 .

[207]  E. Glaser The randomized clinical trial. , 1972, The New England journal of medicine.