Princeton University

This study examined serological testing, antibodies against reinfection, and durability of vaccine protection in order to answer the question of whether or not neutralizing antibodies provide protection against reinfection of SARS-CoV-2 and to determine the length of antibody responses. 

- Important Definitions and Background Information
- Methods
- Patients
- Results
- Discussion

Longitudinal Evaluation and Decline of Antibody Responses in SARS-CoV-2 Infection

Neutralizing Antibody Responses to SARS-CoV-2


Longevity of the Ab Response


65 RT-qPCR confirmed SARS-CoV-2 infected individuals

- 59 admitted and 6 healthcare workers at Guys' and St. Thomas' NHS Foundation Trust 
- 77.2% male
-Average age: 55.2 years (ranging from 23-95 years)
- Information on ethnicity was not collected

Patients in Longitudinal Evaluation and Decline of Antibody Responses in SARS-CoV-2 Infection

SARS-CoV-2 is a betacoronavirus responsible for COVID-19. The viral envelope Spike (S) proteins bind to host cell angiotensin-converting enzyme 2 (ACE-2) receptors via the receptor-binding domain (RBD) to facilitate viral entry. Following infection, IgM, IgA, and IgG antibodies are typically produced within 1 to 2 weeks post-onset of symptoms (POS), with neutralizing antibodies (nAbs) remaining detectable for 12 to 34 months.

SARS-CoV-2 Cellular Entry Mechanism and Antibody Response Longevity

An analysis of serum samples from 31 seropositive healthcare workers (80.6% symptomatic, 19.4% asymptomatic) during SARS-CoV-2 infection shows:
- Neutralizing antibody 50% inhibitory dilution ($$\text{ID}_{50}$$) values correlate well with IgG and IgM optical density values against the Spike (S) protein and its receptor-binding domain (RBD), but correlate poorly with those against the nucleocapsid (N) protein.
- Asymptomatic and symptomatic healthcare workers show similar, lower $$\text{ID}_{50}$$ values compared to hospitalized COVID-19 patients with moderate-to-severe symptoms.
- Because of these lower neutralizing antibody titers, healthcare workers exhibit a more frequent decline in neutralizing antibody levels over time compared to more severely ill patients.

Antibody Responses in a SARS-CoV-2 Healthcare Worker Cohort

- The optical density at 1:50 serum dilution was measured for 300 samples from 65 patients. 2/65 individuals had no measurable antibody response, likely because their sera were only collected 2 and 8 days post-symptom onset (POS); they probably seroconverted later (average seroconversion against at least 1 antigen: 12.6 days POS).
- IgG responses to S, RBD, and N antigens occurred in 92.3%, 89.2%, and 93.8% of individuals; IgM responses occurred in 92.3%, 92.3%, and 95.4%. IgA responses to RBD and N were lower (72.3% and 84.6% seropositive), while IgA to S matched the IgG/IgM rates.
- 51.6% of individuals seroconverted synchronously to IgG, IgM, and IgA, while 9.7% each showed singular seroconversion to only IgG, only IgM, or only IgA.
- 58.1% seroconverted synchronously to S, RBD, and N antigens, whereas 16.1% showed singular seroconversion to either N or S alone.
- IgM and IgA responses to all three antigens declined between 20 and 30 days POS, while the IgG response remained high up to 94 days POS. Responses also differed by disease severity when half-maximal binding ($$EC_{50}$$) was measured.

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