Association between SARS-CoV-2 Symptoms, Ct Values, and Serological Response in Vaccinated and Unvaccinated Healthcare Personnel

Abstract

Background: SARS-CoV-2 vaccines are effective at reducing symptomatic and asymptomatic COVID-19. Limited studies have compared symptoms, threshold cycle (Ct) values from reverse transcription (RT)-PCR testing, and serological testing results between previously vaccinated vs unvaccinated populations with SARS-CoV-2 infection.

Methods: Healthcare personnel (HCP) with a positive SARS-CoV-2 RT-PCR test within the previous 14 to 28 days completed surveys including questions about demographics, medical conditions, social factors, and symptoms of COVID-19. Ct values were observed, and serological testing was performed for anti-nucleocapsid (anti-N) and anti-Spike (anti-S) antibodies at enrollment and 40 to 90 days later. Serological results were compared to HCP with no known SARS-CoV-2 infection and negative anti-N testing.

Results: There were 104 unvaccinated/not fully vaccinated and 77 vaccinated HCP with 2 doses of an mRNA vaccine at time of infection. No differences in type or duration of symptoms were reported (P = 0.45). The median (interquartile range [IQR]) Ct was 21.4 (17.6-24.6) and 21.5 (18.1-24.6) for the unvaccinated and vaccinated HCP, respectively. Higher anti-N IgG was observed in unvaccinated HCP (5.08 S/CO, 3.08-6.92) than vaccinated (3.61 signal to cutoff ratio [S/CO], 2.16-5.05). Anti-S IgG was highest among vaccinated HCP with infection (34 285 aribitrary units [AU]/mL, 17 672-61 775), followed by vaccinated HCP with no prior infection (1452 AU/mL, 791-2943), then unvaccinated HCP with infection (829 AU/mL, 290-1555). Anti-S IgG decreased 1.56% (0.9%-1.79%) per day in unvaccinated and 0.38% (0.03%-0.94%) in vaccinated HCP.

Conclusions: Vaccinated HCP infected with SARS-CoV-2 reported comparable symptoms and had similar Ct values relative to unvaccinated. However, vaccinated HCP had increased and prolonged anti-S and decreased anti-N response relative to unvaccinated.

Fig. 1.

Participant enrollment dates, vaccination status, and local availability of SARS-CoV-2 vaccines and boosters. Each column is the number of individuals recruited in each month. Unvaccinated HCP are represented by the blue column and vaccinated by the red.

Fig. 2.

Ct values in vaccinated and unvaccinated healthcare personnel. Each dot is an individual participant. Previously vaccinated healthcare personnel were at least 14 days from their second dose. (A), Ct relative to vaccination status and (B), Ct values in vaccinated workers in time from second vaccine dose.

Fig. 3.

Association between serologic response to SARS-CoV-2 infection and Ct values in vaccinated and unvaccinated healthcare personnel. (A), Serological response was assessed at 14 to 28 days and (B), 30 to 90 days after positive PCR; (C), Ct-stratified serological positive and negative at enrollment and (D), follow-up; (E), Association between anti-N and Ct values at enrollment and (F), follow-up. Blue squares are vaccinated and black circles are unvaccinated HCP. Dotted lines are the qualitative cutoff for a positive result by the serological assay.

Fig. 4.

Anti-S antibody response in vaccinated and unvaccinated HCP. (A), Serological response was assessed at 14 to 28 days after infection in vaccinated and unvaccinated HCP and in a control (CTR) group that was vaccinated but never infected; (B), Anti-S response relative to Ct value at enrollment and (C), relative to simultaneously measured anti-N response. Blue squares are vaccinated HCP and black circles are unvaccinated HCP. Dotted lines are the qualitative cutoff for a positive result by the serological assay.

Fig. 5.

Kinetics of anti-S antibody response. (A), Comparison of anti-S levels at entry in infected HCP <120 days and ≥120 days after vaccination; (B), Change in anti-S antibody levels over time in those with follow-up visits; (C), Anti-S levels in healthcare personnel at follow-up based on vaccination status and infection status. Infected = infected but not vaccinated (n = 55). Hybrid Immunity = vaccinated after infection (n = 33), Breakthrough = infection after vaccination (n = 54), Breakthrough -> Boost = infected after vaccination than receiving a third vaccination (n = 15), Vaccinated = fully vaccinated, non-infected (n = 58), Vaccinated -> Boost = 3 doses of vaccination (n = 56).