Vaccine-Induced Immunity in Patients Without Detectable Antibodies After COVID-19

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Researchers evaluated the effect of COVID-19 vaccination on immunologic memory response among patients who were previously infected with COVID-19 and had no detectable antibodies following their diagnosis.

Compared with patients with no history of COVID-19 infection, immunologic memory responses were significantly increased after receipt of 1 COVID-19 vaccine dose among those who previously had an undetectable immune response following COVID-19 infection. These findings were published in Clinical Infectious Diseases.

In this study, researchers used serologic data from 2 ongoing cohort studies. The first study included 29 patients with polymerase chain reaction (PCR)-confirmed SARS-CoV-2 infection, of whom 14 were seronegative and 15 were seropositive for immunoglobulin (Ig) G and neutralizing antibodies (NAb) following their diagnosis. The second study comprised 15 individuals (controls) who were health care workers (HCW) with no history of COVID-19 infection. Patients in the seronegative group were matched by age and sex against both those in the seropositive group and those in the control group. Mann-Whitney testing was used to determine significant differences between the groups.

Among the 14 patients with PCR-confirmed SARS-CoV-2 infection included in the seronegative group, significant increases in both IgG geometric mean titers (GMT), 17.44 U/mL; 95% CI, 9.77-31.14) and NAbs (GMT, 1351 U/mL; 95% CI, 220.3-8286) were observed in 13 patients following receipt of 1 COVID-19 vaccine dose.

The researchers then assessed the effect of COVID-19 vaccination among patients in the seropositive group and those in the control group. Following receipt of 1 COVID-19 vaccine dose, patients in the seronegative group experienced a significant increase in both IgG (GMT, 40.45 U/mL; 95% CI, 33.05-49.52) and NAbs (GMT, 13,839 U/mL; 95% CI, 10,127-18,911). Among the HCWs included in the control group, GMTs of IgG and NAbs were 5.2 U/mL (95% CI, 2.97-9.13) and 33.5 U/mL (95% CI, 17.97-62.52), respectively, following 1 COVID-19 vaccine dose. After these patients received a second COVID-19 vaccine dose, both IgG and NAbs significantly increased, with GMTs of 38.1 U/mL (95% CI, 32.31-44.86) and 851 U/mL (95% CI, 363.2-1995), respectively.

This study was limited by its small sample size and the lack of data on T-cell responses.

According to the researchers, “[clinicians] should exercise caution when interpreting protection [against] [COVID-19] infection based only on antibody levels and that, perhaps, immune protection is easier to achieve than anticipated.”

Disclosure: Some authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Lustig Y, Mendelson E, Mandelboim M, et al. Existence of immunological memory response in true sero-negative individuals post COVID-19 molecular diagnosis. Clin Infect Dis. Published online March 10, 2022. doi:10.1093/cid/ciac196