Longitudinal analysis of clinical serology assay performance and neutralising antibody levels in COVID19 convalescents
Authors: Muecksch Frauke , Wise Helen , Batchelor Becky , Squires Maria , Semple Elizabeth , Richardson Claire , McGuire Jacqueline , Clearly Sarah , Furrie Elizabeth , Greig Neil , Hay Gordon , Templeton Kate , Lorenzi Julio C.C. , Hatziioannou Theodora , Jenks Sara , Bieniasz Paul D. 
Published: August 2020

Objectives

To investigate longitudinal trajectory of SARS-CoV-2 neutralising antibodies and the performance of serological assays in diagnosing prior infection and predicting serum neutralisation titres with time

Design

Retrospective longitudinal analysis of a COVID19 case cohort.

Setting

NHS outpatient clinics

Participants

Individuals with RT-PCR diagnosed SARS-CoV-2 infection that did not require hospitalization

Main outcome measures

The sensitivity with which prior infection was detected and quantitative antibody titres were assessed using four SARS-CoV-2 serologic assay platforms. Two platforms employed SARS-CoV-2 spike (S) based antigens and two employed nucleocapsid (N) based antigens. Serum neutralising antibody titres were measured using a validated pseudotyped virus SARS-CoV-2 neutralisation assay. The ability of the serological assays to predict neutralisation titres at various times after PCR diagnosis was assessed.

Results

The three of the four serological assays had sensitivities of 95 to100% at 21-40 days post PCR-diagnosis, while a fourth assay had a lower sensitivity of 85%. The relative sensitivities of the assays changed with time and the sensitivity of one assay that had an initial sensitivity of >95% declined to 85% at 61-80 post PCR diagnosis, and to 71% at 81-100 days post diagnosis. Median antibody titres decreased in one serologic assay but were maintained over the observation period in other assays. The trajectories of median antibody titres measured in serologic assays over this time period were not dependent on whether the SARS-CoV-2 N or S proteins were used as antigen source. A broad range of SARS-CoV-2 neutralising titres were evident in individual sera, that decreased over time in the majority of participants; the median neutralisation titre in the cohort decreased by 45% over 4 weeks. Each of the serological assays gave quantitative measurements of antibody titres that correlated with SARS-CoV-2 neutralisation titres, but, the S-based serological assay measurements better predicted serum neutralisation potency. The strength of correlation between serologic assay results and neutralisation titres deteriorated with time and decreases in neutralisation titres in individual participants were not well predicted by changes in antibody titres measured using serologic assays.

Conclusions

SARS-CoV-2 serologic assays differed in their comparative diagnostic performance over time. Different assays are more or less well suited for surveillance of populations for prior infection versus prediction of serum neutralisation potency. Continued monitoring of declining neutralisation titres during extended follow up should facilitate the establishment of appropriate serologic correlates of protection against SARS-CoV-2 reinfection.