Study demonstrates associations between COVID-19 symptom presentation and antibody assay reactivity

In a recent study posted to the medRxiv* preprint server, researchers tested convalescent sera from individuals who had recovered from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection to demonstrate an association between antibody response and reported coronavirus disease 2019 (COVID-19) symptoms.

Study: Differential antibody production by symptomatology in SARS-CoV-2 convalescent individuals. Image Credit: simona pilolla 2/ShutterstockStudy: Differential antibody production by symptomatology in SARS-CoV-2 convalescent individuals. Image Credit: simona pilolla 2/Shutterstock

About the study

In this study, researchers used stored samples and data of 216 participants who donated COVID-19 convalescent plasma (CCP) and whose accompanying symptom data from April 2020-January 2021 was available. All these individuals were over 18 years of age and were eligible for blood donation, and their average age was 49 years at the time of sample collection.

Plasma samples were analyzed using three serological assays: Euroimmun Anti-SARS-CoV-2 ELISA, the CoronaCHEK™ COVID-19 IgG/IgM Rapid Test Cassette that measured immunoglobulin G (IgG) responses to the SARS-CoV-2 spike (S1) and receptor-binding domain (RBD), respectively, whereas the Bio-Rad Platelia SARS-CoV-2 total antibody ELISA measured total antibody response to the SARS-CoV-2 nucleocapsid (N) protein.

The researchers used a multi-array electrochemiluminescence detection technology to examine 35 cytokine and chemokine analytes in plasma. They used binomial logistic regressions to calculate odds ratios [OR] for associations between serological results and reported symptoms; likewise, they calculated adjusted odds ratios [aOR] for all COVID-19 symptoms.

Study findings

More than 83% of test samples showed a positive antibody response across all three serologic assays. Between 40-60% of individuals with no symptoms and 73-75% with sore throat showed relative stability across all three assays.

Regardless of symptom presentation, antibodies produced by CCP responded similarly to different parts of the SARS-CoV-2, and the assay reactivity was consistent across all COVID-19 symptoms. Additionally, hospitalization, male sex, and persistent cough were associated with seropositive results, suggesting that convalescent individuals displaying these symptoms most likely generated a robust antibody response.

The results of signal to cut-off ratios (S/C) were generated for the Euroimmun and BioRad ELISAs. They were stratified by five COVID-19 symptoms: cough, sore throat, no symptoms, and other symptoms. For the Bio-Rad assay, individuals reporting cough or other symptoms had the highest mean S/C ratio, and those having a sore throat and no symptoms had the lowest mean S/C ratio. For the Euroimmun assay, the highest S/C ratios were generated by samples from individuals reporting cough, other symptoms, sore throat, and no symptoms.

As expected, asymptomatic convalescent individuals were significantly associated with a seronegative result. However, the most striking observation was that sore throat, a presenting symptom of upper respiratory tract infection, was associated with a seronegative result, suggesting variations in the mechanisms governing immunity of the lower and upper respiratory tracts.

Cough strongly associated with antibodies against S1 and RBD with aOR of 5.33 and 4.36, respectively. On the contrary, sore throat and absence of symptoms were related to a seronegative result. While sore throat showed aOR values of 0.25 and 0.31 against S1 and N, respectively, the lack of symptoms with aOR values of 0.16 against both N and RBD was strongly associated with seronegativity. The aORs and confidence intervals did not substantially decrease after adjustment for cough, sore throat, or no symptoms across all three serological assays.

Previous studies have demonstrated that robust IgG responses indicate a lower respiratory tract infection. The authors of the present study noted that study participants with no symptoms or sore throat generated fewer IgG antibodies.

According to another hypothesis, a strong innate immune response compensates for an antibody response and combat SARS-CoV-2 infection. However, the cytokine and chemokine data of the current study does not support this rationalization, raising the possibility that cytokine and chemokine levels may have declined to their basal levels. It might also have occurred because an average of 30 days had passed since COVID-19 symptoms resolved in the subjects at the time of blood collection.

Conclusions

Overall, a strong correlation was observed between cough and antibody response to SARS-CoV-2, and sore throat was strongly associated with a lack of antibody response to SARS-CoV-2 infection. Taken together, these findings strongly support the perception that the severity of SARS-CoV-2- infection correlates with vigorous antibody response.

Future studies should test for IgA levels in nasal or throat samples to evaluate whether a robust mucosal IgA response is associated with some clinical presentations of COVID-19. Studies may also evaluate immune factors other than antibodies and panel of human cytokines used in the current study to characterize the immune responses generated by individuals exhibiting specific symptomatology.

*Important notice


medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:
Neha Mathur

Written by

Neha Mathur

Neha is a digital marketing professional based in Gurugram, India. She has a Master’s degree from the University of Rajasthan with a specialization in Biotechnology in 2008. She has experience in pre-clinical research as part of her research project in The Department of Toxicology at the prestigious Central Drug Research Institute (CDRI), Lucknow, India. She also holds a certification in C++ programming.

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