In March 2020, COVID-19 was declared a pandemic by the WHO. Since then, efforts have been made to increase our knowledge of the disease. The convalescent plasma (CP) donation involves a series of criteria for donor eligibility, such as pre-donation and serological tests. Currently, the antibody response against SARS-CoV-2 remains poorly understood and the usefulness of serological tests is unclear (Long, et al. Nature Medicine, 2020). Based on donor eligibility, one can better assess the antibody response to SARS-CoV-2 from post-infection candidates.
This is an observational, prospective study, without intervention. From 06/26/2020 to 07/31/2020, serological data of candidates for CP donation were collected. Recovered COVID-19 patients who had been previously tested were interviewed. RT-PCR and serological test (chemiluminescence immunoassays) for SARS-CoV-2 were carried out to verify their eligibility for CP collection. The data were related to the time of the onset of symptoms and the collection of the material. Subjects with non-detectable RT-PCR and reagent IgG were considered eligible. Reference values were IgM > 1.2 AU/mL and IgG > 1.4 AU/mL.
The characteristics of the candidates are summarized in Table 1. Of 234 interviewed subjects, 70 were screened for pre-collection tests, 49 were male. The average age was 36 (20 - 57). After serological screening, 44/70 (62.8%) were considered eligible for CP donation. The reasons for ineligibility were: 17/70 (24.3%) non-reagent IgG, 4/70 (5.7%) with detectable RT-PCR and 5/70 (7.1%) due to reasons in clinical screening.
The median between the onset of symptoms and the serology sample collection was 32.5 (21 - 77) days, (IQR 28.75 to 37.25). Those who were more likely to be eligible to donate were the subjects who had a longer time interval between the symptoms onset and the sample collection (p <0.012).
Although viral clearance in the upper airways is expected from the 10th day of symptom onset, only 50% of patients will have an undetectable test (Özçürümez, et al. J Allergy Clin Immunol. 2020). In our sample, 5.7% (4/70) of the subjects had detectable RT-PCR, which can represent residual viral genome and not active infection.
We observed that 20% of the subjects samples were non-reagent. Those who were tested up to the 21st of the onset of symptoms might not have had seroconversion yet. For those tested after the 28th day, we can infer that the antibodies had already been cleared. Some authors state that patients who had mild infections may react with less antibodies (Özçürümez, et al. J Allergy Clin Immunol. 2020), which could explain this fact. Likewise, it was not possible to relate serological titers to the severity of the disease, as this was not one of the selection criteria.In 40/70 donors (57.2%) IgM remained above 1.2 AU / mL after the 21st day of symptom onset. Interestingly, 2 of these had only reagent IgM after the 36th day of symptom onset. Most subjects who had reagent IgM after the 21st of symptoms also had reagent IgG. We inferred that they were in a vigorous convalescence phase.
In addition, 75.7% of the subjects presented reagent IgG regardless of the date of onset of symptoms. Most of them had both reagent IgM and IgG. Only one donor's (1.4%) IgM and IgG were non-reagent 21 days after the onset of symptoms.
As we did not collect serial samples, we could not verify the average amount of days for seroconversion to take place. Some authors recommend that the single collection should occur at least 21 days after the onset of symptoms, so seroconversion is observed (Deeks, et al., Cochrane Database Syst Rev. 2020). In our sample, 4 donors (5%) collected the samples on the 21st day after the symptom onset. Of these, 3 had seroconversion, 2 with IgM and IgG, 1 with IgG and 1 with reagent IgM.
The values suggest that the subjects who could donate CP were those that presented a longer time interval between the onset of symptoms and the blood sample collection, in comparison to those who could not (p=0,012 and 0,409, respectively). The median of days between symptom onset and serology testing was also higher in the non-eligible group. Besides, the eligible group had a higher average concentration of IgM and IgG compared to the non-eligible one.
In conclusion, regarding the serological criteria, about 25% of the studied population could not donate CP. Although a single serology sample collection after the 21st day of symptom onset is recommended, only 1 candidate did not show seroconversion.
Disclosures
No relevant conflicts of interest to declare.
Antibody response in COVID-19 patients with and without re-positive RT-PCR results during the convalescent phase