Longitudinal Follow Up of Immune Responses to SARS-CoV-2 in Health Care Workers in Sweden With Several Different Commercial IgG-Assays, Measurement of Neutralizing Antibodies and CD4(+) T-Cell Responses.
The risk of SARS-CoV-2 infection among health care workers (HCWs) is a concern, but studies that conclusively determine whether HCWs are over-represented remain limited. Furthermore, methods used to confirm past infection vary and the immunological response after mild COVID-19 is still not well defined.
314 HCWs were recruited from a Swedish Infectious Diseases clinic caring for COVID-19 patients. IgG antibodies were measured using two commercial assays (Abbot Architect nucleocapsid (N)-assay and YHLO iFlash-1800 N and spike (S)-assays) at five time-points, from March 2020 to January 2021, covering two pandemic waves. Seroprevalence was assessed in matched blood donors at three time-points. More extensive analyses were performed in 190 HCWs in September/October 2020, including two additional IgG-assays (DiaSorin LiaisonXL S1/S2 and Abbot Architect receptor-binding domain (RBD)-assays), neutralizing antibodies (NAbs), and CD4+ T-cell reactivity using an in-house developed in vitro whole-blood assay based on flow cytometric detection of activated cells after stimulation with Spike S1-subunit or Spike, Membrane and Nucleocapsid (SMN) overlapping peptide pools.
Seroprevalence was higher among HCWs compared to sex and age-matched blood donors at all time-points. Seropositivity increased from 6.4% to 16.3% among HCWs between May 2020 and January 2021, compared to 3.6% to 11.9% among blood donors. We found significant correlations and high levels of agreement between NAbs and all four commercial IgG-assays. At 200-300 days post PCR-verified infection, there was a wide variation in sensitivity between the commercial IgG-assays, ranging from <30% in the N-assay to >90% in the RBD-assay. There was only moderate agreement between NAbs and CD4+ T-cell reactivity to S1 or SMN. Pre-existing CD4+ T-cell reactivity was present in similar proportions among HCW who subsequently became infected and those that did not.
HCWs in COVID-19 patient care in Sweden have been infected with SARS-CoV-2 at a higher rate compared to blood donors. We demonstrate substantial variation between different IgG-assays and propose that multiple serological targets should be used to verify past infection. Our data suggest that CD4+ T-cell reactivity is not a suitable measure of past infection and does not reliably indicate protection from infection in naive individuals.
Marklund E
,Leach S
,Nyström K
,Lundgren A
,Liljeqvist JÅ
,Nilsson S
,Yilmaz A
,Andersson LM
,Bemark M
,Gisslén M
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《Frontiers in Immunology》
Dynamics of Antibody Response to Covishield Vaccine after 6 Months: A Longitudinal Prospective Study.
To study the dynamics of antibody responses in the real world up to 6 months following two Covishield vaccination doses and evaluate its correlation with age.
From March 2021 to February 2022, a prospective, longitudinal study of healthcare workers (HCWs) from a dedicated COVID-19 hospital was conducted. Institutional Ethics Committee permission was obtained. HCWs were divided into two groups. The first group consisted of individuals who had received the first dose of the COVID-19 vaccine, with at least 3 weeks elapsed since the dose, and who had not received the second dose until the initial blood sample for antibody testing was obtained. The second group consisted of individuals who had received both COVID-19 doses and had at least 2 weeks between the administration of the second dose and the collection of the first sample for antibody testing. In March 2021, after undergoing phlebotomy for serum collection, the participants responded to the survey. Electrochemiluminescence immunoassay (ECLIA) was used to perform a quantitative test for antibodies to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein receptor domain [receptor binding domain (RBD)]. The test used had a 98.8% sensitivity and a 99.9% specificity. If the antibody titer was 0.80 U/mL or higher, it was deemed positive; if it was lower, it was deemed negative. Two follow-ups were conducted for both groups, 3 and 6 months following the first sample collection. During both follow-up visits, a blood sample was obtained for testing the amount of antibody response, and the history of COVID-19 disease following the initial sample was taken.
Every HCW had received the Covishield vaccination. After the vaccine's first dosage, 61 HCWs in the first group underwent antibody testing. The information about the 43 HCWs in the first group who attended the two follow-ups is as follows. There were 14 (32.6%) nurses and 5 (11.6%) doctors among the 43 HCWs. The age range was 21-55 years, with the median [interquartile range (IQR)] age being 26 (22-40) years and 20 (60.5%) being females. The vaccination series had a median (IQR) of 34 (29-49) days between doses. There was a statistically significant difference in immunoglobulin G (IgG) levels of the three samples, χ2 = 13.579, p = 0.001. Median (IQR) IgG levels of the three samples at 1 month after the first dose, 3 and 6 months after the second dose were 8511 (51-15400) U/mL, 1471 (249-5050) U/mL, and 978 (220-2854) U/mL, respectively. The antibody titer was negative for two HCWs in the first sample, positive in the rest of the samples, and positive in all samples in both follow-ups. In the second group, following two COVID-19 dosages, a total of 65 HCWs had tested positive for antibodies. The information of the 56 HCWs in group II who attended both follow-ups is as follows. Of the 56 HCWs, 15 (26.8%) were doctors, 27 (48.2%) were nurses, and 14 (25%) were others. The age range was 20-64 years, with a median (IQR) of 29.5 (22-37.7) and 31 (55.3%) female participants. The vaccination series had a median (IQR) interval of 32 (29-35) days between doses. There was a statistically significant difference in IgG levels of the three samples, χ2 = 31.107, p < 0.0001. Median (IQR) IgG levels of the three samples at 20 days, 3.8 months, and 7 months after the second dose were 2377.5, 1345.5, and 1257 U/mL, respectively. Spearman's rank order correlation was used to assess the association between IgG level and age in both groups. The relationship between IgG levels and age was weakly correlated and not statistically significant.
There is a waning of antibody titer over time postimmunization. A lower antibody titer can be a contributing factor for infections that emerge later. IgG levels postvaccination do not differ according to age.
Chavhan SS
,Dhikale PT
,Adsul BB
,Kinge KV
,Ingale AR
,Gokhale CN
,Jadhav N
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