Comprehensive assessment of humoral response after Pfizer BNT162b2 mRNA Covid-19 vaccination: a three-case series

Background. Since universal vaccination is a pillar against coronavirus disease 2019 (COVID-19), monitoring anti-SARS-CoV-2 neutralizing antibodies is essential for deciphering post-vaccination immune response. Methods. Three healthcare workers received 30 μg BNT162b2 mRNA Covid-19 Vaccine, followed by a second identical dose, 21 days afterwards. Venous blood was drawn at baseline and at serial intervals, up to 63 days afterwards, for assessing total immunoglobulins (Ig) anti-RBD (receptor binding domain), IgG anti-S1/S2, IgG anti-RBD, IgM anti-RBD, IgM anti-N/S1 and IgA anti-S1. Results. All subjects were SARS-CoV-2 seronegative at baseline. Total Ig anti-RBD, IgG anti-S1/S2 and IgG anti-RBD levels increased between 91-368 folds until 21 days after the first vaccine dose, then reached a plateau. The levels raised further after the second dose (by ~30-, ~8- and ~8-fold, respectively), peaking at day 35, but then slightly declining and stabilizing ~50 days after the first dose. IgA anti-S1 levels increased between 7-11 days after the first dose, slightly declined before the second dose, after which levels augmented by ~24-fold from baseline. The anti-RBD and anti-N/S1 IgM kinetics were similar to that of anti-S1 IgA, though displaying substantially weaker increases and modest peaks, only 4 to 7-fold higher than baseline. Highly significant inter-correlation was noted between total Ig anti-RBD, anti-S1/S2 and anti-RBD IgG (all r=0.99), whilst other anti-SARS-CoV-2 antibodies displayed lower, though still significant, correlations. Serum spike protein concentration was undetectable at all time points. Conclusions. BNT162b2 mRNA vaccination generates a robust humoral immune response, especially involving IgG and IgA, magnified by the second vaccine dose.

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Comprehensive assessment of humoral response after Pfizer BNT162b2 mRNA Covid-19 vaccination: a three-case series

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2021-0339 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Elisa Danese ◽

Martina Montagnana ◽

Gian Luca Salvagno ◽

Denise Peserico ◽

Laura Pighi ◽

...

Keyword(s):

Immune Response ◽

Neutralizing Antibodies ◽

Healthcare Workers ◽

Protein Concentration ◽

Venous Blood ◽

Case Series ◽

Vaccine Dose ◽

Humoral Response ◽

Post Vaccination ◽

Humoral Immune

Abstract Objectives Since universal vaccination is a pillar against coronavirus disease 2019 (COVID-19), monitoring anti-SARS-CoV-2 neutralizing antibodies is essential for deciphering post-vaccination immune response. Methods Three healthcare workers received 30 μg BNT162b2 mRNA Covid-19 Pfizer Vaccine, followed by a second identical dose, 21 days afterwards. Venous blood was drawn at baseline and at serial intervals, up to 63 days afterwards, for assessing total immunoglobulins (Ig) anti-RBD (receptor binding domain), anti-S1/S2 and anti-RBD IgG, anti-RBD and anti-N/S1 IgM, and anti-S1 IgA. Results All subjects were SARS-CoV-2 seronegative at baseline. Total Ig anti-RBD, anti-S1/S2 and anti-RBD IgG levels increased between 91 and 368 folds until 21 days after the first vaccine dose, then reached a plateau. The levels raised further after the second dose (by ∼30-, ∼8- and ∼8-fold, respectively), peaking at day 35, but then slightly declining and stabilizing ∼50 days after the first vaccine dose. Anti-S1 IgA levels increased between 7 and 11 days after the first dose, slightly declined before the second dose, after which levels augmented by ∼24-fold from baseline. The anti-RBD and anti-N/S1 IgM kinetics were similar to that of anti-S1 IgA, though displaying substantially weaker increases and modest peaks, only 4- to 7-fold higher than baseline. Highly significant inter-correlation was noted between total Ig anti-RBD, anti-S1/S2 and anti-RBD IgG (all r=0.99), whilst other anti-SARS-CoV-2 antibodies displayed lower, though still significant, correlations. Serum spike protein concentration was undetectable at all-time points. Conclusions BNT162b2 mRNA vaccination generates a robust humoral immune response, especially involving anti-SARS-Cov-2 IgG and IgA, magnified by the second vaccine dose.

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Assessment of Post-Vaccination Antibody Response Eight Months after the Administration of BNT1622b2 Vaccine to Healthcare Workers with Particular Emphasis on the Impact of Previous COVID-19 Infection

Vaccines ◽

10.3390/vaccines9121508 ◽

2021 ◽

Vol 9 (12) ◽

pp. 1508

Author(s):

Blanka Wolszczak-Biedrzycka ◽

Anna Bieńkowska ◽

Justyna Dorf

Keyword(s):

Healthcare Workers ◽

Venous Blood ◽

Vaccine Dose ◽

Post Vaccination ◽

Vaccination Programs ◽

Humoral Immune ◽

History Of ◽

Antibody Titers ◽

Antibody Levels ◽

The Impact

At the end of 2020, COVID-19 vaccination programs were initiated in many countries, including Poland. The first vaccine approved in Poland was the BNT162b2 mRNA preparation (Pfizer/BioNTech), and the first vaccinated group were healthcare workers. The aim of the present study was to evaluate post-vaccine antibody titers 8 months after the second vaccine dose had been administered to a group of employees of the Hospital of the Ministry of the Interior and Administration in Olsztyn (Poland). The employees were divided into two groups: persons who had COVID-19 in the fourth quarter of 2020 and were vaccinated in January–February 2021, and persons without a history of COVID-19 who were vaccinated during the same period. The analyzed material was venous blood serum collected from 100 hospital employees on 23–28 September 2021. The level of anti-SARS-CoV-2 S antibodies was measured with a Roche Cobas e411 analyzer using the electrochemiluminescence (ECLIA) method. The study demonstrated that persons with a history of SARS-CoV-2 infection had significantly higher antibody levels (taking into account gender, age, type of work performed, and severity of post-vaccination symptoms) than employees without a history of COVID-19. The study also revealed that the type of work, age, gender, and the course of SARS-CoV-2 infection can influence the humoral immune response. The presented results may prove helpful in the context of administering additional vaccine doses.

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Should be a Third Dose of BNT162b2 mRNA COVID-19-Vaccine Administered in Patients with Myelofibrosis Under Ruxolitinib?

Blood ◽

10.1182/blood-2021-146381 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 2573-2573

Author(s):

Giovanni Caocci ◽

Olga Mulas ◽

Daniela Mantovani ◽

Alessandro Costa ◽

Andrea Galizia ◽

...

Keyword(s):

Immune Response ◽

Humoral Immune Response ◽

Present Report ◽

Univariate Analysis ◽

Vaccine Dose ◽

Humoral Response ◽

The Other ◽

World Health ◽

International Prognostic Scoring System ◽

Humoral Immune

Abstract Introduction. Patients with Myelofibrosis (MF) are considered fragile and thus eligible in Italy for COVID-19 BNT162b2 mRNA vaccination. According to the International Prognostic Scoring System (IPSS), patients with intermediate and high MF, may receive clinical benefits from ruxolitinib, the first approved JAK1/JAK2 inhibitor. Given the potent anti-inflammatory properties of ruxolitinib against immunocompetent cells, we previously reported a lower but non-statistically absolute IgG anti-Spike humoral response in vaccinated MF patients treated with ruxolitinib. In the present report we extended the cohort of MF patients. Methods. All MF patients received 2 injections of 30 ug per dose of BNT162b2 mRNA COVID-19 vaccine 3 weeks apart, according to the standard protocol. After injection, mild pain at the injection site was frequently reported. No serious adverse events were registered. The serum level of IgG anti-Spike glycoprotein was tested after a median time of 45 days (range 40-60) from the second vaccine dose, using the approved anti-SARS-CoV-2 IgG CLIA (LIAISON® SARS-CoV-2 TrimericS IgG assay, Diasorin, Saluggia, Italy). An Arbitrary Units per milliliter (AU/mL) ratio of <12.0 was considered to be negative, 12.0-15.0 AU/mL to be borderline and >15 AU/mL to be positive. A conversion of AU/mL to binding antibody units (BAU/mL) as recommended by the World Health Organization (WHO) guidelines was achieved considering the following equation: BAU/mL = 2.6*AU/mL. Results. Overall, 30 MF patients (median age 65 years, range 48-83) were vaccinated. A diagnosis of primary MF was reported in 21 cases (70%), post essential thrombocythemia-MF in 6 (20%) patients and post polycythemia vera-MF in 3 (10%) patients; 23 out of 30 patients (76.6%) were positive for the JAK2V617F, 5 (16.6%) for CALR mutation, 1 (3.3%) for MPL mutation and 1 patient (3.3%) resulted triple negative. Splenomegaly was observed in 14 patients (46%) and 19 (63.3%) reported comorbidities. Nineteen patients (63.3%) were classified as DIPSS low or intermediate-1 risk, and 11 (36.6%) as intermediate-2 or high risk. Fifteen patients (50%) were receiving ruxolitinib, at a median total dose of 20 mg/die (range 20-40 mg) and the remaining 15 patients other treatments (8 patients hydroxyurea and 7 only supportive therapy). None of the patients reported COVID-19 infection neither previous nor subsequently to vaccination. Overall, a positive immune response against COVID-19 was observed in 8 out of 15 patients (53.3%) in the ruxolitinib group, in comparison with 13 out 15 patients (86.6%) in the other treatment group (p=0,046). The absolute IgG anti-Spike value was lower in the ruxolitinib group (median 35.2±49.81) in comparison with the other group (median 226.1±163.9; p=<0.001), Figure 1. In univariate analysis, only ruxolitinib treatment was found associated with a lower humoral immune response to the vaccine. Conclusions. MF patients under ruxolitinib achieved a lower humoral immune response in comparison with MF patients who underwent other treatments. No COVID-19 infection was observed in both groups after vaccination, after a median follow up of 3 months since the second dose. Whether patients with a potential insufficient humoral response to vaccine will benefit from a third dose of BNT162b2 mRNA COVID-19 vaccine is a matter of further investigation. Our preliminary data need to be confirmed in larger cohort of MF patients. Figure 1 Figure 1. Disclosures Murru: Abbvie: Consultancy, Honoraria, Other: travel and accommodation; Janssen: Consultancy, Honoraria.

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Function is more reliable than quantity to follow up the humoral response to the Receptor Binding Domain of SARS- CoV-2 Spike Protein after Natural Infection or COVID-19 vaccination

10.1101/2021.06.02.21257975 ◽

2021 ◽

Author(s):

Carlos A Sariol ◽

Petraleigh Pantoja ◽

Crisanta Serrano-Collazo ◽

Tiffant Rosa-Arocho ◽

Albersy Armina ◽

...

Keyword(s):

Immune Response ◽

Neutralizing Antibodies ◽

Natural Infection ◽

Vaccine Dose ◽

Humoral Response ◽

Neutralizing Antibody ◽

Viral Neutralization ◽

Neutralizing Activity ◽

Robust Immune Response

On this work we report that despite of a decline in the total anti-Spike antibodies the neutralizing antibodies remains at a similar level for an average of 98 days in a longitudinal cohort of 59 Hispanic/Latino exposed to SARS-CoV-2. We are also reporting that the percentage of neutralization correlates with the IgG titers and that in the first collected samples, IgG1 was the predominant isotype (62.71%), followed by IgG4 (15.25%), IgG3 (13.56%), and IgG2 (8.47%) during the tested period. The IgA was detectable in 28.81% of subjects. Only 62.71% of all subjects have detectable IgM in the first sample despite of confirmed infection by a molecular method. Our data suggests that 100% that seroconvert make detectable neutralizing antibody responses measured by a surrogate viral neutralization test. We also found that the IgG titers and neutralizing activity were higher after the first dose in 10 vaccinated subjects out of the 59 with prior infection compare to a subgroup of 21 subjects naive to SARS-CoV-2. One dose was enough but two were necessary to reach the maximum percentage of neutralization in subjects with previous natural infection or naive to SARS-CoV-2 respectively. Like the pattern seen after the natural infection, after the second vaccine dose, the total anti-S antibodies and titers declined but not the neutralizing activity which remains at same levels for more than 80 days after the first vaccine dose. That decline, however, was significantly lower in pre-exposed individuals which denotes the contribution of the natural infection priming a more robust immune response to the vaccine. Also, our data indicates that the natural infection induces a more robust humoral immune response than the first vaccine dose in unexposed subjects. However, the difference was significant only when the neutralization was measured but not by assessing the total anti-S antibodies or the IgG titers. This work is an important contribution to understand the natural immune response to the novel coronavirus in a population severely hit by the virus. Also provide an invaluable data by comparing the dynamic of the immune response after the natural infection vs. the vaccination and suggesting that a functional test is a better marker than the presence or not of antibodies. On this context our results are also highly relevant to consider standardizing methods that in addition to serve as a tool to follow up the immune response to the vaccines may also provide a correlate of protection.

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Waning of IgG, Total and Neutralizing Antibodies 6 Months Post-Vaccination with BNT162b2 in Healthcare Workers

Vaccines ◽

10.3390/vaccines9101092 ◽

2021 ◽

Vol 9 (10) ◽

pp. 1092

Author(s):

Jean-Louis Bayart ◽

Jonathan Douxfils ◽

Constant Gillot ◽

Clara David ◽

François Mullier ◽

...

Keyword(s):

Half Life ◽

Neutralizing Antibodies ◽

Healthcare Workers ◽

Healthcare Professionals ◽

Humoral Response ◽

Clinical Effectiveness ◽

Antibody Assay ◽

Post Vaccination ◽

Antibody Decline

Data about the long-term duration of antibodies after SARS-CoV-2 vaccination are still scarce and are important to design vaccination strategies. In this study, 231 healthcare professionals received the two-dose regimen of BNT162b2. Of these, 158 were seronegative and 73 were seropositive at baseline. Samples were collected at several time points. The neutralizing antibodies (NAbs) and antibodies against the nucleocapsid and the spike protein of SARS-CoV-2 were measured. At day 180, a significant antibody decline was observed in seronegative (−55.4% with total antibody assay; −89.6% with IgG assay) and seropositive individuals (−74.8% with total antibody assay; −79.4% with IgG assay). The estimated half-life of IgG from the peak humoral response was 21 days (95% CI: 13–65) in seronegative and 53 days (95% CI: 40–79) in seropositive individuals. The estimated half-life of total antibodies was longer and ranged from 68 days (95% CI: 54–90) to 114 days (95% CI: 87–167) in seropositive and seronegative individuals, respectively. The decline of NAbs was more pronounced (−98.6%) and around 45% of the subjects tested were negative at day 180. Whether this decrease correlates with an equivalent drop in the clinical effectiveness against the virus would require appropriate clinical studies.

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Impact of Age and Sex on Antibody Response Following the Second Dose of COVID-19 BNT162b2 mRNA Vaccine in Greek Healthcare Workers

Microorganisms ◽

10.3390/microorganisms9081725 ◽

2021 ◽

Vol 9 (8) ◽

pp. 1725

Author(s):

Niki Vassilaki ◽

Antonios N. Gargalionis ◽

Anastasia Bletsa ◽

Nikolaos Papamichalopoulos ◽

Elisavet Kontou ◽

...

Keyword(s):

Healthcare Workers ◽

Venous Blood ◽

Age Groups ◽

Vaccine Dose ◽

Humoral Response ◽

Continuous Variables ◽

Igg Antibody ◽

Female Population ◽

Significant Difference ◽

Antibody Titers

Anti-SARS-CoV-2 spike RBD (receptor-binding domain) IgG antibody levels were monitored in 1643 volunteer healthcare workers of Eginition, Evangelismos, and Konstantopoulio General Hospitals (Athens, Greece), who underwent vaccination with two doses of COVID-19 BNT162b2 mRNA vaccine (Pfizer) and had no history of SARS-CoV-2 infection. Venous blood was collected 20–30 days after the second vaccine dose and anti-RBD IgG levels were determined using CMIA SARS-CoV-2 IgG II Quant (Abbott) on ARCHITECT i System or ADVIA Centaur SARS-CoV-2 IgG (Siemens) on Centaur XP platform. From the total population of 1643 vaccinees (533 M/1110 F; median age = 49; interquartile range-IQR = 40–56), 1636 (99.6%) had anti-SARS-CoV-2 IgG titers above the positivity threshold of the assay used. One-Way ANOVA Kruskal-Wallis H test showed a statistically significant difference in the median of antibody titers between the different age groups (p < 0.0001). Consistently, Spearman’s correlation coefficient (r) for IgGs and age as continuous variables was −0.2380 (p = 1.98 × 10−17). Moreover, antibody titers were slightly higher by 1.2-mean fold (p = 3 × 10−6) in the total female population of the three hospitals (median = 1594; IQR = 875–2584) as compared to males (median = 1292; IQR = 671.9–2188). The present study supports that BNT162b2 vaccine is particularly effective in producing high anti-SARS-CoV-2 IgG levels in healthy individuals, and this humoral response is age- and gender-dependent.

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Vaccine Breakthrough Infections by SARS-CoV-2 Variants after ChAdOx1 nCoV-19 Vaccination in Healthcare Workers

Vaccines ◽

10.3390/vaccines10010054 ◽

2021 ◽

Vol 10 (1) ◽

pp. 54

Author(s):

Pratibha Kale ◽

Ekta Gupta ◽

Chhagan Bihari ◽

Niharika Patel ◽

Sheetalnath Rooge ◽

...

Keyword(s):

Immune Response ◽

Single Dose ◽

Whole Genome Sequencing ◽

Genome Sequencing ◽

Humoral Immune Response ◽

Neutralizing Antibodies ◽

Healthcare Workers ◽

Genomic Analysis ◽

Whole Genome ◽

Humoral Immune

This study elucidated the clinical, humoral immune response and genomic analysis of vaccine breakthrough (VBT) infections after ChAdOx1 nCoV-19/Covishield vaccine in healthcare workers (HCWs). Amongst 1858 HCWs, 1639 had received either two doses (1346) or a single dose (293) of ChAdOx1 nCoV-19 vaccine. SARS-CoV-2 IgG antibodies and neutralizing antibodies were measured in the vaccinated group and the development of SARS-CoV-2 infection was monitored.Forty-six RT-PCR positive samples from the 203 positive samples were subjected to whole genome sequencing (WGS). Of the 203 (10.92%) infected HCWs, 21.46% (47/219) were non-vaccinated, which was significantly more than 9.52% (156/1639) who were vaccinated and infection was higher in doctors and nurses. Unvaccinated HCWs had 1.57 times higher risk compared to partially vaccinated HCWs and 2.49 times higher risk than those who were fully vaccinated.The partially vaccinated were at higher risk than the fully vaccinated (RR 1.58). Antibody non-response was seen in 3.44% (4/116), low antibody levels in 15.51% (18/116) and medium levels were found in 81.03% (94/116). Fully vaccinated HCWs had a higher antibody response at day 42 than those who were partially vaccinated (8.96 + 4.00 vs. 7.17 + 3.82). Whole genome sequencing of 46 samples revealed that the Delta variant (B.1.617.2) was predominant (69.5%). HCWs who had received two doses of vaccine showed better protection from mild, moderate, or severe infection, with a higher humoral immune response than those who had received a single dose. The genomic analysis revealed the predominance of the Delta variant (B.1.617.2) in the VBT infections.

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Total anti-SARS-CoV-2 antibodies measured 6 months after Pfizer-BioNTech COVID-19 vaccination in healthcare workers

Journal of Medical Biochemistry ◽

10.5937/jomb0-33999 ◽

2021 ◽

Author(s):

Giuseppe Lippi ◽

Gian Luca Salvagno ◽

Brandon Michael Henry ◽

Laura Pighi ◽

Simone De Nitto

Keyword(s):

Healthcare Workers ◽

Venous Blood ◽

Vaccine Dose ◽

Serum Levels ◽

Gradual Decline ◽

Post Vaccination ◽

Median Serum ◽

Study Population ◽

Kinetics Of

Background: This study aimed at monitoring the kinetics of serum total anti-SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) antibodies in a cohort of healthcare workers after voluntary vaccination with Pfizer-BioNTech coronavirus disease 2019 (COVID-19).Methods: The study population consisted of 787 healthcare workers (mean age 44±12 years; 66% females), who received two 30 μg doses of Pfizer-BioNTech COVID-19 vaccine, 3 weeks apart. Venous blood was drawn before the first vaccine dose, immediately before the second vaccine dose, and then at 1, 3 and 6 months after the second vaccine dose. Serological testing employed the total anti-SARS-CoV-2 antibodies measurement with Roche Elecsys Anti-SARS-CoV-2 S chemiluminescent immunoassay.Results: The median serum levels of total anti-SARS-CoV-2 antibodies reached the peak (1762 KU/L) 1 month after the second vaccine dose, but tended to progressively decline at the 3-month (1086 KU/L) and 6-month (802 KU/L) follow-up points. Overall, the values after 3- and 6-months were 37% and 57% lower than the corresponding concentrations measured at the peak. No healthcare worker had total anti-SARS-CoV-2 antibodies below the method-dependent cut-off. The decline compared to the peak was more accentuated in baseline seropositive persons than in those who were baseline seronegative (74% vs. 52%) cohort. The 6-month post-vaccination anti-SARS-CoV-2 antibodies in subjects aged <65 years remained over 2-fold higher than that measured in those aged ≥65 years (813 vs. 343 KU/L). Conclusions: Gradual decline of total anti-SARS-CoV-2 antibodies occurred 6 months after Pfizer-BioNTech COVID-19 vaccination, though values remained higher than the method-dependent cut-off, with no case of seronegativization.

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Longitudinal determination of mRNA-vaccination induced strongly binding SARS-CoV-2 IgG antibodies in a cohort of healthcare workers with and without prior exposure to the novel coronavirus

10.1101/2021.03.17.21253751 ◽

2021 ◽

Author(s):

Monika Korodi ◽

Kinga Rakosi ◽

Zsuzsanna Jenei ◽

Gabriella Hudak ◽

Istvan Horvath ◽

...

Keyword(s):

Immune Response ◽

Immune Responses ◽

Healthcare Workers ◽

Infected Group ◽

The Novel ◽

Post Vaccination ◽

Humoral Immune ◽

Novel Coronavirus

Mass vaccination against the disease caused by the novel coronavirus (COVID-19) is a crucial step in slowing the spread of SARS-CoV-2. The BioNTech/Pfizer (BNT162b2) vaccine has been shown to induce strong immune responses among the vaccinated population. Measuring SARS-CoV-2 anti-spike protein IgG levels is a clinically convenient way to estimate post-vaccination humoral immune responses, but only limited data exists about its short- and long-term dynamics. We present a longitudinal analysis of post-vaccination IgG levels in a cohort of 122 healthcare workers vaccinated with BNT162b2 with weekly follow-up until 35 days past the first dose and results of the first monthly follow-up after that for a subset of these. This prospective, multicenter cohort study consists of two periods for short-term and long-term evaluation of post-vaccination IgG levels. Tests were carried out on 666 samples from 122 participants, using in-house anti-spike 1 and anti-nucleocapsid IgG ELISA assays and a commercial, combined version of these. Participants with previous SARS-CoV-2 infection mount a quick immune response, reaching peak IgG levels two weeks after vaccination. In contrast, the corresponding IgG levels for previously uninfected participants increase gradually, changing abruptly after the booster dose. Overall higher IgG levels are maintained for the previously infected group 35-70 days after vaccination, and we observe age-dependence of immune response as well. Our results show a robust humoral immune response mounting gradually after the first vaccine dose for the uninfected group, and a much stronger immune response within 7-14 days after the first dose for the previously infected group.

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Clinicogenomic analysis of breakthrough infections by SARS CoV2 variants after ChAdOx1 nCoV- 19 vaccination in healthcare workers

10.1101/2021.06.28.21259546 ◽

2021 ◽

Author(s):

Pratibha Kale ◽

Ekta Gupta ◽

Chhagan Bihari ◽

Niharika Patel ◽

Sheetalnath Rooge ◽

...

Keyword(s):

Immune Response ◽

Humoral Immune Response ◽

Neutralizing Antibodies ◽

Healthcare Workers ◽

Genomic Analysis ◽

Hospital Staff ◽

Risk Of Infection ◽

Rt Pcr ◽

Humoral Immune ◽

Antibody Levels

Background: India saw a massive surge and emergence of SARS CoV2 variants. We elucidated clinical and humoral immune response and genomic analysis of vaccine breakthrough (VBT) infections after ChAdOx1 nCoV-19 vaccine in healthcare workers (HCWs). Methods: The study was conducted on 1858 HCWs receiving two doses of ChAdOx1 nCoV- 19 vaccine. Serial blood samples were collected to measure SARS CoV2 IgG and neutralizing antibodies. 46 RT-PCR positive samples from VBT infections were subjected to whole genome sequencing (WGS). Results: Infection was confirmed in 219 (11.79%) HCWs of which 21.46% (47/219) were non-vaccinated, significantly more (p <0.001) than 9.52% (156/1639) vaccinated group. VBT infections were significantly higher in doctors and nurses compared to other hospital staff (p <0.001). Unvaccinated individuals had 1.57 times higher risk of infection compared to partially vaccinated (p 0.02) and 2.49 times than fully vaccinated (<0.001). Partially vaccinated were at higher risk of infection than fully vaccinated (RR 1.58,p 0.01). There were 3 (1.36%) severe cases and 1 death in unvaccinated group compared to none in the vaccinated. Non-response after 14 days of second dose was seen in 6.5% (3/46) and low antibody levels (1-4.62 S/CO) in 8.69% (4/46). Delta variant (B.1.617.2) was dominant (69.5%) and reinfection was documented in 4 (0.06%) HCWs. Conclusions: Nearly one in ten vaccinated HCWs can get infected, more so with only single dose (13.65%) than two doses (8.62%). Fully vaccinated are better protected with higher humoral immune response. Genomic analysis revealed an alarming rise of Delta variant (B.1.617.2) in VBT infections.

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