Skip to main content
main-content
Erschienen in: BMC Infectious Diseases 1/2022

Open Access 28.01.2022 | COVID-19 | Research

Clinical characteristics of healthcare workers with SARS-CoV-2 infection after vaccination with BNT162b2 vaccine

verfasst von: Andrea Lombardi, Giulia Renisi, Dario Consonni, Massimo Oggioni, Patrizia Bono, Sara Uceda Renteria, Alessandra Piatti, Angela Cecilia Pesatori, Silvana Castaldi, Antonio Muscatello, Luciano Riboldi, Ferruccio Ceriotti, Andrea Gori, Alessandra Bandera

Erschienen in: BMC Infectious Diseases | Ausgabe 1/2022

Abstract

Background

The pandemic of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), had a significant impact worldwide. Vaccines against COVID-19 appear as a tool able to curb out mortality and reduce the circulation of the virus. Little is known so far about the clinical characteristics of individuals who developed SARS-CoV-2 infection after having received the vaccination, as well as the temporal relationship between vaccine administration and symptoms onset.

Methods

Retrospective cohort study among the 3219 healthcare workers (HCWs) of the Fondazione IRCCS Ospedale Maggiore Policlinico of Milano who received a full immunization with the BNT162b2 vaccine and who developed SARS-CoV-2 infection (documented through positive RT-PCR on nasopharyngeal swab) in March–April 2021.

Results

Overall, we have identified 15 HCWs with SARS-CoV-2 infection after vaccination, 7 (46.7%) of them were male and the mean age was 38.4 years (SD 14). In 4 of them, the presence of SARS-CoV-2 anti-nucleocapsid (anti-N) antibodies was assessed before vaccination and resulted positive in 1 case. In all HCWs the presence of SARS-CoV-2 anti-spike (anti-S1) antibodies was assessed, on average 42.2 days after the completion of vaccination, with a mean value of 2055 U/mL (SD 1927.3). SARS-CoV-2 infection was ascertained on average 56.2 days after vaccination. The mean cycle threshold (Ct) of SARS-CoV-2 PCR was 26.4, the lineage was characterized in 9 HCWs. None of the HCWs reported a primary or secondary immunodeficiency. Regarding symptoms, they were reported only by 7 (46.7%) HCWs and appeared on average 55 days after the second dose of vaccination. Of those who reported symptoms, one (14.3%) had fever, 7 (100%) rhinitis/conjunctivitis, 4 (57.1%) taste and smell alterations, none had respiratory symptoms, 4 headache/arthralgia (57.1%) and 1 gastrointestinal symptom (14.3%). All symptoms disappeared in a few days and no other unclassified symptoms were reported.

Conclusions

Infections occurring after vaccination with the BNT162b2 vaccine are mostly asymptomatic and are not associated with the serum titre of anti-S1 antibodies. We did not find a predominance of specific viral variants, with several lineages represented.
Hinweise

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Abkürzungen
COVID-19
Coronavirus disease 2019
SARS-CoV-2
Severe acute respiratory syndrome coronavirus 2
HCWs
Healthcare workers
ECLIA
Electrochemiluminescence immunoassay

Background

The pandemic of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused significant morbidity and mortality. Vaccines against COVID-19 appear as a tool able to curb out mortality and reduce the circulation of the virus. Consequently, mass vaccination campaigns are ongoing worldwide [1, 2]. Healthcare workers (HCWs) are a population who has been vaccinated early in the pandemic due to their high exposure to the virus, the corresponding elevated risk of infection and the possible role in spreading the disease [3].
Little is known so far about the clinical characteristics of HCWs who developed SARS-CoV-2 infection after having received the vaccination, as well as the temporal relationship between vaccine administration and symptoms onset. To answer these questions, we conducted a retrospective study among the HCWs vaccinated with BNT162b2 who developed SARS-CoV-2 infection (documented through positive RT-PCR on nasopharyngeal swab) in a large university hospital, collecting their clinical characteristics.

Methods

All the HCWs of the IRCCS Ospedale Maggiore Policlinico, a university hospital in Milan, Italy, were offered the COVID-19 vaccination with BNT162b2 vaccine. Among the 3622 HCWs working in our centre at the time of the study, 3219 (88.9%) received the full schedule, 170 (4.7%) received only the first shot and 233 (6.4%) were not vaccinated. The two prescribed shots were administered during January and February 2021. The HCWs of our hospital who are working in direct contact with proven or possible COVID-19 patients are subject to mandatory surveillance nasopharyngeal swab (NPS) for SARS-CoV-2 every two weeks, irrespective of the presence of symptoms. We collected the demographic, clinical and virologic characteristics of those who had positive NPSs in the period 01/03/2021–30/04/2021. For SARS-CoV-2 RNA detection was used the Alinity m SARS-CoV-2 assay on Alinity m (Abbott Molecular, IL, USA). The test is an rRT-PCR that allow simultaneous detection of RdRp and N genes. Serologic analyses were performed with two electrochemiluminescence immunoassay (ECLIA), Elecsys Anti-SARS-CoV-2 and Elecsys Anti-SARS-CoV-2 Son Cobas e801 (Roche Diagnostic, Mannheim, Germany) for the detection of total antibodies (including IgG) directed against SARS-CoV-2 nucleocapsid (N) antigen and SARS-CoV-2 spike protein receptor-binding domain (RBD) respectively. Full genome sequences were obtained by amplifying using CleanPlex for SARS-CoV-2 Research and Surveillance NGS panel (Paragon Genomics, Hayward CA, USA). A library was prepared with the PCR products and sequencing was performed on the Illumina MiSeq platform. The results were aligned to the reference genome NC_045512.2 by SOPHiA DDM software, v4 (SOPHiA GENETICS, USA). The software used to assign lineages to SARS CoV-2 sequences was Phylogenetic Assignment of Named Global Outbreak LINeages (Pango COVID-19 Lineage Assigner) [4, 5]. Descriptive statistics were obtained for all the variables collected, analyses were performed with Stata 17 (StataCorp. 2019). All the enrolled patients signed written informed consent. The study protocol (#828_2021) was approved by the local (Milano Area 2) Ethics Committee.

Results

Overall, we have identified 15 HCWs with SARS-CoV-2 infection after vaccination, 7 (46.7%) of them were male and the mean age was 38.4 years (SD 14). In 4 of them, the presence of SARS-CoV-2 anti-nucleocapsid (anti-N) antibodies was assessed before vaccination and resulted positive in 1 case. In all HCWs the presence of SARS-CoV-2 anti-spike (anti-S1) antibodies was assessed, on average 42.2 days after the completion of vaccination, with a mean value of 2055 U/mL (SD 1927.3). SARS-CoV-2 infection was ascertained on average 56.2 days after vaccination. The mean cycle threshold (Ct) of SARS-CoV-2 PCR was 26.4, the lineage was characterized in 9 HCWs (Table 1). None of the HCWs reported a primary or secondary immunodeficiency.
Table 1
Demographic and virologic characteristics of patients vaccinated with BNT162b2 with documented SARS-CoV-2 infection through positive RT-PCR on nasopharyngeal swab
ID
Age
Sex
Previous COVID-19
Days between vaccination and serology
Anti-S1 antibodies (U/mL)
Days between vaccination and symptoms
Days between vaccination and positive swab
Ct
Lineage
1
29
M
Unknown
24
2974
No symptoms
36
41
Unknown
2
28
F
Unknown
46
460
No symptoms
29
36.5
Unknown
3
29
M
No
82
866
26
24
21.8
B.1.351
4
28
F
Unknown
63
3787
No symptoms
29
14.2
B.1.1.241
5
60
M
Unknown
36
353
63
65
16.5
C.36
6
28
F
Unknown
35
3838
No symptoms
72
21.6
C.36
7
38
F
Unknown
37
1902
50
51
17.8
P.1
8
22
F
Unknown
65
1925
No symptoms
66
34.5
Unknown
9
46
M
No
34
637
58
58
16.6
B.1.1.7
10
31
M
Unknown
36
1493
34
35
19.8
B.1.525
11
57
M
Unknown
37
162
No symptoms
70
41.9
Unknown
12
39
F
Yes
36
 > 7500
93
95
39.6
Unknown
13
66
M
No
40
1115
No symptoms
109
20.4
C.11
14
48
F
Unknown
28
2790
No symptoms
49
39.4
Unknown
15
26
F
Unknown
34
1005
55
55
14.1
B.1.177.7
CT cycle threshold
Regarding symptoms, they were reported only by 7 (46.7%) HCWs and appeared on average 55 days after the second dose of vaccine. Of those who reported symptoms, one (14.3%) had fever, 7 (100%) rhinitis/conjunctivitis, 4 (57.1%) taste and smell alterations, none had respiratory symptoms, 4 headache/arthralgia (57.1%) and 1 gastrointestinal symptom (14.3%). All symptoms disappeared in a few days and no other unclassified symptoms were reported (Table 2).
Table 2
Symptoms reported at time of positive nasopharyngeal swab in patients vaccinated with BNT162b2 with documented SARS-CoV-2 infection through positive RT-PCR
ID
Symptoms
Fever
Rhinitis/conjunctivitis
Taste/Smell alterations
Cough/dyspnoea
Headache/arthralgia
GI symptoms
Other
1
No
No
No
No
No
No
No
No
2
No
No
No
No
No
No
No
No
3
Yes
No
Yes
Yes
No
Yes
No
No
4
No
No
No
No
No
No
No
No
5
Yes
No
Yes
No
No
Yes
No
No
6
No
No
No
No
No
No
No
No
7
Yes
No
Yes
Yes
No
No
No
No
8
No
No
No
No
No
No
No
No
9
Yes
No
Yes
No
No
Yes
Yes
No
10
Yes
No
Yes
Yes
No
No
No
No
11
No
No
No
No
No
No
No
No
12
Yes
No
Yes
No
No
Yes
No
No
13
No
No
No
No
No
No
No
No
14
No
No
No
No
No
No
No
No
15
Yes
Yes
Yes
Yes
No
No
No
No
GI gastrointestinal

Discussion

We have identified 15 HCWs who developed SARS-CoV-2 infection after completing the vaccination schedule with the BNT162b2 vaccine. Symptoms were reported by less than half of those included in the study, were mild, with only one case of fever, and disappeared quickly. The infections were detected through the mandatory surveillance system applied in our hospital, on average almost 2 months after the completion of the vaccination schedule.
The absence of important symptoms is a reassuring finding, which confirms the data about the efficacy of the BNT162b2 vaccine in preventing the severe form of COVID-19 reported in the registration study [6]. Intriguingly is the high incidence of rhinitis and conjunctivitis, which resulted in the most frequently reported symptom. Conjunctivitis is usually reported in about 1% of COVID-19 patients, with a higher prevalence (3%) among severe cases. The expression on the conjunctiva of the entry receptor for SARS-CoV-2, ACE-2, is disputed [7, 8], even though it has been shown how the inoculation in the ocular conjunctiva of SARS-CoV-2 can cause mild COVID-19 in rhesus macaques [9]. It is possible to speculate that the conjunctiva represents the site with the highest viral concentration in patients with the infection after vaccination, and this is reflected by the presence of a vigorous inflammatory response. Further studies are necessary to assess the concentration of immunoglobulins against SARS-CoV-2 in the ocular fluids after vaccination and their neutralizing activity.
In a previous publication from our group, we described how SARS-CoV-2 reinfections occurring in HCWs with a previous diagnosis of COVID-19 were mostly asymptomatic (7/9) [10]. Instead, we have previously observed during the first wave of COVID-19 pandemic how only a minority of HCWs has asymptomatic SARS-CoV-2 infections (17/139) [11]. This reinforces the concept of reduced/absent symptoms in those who probably have developed immunity against SARS-CoV-2, both through infection or vaccination.
Regarding the mean value of the serum anti-S1 antibodies, we observed in those who developed SARS-CoV-2 infection a value superior to the mean value of all the vaccinated HCWs of our hospital (1577 U/mL) and also superior to the mean value of the vaccinated HCWs without a previous SARS-CoV-2 infection (1374 U/mL) [12]. This suggest that the raw value of the anti-S1 antibodies cannot predict the future development of infection, the neutralizing activity of these antibodies could be a better tool to predict the efficacy of the humoral response.
Interestingly, we did not find a predominance of specific viral variants, with several lineages represented. This is in accordance with published data, which highlighted a reduced but still efficacious immune response against viral variants in those vaccinated with BNT162b2, and suggest that the risk of infection after vaccination is not currently related to the viral genotype but to other variables yet to be uncovered [1, 13]. Of note, the prevalence of SARS-CoV-2 lineages detected is adherent to the Italian scenario at the time, with the Alpha variant the most frequently reported [14].
A limitation of our study is the short observation time post-vaccination, restricted to two months, which led to the identification of only 15 infections post-vaccination in a large cohort of HCWs. A longer observation time might have led to the identification of a higher number of cases, increasing the chance of also finding infections with severe clinical manifestations.

Conclusions

Infections occurring after vaccination with the BNT162b2 vaccine are mostly asymptomatic and are not associated with the serum titre of anti-S1 antibodies.

Acknowledgements

None.

Declarations

All the enrolled patients signed a written informed consent. The study protocol (#828_2021) was approved by the local (Milano Area 2) Ethics Committee.

Competing interests

We declare that we have no conflicts of interest.
Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://​creativecommons.​org/​licenses/​by/​4.​0/​. The Creative Commons Public Domain Dedication waiver (http://​creativecommons.​org/​publicdomain/​zero/​1.​0/​) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Literatur
2.
Zurück zum Zitat Lombardi A, Bozzi G, Ungaro R, Villa S, Castelli V, Mangioni D, et al. Mini review immunological consequences of immunization with COVID-19 mRNA vaccines: preliminary results. Front Immunol. 2021;12:677. CrossRef Lombardi A, Bozzi G, Ungaro R, Villa S, Castelli V, Mangioni D, et al. Mini review immunological consequences of immunization with COVID-19 mRNA vaccines: preliminary results. Front Immunol. 2021;12:677. CrossRef
6.
Zurück zum Zitat Polack FP, Thomas SJ, Kitchin N, Absalon J, Gurtman A, Lockhart S, et al. Safety and efficacy of the BNT162b2 mRNA covid-19 vaccine. N Engl J Med. 2020;383(27):2603–15. CrossRef Polack FP, Thomas SJ, Kitchin N, Absalon J, Gurtman A, Lockhart S, et al. Safety and efficacy of the BNT162b2 mRNA covid-19 vaccine. N Engl J Med. 2020;383(27):2603–15. CrossRef
8.
Zurück zum Zitat Lange C, Wolf J, Auw-Haedrich C, Schlecht A, Boneva S, Lapp T, et al. Expression of the COVID-19 receptor ACE2 in the human conjunctiva. J Med Virol. 2020;92(10):2081–6. CrossRef Lange C, Wolf J, Auw-Haedrich C, Schlecht A, Boneva S, Lapp T, et al. Expression of the COVID-19 receptor ACE2 in the human conjunctiva. J Med Virol. 2020;92(10):2081–6. CrossRef
9.
Zurück zum Zitat Deng W, Bao L, Gao H, Xiang Z, Qu Y, Song Z, et al. Ocular conjunctival inoculation of SARS-CoV-2 can cause mild COVID-19 in rhesus macaques. Nat Commun. 2020;11(1):1–7. CrossRef Deng W, Bao L, Gao H, Xiang Z, Qu Y, Song Z, et al. Ocular conjunctival inoculation of SARS-CoV-2 can cause mild COVID-19 in rhesus macaques. Nat Commun. 2020;11(1):1–7. CrossRef
10.
Zurück zum Zitat Comelli A, Consonni D, Lombardi A, Viero G, Oggioni M, Bono P, et al. Nasopharyngeal testing among healthcare workers (HCWs) of a Large University Hospital in Milan, Italy during two epidemic waves of COVID-19. Int J Environ Res Public Health. 2021;18(16):8748. CrossRef Comelli A, Consonni D, Lombardi A, Viero G, Oggioni M, Bono P, et al. Nasopharyngeal testing among healthcare workers (HCWs) of a Large University Hospital in Milan, Italy during two epidemic waves of COVID-19. Int J Environ Res Public Health. 2021;18(16):8748. CrossRef
11.
Zurück zum Zitat Lombardi A, Consonni D, Carugno M, Bozzi G, Mangioni D, Muscatello A, et al. Characteristics of 1573 healthcare workers who underwent nasopharyngeal swab testing for SARS-CoV-2 in Milan, Lombardy, Italy. Clin Microbiol Infect. 2020;26(10):1413. CrossRef Lombardi A, Consonni D, Carugno M, Bozzi G, Mangioni D, Muscatello A, et al. Characteristics of 1573 healthcare workers who underwent nasopharyngeal swab testing for SARS-CoV-2 in Milan, Lombardy, Italy. Clin Microbiol Infect. 2020;26(10):1413. CrossRef
14.
Zurück zum Zitat Prevalenza e distribuzione delle varianti del virus SARS-CoV-2 di interesse per la sanità pubblica in Italia. Prevalenza e distribuzione delle varianti del virus SARS-CoV-2 di interesse per la sanità pubblica in Italia.
Metadaten
Titel
Clinical characteristics of healthcare workers with SARS-CoV-2 infection after vaccination with BNT162b2 vaccine
verfasst von
Andrea Lombardi
Giulia Renisi
Dario Consonni
Massimo Oggioni
Patrizia Bono
Sara Uceda Renteria
Alessandra Piatti
Angela Cecilia Pesatori
Silvana Castaldi
Antonio Muscatello
Luciano Riboldi
Ferruccio Ceriotti
Andrea Gori
Alessandra Bandera
Publikationsdatum
28.01.2022

Weitere Artikel der Ausgabe 1/2022

BMC Infectious Diseases 1/2022 Zur Ausgabe

Corona-Update

Die aktuelle Entwicklung im Überblick: Nachrichten, Webinare, Übersichtsarbeiten.

Passend zum Thema

ANZEIGE
Update Allergologie

Anaphylaxie – Adrenalin im Fokus

Zum Thema Corona-Impfungen und schwere allergische Reaktionen besteht nach wie vor viel Verunsicherung und ein hoher Informationsbedarf. Was im seltenen Anaphy­laxie-Fall zu tun ist, aktuelle Da­ten und Hin­ter­grün­de erläutert Prof. Ludger Klimek, Zentrum für Rhinologie und Allergologie, Wiesbaden.

Passend zum Thema

ANZEIGE

Fragen und Antworten zur COVID-19-Impfung

In diesem Beitrag finden Sie Antworten auf häufig gestellte Fragen zu den Coronaimpfungen. Beantwortet von Prof. Dr. med. Ulrich Heininger, Basel.

ANZEIGE

Dysphagie Screening Tool Geriatrie (DSTG)

Ende 2019 ist das neue Dysphagie Screening Tool Geriatrie (DSTG) der AG Dysphagie der Deutschen Gesellschaft für Geriatrie (DGG) erschienen.

ANZEIGE

consilium – Expertenwissen zu Themen aus dem Praxisalltag der Allgemeinmedizin und der Geriatrie

Das consilium Allgemeinmedizin/Geriatrie von InfectoPharm vermittelt Ihnen Expertenwissen zu Themen aus Ihrer alltäglichen Praxis. Dabei geht es in der Regel um aktuelle spannende Patientenfälle, relevante Therapiefragen oder Fragen zu geeigneten diagnostischen Maßnahmen sowie möglichen Differenzialdiagnosen. Machen Sie sich selbst ein Bild!

Passend zum Thema

ANZEIGE

COPD und nicht-invasive Behandlungsmethoden

Nicht-medikamentöse Behandlungsmethoden wie die nicht-invasive Beatmung (NIV) können die Leistungsfähigkeit und Lebensqualität von COPD-Patienten erheblich verbessern und das Sterberisiko senken. Die NIV-Therapie zur Behandlung von fortgeschrittener COPD hat Eingang in die neuen S2k-Leitlinien zur COPD-Therapie gefunden.

ANZEIGE

Neue Technologien bei außerklinischer NIV von COPD-Patienten

Einer aktuellen Studie von McDowell et. al.[1] zufolge kann im Gegensatz zur klinischen nicht-invasiven Beatmung (NIV) die außerklinische NIV in Ergänzung mit Telemonitoring und einem Hybridmodus den Zeitraum bis zur Rehospitalisierung oder zum Tod von hyperkapnischen COPD-Patienten verlängern.

ANZEIGE

Auch für ältere Patienten empfiehlt sich nicht-invasive Langzeitbeatmung

Nicht-invasive Beatmung ist für Menschen mit chronisch hyperkapnisch respiratorischer Insuffizienz eine bewährte Therapie. Eine Schweizer Studie untersuchte die Auswirkungen der Beatmung auf über 75-Jährige und belegt nun deren Wirksamkeit.

Passend zum Thema

ANZEIGE

Impfempfehlungen für Gesunde 60+: Johanna F.*

Die gesunde 61-jährige Johanna F.* erwartet ihr 1. Enkelkind: Von ihrem Hausarzt möchte sie erfahren, welche Impfungen bei ihr fehlen könnten. Mehr hier!

ANZEIGE

Masern & Co.: Fallzahlen in Zeiten der Pandemie

Wie hat sich die COVID-19-Pandemie auf die Fallzahlen von Masern, Mumps, Röteln, Keuchhusten und Windpocken ausgewirkt? Und welches Vorgehen empfiehlt die STIKO bei Routineimpfungen in Pandemie-Zeiten? Antworten und 8 Tipps zur Praxis-Organisation bei Routineimpfungen, hier!

ANZEIGE

Impfungen – vom Säugling bis zum Senior

Als eines der global führenden Gesundheitsunternehmen besitzt MSD mehr als 100 Jahre Erfahrung in der Entwicklung von Impfstoffen. Hier finden Sie Informationen zu einigen der von der STIKO empfohlenen Immunisierungen, z.B. der MMRV- und der HPV-Impfung sowie der Pneumokokken-Impfung für Senioren.

Passend zum Thema

ANZEIGE
Starkes Extrakt-Doppel

Thymian und Primel: Sekretolytisch und so bronchienberuhigend

Mit den Fixkombinationen aus Thymiankraut und Primelwurzeln in einigen Bronchicum®-Präparaten gehen Hustenattacken nachweislich [1] spürbar rasch zurück. Dank der guten Verträglichkeit und nachgewiesenen Wirksamkeit [1] ist Bronchicum® eine gute Empfehlung für die ganze Familie.