Abstract
The aim of this study is to investigate the clinical profile of patients who developed coronavirus disease 2019 (COVID‐19) after full vaccination. Demographic, epidemiological and clinical data were collected through medical records and online patient‐reported outcome questionnaire from patients who developed symptomatic SARS‐CoV‐2 infection, confirmed by nasopharyngeal swab, at least 2 weeks after completion of vaccination. A total of 153 subjects were included. The most frequent symptoms were: asthenia (82.4%), chemosensory dysfunction (63.4%), headache (59.5%), runny nose (58.2%), muscle pain (54.9%), loss of appetite (54.3%), and nasal obstruction (51.6%). Particularly, 62.3% and 53.6% of subjects reported olfactory and gustatory dysfunction, respectively. Symptom severity was mild or moderate in almost all cases. Chemosensory dysfunctions have been observed to be a frequent symptom even in subjects who contracted the infection after full vaccination. For this reason, the sudden loss of smell and taste could continue to represent a useful and specific diagnostic marker to raise the suspicion of COVID‐19 even in vaccinated subjects. In the future, it will be necessary to establish what the recovery rate is in these patients.
Level of Evidence
4 Laryngoscope, 132:419–421, 2022
Keywords: COVID‐19, anosmia, ageusia, olfactory dysfunction, gustatory dysfunction, vaccination
INTRODUCTION
Vaccines are the main weapon to protect population from severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection. Vaccine safety has been widely demonstrated as well as their effectiveness in preventing the onset of severe coronavirus disease 2019 (COVID‐19). 1 The effectiveness in preventing symptomatic COVID‐19 is instead variable between 73% and 91% in patients with complete vaccination and for the currently known variants. 2 , 3 Furthermore, vaccines have been shown to be effective in reducing the duration of symptoms and accelerating viral clearance. 2 To the best of our knowledge there are no studies reporting the clinical pattern of COVID‐19 after complete vaccination. The knowledge of these clinical pictures is important for posing the diagnostic suspicion of infection and because probably (and hopefully) these forms of vaccine‐mitigated COVID‐19 will be the ones that will remain after the immunization of the population.
MATERIALS AND METHODS
An online questionnaire was released in August and September 2021 4 across Europe. The survey was aimed exclusively at subjects who had had symptomatic COVID‐19, confirmed by nasopharyngeal swab, at least 2 weeks after completion of vaccination. Compliance with the inclusion criteria was assessed with specific questions and subjects who did not meet them were excluded. The presence and severity of symptoms was investigated using the COVID‐19 symptom index. 5 The study was approved by the ethics committee of the University of Cagliari (PG/2021/7118).
RESULTS
Of the 176 responses collected, 23 were excluded as the subjects did not have a confirmed diagnosis so that 153 responses were considered in the analysis (99 females, 54 males, mean age 41.3 years). The anti‐SARS‐CoV‐2 vaccination was performed with Pfizer/BioNTech (106 cases), AstraZeneca (32 cases), Moderna (12 cases), or Johnson & Johnson (three cases) vaccines.
Table 1 shows the symptoms reported by the subjects. The most frequent were: asthenia (82.4%), chemosensory dysfunctions (CDs) (63.4%), and headache (59.5%). Particularly, 62.3% and 53.6% of subjects reported olfactory and gustatory dysfunction, respectively. Symptom severity was mild or moderate in almost all cases. There were no significant differences in the prevalence of CD between patients who received viral vector or mRNA vaccine.
TABLE 1.
COVID‐19 Symptom Index Results.
| No Problem | Mild Problem | Moderate Problem | Severe Problem | Very Severe Problem | |
|---|---|---|---|---|---|
| I had fever (>38°C) | 88 (57.5%) | 40 (26.1%) | 19 (12.4%) | 6 (3.9%) | 0 (0%) |
| I was tired | 27 (17.6%) | 57 (37.2%) | 57 (37.2%) | 6 (3.9%) | 6 (3.9%) |
| I had cough | 85 (55.6%) | 53 (34.6%) | 15 (9.8%) | 0 (0%) | 0 (0%) |
| I had chest pain | 130 (85%) | 20 (13.1%) | 3 (2%) | 0 (0%) | 0 (0%) |
| I had low/no appetite | 70 (45.7%) | 52 (34%) | 25 (16.3%) | 6 (3.9%) | 0 (0%) |
| I had joint pain | 78 (51%) | 55 (36%) | 12 (7.8%) | 6 (3.9%) | 2 (1.3%) |
| I had muscle pain | 69 (45.1%) | 55 (36%) | 23 (15%) | 6 (3.9%) | 0 (0%) |
| I had headache | 62 (40.5%) | 49 (32%) | 33 (21.6%) | 6 (3.9%) | 3 (2%) |
| I had diarrhea | 136 (88.9%) | 10 (6.5%) | 2 (1.3%) | 2 (1.3%) | 3 (2%) |
| I had abdominal pain | 145 (94.8%) | 3 (2%) | 2 (1.3%) | 3 (2%) | 0 (0%) |
| I had nausea or vomiting | 139 (91%) | 8 (5.2%) | 6 (3.9%) | 0 (0%) | 0 (0%) |
| I had conjunctivitis | 144 (94.1%) | 6 (3.9%) | 3 (2%) | 0 (0%) | 0 (0%) |
| I had urticarias | 145 (94.8%) | 6 (3.9%) | 2 (1.3%) | 0 (0%) | 0 (0%) |
| I had breathing difficulties | 132 (86.3%) | 18 (11.8%) | 3 (2%) | 0 (0%) | 0 (0%) |
| I had sticky throat mucus | 109 (71.2%) | 27 (17.6%) | 14 (9.1%) | 3 (2%) | 0 (0%) |
| I had nasal obstruction | 74 (48.4%) | 34 (22.2%) | 31 (20.3%) | 14 (9.1%) | 0 (0%) |
| I had runny nose | 64 (41.8%) | 54 (35.3%) | 25 (16.3%) | 10 (6.5%) | 0 (0%) |
| I had nasal burning | 76 (49.7%) | 55 (36%) | 22 (14.4%) | 0 (0%) | 0 (0%) |
| I had throat pain | 116 (75.8%) | 35 (22.9%) | 2 (1.3%) | 0 (0%) | 0 (0%) |
| I had ear pain or pressure | 123 (80.4%) | 23 (15%) | 7 (4.6%) | 0 (0%) | 0 (0%) |
| I had face pain or pressure | 122 (79.7%) | 26 (17%) | 2 (1.3%) | 0 (0%) | 3 (2%) |
| I had difficulties to swallow | 128 (83.7%) | 20 (13.1%) | 5 (3.3%) | 0 (0%) | 0 (0%) |
| I had hoarseness/voice difficulties | 113 (73.9%) | 28 (18.3%) | 12 (7.8%) | 0 (0%) | 0 (0%) |
| I had tongue burning | 136 (88.9%) | 15 (9.8%) | 2 (1.3%) | 0 (0%) | 0 (0%) |
| Unchanged | Partially Loss | Completely Loss | |
|---|---|---|---|
| During COVID‐19 my smell was | 58 (37.9%) | 32 (20.9%) | 63 (41.2%) |
| Unchanged | Reduced, Loss, or Modified | |
|---|---|---|
| During COVID‐19 my taste was | 71 (46.4%) | 82 (53.6%) |
DISCUSSION
As social distancing measures relax, vaccine‐mitigated forms of COVID‐19 are likely to become increasingly frequent or even endemic. It is therefore important to know their clinical pictures to predict their social and health impact. In the present series, the prevalence of severe respiratory symptoms such as dyspnea was very low (13.8%) and in any case mild (11.8%) or moderate (2%). The frequency and severity of symptoms is comparable to that reported by other authors in patients with second episodes of COVID‐19 6 while no data on infected subjects after complete vaccination are reported in the literature.
In the present study, CD were observed to be a frequent symptom in COVID‐19 after full vaccination with similar prevalence to that reported in the past in unvaccinated patients. 7 , 8 , 9 For this reason, the sudden loss of smell and taste could continue to represent a useful and specific diagnostic marker to raise the suspicion of COVID‐19 even in vaccinated subjects. In the future, it will be necessary to establish what the recovery rate is in these patients. Residual CD are in fact turning out to be one of the most frequent symptoms of long‐COVID‐19, with persistent anosmia rates beyond 6 months varying between 1% and 11%. 10 , 11 , 12 , 13 , 14 , 15 If this prevalence were so high even in vaccinated subjects, we could still have a high number of subjects who will require assistance for such disabling disorders. The risk factors and causes of persistence of CD in some patients have not yet been identified. 16 , 17 , 18 , 19 , 20 Early studies found no significant correlation between serum immunoglobulin levels and duration of olfactory disfunction. 21 , 22 The correlation is instead significant with nasal immunoglobulin. 22 Interestingly, it seems that patients with severe COVID‐19 had higher serum antibody levels while nasal antibodies were higher in milder disease. 23 The effects of vaccination on the nasal immune response are yet to be verified and could represent a determining factor on the duration of CD in vaccinated patients.
This study has several limitations: First, it is based on self‐reported olfactory and gustatory loss which may underestimate the true prevalence of CD. Second, the survey was aimed only at symptomatic subjects, a comparison with asymptomatic should performed in the future. Third, while immunization can also result in smell loss, an analysis of the differences between nonimmunized and immunized subjects that become infected could not be performed. The role of immunization should be investigated in the future. Fourth, although the delta variant was predominant at the time of the survey, we have no information regarding the virus strain that infected the patients. It is possible that this factor influenced the results of the study and the viral strain will need to be taken into account in future studies.
CONCLUSIONS
Based on the results of this survey, the sudden loss of smell and taste could continue to represent a useful and specific diagnostic marker to raise the suspicion of COVID‐19 even in vaccinated subjects.
Editor's Note: This Manuscript was accepted for publication on November 16, 2021
The authors have no funding, financial relationships, or conflicts of interest to disclose.
BIBLIOGRAPHY
- 1. Polack FP, Thomas SJ, Kitchin N, et al. Safety and efficacy of the BNT162b2 mRNA Covid‐19 vaccine. N Engl J Med 2020;383:2603–2615. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2. Lopez Bernal J, Andrews N, Gower C, et al. Effectiveness of the Pfizer‐BioNTech and Oxford‐AstraZeneca vaccines on covid‐19 related symptoms, hospital admissions, and mortality in older adults in England: test negative case‐control study. BMJ 2021;373:n1088. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3. Thompson MG, Burgess JL, Naleway AL, et al. Prevention and attenuation of Covid‐19 with the BNT162b2 and mRNA‐1273 vaccines. N Engl J Med 2021;385:320–329. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4. International group for the study of COVID‐19 related chemosensory dysfunctions . Investigation of the clinical manifestations of COVID‐19 in vaccinated subjects. Available at: https://www.surveymonkey.com/r/9Y39587. Accessed October 6, 2021.
- 5. Lechien JR, Chiesa‐Estomba CM, Hans S, et al. Validity and reliability of the COVID‐19 symptom index, an instrument evaluating severity of general and otolaryngological symptoms. Acta Otolaryngol 2021;131:615–620. [DOI] [PubMed] [Google Scholar]
- 6. Lechien JR, Chiesa‐Estomba CM, Radulesco T, et al. Clinical features of patients who had two COVID‐19 episodes: a European multicentre case series. J Intern Med 2021;290:421–429. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7. Saniasiaya J, Islam MA, Abdullah B. Prevalence of olfactory dysfunction in coronavirus disease 2019 (COVID‐19): a meta‐analysis of 27,492 patients. Laryngoscope 2021;131:865–878. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8. Vaira LA, Lechien JR, Khalife M, et al. Psychophysical evaluation of the olfactory function: European multicenter study of 774 COVID‐19 patients. Pathogens 2021;10:62. 10.3390/pathogens10010062. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9. Vaira LA, Salzano G, Deiana G, De Riu G. Anosmia and ageusia: common findings in COVID‐19 patients. Laryngoscope 2020;130:1787. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10. Bussière N, Mei J, Lévesque‐Boissonneault C, et al. Chemosensory dysfunctions induced by COVID‐19 can persist up to 7 months: a study of over 700 healthcare workers. Chem Senses 2021. 10.1093/chemse/bjab038. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11. Boscolo‐Rizzo P, Hummel T, Hopkins C, et al. High prevalence of long‐term olfactory, gustatory, and chemesthesis dysfunction in post‐COVID‐19 patients: a matched case‐control study with one‐year follow‐up using a comprehensive psychophysical evaluation. Rhinology 2021. 10.4193/Rhin21-249. [DOI] [PubMed] [Google Scholar]
- 12. Petrocelli M, Cutrupi S, Salzano G, et al. Six‐month smell and taste recovery rates in coronavirus disease 2019 patients: a prospective psychophysical study. J Laryngol Otol 2021;135:436–441. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13. Boscolo‐Rizzo P, Guida F, Polesel J, et al. Self‐reported smell and taste recovery in coronavirus disease 2019 patients: a one‐year prospective study. Eur Arch Otorhinolaryngol 2021. 10.1007/s00405-021-06839. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14. Niklassen AS, Draf J, Huart C, et al. COVID‐19: recovery from chemosensory dysfunction. A multicentre study on smell and taste. Laryngoscope 2021;131:1095–1100. [DOI] [PubMed] [Google Scholar]
- 15. Vaira LA, Salzano G, Le Bon S, et al. Prevalence of persistent olfactory disorders in COVID‐19 patients: a psychophysical case‐control study with 1‐year follow‐up. Otolaryngol Head Neck Surg 2021. 10.1177/01945998211061511. [DOI] [PubMed] [Google Scholar]
- 16. Vaira LA, Lechien JR, De Vito A, et al. Correlations between olfactory psychophysical scores and SARS‐CoV‐2 viral load in COVID‐19 patients. Laryngoscope 2021;131:2312–2318. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17. Vaira LA, De Vito A, Deiana G, et al. Systemic inflammatory markers and spychophysical olfactory scores in coronavirus disease 2019 patients: is there any correlation? J Laryngol Otol 2021;135:723–728. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18. Shahrvini B, Prajapati DP, Said M, et al. Risk factors and characteristics associated with persistent smell loss in coronavirus disease 2019 (COVID‐19) patients. Int Forum Allergy Rhinol 2021;11:1280–1282. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19. Amadu AM, Vaira LA, Lechien JR, et al. Analysis of the correlations between the severity of lung involvement and olfactory spychophysical scores in coronavirus disease 2019 (COVID‐19) patients. Int Forum Allergy Rhinol 2021. 10.1002/alr.22869. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20. Cho RHW, To ZWH, Yeung ZWC, et al. COVID‐19 viral load in the severity and recovery from olfactory and gustatory dysfunction. Laryngoscope 2020;130:2680–2685. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21. Maiorano E, Calastri A, Robotti C, et al. Clinical, virological and immunological evolution of the olfactory and gustatory dysfunction in COVID‐19. Am J Otolaryngol 2021;43:103170. 10.1016/j.amjoto.2021.103170. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22. Saussez S, Sharma S, Thiriard A, et al. Predictive factors of smell recovery in a clinical series of 288 coronavirus disease 2019 patients with olfactory dysfunction. Eur J Neurol 2021;28:3702–3711. 10.1111/ene.14994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23. Cervia C, Nilsson J, Zuerbuchen Y, et al. Systemic and mucosal antibody responses specific to SARS‐CoV‐2 during mild versus severe. COVID‐19 2021;147:545–557. [DOI] [PMC free article] [PubMed] [Google Scholar]