Next Article in Journal
Point-of-Care Ultrasonography in a Pulmonary Hypertension Clinic: A Randomized Pilot Study
Previous Article in Journal
Perioperative Drug Treatment in Pancreatic Surgery—A Systematic Review and Meta-Analysis
 
 
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Article

The COVID-19 Vaccination Coverage in ICU Patients with Severe COVID-19 Infection in a Country with Low Vaccination Coverage—A National Retrospective Analysis

by
Liana Valeanu
1,†,
Stefan Andrei
2,*,†,
Bianca Morosanu
1,2,
Dan Longrois
3,
Serban-Ion Bubenek-Turconi
1,2 and
COVATI-RO Collaborative
1
Cardiac Anesthesiology and Intensive Care Department I, Emergency Institute for Cardiovascular Diseases C. C. Iliescu, 258 Fundeni Road, 022328 Bucharest, Romania
2
Anesthesiology and Intensive Care Department, Carol Davila University of Medicine and Pharmacy, 8 Eroii Sanitari Blvd., 050474 Bucharest, Romania
3
Department of Anesthesiology and Intensive Care, Bichat-Claude Bernard University Hospital, Sorbonne Universités, INSERM UMR 1148, 46 Rue Henri Huchard, 75018 Paris, France
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
All authors belong to COVATI-RO Collaborative and COVATI-RO Collaborators and affiliations are listed in Supplementary Materials.
J. Clin. Med. 2023, 12(5), 1749; https://doi.org/10.3390/jcm12051749
Submission received: 12 January 2023 / Revised: 18 February 2023 / Accepted: 20 February 2023 / Published: 22 February 2023
(This article belongs to the Section Anesthesiology)

Abstract

:
Background: Romania is one of the European countries with low COVID-19 vaccination coverage. The main goal of this study was to describe the COVID-19 vaccination status in patients admitted to Romanian ICUs with a severe COVID-19 infection. The study describes the patients’ characteristics according to their vaccination status and evaluates the association between vaccination status and ICU mortality. Methods: This retrospective, observational, multicenter study included patients with confirmed vaccination status admitted to Romanian ICUs from January 2021 to March 2022. Results: Two thousand, two hundred and twenty-two patients with confirmed vaccination status were included. Five point one three percent of patients were vaccinated with two vaccine doses and one point seventeen percent of patients were vaccinated with one vaccine dose. The vaccinated patients showed a higher rate of comorbidities but had similar clinical characteristics at ICU admission and lower mortality rates compared to non-vaccinated patients. Vaccinated status and higher Glasgow Coma Scale at ICU admission were independently associated with ICU survival. Ischemic heart disease, chronic kidney disease, higher SOFA score at ICU admission and the need for mechanical ventilation in ICU were independently associated with ICU mortality. Conclusion: Lower rates of ICU admission were observed in fully vaccinated patients even in a country with low vaccination coverage. The ICU mortality was lower for fully vaccinated patients compared to non-vaccinated patients. The benefit of vaccination on ICU survival could be more important in patients with associated comorbidities.

1. Introduction

The COVID-19 pandemic has put extreme pressure on medical systems worldwide. Initial social distancing, quarantine, and lockdown measures were effective in limiting viral transmission, but were impossible to maintain indefinitely as social and economic crises were developing [1]. In the long run, global immunity achieved by vaccination rather than herd immunity seemed to be the viable solution.
COVID-19 vaccines were available less than 10 months after the start of the pandemics. By the end of 2021, two mRNA COVID-19 vaccines (BNT162b2, BioNTech/Pfizer, Germany, Mainz/New York, NY, USA and mRNA-1273, Moderna, Cambridge, MA, USA) and two adenoviral vector COVID-19 vaccines (AZD1222, Oxford/AstraZeneca, UK/Sweden and Ad26.COV2.S, Janssen/Johnson&Johnson, Leiden, Netherlands/New Brunswich, USA) were approved in the European Union. Almost one billion doses of vaccine were used in the European Economic Area in 2021 [2]. Clinical trials and reports from various countries showed that COVID-19 vaccines are effective against viral transmission, symptomatic, and severe COVID-19 infection [3,4,5,6]. Moreover, the risk of severe disease, hospitalization, and death remains significantly reduced for novel SARS-CoV-2 variants [7,8,9,10].
Vaccination rates vary tremendously among different European countries, despite similar availability of vaccine doses. Western European countries reached vaccination rates of between 60 and 80% or even higher than 80% for the Iberian countries and Malta by the end of 2021. While Central European countries had vaccination rates of between 40 and 60%, Eastern European countries such as Romania and Bulgaria did not manage to achieve more than 40% vaccination coverage [7,11].
During the surges of the COVID-19 pandemic, the Romanian ICUs faced extreme pressure due to a shortage of equipment and medical personal. The overall mortality of ICU patients admitted with SARS-CoV-2 infection before vaccines were available was 62% [12]. Patients older than 80 years had higher mortality rates, especially if intubated [13]. The almost two-fold increase in total cost for ICU hospitalization during pandemic waves nearly caused the chronically underfinanced medical system to collapse [14], while elective surgical activity decreased [15].
The study’s main objective was to comparatively describe the characteristics of patients who were admitted to the ICU for severe SARS-CoV-2 infection, according to their vaccination status. The secondary objectives were (i) to describe the COVID-19 vaccination status in patients admitted to Romanian ICUs with severe COVID-19 infection and (ii) to evaluate the association between vaccination status and ICU mortality.

2. Materials and Methods

2.1. Patients, Data Collection, and Study Design

This retrospective, observational, multicenter study was conducted in ICUs at a national level. Data were collected anonymously by the treating intensivists using an online platform at the initiative of the Romanian Society of Anaesthesia and Intensive Care. A total of 42 ICUs from university, county, and municipal hospitals across the country participated in this study. Patients with severe SARS-CoV-2 infection admitted to Romanian ICUs from January 2021 to March 2022 were included. For each patient, data about age, gender, associated medical history, vaccination status, clinical severity at the moment of ICU admission, and the need for invasive mechanical ventilation (MV) were retrospectively collected. The patients’ outcomes were dichotomized as survivors (discharged from ICU) or as deceased (ICU death). For study analyses, we considered the patients who had received two vaccine doses to be fully vaccinated. Patients who received one vaccine dose were excluded from the statistical analysis because it was unclear if they were fully vaccinated with a one-dose COVID-19 vaccine or incompletely vaccinated with only one dose of a two-dose COVID-19 vaccine.
The circulating variants of SARS-CoV-2 were not determined for each patient. However, we arbitrarily classified the patients into four periods of surge (A, B, C, D) according to the hospitalization month, based on the official data of the Romanian Government [16]: period A (from January to February 2021, first cases of Alpha variant); period B (from March to June 2021, predominantly Alpha variant); period C (from July to December 2021, predominantly Delta variant); and period D (from January to March 2022, end of data collection) predominantly Omicron variant).

2.2. Ethics

The ethical approval for this study was granted by the Department of Medical Education and Research of the Romanian Society of Anaesthesia and Intensive Care (decision number 7, 4 April 2022). Considering its retrospective, observational design and completely anonymized data collection, the patient’s consent for data inclusion and use was waived by the ethics committee.

2.3. Statistical Analysis

The patients with complete datasets were included in statistical analysis. Numerical variables were presented as mean ± standard deviation or as median with [25–75%] interquartile range (IQR), as appropriate. The parametric distribution was checked using histograms and using the Shapiro–Wilk’s test. The continuous variables were compared using the Student’s test or Mann–Whitney U test, as appropriate. Categorical variables were presented as numbers (percentages). The comparisons between categorical variables were performed using the Chi-square test.
The main study endpoint (the vaccination rate) was descriptively presented as a percentage (95% CI). The secondary endpoints were statistically managed as follows:
(1)
The characteristics of vaccinated and non-vaccinated patients were comparatively presented using appropriate statistical tests (Student, Mann–Whitney U, or Chi-square);
(2)
The association between vaccination status and ICU mortality was evaluated using a logistic regression approach. Non-redundant variables with clinical pertinence or statistical significance in univariate logistic regression analyses (p < 0.05) were introduced in the multivariate logistic model. The validity conditions for logistic regression were verified in order to have at least 10 events for each variable included in the multivariate logistic model.
A bilateral p < 0.05 was, a priori, considered statistically significant. The statistical analyses were performed using RStudio (Version 1.1.447—© 2009–2018 RStudio, Inc., Wien, Austria).

3. Results

3.1. Vaccination Rate in Romanian ICUs

Two thousand, two hundred and twenty-two patients with confirmed vaccination status were included. From this cohort, only 114 patients were vaccinated with two doses, corresponding to a vaccination rate of 5.13%, 95% CI (4.25%; 6.13%). Thirty-eight (1.71%) patients received only one vaccine dose and were further excluded from the statistical analysis (Figure 1).

3.2. Characteristics of Fully Vaccinated Patients Admitted in ICU

The collected patients’ characteristics according to their vaccination status are presented in Table 1.
The vaccinated patients showed a higher rate of ischemic heart disease (36% vs. 25%, p = 0.012), chronic kidney disease (21% vs. 12%, p = 0.003), and chronic dialysis (5% vs. 1%, p < 0.001) as associated comorbidities, compared to the non-vaccinated patients. The age, gender, and rate of the other collected comorbidities were not statistically different between the groups of patients. However, the vaccinated patients had a higher median number of comorbidities (2 [1,2]) compared to the non-vaccinated patients (2 [1–3], p = 0.016). The number of patients with more than four cumulated comorbidities was higher in the vaccinated group. The clinical status and severity were similar between the two groups regarding the initial ICU admission (SOFA score, dyspnea, fever, ARDS, need for MV) and management, excepting the neurological status (Table 1). The non-vaccinated patients had a lower Glasgow Coma Scale (GCS) compared to the vaccinated group (15 [7–15] vs. 15 [12–15], p = 0.010).
Mortality was lower for vaccinated patients compared to non-vaccinated patients (58% vs. 67%, p = 0.045), while the ICU length of stay was similar between vaccinated and non-vaccinated patients.

3.3. Risk Factors for ICU Mortality

The results of the univariate logistic regression analysis with ICU mortality as the dependent variable are presented in Table 2. Several variables were associated with ICU mortality in univariate logistic regression analyses: high blood pressure, OR 2, 95% CI (1.7–2.4), p < 0.001; ischemic heart disease, OR 2.1, 95% CI (1.7–2.6), p < 0.001; chronic heart failure, OR 1.8, 95% CI (1.4–2.3), p < 0.001; diabetes, OR 1.7, 95% CI (1.4–2), p < 0.001, chronic kidney disease, OR 2.7, 95% CI (1.9–3.7), p < 0.001; chronic obstructive pulmonary disease, OR 1.6, 95% CI (1.05–2.5), p = 0.030; past or current neoplasia, OR 2.1, 95% CI (1.4–3.1), p = 0.001; the SOFA score on ICU admission, OR 1.08, 95% CI (1.06–1.1), p < 0.001; the need for non-invasive ventilation, OR 2.5, 95% CI (2–2.9), p < 0.001; and the need for invasive mechanical ventilation, OR 22, 95% CI (17–28), p < 0.001. The vaccinated status, OR 0.68, 95% CI (0.46–0.99), p = 0.046, higher GCS on ICU admission, OR 0.8, 95% CI (0.77–0.82), p < 0.001, and COVID-19 period D, OR 0.03, 95% CI (0.01–0.25), p = 0.001 were inversely associated with ICU mortality.
The multivariate logistic regression analysis with ICU mortality as the dependent variable (Table 2) found that the vaccinated status, OR 0.54, 95% CI (0.31–0.93), p = 0.027, and higher GCS on admission, OR 0.9, 95% CI (0.85–0.92), p < 0.001 were factors independently associated with ICU survival. The same multivariate logistic regression analysis showed that ischemic heart disease, OR 1.9, 95% CI (1.4–2.6), p < 0.001, chronic kidney disease, OR 2.2, 95% CI (1.5–3.3), p < 0.001, admission SOFA, OR 1.03, 95% CI (1.01–1.06), p = 0.003, the need for non-invasive ventilation, OR 2, 95% CI (1.6–2.7), p < 0.001, and the need for invasive mechanical ventilation, OR 14, 95% CI (11–18), p < 0.001 were factors independently associated with ICU mortality.

4. Discussion

Our study found a very low rate of vaccination in ICU patients admitted for severe COVID-19 infection. Only 5.13% of patients were vaccinated with two doses and 1.71% of patients received one dose of the COVID-19 vaccine. This low vaccination rate in ICU patients can be partially explained by the low national vaccination coverage. COVID-19 vaccines were available in Romania at the end of December 2020. The national vaccination strategy focused on healthcare providers and individuals at high risk of complications following COVID-19 infection during the first weeks. After 15th March 2021, the vaccination was available to the general population. By the end of March 2021 (period B), only 5.43% of the Romanian population was fully vaccinated, but the vaccination rate increased slowly to 23.69% at the end of June 2021 (period B), 40.91% at the end of December 2021 (period C), and 42.26% in March 2022 (period D) [18]. This low national vaccination rate is mainly explained by the hesitation of the population to vaccinate, caused by conspiracy theories, lack of medical education, fear of adverse effects, and the belief that vaccines are not effective [19,20]. Although the COVID-19 vaccination campaign received extensive media coverage and was publicly promoted by medical professionals as well as opinion leaders, it did not impact vaccination rates as expected. Even though the vaccination rate was globally low in the Romanian population during the study period, the rate of vaccination in ICU patients was strikingly low. Previous studies already report that COVID-19 vaccination reduces the risk of severe symptoms, hospitalization [21], ARDS, and the need for invasive MV [22,23]. Our findings are coherent with other reports that advocated a lower rate of ICU admission in vaccinated patients [23,24,25,26,27,28,29], although in this cohort there was no difference in the incidence of ARDS or the need for invasive MV between unvaccinated and fully vaccinated patients.
The vaccinated patients with severe COVID-19 infection admitted to ICU presented a higher rate of ischemic heart disease, chronic kidney disease, chronic dialysis, and a higher cumulated number of associated medical conditions. These results are similar to other studies that report a notably higher incidence of comorbidities in vaccinated patients requiring ICU admission [22,30,31,32,33,34,35] and a weaker association between vaccination and reduced risk of hospitalization for patients with impaired immune status [22]. The high rate of comorbidities might be explained by the exacerbation of coexisting diseases requiring ICU hospitalization or by lower vaccine effectiveness in this population [32,33].
The mortality rate was lower for vaccinated patients compared to non-vaccinated patients in this cohort. The vaccinated status was statistically associated with survival for the patients in this cohort, after adjustment on age, gender, comorbidities, and clinical severity. This finding is in line with other studies from countries with high or low vaccination coverage that report lower mortality rates in vaccinated patients [24,25,26,27,29,30,31,32,36,37,38]. Moreover, full vaccination status is associated with lower mortality among intubated patients with COVID-19-related ARDS, even in the presence of comorbidities [34], suggesting an immunity advantage in the case of severe infection [39] in the population with the highest case fatality rates [40,41]. Another study reports no difference in ICU mortality between vaccinated and non-vaccinated patients [33], but in that cohort vaccinated patients had significantly higher rates of immunosuppression or comorbidities compared to non-vaccinated patients. Although no causality could be affirmed, considering the lower mortality observed in vaccinated patients despite the higher incidence of comorbidities, the population at risk might supplementarily benefit from further prevention measures or interventions such as vaccine boosters [33,34]. The perspective of reinfection as new variants of COVID-19 emerges and the higher rate of ICU admission and mortality in cases of reinfection [42], combined with the waning effects of vaccine protection with the increasing time interval since vaccination [43], supplementary support immunization practices. Although there was no statistically significant difference in the ICU length of stay between vaccinated and non-vaccinated patients, the shorter ICU length of stay in the latter group might have been due to a higher mortality rate in non-vaccinated patients.

4.1. Relevance of Our Results

The findings of this study underline once more the importance of vaccination, particularly in patients with a higher number of comorbidities and in countries with underserved ICU and healthcare systems. To limit mortality, national strategies addressing the population’s hesitancy to vaccinate should be developed while preparing the healthcare system to successfully respond in case of following COVID-19 waves.

4.2. Limitations

This study can be discussed on several points. Considering the retrospective, non-randomized study protocol, the results should be taken with caution and no causality can be firmly stated. We did not collect all the variables potentially associated with mortality (detailed comorbidities, presence of immunosuppression, length of hospital stay before ICU admission, ICU management and complications, need for vasopressor therapy, cause of death, centre-effect, etc.) and we did not describe or analyze the time lapse between full vaccination and COVID-19 infection.
Furthermore, the type of vaccination for each patient was not collected and patients fully vaccinated with a one-dose vaccine were excluded from the analysis. Further studies are necessary to confirm the positive effect of vaccination on ICU survival, especially in patients with coexisting diseases.

5. Conclusions

The COVID-19 vaccination rate in ICU patients was very low, even in a population with low vaccination coverage. Patients with coexisting diseases may supplementarily benefit from the protective effect of vaccination against COVID-19 regarding ICU admission and mortality.

Supplementary Materials

The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/jcm12051749/s1, COVATI-RO Collaborative: collaborators, affiliations.

Author Contributions

Conceptualization, L.V., S.A., D.L. and S.-I.B.-T.; methodology, L.V., S.A. and S.-I.B.-T.; formal analysis, S.A.; investigation, L.V., S.A. and S.-I.B.-T.; resources, B.M., S.-I.B.-T. and COVATI-RO Collaborative; data curation, L.V., S.A., B.M. and S.-I.B.-T.; writing—original draft preparation, L.V. and S.A.; writing—review and editing, B.M., D.L. and S.-I.B.-T.; funding acquisition, S.-I.B.-T. All authors have read and agreed to the published version of the manuscript.

Funding

This research was funded by the Romanian Society of Anaesthesia and Intensive Care.

Institutional Review Board Statement

The study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Department of Medical Education and Research of the Romanian Society of Anaesthesia and Intensive Care (decision number 7, 4 April 2022).

Informed Consent Statement

Patient consent was waived due to the fully anonymized and observational design of the study.

Data Availability Statement

Restrictions apply to the availability of these data. The data presented in this study are available on reasonable request from the corresponding author.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Nicola, M.; Alsafi, Z.; Sohrabi, C.; Kerwan, A.; Al-Jabir, A.; Iosifidis, C.; Agha, M.; Agha, R. The socio-economic implications of the coronavirus pandemic (COVID-19): A review. Int. J. Surg. 2020, 78, 185–193. [Google Scholar] [CrossRef]
  2. COVID-19 Vaccine Tracker. Available online: https://vaccinetracker.ecdc.europa.eu/public/extensions/COVID-19/vaccinetracker.html (accessed on 4 December 2022).
  3. Polack, F.P.; Thomas, S.J.; Kitchin, N.; Absalon, J.; Gurtman, A.; Lockhart, S.; Perez, J.L.; Pérez Marc, G.; Moreira, E.D.; Zerbini, C.; et al. Safety and Efficacy of the BNT162b2 mRNA COVID-19 Vaccine. N. Engl J. Med. 2020, 383, 2603–2615. [Google Scholar] [CrossRef]
  4. Baden, L.R.; El Sahly, H.M.; Essink, B.; Kotloff, K.; Frey, S.; Novak, R.; Diemert, D.; Spector, S.A.; Rouphael, N.; Creech, C.B.; et al. Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine. N. Engl. J. Med. 2021, 384, 403–416. [Google Scholar] [CrossRef]
  5. Sadoff, J.; Gray, G.; Vandebosch, A.; Cárdenas, V.; Shukarev, G.; Grinsztejn, B.; Goepfert, P.A.; Truyers, C.; Fennema, H.; Spiessens, B.; et al. Safety and Efficacy of Single-Dose Ad26.COV2.S Vaccine against COVID-19. N. Engl. J. Med. 2021, 384, 2187–2201. [Google Scholar] [CrossRef]
  6. Voysey, M.; Clemens, S.A.C.; Madhi, S.A.; Weckx, L.Y.; Folegatti, P.M.; Aley, P.K.; Angus, B.; Baillie, V.L.; Barnabas, S.L.; Bhorat, Q.E.; et al. Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: An interim analysis of four randomised con-trolled trials in Brazil, South Africa, and the UK. Lancet 2021, 397, 99–111. [Google Scholar] [CrossRef]
  7. Sikora, D.; Rzymski, P. COVID-19 Vaccination and Rates of Infections, Hospitalizations, ICU Admissions, and Deaths in the European Economic Area during Autumn 2021 Wave of SARS-CoV-2. Vaccines 2022, 10, 437. [Google Scholar] [CrossRef]
  8. Grannis, S.J.; Rowley, E.A.; Ong, T.C.; Stenehjem, E.; Klein, N.P.; DeSilva, M.B.; Naleway, A.L.; Natarajan, K.; Thompson, M.G. VISION Network. Interim Estimates of COVID-19 Vaccine Effectiveness Against COVID-19-Associated Emergency Department or Urgent Care Clinic Encounters and Hospitalizations Among Adults During SARS-CoV-2 B.1.617.2 (Delta) Variant Predom-inance-Nine States, June-August 2021. MMWR Morb. Mortal. Wkly Rep. 2021, 70, 1291–1293. [Google Scholar]
  9. Chia, P.Y.; Ong, S.W.X.; Chiew, C.J.; Ang, L.W.; Chavatte, J.M.; Mak, T.M.; Cui, L.; Kalimuddin, S.; Chia, W.N.; Tan, C.W.; et al. Virological and serological kinetics of SARS-CoV-2 Delta variant vaccine breakthrough infections: A multicentre cohort study. Clin Microbiol Infect. 2022, 28, 612.e1–612.e7. [Google Scholar] [CrossRef]
  10. Bernal, J.L.; Andrews, N.; Gower, C.; Gallagher, E.; Simmons, R.; Thelwall, S.; Stowe, J.; Tessier, E.; Groves, N.; Dabrera, G.; et al. Effectiveness of COVID-19 Vaccines against the B.1.617.2 (Delta) Variant. N. Engl. J. Med. 2021, 385, 585–594. [Google Scholar] [CrossRef]
  11. Mathieu, E.; Ritchie, H.; Ortiz-Ospina, E.; Roser, M.; Hasell, J.; Appel, C.; Giattino, C.; Rodés-Guirao, L. Coronavirus (COVID-19) Vaccinations. 2020. Available online: https://ourworldindata.org/covid-vaccinations (accessed on 28 December 2021).
  12. Bubenek-Turconi, Ş.I.; Andrei, S.; Văleanu, L.; Ştefan, M.G.; Grigoraş, I.; Copotoiu, S.; Bodolea, C.; Tomescu, D.; Popescu, M.; Filipescu, D.; et al. Clinical characteris-tics and factors associated with ICU mortality during the first year of the SARS-CoV-2 pandemic in Romania: A prospective, cohort, multicentre study of 9000 patients. Eur. J. Anaesthesiol. 2023, 40, 4–12. [Google Scholar] [CrossRef]
  13. Andrei, S.; Valeanu, L.; Stefan, M.G.; Longrois, D.; Popescu, M.; Stefan, G.; Balan, C.; Arafat, R.; Corneci, D.; Droc, G.; et al. Outcomes of COVID-19 Critically Ill Extremely Elderly Patients: Analysis of a Large, National, Observational Cohort. J. Clin. Med. 2022, 11, 1544. [Google Scholar] [CrossRef]
  14. Popescu, M.; Ştefan, O.M.; Ştefan, M.; Văleanu, L.; Tomescu, D. ICU-Associated Costs during the Fourth Wave of the COVID-19 Pandemic in a Tertiary Hospital in a Low-Vaccinated Eastern European Country. Int. J. Environ. Res. Public Heal. 2022, 19, 1781. [Google Scholar] [CrossRef]
  15. Andrei, S.; Isac, S.; Jelea, D.; Martac, C.; Stefan, M.-G.; Cotorogea-Simion, M.; Buzatu, C.G.S.; Ingustu, D.; Abdulkareem, I.; Vasilescu, C.; et al. COVID-19 Pandemic Was Associated with Lower Activity but Not Higher Perioperative Mortality in a Large Eastern European Center. Experiment 2022, 28, e935809. [Google Scholar] [CrossRef]
  16. COVID 19 Date La Zi—Date Oficiale [Internet]. Available online: https://datelazi.ro/ (accessed on 2 December 2022).
  17. Stevens, P.E.; Levin, A. Kidney Disease: Improving Global Outcomes Chronic Kidney Disease Guideline Development Work Group Members. Evaluation and management of chronic kidney disease: Synopsis of the kidney disease: Improving global outcomes 2012 clinical practice guideline. Ann. Intern. Med. 2013, 158, 825–830. [Google Scholar] [CrossRef] [Green Version]
  18. Raportari Vaccinare COVID. Available online: https://vaccinare-covid.gov.ro/raportari/ (accessed on 17 February 2023).
  19. Mărcău, F.-C.; Purec, S.; Niculescu, G. Study on the Refusal of Vaccination against COVID-19 in Romania. Vaccines 2022, 10, 261. [Google Scholar] [CrossRef]
  20. Vianello, A.; Guarnieri, G.; Lionello, F. Unvaccinated COVID-19 patients in the ICU: Views from both sides of the barrier. Pulmonology 2022, 28, 161–163. [Google Scholar] [CrossRef]
  21. Tartof, S.Y.; Slezak, J.M.; Fischer, H.; Hong, V.; Ackerson, B.K.; Ranasinghe, O.N.; Frankland, T.B.; Ogun, O.A.; Zamparo, J.M.; Gray, S.; et al. Effectiveness of mRNA BNT162b2 COVID-19 vaccine up to 6 months in a large integrated health system in the USA: A retrospective cohort study. Lancet 2021, 398, 1407–1416. [Google Scholar] [CrossRef]
  22. Tenforde, M.W.; Self, W.H.; Adams, K.; Gaglani, M.; Ginde, A.A.; McNeal, T.; Ghamande, S.; Douin, D.J.; Talbot, H.K.; Casey, J.D.; et al. Association Between mRNA Vaccination and COVID-19 Hospitalization and Disease Severity. JAMA 2021, 326, 2043. [Google Scholar] [CrossRef]
  23. Thygesen, J.H.; Tomlinson, C.; Hollings, S.; Mizani, M.A.; Handy, A.; Akbari, A.; Banerjee, A.; Cooper, J.; Lai, A.G.; Li, K.; et al. Longitudinal Health and Wellbeing COVID-19 National Core Study and the CVD-COVID-UK/COVID-IMPACT Consorti-um. COVID-19 trajectories among 57 million adults in England: A cohort study using electronic health records. Lancet Digit Health 2022, 4, e542–e557. [Google Scholar] [CrossRef]
  24. Whittaker, R.; Bråthen Kristofferson, A.; Valcarcel Salamanca, B.; Seppälä, E.; Golestani, K.; Kvåle, R.; Watle, S.V.; Buanes, E.A. Length of hospital stay and risk of intensive care admission and in-hospital death among COVID-19 patients in Norway: A regis-ter-based cohort study comparing patients fully vaccinated with an mRNA vaccine to unvaccinated patients. Clin. Microbiol. Infect. 2022, 28, 871–878. [Google Scholar] [CrossRef]
  25. Sevinc, S.A.; Metin, S.; Basi, N.B.; Ling, J.; Cinar, A.S.; Oba, S. Effectiveness of inactivated SARS-CoV-2 vaccine (CoronaVac) on in-tensive care unit survival. Epidemiol. Infect. 2022, 150, e35. [Google Scholar] [CrossRef]
  26. Grima, A.A.; Murison, K.R.; Simmons, A.E.; Tuite, A.R.; Fisman, D.N. Relative Virulence of SARS-CoV-2 Among Vaccinated and Unvaccinated Individuals Hospitalized with SARS-CoV-2. Clin. Infect. Dis. 2022, 25, ciac412. [Google Scholar] [CrossRef]
  27. Modes, M.E.; Directo, M.P.; Melgar, M.; Johnson, L.R.; Yang, H.; Chaudhary, P.; Bartolini, S.; Kho, N.; Noble, P.W.; Isonaka, S.; et al. Clinical Characteristics and Outcomes Among Adults Hospitalized with Laboratory-Confirmed SARS-CoV-2 Infection During Periods of B.1.617.2 (Delta) and B.1.1.529 (Omicron) Variant Predominance—One Hospital, California, July 15-September 23, 2021, and December 21, 2021-January 27, 2022. MMWR Morb. Mortal. Wkly. Rep. 2022, 71, 217–223. [Google Scholar]
  28. Hilty, M.P.; Keiser, S.; Wendel Garcia, P.D.; Moser, A.; Schuepbach, R.A.; RISC-19-ICU Investigators for Switzerland. mRNA-based SARS-CoV-2 vaccination is associated with reduced ICU admission rate and disease severity in critically ill COVID-19 pa-tients treated in Switzerland. Intensive Care Med. 2022, 48, 362–365. [Google Scholar] [CrossRef]
  29. Bagshaw, S.M.; Abbott, A.; Beesoon, S.; Zuege, D.J.; Wasylak, T.; Manns, B.; Nguyen, T.X. Avoidable intensive care unit resource use and costs of unvaccinated patients with COVID-19: A historical population-based cohort study. Can. J. Anaesth. 2022, 69, 1399–1404. [Google Scholar] [CrossRef]
  30. Contou, D.; Fraissé, M.; Pajot, O.; Tirolien, J.A.; Mentec, H.; Plantefève, G. Comparison between first and second wave among crit-ically ill COVID-19 patients admitted to a French ICU: No prognostic improvement during the second wave? Crit. Care 2021, 25, 3. [Google Scholar] [CrossRef]
  31. Juthani, P.V.; Gupta, A.; A Borges, K.; Price, C.C.; I Lee, A.; Won, C.H.; Chun, H.J. Hospitalisation among vaccine breakthrough COVID-19 infections. Lancet Infect. Dis. 2021, 21, 1485–1486. [Google Scholar] [CrossRef]
  32. Brosh-Nissimov, T.; Orenbuch-Harroch, E.; Chowers, M.; Elbaz, M.; Nesher, L.; Stein, M.; Maor, Y.; Cohen, R.; Hussein, K.; Weinberger, M.; et al. BNT162b2 vaccine breakthrough: Clinical charac-teristics of 152 fully vaccinated hospitalized COVID-19 patients in Israel. Clin. Microbiol. Infect. 2021, 27, 1652–1657. [Google Scholar] [CrossRef]
  33. Motos, A.; López-Gavín, A.; Riera, J.; Ceccato, A.; Fernández-Barat, L.; Bermejo-Martin, J.F.; Ferrer, R.; de Gonzalo-Calvo, D.; Menéndez, R.; Pérez-Arnal, R.; et al. Higher frequency of comorbidities in fully vaccinated patients admitted to the ICU due to severe COVID-19: A prospective, multicentre, observational study. Eur. Respir. J. 2021, 59, 2102275. [Google Scholar] [CrossRef]
  34. Grapsa, E.; Adamos, G.; Andrianopoulos, I.; Tsolaki, V.; Giannakoulis, V.G.; Karavidas, N.; Giannopoulou, V.; Sarri, K.; Mizi, E.; Gavrielatou, E.; et al. Association Between Vaccination Status and Mortality Among Intubated Patients With COVID-19–Related Acute Respiratory Distress Syndrome. JAMA Netw. Open 2022, 5, e2235219–e2235219. [Google Scholar] [CrossRef]
  35. Seo, W.J.; Kang, J.; Kang, H.K.; Park, S.H.; Koo, H.-K.; Park, H.K.; Lee, S.-S.; Song, J.E.; Kwak, Y.G.; Kang, J. Impact of prior vaccination on clinical outcomes of patients with COVID-19. Emerg. Microbes Infect. 2022, 11, 1316–1324. [Google Scholar] [CrossRef]
  36. Lytras, T.; Kontopidou, F.; Lambrou, A.; Tsiodras, S. Comparative effectiveness and durability of COVID-19 vaccination against death and severe disease in an ongoing nationwide mass vaccination campaign. J. Med. Virol. 2022, 94, 5044–5050. [Google Scholar] [CrossRef]
  37. Malli, F.; Lampropoulos, I.C.; Papagiannis, D.; Papathanasiou, I.V.; Daniil, Z.; Gourgoulianis, K.I. Association of SARS-CoV-2 Vac-cinations with SARS-CoV-2 Infections, ICU Admissions and Deaths in Greece. Vaccines 2022, 10, 337. [Google Scholar] [CrossRef]
  38. Mhawish, H.; Mady, A.; Alaklobi, F.; Aletreby, W.; Asad, T.; Alodat, M.; Alharthy, A.; Abdulrahman, B.; Almahwi, S.; Memish, Z.A. Comparison of severity of immunized versus non-immunized COVID-19 patients admitted to ICU: A prospective observa-tional study. Ann. Med. Surg. 2021, 71, 102951. [Google Scholar] [CrossRef]
  39. Yan, Z.; Yang, M.; Lai, C.L. COVID-19 Vaccinations: A Comprehensive Review of Their Safety and Efficacy in Special Popula-tions. Vaccines 2021, 9, 1097. [Google Scholar] [CrossRef]
  40. Alimohamadi, Y.; Tola, H.H.; Abbasi-Ghahramanloo, A.; Janani, M.; Sepandi, M. Case fatality rate of COVID-19: A systematic re-view and meta-analysis. J. Prev. Med. Hyg. 2021, 62, E311–E320. [Google Scholar]
  41. Lim, Z.J.; Subramaniam, A.; Reddy, M.P.; Blecher, G.; Kadam, U.; Afroz, A.; Billah, B.; Ashwin, S.; Kubicki, M.; Bilotta, F.; et al. Case Fatality Rates for Patients with COVID-19 Requiring Invasive Mechanical Ventilation. A Meta-analysis. Am. J. Respir. Crit. Care Med. 2021, 203, 54–66. [Google Scholar] [CrossRef]
  42. Dhillon, R.A.; Qamar, M.A.; Gilani, J.A.; Irfan, O.; Waqar, U.; Sajid, M.I.; Mahmood, S.F. The mystery of COVID-19 reinfections: A global systematic review and meta-analysis. Ann. Med. Surg. 2021, 72, 103130. [Google Scholar] [CrossRef]
  43. Malhotra, S.; Mani, K.; Lodha, R.; Bakhshi, S.; Mathur, V.P.; Gupta, P.; Kedia, S.; Sankar, M.J.; Kumar, P.; Kumar, A.; et al. COVID-19 infection, and reinfection, and vaccine effectiveness against symptomatic infec-tion among health care workers in the setting of omicron variant transmission in New Delhi, India. Lancet Reg. Health 2022, 3, 100023. [Google Scholar]
Figure 1. Study flowchart.
Figure 1. Study flowchart.
Jcm 12 01749 g001
Table 1. Patients’ characteristics. Non-vaccinated versus fully vaccinated.
Table 1. Patients’ characteristics. Non-vaccinated versus fully vaccinated.
VariablesNon-Vaccinated
(n = 2070)
Fully Vaccinated
(n = 114)
p-Value
Age (years), median [IQR]68 [59–75]66 [56–72]0.057
Male gender, n (%)1077 (52)51 (45)0.129
ICU admission and management
Fever (yes), n (%)736 (36)34 (30)0.212
Dyspnea (yes), n (%)1489 (72)84 (84)0.685
ARDS (yes), n (%)938 (41)43 (38)0.558
Invasive mechanical ventilation (yes), n (%)1157 (56)60 (53)0.495
Non-invasive ventilation (yes), n (%)1277 (62)64 (56)0.236
High flow nasal cannula oxygen therapy (yes), n (%)993 (48) 50 (44)0.392
GCS, median [IQR]15 [7–15]15 [12–15]0.010
SOFA, median [IQR]7 [4–12]8 [4–12]0.202
Corticosteroid usage, n (%)1788 (86)87 (76)0.003
Received remdesivir (yes), n (%)828 (40)42 (37)0.503
Associated medical conditions
Ischemic heart disease (yes), n (%)526 (25)41 (36)0.012
Autoimmune disease (yes), n (%)49 (2)6 (5)0.055
Dialysis patient (yes), n (%)16 (1)6 (5)<0.001
COPD (yes), n (%)111 (5)5 (4)0.651
Past or current cancer (yes), n (%)136 (7)12 (11)0.102
Chronic kidney disease 1 (yes), n (%)244 (12)24 (21)0.003
Diabetes (yes), n (%)640 (31)44 (39)0.085
Heart failure (yes), n (%)354 (17)21 (18)0.716
Arterial hypertension (yes), n (%)1328 (64)78 (68)0.354
Number of comorbidities, median [IQR]2 [1–2]2 [1–3]0.016
Comorbidities, n (%) <0.001
- No comorbidity (yes), n (%)455 (22)25 (22)
- 1 comorbidity (yes), n (%)564 (27)21 (18)
- 2 comorbidities (yes), n (%)563 (27)27 (24)
- 3 comorbidities (yes), n (%)295 (14)19 (17)
- 4 comorbidities (yes), n (%)145 (7)9 (8)
- 5 comorbidities (yes), n (%)39 (2)9 (8)
- 6 comorbidities (yes), n (%)9 (0.4)4 (4)
COVID-19 period, n (%) <0.001
- A (01–02/21)136 (7)4 (4)0.240
- B (03–06/21)1169 (57)17 (15)<0.001
- C (07–12/21)752 (36)90 (79)<0.001
- D (01–03/22)13 (0.6)3 (3)0.047
Outcomes
ICU Death, n (%)1387 (67)66 (58)0.045
- No comorbidities 206 (10)9 (8)-
- With comorbidities1181 (57)57 (50)-
ICU LOS (days), median [IQR]7 [4–12]8 [5–16]0.057
1 Chronic kidney disease was defined as creatinine clearance <60 mL/min [17]. Abbreviations: IQR—interquartile range; ICU-Intensive care unit; ARDS—acute respiratory distress syndrome; GCS—Glasgow coma scale; SOFA—sequential organ failure assessment score; COPD—chronic obstructive pulmonary disease; LOS—length of stay.
Table 2. Univariate and multivariate logistic regression analysis with ICU mortality as the dependent variable.
Table 2. Univariate and multivariate logistic regression analysis with ICU mortality as the dependent variable.
VariablesUnivariate AnalysisMultivariate Analysis
OR (95% CI)p-ValueOR (95% CI)p-Value
Study endpoint
Vaccinated (yes)0.68 (0.46–0.99)0.0460.54 (0.31–0.93)0.027
Patients’ baseline characteristics
Age (year)1 (0.99–1)0.777
Gender (male)1.18 (0.98–1.4)0.076
COVID-19 period
- A (01–02/21)comparator
- B (03–06/21)1.02 (0.7–1.5)0.9001.2 (0.7–2)0.485
- C (07–12/21)0.90 (0.6–1.3)0.4891.3 (0.8–2.3)0.262
- D (01–03/22)0.03 (0.01–0.25)0.0010.1 (0.01–1.6)0.107
Comorbidities
AHT (yes)2 (1.7–2.4)<0.0011.2 (0.91–1.6)0.205
IHD (yes)2.1 (1.7–2.6)<0.0011.9 (1.4–2.6)<0.001
CHF (yes)1.8 (1.4–2.3)<0.0011 (0.7–1.5)0.857
Diabetes (yes)1.7 (1.4–2)<0.0011.3 (0.99–1.7)0.056
Autoimmunity (yes)1.13 (0.63–2)0.684
CKD (yes)2.7 (1.9–3.7)<0.0012.2 (1.5–3.3)<0.001
Chronic dialysis (yes)2.3 (0.8–6.7)0.137
COPD (yes)1.6 (1.05–2.5)0.0301.6 (0.91–2.7)0.104
Past or current neoplasia (yes)2.1 (1.4–3.1)0.0011.6 (0.92–2.7)0.101
ICU admission and evolution
Fever (yes)1.1 (0.9–1.3)0.356
Dyspnea (yes)0.96 (0.8–1.2)0.955
SOFA score (each score point)1.08 (1.06–1.1)<0.0011.03 (1.01–1.06)0.003
GCS (each score point)0.8 (0.77–0.82)<0.0010.9 (0.85–0.92)<0.001
Need for non-invasive ventilation (yes)2.5 (2–2.9)<0.0012 (1.6–2.7)<0.001
Need for invasive mechanical ventilation (yes)22 (17–28)<0.00114 (11–18)<0.001
Corticosteroid usage2.2 (1.8–2.8)<0.0010.9 (0.6–1.2)0.475
Received remdesivir 1.2 (0.98–1.4)0.076
Abbreviations: AHT—arterial hypertension, IHD—ischemic heart disease, CHF—chronic heart failure, CKD—chronic kidney disease, COPD—chronic obstructive pulmonary disease, SOFA—sequential organ failure assessment, GCS—Glasgow coma scale, ICU—intensive care unit.
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

Share and Cite

MDPI and ACS Style

Valeanu, L.; Andrei, S.; Morosanu, B.; Longrois, D.; Bubenek-Turconi, S.-I.; COVATI-RO Collaborative. The COVID-19 Vaccination Coverage in ICU Patients with Severe COVID-19 Infection in a Country with Low Vaccination Coverage—A National Retrospective Analysis. J. Clin. Med. 2023, 12, 1749. https://doi.org/10.3390/jcm12051749

AMA Style

Valeanu L, Andrei S, Morosanu B, Longrois D, Bubenek-Turconi S-I, COVATI-RO Collaborative. The COVID-19 Vaccination Coverage in ICU Patients with Severe COVID-19 Infection in a Country with Low Vaccination Coverage—A National Retrospective Analysis. Journal of Clinical Medicine. 2023; 12(5):1749. https://doi.org/10.3390/jcm12051749

Chicago/Turabian Style

Valeanu, Liana, Stefan Andrei, Bianca Morosanu, Dan Longrois, Serban-Ion Bubenek-Turconi, and COVATI-RO Collaborative. 2023. "The COVID-19 Vaccination Coverage in ICU Patients with Severe COVID-19 Infection in a Country with Low Vaccination Coverage—A National Retrospective Analysis" Journal of Clinical Medicine 12, no. 5: 1749. https://doi.org/10.3390/jcm12051749

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop