This study represents the first multicenter research examining the clinical and epidemiological characteristics, including mortality rates, among vaccinated and unvaccinated COVID-19 patients in Venezuela. Vaccination was correlated with a 57% decrease in mortality relative to the unvaccinated cohort. The logistical challenges associated with vaccine distribution and storage in Venezuela were mitigated through the assistance of international organizations such as the United Nations Children’s Fund, PAHO, and COVAX [24], culminating in the vaccination of 66% of the population by May 2023 [27].
A higher representation of healthcare workers was noted in the vaccinated group, likely attributable to this demographic being prioritized for vaccination in accordance with WHO and PAHO guidelines for risk groups [33, 38]. Both the vaccinated and unvaccinated cohorts had comparable characteristics in terms of sex, age, and comorbidities, with the exception of bronchial asthma. However, no significant differences were observed upon calculation of the Charlson Comorbidity Index for each group. The most prevalent symptoms and signs, including dyspnea, fever, dry cough, tachypnea, and decreased oxygen saturation, were consistent with previous studies [39–50]. Unvaccinated patients had a higher prevalence of dyspnea, increased respiratory rate, and lower oxygen saturation values, corroborating findings from similar studies [51–55]. Interestingly, despite a higher incidence of asthma in the vaccinated group, this comorbidity has been linked to reduced mortality in hospitalized patients due to its association with TH2 lymphocyte inflammation, which acts as a protective factor against COVID-19 [56–60]. Consistent with prior documentation [61, 62], D-dimer values at admission showed statistically significant differences between the groups, with higher levels observed in the unvaccinated group, indicative of a hypercoagulable state and increased risk of adverse events and mortality.
This study demonstrated a reduction in COVID-19 mortality among patients vaccinated with Sinopharm and Sputnik-V, consistent with similar studies conducted in Qatar [63] and India [64] that reported a more than threefold increase in mortality among unvaccinated patients. Prior researches have evaluated the efficacy of the Pfizer-BioNTech, Moderna, Sinovac, and Sputnik-V vaccines, concluding that they are all safe and effective against all variants of interest included in their work in several countries around the world, including Chile, Brazil, Colombia, and Ecuador [65–68]. However, the quality of evidence varied across vaccines [69]. A study conducted in China involving the Delta variant demonstrated effective protection following two doses of inactivated virus vaccines such as Sinopharm and Sinovac, while partial vaccination offered no significant protection [70]. Another multicenter case-control study carried out in South American countries such as Argentina, Colombia, Chile, and Brazil, evaluated the efficacy of the Sinovac, Sinopharm, and Sputnik V vaccines (among others) by age and by the predominant circulating variant of SARS-CoV-2, demonstrating that vaccines prevented hospitalizations and deaths even among the oldest population [71, 72]. In a multicenter United States study, progression to death after COVID-19 hospitalization was associated with a lower likelihood of vaccination (OR = 0.41; 95% CI = 0.19–0.88) [67]. Finally, a study in Pakistan found significantly higher percent deaths in the unvaccinated group compared to the vaccinated group. However, they also documented variations according to patient age and type of vaccine. For example, the percent of COVID-19 cases who died among unvaccinated individuals > 50 years of age was 3.83- and 7.49-fold higher compared to recipients of Sinopharm and Sputnik V, respectively [73]. This is similar to our results.
High oxygen saturation, a valuable metric for classifying disease severity, was associated with lower mortality rates in both groups under study. Conversely, low oxygen saturation has been identified as a significant indicator of mortality risk [47, 74]. Additionally, the administration of enoxaparin, a low molecular weight heparin, was found to decrease mortality risk within our cohort, consistent with previous research [75, 76]. The impact of low molecular weight heparins in COVID-19 varies significantly depending on whether thromboprophylaxis or therapeutic doses are used, with the latter demonstrating greater benefit [77]. However, in accordance with the guidelines of the “Ministerio del Poder Popular para la Salud” (the primary national health institute) in Venezuela during the time of our study [78], thromboprophylaxis dosage was employed in this population, still yielding a significant difference.
In our model, no significant association was observed between comorbidities and COVID-19 outcomes, contradicting previous findings [79, 80]. The Charlson Comorbidity Index enabled us to evaluate patients in both groups based on their number of comorbidities and risk. However, well-managed long-term pathologies could potentially influence the accuracy of this measure and the outcomes. Increased age was associated with a higher risk of mortality, potentially due to older patients’ susceptibility to COVID-19 as hypothesized by Ayón-Aguilar et al. [81], which could be attributed to immunosenescence and their dysregulated inflammatory response. Institutions should consider assessing frailty at admission for all older patients admitted with COVID-19 to provide appropriate care for this risk group.
Significant variations in mortality risk were observed across different care centers. The therapeutic management of COVID-19 initially presented an uncertain pathway for providers, and guidelines remained quite open for personal suggestions and individualized treatment adapted on a case-by-case basis [78]. Coupled with the disparities described in healthcare centers in Venezuela, including challenges such as access to basic needs like water supply, continuous electricity, personnel shortage, and medication availability [82, 83], these factors do not remain constant between centers and departments within the same institution. The University Hospital of Caracas, located in the country’s capital, may have had an advantage in terms of resource accessibility and allocation, resulting in better outcomes and highlighting the ethical dilemma in attention care in Venezuela.
This study has several limitations. Despite its multicenter nature, it only included four hospitals in major cities of the country, so the results should be extrapolated with caution, especially in sociodemographic contexts of peri-urban and rural regions. The sample size was limited by the availability of beds in the services responsible for hospitalizing COVID-19 patients at that time. Its non-random methodology limits the estimation of vaccine efficacy, and the small sample size does not allow for secondary analysis in the population that received a partial vaccination schedule or a booster dose, nor does it allow for understanding the individual efficacy of each type of vaccine. In some cases, follow-up was conducted via telephone, but it was not possible in three patients, so the mortality found in this work could be higher. Finally, the absence of molecular tools did not allow for determining the variants involved in each case, which constitutes a significant limitation since we know that they may modify patient outcomes [84, 85]. Despite these limitations, this is the first study conducted in Venezuela that evaluates the effectiveness of the vaccines available in the country. This is an important step in understanding the impact of vaccination in real-world settings and may provide valuable information for public health decision-making.