COVID-19 Vaccination and Mortality Reduction: A Prospective Cohort Study in Venezuela

Abstract

Background
While rigorous randomized clinical trials have substantiated the efficacy of COVID-19 vaccines in reducing hospitalization and mortality rates, there is a paucity of post-authorization analyses conducted in real-world settings. In Venezuela, the primary vaccines administered are Sinopharm and Sputnik-V. However, the performance and effectiveness of these vaccines within this specific population remain to be thoroughly investigated.

Methods
A prospective cohort study was undertaken from October 5, 2021, to March 31, 2022, across four sentinel hospitals in Venezuela. The outcomes were evaluated at two time points: day 28 and day 48, utilizing the WHO’s COVID-19 Clinical Progression Scale. For the purpose of analysis, patients were classified into two groups: vaccinated and unvaccinated.

Results
The study included a total of 175 patients, of which 85 (48.6%) were categorized as vaccinated, with the majority (76.5%) having received two doses. The median age of the patients was 68 years, with a slight predominance of females (53.1%), and the majority being unemployed/retired (60.6%). Hypertension (53.1%) and diabetes (18.3%) were the most prevalent comorbidities. The median Charlson index of the patients was 3 points, with no statistically significant differences observed between the groups (p = 0.2). Upon admission, dyspnea was more commonly observed in unvaccinated patients compared to vaccinated patients (76.7% vs. 62.4%, p = 0.039). Almost all laboratory parameters were comparable in both groups, with the exception of the median D-dimer level, which was significantly higher in unvaccinated patients (7.6 vs. 1.4 µg/mL, p = 0.015). A total of 50 patients (28.6%) died of the disease, with a higher proportion of deaths observed in unvaccinated patients compared to vaccinated patients (35.6% vs. 21.2%, p = 0.035). Factors such as advanced age (OR = 1.043, 95%CI = 1.015–1.071, p = 0.002) were associated with increased odds of death, while factors such as vaccination against COVID-19 (OR = 0.428, 95%CI = 0.185–0.99, p = 0.047), high oxygen saturation (OR = 0.964, 95%CI = 0.934–0.995, p = 0.024), and enoxaparin administration (OR = 0.292, 95%CI = 0.093–0.917, p = 0.035) were associated with decreased odds of death.

Conclusion
In the course of the third and fourth waves of the pandemic, vaccination against COVID-19 was found to be associated with a 57% reduction in mortality among patients treated in four public hospitals in Venezuela.

Full text

Page 1/14
COVID-19 Vaccination and Mortality Reduction: A Prospective Cohort Study in
Venezuela
David A. Forero-Peña (  vacter.cv@gmail.com )
Biomedical Research and Therapeutic Vaccines Institute
Jéssica L. Leyva
Biomedical Research and Therapeutic Vaccines Institute
María V. Valenzuela
Biomedical Research and Therapeutic Vaccines Institute
Óscar D. Omaña-Ávila
Biomedical Research and Therapeutic Vaccines Institute
Daniela L. Mendoza-Millán
Biomedical Research and Therapeutic Vaccines Institute
Elisanny A. Sánchez-Ytriago
“Dr. Luis Razetti” University Hospital
Andrea C. Lahoud-El Hachem
Biomedical Research and Therapeutic Vaccines Institute
Katherine R. Farro
“Dr. Luis Razetti” University Hospital
Ana K. Maita
“Dr. Luis Razetti” University Hospital
Romina del C. González
“Dr. Luis Razetti” University Hospital
Carlis M. Rodriguez-Saavedra
Biomedical Research and Therapeutic Vaccines Institute
Fernando Hernández-Medina
Venezuelan Scientic Research Institute, Altos de Pipe
Natasha A. Camejo-Ávila
Biomedical Research and Therapeutic Vaccines Institute
Diana C. Freitas-De Nobrega
Biomedical Research and Therapeutic Vaccines Institute
Rodrigo T. Celis
Central University of Venezuela
José L. Forero-Peña
Biomedical Research and Therapeutic Vaccines Institute
Alfonso Martínez
Central University of Venezuela
María E. Grillet
Central University of Venezuela
María E. Landaeta
University Hospital of Caracas
Fhabián S. Carrión-Nessi
Biomedical Research and Therapeutic Vaccines Institute
Research Article
Keywords: COVID-19, Vaccination, COVID-19 Vaccines, Prospective Studies, Mortality, Venezuela
Posted Date: October 10th, 2023
DOI: https://doi.org/10.21203/rs.3.rs-3396851/v1
License:   This work is licensed under a Creative Commons Attribution 4.0 International License.  Read Full License

Page 2/14
Abstract
Background
While rigorous randomized clinical trials have substantiated the ecacy of COVID-19 vaccines in reducing hospitalization and mortality rates, there is a
paucity of post-authorization analyses conducted in real-world settings. In Venezuela, the primary vaccines administered are Sinopharm and Sputnik-V.
However, the performance and effectiveness of these vaccines within this specic population remain to be thoroughly investigated.
Methods
A prospective cohort study was undertaken from October 5, 2021, to March 31, 2022, across four sentinel hospitals in Venezuela. The outcomes were
evaluated at two time points: day 28 and day 48, utilizing the WHO’s COVID-19 Clinical Progression Scale. For the purpose of analysis, patients were classied
into two groups: vaccinated and unvaccinated.
Results
The study included a total of 175 patients, of which 85 (48.6%) were categorized as vaccinated, with the majority (76.5%) having received two doses. The
median age of the patients was 68 years, with a slight predominance of females (53.1%), and the majority being unemployed/retired (60.6%). Hypertension
(53.1%) and diabetes (18.3%) were the most prevalent comorbidities. The median Charlson index of the patients was 3 points, with no statistically signicant
differences observed between the groups (
p
= 0.2). Upon admission, dyspnea was more commonly observed in unvaccinated patients compared to vaccinated
patients (76.7% vs. 62.4%,
p
= 0.039). Almost all laboratory parameters were comparable in both groups, with the exception of the median D-dimer level, which
was signicantly higher in unvaccinated patients (7.6 vs. 1.4 µg/mL,
p
= 0.015). A total of 50 patients (28.6%) died of the disease, with a higher proportion of
deaths observed in unvaccinated patients compared to vaccinated patients (35.6% vs. 21.2%,
p
= 0.035). Factors such as advanced age (OR = 1.043, 95%CI =
1.015–1.071,
p
= 0.002) were associated with increased odds of death, while factors such as vaccination against COVID-19 (OR = 0.428, 95%CI = 0.185–0.99,
p
= 0.047), high oxygen saturation (OR = 0.964, 95%CI = 0.934–0.995,
p
= 0.024), and enoxaparin administration (OR = 0.292, 95%CI = 0.093–0.917,
p
= 0.035)
were associated with decreased odds of death.
Conclusion
In the course of the third and fourth waves of the pandemic, vaccination against COVID-19 was found to be associated with a 57% reduction in mortality
among patients treated in four public hospitals in Venezuela.
Background
As of September 27, 2023, the global impact of the coronavirus disease 2019 (COVID-19) has resulted in over 770million conrmed cases and more than
6.9million deaths [1]. The initial impact of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was signicant due to the limited understanding
of its transmission, treatment, and prevention strategies [2]. In response to the pandemic, numerous pharmaceutical companies initiated the development of
vaccines against SARS-CoV-2, resulting in at least 78 conrmed active vaccine candidates by April 2020 [3]. In late 2020, phase III results were reported for
several vaccines, including BNT162b2 (Pzer-BioNTech) with an ecacy of 90–97%, [4, 5], mRNA-1273 (Moderna) with an ecacy of 87–97% [6], ChAdOx1-
S/nCoV-19 (AstraZeneca) with an ecacy of 65–88% [7], Gam-COVID-Vac (Sputnik-V) with an ecacy of 94–100% [8], CoronaVac (Sinovac) with an ecacy
of 50–62%, and BBIBP-CorV (Sinopharm) with an ecacy of 64–86% [9]. The Pzer-BioNTech and Moderna vaccines were the rst to receive emergency use
authorization from the US Food and Drug Administration (FDA) in December 2020 [10–12], followed by approval from the World Health Organization (WHO) in
January 2021 [13, 14]. The Sinopharm and Sinovac vaccines received approval in May 2021 [13, 15, 16]. However, other candidates such as Sputnik-V have
yet to receive WHO approval [17–19].
Despite the slow progress of the vaccination process in Latin America, several countries have undertaken initiatives to expedite the process. Mexico was the
rst country to respond to the United Nations call in April 2021 to provide access to drugs and vaccines to combat COVID-19 [20]. Colombia became the rst
Latin American country to receive Pzer-BioNTech vaccines under the COVID-19 Vaccines Global Access (COVAX) program in March 2021 [21]. Chile donated
20,000 doses of the Chinese vaccine Sinovac to Ecuador and Paraguay [22]. In Venezuela, the vaccination campaign against COVID-19 utilized Sinopharm,
Sinovac, and Sputnik-V vaccines due to agreements with the Russian Federation [23] and global collaboration mechanisms such as COVAX [24].
The Venezuelan government initially planned to launch the “Mass Vaccination Plan” in January 2021, but the rst batch of vaccines arrived in February [25].
The process was divided into ve stages, with healthcare workers prioritized in the rst stage [24]. Subsequently, the supply of vaccines to Venezuela
continued sporadically and without prior planning, including the arrival of other vaccines such as Sinopharm, Sputnik-V, and vaccine candidates such as
Abdala, Soberana-2, and EpiVacCorona [24, 26]. By September 2021, the Pan American Health Organization (PAHO) reported a vaccination coverage of 14.9%
in Venezuela. By May 2022, Venezuela had administered a total of 38million doses, vaccinating 66% of its population [27]. Although some studies have
demonstrated that Sputnik-V vaccines are effective in eliciting a neutralizing antibody response in Venezuelan patients [28, 29], the clinical ecacy in this
population remains unknown.
While randomized clinical trials are considered the “gold standard” for evaluating the effects of a medical intervention, they have several limitations, including
sample size, subgroup analysis, restrictive inclusion criteria, and a highly controlled environment that may not be replicated during a mass launch. In addition,

Page 3/14
patient inclusion is often based on their clinical stability [30]. Suboptimal adherence to schedules and logistics also inuences its effectiveness. Therefore,
post-authorization analyses are crucial for evaluating the actual ecacy and behavior in real populations [31]. This study aims to describe the clinical
behavior and outcome of vaccinated and unvaccinated patients during the third and fourth pandemic waves in four hospitals in Venezuela.
Methods
Study design and population
A prospective cohort study was conducted among patients diagnosed with SARS-CoV-2 infection from October 5, 2021, and March 31, 2022, across various
sentinel hospitals in Venezuela. These included the University Hospital of Caracas (Capital District), “Dr. Luis Razetti” University Hospital (Anzoategui state),
“Ruiz y Páez” University Hospital Complex (Bolivar state), and “Uyapar” Hospital (Bolivar state). The diagnosis of SARS-CoV-2 infection was conrmed via
antigen testing and reverse transcription polymerase chain reaction (RT-PCR) [32] at the “Rafael Rangel” National Institute of Hygiene (Venezuela). The study
period included cases from the third (June to December 2021) and fourth (January to February 2022) waves of the pandemic in Venezuela [33], each
characterized by different variants of SARS-CoV-2. A national genomic surveillance study analyzed samples from nasopharyngeal or nasal swabs conrmed
positive by RT-PCR during routine COVID-19 diagnosis in Venezuela. The third wave presented variants of both interest and concern, starting with Gamma
(B.1.1.248) and ending with Delta (B.1.617). The fourth wave was predominantly characterized by the circulation of the Omicron variant (B.1.1.529) [34].
The severity of COVID-19 was categorized as mild (dened as the presence of various signs and symptoms of COVID-19, excluding shortness of breath,
dyspnea, or abnormal chest imaging), moderate (dened as evidence of lower respiratory disease during clinical assessment or imaging and an oxygen
saturation ≥ 94% on room air at sea level), severe (dened as oxygen saturation < 94% on room air at sea level, a ratio of arterial partial pressure of oxygen to
fraction of inspired oxygen < 300 mm Hg, a respiratory rate > 30 breaths/min, or lung inltrates > 50%), or critical (dened as respiratory failure, septic shock,
and/or multiple organ dysfunction). These categories were dened according to the guidelines provided by the National Institutes of Health (United States of
America) [35].
Epidemiological and clinical assessment
Patient data were collected by trained staff at sentinel centers through interviews and review of medical records. This data included epidemiological
characteristics (such as age, sex, education level, marital status, race, occupation, domicile), clinical characteristics (including symptoms on admission,
pathological history, psychobiological habits, physical examination), paraclinical characteristics (such as hematology, blood chemistry, coagulation tests),
vaccination status against COVID-19, and treatment received for COVID-19 (including antivirals, antibiotics, antiparasitics, corticosteroids, thromboprophylaxis,
immunomodulators, ventilatory support). The timely use of Remdesivir was dened as its administration within 7 days following symptom onset, while the
timely use of Favipiravir and Molnupiravir was dened as their administration within 5 days following symptom onset. The appropriate use of
Dexamethasone and Methylprednisolone was dened as their administration for up to 10 days.
The Charlson Comorbidity index was calculated to predict patient mortality [36]. Patient outcomes was assessed at day 28 and 48 post-admission using the
WHO’s COVID-19 Clinical Progression Scale [37]. The dates of patients who died prior to evaluation were recorded. For patients discharged alive prior to day 28
or 48, assessments were performed either face-to-face or via telephone to determine their outcome. For the purpose of analysis, patients were classied into
two groups based on their vaccination status: vaccinated and unvaccinated. Individuals were dened as “vaccinated” if they had received at least one dose of
a COVID-19 vaccine 14 days prior.
Statistical analysis
Patients’ data were summarized using descriptive statistics, including mean, standard deviation (SD), median, interquartile range (IQR), frequency, and
percentage (%). The distribution of numerical variables was evaluated using the Kolmogorov–Smirnov test. For variables with a non-normal distribution, the
Mann–Whitney U test was employed, while Student’s
t
-test was used for variables with a normal distribution. Categorical variables were analyzed using
Pearson’s chi-squared and Fisher’s exact tests. In instances where
post-hoc
analysis was required, the Bonferroni correction was applied to adjust the
p
-value.
A
p
-value of less than 0.05 was considered statistically signicant. Survival analysis was conducted using the Mantel–Cox test and visualized using Kaplan–
Meier curves. Binomial logistic regression with backward stepwise selection was utilized to identify factors associated with mortality. The most valid model,
which classied the highest percentage of patients and demonstrated a good t based on R2 Nagelkerke and the Hosmer–Lemeshow test, was selected.
Statistical analysis was performed using the Statistical Package for the Social Sciences (SPSS) version 26 (International Business Machines Corporation,
Armonk, NY, United States of America). Figures were generated using SPSS version 26 and Microsoft® Excel® version 2019 (Microsoft, Redmond, WA, United
States of America).
Results
Patients’ sociodemographics
During the study period, a total of 175 patients were included. Among these, 85 (48.6%) were categorized as vaccinated. Within the vaccinated group, 15/85
(17.6%) received one dose (86.7% received Sinopharm, and 13.3% received Sputnik-V), 65/85 (76.5%) received two doses (64.6% Sinopharm, and 35.4%
Sputnik-V), and 5/85 (5.9%) received three doses (20% Sinopharm, and 80% Sputnik-V) of the COVID-19 vaccine. All patients reported receiving homologous
vaccines. The mean duration between the onset of COVID-19 symptoms and the administration of the last dose of the COVID-19 vaccine was 123.6 (SD 88.9)
days.

Page 4/14
The patients had a median age of 68 (IQR 28) years, with a majority being female (53.1%), of mestizo race (85.1%), and unemployed/retired (60.6%) (Table1).
Geographically, 67 (38.3%) patients resided in Bolivar state, 48 (27.4%) in Anzoategui state, 52 (29.8%) in the Metropolitan Area of Caracas, and the remaining
8 (4.5%) in other states. A signicant association was observed between the categories “healthcare worker” and “vaccinated” (
p
= 0.0037).
Table 1
Sociodemographic characteristics of patients with COVID-19 according to their vaccination status
Characteristics Total (
n
= 175, 100%) Vaccinated (
n
= 85, 48.6%) Unvaccinated (
n
= 90, 51.4%)
P
-value
Age, median (IQR), years 68 (28) 67 (27) 69 (24) 0.304*
Sex, female/male (%) 93/82 (53.1/46.9) 43/42 (50.6/49.4) 50/40 (55.6/44.4) 0.51†
Level of education,
n
(%)    0.002†
None 21 (12) 5 (5.9) 16 (17.8) 
Primary school 65 (37.1) 36 (42.4) 29 (32.2) 
High school 46 (26.3) 16 (18.8) 30 (33.3) 
Associate degree/University 43 (24.6) 28 (32.9) 15 (16.7) 
Marital status,
n
(%)    0.152‡
Married 68 (38.9) 39 (45.9) 29 (32.2) 
Single 64 (36.6) 32 (37.6) 32 (35.6) 
Widowed 29 (16.6) 10 (11.8) 19 (21.1) 
Divorced 8 (4.6) 2 (2.4) 6 (6.7) 
Cohabiting (common-law) 6 (3.4) 2 (2.4) 4 (4.4) 
Race,
n
(%)    0.045‡
Mestizo 149 (85.1) 74 (87.1) 75 (83.3) 
White 19 (10.9) 11 (12.9) 8 (8.9) 
Black 6 (3.4) 0 (0) 6 (6.7) 
Indigenous 1 (0.6) 0 (0) 1 (1.1) 
Occupation,
n
(%)    0.02†§
Unemployed/Retired 106 (60.6) 51 (60) 55 (61.1) 
Employed 29 (16.6) 15 (17.6) 14 (15.6) 
Self-employed 25 (14.3) 8 (9.4) 17 (18.9) 
Healthcare worker 11 (6.3) 10 (11.8) 1 (1.1) 
Student 4 (2.3) 1 (1.2) 3 (3.3) 
*Mann–Whitney U test; †Pearson’s chi-square; ‡Fisher’s exact test; §Signicant association only between “healthcare worker” and “vaccinated” (
p
= 0.0037)
for a value α = 0.005 by Bonferroni correction. IQR: interquartile range
Medical history
Less than 10% of all patients reported having at least one previous SARS-CoV-2 infection; this background was less frequent among the unvaccinated
compared to the vaccinated (4.4% vs. 14.1%,
p
= 0.026). Hypertension was the most common comorbidity, affecting 53.1% (
n
= 93) of patients. This was
followed by diabetes (18.3%,
n
= 32), and asthma (9.1%,
n
= 16). A total of 10 patients (5.7%) had a history of oncologic conditions, including breast cancer
(four patients), acute lymphoblastic leukemia (three patients), cervical cancer (one patient), lung cancer (one patient), and thyroid cancer (one patient).
Additionally, three patients (1.7%) were diagnosed with the human immunodeciency virus. Interestingly, a higher proportion of vaccinated patients had
asthma compared to unvaccinated patients (14.1% vs. 4.4%,
p
= 0.026). The median Charlson index of patients was 3 (IQR 3) points, with no signicant
differences observed between groups (
p
= 0.2). Furthermore, no signicant differences were found between the vaccinated and unvaccinated patients in terms
of smoking habits, alcohol consumption, and illicit drug use (Table2).

Page 5/14
Table 2
Medical history of patients with COVID-19 according to their vaccination status
Characteristics Total (
n
= 175, 100%) Vaccinated (
n
= 85, 48.6%) Unvaccinated (
n
= 90, 51.4%)
P
-value
Previous SARS-CoV-2 infection, yes (%) 16 (9.1) 12 (14.1) 4 (4.4) 0.026*
Comorbidities, yes (%)    
Hypertension 93 (53.1) 40 (47.1) 53 (58.9) 0.117*
Diabetes 32 (18.3) 16 (18.8) 16 (17.8) 0.858*
Asthma 16 (9.1) 12 (14.1) 4 (4.4) 0.026*
COPD 10 (5.7) 4 (4.7) 6 (6.7) 0.576*
Cancer 10 (5.7) 3 (3.5) 7 (7.8) 0.226*
CKD 5 (2.9) 1 (1.2) 4 (4.4) 0.369†
Obesity 5 (2.9) 2 (2.4) 3 (3.3) 1†
CVD 4 (2.3) 2 (2.4) 2 (2.2) 1†
HIV 3 (1.7) 1 (1.2) 2 (2.2) 1†
Other 9 (5.1) 4 (4.7) 5 (5.6) 1†
Charlson Index, median (RIQ), points 3 (3) 2 (3) 3 (3) 0.2‡
Smoking, yes (%) 33 (18.9) 16 (18.8) 17 (18.9) 0.991*
Pack-year index, mean (SD) 17.7 (18.3) 21.8 (23.4) 13.8 (11.2) 0.215§
Alcoholics, yes (%) 23 (13.1) 13 (15.3) 10 (11.1) 0.413*
Illicit drug use, yes (%) 2 (1.1) 1 (1.2) 1 (1.1) 1†
*Pearson’s chi-square; †Fisher’s exact test; ‡Mann–Whitney U test; §Student’s
t
-test for independent samples. SARS-CoV-2: severe acute respiratory
syndrome coronavirus 2. COPD: chronic obstructive pulmonary disease. CKD: chronic kidney disease. CVD: cerebrovascular disease. HIV: human
immunodeciency virus. IQR: interquartile range. SD: standard deviation
Clinical characteristics upon admission
The median duration between the onset of COVID-19 symptoms and hospitalization was 6 (IQR 8) days, with no signicant differences observed between the
vaccinated and unvaccinated groups (7 vs. 5 days, respectively,
p
= 0.343 by Mann–Whitney U test). The most common symptoms upon admission were fever
(71.4%,
n
= 125), dyspnea (69.7%,
n
= 122), and dry cough (56.6%,
n
= 99). Less common symptoms included low back pain (2.9%,
n
= 5), dysphonia (3.4%,
n
=
6), and dysphagia (4%,
n
= 7). A higher proportion of vaccinated patients reported myalgias compared to unvaccinated patients (29.4% vs. 14.4%,
p
= 0.016),
while dyspnea was more prevalent in unvaccinated patients (76.7% vs. 62.4%,
p
= 0.039) (Fig.1).
Upon physical examination, the median heart rate, respiratory rate, and oxygen saturation at admission were 90 (IQR 24) bpm, 22 (IQR 6) rpm, and 89 (IQR 14)
%, respectively. Notably, the median respiratory rate was signicantly higher in unvaccinated patients compared to vaccinated patients (24 vs. 22 rpm,
p
=
0.005). Crackles (73.1%,
n
= 128) and decreased breath sounds (50.3%,
n
= 88) were the most common pathological ndings on chest auscultation, and
altered consciousness was observed in 14.3% (
n
= 25) of all patients upon admission. Furthermore, the most frequently documented radiographic thoracic
pathological ndings were an interstitial pattern (51.7%,
n
= 62) and lung elds with a reinforced bronchovascular tract (20%,
n
= 24) (Table3).

Page 6/14
Table 3
Physical exam ndings on admission of patients with COVID-19 according to their vaccination status
Characteristics Total (
n
= 175, 100%) Vaccinated (
n
= 85, 48.6%) Unvaccinated (
n
= 90, 51.4%)
P
-value
Hemodynamic parameters    
Heart rate, median (IQR), bpm 90 (24) 88 (23) 90 (23) 0.916*‡
Breathing rate, median (IQR), rpm 22 (6) 22 (6) 24 (7) 0.004*‡
SBP, median (IQR), mm Hg 122 (30) 124 (30) 122 (29) 0.646*‡
DBP, median (IQR), mm Hg 75 (18) 75 (16) 76 (20) 0.821*‡
Oxygen saturation, median (IQR), % 89 (14) 90 (10) 87 (14) 0.02*‡
Chest pathologic ndings on auscultation, yes (%)    
Crackles 128 (73.1) 63 (74.1) 65 (72.2) 0.777†*
Decreased breath sounds 88 (50.3) 44 (51.8) 44 (48.9) 0.704†*
Intercostal pull 23 (13.1) 13 (15.3) 10 (11.1) 0.413†*
Hypoexpansible chest 20 (11.4) 8 (9.4) 12 (13.3) 0.415†*
Roncus 18 (10.3) 11 (12.9) 7 (7.8) 0.261†*
Wheezing 16 (9.1) 10 (11.8) 6 (6.7) 0.242†*
Other 2 (1.1) 0 (0) 2 (2.2) 0.498‡†
Thoracic radiographic pathological ndings,
n
(%)    0.301‡†
Interstitial pattern 62 (51.7) 26 (44.8) 36 (58.1) 
Lung elds with reinforced bronchovascular tract 24 (20) 16 (27.6) 8 (12.9) 
Inltrates 19 (15.8) 8 (13.8) 11 (17.7) 
Consolidation 10 (8.3) 5 (8.6) 5 (8.1) 
Pleural effusion 5 (4.2) 3 (5.2) 2 (3.2) 
Altered neurological status, yes (%) 25 (14.3) 14 (16.5) 11 (12.2) 0.422†*
*Mann–Whitney U test; †Pearson’s chi-square; ‡Fisher’s exact test. IQR: interquartile range. SBP: systolic blood pressure. DBP: diastolic blood pressure
Paraclinical ndings upon admission
Table4 presents the paraclinical ndings of the patients upon admission. The majority of the laboratory parameters were comparable between both groups.
However, an exception was the median D-dimer level, which was signicantly higher in unvaccinated patients compared to vaccinated patients (7.6 vs. 1.4
µg/mL,
p
= 0.015).

Page 7/14
Table 4
Paraclinical ndings on admission of patients with COVID-19 according to their vaccination status
Characteristics Total (
n
= 175, 100%) Vaccinated (
n
= 85, 48.6%) Unvaccinated (
n
= 90, 51.4%)
P
-value
Hemoglobin, mean (SD), g/dL 12.2 (2.2) 12.5 (2.4) 12 (2) 0.212*
Hematocrit, mean (SD), % 39.9 (6.7) 38 (6.8) 37.8 (6.6) 0.85*
White blood cells, median (IQR), ×103/mL 9.4 (6.1) 10.2 (7.5) 8.9 (5.6) 0.097†
Neutrophils, median (IQR), ×103/mL 81 (18) 81 (15) 80.9 (18.5) 0.997†
Lymphocytes, median (IQR), ×103/mL 15 (14.8) 13.4 (12) 16.8 (17.3) 0.7†
Platelets, mean (SD), ×103/mL 245.5 (114.2) 254.6 (118.8) 236.1 (109.5) 0.39*
Glycemia, median (IQR), mg/dL 117 (69) 117 (70) 116.9 (70) 0.856†
Urea, median (IQR), mg/dL 36.5 (25.7) 38.5 (22) 36 (24.7) 0.729†
Creatinine, median (IQR), mg/dL 1 (0.4) 1 (0.4) 0.9 (0.5) 0.695†
PT, mean (SD), sec 12.4 (3.2) 12.3 (3.4) 12.4 (3.1) 0.905*
PTT, mean (SD), sec 30.5 (12.3) 32.4 (14.7) 28.1 (8.5) 0.312*
Fibrinogen, mean (SD), mg/dL 535.5 (454.6) 469.3 (232.9) 668.1 (742.7) 0.398*
AST, mean (SD), U/L 37.5 (17.6) 39 (19.4) 35.4 (15) 0.513*
ALT, mean (SD), U/L 40 (18.5) 40.6 (20.5) 39.1 (15.8) 0.808*
Total bilirubin, mean (SD), mg/dL 1 (1.1) 0.8 (0.6) 1 (1.4) 0.702*
LDH, mean (SD), U/L 430.8 (238.6) 438.5 (271) 423.1 (204.6) 0.783*
ESR, mean (SD), mm/h 41.5 (28.8) 31.4 (22.1) 51.5 (32.8) 0.204*
CRP, median (IQR), mg/L 12 (42.4) 14.7 (54.8) 11 (26.9) 0.134†
D-dimer, median (IQR), µg/mL 2.2 (14.3) 1.4 (3.9) 7.6 (118) 0.015†
Ferritin, median (IQR), ng/mL 336.1 (406.4) 405 (243.9) 314 (287.5) 0.222†
Procalcitonin, median (IQR), ng/mL 0.4 (0.6) 0.4 (1.6) 0.4 (0.2) 1†
Albumins, mean (SD), g/L 3.3 (0.5) 3.3 (0.5) 3.3 (0.6) 0.999*
*Student’s
t
-test for independent samples; †Mann–Whitney U test. SD: standard deviation. IQR: interquartile range. PT: prothrombin time. PTT: partial
thromboplastin time. AST: aspartate aminotransferase. ALT: alanine aminotransferase. LDH: lactate dehydrogenase. ERS: erythrocyte sedimentation rate.
CRP: C-reactive protein
Medications administered
In this cohort, the antivirals administered were Remdesivir (14.9%,
n
= 26), Favipiravir (4.7%,
n
= 13), and Molnupiravir (1.7%,
n
= 3). These were administered in
a timely manner in 50% (
n
= 13/26), 84.6% (
n
= 11/13), and 66.7% (
n
= 2/3) of cases, respectively. Furthermore, 45.7% (
n
= 80) of patients received antibiotic
treatment, predominantly Levooxacin (23%), followed by Ceftriaxone and Meropenem. Meropenem was administered in a higher proportion of vaccinated
patients compared to unvaccinated patients (9.4% vs. 2.2%,
p
= 0.041). Regarding corticosteroids, Dexamethasone was administered to 59.4% (
n
= 104) of
patients and was used appropriately in 88.2% (n = 60/104) of these cases. Tocilizumab was only used in two patients (1.1%) (Supplementary Data 1).
Clinical outcome
The median time between hospitalization and discharge was 10 (IQR 12) days, with no statistically signicant differences between the vaccinated and non-
vaccinated groups (11 vs. 10 days, respectively,
p
= 0.526 by Mann–Whitney U test). In the vaccinated group, two patients required admission to the intensive
care unit, whereas, in the unvaccinated group, four did (
p
= 0.683 by Pearson’s chi-square test). During the study period, 50 (28.6%) patients died, and a higher
proportion of deaths was found in unvaccinated patients compared to vaccinated patients (35.6% vs. 21.2%,
p
= 0.035 by Pearson’s chi-squared test).
Moreover, it was found that being vaccinated against COVID-19 decreased the probability of mortality (
p
= 0.028) (Fig.2).
The median duration between hospitalization and discharge was 10 (IQR 12) days, with no signicant differences observed between the vaccinated and
unvaccinated groups (11 vs. 10 days, respectively,
p
= 0.526 by Mann–Whitney U test). In the vaccinated group, two patients required admission to the
intensive care unit, compared to four patients in the unvaccinated group (
p
= 0.683 by Pearson’s chi-square test). During the study period, there were 50 deaths
(28.6% of patients), with a higher proportion observed among unvaccinated patients compared to vaccinated patients (35.6% vs. 21.2%,
p
= 0.035 by Pearson’s
chi-squared test). Furthermore, it was determined that vaccination against COVID-19 reduced the probability of mortality (
p
= 0.028) (Fig.2).

Page 8/14
Factors associated with mortality
The most valid model (
p
< 0.001, R2 Nagelkerke = 0.341, Hosmer–Lemeshow test = 0.238) accurately classied 78.9% (
n
= 138) of patients. Factors associated
with increased odds of mortality included advanced age (OR = 1.043, 95% CI = 1.015–1.071,
p
= 0.002), and receiving treatment at the “Dr. Luis Razetti”
University Hospital (OR = 3.897, 95% CI = 1.053–14.418,
p
= 0.042) or “Uyapar” Hospital (OR = 7.317, 95% CI = 1.798–29.776,
p
= 0.005) compared to the
University Hospital of Caracas. On the other hand, factors associated with decreased odds of mortality included vaccination against COVID-19 (OR = 0.428,
95% CI = 0.185–0.99,
p
= 0.047), high oxygen saturation (OR = 0.964, 95% CI = 0.934–0.995,
p
= 0.024), and administration of enoxaparin (OR = 0.292, 95% CI =
0.093–0.917,
p
= 0.035) (Table5).
Table 5
Risk factors associated with mortality patients with COVID-19
β
P
-value OR adjusted (95% condence interval)
Vaccinated against COVID-19, yes -0.848 0.047 0.428 (0.185–0.99)
Age 0.042 0.002 1.043 (1.015–1.071)
Sex, male 0.412 0.307 1.51 (0.687–3.326)
Care center (reference: University Hospital of Caracas)   
“Dr. Luis Razetti” University Hospital 1.36 0.042 3.897 (1.053–14.418)
“Ruiz y Páez” University Hospital Complex 0.874 0.103 2.397 (0.839–6.846)
“Uyapar” Hospital 1.99 0.005 7.317 (1.798–29.776)
Hypertension, yes -0.109 0.8 0.897 (0.386–2.083)
Dyspnea, yes -0.234 0.614 0.791 (0.318–1.967)
Oxygen saturation -0.037 0.024 0.964 (0.934–0.995)
Crackles, yes 0.447 0.375 1.563 (0.583–4.191)
Dexamethasone, yes -0.467 0.386 0.627 (0.218–1.803)
Enoxaparin, yes -1.231 0.035 0.292 (0.093–0.917)
Discussion
This study represents the rst 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 signicant 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 ndings 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 inammation, which acts as a protective
factor against COVID-19 [56–60]. Consistent with prior documentation [61, 62], D-dimer values at admission showed statistically signicant 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 ecacy of the Pzer-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 signicant protection [70]. Another multicenter case-control study carried out in
South American countries such as Argentina, Colombia, Chile, and Brazil, evaluated the ecacy 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 signicantly 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

Page 9/14
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 identied as a signicant 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 signicantly depending on whether thromboprophylaxis or therapeutic doses are used, with the latter demonstrating greater benet [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 signicant difference.
In our model, no signicant association was observed between comorbidities and COVID-19 outcomes, contradicting previous ndings [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 inuence 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 inammatory response. Institutions should consider assessing frailty at admission for all older patients admitted with COVID-19 to provide
appropriate care for this risk group.
Signicant 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 ecacy, 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 ecacy 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 signicant limitation since we know that they may modify patient outcomes [84, 85]. Despite these limitations, this is the rst 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.
Conclusions
This study found an association between COVID-19 vaccination and a reduction in mortality among COVID-19 patients treated in four public hospitals in
Venezuela during the third and fourth pandemic waves. However, to ascertain the individual ecacy of each vaccine and its correlation with the number of
doses administered, further multicenter studies involving larger populations are warranted.
Abbreviations
COVID-19
coronavirus disease 2019,
SARS-CoV-2
severe acute respiratory syndrome coronavirus 2,
FDA
US Food and Drug Administration,
WHO
World Health
Organization,
COVAX
COVID-19 Vaccines Global Access,
PAHO
Pan American Health Organization,
RT-PCR
reverse transcription polymerase chain reaction,
SD
standard deviation,
IQR
interquartile range,
SPSS
Statistical Package for the Social Sciences
Declarations
Ethics approval and consent to participate
The study protocol was reviewed and approved by the Independent Bioethics Committee for Research of the National Center for Bioethics (CIBI-CENABI, in
Spanish) of Venezuela (CIBI-CENABI-14/2021). The study was conducted in accordance with the ethical principles for medical research in humans of the
Declaration of Helsinki and the Venezuelan regulations for this type of research, with the corresponding signed informed consent of all patients.
Consent for publication
Not applicable.
Availability of data and materials
All data generated or analyzed during this study are included in the article.
Competing interests
The authors declare no competing interests.

Page 10/14
Funding
This research did not receive any specic grant from funding agencies in the public, commercial, or not-for-prot sectors.
Authors’ contributions
DAFP, JLL, MVV, and FSCN conceived and designed the study. DAFP, JLL, MVV, DCFDN, EAS, KRF, AKM, RdCG, DLMM, and FSCN collected clinical data. ÓDOÁ,
ACLEH, CMRS, FHM, NACÁ, DLMM, and FSCN analyzed and interpreted the data. JLL, MVV, ÓDOÁ, ACLEH, CMRS, RTC, JLFP, DLMM, AM, and FSCN wrote the
manuscript. DAFP, FHM, MEG, JE, MEL, and FSCN critically reviewed the manuscript. All authors reviewed and approved the nal version of the manuscript.
Acknowledgements
Not applicable.
References
1. (WHO) WHO: Who coronavirus (COVID-19) dashboard (no date) Available at: https://covid19whoint/ (Accessed: May. 2023) 2023.
2. Novelli G, Biancolella M, Mehrian-Shai R, Erickson C, Godri Pollitt KJ, Vasiliou V, Watt J. Reichardt JKJHg: COVID-19 update: the rst 6 months of the
pandemic. 2020, 14(1):1–9.
3. Le TT, Andreadakis Z, Kumar A, Román RG, Tollefsen S, Saville M, Mayhew SJNRDD. The COVID-19 vaccine development landscape. 2020, 19(5):305–6.
4. Polack FP, Thomas SJ, Kitchin N, Absalon J, Gurtman A, Lockhart S, Perez JL, Pérez Marc G, Moreira ED. Zerbini CJNEjom: Safety and ecacy of the
BNT162b2 mRNA Covid-19 vaccine. 2020, 383(27):2603–15.
5. Gargano JW. Grading of recommendations, assessment, development, and evaluation (GRADE): Pzer BioNTech COVID-19 vaccine. 2020.
. Baden LR, El Sahly HM, Essink B, Kotloff K, Frey S, Novak R, Diemert D, Spector SA, Rouphael N. Creech CBJNEjom: Ecacy and safety of the mRNA-1273
SARS-CoV-2 vaccine. 2021, 384(5):403–16.
7. Voysey M, Clemens SAC, Madhi SA, Weckx LY, Folegatti PM, Aley PK, Angus B, Baillie VL, Barnabas SL, Bhorat QEJTL. Single-dose administration and the
inuence of the timing of the booster dose on immunogenicity and ecacy of ChAdOx1 nCoV-19 (AZD1222) vaccine: a pooled analysis of four
randomised trials. 2021, 397(10277):881–91.
. Logunov DY, Dolzhikova IV, Shcheblyakov DV, Tukhvatulin AI, Zubkova OV, Dzharullaeva AS, Kovyrshina AV, Lubenets NL, Grousova DM, Erokhova ASJTL.
Safety and ecacy of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine: an interim analysis of a randomised controlled
phase 3 trial in Russia. 2021, 397(10275):671–81.
9. Kim JH, Marks F. Clemens JDJNm: Looking beyond COVID-19 vaccine phase 3 trials. 2021, 27(2):205–11.
10. Bok K, Sitar S, Graham BS, Mascola JRJI. Accelerated COVID-19 vaccine development: milestones, lessons, and prospects. 2021, 54(8):1636–51.
11. Vahidy F, Boom ML, Drews AL, Hackett C, Miller SM, Phillips RA, Schwartz RL. Sostman HDJNCIiCD: Houston Methodist’s Mandate of COVID-19 Vaccine
Boosters Among Health Care Workers. Volume 3. Setting Precedents During Unprecedented Times; 2022. 1.
12. Basheeruddin Asdaq SM, Jomah S, Rabbani SI, Alamri AM, Salem Alshammari SK, Duwaidi BS, Alshammari MS, Alamri AS, Alsanie WF, Alhomrani
MJCJID et al. Insight into the advances in clinical trials of SARS-CoV-2 vaccines. 2022, 2022.
13. World Health O. Interim recommendations for use of the Pzer–BioNTech COVID-19 vaccine, BNT162b2, under emergency use listing: interim guidance,
rst issued 8 January 2021, updated 15 June 2021, updated 19 November 2021, updated 21 January 2022. In. Geneva: World Health Organization; 2022.
14. World Health O. Interim recommendations for use of the Moderna mRNA-1273 vaccine against COVID-19: interim guidance, rst issued 25 January 2021,
updated 15 June 2021, updated 19 November 2021, updated 23 February 2022. In. Geneva: World Health Organization; 2022.
15. World Health O. Interim recommendations for use of the inactivated COVID-19 vaccine BIBP developed by China National Biotec Group (CNBG),
Sinopharm: interim guidance, rst issued 7 May 2021, updated 28 October 2021, updated 15 March 2022. In. Geneva: World Health Organization; 2022.
1. World Health O. Interim recommendations for use of the inactivated COVID-19 vaccine, CoronaVac, developed by Sinovac: interim guidance, rst issued
24 May 2021, updated 21 October 2021, updated 15 March 2022. In. Geneva: World Health Organization; 2022.
17. Sputnik Vaccine Ecacy Data Published in Lancet Are. ‘Statistically Impossible’ [https://healthpolicy-watch.news/sputnik-vaccine-ecacy-
data/#:~:text=To%20date%2C%20the%20World%20Health,necessary%20data%20has%20been%20submitted].
1. Sputnik V. WHO suspends approval process for COVID vaccine due to 'manufacturing' concerns [https://www.euronews.com/next/2021/09/16/sputnik-v-
who-suspends-approval-process-for-covid-vaccine-due-to-manufacturing-
concerns#:~:text=Next%20Health-,Sputnik%20V%3A%20WHO%20suspends%20approval%20process%20for,vaccine%20due%20to%20'manufacturing'%20
19. The W H. .O. puts off assessing Russia’s Sputnik vaccine because of the war in Ukraine. [https://www.nytimes.com/2022/03/16/world/europe/who-
sputnik-covid-vaccine.html].
20. Olabuenaga PAJRMPE. Un faro en la oscuridad: México y la resolución 74/274 de la Asamblea General de las Naciones Unidas. 2021(119):239–258.
21. Salud, OOOPdl. Colombia recibe Las Primeras Vacunas Que Llegan a las américas a través del Mecanismo COVAX. In. Edited by 2023). Aahwpoen—c-r-p-
v-q-l-a-t-m-cAM; 2021, 1 Mar.
22. Horwitz L, Zissis CJASCARM. Timeline: Tracking Latin America’s road to vaccination. 2021, 5:2021.
23. Tecnología, MdPPpCy. Otras 500 mil dosis de Sputnik V arribaron al país para fortalecer vacunación masiva. In: i>https://wwwmincytgobve/otras-500-
mil-dosis-de-sputnik-v-arribaron-al-pais-para-fortalecer-vacunacion-masiva/. 13 junio 2021.

Page 11/14
24. López-Loyo ES, Urbina-Medina H, Esparza JJGMC. Aporte institucional de la Academia Nacional de Medicina de Venezuela en tiempos de pandemia:
vacunación contra la COVID-19. 2021, 129(4):801–13.
25. 24 F. “Venezuela Recibe El Primer Lote De La Vacuna Sputnik V.”. In. Edited by https://www.france24.com/es/europa/20210213-covid19-astrazeneca-
estudia-vacuna-ni%C3%B1os-oms.; February 13, 2021.
2. Loyo ESL, González MJ, Esparza JJL. Venezuela is collapsing without COVID-19 vaccines. 2021, 397(10287):1806.
27. COVID-19 Data Explorer. : Global Humanitarian Operations.
2. Claro F, Silva D, Bogado JAP, Rangel HR. de Waard JHJIJoID: Lasting SARS-CoV-2 specic IgG Antibody response in health care workers from Venezuela,
6 months after vaccination with Sputnik V. 2022, 122:850–4.
29. Claro F, Silva D, Rodriguez M, Rangel HR, de Waard JH. Immunoglobulin G antibody response to the Sputnik V vaccine: previous SARS-CoV-2 seropositive
individuals may need just one vaccine dose. Int J Infect diseases: IJID : ocial publication Int Soc Infect Dis. 2021;111:261–6.
30. BioNTech SJCN. Study to describe the safety, tolerability, immunogenicity, and ecacy of RNA vaccine candidates against COVID-19 in healthy
individuals. 2020.
31. Covid-19 vaccine effectiveness research.
32. World Health Organization %J World Health Organization GAvhwwidd-scr-t-. Protocol: real-time RT-PCR assays for the detection of SARS-CoV-2. Paris:
Institut Pasteur; 2020. r-p-a-f-t-d-o-s-.
33. Arvelo MC, Montes de Oca M, Sánchez-Traslaviña L, Pujol FH, Jaspe RC, Silva IC, Stulin I, Blanco G, Quevedo J. Valera NJRPdMEySP: Cambios en las
características clínicas y desenlaces de pacientes hospitalizados por COVID-19 durante dos años de pandemia: experiencia en un hospital venezolano.
2022, 39:292–301.
34. Jaspe RC, Loureiro CL, Sulbaran Y, Moros ZC, D’Angelo P, Hidalgo M, Rodríguez L, Alarcón V, Aguilar M, Sánchez D et al. Description of a One-Year
Succession of Variants of Interest and Concern of SARS-CoV-2 in Venezuela. 2022, 14(7):1378.
35. In:
Coronavirus Disease 2019 (COVID-19) Treatment Guidelines
. edn. Bethesda (MD): National Institutes of Health (US); 2021.
3. Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation.
J chronic Dis. 1987;40(5):373–83.
37. A minimal common. outcome measure set for COVID-19 clinical research. Lancet Infect Dis. 2020;20(8):e192–7.
3. Organization WH. Protocol: real-time RT-PCR assays for the detection of SARS-CoV-2, Institut Pasteur, Paris.
World Health Organization, Geneva Available
via https://www
i>who int/docs/default-source/coronaviruse/real-time-rt-pcr-assays-for-the-detection-of-sars-cov-2-institut-pasteur-paris pdf 2020.
39. Goyal P, Choi JJ, Pinheiro LC, Schenck EJ, Chen R, Jabri A, Satlin MJ, Campion TR Jr., Nahid M, Ringel JB, et al. Clinical Characteristics of Covid-19 in New
York City. N Engl J Med. 2020;382(24):2372–4.
40. Colaneri M, Sacchi P, Zuccaro V, Biscarini S, Sachs M, Roda S, Pieri TC, Valsecchi P, Piralla A, Seminari E et al. Clinical characteristics of coronavirus
disease (COVID-19) early ndings from a teaching hospital in Pavia, North Italy, 21 to 28 February 2020. Euro Surveill 2020, 25(16).
41. Tomlins J, Hamilton F, Gunning S, Sheehy C, Moran E, MacGowan A. Clinical features of 95 sequential hospitalised patients with novel coronavirus 2019
disease (COVID-19), the rst UK cohort. J Infect. 2020;81(2):e59–e61.
42. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan,
China. Lancet. 2020;395(10223):497–506.
43. Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, Wang B, Xiang H, Cheng Z, Xiong Y, et al. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel
Coronavirus-Infected Pneumonia in Wuhan, China. JAMA. 2020;323(11):1061–9.
44. Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, Qiu Y, Wang J, Liu Y, Wei Y, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel
coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020;395(10223):507–13.
45. Liu K, Fang YY, Deng Y, Liu W, Wang MF, Ma JP, Xiao W, Wang YN, Zhong MH, Li CH, et al. Clinical characteristics of novel coronavirus cases in tertiary
hospitals in Hubei Province. Chin Med J. 2020;133(9):1025–31.
4. Guan W-j, Ni Z-y, Hu Y, Liang W-h, Ou C-q, He J-x, Liu L, Shan H. Lei C-l, Hui DSJNEjom: Clinical characteristics of coronavirus disease 2019 in China. 2020,
382(18):1708–20.
47. Forero-Peña DA, Carrión-Nessi FS, Mendoza-Millán DL, Omaña-Ávila ÓD, Mejía-Bernard MD, Camejo-Ávila NA, Flora-Noda DM, Velásquez VL, Chacón-
Labrador FR, Doval-Fernández JM, et al. First wave of COVID-19 in Venezuela: Epidemiological, clinical, and paraclinical characteristics of rst cases. J
Med Virol. 2022;94(3):1175–85.
4. Martínez C, Serrano-Coll H, Faccini Á, Contreras V, Galeano K, Botero Y, Herrera Y, Garcia A, Garay E, Rivero R, et al. SARS-CoV-2 in a tropical area of
Colombia, a remarkable conversion of presymptomatic to symptomatic people impacts public health. BMC Infect Dis. 2022;22(1):644.
49. González FJ, Miranda FA, Chávez SM, Gajardo AI, Hernández AR, Guiñez DV, Díaz GA, Sarmiento NV, Ihl FE, Cerda MA, et al. Clinical characteristics and in-
hospital mortality of patients with COVID-19 in Chile: A prospective cohort study. Int J Clin Pract. 2021;75(12):e14919.
50. Estenssoro E, Loudet CI, Ríos FG, Kanoore Edul VS, Plotnikow G, Andrian M, Romero I, Piezny D, Bezzi M, Mandich V, et al. Clinical characteristics and
outcomes of invasively ventilated patients with COVID-19 in Argentina (SATICOVID): a prospective, multicentre cohort study. Lancet Respir Med.
2021;9(9):989–98.
51. Sayeed MA, Shalim E, Farooqui F, Farman S, Khan M, Iqbal A, Ahmed I, Rajput AW, Razzaque A, Quraishy S. Comparison of the Disease Severity and
Outcome of Vaccinated COVID-19 Patients with Unvaccinated Patients in a Specialized COVID-19 Facility: A Retrospective Cohort Study from Karachi,
Pakistan.
Vaccines (Basel)
2023, 11(7).

Page 12/14
52. Aslam J, Rauf Ul Hassan M, Fatima Q, Bashir Hashmi H, Alshahrani MY, Alkhathami AG, Aneela I. Association of disease severity and death outcome with
vaccination status of admitted COVID-19 patients in delta period of SARS-COV-2 in mixed variety of vaccine background. Saudi J Biol Sci.
2022;29(7):103329.
53. Korishettar G, Chikkahonnaiah P, Tulimilli SV, Dallavalasa S, Byrappa SH, Madhunapantula SV, Veeranna RP. Assessment of Clinical Prole and Treatment
Outcome in Vaccinated and Unvaccinated SARS-CoV-2 Infected Patients. Vaccines (Basel) 2022, 10(7).
54. Freund O, Tau L, Weiss TE, Zornitzki L, Frydman S, Jacob G, Bornstein G. Associations of vaccine status with characteristics and outcomes of
hospitalized severe COVID-19 patients in the booster era. PLoS ONE. 2022;17(5):e0268050.
55. Ruiz-Giardin JM, Rivilla M, Mesa N, Morales A, Rivas L, Izquierdo A, Escribá A, San Martín JV, Bernal-Bello D, Madroñal E et al. Comparative Study of
Vaccinated and Unvaccinated Hospitalised Patients: A Retrospective Population Study of 500 Hospitalised Patients with SARS-CoV-2 Infection in a
Spanish Population of 220,000 Inhabitants. Viruses 2022, 14(10).
5. Adir Y, Saliba W, Beurnier A, Humbert MJERR. Asthma and COVID-19: an update. 2021, 30(162).
57. Eggert LE, He Z, Collins W, Lee AS, Dhondalay G, Jiang SY, Fitzpatrick J, Snow TT, Pinsky BA, Artandi MJA. Asthma phenotypes, associated comorbidities,
and long-term symptoms in COVID‐19. 2022, 77(1):173–85.
5. Sansone NMS, Valencise FE, Bredariol RF, Peixoto AO, Marson FAL. Prole of coronavirus disease enlightened asthma as a protective factor against
death: An epidemiology study from Brazil during the pandemic. Front Med (Lausanne). 2022;9:953084.
59. Zhang JJ, Dong X, Liu GH, Gao YD. Risk and Protective Factors for COVID-19 Morbidity, Severity, and Mortality. Clin Rev Allergy Immunol. 2023;64(1):90–
107.
0. Lombardi C, Gani F, Berti A, Comberiati P, Peroni D, Cottini M. Asthma and COVID-19: a dangerous liaison? Asthma Res Pract. 2021;7(1):9.
1. Eljilany I, Elzouki A-N. D-Dimer, Fibrinogen, and IL-6 in COVID-19 Patients with Suspected Venous Thromboembolism: A Narrative Review. Vasc Health Risk
Manag. 2020;16:455–62.
2. Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, Xiang J, Wang Y, Song B, Gu X, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19
in Wuhan, China: a retrospective cohort study. Lancet. 2020;395(10229):1054–62.
3. Butt AA, Nafady-Hego H, Chemaitelly H, Abou-Samra AB, Khal AA, Coyle PV, Kanaani ZA, Kaleeckal AH, Latif AN, Masalmani YA, et al. Outcomes Among
Patients with Breakthrough SARS-CoV-2 Infection After Vaccination. Int J Infect Dis. 2021;110:353–8.
4. Balachandran S, Moni M, Sathyapalan DT, Varghese P, Jose MP, Murugan MR, Rajan C, Saboo D, Nair SS, Varkey RA, et al. A comparison of clinical
outcomes between vaccinated and vaccine-naive patients of COVID-19, in four tertiary care hospitals of Kerala, South India. Clin Epidemiol global health.
2022;13:100971.
5. Dagan N, Barda N, Kepten E, Miron O, Perchik S, Katz MA, Hernán MA, Lipsitch M, Reis B, Balicer RD. BNT162b2 mRNA Covid-19 Vaccine in a Nationwide
Mass Vaccination Setting. N Engl J Med. 2021;384(15):1412–23.
. Papagoras C, Fragoulis GE, Zioga N, Simopoulou T, Deftereou K, Kalavri E, Zampeli E, Gerolymatou N, Kataxaki E, Melissaropoulos K, et al. Better
outcomes of COVID-19 in vaccinated compared to unvaccinated patients with systemic rheumatic diseases. Ann Rheum Dis. 2022;81(7):1013–6.
7. Tenforde MW, Self WH, Adams K, Gaglani M, Ginde AA, McNeal T, Ghamande S, Douin DJ, Talbot HK, Casey JD, et al. Association Between mRNA
Vaccination and COVID-19 Hospitalization and Disease Severity. JAMA. 2021;326(20):2043–54.
. Delgado PC. Vélez JCCJRCFI-XPdC, Investigación y Publicación: Ecacia de las vacunas disponibles contra el virus SARS-CoV-2 en Latinoamérica y
Europa. 2022, 7(4):1526–55.
9. Fiolet T, Kherabi Y, MacDonald CJ, Ghosn J, Peiffer-Smadja N. Comparing COVID-19 vaccines for their characteristics, ecacy and effectiveness against
SARS-CoV-2 and variants of concern: a narrative review. Clin Microbiol Infect. 2022;28(2):202–21.
70. Hu Z, Tao B, Li Z, Song Y, Yi C, Li J, Zhu M, Yi Y, Huang P, Wang J. Effectiveness of inactivated COVID-19 vaccines against severe illness in B.1.617.2
(Delta) variant–infected patients in Jiangsu, China. Int J Infect Dis. 2022;116:204–9.
71. Kahn R, Janusz CB, Castro MC, da Rocha Matos A, Domingues C, Ponmattam J, Rey-Benito G, Toscano CM, Helena de Oliveira L. The effectiveness of
COVID-19 vaccines in Latin America, 2021: a multicenter regional case-control study. Lancet Reg Health Am. 2023;20:100474.
72. Spinardi J, Dantas AC, Carballo C, Thakkar K, Akoury NA, Kyaw MH, Del Carmen Morales Castillo G, Srivastava A, Sáfadi MAP. Narrative Review of the
Evolution of COVID-19 Vaccination Recommendations in Countries in Latin America, Africa and the Middle East, and Asia. Infect Dis therapy.
2023;12(5):1237–64.
73. AlQahtani M, Du X, Bhattacharyya S, Alawadi A, Al Mahmeed H, Al Sayed J, Justman J, El-Sadr WM, Hidary J, Mukherjee S. Post-vaccination outcomes in
association with four COVID-19 vaccines in the Kingdom of Bahrain. Sci Rep. 2022;12(1):9236.
74. Liu W, Yang C, Liao YG, Wan F, Lin L, Huang X, Zhang BH, Yuan Y, Zhang P, Zhang XJ, et al. Risk factors for COVID-19 progression and mortality in
hospitalized patients without pre-existing comorbidities. J Infect Public Health. 2022;15(1):13–20.
75. Joanico-Morales B, Gaspar-Chamu AD, Salgado-Jiménez M, Rodríguez-Echeverría G. [Enoxaparin dose associated with decreased risk of death in COVID-
19]. Revista Med del Instituto Mexicano del Seguro Social. 2022;60(1):33–9.
7. Gupta S, Hayek SS, Wang W, Chan L, Mathews KS, Melamed ML, Brenner SK, Leonberg-Yoo A, Schenck EJ, Radbel J, et al. Factors Associated With Death
in Critically Ill Patients With Coronavirus Disease 2019 in the US. JAMA Intern Med. 2020;180(11):1436–47.
77. Spyropoulos AC, Goldin M, Giannis D, Diab W, Wang J, Khanijo S, Mignatti A, Gianos E, Cohen M, Sharifova G, et al. Ecacy and Safety of Therapeutic-
Dose Heparin vs Standard Prophylactic or Intermediate-Dose Heparins for Thromboprophylaxis in High-risk Hospitalized Patients With COVID-19: The
HEP-COVID Randomized Clinical Trial. JAMA Intern Med. 2021;181(12):1612–20.

Page 13/14
7. MPPS, Caracas DF. Guía para el manejo y tratamiento de contactos y pacientes con COVID-19 - Comité Terapéutico COVID-19. In. Ministerio del Poder
Popular para la Salud de Venezuela; 2020. p. 21.
79. Sezen YI, Senoglu S, Karabela SN, Yesilbag Z, Borcak D, Canbolat Unlu E, Korkusuz R, Ozdemir Y, Kart Yasar K. Risk factors and the impact of vaccination
on mortality in COVID-19 patients. Bratisl Lek Listy. 2022;123(6):440–3.
0. Christensen DM, Strange JE, Gislason G, Torp-Pedersen C, Gerds T, Fosbøl E, Phelps M. Charlson Comorbidity Index Score and Risk of Severe Outcome
and Death in Danish COVID-19 Patients. J Gen Intern Med. 2020;35(9):2801–3.
1. Ayón-Aguilar J, Méndez-Martínez S, Toledo-Tapia R, García-Flores MA, Mayoral-Ortiz A, Tlecuitl-Mendoza N, Toledo-Tapia M, Ortega-Aguirre M, Amaro-
Balderas E. [Inuence of risk factors on mortality from COVID-19]. Revista Med del Instituto Mexicano del Seguro Social. 2022;60(4):433–9.
2. Mendoza Millán DL, Carrión-Nessi FS, Mejía Bernard MD, Marcano-Rojas MV, Omaña Ávila ÓD, Doval Fernández JM, Chacón Labrador FR, Quintero
Rodríguez A, Gasparini Vega S, Tami A, et al. Knowledge, Attitudes, and Practices Regarding COVID-19 Among Healthcare Workers in Venezuela: An Online
Cross-Sectional Survey. Front Public Health. 2021;9:633723.
3. Paniz-Mondol AE, Sordillo EM, Márquez-Colmenarez MC, Delgado-Noguera LA, Rodriguez-Morales AJ. The arrival of SARS-CoV-2 in Venezuela. Lancet.
2020;395(10236):e85–6.
4. Stepanova M, Lam B, Younossi E, Felix S, Ziayee M, Price J, Pham H, de Avila L, Terra K, Austin P, et al. The impact of variants and vaccination on the
mortality and resource utilization of hospitalized patients with COVID-19. BMC Infect Dis. 2022;22(1):702.
5. Bakhshandeh B, Jahanafrooz Z, Abbasi A, Goli MB, Sadeghi M, Mottaqi MS, Zamani M. Mutations in SARS-CoV-2; Consequences in structure, function,
and pathogenicity of the virus. Microb Pathog. 2021;154:104831.
Figures
Figure 1
Symptoms on admission of patients with COVID-19 according to their vaccination status. Data are graphed as percentage. *
p
< 0.05 (
p
‐values by Pearson’s
chi-square)

Page 14/14
Figure 2
Kaplan-Meier curves showing the probability of survival patients with COVID-19 according to their vaccination status.Log Rank (Mantel–Cox test) = 4.811,
p
=
0.028.
Supplementary Files
This is a list of supplementary les associated with this preprint. Click to download.
SupplementaryData1.docx