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Covid-19 Clinical Course and Blood Groups: Turkish Population-Based Study
Dal MS, Ata N, Altuntaş F, Başci S, Yiğenoğlu TN, Korkmaz S, Namdaroğlu S, Baştürk A, Hacibekiroğlu T, Doğu MH, et al
Turkish journal of medical sciences. 2021
Abstract
BACKGROUND/AIM: SARS-CoV-2 enters the cell through the binding of the S glycoprotein on the surface of the virus to the angiotensin-converting enzyme 2 (ACE-2) in the host cells and also SARS-CoV S protein binding to ACE-2 was inhibited by anti-A antibodies. The aim of the study was to investigate the relationship between blood groups and the course of COVID-19 in Turkey. MATERIALS AND METHODS Laboratory confirmed COVID-19 patients aged 18 and over (n=39.850) were randomized in age and gender-matched groups according to blood groups Results: Advanced age, male gender and blood group A were found to be related with increased rate of intensive care unit (ICU) admission (OR =1.089, 95% CI: 1.085-1.093 for age; OR=1.963, 95% CI: 1.737-2.218 for male gender; OR=1.216, 95% CI: 1.023-1.446 for blood group A). When blood group O individuals were compared to non-O individuals, no significant difference was observed regarding the rate of hospital and ICU admission, mechanical ventilation (MV) support, length of hospital and ICU stay, and case fatality rate (CFR). The CFR in patients with blood group A, B, O, and AB were 2.6%, 2.2%, 3.1%, and 2.3%, respectively. There were no significant differences between Rh-negative and positive patients regarding the rate of hospital and ICU admission (p=0.280 and p=0.741, respectively), also the rate of MV support and CFR was similar (p=0.933 and p= 0.417). CONCLUSION Our study revealed that ABO and Rh blood groups do not have any impact on the rate of hospital admission, hospital and ICU stay, MV support, and CFR.
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Intracranial Pressure and Cerebral Perfusion Pressure in Large Spontaneous Intracranial Hemorrhage and Impact of Minimally Invasive Surgery
Al-Kawaz MN, Li Y, Thompson RE, Avadhani R, de Havenon A, Gruber J, Awad I, Hanley DF, Ziai W
Frontiers in neurology. 2021;12:729831
Abstract
Introduction: We investigated the effect of hematoma volume reduction with minimally invasive surgery (MIS) on intracranial pressure (ICP) and cerebral perfusion pressure (CPP) in patients with large spontaneous intracerebral hemorrhage (ICH). Methods: Post-hoc analysis of the Minimally Invasive Surgery Plus Alteplase for Intracerebral Hemorrhage Evacuation (MISTIE III) study, a clinical trial with blinded outcome assessments. The primary outcome was the proportion of ICP readings ≥20 and 30 mmHg, and CPP readings <70 and 60 mm Hg. Secondary outcomes included major disability (modified Rankin scale >3) and mortality at 30 and 365 days. We assessed the relationship between proportion of high ICP and low CPP events and MIS using binomial generalized linear models, and outcomes using multiple logistic regression. Results: Of 499 patients enrolled in MISTIE III, 72 patients had guideline based ICP monitors placed, 34 in the MIS group and 38 in control (no surgery) group. Threshold ICP and CPP events ≥20/ <70 mmHg occurred in 31 (43.1%) and 52 (72.2%) patients respectively. On adjusted analyses, proportion of ICP readings ≥20 and 30 mmHg were significantly lower in the MIS group vs. control group [Odds Ratio (OR) 0.27, 95% Confidence Interval [CI] 0.11-0.63 (p = 0.002); OR = 0.18, 0.04-0.75, p = 0.02], respectively. Proportion of CPP readings <70 and 60 mm Hg were also significantly lower in MIS patients [OR 0.31, 95% CI 0.15-0.63 (p = 0.001); OR 0.30, 95% CI 0.11-0.83 (p = 0.02)], respectively. Higher proportions of CPP readings <70 and 60 mm were significantly associated with short term mortality (p = 0.04), and (p = 0.006), respectively. Long term mortality was significantly associated with higher proportion of time with ICP ≥ 20 (p = 0.04), ICP ≥ 30 (p = 0.04), and CPP <70 mmHg (p = 0.01). Conclusion: Our results are consistent with the hypothesis that surgical reduction of ICH volume decreases proportion of high ICP and low CPP events and that these variables are associated with short- and long-term mortality.
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A Prospective Randomized Double-Blind Clinical Trial to Assess the Effects of Leukocyte-reduced Platelet-Rich Plasma on Pro-inflammatory, Degradative, and Anabolic Biomarkers after Closed Pilon Fractures
Zitsch BP, James CR, Crist BD, Stoker AM, Della Rocca GJ, Cook JL
Journal of orthopaedic research : official publication of the Orthopaedic Research Society. 2021
Abstract
Post-traumatic osteoarthritis (PTOA) significantly affects patients with pilon fractures even after adequate anatomical reduction, and treatment strategies targeting the biologic mediators of PTOA are needed. This study was designed to determine the effects of intra-articular injection of platelet-rich plasma (PRP) on synovial fluid (SF) biomarkers for patients undergoing open reduction and internal fixation (ORIF) of pilon fractures. Patients undergoing staged management of pilon fractures were enrolled in a prospective, double-blinded, randomized, placebo-controlled clinical trial to determine the effects of a single intra-articular injection of leukocyte-reduced PRP on SF biomarkers. Arthrocentesis of the injured and uninjured ankles was performed at time of external skeletal fixation (ESF) and ORIF. Patients were randomized to receive either autogenous leukocyte-reduced PRP or saline (control) via intra-articular injection into the injured ankle at time of ESF. SF biomarker concentrations were compared--uninjured, injured pre-treatment, and saline-injected or PRP-injected. Eleven patients (PRP, n=5; saline, n=6) completed the study. 21 un-injured, and 11 injured pre-treatment, 5 PRP-treated, and 6 saline-treated SF samples were analyzed. PRP-treated SF contained significantly higher levels of PDGF-AA (p=0.046) and significantly lower levels of MMP-3 (p=0.042), MMP-9 (p=0.009), IL-1β (p=0.049), IL-6 (p<0.01), IL-8 (p=0.048) and PGE2 (p<0.04). This study provided mechanistic data to suggest that a single intraarticular injection of leukocyte-reduced PRP is associated with anti-inflammatory, anti-degradative and anabolic responses compared to saline control. These findings provide the impetus for investigating long-term clinical outcomes after PRP injection as an orthobiologic adjunct to ORIF for mitigating the incidence and severity of PTOA after pilon fractures. This article is protected by copyright. All rights reserved.
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Clinical and Microbiological Outcomes Associated With Use of Platelet-Rich Plasma in Chronic Venous Leg Uclers: A Randomized Controlled Trial
Pires Bmfb, Baptista de Oliveira BGR, Bokehi LC, Luiz RR, Carvalho BTF, Santana RF, Alfradique de Souza P, Renato de Paula G, Teixeira LA
Journal of wound, ostomy, and continence nursing : official publication of The Wound, Ostomy and Continence Nurses Society. 2021;48(4):292-299
Abstract
PURPOSE To evaluate the susceptibility profiles of Staphylococcus aureus and Pseudomonas aeruginosa strains identified in chronic venous ulcers treated with platelet-rich plasma (PRP) and petrolatum gauze or petrolatum gauze alone and to quantitatively evaluate the bacterial load and biofilm-forming capacities of the detected S. aureus and P. aeruginosa strains. DESIGN Randomized controlled trial. SUBJECTS AND SETTING The convenience sample included 36 participants; 18 were allocated to the PRP combined with the petrolatum gauze group, and 18 were allocated to the control group, which was treated with petrolatum gauze alone. METHODS Thirty-six patients presenting with chronic venous ulcers were consecutively randomized to the PRP group (n = 18) or the petrolatum gauze control group (n = 18). We followed participants for 3 months during treatment and collected swab cultures from their wounds during weeks 1, 6, and 12 or until the wounds healed. The samples were analyzed using mass spectrometry. Antimicrobial susceptibility tests were performed using disk diffusion. RESULTS P. aeruginosa was identified in 39 (39%) of 100 samples, and S. aureus was detected in only 10 (10%) samples collected over the study period. At the end of the 12-week treatment period, the wound infections reduced in both the PRP (P = .0078) and control groups (P = .01). The microorganisms were susceptible to most of the tested antimicrobials. The PRP did not increase the bacterial load in the wounds. All S. aureus strains identified showed biofilm-forming capacities and were classified as weak biofilm producers. All P. aeruginosa strains produced biofilm, with 17 strains being classified as weak, 14 as moderate, and 8 as strong biofilm producers. CONCLUSIONS The PRP plus petrolatum gauze did not increase bacteriological growth or the microbial load in chronic venous ulcers compared with petrolatum gauze alone and could be a considered as an advanced treatment option for these types of chronic wounds.
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A Trial of Hyperimmune Globulin to Prevent Congenital Cytomegalovirus Infection
Hughes BL, Clifton RG, Rouse DJ, Saade GR, Dinsmoor MJ, Reddy UM, Pass R, Allard D, Mallett G, Fette LM, et al
The New England journal of medicine. 2021;385(5):436-444
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Abstract
BACKGROUND Primary cytomegalovirus (CMV) infection during pregnancy carries a risk of congenital infection and possible severe sequelae. There is no established intervention for preventing congenital CMV infection. METHODS In this multicenter, double-blind trial, pregnant women with primary CMV infection diagnosed before 24 weeks' gestation were randomly assigned to receive a monthly infusion of CMV hyperimmune globulin (at a dose of 100 mg per kilogram of body weight) or matching placebo until delivery. The primary outcome was a composite of congenital CMV infection or fetal or neonatal death if CMV testing of the fetus or neonate was not performed. RESULTS From 2012 to 2018, a total of 206,082 pregnant women were screened for primary CMV infection before 23 weeks of gestation; of the 712 participants (0.35%) who tested positive, 399 (56%) underwent randomization. The trial was stopped early for futility. Data on the primary outcome were available for 394 participants; a primary outcome event occurred in the fetus or neonate of 46 of 203 women (22.7%) in the group that received hyperimmune globulin and of 37 of 191 women (19.4%) in the placebo group (relative risk, 1.17; 95% confidence interval [CI] 0.80 to 1.72; P = 0.42). Death occurred in 4.9% of fetuses or neonates in the hyperimmune globulin group and in 2.6% in the placebo group (relative risk, 1.88; 95% CI, 0.66 to 5.41), preterm birth occurred in 12.2% and 8.3%, respectively (relative risk, 1.47; 95% CI, 0.81 to 2.67), and birth weight below the 5th percentile occurred in 10.3% and 5.4% (relative risk, 1.92; 95% CI, 0.92 to 3.99). One participant in the hyperimmune globulin group had a severe allergic reaction to the first infusion. Participants who received hyperimmune globulin had a higher incidence of headaches and shaking chills while receiving infusions than participants who received placebo. CONCLUSIONS Among pregnant women, administration of CMV hyperimmune globulin starting before 24 weeks' gestation did not result in a lower incidence of a composite of congenital CMV infection or perinatal death than placebo. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Center for Advancing Translational Sciences; ClinicalTrials.gov number, NCT01376778.).
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Intermediate vs Standard-dose Prophylactic Anticoagulation in Patients with COVID-19 Admitted to ICU: Ninety-day Results from the INSPIRATION Trial
Bikdeli, B., Talasaz, A. H., Rashidi, F., Bakhshandeh, H., Rafiee, F., Matin, S., Baghizadeh, E., Rezaeifar, P., Jamalkhani, S., Tahamtan, O., et al
Thrombosis and Haemostasis. 2021
Abstract
BACKGROUND Thrombotic complications are considered among the main extrapulmonary manifestations of COVID-19. The optimal type and duration of prophylactic antithrombotic therapy in these patients remain unknown. METHODS This manuscript reports the final (90-day) results of the Intermediate versus Standard-dose Prophylactic anticoagulation In cRitically-ill pATIents with COVID-19: An opeN label randomized controlled trial (INSPIRATION) study. Patients with COVID-19 admitted to intensive care were randomized to intermediate-dose versus standard-dose prophylactic anticoagulation for 30 days, irrespective of hospital discharge status. The primary efficacy outcome was a composite of adjudicated venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation (ECMO), or all-cause death. The main safety outcome was major bleeding. RESULTS Of 600 randomized patients, 562 entered the modified intention-to-treat analysis (median age [Q1, Q3]; 62 (50, 71) years; 237 (42.2%) women), of whom 336 (59.8%) survived to hospital discharge. The primary outcome occurred in 132 (47.8%) of patients assigned to intermediate-dose and 130 (45.4%) patients assigned to standard-dose prophylactic anticoagulation (hazard ratio [HR]: 1.21, 95% confidence interval [CI]: 0.95-1.55, P=0.11). No significant differences were observed between the two groups for other efficacy outcomes, or in the landmark analysis from days 31-90. Overall, there were 7 (2.5%) major bleeding events in the intermediate-dose group (including 3 fatal events) and 4 (1.4%) major bleeding events in the standard-dose group (none fatal) (HR: 1.82, 95% CI: 0.53-6.24, P=0.33). CONCLUSION Intermediate-dose compared with standard-dose prophylactic anticoagulation did not reduce a composite of death, treatment with ECMO, or venous or arterial thrombosis at 90-day follow-up.
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Severe Acute Respiratory Syndrome Coronavirus 2 Convalescent Plasma Versus Standard Plasma in Coronavirus Disease 2019 Infected Hospitalized Patients in New York: A Double-Blind Randomized Trial
Bennett-Guerrero, E., Romeiser, J. L., Talbot, L. R., Ahmed, T., Mamone, L. J., Singh, S. M., Hearing, J. C., Salman, H., Holiprosad, D. D., Freedenberg, A. T., et al
Critical Care Medicine. 2021
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Abstract
OBJECTIVES Four peer-reviewed publications have reported results from randomized controlled trials of convalescent plasma for coronavirus disease 2019 infection; none were conducted in the United States nor used standard plasma as a comparator. To determine if administration of convalescent plasma to patients with coronavirus disease 2019 increases antibodies to severe acute respiratory syndrome coronavirus 2 and improves outcome. DESIGN Double-blind randomized controlled trial. SETTING Hospital in New York. PATIENTS Patients with polymerase chain reaction documented coronavirus disease 2019 infection. INTERVENTIONS Patients were randomized (4:1) to receive 2 U of convalescent plasma versus standard plasma. Antibodies to severe acute respiratory syndrome coronavirus 2 were measured in plasma units and in trial recipients. MEASUREMENTS AND MAIN RESULTS Enrollment was terminated after emergency use authorization was granted for convalescent plasma. Seventy-four patients were randomized. At baseline, mean (SD) Acute Physiology and Chronic Health Evaluation II score (23.4 [5.6] and 22.5 [6.6]), percent of patients intubated (19% and 20%), and median (interquartile range) days from symptom onset to randomization of 9 (6-18) and 9 (6-15), were similar in the convalescent plasma versus standard plasma arms, respectively. Convalescent plasma had high neutralizing activity (median [interquartile range] titer 1:526 [1:359-1:786]) and its administration increased antibodies to severe acute respiratory syndrome coronavirus 2 by 14.4%, whereas standard plasma administration led to an 8.6% decrease (p = 0.005). No difference was observed for ventilator-free days through 28 days (primary study endpoint): median (interquartile range) of 28 (2-28) versus 28 (0-28; p = 0.86) for the convalescent plasma and standard plasma groups, respectively. A greater than or equal to 2 point improvement in the World Health Organization scale was achieved by 20% of subjects in both arms (p = 0.99). All-cause mortality through 90 days was numerically lower in the convalescent plasma versus standard plasma groups (27% vs 33%; p = 0.63) but did not achieve statistical significance. A key prespecified subgroup analysis of time to death in patients who were intubated at baseline was statistically significant; however, sample size numbers were small. CONCLUSIONS Administration of convalescent plasma to hospitalized patients with coronavirus disease 2019 infection increased antibodies to severe acute respiratory syndrome coronavirus disease 2 but was not associated with improved outcome.
PICO Summary
Population
Patients with coronavirus disease 2019 (n= 74).
Intervention
Convalescent plasma (n= 59).
Comparison
Standard plasma (n= 15).
Outcome
At baseline, mean (SD) Acute Physiology and Chronic Health Evaluation II score (23.4 [5.6] and 22.5 [6.6]), percent of patients intubated (19% and 20%), and median (interquartile range) days from symptom onset to randomization of 9 (6-18) and 9 (6-15), were similar in the convalescent plasma versus standard plasma arms, respectively. Convalescent plasma had high neutralizing activity (median [interquartile range] titre 1:526 [1:359-1:786]) and its administration increased antibodies to severe acute respiratory syndrome coronavirus 2 by 14.4%, whereas standard plasma administration led to an 8.6% decrease. No difference was observed for ventilator-free days through 28 days: median (interquartile range) of 28 (2-28) versus 28 (0-28) for the convalescent plasma and standard plasma groups, respectively. A greater than or equal to 2 point improvement in the World Health Organization scale was achieved by 20% of subjects in both arms. All-cause mortality through 90 days was numerically lower in the convalescent plasma versus standard plasma groups (27% vs 33%) but did not achieve statistical significance.
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Nature and Dimensions of Systemic Hyperinflammation and its Attenuation by Convalescent Plasma in Severe COVID-19
Bandopadhyay, P., D'Rozario, R., Lahiri, A., Sarif, J., Ray, Y., Paul, S. R., Roy, R., Maiti, R., Chaudhuri, K., Bagchi, S., et al
The Journal of Infectious Diseases. 2021;224(4):565-574
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Abstract
BACKGROUND Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing coronavirus disease 2019 (COVID-19), has led to significant morbidity and mortality. While most suffer from mild symptoms, some patients progress to severe disease with acute respiratory distress syndrome (ARDS) and associated systemic hyperinflammation. METHODS First, to characterize key cytokines and their dynamics in this hyperinflammatory condition, we assessed abundance and correlative expression of a panel of 48 cytokines in patients progressing to ARDS as compared to patients with mild disease. Then, in an ongoing randomized controlled trial of convalescent plasma therapy (CPT), we analyzed rapid effects of CPT on the systemic cytokine dynamics as a correlate for the level of hypoxia experienced by the patients. RESULTS We identified an anti-inflammatory role of CPT independent of its neutralizing antibody content. CONCLUSIONS Neutralizing antibodies, as well as reductions in circulating interleukin-6 and interferon-γ-inducible protein 10, contributed to marked rapid reductions in hypoxia in response to CPT. CLINICAL TRIAL REGISTRY OF INDIA CTRI/2020/05/025209. http://www.ctri.nic.in/.
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Early versus deferred anti-SARS-CoV-2 convalescent plasma in patients admitted for COVID-19: A randomized phase II clinical trial
Balcells, M. E., Rojas, L., Le Corre, N., Martínez-Valdebenito, C., Ceballos, M. E., Ferrés, M., Chang, M., Vizcaya, C., Mondaca, S., Huete, Á, et al
Plos Medicine. 2021;18(3):e1003415
Abstract
BACKGROUND Convalescent plasma (CP), despite limited evidence on its efficacy, is being widely used as a compassionate therapy for hospitalized patients with COVID-19. We aimed to evaluate the efficacy and safety of early CP therapy in COVID-19 progression. METHODS AND FINDINGS The study was an open-label, single-center randomized clinical trial performed in an academic medical center in Santiago, Chile, from May 10, 2020, to July 18, 2020, with final follow-up until August 17, 2020. The trial included patients hospitalized within the first 7 days of COVID-19 symptom onset, presenting risk factors for illness progression and not on mechanical ventilation. The intervention consisted of immediate CP (early plasma group) versus no CP unless developing prespecified criteria of deterioration (deferred plasma group). Additional standard treatment was allowed in both arms. The primary outcome was a composite of mechanical ventilation, hospitalization for >14 days, or death. The key secondary outcomes included time to respiratory failure, days of mechanical ventilation, hospital length of stay, mortality at 30 days, and SARS-CoV-2 real-time PCR clearance rate. Of 58 randomized patients (mean age, 65.8 years; 50% male), 57 (98.3%) completed the trial. A total of 13 (43.3%) participants from the deferred group received plasma based on clinical aggravation. We failed to find benefit in the primary outcome (32.1% versus 33.3%, odds ratio [OR] 0.95, 95% CI 0.32-2.84, p > 0.999) in the early versus deferred CP group. The in-hospital mortality rate was 17.9% versus 6.7% (OR 3.04, 95% CI 0.54-17.17 p = 0.246), mechanical ventilation 17.9% versus 6.7% (OR 3.04, 95% CI 0.54-17.17, p = 0.246), and prolonged hospitalization 21.4% versus 30.0% (OR 0.64, 95% CI, 0.19-2.10, p = 0.554) in the early versus deferred CP group, respectively. The viral clearance rate on day 3 (26% versus 8%, p = 0.204) and day 7 (38% versus 19%, p = 0.374) did not differ between groups. Two patients experienced serious adverse events within 6 hours after plasma transfusion. The main limitation of this study is the lack of statistical power to detect a smaller but clinically relevant therapeutic effect of CP, as well as not having confirmed neutralizing antibodies in donor before plasma infusion. CONCLUSIONS In the present study, we failed to find evidence of benefit in mortality, length of hospitalization, or mechanical ventilation requirement by immediate addition of CP therapy in the early stages of COVID-19 compared to its use only in case of patient deterioration. TRIAL REGISTRATION NCT04375098.
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Safety and Seroconversion of Immunotherapies against SARS-CoV-2 Infection: A Systematic Review and Meta-Analysis of Clinical Trials
Ma KS, Lee CC, Liu KJ, Wei JC, Lee YT, Wang LT
Pathogens (Basel, Switzerland). 2021;10(12)
Abstract
Clinical trials evaluating the safety and antibody response of strategies to manipulate prophylactic and therapeutic immunity have been launched. We aim to evaluate strategies for augmentation of host immunity against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. We searched clinical trials registered at the National Institutes of Health by 25 May 2021 and conducted analyses on inoculated populations, involved immunological processes, source of injected components, and trial phases. We then searched PubMed, Embase, Scopus, and the Cochrane Central Register of Controlled Trials for their corresponding reports published by 25 May 2021. A bivariate, random-effects meta-analysis was used to derive the pooled estimate of seroconversion and adverse events (AEs). A total of 929,359 participants were enrolled in 389 identified trials. The working mechanisms included heterologous immunity, active immunity, passive immunity, and immunotherapy, with 62.4% of the trials on vaccines. A total of 9072 healthy adults from 27 publications for 22 clinical trials on active immunity implementing vaccination were included for meta-analyses. The pooled odds ratios (ORs) of seroconversion were 13.94, 84.86, 106.03, and 451.04 (all p < 0.01) for vaccines based on protein, RNA, viral vector, and inactivated virus, compared with that of respective placebo/control treatment or pre-vaccination sera. The pooled ORs for safety, as defined by the inverse of systemic adverse events (AEs) were 0.53 (95% CI = 0.27-1.05; p = 0.07), 0.35 (95% CI = 0.16-0.75; p = 0.007), 0.32 (95% CI = 0.19-0.55; p < 0.0001), and 1.00 (95% CI = 0.73-1.36; p = 0.98) for vaccines based on protein, RNA, viral vector, and inactivated virus, compared with that of placebo/control treatment. A paradigm shift from all four immune-augmentative interventions to active immunity implementing vaccination was observed through clinical trials. The efficacy of immune responses to neutralize SARS-CoV-2 for these vaccines was promising, although systemic AEs were still evident for RNA-based and viral vector-based vaccines.