Real-world effectiveness of mRNA COVID-19 vaccines in the elderly during the Delta and Omicron variants:Systematic review

BACKGROUND As of 31 December 2022,there were over 6.6 million coronavirus disease 2019(COVID-19)deaths and over 651 million cases across 200 countries worldwide.Despite the increase in vaccinations and booster shots,COVID-19 cases and deaths continue to remain high.While the effectiveness of these vaccines has already been established by different manufacturers,the fact remains that these vaccines were created quickly for global emergency use,tested under controlled clinical conditions from voluntary subjects and age groups whose general characteristics may differ from the actual general population.AIM To conduct a systematic review to determine the real-world effectiveness of mRNA COVID-19 vaccines in the elderly during the predominance of Delta and Omicron variants in preventing COVID-19 related infection,hospital,intensive care unit(ICU)admission and intubation,and death.METHODS A combination of Medical Subject Headings and non–Medical Subject Headings was carried out to identify all relevant research articles that meets the inclusion and exclusion criteria from PubMed,Cochrane,CINAHL,Scopus,ProQuest,EMBASE,Web of Science,and Google Scholar databases,as well as qualified research studies from pre–print servers using medRxiv and Research Square,published from January 1,2021-December 31,2022.RESULTS As per the inclusion and exclusion criteria,the effectiveness of Pfizer-BioNTech and Moderna vaccines were evaluated from an estimated total study population of 26535692 using infection,hospital,ICU admission and intubation,and death as outcome measures from studies published between 2021 and 2022,conducted in New York,Finland,Canada,Costa Rica,Qatar,Greece,and Brazil.The risk of bias was evaluated using risk of bias in nonrandomized studies of interventions(ROBINS-I)tool for cohort,case-control,and cross-sectional studies.While clinical trial data on Pfizer-BioNTech and Moderna vaccines demonstrated 94%vaccine effectiveness in the elderly,the results in this study showed that vaccine effectiveness in real-world settings is marginally lower against infection(40%-89%),hospitalization(92%),ICU admission and intubation(98%-85%),and death(77%-87%)with an indication of diminished effectiveness of vaccine over time.Furthermore,2 doses of mRNA vaccines are inadequate and only provides interim protection.CONCLUSION Because of the natural diminishing effectiveness of the vaccine,the need for booster dose to restore its efficacy is vital.From a research perspective,the use of highly heterogeneous outcome measures inhibits the comparison,contrast,and integration of the results which makes data pooling across different studies problematic.While pharmaceutical intervention like vaccination is important to fight an epidemic,utilizing common outcome measurements or carrying out studies with minimal heterogeneity in outcome measurements,is equally crucial to better understand and respond to an international health crisis.

Drug-induced sarcoidosis-like reaction three months after BNT162b2 mRNA COVID-19 vaccination:A case report and review of literature

BACKGROUND A 70-year-old man with hepatitis C virus-related recurrent hepatocellular carcinoma was admitted for further diagnosis of a 1 cm iso-hyperechoic nodule in segment(S)5.CASE SUMMARY Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging(EOB-MRI)revealed the nodule in S5 with a defect at the hepatobiliary phase,hyperintensity on diffusion weighted imaging(DWI)and hypointensity on apparent diffusion coefficient(ADC)map.Contrast-enhanced computed tomography revealed hypervascularity at the early phase,and delayed contrast-enhancement was observed at the late phase.Contrast-enhanced ultrasound(US)revealed incomplete defect at the late vascular phase.Inflammatory liver tumor,lymphoproliferative disease,intrahepatic cholangiocarcinoma(small duct type)and bile duct adenoma were suspected through the imaging studies.US guided biopsy,however,showed a noncaseating hepatic sarcoid-like epithelioid granuloma(HSEG),and histopathological analysis disclosed spindle shaped epithelioid cells harboring Langhans-type multinucleated giant cells.One month after admission,EOB-MRI signaled the disappearance of the defect at the hepatobiliary phase,of hyperintensity on DWI,of hypointensity on ADC map,and no stain at the early phase.CONCLUSION That the patient had received BNT162b2 messenger RNA(mRNA)coronavirus disease 2019 vaccination 3 mo before the occurrence of HSEG,and that its disappearance was confirmed 4 mo after mRNA vaccination suggested that the drug-induced sarcoidosis-like reaction(DISR)might be induced by the mRNA vaccination.Fortunately,rechallenge of drug-induced DISR with the third mRNA vaccination was not confirmed.

Status epilepticus as a complication after COVID-19 mRNA-1273 vaccine:A case report

BACKGROUND We present a rare case of status epilepticus in a 56-year-old man which arose as a complication after vaccination with the coronavirus disease 2019(COVID-19)mRNA-1273 vaccine.The patient's history included well-compensated secondary epilepsy.The root cause of the situation was a fever which had developed as a side effect of the vaccination.CASE SUMMARY A 56-year-old man received the first dose of mRNA-1273 vaccine against the severe acute respiratory syndrome-coronavirus-2.The vaccine was administered intramuscularly(100 mg,0.5 mL).The next morning the man was found to be suffering from fever and headaches while at the same time experiencing general weakness.He lost consciousness suddenly and experienced generalized clonic seizures which turned into status epilepticus.When the Emergency Medical Service arrived the patient was unconscious with spontaneous breathing and generalized clonic seizures.It was necessary to administer diazepam repeatedly.It was also necessary to administer high doses of levetiracetam and temporary propofol.The status epilepticus was brought under control approximately 90 min after the patient’s transport to the Emergency Department.A follow-up electroencephalogram no longer revealed abnormal indications of epileptic fit.The patient was temporarily hospitalized in the Intensive Care Unit and after seven days care was discharged without any further apparent effects.CONCLUSION There is currently no specific treatment against COVID-19.Therefore,the benefits of COVID-19 vaccine protection outweigh the risks.

Case mistaken for leukemia after mRNA COVID-19 vaccine administration:A case report

BACKGROUND Following the global outbreak of coronavirus disease 2019(COVID-19),unlike other vaccines,COVID-19 vaccines were developed and commercialized in a relatively short period of time.The large-scale administration of this vaccine in a short time-period led to various unexpected side effects,including severe cytopenia and thrombosis with thrombocytopenia syndrome.Despite many reports on adverse reactions,vaccination was necessary to prevent the spread of COVID-19;thus,it is essential to understand and discuss various cases of adverse reactions after vaccination.CASE SUMMARY A 77-year-old woman was administered the second dose of Pfizer mRNA COVID-19 vaccine.After vaccination she experienced fever,myalgia,and weakness.Antibiotics were subsequently administered for several days,but there was no improvement in the symptoms.The patient showed severe thrombocytopenia and leukocytosis.Thoracic and abdominopelvic computed tomography showed no infection related findings,but splenomegaly and cirrhotic liver features were observed.A large number of immature cells were observed in the peripheral blood smear;thus,bone marrow examination was performed for acute leukemia.However,there were no abnormalities.The patient recovered after administration of hepatotoxins and transfusion treatment for cytopenia and was diagnosed with an adverse reaction to COVID-19 vaccination.CONCLUSION Adverse reactions of vaccination could be mistaken for hematologic malignancies including leukemia.We report a patient with leukocytosis following COVID-19 vaccination.

Current state of knowledge on the excretion of mRNA and spike produced by anti-COVID-19 mRNA vaccines;possibility of contamination of the entourage of those vaccinated by these products

The massive COVID-19 vaccination campaign is the first time that mRNA vaccines have been used on a global scale.The mRNA vaccines correspond exactly to the definition of gene therapy of the American and European regulatory agencies.The regulations require excretion studies of these drugs and their products(the translated proteins).These studies have not been done for mRNA vaccines(nor for adenovirus vaccines).There are numerous reports of symptoms and pathologies identical to the adverse effects of mRNA vaccines in unvaccinated persons in contact with freshly vaccinated persons.It is therefore important to review the state of knowledge on the possible excretion of vaccine nanoparticles as well as mRNA and its product,the spike protein.Vaccine mRNA-carrying lipid nanoparticles spread after injection throughout the body according to available animal studies and vaccine mRNA(naked or in nanoparticles or in natural exosomes)is found in the bloodstream as well as vaccine spike in free form or encapsulated in exosomes(shown in human studies).Lipid nanoparticles(or their natural equivalent,exosomes or extracellular vesicles(EVs))have been shown to be able to be excreted through body fluids(sweat,sputum,breast milk)and to pass the transplacental barrier.These EVs are also able to penetrate by inhalation and through the skin(healthy or injured)as well as orally through breast milk(and why not during sexual intercourse through semen,as this has not been studied).It is urgent to enforce the legislation on gene therapy that applies to mRNA vaccines and to carry out studies on this subject while the generalization of mRNA vaccines is being considered.

Immune-mediated liver injury following COVID-19 vaccination

Liver injury secondary to vaccination is a rare adverse event that has recently come under attention thanks to the continuous pharmacovigilance following the widespread implementation of coronavirus disease 2019(COVID-19)vaccination protocols.All three most widely distributed severe acute respiratory syndrome coronavirus 2 vaccine formulations,e.g.,BNT162b2,mRNA-1273,and ChAdOx1-S,can induce liver injury that may involve immune-mediated pathways and result in autoimmune hepatitis-like presentation that may require therapeutic intervention in the form of corticosteroid administration.Various mechanisms have been proposed in an attempt to highlight immune checkpoint inhibition and thus establish causality with vaccination.The autoimmune features of such a reaction also prompt an in-depth investigation of the newly employed vaccine technologies.Novel vaccine delivery platforms,e.g.,mRNA-containing lipid nanoparticles and adenoviral vectors,contribute to the inflammatory background that leads to an exaggerated immune response,while patterns of molecular mimicry between the spike(S)protein and prominent liver antigens may account for the autoimmune presentation.Immune mediators triggered by vaccination or vaccine ingredients per se,including autoreactive antibodies,cytokines,and cytotoxic T-cell populations,may inflict hepatocellular damage through wellestablished pathways.We aim to review available data associated with immunemediated liver injury associated with COVID-19 vaccination and elucidate potential mechanisms underlying its pathogenesis.

COVID-19 vaccine-associated myocarditis

Myocarditis is now recognized as a rare complication of coronavirus disease 2019(COVID-19)mRNA vaccination,particularly in adolescent and young adult males.Since the authorization of the Pfizer-BioNTech^(TM)and Moderna^(TM)mRNA vaccines targeting the severe acute respiratory syndrome coronavirus-2(SARSCoV-2)spike protein,the Centers for Disease Control and Prevention(CDC)has reported 1175 confirmed cases of myocarditis after COVID-19 vaccination in individuals ages 30 years and younger as of January 2022.According to CDC data in June 2021,the incidence of vaccine-mediated myocarditis in males ages 12-29 years old was estimated to be 40.6 cases per million second doses of COVID-19 mRNA vaccination administered.Individuals with cases of COVID-19 vaccinemediated myocarditis typically present with acute chest pain and elevated serum troponin levels,often within one week of receiving the second dose of mRNA COVID-19 vaccination.Most cases follow a benign clinical course with prompt resolution of symptoms.Proposed mechanisms of COVID-19 vaccine myocarditis include molecular mimicry between SARS-CoV-2 spike protein and self-antigens and the triggering of preexisting dysregulated immune pathways in predisposed individuals.The higher incidence of COVID-19 vaccine myocarditis in young males may be explained by testosterone and its role in modulating the immune response in myocarditis.There is limited data on long-term outcomes in these cases given the recency of their occurrence.The CDC continues to recommend COVID-19 vaccination for everyone 5 years of age and older given the greater risk of serious complications related to natural COVID-19 infection including hospitalization,multisystem organ dysfunction,and death.Further study is needed to better understand the immunopathology and long-term outcomes behind COVID-19 mRNA vaccine-mediated myocarditis.

Transient ischemic attack after mRNA-based COVID-19 vaccination during pregnancy:A case report

BACKGROUND Thrombocytopenia with thrombosis syndrome has been reported after vaccination against severe acute respiratory syndrome coronavirus 2 with two mRNA vaccines.The syndrome is characterized by thrombosis,especially cerebral venous sinus thrombosis,and may lead to stroke.Pregnant women with stroke show higher rates of pregnancy loss and experience serious pregnancy complications.We present the case of a 24-year-old pregnant woman with a transient ischemic attack(TIA) that developed after vaccination with the Moderna mRNA-1273 vaccine(at 37 2/7 wk).CASE SUMMARY TIA occurred 13 d following the coronavirus disease vaccination.At 39 1/7 wk of pregnancy,the patient presented with sudden onset of right eye blurred vision with headache,dizziness with nausea,right-hand weakness,anomia,and alexia.The symptoms lasted 3 h;TIA was diagnosed.Blood test results revealed elevated D-dimer,cholesterol,and triglyceride levels.Brain magnetic resonance imaging showed no acute hemorrhagic or ischemic stroke.At pregnancy 37 6/7 wk,she was admitted for cesarean delivery to reduce subsequent risk of stroke during labor.Body mass index on admission was 19.8 kg/m~2.Magnetic resonance angiography and transesophageal echocardiography showed no abnormalities.The next day,a mature female baby weighing 2895 g and measuring 50 cm was delivered.Apgar scores were 8 and 9 in the first and fifth minutes.D-dimer levels decreased on postoperative day 4.After discharge,the autoimmune panel was within normal limits,including antinuclear and antiphospholipid antibodies.CONCLUSION TIA might be developed after the mRNA vaccines in pregnant women.

Vaccines’ Safety and Effectiveness in the Midst of Covid-19 Mutations

We examined the coronavirus classification and evolution through its multiple mutations that have increased its transmissibility rate up to 70% globally, threatening to undermine the promise of a number of emerging vaccines that primarily focus on the immune detection of the Spike trimer. The safety and effectiveness of different vaccination methods are evaluated and compared, including the mRNA version, the Adenovirus DNA, Spike protein subunits, the deactivated virus genres, and the live attenuated coronavirus. Mutations have been long considered as random events, or mistakes during the viral RNA replication. Usually, what can go wrong will go wrong;therefore, repeated transformations lead to the extinction of a virus. On the contrary, the aggregate result of over 300,000 Covid-19 variants has expanded its transmissibility and infectiousness. Covid-19 mutations do not degrade the virus;they empower and facilitate its disguise to evade detection. Unlike other coronaviruses, Covid-19 amino acid switches do not reflect the random unfolding of errors that eventually eradicate the virus. Covid-19 appears to use mutations adaptively in the service of its survival and expansion. We cite evidence that Covid-19 inhibits the interferon type I production, compromising adaptive immunity from recognizing the virus. The deleterious consequences of the cytokine storm where the CD8+ killer cells injure the vital organs of the host may well be a Covid-19 manoeuvring to escape exposure. It is probable that evolution has programmed Covid-19 with an adeptness designed to debilitate key systemic defences to secure its subsistence. To date the infectiousness of the Covid-19 pandemic is exponentially increasing, denoting the possibility of an even more dangerously elusive, inconspicuous, and sophisticated version of the disease.

Covid-19 Mutations and the Effect of Different Vaccines on Immune Memory

We traced the coronavirus classification and evolution,analyzed the Covid-19 composition and its distinguishing characteristics when compared to SARS-CoV and MERS-CoV.Despite their close kinship,SARS-CoV and Covid-19 display significant structural differences,including 380 amino acid substitutions,and variable homology between certain open reading frames that are bound to diversify the pathogenesis and virulence of the two viral compounds.A single amino acid substitution such as replacing Aspartate(D)with Glycine(G)composes the D614G mutation that is around 20%more infectious than its predecessor 614D.The B117 variant,that exhibits a 70%transmissibility rate,harbours 23 mutants,each reflecting one amino acid exchange.We examined several globally spreading mutations,501.V2,B1351,P1,and others,with respect to the specific amino acid conversions involved.Unlike previous versions of coronavirus,where random mutations eventually precipitate extinction,the multiplicity of over 300,000 mutations appears to have rendered Covid-19 more contagious,facilitating its ability to evade detection,thus challenging the effectiveness of a large variety of emerging vaccines.Vaccination enhances immune memory and intelligence to combat or obstruct viral entry by generating antibodies that will prohibit the cellular binding and fusion with the Spike protein,restricting the virus from releasing its contents into the cell.Developing antibodies during the innate response,appears to be the most compelling solution in light of the hypothesis that Covid-19 inhibits the production of Interferon type I,compromising adaptive efficiency to recognize the virus,possibly provoking a cytokine storm that injures vital organs.With respect to that perspective,the potential safety and effectiveness of different vaccines are evaluated and compared,including the Spike protein mRNA version,the Adenovirus DNA,Spike protein subunits,the deactivated virus genres,or,finally,the live attenuated coronavirus that appears to demonstrate the greatest effectiveness,yet,encompass a relatively higher risk.

mRNA vaccines: Past, present, future

mRNA vaccines have emerged as promising alternative platforms to conventional vaccines.Their ease of production,low cost,safety profile and high potency render them ideal candidates for prevention and treatment of infectious diseases,especially in the midst of pandemics.The challenges that face in vitro transcribed RNA were partially amended by addition of tethered adjuvants or co-delivery of naked mRNA with an adjuvanttethered RNA.However,it wasn’t until recently that the progress made in nanotechnology helped enhance mRNA stability and delivery by entrapment in novel delivery systems of which,lipid nanoparticles.The continuous advancement in the fields of nanotechnology and tissue engineering provided novel carriers for mRNA vaccines such as polymeric nanoparticles and scaffolds.Various studies have shown the advantages of adopting mRNA vaccines for viral diseases and cancer in animal and human studies.Self-amplifying mRNA is considered today the next generation of mRNA vaccines and current studies reveal promising outcomes.This review provides a comprehensive overview of mRNA vaccines used in past and present studies,and discusses future directions and challenges in advancing this vaccine platform to widespread clinical use.

COVID-19 vaccination and cardiac dysfunction

The coronavirus disease 2019(COVID-19)mRNA vaccine against severe acute respiratory syndrome coronavirus 2 infections has reduced the number of symptomatic patients globally.A case series of vaccine-related myocarditis or pericarditis has been published with extensive vaccination,most notably in teenagers and young adults.Men seem to be impacted more often,and symptoms commonly occur within 1 wk after immunization.The clinical course is mild in the majority of cases.Based on the evidence,a clinical framework to guide physicians to examine,analyze,identify,and report suspected and confirmed cardiac dysfunction cases is needed.A standardized workup for every patient with strongly suspicious symptoms associated with the COVID-19 mRNA vaccine comprises serum cardiac troponin measurement and a 12-lead electrocardiogram(ECG).For patients with unexplained elevation of cardiac troponin and pathologic ECG,echocardiography is recommended.Consultation with a cardiovascular expert and hospitalization should be considered in this group of patients.Treatment is primarily symptomatic and supportive.Deferring a 2^(nd) dose of the COVID-19 mRNA vaccination in individuals with suspected myocarditis or pericarditis after the 1^(st) dose is suggested until further safety data become available.

A novel deep generative model for mRNA vaccine development: Designing 5′ UTRs with N1-methyl-pseudouridine modification

Efficient translation mediated by the 5'untranslated region(5'UTR)is essential for the robust efficacy of mRNA vaccines.However,the N1-methyl-pseudouridine(m1)modification of mRNA can impact the translation efficiency of the 5'UTR.We discovered that the optimal 5'UTR for m1y-modified mRNA(m1y-5'UTR)differs significantly from its unmodified counterpart,high-lighting the need for a specialized tool for designing mly-5'UTRs rather than directly utilizing high-expression endogenous gene 5'UTRs.In response,we developed a novel machine learning-based tool,Smart5UTR,which employs a deep generative model to identify superior m1y-5'UTRs in silico.The tailored loss function and network architecture enable Smart5UTR to overcome limitations inherent in existing models.As a result,Smart5UTR can successfully design superior 5'UTRs,greatly benefiting mRNA vaccine development.Notably,Smart5UTR-designed superior 5'UTRs significantly enhanced antibody titers induced by COVID-19 mRNA vaccines against the Delta and Omicron variants of SARS-CoV-2,surpassing the performance of vaccines using high-expression endogenous gene 5'UTRs.

Safety,immunogenicity,and preliminary efficacy of a randomized clinical trial ofomicron XBB.1.5-containing bivalent mRNA vaccine

Periodically updating coronavirus disease 19(COVID-19)vaccines that offer broad-spectrum protection is needed giventhe strong immune evasion by the circulating omicron sublineages.The effectiveness of prototype and BA.4/5-containing bivalent mRNA vaccines is reduced when XBB subvariants predominate.We initiated an observer-blinded,threearms study in 376 patients in Chinese individuals aged from 18 to 55 years old who had previously received three dosesCOVID-19 vaccine.Immunogenicity in terms of neutralizing antibodies elicited by a 30-mg dose of XBB.1.5-containingbivalent vaccine(RQ3027),a 30-mg dose of BA.2/BA.5-Alpha/Beta bivalent vaccine(RQ3025)and their precedent 30-mg Alpha/Beta(combined mutations)monovalent mRNA vaccine(RQ3013)and safety are primary and secondary endpoints,respectively.We recorded prescribed COVID-19 cases to explore the preliminary efficacy of three vaccines.RQ3027 and RQ3025 boosters elicited superior neutralizing antibodies(NAbs)against XBB.1.5,XBB.1.16,XBB.1.9.1,and JN.1 compared to RQ3013 at day 14 in participants without SARS-CoV-2 infection.All study vaccines were welltolerated without serious adverse reactions identified.The incidence rates per 1000 person-years of COVID-19 casesduring the 2nd-19th week after randomization were lowest in RQ3027.Overall,our data show that XBB.1.5-containingbivalent booster generated superior immunogenicity and better protection against newer severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)variants compared to BA.2/BA.5-containing bivalent and Alpha/Beta monovalentwith no new safety concerns.

Should we continue breastfeeding after SARS-CoV-2 infection or mRNA vaccination?

The coronavirus disease 2019(COVID-19),which is caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has posed a potential threat to infant health.The World Health Organization recommended that the benefits of breastfeeding far outweigh the potential risk of transmission,but there is no denying that the current evidence is insufficient.Moreover,although the COVID-19 mRNA vaccine has played an effective role in protection against infection,individuals have increasing concerns about the safety of breastfeeding after vaccination,and which have caused some breastfeeding women to postpone vaccination or stop breastfeeding early.Thus,in this review,we provide an in-depth discussion of whether SARS-CoV-2 and the vaccine will affect babies through breast milk.On one hand,only a very small number of milk samples were identified positive for viral RNA and almost impossible to be live virus particles.The milk of most lactating women after vaccination did not contain vaccine-related mRNA and polyethylene glycol.On the other hand,the antibodies and biologically active molecules like lactoferrin are abundant in the milk of lactating women who have been infected or vaccinated,which can provide potential protection against infants’respiratory and gastrointestinal infections.Therefore,in terms of implications for clinical practice,the results of our study support that lactating women who have been infected or vaccinated should be encouraged to breastfeed their infants under the premise of taking appropriate sanitary measures.

Emerging Frontiers in Vaccine Development: A Review of Changing Paradigm

The technology behind vaccine development varies significantly from one vaccine to another depending on the time when the vaccine was first developed. Over the years, the vaccine innovation time has significantly shortened with the advancement of knowledge in the fields of molecular and cell biology, and discoveries in the field of biotechnology. The first vaccines created were tested in a kind of trial-and-error approach which sometimes had deadly side effects. These vaccines used either living, weakened, or completely dead pathogens. The use of whole pathogen vaccines was seen to be time consuming and unpredictable because even though it would cause an immune response, it could vary from person to person, and always had the risk of pathogens returning to virulence causing sometimes fatal outcomes. The next major technology used to create vaccines was subunit vaccines which utilize purified antigens inactivated through various methods. This technology is quite prevalent among the vaccines that are currently in circulation, making them quite effective, and free from fatal side effects. The viral vector vaccine technology has been around for a few decades and utilizes knowledge of molecular genetics to the greatest extent. It uses intermediate vectors to deliver genetic instructions to trigger an immune response within the subject body. The introduction of nucleic acid vaccines is the newest technology and has come to a great deal of attention during the SARS-CoV-2 immunization efforts. The technology primarily utilizes the delivery of genetic information using messenger ribonucleic acid (mRNA) to create characteristic pathogen-specific proteins that in turn generate an immune response in the recipients.

The effect of COVID-19 vaccines on sperm parameters: a systematic review and meta-analysis

Published data were gathered for a meta-analysis to determine the difference in sperm parameters before and after administration of different types of coronavirus disease 2019(COVID-19)vaccines,because the reproductive toxicity of COVID-19 vaccines has not yet been evaluated in clinical trials and COVID-19 has been associated with decreases in sperm quality.The preferred procedures for systematic reviews and meta-analyses were followed in the conduct and reporting of this study.The average sperm parameters of all sperm donors’multiple sperm donations were compared before and after receiving various COVID-19 vaccinations.Semen volume,total sperm motility,total sperm count,morphological change,and sperm concentration were the primary outcome measures.We compiled and analyzed the results of six studies on total sperm motility,six studies on semen volume,six studies on sperm concentration,two studies on morphological change,and two studies on total sperm count.Parameter comparisons with patients who had and had not been vaccinated were only reported in one of the included studies.When different types of COVID-19 vaccine injections were compared,no discernible differences in parameters were observed.According to the available data,the parameters of semen are unaffected by inactivated or messenger RNA(mRNA)COVID-19 vaccinations.To support these findings,additional prospectively designed research is required.

Immunogenicity of mucosal COVID-19 vaccine candidates based on the highly attenuated vesicular stomatitis virus vector(VSV_(MT))in golden syrian hamster

COVID-19 is caused by coronavirus SARS-CoV-2.Current systemic vaccines generally pro-vide limited protection against viral replication and shedding within the airway.Recombinant VSV(rVSV)is an effective vector which inducing potent and comprehensive immunities.Currently,there are two clinical trials investigating COVID-19vaccines based on VSV vectors.These vaccines were developed with spike protein of WA1 which administrated intramuscularly.Although intranasal route is ideal for activating mucosal immunity with VSV vector,safety is of concern.Thus,a highly attenuated rVSV with three amino acids mutations in matrix protein(VSV_(MT))was developed to construct safe mucosal vaccines against multiple SARS-CoV-2 variants of concern.It demonstrated that spike protein mutant lacking 21 amino acids in its cytoplasmic domain could rescue rVSV efficiently.VSV_(MT) indicated improved safeness compared with wild-type VSV as the vector encoding SARS-CoV-2 spike protein.With a single-dosed intranasal inoculation of rVSV_(ΔGMT)-S_(Δ21),potent SARS-CoV-2specific neutraliza-tion antibodies could be stimulated in animals,particularly in term of mucosal and cellular immunity.Strikingly,the chimeric VSV encoding S_(Δ21) of Delta-variant can induce more potent immune responses compared with those encoding S_(Δ21) of Omicron-or WA1-strain.VSV_(MT) is a promising platform to develop a mucosal vaccine for countering COVID-19.

Efficacy of Vaccine Protection Against COVID-19 Virus Infection in Patients with Chronic Liver Diseases

The outbreak of coronavirus disease 2019 (COVID-19) has resulted in significant morbidity and mortality worldwide. Vaccination against coronavirus disease 2019 is a use-ful weapon to combat the virus. Patients with chronic liver diseases (CLDs), including compensated or decompensated liver cirrhosis and noncirrhotic diseases, have a decreased immunologic response to coronavirus disease 2019 vaccines. At the same time, they have increased mortality if infected. Current data show a reduction in mortality when patients with chronic liver diseases are vaccinated. A suboptimal vac-cine response has been observed in liver transplant recipi-ents, especially those receiving immunosuppressive therapy, so an early booster dose is recommended to achieve a better protective effect. Currently, there are no clinical data com-paring the protective efficacy of different vaccines in patients with chronic liver diseases. Patient preference, availability of the vaccine in the country or area, and adverse effect profiles are factors to consider when choosing a vaccine. There have been reports of immune-mediated hepatitis after coronavi-rus disease 2019 vaccination, and clinicians should be aware of that potential side effect. Most patients who developed hepatitis after vaccination responded well to treatment with prednisolone, but an alternative type of vaccine should be considered for subsequent booster doses. Further prospec-tive studies are required to investigate the duration of immu-nity and protection against different viral variants in patients with chronic liver diseases or liver transplant recipients, as well as the effect of heterologous vaccination.

SARS-CoV-2 infection rates after different vaccination schemes:An online survey in Turkey

Objective:To identify effects of various nationwide vaccination protocols on the evolution of new SARS-CoV-2 infections among adult population and to evaluate the safety of mRNA(BioNTech/Pfizer)vaccine.Methods:Totally 10735 adult volunteers that received at least one dose of BioNTech/Pfizer or triple doses of CoronaVac participated in this cross-sectional-online survey between 1 and 10 September 2021.The information was collected covering a 5-month period from April 2021 to September 2021.Information about people who were vaccinated with only single and double dose CoronaVac were not included in this study.Results:At least one side effect after single and double dose of BioNTech/Pfizer and triple doses of CoronaVac were observed in 42.1%,42.5%and 10.9%,respectively.The most common side effects were shoulder/arm pain,weakness/fatigue,muscle/joint pain and headache.The side effects were the most frequent in single BioNTech/Pfizer,while it was the least in triple CoronaVac.The rate of positive PCR tests before vaccination was 17.6%,and decreased to 3.0%after vaccination.The rates of positive SARS CoV-2-PCR were 18.8%,3.5%,3.1%,0.5%and 4.6%in single BioNTech/Pfizer,double BioNTech/Pfizer,double CoronaVac+single BioNTech/Pfizer,double CoronaVac+double BioNTech/Pfizer and triple CoronaVac,respectively.While 1.8%of PCR positive COVID-19 cases needed intensive unit care in the pre-vaccination period,intensive care unit was required in 0%,1.5%,2.4%,0%and 4.2%after single BioNTech/Pfizer,double BioNTech/Pfizer,double CoronaVac+single BioNTech/Pfizer,double CoronaVac+double BioNTech/Pfizer and triple CoronaVac,respectively.Reinfection rate after vaccination was 0.4%.Conclusions:The rarity of COVID-19 infection after vaccination suggests that efficacy of vaccines is maintained.On the other hand,the data underscore the critical importance of continued public health mitigation.