Systemic Adverse Reactions Research Articles

Safety and immunogenicity of intradermal administration of fractional dose CoronaVac®, ChAdOx1 nCoV-19 and BNT162b2 as primary series vaccination.

There is a limited supply of COVID-19 vaccines, with less than 20% of eligible populations in low-income countries having received one dose. Intradermal delivery of fractional dose vaccines is one way to improve global vaccine access, but no studies have reported data on intradermal delivery of COVID-19 primary series vaccination. We conducted a pilot study to examine the safety and immunogenicity of three intradermal primary series regimens – heterologous regimen of CoronaVac and ChAdOx1 (CoronaVac-ChAdOx1), homologous regimen of ChAdOx1 (ChAdOx1-ChAdOx1), and homologous regimen of BNT162b2 (BNT162b2-BNT162b2). Each dose was 1/5th or 1/6th of the standard dose. Two additional exploratory arms of intradermal vaccination for the second dose following an intramuscular first dose of ChAdOx1 and BNT162b2 were included. Intradermal vaccination was found to be immunogenic and safe. The antibody responses generated by the intradermal primary series were highest in the BNT162b2 arms. The anti-receptor binding domain (anti-RBD) IgG concentration following fractional dose intradermal vaccination was similar to that of standard dose intramuscular vaccination of the same regimen for all study arms except for BNT162b2. The BNT162b2 intradermal series generated a lower antibody concentration than the reference intramuscular series, despite generating the highest antibody concentration of all three intradermal primary series regimens. Neutralizing antibody responses against the SARS-CoV-2 ancestral strain were consistent with what was observed for anti-RBD IgG, with lower titers for SARS-CoV-2 variants. Neutralizing titers were lowest against the omicron variant, being undetectable in about a quarter of study participants. T-cell responses against spike- and nucleocapsid-membrane-open reading frame proteins were also detected following intradermal vaccination. Adverse effects following intradermal vaccination were generally comparable with post-intramuscular vaccination effects. Taken together, our data suggest that intradermal vaccination using 1/5th or 1/6th of standard COVID-19 intramuscular vaccination dosing were immunogenic with tendency of lower systemic adverse reactions than intramuscular vaccination. Our findings have implications in settings where COVID-19 vaccines are in shortage.

Efficacy, Immunogenicity, and Safety of COVID-19 Vaccines in Randomized Control Trials in the Pre-Delta Era: A Systematic Review and Network Meta-Analysis

The most effective method of limiting the coronavirus disease pandemic of 2019 (COVID-19) is vaccination. For the determination of the comparative efficacy and safety of COVID-19 vaccines and their platforms during the pre-Delta era, a systematic review and network meta-analysis was conducted. The MEDLINE, Embase, and MedRxiv databases were searched, and the gray literature was manually searched up to 8 July 2021. The review includes the phase II and III randomized controlled trials (RCTs) that assessed the efficacy, immunogenicity, and safety of the COVID-19 vaccines. The network meta-analysis used a Bayesian model and used the surface under the cumulative ranking to rank the comparisons between the vaccines. All included studies were quality appraised according to their design, and the heterogeneity of the analyses was assessed using I2. In terms of vaccine efficacy, the mRNA-1273 vaccine ranked the highest, and the CoronaVac vaccine ranked the lowest. The mRNA-1273 ranked the highest for neutralizing antibody responses to live SARS-CoV-2. The WIV04 vaccine was associated with the lowest incidence of both local and systemic adverse reactions. All studies except one had a low to moderate risk of bias. The mRNA platform vaccines showed higher efficacy and more adverse reactions than the other vaccines.

Evaluation of the Safety and Immunogenicity of Fractional Intradermal COVID-19 Vaccines as a Booster: A Pilot Study.

Intradermal vaccination using fractional dosages of the standard vaccine dose is one strategy to improve access to COVID-19 immunization. We conducted a pilot study in healthy adults in Thailand to evaluate the safety and immunogenicity of intradermal administration of fractional doses of ChAdOx1 (1/5th of standard dosage) or BNT162b2 (1/6th of standard dosage) to individuals previously vaccinated (prime) with two-dose intramuscular CoronaVac, ChAdOx1 or BNT162b2. Following an initial immunogenicity exploratory phase for each vaccine combination group (n = 10), a total of 135 participants (n = 45 per group) were recruited to 3 groups (CoronaVac prime-intradermal BNT162b2 boost, CoronaVac prime-intradermal ChAdOx1 boost and ChAdOx1 prime-intradermal BNT162b2 boost) and their immunogenicity data were compared to a previous cohort who received the same vaccine intramuscularly. Two weeks following booster vaccination, neutralizing antibodies against the delta variant were similar between the participants who received intradermal and intramuscular vaccination. However, neutralizing antibodies against the omicron variant in the intradermal BNT162b2 boost groups were ~6-fold lower, while the levels in the ChAdOx1 boost group were similar compared to their respective vaccine regimen given intramuscularly. The intradermal booster significantly increased spike-specific T cell responses in all three groups from pre-booster levels. Local and systemic adverse reactions were milder in intradermal compared to intramuscular injections. Further studies are needed to evaluate the clinical relevance of these findings and the feasibility of administration of intradermal COVID-19 vaccines.

A web-based survey of SARS-CoV-2 vaccination and its adverse effects in Chinese postoperative patients with breast cancer: a cross-sectional study.

BackgroundVaccination against SARS-CoV-2 has been the most important strategy for preventing infection and controlling pandemics of coronavirus disease 2019 (COVID-19). Cancer patients have a significantly higher risk of infection with COVID-19 because of their impaired immunity. Breast cancer is the most common female malignant tumor in the world. However, studies on COVID-19 vaccination in breast cancer patients are scarce, so that more information is needed to guide vaccination in these.MethodsWe conducted a web-based questionnaire survey on SARS-CoV-2 vaccination in breast cancer patient. Questionnaires completed by non-postoperative patients will be considered invalid. The main variables in the questionnaire including vaccination status, willingness to get the vaccines, candidate factors, and measures of adverse events in vaccinated individuals were used for analysis. Univariate and multivariate logistic regression was used to estimate the associations.ResultsAmong 947 valid online questionnaires, 341 (36.0%) accepted SARS-CoV-2 vaccination, while 606 (64.0%) did not. There were significant differences in age, current treatment, time since surgery, and symptoms of anxiety and depression between the two groups. Compared to vaccinated patients, we identified current treatment [odds ratio (OR) =0.51 for endocrine therapy; 95% confidence interval (CI): 0.29–0.89], time since surgery (OR =22.49 for 1–2 years; 95% CI: 12.31–41.10; OR =8.49 for 2–5 years; 95% CI: 4.98–14.46; OR =1.79 for >5 years; 95% CI: 1.11–2.89), and symptoms of depression (OR =2.48; 95% CI: 1.19–5.15) as significant factors for being unvaccinated. The overall incidence of adverse reactions was 43.1%, and the most common local and systemic adverse reactions were pain (28.4%) and fatigue (8.8%). However, about 76.6% of the unvaccinated participants were willing to be vaccinated.ConclusionsCompared to the general population, postoperative patients with breast cancer had a lower rate of vaccination for SARS-CoV-2. Receiving treatment, a shorter time since surgery, and symptoms of depression were associated with being unvaccinated. However, about 76.6% of the unvaccinated participants were willing to be vaccinated. Although our study showed that there were adverse effects of SARS-CoV-2 vaccines, such as pain, fatigue, they are common adverse effects of routine vaccination. We believe that vaccination against COVID-19 is safe in postoperative patients with breast cancer.

COVID-19 vaccination delivery in long-term-care using the CARD (Comfort Ask Relax Distract) system: Mixed methods study of implementation drivers

ABSTRACT Objectives CARD (comfort, ask, relax, distract) is a vaccine delivery framework that includes interventions to improve the patient’s experience. CARD has not been previously implemented in long-term care (LTC) settings. This study evaluated drivers to implementation for COVID-19 vaccinations in an LTC facility. Methods Postimplementation interpretive evaluation including qualitative interviews and quantitative surveys with eight participants. The Consolidated Framework for Implementation Research (CFIR) was used for analysis. Adverse reactions to vaccinations and CARD interventions, including local reactogenicity and systemic reactions, were abstracted from medical charts of residents. Results Eight CFIR constructs emerged. Staff perceived CARD was complex because it added steps to vaccination delivery. Motivated to meet residents’ needs, a receptive implementation climate of support among staff led to using strategies within CARD, such as administering topical anesthetics and omitting alcohol skin antisepsis prior to injections. Having an effective network like the residents council positively influenced implementation by allowing residents to voice their opinions. Facilitators to implementation included staff knowledge and beliefs and staff’s commitment to their organization, which was focused on person-centered care. Barriers included lack of available resources (inadequate staffing), insufficient communication between management and staff and lack of awareness of CARD, and external policies not aligned with CARD. Chart reviews conducted for 93 vaccinated residents corroborated perceptions of vaccination and CARD intervention safety, revealing a low rate of local and systemic adverse reactions and no cases of skin infection. Discussion We identified positive and negative implementation drivers. Future research is recommended to expand the strategies employed and involve residents more directly.

Targeting Telomerase Enhances Cytotoxicity of Salinomycin in Cancer Cells.

Salinomycin exhibits significant systemic adverse reactions such as tachycardia and myoglobinuria in mammals, which hinders its application as a drug for human cancers. Although many strategies aimed at increasing salinomycin’s toxicity to cancer cells have been identified to allow a lower dose of salinomycin to be used, they often cause normal cell damage by themselves. Thus, it is urgent to find more effective methods to increase salinomycin’s toxicity to cancer cells with little influences on normal cells. Telomerase, which is expressed highly in most cancer cells rather than normal somatic cells, plays central roles in cancer cell fate regulation. Targeting telomerase represents a potential method for enhancing salinomycin’s cytotoxicity to cancer cells with little effects on normal cells. Herein, we improve the toxicity of salinomycin against cancer cells by telomerase inhibition BIBR1532 (BIBR), which binds to the active site of telomerase reverse transcriptase. We find that a non-toxic dose of BIBR can enhance cytotoxicity of salinomycin in MCF-7 and MDA-MB-231 cells. Moreover, BIBR enhances mammosphere formation inhibition mediated by salinomycin in MCF-7 and MDA-MB-231 cells. Further studies show that BIBR enhances tumor growth inhibition induced by salinomycin in vivo. To our knowledge, this is the first example that targeting telomerase improves anti-cancer effects of salinomycin.

Outcome of Post-resection Intravesical BCG and Mitomycin C Therapy on Non-muscle Invasive High- Grade Transitional Cell Carcinoma of Urinary Bladder

Objective: This study aimed to compare the outcome of postoperative intravesical BCG and Mitomycin C therapy on non-muscle invasive high grade superficial bladder tumor. Methods: This prospective quasi experimental study was carried out among the patients with non-muscle invasive high grade transitional cell carcinoma (TCC) of urinary bladder, who underwent complete transurethral resection of bladder tumor of primary tumor attended at the urology department of DMCH, during March 2017 to August 2019. After pre-operative evaluation and counselling, 70 patients with histologically documented high grade superficial bladder tumor were included and divided in two groups. We instilled intravesical BCG in one group and Mitomycin C (MMC) therapy in other group. The patients were followed up at 3rd ,6th , 9th , 12th and 18th month. Results: The mean age of BCG group was 55.8 years while 60.2years in MMC group with majority between 45 to 65 years (>80%). Sex distribution in both groups were almost equal (p=0.062). There were equal number of TaG3 and T1G3 disease in each group (p=0.809). Local adverse reactions were significant in BCG group (p= 0.016), among them UTI, between two groups, was statistically significant (p=0.039). Incidence of hematuria (p=0.324), voiding frequency (p=0.163) and local rash (P=0.642) had no statistically significant difference. The incidence of post-instillation systemic adverse reactions between two groups were statistically significant (p=0.034). Fever (p=0.028) was significant among them. Intavesical BCG was significantly more effective than MMC in terms of disease recurrence (p=0.047) and progression (p=0.008). Conclusions: We analysed the efficacy and safety of intravesical BCG and MMC in two groups, showing that BCG was more effective in terms of disease recurrence and progression but local and systemic side effects were higher in BCG group. Bangladesh J. Urol. 2021; 24(1): 62-71

Local Adverse Drug Reactions in Ambulatory Asthma Patients Treated With Inhaled Corticosteroids: An Experience from a South Indian Teaching Hospital

Background:Inhaled corticosteroids (ICS) have an essential and established role in the treatment of asthma. Both systemic and local adverse effects may accompany the long-term use of ICS. Systemic adverse drug reactions (ADRs) of ICS are well established. However, there is a pau-city of information on local ADRs, especially in the Indian population.Objectives:This study aimed to determine the prevalence, severity, predictability, and preventabil-ity of local ADRs to ICS and their associated risk factors.Methods:Patients with asthma who need ICS were enrolled. Study patients were interviewed with open-ended questions to assess local ADRs to ICS at baseline and each follow-up visit, once a month for three months. Causality (Naranjo’s algorithm and WHO scale), severity (Hartwig SC scale), predictability (based on the frequency of occurrence of ADR and history of drug exposure), and preventability (Schumock and Thornton criteria) of local ADRs were assessed. Bivariate analy-sis and subsequently multivariate logistic regression were used to identify the risk factors for local ADRs to ICS.Results:A total of 243 patients (134 female) were included in the study. A total of 74 local ADRs were observed in 59 patients (a prevalence of 24.3%). The most common local ADRs included the feeling of thirst (14.8%), followed by cough during inhalation (8.6%) and taste disturbance (4.5%). All ADRs were predictable and mild in severity. Preventability assessment found 85.1% of local ADRs as ‘probably preventable’. Two out of five patients who had ADRs reduced or skipped doses because of the discomfort, despite their physician’s recommendation to continue their regular dose of ICS. Age >41 years, use of MDI without spacer, and use of budesonide were identified as the risk factors for developing ADRs to ICS.Conclusion:Local ADRs to ICS were observed in approximately one in four patients with asthma. Two out of five patients who had ADRs reduced or skipped doses. Strategies to prevent local ADRs to ICS should focus on patients aged >41 years, receiving budesonide, and using MDI without a spacer. We need to establish standards on the best practices for preventing ADRs, such as identify-ing the most suited device or ICS that is best tolerated by the individual patient and identifying the least ICS dose that maintains ideal asthma control.

Association between Adverse Reactions to the First and Second Doses of COVID-19 Vaccine.

This study investigated the frequency of adverse reactions to COVID-19 vaccines in Japan and the impact of first-dose adverse reactions on second-dose adverse reactions. Individuals who received an mRNA COVID-19 vaccine at our center in March or April 2021 were included. Data were collected using questionnaires. The main factors were age (<40, 40–59, and >60 years), sex, underlying disease, and first-dose adverse reaction. The primary outcomes were incidence of local and systemic adverse reactions (ARs) attributable to the vaccine. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Among 671 participants, 90% experienced local or systemic ARs. An AR to the first dose was associated with a significantly increased risk of an AR to the second dose (OR: 49.63, 95% CI: 21.96–112.16). ARs were less common among men than among women (OR: 0.36, 95% CI: 0.17–0.76). Local ARs were less common among those aged 60 years or older (OR: 0.35, 95% CI: 0.18–0.66), whereas systemic ARs were more common among those aged under 40 years. Information on ARs to the first dose is important for healthcare providers and recipients when making vaccination decisions.

A Study of Adverse Effects Following Administration of Anti-Rabies Vaccination - A Hospital Based Study

Rabies is an acute viral zoonotic disease that affects all warm-blooded animals including mammals and occurs in more than 150 countries and territories. Although rabies is a 100% fatal disease, it can be prevented by the use of potent anti-rabies vaccines (ARV). The present study was a hospital based descriptive longitudinal study conducted during February 2019 to July 2020 amongst the animal bite patients attending the Anti -Rabies clinic (ARC) of Vardhman Mahavir Medical College and Safdarjung Hospital (VMMC &amp; SJH), New Delhi, to study the adverse events (vaccine reactions) if any following administration of the ARV. The age of the study participants ranged from 2 to 65 years and the mean age was (29.3±15.2) years. No severe or serious adverse events were reported. Of the minor reactions, the most commonly reported symptom was pain at the injection site (34; 9.4%) followed by occurrence of tingling sensation (29; 8.1%), headache (22; 6.1%) and itching at the injection site (19; 5.3%). These findings corroborate with those found in previous studies in the literature. It was concluded that although there are possible local or mild or systemic adverse reactions to rabies vaccination, but once initiated, rabies prophylaxis should not be interrupted or discontinued.

Reactogenicity to the mRNA-1273 Booster According to Previous mRNA COVID-19 Vaccination.

The objective of this study was to assess the local and systemic adverse reactions after the administration of a COVID-19 mRNA-1273 booster between December 2021 and February 2022 by comparing the type of mRNA vaccine used as primary series (mRNA-1273 or BNT162b2) and homologous versus heterologous booster in health care workers (HCW). A cross-sectional study was performed in HCW at a tertiary hospital in Barcelona, Spain. A total of 17% of booster recipients responded to the questionnaire. The frequency of reactogenicity after the mRNA-1273 booster (88.5%) was similar to the mRNA-1273 primary doses (85.8%), and higher than the BNT162b2 primary doses (71.1%). The reactogenicity was similar after receiving a heterologous booster compared to a homologous booster (88.0% vs. 90.2%, p = 0.3), and no statistically significant differences were identified in any local or systemic reactions. A higher frequency of medical leave was identified in the homologous booster dose group vs. the heterologous booster dose group (AOR 1.45; 95% CI: 1.00–2.07; p = 0.045). Our findings could be helpful in improving vaccine confidence toward heterologous combinations in the general population and in health care workers.

Adverse drug reactions to the three doses of the severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) mRNA-1273 vaccine in a cohort of cancer patients under active treatment of a tertiary hospital in Madrid, Spain

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines efficacy and safety have been tested in phase 3 studies in which cancer patients were not included or were underrepresented. Methods: The objective of this study is to evaluate the safety profile of the mRNA-1273 vaccine across cancer patients and its relationship to patients' demographics. We selected from our records all 18-years or older solid cancer patients under active treatment vaccinated with the complete three-dose schedule mRNA-1273 vaccine whose adverse drug reactions (ADRs) after each dose were recorded. Medical records were reviewed retrospectively to collect data between April 19, 2021, and December 31, 2021. Patients with documented previous infection by SARS-Cov-2 were excluded. Results: A total of 93 patients met the inclusion criteria. Local ADRs were reported more frequently after the first and second dose than after the third (41.9%, 43% and 31.1% of the patients respectively), while systemic ADRs followed the opposite pattern (16.1%, 34.4% and 52.6% of the patients respectively). We found a statistically significant association between sex and systemic adverse reactions after the third dose, p < 0.001 and between systemic adverse reactions after the second dose and systemic adverse reactions after the third dose, p = 0.001 A significant linear trend, p = 0.012, with a higher Eastern Cooperative Oncology Group (ECOG) score associated with a lower proportion of patients suffering from systemic side effects was found. Women had 5.79 times higher odds to exhibit systemic ADRs after the third dose (p=0.01) compared to males. Increasing age was associated with a decreased likelihood of exhibiting ADRs (p=0.016). Conclusion:The mRNA-1273 vaccine shows a tolerable safety profile. The likelihood of ADRs appears to be associated with gender and age. Its association with ECOG scores is less evident. Further studies are needed to elucidate this data in cancer patients.

A non-retinol retinoic acid receptor-γ (RAR-γ/NR1B3) selective agonist, tectorigenin, can effectively inhibit the ultraviolet A-induced skin damage.

Long-term ultraviolet (UV) exposure can cause inflammation, pigmentation and photoaging. All-trans retinoic acid (ATRA/tretinoin) is a commonly used retinoic acid receptor (RAR) agonist in the clinical treatment of UV-induced skin problems. However, the use of such drugs is often accompanied by systemic adverse reactions caused by nonspecific activation of RARs. Therefore, this study was designed to screen for a novel RAR-γ-selective agonist with high safety. Molecular docking, dynamic simulation and Biacore were used to screen and identify novel RAR-γ-selective agonists. RT-PCR, ELISA, western blotting, immunofluorescence staining, flow cytometry and proteomic analysis were used to detect the effects of these novel RAR-γ selective agonists on UVA-induced inflammation and photoaging cell models. UVA-induced mouse models were used to evaluate the effects of tectorigenin on skin repair, ageing and inflammation. Tectorigenin is a novel RAR-γ-selective agonist, which inhibits UV-induced oxidative damage, inflammatory factor release and matrix metalloproteinase (MMP) production. Tectorigenin can also reverse the UVA-induced loss of collagen. The results of the signalling pathway research showed that tectorigenin mainly affects the MAPK/JNK/AP-1 pathway. In animal experiments, tectorigenin showed better anti-inflammatory and anti-photoaging effects, and caused less skin irritation than ATRA. Nano-particle loaded tectorigenin significantly improved the utilization of tectorigenin. Tectorignen is a non-retinol RAR-γ-selective agonist that can inhibit UV-induced skin damage and could be developed as a safe pharmaceutical component for the prevention of photoaging and skin inflammation.

Anti-Inflammatory Therapy for Acute Coronary Syndromes: Is It Time for a Shift in the Treatment Paradigm?

Anti-Inflammatory Therapy for Acute Coronary Syndromes: Is It Time for a Shift in the Treatment Paradigm?

Cutaneous reactions after COVID-19 vaccination in Turkey: A multicenter study.

ObjectivesIn this study covering all of Turkey, we aimed to define cutaneous and systemic adverse reactions in our patient population after COVID‐19 vaccination with the Sinovac/CoronaVac (inactivated SARS‐CoV‐2) and Pfizer/BioNTech (BNT162b2) vaccines.MethodsThis prospective, cross‐sectional study included individuals presenting to the dermatology or emergency outpatient clinics of a total of 19 centers after having been vaccinated with the COVID‐19 vaccines. Systemic, local injection site, and non‐local cutaneous reactions after vaccination were identified, and their rates were determined.ResultsOf the 2290 individuals vaccinated between April 15 and July 15, 2021, 2097 (91.6%) received the CoronaVac vaccine and 183 (8%) BioNTech. Systemic reactions were observed at a rate of 31.0% after the first CoronaVac dose, 31.1% after the second CoronaVac dose, 46.4% after the first BioNTech dose, and 46.2% after the second BioNTech dose. Local injection site reactions were detected at a rate of 35.6% after the first CoronaVac dose, 35.7% after the second CoronaVac dose, 86.9% after the first BioNTech dose, and 94.1% after the second BioNTech dose. A total of 133 non‐local cutaneous reactions were identified after the CoronaVac vaccine (2.9% after the first dose and 3.5% after the second dose), with the most common being urticaria/angioedema, pityriasis rosea, herpes zoster, and maculopapular rash. After BioNTech, 39 non‐local cutaneous reactions were observed to have developed (24.8% after the first dose and 5% after the second dose), and the most common were herpes zoster, delayed large local reaction, pityriasis rosea, and urticaria/angioedema in order of frequency. Existing autoimmune diseases were triggered in 2.1% of the patients vaccinated with CoronaVac and 8.2% of those vaccinated with BioNTech.ConclusionsThere are no comprehensive data on cutaneous adverse reactions specific to the CoronaVac vaccine. We determined the frequency of adverse reactions from the dermatologist's point of view after CoronaVac and BioNTech vaccination and identified a wide spectrum of non‐local cutaneous reactions. Our data show that CoronaVac is associated with less harmful reactions while BioNTech may result in more serious reactions, such as herpes zoster, anaphylaxis, and triggering of autoimmunity. However, most of these reactions were self‐limiting or required little therapeutic intervention.

Timing of COVID-19 Vaccination in Relation to Elective Surgery.

With the outbreak of the COVID-19 pandemic, the medical profession has had to adapt and transform in order to ensure comprehensive and safe patient care. This has affected the way surgeons triage patients and book and perform operations. The introduction of COVID-19 vaccines was an exciting advancement in disease prevention, but their long-term efficacy and effects remain unknown. We are often asked by patients when we would recommend they receive a COVID-19 vaccine in relation to undergoing surgery. Our goal was to investigate current recommendations regarding timing of COVID-19 vaccination in patients who are undergoing or have recently undergone surgery in an attempt to better inform our plastic surgery patient population. Centers for Disease Control and Prevention recommendations surrounding vaccinations suggest that “current, recent or upcoming anesthesia/surgery/hospitalization” is not a contraindication to receiving any vaccine.1 If patients are acutely ill during the perioperative period, it has been recommended that they wait to receive vaccines as soon as possible once they have improved clinically.1 It is not unusual for patients to exhibit a myriad of acute symptoms related to receiving a vaccine that may confuse the picture of a perioperative illness or infection. Recent phase III trials have shown a significant incidence of side effects following COVID-19 vaccination. The majority appear to be self-limiting and a few days in duration. Such symptoms include flu-like symptoms and reactions restricted to the injection site (Table 1), but severe effects, such as anaphylaxis, although rare, may occur.1,2 These symptoms overlap with those observed in the setting of systemic illness, infection, or adverse drug reaction, all of which are a concern in the acute perioperative period. For example, if a patient presents with a concern for illness preoperatively, we are likely to delay surgery, and in the postoperative setting we may have a heightened suspicion for a surgically related pathogenesis. Table 1. - Side Effects Associated with Various COVID-19 Vaccinations Common Side Effects Uncommon Side Effects Fatigue Anaphylaxis Headache Death Fever and/or chills Nausea and/or vomiting Pain, swelling, or redness at injection site Enlarged lymph nodes Recently there have been reports of facial or lip swelling following receipt of the Moderna (Cambridge, Mass.) COVID-19 vaccine in patients who have a history of facial filler. This appears to be a relatively rare delayed hypersensitivity reaction that resolves when treated with oral steroids and antihistamines. It has been postulated this may result from a vaccine-driven immune response provoking a local inflammatory reaction targeting tissue containing filler.3,4 At this time, there is not enough information to determine with certainty whether this was the cause or how many people with a history of facial filler are likely to have a similar reaction. The Centers for Disease Control and Prevention currently states that people with a history of dermal fillers who have no contraindications to vaccines should proceed with vaccination.1 This is important for plastic surgeons to be aware of and disclose when counseling patients with a history of facial filler or who are considering facial filler in adjunct with the COVID-19 vaccine and may consider delaying such elective procedures until the final vaccine has been received. There is currently no uniform recommendation regarding COVID-19 vaccination timing in respect to elective surgery. Surgery results in a generalized state of immunosuppression and we do not yet have a full understanding of the potential for immunocompromise after COVID-19 vaccination.5 We have therefore taken Centers for Disease Control and Prevention guidelines, available literature, as well as risk factors of surgical procedures into consideration when determining how to most safely and appropriately counsel our patients who are undergoing or have recently undergone surgery. For patients who are undergoing minor elective procedures without prolonged anesthesia and are at lower risk for postoperative complications (e.g., cutaneous oncologic excision and reconstruction, scar revision), we recommend they receive the vaccination at the earliest date possible without any limitation. For patients undergoing more extensive procedures (e.g., autologous and implant-based breast reconstruction, abdominal reconstruction, abdominal or lower body contouring), we recommend patients do not receive the vaccine within a week before or after the operation. We believe this may help prevent misinterpretation of any vaccine-related side effects as perioperative infection that may prompt an extensive workup or intervention. At this time, we have limited available data with which to guide our vaccine recommendations in regard to elective surgery, and our priority is, first and foremost, the safety of our patients. In discussion with our institutions and after reviewing current recommendations and literature, we believe this is a safe and effective way to counsel our patients. We are prepared to make adjustments as we learn more about the impact of COVID-19 vaccination. DISCLOSURE The authors have no financial interest to declare in relation to the content of this article.

Local and systemic adverse reactions following COVID-19 vaccine

The mass vaccination against novel coronavirus infection (COVID-19) requires to dynamically evaluate risks of adverse events following immunization to prevent them and develop vaccination tactics for various population groups. We describe a clinical case of reaction following administration of the second dose of the heterologous recombinant adenovirus based COVID-19 vaccine Gam-COVID-Vac (Sputnik V) in 48-year-old female healthcare worker. No adverse events after administration of the first dose were recorded. After vaccination, the patient complained of weakness, malaise, headache, loss of appetite, and nausea that lasted for a single day. Reaction at the injection site appeared 10 hours after vaccination manifested as pruritic erythema, induration area up to 1.5 cm size, sharp pain, which resolved within 24 hours. On the second day post-vaccination, an inflammation area up to 1.5 cm size within the Bacillus CalmetteGurin (BCG) scar site was noted and manifested as erythema, induration, painful to palpate, pruritus located 2 cm away from the injection site. BCG scar reaction with dull pain and severe pruritus lasted for three weeks. Erythema and induration at the BCG scar site resolved two months after the onset, which were resolved by using antihistaminic agent. The patient was vaccinated according to the Russian Federation Immunization Program, not associated with any adverse events following immunization. The patient had comorbidities such as vasomotor rhinitis, urolithiasis, stomach, duodenal ulcer, type 2 diabetes, arterial hypertension, and her body mass index of 35.2. The patient permanently receives antihypertensive and antihyperglycemic drugs, and has allergic reaction in the form of urticaria to Berodual. The patient has menopause during two years, but a five-day postmenopausal bleeding three days after vaccination with the second dose was noted. Thus, a high-quality surveillance of any local and systemic reactions associated with vaccination is needed to reveal adverse events to the vaccines against COVID-19 and elaborate a safe immunization program for preventing COVID-19.

Adverse drug reactions following lymphocyte immunotherapy for the treatment of infertility: A retrospective study.

Unexplained infertility is a major burden for couples who want to have children. Lymphocyte immunotherapy (LIT) could be a therapeutic help for these couples. Although LIT has been carried out for decades, the data on the success of therapy are still controversial and there is hardly information on possible adverse drug reactions. In this study, we used a questionnaire to determine the frequency of local and systemic adverse drug reactions in our patients who were treated with LIT between 2017 and 2020 (n=302). In addition, we asked about pregnancies and/or live births after LIT in a 2-year follow-up (n=140). Most of the patients reported the occurrence of mild local adverse drug reactions in a period of less than 4 weeks: Over 75% reported moderate erythema, itching or swelling, over 10% erythema, itching or swelling as more pronounced adverse drug reaction. Blistering was specified in 10% of the cases. Serious adverse drug reactions or adverse events were not described. In the follow-up, 69% of our patients stated a pregnancy after LIT, and 50% a life birth. Overall, LIT represents a well-tolerated therapy for couples with unexplained infertility, however, more evidence is needed on the benefits.

Integrating the evidence in allergen immunotherapy: Why real-world data should be important for the practicing clinician?

Data obtained from controlled clinical trials are the gold standard for evaluation of allergen immunotherapy (AIT) efficacy and safety. Less prone to biases (with a strong internal validity), they allow their use and external validation in the real world. The quantity and diversity of real-world data has increased exponentially, and access to large cohorts and electronic medical records have made this information increasingly accessible and useful for research and regulatory purposes. New retrospective database studies have confirmed the sustained benefits of grass, birch pollen, and house dust mite AIT for both allergic rhinitis and asthma symptom and medication scores, the prevention of asthma (when used in nonasthmatic rhinitics), and the real rate of adverse systemic reactions. They also have addressed clinical practice issues not elsewhere analyzed, including the management of polysensitized patients with respiratory allergies and adherence to AIT. Real-world evidence has its own biases and limits that need to be taken into account. In this article we present a concise summary of the literature about the role of real-world evidence in AIT.

Uterine Inflammatory Response After Prostaglandin E1 (Misoprostol) Infusion Prebreeding or Immediately After Embryo Flushing in Commercial Donor Mares

Misoprostol, a synthetic PGE1, is becoming a common therapy for mares with suspected uterine tube obstruction. Recently, there have been concerns that uterine administration of misoprostol induces exacerbated uterine inflammation; however, this has not been critically evaluated. This study aimed to assess the inflammatory response and potential systemic reactions after uterine administration of misoprostol, either during prebreeding or immediately after postembryo flushing. Privately owned embryo donor mares (n = 11) were randomly assigned in a crossover design to receive misoprostol (3 mL +200 µg) or sham (3 mL of lactate Ringer's solution) infusions, bilaterally deposited via deep-horn, at least 72 hours prebreeding (experiment 1) or immediately after embryo flushing (experiment 2). Each mare had one cycle for misoprostol and sham in both experiments and a breeding cycle (no sham or misoprostol) between experiments. Uterine edema, fluid accumulation, and the number of uterine PMN were assessed before each infusion and then daily for 72 hours. Uterine lavage was performed the day after each infusion across groups and experiments. Ovulation was hastened with a GnRH agonist and confirmed at 24 hour-intervals. Mares were bred with semen from one of six stallions per owner's choice. Embryo flushing was performed 8 to 9 days postovulation. In either experiment, misoprostol did not affect uterine edema or fluid accumulation (P > .05). However, both the sham and misoprostol infusions increased the number of PMN up to 48 hours postinfusion in both experiments. Embryo recoveries were similar between sham (45%, 5/11) and misoprostol cycles in experiments 1 (45%, 5/11; P > .05) and 2 (sham, 68%, 7/11; misoprostol, 45%, 5/11; P > .05). In conclusion, misoprostol did not induce exacerbated uterine inflammation in mares or systemic adverse reactions when infused prebreeding or immediately after embryo flushing.