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1.
Thyroid ; 31(9): 1436-1439, 2021 09.
Article in English | MEDLINE | ID: covidwho-1189426

ABSTRACT

Background: The autoimmune/inflammatory syndrome induced by adjuvants (ASIA) comprises four entities, including the postvaccination phenomenon, which appears after being exposed to adjuvants in vaccines that increase the immune response. There is limited information about autoimmune endocrine diseases and ASIA after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. Patient's Findings: Two female health care workers received a SARS-CoV-2 vaccine, and three days later developed clinical manifestations of thyroid hyperactivity, with increased thyroid hormone levels on thyroid function tests, suppressed thyroid-stimulating hormone, and elevated antithyroid antibodies. Summary: Vaccines have been shown to trigger an immune response that leads to a broad spectrum of autoimmune diseases, including autoimmune thyroid disease. Our patients met the diagnostic criteria for ASIA; they were exposed to an adjuvant (vaccine), and they developed clinical manifestations of thyroid hyperfunction within a few days, with the appearance of antithyroid antibodies, despite being healthy before vaccination. Conclusion: Graves' disease can occur after SARS-CoV-2 vaccination.


Subject(s)
Adjuvants, Immunologic/adverse effects , COVID-19 Vaccines/adverse effects , Graves Disease/chemically induced , Thyroid Hormones/blood , Vaccination/adverse effects , Adult , Autoantibodies/blood , Biomarkers/blood , COVID-19 Vaccines/chemistry , Drug Compounding , Female , Graves Disease/blood , Graves Disease/diagnosis , Graves Disease/immunology , Humans , Risk Factors
2.
Medicina (Kaunas) ; 57(3)2021 Mar 09.
Article in English | MEDLINE | ID: covidwho-1167649

ABSTRACT

The current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic warrants an imperative necessity for effective and safe vaccination, to restrain Coronavirus disease 2019 (COVID-19) including transmissibility, morbidity, and mortality. In this regard, intensive medical and biological research leading to the development of an arsenal of vaccines, albeit incomplete preconditioned evaluation, due to emergency. The subsequent scientific gap raises some concerns in the medical community and the general public. More specifically, the accelerated vaccine development downgraded the value of necessary pre-clinical studies to elicit medium- and long-term beneficial or harmful consequences. Previous experience and pathophysiological background of coronaviruses' infections and vaccine technologies, combined with the global vaccines' application, underlined the obligation of a cautious and qualitative approach, to illuminate potential vaccination-related adverse events. Moreover, the high SARS-CoV-2 mutation potential and the already aggregated genetical alterations provoke a rational vagueness and uncertainty concerning vaccines' efficacy against dominant strains and the respective clinical immunity. This review critically summarizes existing evidence and queries regarding SARS-CoV-2 vaccines, to motivate scientists' and clinicians' interest for an optimal, individualized, and holistic management of this unprecedented pandemic.


Subject(s)
COVID-19 Vaccines/therapeutic use , COVID-19/prevention & control , Adjuvants, Immunologic/adverse effects , Autoimmune Diseases/chemically induced , Drug Approval , Drug Evaluation, Preclinical , Hippocratic Oath , Humans , Long Term Adverse Effects/chemically induced , Models, Animal , Risk Assessment , SARS-CoV-2 , Vaccines, Inactivated/therapeutic use , Vaccines, Synthetic/therapeutic use
3.
Clin Exp Allergy ; 51(6): 770-777, 2021 06.
Article in English | MEDLINE | ID: covidwho-1165861

ABSTRACT

COVID-19-related mortality in high-risk individuals is substantial and current treatment options are limited. There is convincing evidence that the COVID-19 vaccines reduce the severity of infection and prevent deaths. Three COVID-19 vaccines are approved in the United Kingdom with many more in development. There are limited data on the triggers and mechanisms of anaphylaxis to these vaccines. We review the potential allergenic compounds in the COVID-19 vaccines and describe an innovative allergy support model for the vaccination hubs that allows most patients with severe allergy be immunized. Finally, we propose a practical algorithm for the investigations of anaphylaxis to these vaccines.


Subject(s)
Algorithms , Anaphylaxis/chemically induced , COVID-19 Vaccines/adverse effects , COVID-19/drug therapy , Decision Support Techniques , Drug Hypersensitivity/etiology , Vaccination/adverse effects , Adjuvants, Immunologic/adverse effects , Anaphylaxis/diagnosis , Anaphylaxis/therapy , COVID-19/diagnosis , COVID-19/immunology , Clinical Decision-Making , Drug Hypersensitivity/diagnosis , Drug Hypersensitivity/therapy , Humans , Risk Assessment , Risk Factors , Treatment Outcome , Vaccine Excipients/adverse effects
4.
JAMA Netw Open ; 4(1): e2031266, 2021 01 04.
Article in English | MEDLINE | ID: covidwho-1130416

ABSTRACT

Importance: Trivalent adjuvanted inactivated influenza vaccine (aIIV3) and trivalent high-dose inactivated influenza vaccine (HD-IIV3) are US-licensed for adults aged 65 years and older. Data are needed on the comparative safety, reactogenicity, and health-related quality of life (HRQOL) effects of these vaccines. Objective: To compare safety, reactogenicity, and changes in HRQOL scores after aIIV3 vs HD-IIV3. Design, Setting, and Participants: This randomized blinded clinical trial was a multicenter US study conducted during the 2017 to 2018 and 2018 to 2019 influenza seasons. Among 778 community-dwelling adults aged at least 65 years and assessed for eligibility, 13 were ineligible and 8 withdrew before randomization. Statistical analysis was performed from August 2019 to August 2020. Interventions: Intramuscular administration of aIIV3 or HD-IIV3 after age-stratification (65-79 years; ≥80 years) and randomization. Main Outcomes and Measures: Proportions of participants with moderate-to-severe injection-site pain and 14 other solicited reactions during days 1 to 8, using a noninferiority test (5% noninferiority margin), and serious adverse events (SAE) and adverse events of clinical interest (AECI), including new-onset immune-mediated conditions, during days 1 to 43. Changes in HRQOL scores before and after vaccination (days 1, 3) were also compared between study groups. Results: A total of 757 adults were randomized, 378 to receive aIIV3 and 379 to receive HD-IIV3. Of these participants, there were 420 women (55%) and 589 White individuals (78%) with a median (range) age of 72 (65-97) years. The proportion reporting moderate-to-severe injection-site pain, limiting or preventing activity, after aIIV3 (12 participants [3.2%]) (primary outcome) was noninferior compared with HD-IIV3 (22 participants [5.8%]) (difference -2.7%; 95% CI, -5.8 to 0.4). Ten reactions met noninferiority criteria for aIIV3; 4 (moderate-to-severe injection-site tenderness, arthralgia, fatigue, malaise) did not. It was inconclusive whether these 4 reactions occurred in higher proportions of participants after aIIV3. No participant sought medical care for a vaccine reaction. No AECI was observed. Nine participants had at least SAE after aIIV3 (2.4%; 95% CI,1.1% to 4.5%); 3 had at least 1 SAE after HD-IIV3 (0.8%; 95% CI, 0.2% to 2.2%). No SAE was associated with vaccination. Changes in prevaccination and postvaccination HRQOL scores were not clinically meaningful and not different between the groups. Conclusions and Relevance: Overall safety and HRQOL findings were similar after aIIV3 and HD-IIV3, and consistent with prelicensure data. From a safety standpoint, this study's results support using either vaccine to prevent influenza in older adults. Trial Registration: ClinicalTrials.gov Identifier: NCT03183908.


Subject(s)
Adjuvants, Immunologic , Influenza Vaccines , Influenza, Human/prevention & control , Quality of Life , Vaccines, Inactivated , Adjuvants, Immunologic/administration & dosage , Adjuvants, Immunologic/adverse effects , Aged , Aged, 80 and over , Drug-Related Side Effects and Adverse Reactions/epidemiology , Female , Humans , Influenza Vaccines/administration & dosage , Influenza Vaccines/adverse effects , Influenza Vaccines/immunology , Injections, Intramuscular , Male , Vaccines, Inactivated/administration & dosage , Vaccines, Inactivated/adverse effects , Vaccines, Inactivated/immunology
5.
Lancet ; 397(10275): 682-694, 2021 02 20.
Article in English | MEDLINE | ID: covidwho-1091574

ABSTRACT

BACKGROUND: As part of the accelerated development of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), we report a dose-finding and adjuvant justification study of SCB-2019, a protein subunit vaccine candidate containing a stabilised trimeric form of the spike (S)-protein (S-Trimer) combined with two different adjuvants. METHODS: Our study is a phase 1, randomised, double-blind placebo-controlled trial at a specialised clinical trials centre in Australia. We enrolled healthy adult volunteers in two age groups: younger adults (aged 18-54 years) and older adults (aged 55-75 years). Participants were randomly allocated either vaccine or placebo using a list prepared by the study funder. Participants were to receive two doses of SCB-2019 (either 3 µg, 9 µg, or 30 µg) or a placebo (0·9% NaCl) 21 days apart. SCB-2019 either had no adjuvant (S-Trimer protein alone) or was adjuvanted with AS03 or CpG/Alum. The assigned treatment was administered in opaque syringes to maintain masking of assignments. Reactogenicity was assessed for 7 days after each vaccination. Humoral responses were measured as SCB-2019 binding IgG antibodies and ACE2-competitive blocking IgG antibodies by ELISA and as neutralising antibodies by wild-type SARS-CoV-2 microneutralisation assay. Cellular responses to pooled S-protein peptides were measured by flow-cytometric intracellular cytokine staining. This trial is registered with ClinicalTrials.gov, NCT04405908; this is an interim analysis and the study is continuing. FINDINGS: Between June 19 and Sept 23, 2020, 151 volunteers were enrolled; three people withdrew, two for personal reasons and one with an unrelated serious adverse event (pituitary adenoma). 148 participants had at least 4 weeks of follow-up after dose two and were included in this analysis (database lock, Oct 23, 2020). Vaccination was well tolerated, with two grade 3 solicited adverse events (pain in 9 µg AS03-adjuvanted and 9 µg CpG/Alum-adjuvanted groups). Most local adverse events were mild injection-site pain, and local events were more frequent with SCB-2019 formulations containing AS03 adjuvant (44-69%) than with those containing CpG/Alum adjuvant (6-44%) or no adjuvant (3-13%). Systemic adverse events were more frequent in younger adults (38%) than in older adults (17%) after the first dose but increased to similar levels in both age groups after the second dose (30% in older and 34% in younger adults). SCB-2019 with no adjuvant elicited minimal immune responses (three seroconversions by day 50), but SCB-2019 with fixed doses of either AS03 or CpG/Alum adjuvants induced high titres and seroconversion rates of binding and neutralising antibodies in both younger and older adults (anti-SCB-2019 IgG antibody geometric mean titres at day 36 were 1567-4452 with AS03 and 174-2440 with CpG/Alum). Titres in all AS03 dose groups and the CpG/Alum 30 µg group were higher than were those recorded in a panel of convalescent serum samples from patients with COVID-19. Both adjuvanted SCB-2019 formulations elicited T-helper-1-biased CD4+ T-cell responses. INTERPRETATION: The SCB-2019 vaccine, comprising S-Trimer protein formulated with either AS03 or CpG/Alum adjuvants, elicited robust humoral and cellular immune responses against SARS-CoV-2, with high viral neutralising activity. Both adjuvanted vaccine formulations were well tolerated and are suitable for further clinical development. FUNDING: Clover Biopharmaceuticals and the Coalition for Epidemic Preparedness Innovations.


Subject(s)
Adjuvants, Immunologic/pharmacology , COVID-19 Vaccines/adverse effects , COVID-19 Vaccines/immunology , SARS-CoV-2/immunology , Adjuvants, Immunologic/adverse effects , Adult , Aged , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , Australia , COVID-19/prevention & control , COVID-19 Vaccines/administration & dosage , Double-Blind Method , Female , Humans , Immunogenicity, Vaccine , Immunoglobulin G/blood , Male , Middle Aged , Protein Subunits , Vaccines, Subunit/immunology
6.
Int Immunopharmacol ; 88: 106873, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-1002650

ABSTRACT

BACKGROUND: COVID-19 characterized by refractory hypoxemia increases patient mortality because of immunosuppression effects. This study aimed to evaluate the efficacy of immunomodulatory with thymosin α1 for critical COVID-19 patients. METHODS: This multicenter retrospective cohort study was performed in 8 government-designated treatment centers for COVID-19 patients in China from Dec. 2019 to Mar. 2020. Thymosin α1 was administrated with 1.6 mg qd or q12 h for >5 days. The primary outcomes were the 28-day and 60-day mortality, the secondary outcomes were hospital length of stay and the total duration of the disease. Subgroup analysis was carried out according to clinical classification. RESULTS: Of the 334 enrolled COVID-19 patients, 42 (12.6%) died within 28 days, and 55 (16.5%) died within 60 days of hospitalization. There was a significant difference in the 28-day mortality between the thymosin α1 and non-thymosin α1-treated groups in adjusted model (P = 0.016), without obvious differences in the 60-day mortality and survival time in the overall cohort (P > 0.05). In the subgroup analysis, it was found that thymosin α1 therapy significantly reduced 28-day mortality (Hazards Ratios HR, 0.11, 95% confidence interval CI 0.02-0.63, P=0.013) via improvement of Pa02/FiO2 (P = 0.036) and prolonged the hospital length of stay (P = 0.024) as well as the total duration of the disease (P=0.001) in the critical type patients, especially those aged over 64 years, with white blood cell >6.8×109/L, neutrophil >5.3×109/L, lymphocyte < 0.73 × 109/L, PaO2/FiO2 < 196, SOFA > 3, and acute physiology and chronic health evaluation (APACHE) II > 7. CONCLUSION: These results suggest that treatment with thymosin α1 can markedly decrease 28-day mortality and attenuate acute lung injury in critical type COVID-19 patients.


Subject(s)
Adjuvants, Immunologic/therapeutic use , Coronavirus Infections/drug therapy , Critical Care/methods , Pneumonia, Viral/drug therapy , Thymalfasin/therapeutic use , APACHE , Adjuvants, Immunologic/administration & dosage , Adjuvants, Immunologic/adverse effects , Aged , Betacoronavirus , COVID-19 , China/epidemiology , Cohort Studies , Coronavirus Infections/immunology , Coronavirus Infections/mortality , Critical Illness , Female , Humans , Male , Middle Aged , Mortality/trends , Pandemics , Pneumonia, Viral/immunology , Pneumonia, Viral/mortality , Proportional Hazards Models , Retrospective Studies , SARS-CoV-2 , Thymalfasin/administration & dosage , Thymalfasin/adverse effects
7.
J Clin Pharm Ther ; 46(3): 724-730, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-991463

ABSTRACT

WHAT IS KNOWN AND OBJECTIVE: Initial treatment recommendations of COVID-19 were based on the use of antimicrobial drugs and immunomodulators. Although information on drug interactions was available for other pathologies, there was little evidence in the treatment of COVID-19. The objective of this study was to analyse the potential drug-drug interactions (pDDIs) derived from the medication used in COVID-19 patients in the first pandemic wave and to evaluate the real consequences of such interactions in clinical practice. METHODS: Cohort, retrospective and single-centre study carried out in a third-level hospital. Adult patients, admitted with suspected COVID-19, that received at least one dose of hydroxychloroquine, lopinavir/ritonavir, interferon beta 1-b or tocilizumab and with any pDDIs according to "Liverpool Drug Interaction Group" between March and May 2020 were included. The possible consequences of pDDIs at the QTc interval level or any other adverse event according to the patient's medical record were analysed. A descriptive analysis was carried out to assess possible factors that may affect the QTc interval prolongation. RESULTS AND DISCUSSION: Two hundred and eighteen (62.3%) patients of a total of 350 patients admitted with COVID-19 had at least one pDDI. There were 598 pDDIs. Thirty-eight pDDIs (6.3%) were categorized as not recommended or contraindicated. The mean value difference between baseline and pDDI posterior ECG was 412.3 ms ± 25.8 ms vs. 426.3 ms ± 26.7 ms; p < 0.001. Seven patients (5.7%) had a clinically significant alteration of QTc. A total of 44 non-cardiological events (7.3%) with a possible connection to a pDDI were detected. WHAT IS NEW AND CONCLUSION: The number of pDDIs in patients admitted for COVID-19 in the first pandemic wave was remarkably high. However, clinical consequences occurred in a low percentage of patients. Interactions involving medications that would be contraindicated for concomitant administration are rare. Knowledge of these pDDIs and their consequences could help to establish appropriate therapeutic strategies in patients with COVID-19 or other diseases with these treatments.


Subject(s)
Antibodies, Monoclonal, Humanized/adverse effects , COVID-19/drug therapy , Hydroxychloroquine/adverse effects , Interferon beta-1b/adverse effects , Lopinavir/adverse effects , Ritonavir/adverse effects , Adjuvants, Immunologic/adverse effects , Aged , COVID-19/complications , Cohort Studies , Cytochrome P-450 CYP3A Inhibitors/adverse effects , Drug Interactions , Enzyme Inhibitors/adverse effects , Female , Humans , Male , Prevalence , Retrospective Studies , Risk Factors , SARS-CoV-2
8.
Int J Clin Pract ; 75(3): e13752, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-916230

ABSTRACT

AIM: We evaluated the COVID-19 infection threat in patients receiving intravesical BCG therapy which has immunotherapeutic effects and is of vital importance in most of the individuals with high-risk non-muscle-invasive bladder cancer (NMIBC) and investigated the need for postponement of this therapy. METHODS: A total of 71 patients, who were diagnosed with high-risk NMIBC and on intravesical BCG treatment regularly (induction or maintenance), were enrolled in the study. The patients were classified into two groups depending on whether they were diagnosed with COVID-19 during the pandemic period or not. RESULTS: Of 71 patients, 26 underwent a COVID-19 polymerase chain reaction test with clinical suspicion during the pandemic period. Of these 26 patients, 4 were diagnosed with COVID-19. Age of the patients, working status (working/retired), compliance with containment measures against the pandemic, number of BCG courses, adverse effects after BCG therapy and systemic immune-inflammation index, which is an inflammation-related parameter, were not different between groups (P > .05). Neutrophil/lymphocyte ratio was significantly higher in the COVID-19 positive group (P < .05). COVID-19 positivity was higher in age groups 50-64 (6.6%) and 65-80 (5.8%) years than that in similar age groups of the normal population. CONCLUSION: Every effort should be made to administer intravesical BCG treatment in high-risk NMIBC patients even during the pandemic period. However, increased risk of COVID-19 transmission should be kept in mind and protective measures against COVID-19 for healthcare providers and patients before the procedure should be taken optimally. The procedure should be postponed in patients with lymphopenia in recent complete blood count.


Subject(s)
COVID-19 , Urinary Bladder Neoplasms , Adjuvants, Immunologic/adverse effects , Administration, Intravesical , BCG Vaccine/adverse effects , Humans , SARS-CoV-2 , Urinary Bladder Neoplasms/drug therapy
9.
JAMA ; 324(10): 951-960, 2020 09 08.
Article in English | MEDLINE | ID: covidwho-911581

ABSTRACT

Importance: A vaccine against coronavirus disease 2019 (COVID-19) is urgently needed. Objective: To evaluate the safety and immunogenicity of an investigational inactivated whole-virus COVID-19 vaccine in China. Interventions: In the phase 1 trial, 96 participants were assigned to 1 of the 3 dose groups (2.5, 5, and 10 µg/dose) and an aluminum hydroxide (alum) adjuvant-only group (n = 24 in each group), and received 3 intramuscular injections at days 0, 28, and 56. In the phase 2 trial, 224 adults were randomized to 5 µg/dose in 2 schedule groups (injections on days 0 and 14 [n = 84] vs alum only [n = 28], and days 0 and 21 [n = 84] vs alum only [n = 28]). Design, Setting, and Participants: Interim analysis of ongoing randomized, double-blind, placebo-controlled, phase 1 and 2 clinical trials to assess an inactivated COVID-19 vaccine. The trials were conducted in Henan Province, China, among 96 (phase 1) and 224 (phase 2) healthy adults aged between 18 and 59 years. Study enrollment began on April 12, 2020. The interim analysis was conducted on June 16, 2020, and updated on July 27, 2020. Main Outcomes and Measures: The primary safety outcome was the combined adverse reactions 7 days after each injection, and the primary immunogenicity outcome was neutralizing antibody response 14 days after the whole-course vaccination, which was measured by a 50% plaque reduction neutralization test against live severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Results: Among 320 patients who were randomized (mean age, 42.8 years; 200 women [62.5%]), all completed the trial up to 28 days after the whole-course vaccination. The 7-day adverse reactions occurred in 3 (12.5%), 5 (20.8%), 4 (16.7%), and 6 (25.0%) patients in the alum only, low-dose, medium-dose, and high-dose groups, respectively, in the phase 1 trial; and in 5 (6.0%) and 4 (14.3%) patients who received injections on days 0 and 14 for vaccine and alum only, and 16 (19.0%) and 5 (17.9%) patients who received injections on days 0 and 21 for vaccine and alum only, respectively, in the phase 2 trial. The most common adverse reaction was injection site pain, followed by fever, which were mild and self-limiting; no serious adverse reactions were noted. The geometric mean titers of neutralizing antibodies in the low-, medium-, and high-dose groups at day 14 after 3 injections were 316 (95% CI, 218-457), 206 (95% CI, 123-343), and 297 (95% CI, 208-424), respectively, in the phase 1 trial, and were 121 (95% CI, 95-154) and 247 (95% CI, 176-345) at day 14 after 2 injections in participants receiving vaccine on days 0 and 14 and on days 0 and 21, respectively, in the phase 2 trial. There were no detectable antibody responses in all alum-only groups. Conclusions and Relevance: In this interim report of the phase 1 and phase 2 trials of an inactivated COVID-19 vaccine, patients had a low rate of adverse reactions and demonstrated immunogenicity; the study is ongoing. Efficacy and longer-term adverse event assessment will require phase 3 trials. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR2000031809.


Subject(s)
Betacoronavirus/immunology , Coronavirus Infections/prevention & control , Immunogenicity, Vaccine , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Viral Vaccines/immunology , Adjuvants, Immunologic/administration & dosage , Adjuvants, Immunologic/adverse effects , Adolescent , Adult , Aluminum Hydroxide/administration & dosage , Aluminum Hydroxide/adverse effects , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , Betacoronavirus/genetics , COVID-19 , COVID-19 Vaccines , Coronavirus Infections/immunology , Dose-Response Relationship, Immunologic , Double-Blind Method , Female , Humans , Injections, Intramuscular , Male , Pneumonia, Viral/immunology , Propiolactone , SARS-CoV-2 , Vaccines, Inactivated/immunology , Viral Vaccines/administration & dosage , Viral Vaccines/adverse effects , Young Adult
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