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1.
Mol Ther ; 30(5): 1941-1951, 2022 05 04.
Article in English | MEDLINE | ID: covidwho-1663945

ABSTRACT

Lipid nanoparticle (LNP)-formulated nucleoside-modified mRNA vaccines have proven to be very successful in the fight against the coronavirus disease 2019 (COVID-19) pandemic. They are effective, safe, and can be produced in large quantities. However, the long-term storage of mRNA-LNP vaccines without freezing is still a challenge. Here, we demonstrate that nucleoside-modified mRNA-LNPs can be lyophilized, and the physicochemical properties of the lyophilized material do not significantly change for 12 weeks after storage at room temperature and for at least 24 weeks after storage at 4°C. Importantly, we show in comparative mouse studies that lyophilized firefly luciferase-encoding mRNA-LNPs maintain their high expression, and no decrease in the immunogenicity of a lyophilized influenza virus hemagglutinin-encoding mRNA-LNP vaccine was observed after 12 weeks of storage at room temperature or for at least 24 weeks after storage at 4°C. Our studies offer a potential solution to overcome the long-term storage-related limitations of nucleoside-modified mRNA-LNP vaccines.


Subject(s)
COVID-19 , Influenza Vaccines , Nanoparticles , Animals , COVID-19/prevention & control , Freeze Drying , Liposomes , Mice , Nanoparticles/chemistry , Nucleosides , RNA, Messenger/genetics , Vaccines, Synthetic , mRNA Vaccines
2.
Sci Rep ; 12(1): 11298, 2022 Jul 04.
Article in English | MEDLINE | ID: covidwho-2028705

ABSTRACT

Reliable serological assays are needed to understand the real impact of COVID-19. In order to compare the efficiency of different COVID-19 vaccines used in the National Vaccination Program in Tunisia, we have developed a quantitative in-house ELISA. The ELISA is based on the ectodomain of the SARS-CoV-2 Spike Baculovirus recombinant protein. We used a panel of 145 COVID-19 RT-PCR positive serum samples and 116 pre-pandemic serum samples as a negative panel. The validation was carried out by comparison to four commercial techniques (Vidas SARS-CoV-2 IgG anti-RBD Biomérieux, Elecsys Anti-Nucleocapsid of SARS-CoV-2 Roche, cPass GenScript and the quantitative Elecsys Anti-RBD of SARS-CoV-2, Roche). For the evaluation of the National Vaccination campaign, we have included 115 recipients who received one of the approved vaccines. The qualitative performances of the developed ELISA gave 96% sensitivity, 97.5% specificity and 0.968 accuracy. For the evaluation of the different brand of vaccines in recipients not previously infected with SARS-CoV-2, it seems that mRNA vaccine of Pfizer/BioNTech has shown a higher efficacy compared to inactivated virus vaccines. COVID-19 convalescent individuals have generated poor antibody responses. Nevertheless, when they are vaccinated with any brand of the COVID-19 vaccines, many of them mounted an exponential increase of the induced immune responses, qualified as a "hybrid vigor immunity". Our developed in-house ELISA seems to be very efficient in evaluating the effectiveness of anti-COVID-19 vaccination. Platforms based on mRNA vaccine are better performing than those based on inactivated virus.


Subject(s)
COVID-19 , Viral Vaccines , COVID-19/prevention & control , COVID-19 Vaccines , Enzyme-Linked Immunosorbent Assay , Humans , SARS-CoV-2 , Vaccines, Inactivated , Vaccines, Synthetic , mRNA Vaccines
3.
PLoS One ; 17(6): e0269727, 2022.
Article in English | MEDLINE | ID: covidwho-2021799

ABSTRACT

As a member state of the European Union, where vaccines against COVID-19 are available and affordable, Bulgaria reports the lowest immunization coverage and the most pronounced vaccine distrust. The present study aimed to assess the self-reported adverse reactions following COVID-19 vaccination as a possible tool to increase the trust in vaccines. A cross-sectional survey-based study, covering 761 vaccinated respondents, was conducted in Plovdiv (469 with an mRNA vaccine and 292 with an adenoviral vector vaccine). Descriptive statistics parametric and non-parametric methods were applied. Statistical significance was set at p<0.05. The median age of the respondents was 42 years, females (72.5%). At least one adverse reaction was reported in 89.9% of those immunized with mRNA vaccine and 93.8% in the adenoviral vector vaccine group (p>0.05). They were mild to moderate and resolved within several days. The levels of local reactions were comparable: 91.7% in those who received mRNA and 89.7% in those who received an adenoviral vector vaccine (p = 0.366). The most common types of systemic reactions were fatigue, headache, and muscle pains. An association was found between the systemic reactions and the type of vaccine administered: 59.7% in mRNA recipients and 89.4% in adenoviral vector vaccinees (p<0.001). None of the registered systemic reactions required medical attention. There were 3 reports of generalized urticaria after an mRNA and 2 after an adenoviral vector vaccine. The reported reactions are relatively high but expected and no adverse events have been reported that are not listed in the official Summary of Product Characteristics.


Subject(s)
COVID-19 Vaccines , COVID-19 , Viral Vaccines , Adult , Bulgaria , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Cross-Sectional Studies , Female , Humans , RNA, Messenger , Self Report , Vaccination , Vaccines, Synthetic/adverse effects , Viral Vaccines/adverse effects , mRNA Vaccines
5.
Lupus Sci Med ; 9(1)2022 Aug.
Article in English | MEDLINE | ID: covidwho-1993063

ABSTRACT

OBJECTIVES: Numerous case reports have referred to new onset or flare of SLE after SARS-CoV-2 messenger RNA (mRNA) vaccines. Several observational studies showed that the short-term flare rate of SLE after SARS-CoV-2 vaccination is low. However, well-controlled clinical surveys are unavailable and the medium-term impact of the SARS-CoV-2 mRNA vaccines against the flare of SLE is uncertain. Therefore, we aimed to analyse the association between vaccination and medium-term subjective and objective disease activities of SLE and flares using matched pair methods. METHODS: Altogether, 150 patients with SLE from the Kyoto Lupus Cohort were included. Patients who received two doses of the SARS-CoV-2 mRNA vaccines were 1:1 matched with unvaccinated patients based on the first vaccination date. The outcome measures were the SLE Disease Activity Index-2000 (SLEDAI-2K), the Japanese version of the SLE Symptom Checklist Questionnaire (SSC-J) and the Safety of Estrogens in Lupus Erythematosus National Assessment-SLEDAI flare index at 30, 60 and 90 days after vaccination. RESULTS: SLEDAI-2K levels were not significantly different in vaccinated and unvaccinated patients with SLE at 30, 60 and 90 days after the second vaccination (adjusted estimate (95% CI): 30 days: -0.46 (-1.48 to 0.56), p=0.39; 60 days: 0.38 (-0.64 to 1.40), p=0.47; 90 days: 0.40 (-0.54 to 1.34), p=0.41). Similar results were observed in the SSC-J score (adjusted estimate (95% CI), 30 days: 0.05 (-1.46 to 1.56), p=0.95; 60 days: -0.63 (-2.08 to 0.82), p=0.40; 90 days: 0.27 (-1.04 to 1.58), p=0.69) and flare index (adjusted OR (95% CI), 30 days: 0.81 (0.36 to 1.85), p=0.62; 60 days: 1.13 (0.50 to 2.54), p=0.77; 90 days: 0.85 (0.32 to 2.26), p=0.74). CONCLUSION: SARS-CoV-2 vaccination did not significantly influence the medium-term subjective and objective disease activities or flares of SLE until 90 days after the second vaccination.


Subject(s)
COVID-19 , Lupus Erythematosus, Systemic , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Humans , Lupus Erythematosus, Systemic/diagnosis , RNA, Messenger , SARS-CoV-2 , Severity of Illness Index , Vaccines, Synthetic , mRNA Vaccines
7.
J Infect Dis ; 226(1): 32-37, 2022 Aug 12.
Article in English | MEDLINE | ID: covidwho-1992204

ABSTRACT

Several studies reported that severe acute respiratory syndrome coronavirus-2 antibody levels change over 6 months in participants receiving the vaccination. From the enrolled 272 health care workers (HCWs), blood samples were obtained at 2, 16, and 24 weeks after the second vaccination dose. In the 267 noninfected HCWs, the neutralizing antibodies decreased by 23.9%, and the anti-spike/receptor binding domain antibody decreased by 53.8% at 24 weeks. We observed no significant difference in antibody reduction between the sexes; however, in younger individuals, there was higher antibody formation and lower reduction rates of the neutralizing antibody. In 3 HCWs with breakthrough infections, the antibody levels were relatively low just before the coronavirus disease 2019 infection. In conclusion, as antibody titers decrease over time after the second vaccination dose and HCWs with low antibody titers tend to have a high probability of breakthrough infection, an additional dose should be considered after several months. Blood samples were obtained from health care workers at 2, 16, and 24 weeks after a second vaccination dose. Antibody titers decreased over time and the participants with low antibody titers tended to have a high probability of breakthrough infection.


Subject(s)
BNT162 Vaccine , COVID-19 , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/prevention & control , Health Personnel , Humans , Prospective Studies , SARS-CoV-2 , Vaccines, Synthetic , mRNA Vaccines
8.
Clin Infect Dis ; 75(Supplement_1): S61-S71, 2022 Aug 15.
Article in English | MEDLINE | ID: covidwho-1992145

ABSTRACT

BACKGROUND: Male sex and old age are risk factors for severe coronavirus disease 2019, but the intersection of sex and aging on antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines has not been characterized. METHODS: Plasma samples were collected from older adults (aged 75-98 years) before and after 3 doses of SARS-CoV-2 mRNA vaccination, and from younger adults (aged 18-74 years) post-dose 2, for comparison. Antibody binding to SARS-CoV-2 antigens (spike protein [S], S receptor-binding domain, and nucleocapsid), functional activity against S, and live-virus neutralization were measured against the vaccine virus and the Alpha, Delta, and Omicron variants of concern (VOCs). RESULTS: Vaccination induced greater antibody titers in older females than in older males, with both age and frailty associated with reduced antibody responses in males but not females. Responses declined significantly in the 6 months after the second dose. The third dose restored functional antibody responses and eliminated disparities caused by sex, age, and frailty in older adults. Responses to the VOCs, particularly the Omicron variant, were significantly reduced relative to the vaccine virus, with older males having lower titers to the VOCs than older females. Older adults had lower responses to the vaccine and VOC viruses than younger adults, with greater disparities in males than in females. CONCLUSIONS: Older and frail males may be more vulnerable to breakthrough infections owing to low antibody responses before receipt of a third vaccine dose. Promoting third dose coverage in older adults, especially males, is crucial to protecting this vulnerable population.


Subject(s)
COVID-19 , Frailty , Viral Vaccines , Aged , COVID-19/prevention & control , Humans , Male , SARS-CoV-2/genetics , Vaccines, Synthetic , mRNA Vaccines
9.
Proc Natl Acad Sci U S A ; 119(34): e2207841119, 2022 Aug 23.
Article in English | MEDLINE | ID: covidwho-1991768

ABSTRACT

The targeted delivery of messenger RNA (mRNA) to desired organs remains a great challenge for in vivo applications of mRNA technology. For mRNA vaccines, the targeted delivery to the lymph node (LN) is predicted to reduce side effects and increase the immune response. In this study, we explored an endogenously LN-targeting lipid nanoparticle (LNP) without the modification of any active targeting ligands for developing an mRNA cancer vaccine. The LNP named 113-O12B showed increased and specific expression in the LN compared with LNP formulated with ALC-0315, a synthetic lipid used in the COVID-19 vaccine Comirnaty. The targeted delivery of mRNA to the LN increased the CD8+ T cell response to the encoded full-length ovalbumin (OVA) model antigen. As a result, the protective and therapeutic effect of the OVA-encoding mRNA vaccine on the OVA-antigen-bearing B16F10 melanoma model was also improved. Moreover, 113-O12B encapsulated with TRP-2 peptide (TRP2180-188)-encoding mRNA also exhibited excellent tumor inhibition, with the complete response of 40% in the regular B16F10 tumor model when combined with anti-programmed death-1 (PD-1) therapy, revealing broad application of 113-O12B from protein to peptide antigens. All the treated mice showed long-term immune memory, hindering the occurrence of tumor metastatic nodules in the lung in the rechallenging experiments that followed. The enhanced antitumor efficacy of the LN-targeting LNP system shows great potential as a universal platform for the next generation of mRNA vaccines.


Subject(s)
COVID-19 , Cancer Vaccines , Nanoparticles , Neoplasms , Amino Alcohols , Animals , Antigens/metabolism , CD8-Positive T-Lymphocytes , COVID-19 Vaccines , Decanoates , Humans , Liposomes , Lymph Nodes , Mice , Neoplasms/metabolism , Ovalbumin , RNA, Messenger/metabolism , Vaccines, Synthetic , mRNA Vaccines
10.
Transplant Proc ; 54(4): 901-904, 2022 May.
Article in English | MEDLINE | ID: covidwho-1991307

ABSTRACT

BACKGROUND: The SARS-CoV-2 pandemic is ongoing. In this context, patients after organ transplantation are especially endangered because of their increased susceptibility to infections. Real effectiveness of vaccinations against SARS-CoV-2 and exposition to the virus in populations after organ transplantation is still being assessed. METHODS: We investigated 371 adult patients (82.7% men, 17.3% women), aged 54 ± 14 years, with a median time from transplantation of 1296 days (interquartile range, 473-400 days) after orthotopic heart transplantation consecutively admitted to the transplant center between February and September 2021. SARS-CoV-2 spike protein antibodies were assessed quantitatively by Elecsys Anti-SARS-CoV-2 S. Data according to past COVID-19 infection and vaccination were compared with the test results. Among the whole group, 59 patients were unvaccinated and had no past COVID-19 infection, 200 patients had a full course of vaccination (2 doses) with an mRNA vaccine, 1 patient had received a viral vector vaccine, 11 patients had had a single dose of an mRNA vaccine, and 99 patients had previously had a COVID-19 infection. Median time from vaccination to antibody assessment was 54 days (interquartile range, 30-76 days). AIM: The aim of this study was to determine exposure to the virus among patients after heart transplantation before vaccination and humoral response to the vaccination and assess the role of antispike antibodies in the prevention of infection. RESULTS: After vaccination, 22.3% had no antibodies (45 patients), 47.3% had titers between 0.8 U/mL [0.82 binding antibody units (BAU)/mL] and 250 U/mL (257.25 BAU/mL; 95 patients), and 30.2% had titers above 250 U/mL (257.25 BAU/mL; 61 patients). After a single dose of vaccine, 63% patients had no antibodies. In the group of unvaccinated patients, 3 patients had titers above 250 U/mL (257.25 BAU/mL; 5.1%) and 12 patients had titers up to 250 U/mL (257.25 BAU/mL; 20.3%). In patients after COVID-19 infection, only 2% did not show antispike antibodies, and in 61.4% the titers were above 250 U/mL (257.25 BAU/mL). In the group of patients infected after the full course of vaccination (4 patients after a single dose and 2 after 2 doses), none of the patients developed antibodies after vaccination. Up to the end of September 2021, none of the patients with antibodies against SARS-CoV-2 developed COVID-19. CONCLUSIONS: The presence of spike protein antibodies may be a relevant marker of effective vaccination. In patients after heart transplantation, exposure to SARS-CoV-2 is high.


Subject(s)
COVID-19 , Heart Transplantation , Viral Vaccines , Adult , Antibodies, Viral , COVID-19/epidemiology , COVID-19 Testing , Female , Heart Transplantation/adverse effects , Humans , Male , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Vaccination , Vaccines, Synthetic , mRNA Vaccines
11.
J Neuroimmunol ; 368: 577883, 2022 07 15.
Article in English | MEDLINE | ID: covidwho-1991160

ABSTRACT

INTRODUCTION: Large-scale vaccination is considered one of the most effective strategies to control the pandemic of COVID-19. Since its start, different complications have been described thought to be related to vaccination. Here, we present a rare case where encephalopathy, myocarditis, and thrombocytopenia developed simultaneously following the second dose of Pfizer-BioNTech mRNA vaccine (BNT162b2). CASE PRESENTATION: A 15-years-old female presented with fever, altered consciousness, and convulsions after taking the second shot of the vaccine. Clinical and laboratory workup was notable for the presence of thrombocytopenia and myocarditis. No alternative causes of encephalitis were found. The patient responded significantly to methylprednisolone suggesting underlying immune pathogenesis responsible for the clinical features. The diagnostic criteria for possible autoimmune encephalitis were also fulfilled. CONCLUSION: Although rare, the clinician should be aware of the possible adverse events following COVID-19 vaccination. Further research with large pooled data is needed to get more insight into its pathogenesis and causal relationship.


Subject(s)
Brain Diseases , COVID-19 , Encephalitis , Myocarditis , Thrombocytopenia , Adolescent , BNT162 Vaccine , COVID-19 Vaccines/adverse effects , Encephalitis/complications , Female , Humans , Methylprednisolone/therapeutic use , Myocarditis/diagnosis , Myocarditis/etiology , Thrombocytopenia/chemically induced , Vaccines, Synthetic , mRNA Vaccines
12.
Eur Radiol ; 32(9): 5921-5929, 2022 Sep.
Article in English | MEDLINE | ID: covidwho-1990616

ABSTRACT

OBJECTIVES: To evaluate if radiomics with machine learning can differentiate between F-18-fluorodeoxyglucose (FDG)-avid breast cancer metastatic lymphadenopathy and FDG-avid COVID-19 mRNA vaccine-related axillary lymphadenopathy. MATERIALS AND METHODS: We retrospectively analyzed FDG-positive, pathology-proven, metastatic axillary lymph nodes in 53 breast cancer patients who had PET/CT for follow-up or staging, and FDG-positive axillary lymph nodes in 46 patients who were vaccinated with the COVID-19 mRNA vaccine. Radiomics features (110 features classified into 7 groups) were extracted from all segmented lymph nodes. Analysis was performed on PET, CT, and combined PET/CT inputs. Lymph nodes were randomly assigned to a training (n = 132) and validation cohort (n = 33) by 5-fold cross-validation. K-nearest neighbors (KNN) and random forest (RF) machine learning models were used. Performance was evaluated using an area under the receiver-operator characteristic curve (AUC-ROC) score. RESULTS: Axillary lymph nodes from breast cancer patients (n = 85) and COVID-19-vaccinated individuals (n = 80) were analyzed. Analysis of first-order features showed statistically significant differences (p < 0.05) in all combined PET/CT features, most PET features, and half of the CT features. The KNN model showed the best performance score for combined PET/CT and PET input with 0.98 (± 0.03) and 0.88 (± 0.07) validation AUC, and 96% (± 4%) and 85% (± 9%) validation accuracy, respectively. The RF model showed the best result for CT input with 0.96 (± 0.04) validation AUC and 90% (± 6%) validation accuracy. CONCLUSION: Radiomics features can differentiate between FDG-avid breast cancer metastatic and FDG-avid COVID-19 vaccine-related axillary lymphadenopathy. Such a model may have a role in differentiating benign nodes from malignant ones. KEY POINTS: • Patients who were vaccinated with the COVID-19 mRNA vaccine have shown FDG-avid reactive axillary lymph nodes in PET-CT scans. • We evaluated if radiomics and machine learning can distinguish between FDG-avid metastatic axillary lymphadenopathy in breast cancer patients and FDG-avid reactive axillary lymph nodes. • Combined PET and CT radiomics data showed good test AUC (0.98) for distinguishing between metastatic axillary lymphadenopathy and post-COVID-19 vaccine-associated axillary lymphadenopathy. Therefore, the use of radiomics may have a role in differentiating between benign from malignant FDG-avid nodes.


Subject(s)
Breast Neoplasms , COVID-19 , Lymphadenopathy , Breast Neoplasms/pathology , COVID-19 Vaccines/adverse effects , Female , Fluorodeoxyglucose F18 , Humans , Lymph Nodes/diagnostic imaging , Lymph Nodes/pathology , Lymphadenopathy/diagnostic imaging , Lymphadenopathy/etiology , Lymphadenopathy/pathology , Lymphatic Metastasis/pathology , Pilot Projects , Positron Emission Tomography Computed Tomography , Retrospective Studies , Vaccination , Vaccines, Synthetic , mRNA Vaccines
13.
JAMA Netw Open ; 5(8): e2226236, 2022 Aug 01.
Article in English | MEDLINE | ID: covidwho-1990379

ABSTRACT

Importance: Kawasaki disease (KD) symptoms significantly overlap with multisystem inflammatory syndrome in children due to COVID-19. Patients with KD may be at risk for adverse outcomes from exposure to SARS-CoV-2 infection or vaccination. Objective: To describe the outcomes of patients with KD to SARS-CoV-2 infection or vaccination. Design, Setting, and Participants: This case series evaluated 2 cohorts using an existing KD database and reviewed individual electronic medical records for the period spanning January 1, 2020, through January 31, 2022, via electronic medical records that include Washington state immunization records. Vaccine cohort inclusion criteria consisted of being 21 years or younger at immunization and receiving 1 or more BNT162b2 (Pfizer-BioNTech) or messenger RNA (mRNA)-1273 (Moderna) vaccine doses. The COVID-19 cohort included patients 21 years or younger with positive polymerase chain reaction or nuclear capsid IgG findings for SARS-CoV-2. Participants included 826 patients from a preexisting KD database. One hundred fifty-three patients received at least 1 BNT162b2 or mRNA-1273 vaccine dose and were included in the mRNA vaccine cohort. Thirty-seven patients had positive test results for SARS-CoV-2 and were included in the COVID-19 cohort. Exposures: SARS-CoV-2 vaccination and/or infection. Main Outcomes and Measures: Adverse events after mRNA vaccination and/or COVID-19, including clinician visits, emergency department encounters, or hospitalizations. Results: Among the 153 patients included in the mRNA vaccination cohort (mean [SD] age, 13.0 [4.3] years; 94 male [61.4%]), the BNT162b2 vaccine was provided for 143 (93.5%), and the remaining 10 (6.5%) received mRNA-1273 or a combination of both. Among patients in the vaccine cohort, 129 (84.3%) were fully vaccinated or received a third-dose booster. No clinically severe adverse events occurred, and there were no reports of vaccine-related hospitalizations or outpatient visits. The COVID-19 cohort included 37 patients (mean [SD] age, 11.0 [5.5] years; 22 male [59.5%]). No patients required hospitalization due to COVID-19. The most common symptoms included low-grade fever, fatigue, cough, and myalgia with resolution within a few days. Two patients, aged 9 and 19 years, had extended cough and fatigue for 3 to 4 weeks. One patient developed COVID-19 within 6 weeks of receiving intravenous immunoglobulin for KD. Conclusions and Relevance: These findings suggest that the mRNA vaccines may be safe and COVID-19 may not be severe for patients with a history of KD.


Subject(s)
COVID-19 , Mucocutaneous Lymph Node Syndrome , Viral Vaccines , 2019-nCoV Vaccine mRNA-1273 , Adolescent , BNT162 Vaccine , COVID-19/complications , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Child , Cough/etiology , Fatigue/etiology , Humans , Male , RNA, Messenger , SARS-CoV-2 , Systemic Inflammatory Response Syndrome , Vaccination/adverse effects , Vaccines, Inactivated/adverse effects , Vaccines, Synthetic , Viral Vaccines/adverse effects , mRNA Vaccines
14.
Brain Nerve ; 74(8): 1025-1030, 2022 Aug.
Article in Japanese | MEDLINE | ID: covidwho-1988498

ABSTRACT

We report a 71-year-old woman who presented with paresthesia, progressive weakness, difficulty walking, diarrhea, and bladder dysfunction one week after she received the BNT162b2 COVID-19 vaccine. Her neurological signs and symptoms gradually worsened up to 27 days after onset, after which her weakness slowly improved without immunotherapy. Analysis of serial cerebrospinal fluid specimens showed gradually increasing protein levels. Results of a nerve conduction study suggested functional axonal disturbance. The clinical findings together with the monophasic clinical course were consistent with Guillain-Barré syndrome. Her previous history was negative for symptomatic infection. Serological and bacterial tests, including the presence of anti-glycolipid antibodies, were negative for prior infection. Few cases have been reported on the development of Guillain-Barré syndrome after the BNT162b2 vaccine. Our patient's syndrome was characterized by atypical proximal weakness of the dominant lower limb. (Received January 28, 2022; Accepted April 4, 2022; Published August 1, 2022).


Subject(s)
COVID-19 , Guillain-Barre Syndrome , Aged , BNT162 Vaccine , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Female , Guillain-Barre Syndrome/diagnosis , Guillain-Barre Syndrome/etiology , Humans , RNA, Messenger , Vaccines, Synthetic , mRNA Vaccines
15.
PLoS One ; 17(6): e0268780, 2022.
Article in English | MEDLINE | ID: covidwho-1987133

ABSTRACT

OBJECTIVES: Although mRNA-based vaccines against SARS-CoV-2 induce a robust immune response and prevent infections and hospitalizations, there are limited data on the antibody response in individuals with humoral immunodeficiency. The aim of this study was to evaluate the humoral immune response after two vaccine doses with BNT162b2 or mRNA-1273 in patients with humoral immunodeficiency disease. METHODS: This cross-sectional study assessed 39 individuals with hypogammaglobulinemia under immunoglobulin replacement therapy. IgG anti-SARS-CoV-2 spike protein antibodies (anti-S) were measured 4 weeks to 4 months after two doses of an mRNA vaccine against SARS-CoV-2. The proportion of patients, who developed a humoral immune response to the spike protein were evaluated and compared to 19 healthy controls. RESULTS: After vaccination with two vaccine doses, 26/39 patients (66.7%) with humoral immunodeficiency disease and all healthy controls developed anti-S. In subjects with baseline IgG <3 g/l, only 1/5 (20%) showed a humoral immune response. 10 out of 26 with CVID (38.5%) and 7/9 under immunosuppressive drugs (77.8%) developed no immune response (13 subjects with no response) compared to 0/19 in healthy controls. Subgroup analysis in patients without immunosuppressive drugs revealed lower anti-S in patients with moderate to severe humoral immunodeficiency disease: baseline IgG <3 g/l: 12.0 AU/ml (95%CI 12.0-125.0), baseline IgG 3-5 g/l: 99.9 AU/ml (95%CI 14.4-400.0), baseline IgG >5 g/l: 151.5 AU/ml (95%CI 109.0-400.0), healthy controls 250.0 AU/ml (95%CI 209.0-358.0), p = 0.007. CONCLUSION: In most patients with mild to moderate humoral immunodeficiency we found only slightly lower anti-S antibodies compared with healthy controls after two vaccine doses with BNT162b2 and mRNA-1273. However, in patients with a decreased baseline IgG below 3 g/l and/or under immunosuppressive drugs, we found severely impaired humoral immune responses.


Subject(s)
COVID-19 , Vaccines , Antibodies, Viral , BNT162 Vaccine , COVID-19/prevention & control , COVID-19 Vaccines , Cross-Sectional Studies , Humans , Immunity, Humoral , Immunoglobulin G , SARS-CoV-2 , Vaccination , Vaccines, Synthetic , mRNA Vaccines
16.
Lancet Respir Med ; 10(7): 689-699, 2022 07.
Article in English | MEDLINE | ID: covidwho-1984281

ABSTRACT

BACKGROUND: The duration of protection against the omicron (B.1.1.529) variant for current COVID-19 vaccines is not well characterised. Vaccine-specific estimates are especially needed. We aimed to evaluate the effectiveness and durability of two and three doses of the BNT162b2 (Pfizer-BioNTech) mRNA vaccine against hospital and emergency department admissions due to the delta (B.1.617.2) and omicron variants. METHODS: In this case-control study with a test-negative design, we analysed electronic health records of members of Kaiser Permanente Southern California (KPSC), a large integrated health system in California, USA, from Dec 1, 2021, to Feb 6, 2022. Vaccine effectiveness was calculated in KPSC patients aged 18 years and older admitted to hospital or an emergency department (without a subsequent hospital admission) with a diagnosis of acute respiratory infection and tested for SARS-CoV-2 via PCR. Adjusted vaccine effectiveness was estimated with odds ratios from adjusted logistic regression models. This study is registered with ClinicalTrials.gov (NCT04848584). FINDINGS: Analyses were done for 11 123 hospital or emergency department admissions. In adjusted analyses, effectiveness of two doses of the BNT162b2 vaccine against the omicron variant was 41% (95% CI 21-55) against hospital admission and 31% (16-43) against emergency department admission at 9 months or longer after the second dose. After three doses, effectiveness of BNT162b2 against hospital admission due to the omicron variant was 85% (95% CI 80-89) at less than 3 months but fell to 55% (28-71) at 3 months or longer, although confidence intervals were wide for the latter estimate. Against emergency department admission, the effectiveness of three doses of BNT162b2 against the omicron variant was 77% (72-81) at less than 3 months but fell to 53% (36-66) at 3 months or longer. Trends in waning against SARS-CoV-2 outcomes due to the delta variant were generally similar, but with higher effectiveness estimates at each timepoint than those seen for the omicron variant. INTERPRETATION: Three doses of BNT162b2 conferred high protection against hospital and emergency department admission due to both the delta and omicron variants in the first 3 months after vaccination. However, 3 months after receipt of a third dose, waning was apparent against SARS-CoV-2 outcomes due to the omicron variant, including hospital admission. Additional doses of current, adapted, or novel COVD-19 vaccines might be needed to maintain high levels of protection against subsequent waves of SARS-CoV-2 caused by the omicron variant or future variants with similar escape potential. FUNDING: Pfizer.


Subject(s)
COVID-19 , BNT162 Vaccine , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines , Case-Control Studies , Emergency Service, Hospital , Hospitals , Humans , SARS-CoV-2/genetics , Vaccines, Synthetic , mRNA Vaccines
17.
JAMA Netw Open ; 5(8): e2226335, 2022 Aug 01.
Article in English | MEDLINE | ID: covidwho-1981507

ABSTRACT

Importance: Antibody responses elicited by current messenger RNA (mRNA) COVID-19 vaccines decline rapidly and require repeated boosting. Objective: To evaluate the immunogenicity and durability of heterologous and homologous prime-boost regimens involving the adenovirus vector vaccine Ad26.COV2.S and the mRNA vaccine BNT162b2. Design, Setting, and Participants: In this cohort study at a single clinical site in Boston, Massachusetts, 68 individuals who were vaccinated at least 6 months previously with 2 immunizations of BNT162b2 were boosted with either Ad26.COV2.S or BNT162b2. Enrollment of participants occurred from August 12, 2021, to October 25, 2021, and this study involved 4 months of follow-up. Data analysis was performed from November 2021 to February 2022. Exposures: Participants who were previously vaccinated with BNT162b2 received a boost with either Ad26.COV2.S or BNT162b2. Main Outcomes and Measures: Humoral immune responses were assessed by neutralizing, binding, and functional antibody responses for 16 weeks following the boost. CD8+ and CD4+ T-cell responses were evaluated by intracellular cytokine staining assays. Results: Among 68 participants who were originally vaccinated with BNT162b2 and boosted with Ad26.COV2.S (41 participants; median [range] age, 36 [23-84] years) or BNT162b2 (27 participants; median [range] age, 35 [23-76] years), 56 participants (82%) were female, 7 (10%) were Asian, 4 (6%) were Black, 4 (6%) were Hispanic or Latino, 3 (4%) were more than 1 race, and 53 (78%) were White. Both vaccines were found to be associated with increased humoral and cellular immune responses, including against SARS-CoV-2 variants of concern. BNT162b2 boosting was associated with a rapid increase of Omicron neutralizing antibodies that peaked at a median (IQR) titer of 1018 (699-1646) at week 2 and declined by 6.9-fold to a median (IQR) titer of 148 (95-266) by week 16. Ad26.COV2.S boosting was associated with increased Omicron neutralizing antibodies titers that peaked at a median (IQR) of 859 (467-1838) week 4 and declined by 2.1-fold to a median (IQR) of 403 (208-1130) by week 16. Conclusions and Relevance: Heterologous Ad26.COV2.S boosting was associated with durable humoral and cellular immune responses in individuals who originally received the BNT162b2 vaccine. These data suggest potential benefits of heterologous prime-boost vaccine regimens for SARS-CoV-2.


Subject(s)
COVID-19 Vaccines , COVID-19 , Ad26COVS1 , Adult , Antibodies, Neutralizing , BNT162 Vaccine , COVID-19/prevention & control , Cohort Studies , Female , Humans , Male , SARS-CoV-2 , Vaccines, Synthetic , mRNA Vaccines
18.
Orv Hetil ; 163(27): 1055-1060, 2022 Jul 03.
Article in English | MEDLINE | ID: covidwho-1978877

ABSTRACT

Parsonage-Turner syndrome (PTS; neuralgic amyotrophy) is a generally unilateral neuritis with sudden onset, severe shoulder or upper arm pain. Although the intense pain is usually self-limiting, two-thirds of patients experience progressive motor weakness, narrowed range of motion, reflex changes, dysesthesias and chronic neuropathic pain in the shoulder girdle musculature and proximal upper limb muscles. The aetiology is unclear, in addition to some idiopathic cases the most common triggers of PTS are surgery, trauma, infection or vaccination. It is reported after SARS-CoV-2 infection, and unilateral PTS has been described in some cases following different types of COVID-19 vaccines. We are currently presenting the case of a middle-aged woman who developed partial neuralgic amyotrophy on the right shoulder one month after receiving the second dose of the BNT162b2 COVID-19 mRNA vaccine (Pfizer-BioNTech), and seven months later the symptoms appeared in the contralateral upper limb. The diagnosis of PTS was also confirmed by magnetic resonance and electrodiagnostic examination. The PTS is not an uncommon condition, but in the absence of knowledge it is rarely thought of. The purpose of this report is to draw attention to the possibility of PTS in shoulder or upper arm pain following both SARS-CoV-2 infection and COVID-19 vaccination, as early diagnosis and adequate therapy may help to shorten the course of the disease. Orv Hetil. 2022; 163(27): 1055-1060.


Subject(s)
Brachial Plexus Neuritis , COVID-19 , BNT162 Vaccine , Brachial Plexus Neuritis/diagnosis , Brachial Plexus Neuritis/drug therapy , Brachial Plexus Neuritis/etiology , COVID-19/complications , COVID-19 Vaccines , Female , Humans , Middle Aged , Pain , SARS-CoV-2 , Vaccines, Synthetic , mRNA Vaccines
19.
Virol J ; 19(1): 132, 2022 Aug 08.
Article in English | MEDLINE | ID: covidwho-1978780

ABSTRACT

BACKGROUND: Immunocompromised (IC) patients are at higher risk of more severe COVID-19 infections than the general population. Special considerations should be dedicated to such patients. We aimed to investigate the efficacy of COVID-19 vaccines based on the vaccine type and etiology as well as the necessity of booster dose in this high-risk population. MATERIALS AND METHODS: We searched PubMed, Web of Science, and Scopus databases for observational studies published between June 1st, 2020, and September 1st, 2021, which investigated the seroconversion after COVID-19 vaccine administration in adult patients with IC conditions. For investigation of sources of heterogeneity, subgroup analysis and sensitivity analysis were conducted. Statistical analysis was performed using R software. RESULTS: According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, we included 81 articles in the meta-analysis. The overall crude prevalence of seroconversion after the first (n: 7460), second (n: 13,181), and third (n: 909, all population were transplant patients with mRNA vaccine administration) dose administration was 26.17% (95% CI 19.01%, 33.99%, I2 = 97.1%), 57.11% (95% CI: 49.22%, 64.83%, I2 = 98.4%), and 48.65% (95% CI: 34.63%, 62.79%, I2 = 94.4%). Despite the relatively same immunogenicity of mRNA and vector-based vaccines after the first dose, the mRNA vaccines induced higher immunity after the second dose. Regarding the etiologic factor, transplant patients were less likely to develop immunity after both first and second dose rather than patients with malignancy (17.0% vs 37.0% after first dose, P = 0.02; 38.3% vs 72.1% after second dose, P < 0.001) or autoimmune disease (17.0% vs 36.4%, P = 0.04; 38.3% vs 80.2%, P < 0.001). To evaluate the efficacy of the third dose, we observed an increasing trend in transplant patients after the first (17.0%), second (38.3%), and third (48.6%) dose. CONCLUSION: The rising pattern of seroconversion after boosting tends to be promising. In this case, more attention should be devoted to transplant patients who possess the lowest response rate.


Subject(s)
COVID-19 Vaccines , COVID-19 , Adult , Antibodies, Viral , COVID-19/prevention & control , Humans , SARS-CoV-2 , Seroconversion , Vaccination , Vaccines, Synthetic , mRNA Vaccines
20.
Nat Commun ; 13(1): 4631, 2022 Aug 08.
Article in English | MEDLINE | ID: covidwho-1977998

ABSTRACT

Immunization with two mRNA vaccine doses elicits robust spike-specific CD8+ T cell responses, but reports of waning immunity after COVID-19 vaccination prompt the introduction of booster vaccination campaigns. However, the effect of mRNA booster vaccination on the spike-specific CD8+ T cell response remains unclear. Here we show that spike-specific CD8+ T cells are activated and expanded in all analyzed individuals receiving the 3rd and 4th mRNA vaccine shots. This CD8+ T cell boost response is followed by a contraction phase and lasts only for about 30-60 days. The spike-specific CD8+ T memory stem cell pool is not affected by the 3rd vaccination. Both 4th vaccination and breakthrough infections with Delta and Omicron rapidly reactivate CD8+ T memory cells. In contrast, neutralizing antibody responses display little boost effect towards Omicron. Thus, COVID-19 mRNA booster vaccination elicits a transient T effector cell response while long-term spike-specific CD8+ T cell immunity is conserved to mount robust memory recall targeting emerging variants of concern.


Subject(s)
CD8-Positive T-Lymphocytes , COVID-19 , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines , Humans , RNA, Messenger , Vaccines, Synthetic , mRNA Vaccines
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