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1.
Front Immunol ; 13: 814365, 2022.
Article in English | MEDLINE | ID: covidwho-1952314

ABSTRACT

To effectively control and prevent the pandemic of coronavirus disease 2019 (COVID-19), suitable vaccines have been researched and developed rapidly. Currently, 31 COVID-19 vaccines have been approved for emergency use or authorized for conditional marketing, with more than 9.3 billion doses of vaccines being administered globally. However, the continuous emergence of variants with high transmissibility and an ability to escape the immune responses elicited by vaccines poses severe challenges to the effectiveness of approved vaccines. Hundreds of new COVID-19 vaccines based on different technology platforms are in need of a quick evaluation for their efficiencies. Selection and enrollment of a suitable sample of population for conducting these clinical trials is often challenging because the pandemic so widespread and also due to large scale vaccination. To overcome these hurdles, methods of evaluation of vaccine efficiency based on establishment of surrogate endpoints could expedite the further research and development of vaccines. In this review, we have summarized the studies on neutralizing antibody responses and effectiveness of the various COVID-19 vaccines. Using this data we have analyzed the feasibility of establishing surrogate endpoints for evaluating the efficacy of vaccines based on neutralizing antibody titers. The considerations discussed here open up new avenues for devising novel approaches and strategies for the research and develop as well as application of COVID-19 vaccines.


Subject(s)
COVID-19 Vaccines , COVID-19 , Antibodies, Neutralizing , Antibodies, Viral , Biomarkers , COVID-19/prevention & control , Feasibility Studies , Humans , SARS-CoV-2
2.
Infect Drug Resist ; 15: 2723-2728, 2022.
Article in English | MEDLINE | ID: covidwho-1951766

ABSTRACT

Previous studies have demonstrated that the appropriate production of serum anti-severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) neutralizing antibody (nAb) plays a critical role in the recovery from coronavirus disease 2019 (COVID-19); however, the role of nAb production in the recovery from a flare-up of chronic immune thrombocytopenia (ITP) has been unknown. We here report the first retrospectively investigated case of serum anti-SARS-Cov-2 nAb production during chronic ITP flare-up triggered by COVID-19. A 79-year-old woman with a history of corticosteroid-refractory ITP visited our hospital complaining of fever, cough, and sore throat for 4 days. Although chronic ITP was controlled by 12.5 mg of eltrombopag (EPAG) every other day, laboratory tests showed a decreased peripheral blood platelet count of 15.0 × 109/L, which indicated worsening thrombocytopenia. Meanwhile, PCR testing of a nasopharyngeal swab revealed that the patient was positive for SARS-Cov-2, and a computed tomography scan revealed bilateral pneumonia. On the basis of the flare-up of chronic ITP associated with COVID-19 pneumonia which was determined as a moderately severe status according to the WHO clinical progression scale, intravenous immunoglobulin therapy for 5 days (days 0-4) and antiviral therapy were added on top of EPAG, which only resulted in a transient increase in the platelet count for several days. After decreasing to 8.0 × 109/L on day 13, the platelet count increased from day 16, coinciding with a positive detection for serum nAb against SARS-Cov-2. Although the increased dose up to 50 mg/day of EPAG was challenged during the clinical course, rapid dose reduction did not cause another relapse. In addition, no thrombotic or bleeding event was seen. These collectively suggest the vital role of the production of anti-SARS-Cov-2 nAb and improvement of clinical symptoms for recovery from a flare-up of chronic ITP in our case.

3.
Biosens Bioelectron ; 213: 114449, 2022 Oct 01.
Article in English | MEDLINE | ID: covidwho-1944326

ABSTRACT

Currently, vaccination is the most effective medical measure to improve group immunity and prevent the rapid spread of COVID-19. Since the individual difference of vaccine effectiveness is inevitable, it is necessary to evaluate the vaccine effectiveness of every vaccinated person to ensure the appearance of herd immunity. Here, we developed an artificial intelligent (AI)-assisted colorimetric polydopamine nanoparticle (PDA)-based lateral flow immunoassay (LFIA) platform for the sensitive and accurate quantification of neutralizing antibodies produced from vaccinations. The platform integrates PDA-based LFIA and a smartphone-based reader to test the neutralizing antibodies in serum, where an AI algorithm is also developed to accurately and quantitatively analyze the results. The developed platform achieved a quantitative detection with 160 ng/mL of detection limit and 625-10000 ng/mL of detection range. Moreover, it also successfully detected totally 50 clinical serum samples, revealing a great consistency with the commercial ELISA kit. Comparing with commercial gold nanoparticle-based LFIA, our PDA-based LFIA platform showed more accurate quantification ability for the clinical serum. Therefore, we envision that the AI-assisted PDA-based LFIA platform with sensitive and accurate quantification ability is of great significance for large-scale evaluation of vaccine effectiveness and other point-of-care immunoassays.


Subject(s)
Biosensing Techniques , COVID-19 , Metal Nanoparticles , Antibodies, Neutralizing , Artificial Intelligence , COVID-19/diagnosis , Colorimetry , Gold , Humans , Immunoassay/methods , Limit of Detection
4.
Int J Infect Dis ; 2022 Jul 18.
Article in English | MEDLINE | ID: covidwho-1936537

ABSTRACT

OBJECTIVES: The SARS-CoV-2 Omicron variant presents numerous mutations potentially able to evade neutralizing antibodies (NAbs) elicited by COVID-19 vaccines. Therefore, this study aimed to provide evidence on a heterologous booster strategy to overcome the waning immunity against Omicron variants. METHODS: Participants who completed Oxford/AstraZeneca (hereafter AZD1222) for 5-7 months were enrolled. The reactogenicity and persistence of immunogenicity in both humoral and cellular response after a homologous or heterologous booster with the AZD1222 and mRNA vaccines (BNT162B2, full or half-dose mRNA-1273) administered six months after primary vaccination were determined. RESULTS: A total of 229 individuals enrolled, a waning of immunity was observed 5-7 months after the AZD1222-primed. Total RBD immunoglobulin (Ig) levels, anti-RBD IgG and focus reduction neutralization test against Omicron BA.1 and BA.2 and T-cell response peaked at 14-28 days after booster vaccination. Both the full and half dose of mRNA-1273 induced the highest response, followed by BNT162b2 and AZD1222. At 90 days, the persistence of immunogenicity was observed among all mRNA-boosted individuals. Adverse events were acceptable for all vaccines. CONCLUSIONS: A heterologous mRNA booster provided a significantly superior boost of binding and NAbs levels against the Omicron variant compared to a homologous booster in individuals with AZD1222-primed vaccinations.

5.
Vaccines (Basel) ; 10(7)2022 Jul 15.
Article in English | MEDLINE | ID: covidwho-1939054

ABSTRACT

BACKGROUND: In December 2021, Omicron replaced Delta as the dominant coronavirus disease 2019 (COVID-19) variant in Thailand. Both variants embody diverse epidemiological trends and immunogenicity. We investigated whether Delta and Omicron patients' biological and clinical characteristics and immunogenicity differed post-COVID-19 infection. METHODS: This retrospective cohort study investigated the clinical outcomes and laboratory data of 5181 patients with mild-to-moderate COVID-19 (Delta, 2704; Omicron, 2477) under home isolation. We evaluated anti-receptor-binding domain immunoglobulin G (anti-RBD IgG) and surrogate viral neutralizing (sVNT) activity in 495 individuals post-COVID-19 infection during the Delta pandemic. RESULTS: Approximately 84% of all patients received favipiravir. The median cycle threshold (Ct) values were lower for Omicron patients than Delta patients (19 vs. 21; p < 0.001), regardless of vaccination status. Upper respiratory tract symptoms were more frequent with Omicron patients than Delta patients. There were no significant associations between Ct and Omicron symptoms (95% confidence interval 0.98-1.02). A two-dose vaccine regimen reduced hospital readmission by 10% to 30% and death by under 1%. Anti-RBD IgG and sVNT against Delta were higher among older individuals post-COVID-19 infection. Older individuals expressed anti-RBD IgG and sVNT for a more extended period after two-dose vaccination than other age groups. CONCLUSIONS: After a full vaccination course, breakthrough mild-to-moderate Delta and Omicron infections have limited immunogenicity. Prior infections exert reduced protection against later reinfection or infection from novel variants. However, this protection may be sufficient to prevent hospitalization and death, particularly in countries where vaccine supplies are limited.

6.
Viruses ; 14(7)2022 07 18.
Article in English | MEDLINE | ID: covidwho-1939023

ABSTRACT

We aimed to review the existing literature on the different types of neutralization assays and international standards for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We comprehensively summarized the serological assays for detecting neutralizing antibodies against SARS-CoV-2 and demonstrated the importance of an international standard for calibrating the measurement of neutralizing antibodies. Following the coronavirus disease outbreak in December 2019, there was an urgent demand to detect neutralizing antibodies in patients or vaccinated people to monitor disease outcomes and determine vaccine efficacy. Therefore, many approaches were developed to detect neutralizing antibodies against SARS-CoV-2, such as microneutralization assay, SARS-CoV-2 pseudotype virus assay, enzyme-linked immunosorbent assay (ELISA), and rapid lateral flow assay. Given the many types of serological assays for quantifying the neutralizing antibody titer, the comparison of different assay results is a challenge. In 2020, the World Health Organization proposed the first international standard as a common unit to define neutralizing antibody titer and antibody responses against SARS-CoV-2. These standards are useful for comparing the results of different assays and laboratories.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/diagnosis , Enzyme-Linked Immunosorbent Assay , Humans , Neutralization Tests/methods , Spike Glycoprotein, Coronavirus
7.
Expert Rev Vaccines ; : 1-9, 2022 Jul 29.
Article in English | MEDLINE | ID: covidwho-1937581

ABSTRACT

BACKGROUND: As of 2022, inactivated SARS-CoV-2 vaccines had been used in more than 91 countries. However, limited real world information was available on the immune responses of the inactivated SARS-CoV-2 vaccine. METHODS: We used SARS-CoV-2 pseudovirues to determine the neutralizing antibodies (NAbs) to wild type and several global variants and utilized enzyme-linked immunosorbent assay to investigate IFN-γ-secreting T-cell responses to SARS-CoV-2 among 240 vaccinated individuals after two doses of inactivated vaccine in China. RESULTS: A majority of the vaccinated (>90%) developed robust NAbs and T-cell responses to SARS-CoV-2 in the first two months after the second dose. After six months, only 37.0% and 44.0% of vaccinees had NAbs and T-cell immunity to SARS-CoV-2, respectively. Immune serum retained most of its neutralizing potency against the Alpha and Iota variants, but lost significant neutralizing potency against the Beta, Kappa, Delta, and Omicron variants. Only 40% of vaccine-sera retained low-level neutralization activities to Omicron, with a 14.7-fold decrease compared to the wild type. CONCLUSION: The inactivated SARS-CoV-2 vaccine stimulated robust NAbs and T-cell immune responses in the first two months after the second dose but the immune effect dropped rapidly, highlighing that a third dose or additional booster immunizations may be required to boost immunity against SARS-CoV-2.

8.
Structure ; 2022 Jul 12.
Article in English | MEDLINE | ID: covidwho-1937225

ABSTRACT

Immunization with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike elicits diverse antibodies, but it is unclear if any of the antibodies can neutralize broadly against other beta-coronaviruses. Here, we report antibody WS6 from a mouse immunized with mRNA encoding the SARS-CoV-2 spike. WS6 bound diverse beta-coronavirus spikes and neutralized SARS-CoV-2 variants, SARS-CoV, and related sarbecoviruses. Epitope mapping revealed WS6 to target a region in the S2 subunit, which was conserved among SARS-CoV-2, Middle East respiratory syndrome (MERS)-CoV, and hCoV-OC43. The crystal structure at 2 Å resolution of WS6 revealed recognition to center on a conserved S2 helix, which was occluded in both pre- and post-fusion spike conformations. Structural and neutralization analyses indicated WS6 to neutralize by inhibiting fusion and post-viral attachment. Comparison of WS6 with other recently identified antibodies that broadly neutralize beta-coronaviruses indicated a stem-helical supersite-centered on hydrophobic residues Phe1148, Leu1152, Tyr1155, and Phe1156-to be a promising target for vaccine design.

9.
Chinese Journal of Microbiology and Immunology (China) ; 42(1):1-10, 2022.
Article in Chinese | EMBASE | ID: covidwho-1928716

ABSTRACT

The COVID-19 epidemic that occurred at the end of 2019 spreads rapidly to all parts of the world, putting the global public health system to a severe test. With the continuation of the epidemic, SARS-CoV-2 variants are constantly emerging. In particular, the mutation of the spike protein can cause changes in the infectivity and antigenicity of the virus, resulting in an increase in the infectivity and a decline in the protective efficacy of existing vaccines, and even the replacement of epidemic strains. This is also one of the reasons why the epidemic has not been effectively controlled so far. Nowadays, the main circulating variants have changed their characteristics to a certain extent, and the neutralization sensitivity of some variants to neutralizing monoclonal antibodies, immune sera and convalescent sera has decreased to a certain extent compared with the original strains. The emergence of variants is not only related to the characteristics of the virus itself, but also to the changes of transmission host and the chronic infection in people with deficient immunity. The emerging variants should be closely monitored, and their functional characteristics should be systematically studied so as to provide data for vaccine research and development and the designation of immunization strategies.

10.
Chinese Journal of Microbiology and Immunology (China) ; 42(3):161-170, 2022.
Article in Chinese | EMBASE | ID: covidwho-1928715

ABSTRACT

Objective To investigate the immune characteristics of SARS-CoV-2 membrane (M) protein, especially the possibility of inducing antibody-dependent enhancement effect (ADE) .Methods Full-length SARS-CoV-2 M protein was prepared by prokaryotic expression system and purified.BALB/ c mice were immunized subcutaneously three times (on day 1, day 14 and day 21) by purified M protein.Serum samples were collected before immunization and after each immunization.The specificity of immune sera against M protein was identified by Western blot, and the antibody titers were detected by ELISA and neutralization test.In the presence of anti-M protein serum, the proliferation of SARS-CoV-2 in dendritic cells, nature killer cells, T and B cells was detected in vitro.Results The immune sera from BALB/ c mice immunized with purified full-length M protein of SARS-CoV-2 specifically recognized viral M protein.The titer of anti-whole virus antibody in immune sera was about 1 ∶ 400, but the antibody could not neutralize live virus.Moreover, the antibody could not help the virus to infect and proliferate in the various types of immune cells with Fc receptor (FcR).Conclusions Non-neutralizing antibody induced by M protein could not cause ADE through FcR pathway.

11.
American Journal of Respiratory and Critical Care Medicine ; 205(1), 2022.
Article in English | EMBASE | ID: covidwho-1927874

ABSTRACT

RATIONALE: Some biomarkers of host response to viral infection are associated with COVID-19 outcomes, but these biomarkers do not directly measure viral burden. The association between plasma viral antigen levels and clinical outcomes has not been previously studied. Our aim was to investigate the relationship between plasma SARS-CoV-2 viral antigen concentration and proximal clinical deterioration in hospitalized patients. METHODS: SARS-CoV-2 nucleocapsid antigen concentrations were measured using a validated microbead immunoassay (Quanterix, NIH/NIAID laboratory) in plasma collected at enrollment from 256 subjects in a prospective observational cohort of hospitalized patients with COVID-19 from 3 hospitals, admitted between March 2020 and August 2021. Relationships between viral antigen concentration and clinical status at 1 week as measured by the World Health Organization (WHO) ordinal scale as well as ICU admission were assessed. Models were adjusted for age and sex, baseline comorbidities including immunosuppression, endogenous neutralizing antibodies, baseline COVID-19 severity, smoking status, remdesivir therapy, steroid therapy, and vaccine status. Missing covariate data were imputed using multiple imputation by chained equations. RESULTS: The median viral antigen concentration for the 35 subjects who deteriorated by 1 week was 4507 (IQR 1225-9665) pg/mL compared to 494 (IQR 18-3882) pg/mL in the 212 subjects who did not (p = 0.0004 Figure a). Using ordinal regression, each doubling in viral antigen concentration was significantly associated with a worse WHO ordinal scale at 1 week (unadjusted OR 1.07, 95% CI 1.02-1.13;adjusted OR 1.10, 95% CI 1.02-1.18). Among 168 patients not in the ICU at baseline, the median viral antigen concentration for the 40 patients who progressed to the ICU was 4697 (IQR 482- 10410) pg/mL vs. 459 (IQR 15-3062) pg/mL in the 128 patients who did not progress to require ICU care (p = 0.0001 Figure b). Using logistic regression, each doubling in viral antigen concentration was significantly associated with ICU admission (unadjusted OR 1.18, 95% CI 1.06-1.32, adjusted OR 1.40, 95% CI 1.11-1.76). CONCLUSIONS: Higher plasma viral antigen concentration at hospital admission is independently associated with a significantly worse clinical status at 1 week and a higher odds of ICU admission among hospitalized patients with COVID-19. This novel finding indicates that plasma viral antigen concentration may identify hospitalized COVID-19 patients at highest risk of short-term clinical deterioration in both clinical practice and research. Results of plasma antigen tests are available within 2-3 hours and could be integrated for identifying hospitalized COVID-19 patients who might benefit from early intervention.

12.
American Journal of Reproductive Immunology ; 87(SUPPL 1):91, 2022.
Article in English | EMBASE | ID: covidwho-1927549

ABSTRACT

Primary versus recurrent herpes simplex virus 1 or 2 (HSV-1 or HSV- 2) infection during pregnancy carries a higher risk of neonatal herpes suggesting that placental transfer of antibodies protects against transmission and infection. Murine and clinical studies demonstrate that antibody-dependent cellular cytotoxicity (ADCC) provides greater protection than neutralizing antibodies (nAbs) against disseminated neonatal disease. To quantify the relative transfer of HSV-specific Abs with different functions and targets and whether SARS-CoV-2 coinfection modified transfer, we conducted a prospective cohort study of mother-infant dyads prior to and during COVID-19. Total and HSV lysate, glycoprotein D (gD) and glycoprotein B (gB)- specific IgG, IgG1 and IgG3, nAbs, and ADCC were quantified in paired 3rd trimester maternal and cord blood. Transfer ratios (TR) were defined as cord: maternal Ab levels. IgG1 and IgG3 subclass and gD or gB-specific Abs were isolated by column purification and glycan profiles were assessed using mass spectrometry. The pre-COVID study population included 21 term and 15 preterm dyads who were HSV-1 (± HSV-2) seropositive (+) enrolled between 2018-2019 and the peri- COVID cohort included 25 HSV-1 (±HSV-2)+term dyadswhosemothers were also SARS-CoV-2 PCR and COVID Ab+ at delivery;14 were asymptomatic and 11 had mild-moderate COVID disease. None of the mothers had active genital HSV lesions during delivery. HSV-specific IgG, IgG1, and IgG3 TR were higher in term compared to preterm pre-COVID dyads (all p< 0.05). Similarly, the neutralizing Ab TR was 2.4[1.5, 4.0] in term vs 0.8[0.6, 1] in preterm (median [95%CI], p< 0.0001) but the ADCC TR was < 1.0 for both groups. To determine if the low ADCC TR reflected antigenic target, subclass, and/or glycans, we enriched for anti-gD and anti-gB specific and IgG1 and IgG3 Abs. These envelope glycoproteins are primary targets of neutralizing and ADCC responses, respectively. The anti-gD Abs were exclusively IgG1 and had only neutralizing activity. In contrast, anti-gB Abs were both IgG1 and IgG3;the IgG1 gB Abs had both neutralizing and ADCC activity whereas the IgG3 were only neutralizing. The anti-gD Abs were enriched for glycans associated with an affinity for FcRn, whereas anti-gB Abs expressed glycans associated with both FcRn and FcγRIIIa (receptor-associated with ADCC activity) binding. There was no significant difference in HSV-specific IgG TR in pre-COVID vs COVID dyads (0.42) but the nAb TR was lower (p = 0.018) and ADCC TR higher (p<0.001) in COVID compared to pre-COVID patients. Studies are in progress to assess whether this reflects increased placental colocalization of FcRn and FcgRIIIA, which would favor the transfer of ADCCAbs or modified Fc glycans. ADCC Abs transfer relatively inefficiently compared to nAbs, particularly in preterm infants and this may contribute to an increased risk of HSV disease. ADCC Ab transfer increased with SARS-CoV-2 coinfection, which may reflect differences in glycans and/or alterations in the placental architecture. Defining the determinants of ADCC transfer has implications for future vaccine and monoclonal Ab strategies to prevent/treat neonatal herpes. We speculate that increasing the transfer of ADCC may be a key element in providing immune protection.

13.
Med (N Y) ; 3(6): 406-421.e4, 2022 06 10.
Article in English | MEDLINE | ID: covidwho-1926779

ABSTRACT

BACKGROUND: The Omicron variant of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) was identified in Japan in November 2021. This variant contains up to 36 mutations in the spike protein, the target of neutralizing antibodies, and can escape vaccine-induced immunity. A booster vaccination campaign began with healthcare workers and high-risk groups. The safety and immunogenicity of the three-dose vaccination against Omicron remain unknown. METHODS: A total of 272 healthcare workers were initially evaluated for long-term vaccine safety and immunogenicity. We further established a vaccinee panel to evaluate the safety and immunogenicity against variants of concern (VOCs), including the Omicron variants, using a live virus microneutralization assay. FINDINGS: Two-dose vaccination induced robust anti-spike antibodies and neutralization titers (NTs) against the ancestral strain WK-521, whereas NTs against VOCs were significantly lower. Within 93-247 days of the second vaccine dose, NTs against Omicron were completely abolished in up to 80% of individuals in the vaccinee panel. Booster dose induced a robust increase in anti-spike antibodies and NTs against the WK-521, Delta, and Omicron variants. There were no significant differences in the neutralization ability of sera from boosted individuals among the Omicron subvariants BA.1, BA.1.1, and BA.2. Boosting increased the breadth of humoral immunity and cross-reactivity with Omicron without changes in cytokine signatures and adverse event rate. CONCLUSIONS: The third vaccination dose is safe and increases neutralization against Omicron variants. FUNDING: This study was supported by grants from AMED (grants JP21fk0108104 and JP21mk0102146).


Subject(s)
Antibodies, Viral , BNT162 Vaccine , COVID-19 , Immunization, Secondary , Immunogenicity, Vaccine , Antibodies, Neutralizing , BNT162 Vaccine/immunology , COVID-19/prevention & control , Cross Reactions , Humans , Immunity, Humoral , Neutralization Tests , RNA, Messenger , SARS-CoV-2/genetics
14.
Vaccines (Basel) ; 10(7)2022 Jul 08.
Article in English | MEDLINE | ID: covidwho-1928700

ABSTRACT

Despite the BNT162b2 vaccination coverage, rapid transmission of Omicron SARS-CoV-2 has occurred, which is suspected to be due to the immune escape of the variant or waning vaccine efficacy of multiple BNT162b2 vaccination doses. Our study aims to compare immunogenicity against Omicron prior to and post a booster dose of BNT162b2 in healthy adolescents, and to evaluate their attitudes toward booster dose vaccination. A cross sectional study was conducted among healthy adolescents aged 12-17 who received two doses of BNT162b2 more than 5 months ago. Participants and their guardians performed self-reported questionnaires regarding reasons for receiving the booster. A 30 ug booster dose of BNT162b2 was offered. Immunogenicity was evaluated by a surrogate virus neutralization test (sVNT) against the Omicron variant, and anti-spike-receptor-binding-domain IgG (anti-S-RBD IgG) taken pre-booster and 14-days post-booster. From March to April 2022, 120 healthy Thai adolescents with a median age of 15 years (IQR 14-16) were enrolled. sVNT against Omicron pre- and post-booster had 11.9 (95%CI 0-23.9) and 94.3 (90.6-97.4) % inhibition. Geometric means (GMs) of anti-S-RBD IgG increased from 837 (728, 953) to 3041 (2893, 3229) BAU/mL. Major reasons to receive the booster vaccination were perceived as vaccine efficacy, reduced risk of spreading infection to family, and safe resumption of social activities. A booster dose of BNT162b2 elicits high immunogenicity against the Omicron variant. Motivation for receiving booster doses is to reduce risk of infection.

15.
Farmaceutski Glasnik ; 78(1-2):29-44, 2022.
Article in Croatian | EMBASE | ID: covidwho-1925483

ABSTRACT

The SARS-CoV-2 virus is the cause of COVID-19 disease. The SARS-CoV-2 virus binds to ACE-2 receptors in the human lung via spike protein and causes COVID-19 disease. SARS-CoV-2 virus infection most often leads to the development of severe respiratory conditions, sore throat, and dry cough. By administering the vaccine, the human immune system recognizes the viral antigen, thereby activating immune system cells that produce neutralizing antibodies to remove the viral antigen. To combat the COVID-19 disease pandemic vaccines have been developed. Most commonly used vaccines in Europe are mRNA (messenger ribonucleic acid) vaccines and adenoviral vaccines. In this paper, suspected adverse reactions to the COVID-19 vaccine were analyzed according to patient age, sex, the severity of reporting, severity criteria, type of notifier, reported reaction, and adverse reactions according to the MedDRA classification of organ systems. Analyzed reports of suspected adverse effects were evaluated in the period from 27.12.2020. to 1.7.2021. A total of 2932 reports of suspected adverse reactions to the COVID-19 vaccine were analyzed, of which 730 were considered serious (24.9%). Out of 730 seriously evaluated reports, the largest number of reports refers to the development of other medically significant conditions, 583 of them (70.3%). The largest number of reports relates to the vaccine Comirnaty, 1610 of them (54.9%). This is followed by reports of suspected adverse reactions to Vaxzevria with 1098 reports (27.4%) and Spikevax with 206 reports (7.0%). The lowest number of suspected adverse reactions relates to Vaccine Janssen's COVID-19 vaccine (15;0.5%), while for three suspected adverse reactions the vaccine is unknown (0.1%). 34 cases of suspected adverse reactions, which amounts to only 4.1% of the total number of serious reports, or 1.15% of the total number of all received reports. The most commonly reported reactions to COVID-19 vaccines were fever, headache, and chills.

16.
Neurology ; 98(18 SUPPL), 2022.
Article in English | EMBASE | ID: covidwho-1925472

ABSTRACT

Objective: To examine the temporal trends of humoral and cell-mediated immune responses to SARS-CoV-2 mRNA vaccines among multiple sclerosis (MS) patients on different immunomodulatory therapies. Background: The impact of various MS medications on the immune responses to SARS-CoV-2 vaccine is of acute interest to patients and clinicians. Design/Methods: 22 MS patients treated with ocrelizumab (OCR, n=9), natalizumab (NTZ, n=8), fumarates (FUM, n=5;diroximel fumarate, 3 and dimethyl fumarate, 2) received BNT162b2 (Pfizer, n=15) or mRNA-1273 (Moderna, n=7) vaccines. Blood samples were collected before and after each of the two vaccine doses, and 2 months after second vaccine dose. AntiSARS-CoV-2 spike protein titers were measured using quantitative assay (Labcorp). Antibody neutralization was measured with a lentivirus-based pseudovirus particle expressing the D614 spike protein (Labcorp-Monogram Biosciences). T-cell reactivity was determined by measuring interferon-gamma and interleukin-2 in response to stimulation with SARS-CoV-2 peptides. Results: All patients in NTZ and FUM cohorts, but only 22% (2/9) of OCR cohort developed anti-spike and neutralizing antibodies. The highest titers were measured after the second vaccine dose, without significant difference between the NTZ and FUM cohorts in anti-spike IgG (69.7+/-55.1 vs 56.0+/-36.7 arbitrary units/ml) or neutralizing ID50 (1513+/-1317 vs 942+/ -566). Two months after the second vaccine, the antibody titers and neutralizing ID50 decreased by 72% and 79% in NTZ cohort, respectively, and by 45% and 49% in FUM cohort. T-cell reactivity was observed in all cohorts as early as 7 days after the first vaccine, and further increased following the second vaccine. Conclusions: Patients on NTZ and FUM mounted robust antibody responses to SARS-CoV-2 mRNA vaccines, in contrast to OCR-treated patients. T-cell responses were comparable among all three treatment cohorts. Two months after the second vaccine, the serological responses decreased by 45-79%. These findings may inform the optimal timing of additional vaccine doses for MS patients.

17.
Neurology ; 98(18 SUPPL), 2022.
Article in English | EMBASE | ID: covidwho-1925465

ABSTRACT

Objective: We are aiming to understand the longitudinal cellular and humoral immune responses to SARS-CoV-2 mRNA vaccines depending on the timing of vaccination and SPMS treatment. Background: SARS-CoV-2 mRNA vaccines are a key factor fighting the COVID-19 pandemic across the globe. However, data are lacking on efficacy of vaccination in patients with secondary progressive multiple sclerosis (SPMS) on disease-modifying therapies (DMTs) both over time and after a booster vaccination. Design/Methods: AMA-VACC is an open-label, three-cohort, prospective study in Germany with 41 multiple sclerosis patients currently treated with siponimod, first-line DMT or without treatment in clinical routine. Cohort 1 receives SARS-CoV-2 mRNA vaccination while continuing their current siponimod treatment, cohort 2 interrupts siponimod treatment for the purpose of a full vaccination cycle and cohort 3 receives vaccination during continuous treatment with first-line DMTs (glatirameracetate, interferons, teriflunomide) or no current treatment in clinical routine. Primary endpoint is the rate of patients achieving seroconversion assessed by detection of serum neutralizing antibodies one week after SARS-CoV-2 mRNA vaccination. Furthermore, development and maintenance of SARS-CoV-2 specific T-cells is evaluated in all patients. Both parameters are analyzed in week one and month one and six after initial vaccination cycle and one month after a potential booster vaccination. Results: After a positive first interim analysis showing both SARS-CoV-2 neutralizing antibodies and T-cell responses one week after complete vaccination in siponimod patients data will be available in early 2022 for all patients at week one and later time points including first booster vaccinations. If possible, AMA-VACC results will be compared to findings from other clinical SARS-CoV-2 vaccination studies in patients with MS. Conclusions: This analysis will provide first longitudinal data on the immune response after SARS-CoV-2 mRNA vaccination in siponimod treated SPMS patients and enable physicians and patients to make an informed decision on the coordination of SARS-CoV-2 mRNA vaccination and SPMS treatment.

18.
Neurology ; 98(18 SUPPL), 2022.
Article in English | EMBASE | ID: covidwho-1925324

ABSTRACT

Objective: To compare humoral and cellular responses to COVID-19 vaccines in 400 consecutive MS patients who were on Ocrelizumab ('OCR') and other disease-modifying therapies ('nonOCR') at the time of vaccination. Background: Peripheral B-cell depletion with anti-CD20 therapies, attenuates humoral responses to vaccines, but less is known about cellular responses. Design/Methods: Consecutive MS patients from NYU MS Care Center were invited to participate if they completed COVID-19 vaccination ≥6 weeks previously. Immune testing included anti-spike RBD antibody (Elecsys Anti-SARS-CoV-2) (Roche Diagnostics);multiepitope bead-based immunoassays (MBI) of antibody-responses to SARS-COV-2 spike proteins (threshold of 'positivity'was chosen as 2 SD below non-OCR mean);T-cell responses to SARSCoV-2 Spike protein using IFNγ enzyme-linked immune-absorbent spot (Invitrogen) and TruCulture (Myriad RBM) assays;high dimensional immunophenotyping;live virus immunofluorescence-based microneutralization assay. Results: Antibody and T cell data was available on 145/355 patients enrolled to date (mean age: 40.0 years;75% female;48% non-white;39% on OCR;12% with prior COVID-19 infection;vaccines: 58% Pfizer/BioNTech, 36% Moderna and 6% Johnson&Johnson;median vaccine-tosample time: 93 (+/-32) days). In OCR, Elecsys Anti-SARS-CoV-2 Ab titers were detected in 30/63 (48%;mean antibody titer in log scale: 1.63) and in non-OCR - in 78/81 (96%, mean Ab titer in log scale: 2.83;p<0.0001). In OCR, antibody response by MBI were detected in 41/57 (72%, mean level in log scale: 3.09) and in non OCR - in 68/72 (94%, mean level in log scale: 4.08;p<0.001). Neutralizing antibodies were detected in 10/42 (38%) of OCR and 24/43 (56%) of non-OCR (p=0.1). T-cell activation based on induced IFNg secretion (TruCulture) was observed in 50/64 (78%) OCR and 43/81 (53%) non-OCR (p=0.002). Conclusions: Preliminary results suggest robust vaccine-specific T-cell immune response to SARS-CoV2 vaccines in B-cell depleted patients, but markedly attenuated antibody responses. Final results of pre-planned multivariable analyses stratified by DMT class and high-dimensional immunophenotyping will be presented.

19.
Neurology ; 98(18 SUPPL), 2022.
Article in English | EMBASE | ID: covidwho-1925265

ABSTRACT

Objective: To investigate the humoral immune response following SARS-CoV-2 vaccination in patients with multiple sclerosis (pwMS) and to determine the effect of disease modifying therapies (DMT) on the vaccination response. Background: Coronavirus disease 19 (COVD-19), a highly transmissible and potentially fatal illness caused by SARS-CoV-2, emerged as a global pandemic in early 2020. Several vaccines, including 2 innovative mRNA vaccines, were developed against this virus. To reduce relapse rates and slow disability accumulation, pwMS are often treated with DMTs which have anti-inflammatory properties and regulate adaptive immunity. An important clinical issue concerns the impact of DMTs on the efficacy of SARS-CoV-2 vaccination, and the eventual need for booster doses. In this study, we measured the titers of anti-SARS-CoV-2 neutralizing antibodies (nAbs) in pwMS following SARS-CoV-2 vaccination. Design/Methods: We conducted a prospective longitudinal study in pwMS at the Ohio State University (OSU) MS Center. Longitudinal serum samples were obtained from pwMS prior to and after the administration of the SARS-CoV-2 vaccine. These samples were analyzed for nAbs against SARS-CoV-2 spike protein using a novel pseudotyped-lentivirus-based virus neutralization assay. OSU health care workers (HCWs) served as healthy controls. Results: Of eighty-three consented subjects, fifty-two had post vaccination serum samples analyzed. Although pwMS did not exhibit drastically different nAb titers compared to HCWs, 21% (n=11) did not have detectable nAb titers post-vaccination (NT50 < 40)-including 9 patients on B-cell depleting therapies, 1 on sphingosine 1-phosphate modulator, and 1 on no DMT. Compared to patients not on DMT, pwMS on B-cell depleting therapies exhibited 7-fold lower nAb titers, while those on fumarates or beta-interferon exhibited no significant difference to patients not on DMT. Conclusions: Humoral immune response to the SARS-CoV-2 vaccine may be attenuated by certain DMTs, most notably B-cell depleting drugs. Further studies are underway to determine the effect of booster vaccine on nAb levels.

20.
Neurology ; 98(18 SUPPL), 2022.
Article in English | EMBASE | ID: covidwho-1925258

ABSTRACT

Objective: This study aims at understanding the impact of ofatumumab treatment on the development of cellular and humoral immune responses to initial and booster SARS-CoV-2 mRNA vaccines. Background: Recently developed SARS-CoV-2 mRNA vaccines have been shown to efficiently protect healthy individuals against COVID-19 and contribute greatly towards fighting the COVID-19 pandemic. However, only limited data is available about vaccine-induced immune responses in immunosuppressed patients. Design/Methods: KYRIOS is an open-label, prospective, two-cohort study at eight sites in Germany including 40 MS patients who receive SARS-CoV-2 mRNA vaccination either before starting ofatumumab treatment (cohort 1) or during stable ofatumumab treatment for at least 4 weeks (cohort 2). The impact of ofatumumab treatment on the proportion of patients having established SARS-CoV-2 reactive T-cells (primary endpoint) and developing SARS-CoV-2 neutralizing antibodies (secondary endpoint) after initial and booster vaccination will be assessed. Additionally, cellular and humoral immune responses will be monitored for up to 18 months and cellular response will be further described by immunophenotyping. Results: Results of this second interim analysis show the efficacy of SARS-CoV-2 mRNA vaccines to induce cellular and humoral immune responses in MS patients depending on the timing of ofatumumab treatment initiation. First data indicate that in patients vaccinated during stable ofatumumab treatment, specific immune response is detectable as soon as 1 week after the initial vaccination cycle and further increases afterwards. Conclusions: KYRIOS data show for the first time that patients vaccinated during stable ofatumumab treatment can mount immune responses to SARS-CoV-2 mRNA vaccines. The presented data further emphasize the importance of considering both, humoral and cellular immune response, for interpretation of vaccine efficacy.

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