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1.
British Journal of Dermatology ; 186(6):e257, 2022.
Article in English | EMBASE | ID: covidwho-1956712

ABSTRACT

A 27-year-old man presented to Accident and Emergency with an itchy rash over the thighs and buttocks. This followed 2 days of fever, headache and malaise. His past medical history was unremarkable and there was no regular medication use. He was unvaccinated. There was no history of previous erythema multiforme (EM) or herpes simplex virus (HSV) infection. He was febrile but otherwise haemodynamically stable. Clinically, over the thighs and buttocks there was a symmetrical rash consisting of striking urticated targetoid lesions. Some had a dusky centre and had coalesced over the thighs. There was no mucosal involvement. A SARS-CoV-2 polymerase chain reaction test was positive. Mycoplasma serology and swabs for HSV were negative. Other bloods were unremarkable. A skin biopsy from affected skin showed spongiosis and a mild dermal lymphocytic infiltrate. There was an absence of necrotic keratinocytes. He was treated with 5 days of prednisolone (30 mg) and potent topical steroids. There was complete clinical resolution of the rash in a week. In the published literature there are a small number of EM-like eruptions in the context of COVID-19 infection. Similar to our patient, skin biopsies often show features not typical of EM, including spongiosis and a lymphocytic perivascular and interstitial infiltrate (Torrelo A, Andina D, Santonja C et al. Erythema multiforme-like lesions in children and COVID-19.

2.
Jpn J Infect Dis ; 75(4): 334-340, 2022 Jul 22.
Article in English | MEDLINE | ID: covidwho-1957583

ABSTRACT

The new coronavirus severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for severe respiratory illness (i.e., COVID-19). RT-PCR of respiratory samples is the gold standard for COVID-19 diagnosis, and serological tests may contribute to the detection of post-infection and post-vaccination immunity and enable seroprevalence studies. The lateral flow immunoassay (LFIA) COVIDTECH® SARS-CoV-2 IgM/IgG antibody rapid test that detects anti-SARS-CoV-2 IgM and IgG using an S protein recombinant antigen has been independently evaluated in two laboratories. The specificity evaluated for 65 pre-pandemic samples was 100% for IgM/IgG. An analysis of samples from patients with RT-PCR-confirmed infection revealed that IgM/IgG antibodies were detected in 18/26 (69%) samples before day 13 and in 58/58 (100%) samples from day 14 post-symptom onset. Before day 14 post-symptom onset, the COVIDTECH Test was less sensitive than other LFIA method (BIOSYNEX COVID-19 BSS IgM/IgG) and a chemiluminescent immunoassay (LIAISON® SARS-CoV-2 TrimericS IgG assay). Overall, this LFIA method is suitable for SARS-CoV-2 serological diagnosis for patients after > 14 days since the onset of symptoms.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Viral , COVID-19/diagnosis , COVID-19 Testing , Humans , Immunoassay/methods , Immunoglobulin G , Immunoglobulin M , Sensitivity and Specificity , Seroepidemiologic Studies
3.
Biosensors (Basel) ; 12(8)2022 Jul 22.
Article in English | MEDLINE | ID: covidwho-1957225

ABSTRACT

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic has once more emphasized the urgent need for accurate and fast point-of-care (POC) diagnostics for outbreak control and prevention. The main challenge in the development of POC in vitro diagnostics (IVD) is to combine a short time to result with a high sensitivity, and to keep the testing cost-effective. In this respect, sensors based on photonic integrated circuits (PICs) may offer advantages as they have features such as a high analytical sensitivity, capability for multiplexing, ease of miniaturization, and the potential for high-volume manufacturing. One special type of PIC sensor is the asymmetric Mach-Zehnder Interferometer (aMZI), which is characterized by a high and tunable analytical sensitivity. The current work describes the application of an aMZI-based biosensor platform for sensitive and multiplex detection of anti-SARS-CoV-2 antibodies in human plasma samples using the spike protein (SP), the receptor-binding domain (RBD), and the nucleocapsid protein (NP) as target antigens. The results are in good agreement with several CE-IVD marked reference methods and demonstrate the potential of the aMZI biosensor technology for further development into a photonic IVD platform.


Subject(s)
Biosensing Techniques , COVID-19 , Antibodies, Viral , Biosensing Techniques/methods , COVID-19/diagnosis , Humans , Interferometry , Pandemics , SARS-CoV-2
4.
Era's Journal of Medical Research ; 8(2):209-217, 2021.
Article in English | ProQuest Central | ID: covidwho-1955362

ABSTRACT

The pandemic of Coronavirus Disease 2019 (COVID19) has compelled scientists to create highly reliable diagnostic tools quickly in order to successfully and properly diagnose this pathology and thereby prevent infection transmission. Even though structural and molecular properties of the severe acute respiratory syndrome coronavirus 2 (SARSCoV2) were previously unknown, private research institutes and biomedical firms quickly developed numerous diagnostic procedures beneficial for making a correct detection of COVID19. Rapid antigen or antibody testing, immunoenzymatic serological tests, and RT-PCR based molecular assays are the most frequently used and validated procedures now available. The PCR has grown in popularity in molecular diagnostics to the point where it is still considered the gold standard for finding nucleotides from a variety of sources becoming an indispensable tool in the research lab. Because of its improved speed, sensitivity, reproducibility, and lower likelihood of carry-over contamination, real-time PCR has gained greater popularity. Currently, five different chemistries are employed to detect PCR product during real-time PCR. The selffluorescing amplicons, DNA binding fluorophores, 5' endonuclease, neighbouring linear and hairpin oligoprobes, and self-fluorescing amplicons are all detailed in depth. We also go through the problems that have hampered the development of multiplex real-time PCR and the importance of real-time PCR in nucleic acid quantification.

5.
Am J Clin Pathol ; 2022 Jul 16.
Article in English | MEDLINE | ID: covidwho-1948149

ABSTRACT

OBJECTIVES: Automated qualitative serology assays often measure quantitative signals that are compared against a manufacturer-defined cutoff for qualitative (positive/negative) interpretation. The current general practice of assessing serology assay performance by overall concordance in a qualitative manner may not detect the presence of analytical shift/drift that could affect disease classifications. METHODS: We describe an approach to defining bias specifications for qualitative serology assays that considers minimum positive predictive values (PPVs) and negative predictive values (NPVs). Desirable minimum PPVs and NPVs for a given disease prevalence are projected as equi-PPV and equi-NPV lines into the receiver operator characteristic curve space of coronavirus disease 2019 serology assays, and the boundaries define the allowable area of performance (AAP). RESULTS: More stringent predictive values produce smaller AAPs. When higher NPVs are required, there is lower tolerance for negative biases. Conversely, when higher PPVs are required, there is less tolerance for positive biases. As prevalence increases, so too does the allowable positive bias, although the allowable negative bias decreases. The bias specification may be asymmetric for positive and negative direction and should be method specific. CONCLUSIONS: The described approach allows setting bias specifications in a way that considers clinical requirements for qualitative assays that measure signal intensity (eg, serology and polymerase chain reaction).

6.
Biosens Bioelectron X ; 11: 100176, 2022 Sep.
Article in English | MEDLINE | ID: covidwho-1944334

ABSTRACT

A novel test strategy is proposed with dual-modality detection techniques for COVID-19 antibody detection. The full-length S protein of SARS-CoV-2 was chemically immobilized on a glass surface to capture anti-SARS-CoV-2 IgG in patient serum and was detected through either Electrochemical Impedance Spectroscopy (EIS) or fluorescence imaging with labeled secondary antibodies. Gold nanoparticles conjugated with protein G were used as the probe and the bound GNP-G was detected through EIS measurements. Anti-human-IgG conjugated with the fluorescent tag Alexa Fluor 488 was used as the probe for fluorescence imaging. Clinical SARS-CoV-2 IgG positive serum and negative controls were used to validate both modalities. For fluorescence-based detection, a high sensitivity was noticed with a quantification range of 0.01-0.1 A.U.C. and a LOD of 0.004 A.U.C. This study demonstrates the possibility of utilizing different measurement techniques in conjunction for improved COVID-19 serology testing.

7.
Biosens Bioelectron ; 213: 114476, 2022 Oct 01.
Article in English | MEDLINE | ID: covidwho-1944329

ABSTRACT

Coronavirus disease 2019 (COVID-19) has caused significant global morbidity and mortality. The serology test that detects antibodies against the disease causative agent, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has often neglected value in supporting immunization policies and therapeutic decision-making. The ELISA-based antibody test is time-consuming and bulky. This work described a gold micro-interdigitated electrodes (IDE) biosensor for COVID antibody detection based on Electrochemical Impedance Spectroscopy (EIS) responses. The IDE architecture allows easy surface modification with the viral structure protein, Spike (S) protein, in the gap of the electrode digits to selectively capture anti-S antibodies in buffer solutions or human sera. Two strategies were employed to resolve the low sensitivity issue of non-faradic impedimetric sensors and the sensor fouling phenomenon when using the serum. One uses secondary antibody-gold nanoparticle (AuNP) conjugates to further distinguish anti-S antibodies from the non-specific binding and obtain a more significant impedance change. The second strategy consists of increasing the concentration of target antibodies in the gap of IDEs by inducing an AC electrokinetic effect such as dielectrophoresis (DEP). AuNP and DEP methods reached a limit of detection of 200 ng/mL and 2 µg/mL, respectively using purified antibodies in buffer, while the DEP method achieved a faster testing time of only 30 min. Both strategies could qualitatively distinguish COVID-19 antibody-positive and -negative sera. Our work, especially the impedimetric detection of COVID-19 antibodies under the assistance of the DEP force presents a promising path toward rapid, point-of-care solutions for COVID-19 serology tests.


Subject(s)
Biosensing Techniques , COVID-19 , Metal Nanoparticles , Biosensing Techniques/methods , COVID-19/diagnosis , Electrodes , Gold/chemistry , Humans , Metal Nanoparticles/chemistry , SARS-CoV-2
8.
Journal of Mazandaran University of Medical Sciences ; 32(210):26-36, 2022.
Article in Arabic | EMBASE | ID: covidwho-1935328

ABSTRACT

Background and purpose: Coronavirus disease 2019 (COVID-19) is a respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this study, an indirect ELISA method was designed to measure the human IgM and IgG antibodies against SARS-CoV-2. Materials and methods: Protein sequence of nucleocapsid antigen from SARS-CoV-2 was expressed in E. coli BL21 and then was purified by chromatography. The purified protein was confirmed by SDS-PAGE and Western blotting. An indirect ELISA method was designed to measure the specific IgG and IgM antibodies against SARS-CoV-2 using recombinant N protein. The optimized ELISA method was then applied to measure the IgG and IgM antibodies in 61 infected or recovered COVID-19 patients and in 31 healthy controls. Finally, data obtained from the designed ELISA method were compared with those of a commercially approved ELISA kit. Results: The recombinant nucleocapsid protein was successfully expressed and purified which was confirmed by SDS-PAGE and Western blotting. The amount of optical densities obtained from the designed ELISA method was similar to those of the commercial kit in 61 patients and 31 controls. The sensitivity and specificity of the designed ELISA method for IgG were 100% compared with the commercial ELISA kit, while the sensitivity and specificity for IgM were 96.72 and 96.77, respectively. Conclusion: Serological tests alone are not suitable for diagnosis;however, their combination with molecular tests increases the accuracy and sensitivity of the COVID-19 diagnosis. These tests are also vauable for epidemiological studies.

9.
Langenbecks Arch Surg ; 2022 Apr 29.
Article in English | MEDLINE | ID: covidwho-1941630

ABSTRACT

PURPOSE: The primary objective of the current study is to determine whether bariatric surgery reversed the negative impact of obesity on the serological response after the COVID-19 vaccination. This objective is achieved in two steps: (a) quantifying the negative impact of obesity on the serological response after COVID-19 vaccination if it is present, and (b) testing whether bariatric surgery reversed this impact. The secondary objective was to monitor the occurrence of adverse events. METHODS: This is a prospective cohort study between May 2021 and August 2021 on the strength of serological response after COVID-19 vaccination. Patients were classified into three groups. Group A (controls with normal or overweight), Group B (bariatric patients pre-operative), and Group C (bariatric patients post-operative). Quantitative antibodies against SARS­CoV­2 RBD with a strong neutralizing capacity were quantified from sera after at least 2 weeks post-vaccination. RESULTS: Of the 276 participants, Group A had n = 73, Group B had n = 126, and Group C had n = 77 patients. Overall, a strongly positive vaccine serological response was observed among 86% in group A, 63% in Group B, and 88% in Group C. Group C showed 5.33 times [95% CI 2.15 to 13.18] higher immune response than group B. Mild to moderate adverse events occurred in 30.1% [95% CI 24.7 to 35.9] of the study samples. Adverse events with the whole virus, mRNA, and vector vaccines occurred in 25%, 28%, and 37%, respectively. CONCLUSION: Vaccinating and bariatric surgery are safe and effective treatments in the serological response in patients who suffer from obesity.

10.
Methods Mol Biol ; 2511: 307-319, 2022.
Article in English | MEDLINE | ID: covidwho-1941385

ABSTRACT

Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) has been identified as the causative agent of COVID-19. Accurate detection of SARS-CoV-2 infection is not only important for management of infected individuals but also to break the chain of transmission. Although the polymerase chain reaction (PCR) is the gold standard for diagnosis of acute SARS-CoV-2 infection, there are a number of limitations of these assays, which include the inability to detect past infection and decline in sensitivity 14 days post-symptom onset. There are several serology tests developed for the detection of SARS-CoV-2 antibodies including high-throughput serology platforms and lateral flow immunoassays. These tests should be evaluated for their performance to meet local regulations acceptance criteria. To optimize the diagnostic algorithm for SARS-CoV-2, this protocol describes the evaluation of serological antibody testing using various automated serology platforms and lateral flow immunoassays. This protocol was evaluated in both serum and plasma samples. The sample preparation, procedure, and data analysis are described. The protocol can be adapted for any serological testing.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Viral , COVID-19/diagnosis , COVID-19 Testing , Humans , Immunoassay/methods , Sensitivity and Specificity
11.
Methods Mol Biol ; 2511: 257-271, 2022.
Article in English | MEDLINE | ID: covidwho-1941381

ABSTRACT

Serological assays have been a useful tool for detection of antibodies to SARS-CoV-2 during the COVID-19 pandemic. These assays are used for epidemiology and serosurveillance to monitor the progression of the pandemic, to identify and differentiate individuals who have developed antibodies from natural infection versus vaccine-induced immunity, and to identify potential donors of convalescent plasma for therapeutic purposes. In this chapter, we describe a commercially available bead-based serological assay, the Luminex® xMAP® SARS-CoV-2 Multi-Antigen IgG Assay, that detects and identifies antibodies against three SARS-CoV-2 antigens. In addition to the assay principle and workflow, we describe modifications that may be used to evaluate alternate sample types, antibody isotypes, and potential neutralizing antibody responses.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/diagnosis , COVID-19/therapy , Humans , Immunization, Passive , Immunoglobulin G , Pandemics , Sensitivity and Specificity
12.
Bioanalysis ; 14(1):1-5, 2022.
Article in English | EMBASE | ID: covidwho-1939236
13.
Journal of Hypertension ; 40:e29, 2022.
Article in English | EMBASE | ID: covidwho-1937692

ABSTRACT

Objective: The world is currently facing the fourth wave of the COVID-19 pandemic. The purpose of this study was to assess the effect of this pandemic on ambulatory blood pressure measurements and to compare the blood pressure profile between COVID-19 positive and negative patients. Design and method: We performed a unicentric, retrospective study on the register of ambulatory blood pressure measurements (ABPM) of the ERASME Hospital from 2010 to 2021. ABPMs performed during the pandemic period (January 2020 to October 2021) were compared with those from 5 previous control periods. In order to improve the comparison of the different periods, we considered variations (delta) of each period from the previous 3 months. For all patients whose ABPM was performed during the COVID-19 period, we looked for COVID test results preceding the ABPM. These patients were classified into 2 groups COVID positive, if at least one PCR or serological test was positive, and COVID negative if not. Data analysis was performed using SPSS version 23.0. Results: After exclusion of incomplete and poor-quality ABPMs, 18766 were retained, of which 1796 (9.57%) were for the COVID-19 period. The control periods represented 14.77% to 18.81% of the MAPAs in the study. We observed that diurnal, nocturnal and 24-hour diastolic blood pressures (BP) were higher in the COVID-19 period than in the previous 5 periods ranging from January 2010 to October 2019. Pulse pressure was lower in the COVID-19 period compared to the previous periods. Of the 1796 patients in the COVID-19 period, pre-ABPM COVID- 19 status were obtained from 368 patients, 322 negatives and 46 positives. In COVID-19 positive patients, daytime systolic BP was higher than in COVID-19 negative patients (88,41 ± 11,74 vs 84,63 ± 12,24;p = 0.047). Also, the pulse pressure of COVID-19 positive patients was lower (44,46 ± 7,72 vs 47,57 ± 8,84). No significant differences were observed between the two groups for the other parameters. Conclusions: The COVID-19 pandemic resulted in increased daytime and nighttime diastolic blood pressures. Also, this study suggests an increase in diurnal diastolic blood pressure after COVID-19 infection.

14.
Microbiol Spectr ; : e0115422, 2022 Jul 05.
Article in English | MEDLINE | ID: covidwho-1938018

ABSTRACT

In August 2020, the Food and Drug Administration (FDA) Emergency Use Authorization (EUA) for COVID-19 convalescent plasma (CCP) specified 12 authorized serologic assays and associated assay-specific cutoff values for the selection of high-titer CCP for use in hospitalized patients. The criteria used for establishing these cutoff values remains unclear. Here, we compare the overall agreement and concordance of five serologic assays included in the August 2020 FDA EUA at both the manufacturer-recommended qualitative cutoff thresholds and at the FDA-indicated thresholds for high-titer CCP, using serum samples collected as part of the CCP Expanded Access Program (EAP). The qualitative positive percent agreement (PPA) across assays ranged from 92.3% to 98.8%. However, the high-titer categorization across assays varied significantly, with the PPA ranging from 26.5% to 82.7%. The Roche anti-NC ECLIA provided the lowest agreement compared to all other assays. Efforts to optimize high-titer cutoffs could reduce, although not eliminate, the discordance across assays. The consequences of using nonstandardized assays are apparent in our study, and the high-titer cutoffs chosen for each assay are not directly comparable to each other. The generalized findings in our study will be relevant to any future use of convalescent plasma for either COVID-19 or future pandemics of newly emerged pathogens. IMPORTANCE COVID-19 convalescent plasma (CCP) was one of the first therapeutic options available for the treatment of SARS-CoV-2 infections and continues to be used selectively for immunosuppressed patients. Given the emergence of novel SARS-CoV-2 variants which are resistant to treatment with available monoclonal antibody (MAb) therapy, CCP remains an important therapeutic consideration. The FDA has released several emergency use authorizations (EUA) that have specified which serological assays can be used for qualification of CCP, as well as assay-specific cutoffs that must be used to identify high-titer CCP. In this study, a cohort of donor CCP was assessed across multiple serological assays which received FDA EUA for qualification of CCP. This study indicates a high degree of discordance across the assays used to qualify CCP for clinical use, which may have precluded the optimal use of CCP, including during clinical trials. This study highlights the need for assay standardization early in the development of serological assays for emerging pathogens.

15.
Transbound Emerg Dis ; 2022 Jul 16.
Article in English | MEDLINE | ID: covidwho-1937993

ABSTRACT

In the French region of Brittany, mainly in the department of the Côtes d'Armor, during the first half of 2021, seropositivity for SARS-CoV-2 was detected in five wild mustelids out of 33 animals tested (15.6%). Anti-SARS-CoV-2 IgG was detected against at least four out of five recombinant viral proteins (S1 receptor binding domain, nucleocapsid, S1 subunit, S2 subunit and spike) in three pine martens (Martes martes) and in two badgers (Meles meles) using the automated western blot technique. An ELISA test also identified seropositive cases, although these did not align with western blot results. Although the 171 qPCRs carried out on samples from the 33 mustelids were all negative, these preliminary results from this observational study nevertheless bear witness to infections of unknown origin. The epidemiological surveillance of Covid-19 in wildlife must continue, in particular with effective serology tools.

16.
Med J Armed Forces India ; 2022 Jul 19.
Article in English | MEDLINE | ID: covidwho-1936999

ABSTRACT

Background: The change in serological status of community may be used as input for guiding the public health policy. Hence, the present study was conducted to determine change in seroprevalence of COVID-19 among healthcare workers (HCWs). Methods: From the baseline multicentric study sample, a subsample was followed up, and a seroepidemiological study was conducted among them between 6 and 22 weeks after the second dose of the vaccination. Multistage population proportion to size sampling was performed for the selection of subsample of HCWs. The serosurvey was conducted using the enzyme-linked immunosorbent assay-based IgG antibody test (COVID KAVACH). Results: Follow-up serological testing was done in subsample of 1122 participants of original 3253 participants. The mean age of the participants was 34.6 (8.13) years. A total of 300 (26.7%) participants were females. The seroprevalence was 78.52, (95%CI:76-80.1). Among those who were seronegative at initial test, 708 (77.04%) were seroconverted. Those who were not seroconverted (241 (21.5%)) have longer duration from the second dose of the vaccination (93 (31.4) vs. 56 (38.4); p value < 0.001). The COVID-19 infection was significantly associated with seropositive status and being a medical staff was associated with remaining seronegative on follow-up. The higher age (≥50 years) was found to be significantly associated with seroreversion. Conclusion: Four in five HCWs had detectable antibodies. Seroepidemiological studies carry vital information to control the public health response in the course of the pandemic. The study can also further help as a platform to study the seroconversion and effect of vaccination among HCWs for newer variants of SARS-CoV-2.

17.
Oman Journal of Ophthalmology ; 15(2):234-236, 2022.
Article in English | ProQuest Central | ID: covidwho-1934429

ABSTRACT

Thromboembolic complications are being increasingly reported in patients with COVID-19 due to the associated hypercoagulability and are an important cause for morbidity and mortality. Retinal vascular occlusions especially arterial occlusions are one of the gravest ocular complications reported. This complication may occur in severe cases with cytokine storm or even in mild or asymptomatic patients and presentation can be anytime from few days to weeks after the onset of symptoms. Ophthalmologists should be aware of this new etiology when dealing with patients having features of retinal vascular occlusions and should investigate for the same in this pandemic situation. Although reverse transcriptase polymerase chain reaction is the diagnostic test for COVID-19, serological assays have a role in patients with delayed presentation. We describe the clinical features and multimodal imaging findings in a patient who presented with features of central retinal artery occlusion with cilioretinal artery sparing wherein his ophthalmic condition led to the diagnosis of previously undetected COVID-19 through serology. To the best of our knowledge, this is the first documentation of a case of isolated central retinal artery occlusion leading to a retrospective diagnosis of COVID-19.

18.
Journal of Family Medicine and Primary Care ; 11(6):2667-2671, 2022.
Article in English | CAB Abstracts | ID: covidwho-1934399

ABSTRACT

Background: The tide of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) pandemic has scoured the global community with India, from 30 January 2020 to 30 September 2021, reporting 33,739,980 confirmed cases and over 448,090 deaths from coronavirus disease (COVID-19). Serologic testing for SARS-CoV-2 infection among the general public will provide essential information regarding the risk of infection. So, the present study was conducted to provide relevant information on the proportion of people who hadexperienced either a recent or past infection. Methodology: A cross-sectional study was conducted among adults >18 years in the Department of Community Medicine, Government medical college, Srinagar. Blood samples of the participants were tested for the presence of SARS-CoV-2-specific IgG antibodies using a chemiluminescent microparticle immunoassay-based serologic test.

19.
Statistical Science ; 37(3):306-321, 2022.
Article in English | Scopus | ID: covidwho-1933181

ABSTRACT

This paper concerns the construction of confidence intervals in standard seroprevalence surveys. In particular, we discuss methods for constructing confidence intervals for the proportion of individuals in a population infected with a disease using a sample of antibody test results and measurements of the test’s false positive and false negative rates. We begin by documenting erratic behavior in the coverage probabilities of standard Wald and percentile bootstrap intervals when applied to this problem. We then consider two alternative sets of intervals constructed with test inversion. The first set of intervals are approximate, using either asymptotic or bootstrap approximation to the finite-sample distribution of a chosen test statistic. We consider several choices of test statistic, including maximum likelihood estimators and generalized likelihood ratio statistics. We show with simulation that, at empirically relevant parameter values and sample sizes, the coverage probabilities for these intervals are close to their nominal level and are approximately equi-tailed. The second set of intervals are shown to contain the true parameter value with probability at least equal to the nominal level, but can be conservative in finite samples. © Institute of Mathematical Statistics, 2022

20.
Mult Scler Relat Disord ; 63: 103863, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1931042

ABSTRACT

BACKGROUND: Multiple sclerosis (MS) patients receive immunomodulatory treatments which can influence their ability to maintain vaccine specific serological response overtime. MS patients treated with cladribine tablets developed a positive serology response following two doses of mRNA COVID-19 vaccine. However, there is only limited data regarding the effect of cladribine tablets on long-term humoral response after the second and the third booster. METHODS: Serology response to SARS-CoV-2 was tested in healthy controls (HCs) and MS patients treated with cladribine tablets 6 and 9-12 months after the second dose, and 1 and 3-6 months following the third booster-dose of the BTN162b2 mRNA vaccine. RESULTS: Thirty-five out of 36 MS patients treated with cladribine tablets and 100% (46/46) of HCs had a positive serology response up to 10 months after the second vaccine dose. In addition, all cladribine tablets -treated MS patients (22/22) and HCs (24/24) had a positive robust serology response following the third vaccine with a positive humoral response sustain up to 6 months. One month after the third vaccine dose IgG levels were significantly lower in patients treated with cladribine tablets compared to HCs (15,598+11,313 vs 26,394+11,335, p<0.01). Six-month post second vaccine and 3-6 months post third vaccine there was no difference in IgG levels between the groups (1088.0 ± 1072.0 vs 1153.0 ± 997.1, p = 0.79; 5234+4097 vs 11,198+14,679, p = 0.4). CONCLUSION AND RELEVANCE: MS patients treated with cladribine tablets have sustained positive vaccine specific serology response following the second and third SARS-CoV-2 vaccine dose.


Subject(s)
COVID-19 , Multiple Sclerosis, Relapsing-Remitting , Multiple Sclerosis , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines , Cladribine/adverse effects , Humans , Immunoglobulin G/therapeutic use , Immunosuppressive Agents/adverse effects , Multiple Sclerosis/drug therapy , Multiple Sclerosis, Relapsing-Remitting/drug therapy , SARS-CoV-2 , Tablets , Vaccines, Synthetic , mRNA Vaccines
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