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1.
Anal Bioanal Chem ; 2022 Nov 08.
Article in English | MEDLINE | ID: covidwho-2103859

ABSTRACT

The SARS-CoV-2 pandemic has shown the importance of rapid and comprehensive diagnostic tools. While there are numerous rapid antigen tests available, rapid serological assays for the detection of neutralizing antibodies are and will be needed to determine not only the amount of antibodies formed after infection or vaccination but also their neutralizing potential, preventing the cell entry of SARS-CoV-2. Current active-virus neutralization assays require biosafety level 3 facilities, while virus-free surrogate assays are more versatile in applications, but still take typically several hours until results are available. To overcome these disadvantages, we developed a competitive chemiluminescence immunoassay that enables the detection of neutralizing SARS-CoV-2 antibodies within 7 min. The neutralizing antibodies bind to the viral receptor binding domain (RBD) and inhibit the binding to the human angiotensin-converting enzyme 2 (ACE2) receptor. This competitive binding inhibition test was characterized with a set of 80 samples, which could all be classified correctly. The assay results favorably compare to those obtained with a more time-intensive ELISA-based neutralization test and a commercial surrogate neutralization assay. Our test could further be used to detect individuals with a high total IgG antibody titer, but only a low neutralizing titer, as well as for monitoring neutralizing antibodies after vaccinations. This effective performance in SARS-CoV-2 seromonitoring delineates the potential for the test to be adapted to other diseases in the future.

2.
Journal of Clinical and Diagnostic Research ; 16(9):DC12-DC17, 2022.
Article in English | EMBASE | ID: covidwho-2067199

ABSTRACT

Introduction: Bharat Biotech International Ltd in partnership with National Institute of Virology (NIV), has developed an indigenous whole virion inactivated Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) viral vaccine BBV-152 (Covaxin), formulated with Toll Like Receptors 7/8 agonist Imidazoquinoline (IMDG) molecule adsorbed to alum (Algel). Variety of factors other than environmental ones can affect vaccines efficiency outside the strict setting of clinical trials, like how the vaccine is stored or transported, and even how patients are vaccinated. In addition, the intrinsic capacity of the recipient to respond to a vaccine which is determined by sex, genetic factors, age, psychological stress, nutrition and other diseases are also likely to have an impact. Aim(s): To determine the safety, reactogenicity and immunogenicity of the inactivated whole virus vaccine (Covaxin) amongst hospital-based population groups. Material(s) and Method(s): The prospective analytical study was conducted in the Department of Microbiology, Sawai Man Singh Medical College, Jaipur, Rajasthan, India, from January 2021 to March 2021.The study primarily included Healthcare Workers (HCWs) employed at SMS Medical college and attached hospitals. In-vitro quantitative IgG antibodies against SARS-CoV-2 spike Receptor Binding Domain (RBD) were measured using Chemiluminescence Immunoassay (CLIA) based Advia centaur SARS-CoV-2 IgG, manufactured by Siemens Pvt Ltd, Munich, Germany, as per manufacture's instructions. Result(s): Out of total 223 individuals, 61.88 % (138/223) showed neutralising antibody titre of >1 index value by CLIA, rest 38.12% (85/223) were non reactive i.e., titre <1 index value, after four weeks of receiving first dose of Covaxin. After 2 to 4 weeks of receiving second dose 84.30% (188/223) showed neutralising antibody titre of >1 index value by CLIA, rest 15.70% (35/223) were non reactive i.e., titre <1 index value. After receiving first dose, 100% (223/223) of the participants developed localised pain and bodyache 33.63% (75/223). None of the participants showed any anaphylactic reaction or any emergency condition just after vaccination. Conclusion(s): Covaxin is a well-tolerated vaccine, and induces good humoral response against SARS-CoV-2 with a significant rise in the neutralising antibody titres. Copyright © 2022 Journal of Clinical and Diagnostic Research. All rights reserved.

3.
Pharmacia ; 69(3):791-800, 2022.
Article in English | EMBASE | ID: covidwho-2010396

ABSTRACT

The aim of current study was to determine, retrospectively, possible correlations between smoking and the incidence, course severity, intubation rate, and mortality (by gender and age) in patients treated for complicated coronavirus infection in the internal medicine clinic at UMHATEM ”N. I. Pirogov” Sofia for the period 01.03.2020–31.12.2020. In a prospective study, the recovery period and immunogenesis in smokers and non-smokers within a one-year period after hospital discharge was investigated. The applied methods were: 1) computed tomography and blood gas analysis 2) chemiluminescent immunoassay for the qualitative determination of total IgM, IgA and IgG anti-SARS-CoV2 AB. Results showed that the part of non-smokers with a positive PCR test is significantly higher compared to the group of former and current smokers. The data obtained from the study confirmed that Covid infection is much more severe among smokers and former smokers with a higher levels of inflammatory markers noticed among the smoking group.

4.
Journal of the ASEAN Federation of Endocrine Societies ; 37:48, 2022.
Article in English | EMBASE | ID: covidwho-2006561

ABSTRACT

Introduction COVID-19 may have widespread effects throughout the body, including the endocrine glands, which can be impaired by different mechanisms. Several recent reports have described the onset of thyroid dysfunction in previously healthy patients diagnosed with COVID-19. Thus, we aimed to describe the pattern of abnormal thyroid function tests (TFTs) in severe COVID-19 patients in Hospital Sungai Buloh. METHODOLOGY Thyroid stimulating hormone (TSH) and free thyroxine (fT4) were received from all critical care wards catering for severe COVID-19 adult patients (Clinically Stage 4 and 5) from December 2020 till June 2021. It was retrospectively reviewed in Laboratory Information System (LIS) with exclusion of thyroid disease, pregnancy or immunotherapy. SARS-CoV-2 infection was confirmed by RT-PCR of nasopharyngeal swab samples and severity classification was based on the Malaysia MOH guideline. Analysis of TFT was performed on Siemens Atellica using chemiluminescent immunoassay Results From 184 TFT results analysed, about 120 patients (65%) had abnormal thyroid function, of which 62.5% had low TSH level with normal fT4 and 15.8% had low TSH with high fT4. This indicated that abnormal TFT is common among COVID-19 patients, with low TSH being most common. However, we are unable to exclude steroid use as a cause of low TSH levels, as steroid are one of the main treatments prescribed in severe COVID-19 cases. Conclusion There was a high proportion of abnormal TFT in severe COVID-19 patients even in the absence of pre-existing thyroid conditions. Clinicians directly involved in treating these patients need to be vigilant in interpreting thyroid function abnormalities in COVID-19 infection.

5.
Indian Journal of Critical Care Medicine ; 26:S116, 2022.
Article in English | EMBASE | ID: covidwho-2006404

ABSTRACT

Background: Hospitalised COVID-19 patients are known to exhibit varying degrees of immune dysfunction, few modifiable risk factors have been identified to improve this state of which one is the immune modulator effects of vitamin D. Vitamin D is being prescribed as a treatment of COVID-19 in a few guidelines as there is generalised assumption that vitamin D enhances immunity during this illness. So this is an attempt to find out whether a deficiency of vitamin D is associated with the severity of COVID-19. Aim: To study the relationship of serum 25 hydroxy vitamin D [25(OH)D] deficiency with disease severity in hospitalised COVID-19 patients. Materials and methods: The present case-control study compared serum 25(OH)D levels among Mild to moderate and severe COVID- 19 patients. Around 39 diagnosed and Hospitalised Severe COVID- 19 disease are compared with 39 Hospitalised Mild and Moderate COVID-19 disease in Care Hospital, Bhubaneswar, Odisha, India between April 1, 2021, ad August 31, 2021. Patients were divided into 2 groups. The Group 1-Mild to Moderate infection with CT Severity index < 10/25 and Group 2-Severe Infection with HRCT Chest of CTSI >10/25. As per hospital policy, severe infection patients were kept in Critical Care Area and Mild infection patients were kept in Ward/Cabin areas. Any patients becoming sick and being transferred to critical areas are shifted from Group 1 to Group 2 after HRCT chest. Vitamin D levels (25 D Cholecalciferol) are done on the day of admission by chemiluminescence immunoassay test after taking due consent from the patients/attenders. The level of cut-off used in our study is 20 ng/mL. The association was analysed using regression analysis and other statistical methods. Results: The status of 25(OH)D deficiency (present/absent with cut-off being 20 ng/mL) showed no significant difference among cases and control at p < 0.05. Chi-square statistics with Yates correction is 1.8909. The p value is 0.169099. So there were no significant differences in vitamin D3 levels between Mild to moderate and Severe COVID- 19 patients. Conclusion: 25(OH)D levels appear to have no strong association with disease severity amongst hospitalised COVID-19 patients. Hence, its prescription for COVID-19 treatment as well as prevention needs to be reconsidered.

6.
Journal of Clinical Oncology ; 40(16), 2022.
Article in English | EMBASE | ID: covidwho-2005673

ABSTRACT

Background: Thymic epithelial tumors (TET) are rare malignancies associated with dysregulation of the immune system and humoral and cell mediated immunity abnormalities. Anti-syndrome coronavirus type 2 (SARS-CoV-2) vaccine is effective at preventing COVID-19 morbidity and mortality. No published data are available regarding the immunization in TET patients (pts). The aim of this study was to evaluate the immunization in TET pts who received two doses of mRNA vaccine, by longitudinal serological detection of SARS-COV-2 spike-binding IgG antibody. Methods: Starting from April 2021 to October 2021, consecutive TET pts referred to the Rare Tumors Coordinating Center of Campania Region (CRCTR - Naples, Italy) were enrolled. All study subjects received two doses of COVID-19 mRNA vaccine (BNT162b2 by Pfizer-BioNTech). SARS-CoV-2 spike-binding IgG antibody (Ab) serological levels were analyzed by centralized chemiluminescent immunoassay (CLIA) at different time-points, including before 1st vaccine dose (T0) and 1 month after 2nd dose (T2). Cut-off for Ab titers positivity was > 25 AU/mL. Results: Forty pts were enrolled;23 (57.5%) were female and 17 (42.5%) male. Eleven pts (27.5%) suffered from thymic carcinoma, 28 (70%) thymoma, and 1 (2.5%) thymic hyperplasia. At the time of study enrollment, 20 pts (50%) had no evidence of disease (NED) and were in followup;the remaining 20 pts had evidence of disease (ED) by imaging and were receiving systemic treatment (55% oral low-dose etoposide-based therapy, 40% somatostatin analogs + prednisone, 5% supportive care). Immune system disorders were diagnosed in 29 TET pts (72.5%): 19 pts (47.5%) had Good's Syndrome (GS) and 10 (25%) other immune disorders. At T0, all enrolled pts had negative Ab titers and no prior SARS-CoV-2 infection. At T2, Ab data were available for 37 pts (92.5%): 18 pts (48.7%) had positive Ab titers, whereas 19 (51.3%) did not achieve seroconversion. Among pts with ED, seroconversion was achieved only in 2 cases (11.8%). Lack of seroconversion at T2 was significantly associated with ED (Fisher's exact test p: 0.0001) and with the presence of GS (Fisher's exact test p: 0.0489). No significant association of seroconversion with other immune disorders and disease features was found. Conclusions: Our data showed that TET pts with ED had substantially higher probability of impaired seroconversion after SARS-COV-2 vaccine as compared with NED pts. We warrant further studies to evaluate the role of disease status, anti-tumor treatments and immune disorders in post-vaccine immunization of TET pts.

7.
Journal of Hepatology ; 77:S782, 2022.
Article in English | EMBASE | ID: covidwho-1996647

ABSTRACT

Background and aims: The effectiveness of SARS-CoV-2 vaccination in liver transplant (LT) recipients varies between 47.5% to 81% with majority of reports focusing on the immune response assessed in the first month after the vaccination. Data on LT recipients willingness to receive vaccine is limited to only a few reports. Here, we analysed the immune response to the SARS-CoV-2 vaccination, factors affecting response and reasons for refusal to receive this vaccine. Method: Among 300 consecutive LT recipients, 225 (75%) were vaccinated. Seventy-four (25%) subjects were not vaccinated, including 45 (15%) who refused to be vaccinated and 29 (10%) who did not get the vaccine due to medical reasons. The humoral response was assessed by quantitative determination of anti-trimeric spikeprotein- specific-IgG antibodies to SARS-CoV-2 by LIAISON® SARSCoV- 2 TrimericS IgG assay (Diasorin, Italy), which is a chemiluminescence immunoassay (CLIA). Thirty-four vaccinated patients with prior COVID-19 infection were analysed separately. Results: Among 192 LT recipients vaccinated without prior COVID-19, 69% of them had an immune response (median time of 125 days after the second dose). Older age, worse kidney function and dual immunosuppression negatively affected the humoral response. Mycophenolate mofetil increased the risk of non-response (OR 3.0, 95% CI 1.43–6.25). LT recipients with prior COVID-19 presented with a robust immune response (100%) and with significantly higher IgG antibodies (median 2080 vs 134 BAU/ml;p <0.001). The antibodies concentrationwas higher in the first 90 days fromthe second dose (p = 0.034) and stabile when compared between patients who received the vaccination within 90–150 or more than 150 days (Figure 1). Female gender, living in rural area, lower BMI (all p < 0.05) and younger age (p < 0.001) were associated with refusal of the vaccine due to non-medical reasons. In contrast, liver recipients with diabetes and impaired kidney function (both p <0.01)were more prone to get a vaccine. (Figure Presented) Figure: Median SARS-CoV-2 TrimericS IgG concentration among liver transplant recipients (without prior COVID-19) compared between time from the second dose of the vaccine: <90 days, 90–150 days and >150 days. Conclusion: Lower immune response after the vaccine among LT recipients may support administration of a third dose. Previous COVID-19 infection dramatically improves response to vaccination in these patients. Sociodemographic factors may play a role in refusal of being vaccinated but this finding require further investigations in other cohorts of transplanted patients.

8.
Chinese Journal of Microbiology and Immunology (China) ; 42(1):16-22, 2022.
Article in Chinese | EMBASE | ID: covidwho-1928714

ABSTRACT

Objective To detect the serum levels of SARS-CoV-2-specific IgM and IgG antibodies in patients infected with SARS-CoV-2 and recipients of inactivated vaccine in different periods for understanding their variation patterns in vivo. Methods Chemiluminescence immunoassay was used to detect the levels of SARS-CoV-2-specific IgM and IgG antibodies in 144 serum samples of 44 COVID-19 patients, 381 serum samples of 118 asymptomatic infected cases and 398 serum samples of 273 inactivated vaccine recipients collected at different periods. The results were statistically analyzed together with basic characteristics and vaccination status. Results The positive rates of IgM antibody in COVID-19 patients, asymptomatic infected cases and inactivated vaccine recipients were 52. 27% (23 / 44), 23. 73% (28 / 118) and 14. 29% (39 / 273). The positive rate of IgM antibody was higher in COVID-19 patients than in asymptomatic infected cases and vaccine recipients (χ2 = 12. 106, P = 0. 001;χ2 = 34. 755, P<0. 001). The positive rates of IgG antibody in the three populations were 100. 00% (44 / 44), 97. 46% (115 / 118) and 98. 81% (166 / 168), and the differences were not statistically significant (χ2 = 2. 944, P = 0. 229). In COVID-19 patients, the concentration of IgM antibody in <40 years old group was lower than that in ≥40 years old group (Waldχ2 = 6. 609, P = 0. 010), and the concentration of IgG antibody in patients with vaccination was higher than that in patients without vaccination (Waldχ2 = 12. 402,P<0. 001). In asymptomatic infected cases, the concentration of IgG antibody was higher in people with vaccination than in those without vaccination (Waldχ2 = 4. 530, P = 0. 033). In SARS-CoV-2 vaccine recipients, the concentration of IgG antibody in <40 years old group was higher than that in ≥40 years old group (Waldχ2 = 9. 565, P = 0. 002). Dynamic analysis of antibody levels showed that from week 1 to week 9, the concentrations of IgM and IgG antibodies in COVID-19 patients were higher than those in asymptomatic infected cases and vaccine recipients. Conclusions The concentrations of IgM and IgG antibodies in COVID-19 patients were higher than those in asymptomatic infected cases and inactivated vaccine recipients. COVID-19 patients aged ≥40 years had higher level of IgM antibody. COVID-19 patients and asymptomatic infected cases who had received vaccination had higher concentration of IgG antibody. Inactivated vaccine showed good immunogenicity after whole course of immunization, and the IgG antibody level in <40 years old group was higher.

9.
Nephrology Dialysis Transplantation ; 37(SUPPL 3):i664-i665, 2022.
Article in English | EMBASE | ID: covidwho-1915783

ABSTRACT

BACKGROUND AND AIMS: Previous data has shown a reduced immune response shortly after SARS-CoV-2 vaccinations in haemodialysis patients. We therefore investigated the long-term antibody response in patients from different outpatient dialysis centres at 4 weeks and 6 months after a complete vaccination against COVID-19. The results were compared with the humoral responses of non-dialysis subjects. METHODS: We designed a retrospective multicentric cohort study, enrolling 106 haemodialysis patients and 50 non-dialysis patients after the SARS-CoV-2 vaccination. SARS-CoV-2 antibody testing was performed as part of routine clinical practice 4 weeks as well as 6 months after the immunization with chemiluminescence immunoassays designed to detect antibodies against the SARS-CoV-2 spike protein (Elecsys Anti-SARS-CoV-2 S, Roche Diagnostics, Mannheim, Germany). Testing was performed in the Institute of Laboratory Medicine of the University Hospital Munich. According to the manufacturer's specifications, anti-SARS-CoV-2 S titres >0.8 U/mL are considered reactive (sensitivity 98.8% and specificity 99.9%). Anti-SARS-CoV-2 S titres < 100 U/mL were defined as a low antibody response. RESULTS: A total of 106 haemodialysis patients with a median age of 73 years received a SARS-CoV-2 vaccination (n = 105 mRNA, n = 1 AstraZeneca). Of these, 50 non-dialysis patients with a median age of 56 years received a SARS-CoV-2 vaccination (n = 45 mRNA, n = 5 mRNA/AstraZeneca). During the observational period, 8 haemodialysis patients and 2 non-dialysis patients additionally contracted a SARS-CoV-2 infection. Between the two testings, an overall decrease in anti-SARS-CoV-2 S antibody titres was observed (haemodialysis patients from a median of 252 to 95 U/mL, nondialysis patients from a median of 1621 to 441 U/mL). At 6 months after the complete vaccination, 99 (93%) haemodialysis patients still presented with a detectable anti-SARS-CoV-2 spike antibody response (>0.8 U/mL), comparable to 100% of the non-dialysis subjects. However, 60 (57%) haemodialysis patients showed low antibody response (<100 U/mL), whereas only 5 (10%) non-dialysis patients presented with low antibody response. Patients with an additional infection showed an increased titre of antibodies during follow-up. CONCLUSIONS: Our data suggest regular antibody testing as well as a need for booster vaccination in the vulnerable population of haemodialysis patients.

10.
Microchemical Journal ; : 107719, 2022.
Article in English | ScienceDirect | ID: covidwho-1895334

ABSTRACT

The 10-kDa chemokine interferon-gamma-inducible protein 10 (IP-10) is considered one of the most promising biomarkers for diagnosing both tuberculosis and COVID-19 infections. The blood samples of patients at different disease states contain different levels of IP-10, which need to be detected in a rapid, specific and ultrasensitive manner. Here, we report a bienzymatic chemiluminescence sandwich immunoassay (BCSI) assay for the ultrasensitive and stable detection of IP-10. In this assay, IP-10 is first efficiently captured using a double-antibody sandwich strategy. The detection antibody is linked to catalase (CAT) via a streptavidin-biotin signal amplification system to achieve highly efficient conversion of hydrogen peroxide (H2O2) to oxygen and water. In the chemiluminescence (CL) reaction, horseradish peroxidase (HRP) acts as an efficient catalyst, and 4-bromophenol acts as an enhancer for the cyclic transition of HRP, which results in a strong and durable CL signal. The bienzymatic catalysis with CAT and HRP and the potentiation of 4-bromophenol enables the assay to be ultrasensitive and stable. The CL intensity was found to be well correlated with the detection of IP-10 at levels in the range of 0.71 to 125,000 pg/mL, which covers more than 6 orders of magnitude, with a detection limit of 0.63 pg/mL. The coefficient of variation was 1.49%, and the recovery range of IP-10 in serum was 86.21%-104.57%. This assay provides a wide linear range and high sensitivity and may be a promising method for the high-throughput detection of IP-10 in the diagnosis of tuberculosis and COVID-19.

11.
Journal of Pure and Applied Microbiology ; 16(2):1187-1191, 2022.
Article in English | EMBASE | ID: covidwho-1887409

ABSTRACT

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS CoV-2) possess high mortality and morbidity across the globe. In India, BBV-152 (CovaxinTM) and ChAdOx1-nCOV (CovishieldTM) vaccines are now being used to limit the spread of SARS-CoV-2 Infection. A Cross sectional observational study was designed to analyze the Antibody immune response to SARS CoV-2 vaccine quantitatively among Health Care Workers and it was correlated with age, sex, other comorbidities and blood group. A total of 160 fully vaccinated HCWs, the Anti-SARS-CoV-2 level was estimated by using Chemiluminescence Immuno Assay. A protective immune response following the complete course of the SARS-CoV-2 vaccine should be ≥ 1.00 S/C. A total of 160 HCWs (82 Male, 78 Female) who had completed both the doses of Covishield (n=128) and Covaxin (n=32). Both the vaccine recipient had mild to moderate symptoms and none of the HCWs had severe adverse events after administration of vaccine. Out of which, 143 (89.3%) HCWs showed seropositive and 17 (10.7%) HCWs showed seronegative. There was no notable variation in sex and other co-morbidities. Significantly, reduced antibody titers towards SARS-CoV-2 vaccine was noted among individuals aged ≤ 60 years and O+ve Blood group. Both the vaccines obtained successful immune response after their complete course, even though there was a significantly higher seropositivity rate in Covishield in spite of Covaxin recipients. Further, genomic correlative advanced studies can conclude the significance of non-responsiveness to SARS-CoV-2 vaccines among the HCWs.

12.
Topics in Antiviral Medicine ; 30(1 SUPPL):110-111, 2022.
Article in English | EMBASE | ID: covidwho-1880985

ABSTRACT

Background: In Italy in September 2021, administration of a booster shot (BS) of COVID-19 vaccine was approved for PLWH with advanced disease (current CD4 count<200 cell/mm3 and/or previous AIDS). The aim of this analysis was to investigate the degree of immunogenicity after BS by current CD4 count. Methods: In PLWH attending INMI Spallanzani Hospital in Rome, Italy and receiving a BS of BNT162b2 or mRNA-1273 >28 days after a complete mRNA vaccination cycle, immunogenicity was assessed at time of BS (T0) and at day 15 (T1) by anti-RBD CLIA, microneutralization assay [MNA90] and IFNγ production. Participants were stratified by CD4 count at T0 (severe immunodeficiency, SID: <200/mm3;minor immunodeficiency, MID: 200-500/mm3;no immunodeficiency, NID: >500/mm3). Immune response was defined: anti-RBD >7.1 BAU/mL, MNA90 titres >1:10 and IFNγ >12 pg/mL. A paired t-test was used to test overall changes (log2 scale) over T0-T1. ANOVA and truncated regression models were used to compare change in titers from T0 to T1, association between current CD4 count and the lack of immune response was determined by fitting a multivariable logistic regression adjusted for age, time from HIV diagnosis, CD4 nadir, cancer and HIV-RNA a T0. Results: We included 216 PLWH on ART (n=76 SID, n=96 MID, n=44 NID): median age 54 yrs (IQR 47-59), median CD4 nadir 45 cell/mm3 (20-122), 93% HIV-RNA <50 c/mL, 7yrs (3-12) since HIV diagnosis and 5yrs (2-8) since AIDS if diagnosed. Participants received BS after a median of 142 (132-156) days from second dose. Response rate was 95.5% in SID, 100% in MID, 100% in NID for anti-RBD (p=0.02);86.3%, 97.9% and 98.7% for nAbs (p=0.002), and 70%, 95.6% and 97.2% for IFNγ (p<0.0001). Overall we observed a significant increase of BS immunogenicity [anti RBD: mean Log2 4.5 (SD 1.9),p<0.0001;nAbs: 3.7 (2.2),p<0.0001;IFNγ: 0.77 (2.9),p=0.0003]. However, there was no evidence for a difference in mean change of humoral immunogenicity, anti-RBD, nAbs and IFNγ changes by CD4 count groups (Figure 1 A-C). A current CD4 count <200 cell/mm3 was not associated with the risk of failing to elicit neutralizing and cell-mediated response by logistic regression (Figure1D). Conclusion: A mRNA BS strongly boosted humoral response in PLWH with advanced disease, regardless of CD4 count at the time of booster. Although clinical implications of the observed immunological response remain uncertain, our data support the usefulness of BS in PLWH with immune dysregulation.

13.
Topics in Antiviral Medicine ; 30(1 SUPPL):109-110, 2022.
Article in English | EMBASE | ID: covidwho-1880108

ABSTRACT

Background: Waning of vaccine protection against SARS-CoV-2 infection is currently a concern and durability of specific immunity after vaccination in PLWH is still unknown. The aim of this analysis was to evaluate persistence of immune response to mRNA vaccines in PLWH with advanced disease. Methods: PLWH with a CD4 count ≤200/mm3 and/or previous AIDS, enrolled in a SARS-CoV-2 vaccination program at INMI hospital in Rome, Italy, were evaluated >90 days after 2nd dose of BNT162b2 or mRNA-1273 (time T1). Anti-RBD by CLIA, neutralizing antibody (nAb) titers by microneutralization assay (MNA90) and IFNγ production were assessed and response defined as having anti-RBD >7.1 BAU/mL, nAbs ≥1:10, IFNγ >12 pg/mL. Participants were stratified by CD4 count (severe immunodeficiency, SID, ≤200/mm3;minor immunodeficiency, MID, 201-500/mm3;no immunodeficiency, NID, >500/mm3). Waning of immune response was evaluated in a subgroup of responders for whom two values post 2nd dose were available. Paired t-test was used to test the overall decline. ANOVA and logistic regression analysis controlling for age, viral load, CD4 nadir and cancer were used for comparisons by CD4 groups. Results: 221 pts were included (SID=47;MID=98;NID=76);81% male;median age 55 yrs (IQR 49-60);median time from HIV diagnosis 7 yrs (3-15);74% previous AIDS diagnosis;median CD4 nadir 44/mm3 (16-122). All pts receiving ART, 87% with HIV-RNA<50 cp/mL. After a median of 145 (133-157) days after 2nd dose, a detectable anti-RBD response was still present in 83% of SID, 96% of MID and 98% of NID (P=0.0009);nAbs in 38% of SID, 78% of MID and 88% of NID (P<0.0001);IFNγ in 67% of SID, 90% of MID and 92% of NID (P=0.0002). Magnitude of residual immune response at T1 was significantly lower in SID (Figure 1a). By logistic regression, risk of nAbs undetectability was higher in SID (aOR 5.03;95% CI 1.22-20.81) and in MID (aOR 3.77;11.4-12.48) vs NID, while no evidence for a difference was found for anti-RBD and IFNγ. A significant decline of immune response was observed for all immune parameters [mean log2 (SD):-2.66 (1.08), p<0.001, for anti-RBD;-1.23 (1.26), p<0.001, for nAbs;and-0.51 (2.3), p=0.05, for IFNγ], regardless of CD4 groups (Figure 1b/c). Conclusion: A high proportion of PLWH with advanced disease showed a lack of immune response after a median of 5 months from SARS-CoV-2 mRNA vaccination, suggesting an urgent need for a booster dose. A current CD4 ≤200/mm3 was associated with higher risk of vanishing of neutralizing activity.

14.
Topics in Antiviral Medicine ; 30(1 SUPPL):103, 2022.
Article in English | EMBASE | ID: covidwho-1880096

ABSTRACT

Background: Understanding the long-term kinetics of the immune response against SARS-CoV-2 infection is crucial in guiding public health policies and optimizing of vaccination strategies. While it is known that SARS-CoV-2 specific antibodies may persist in adults 12 months after infection, data are lacking in the pediatric population. We herein describe the long-term immune response in children following SARS-CoV-2 infection. Methods: Single-centre, prospective observational study analyzing family clusters of COVID-19 attending the Pediatric Department, University of Padua (Italy). Confirmed COVID-19 infection was defined by positive SARS-CoV-2 PCR and/or IgG serology. All patients with confirmed infection at enrolment underwent serological follow-up at 1-4, 5-10, and >10 months after infection. Plasma was analyzed to quantify anti-SARS-CoV-2 S-RBD IgG, by chemiluminescent immunoassay, performed on MAGLUMI™2000 Plus (Snibe Diagnostics). IgG title >4.3 kBAU/L was considered positive. Results: Among 902 subjects (252 COVID-19 family clusters), 698 had confirmed COVID-19, including 352 children/older siblings aged 8.6 ±5.1 years, and 346 parents aged 42.5 ±7.1 years;of those, 96.5% cases had asymptomatic/mild COVID-19. Children showed significantly higher S-RBD IgG titers than older subjects across all follow-up time points, with an overall mean S-RBD IgG titer <3 years of age five-fold higher than adults (282.3 [139-516.6] kBAU/L vs 56.7 [24.6-136.9] kBAU/L, p<0.001) (Table). The longitudinal analysis of 60 subjects sampled at least twice during follow-up demonstrated the persistence of antibodies up to 10 months from infection in all age classes. Subjects >6 years of age showed a significant progressive decline of the S-RBD IgG titer from the first serological follow-up. While, in younger children antibodies remained stable at 5-10 months of follow-up (p=0.0625), with a subsequent significant decline afterwards (p<0.001). Conclusion: In our unique family cluster cohort, we confirmed the different kinetics of the COVID-19 humoral response across several age groups of asymptomatic/mild COVID-19 cases in our family-cluster cohort. Children presented with higher S-RBD IgG titer at every time point up to 10 months of follow-up. Children less than 3 years demonstrated a more intense long-term resilience of their immune response, which started to decline significantly only after ten months from infection.

15.
Clinical Cancer Research ; 27(6 SUPPL 1), 2021.
Article in English | EMBASE | ID: covidwho-1816883

ABSTRACT

Background The SARS-CoV-2 pandemic has assaulted all aspects of daily life. Medical professionals in oncology face additional challenges with balancing prompt cancer diagnosis and urgent treatment against potential COVID-19 exposure risk in these high-risk patients. We designed this prospective freewill study to offer testing for SAR2-CoV-2 viral RNA and/or anti-COVID-19, respectively in asymptomatic medical and research staff who work in direct contact with cancer patients. The overall goal was to evaluate the prevalence of infection in this group of asymptomatic healthcare providers to reduce exposure of cancer patients to asymptomatic staff. Methods Asymptomatic medical and research staff who work in direct contact with cancer patients were asked to voluntarily be tested for either SARS-CoV-2 viral RNA or antibodies or both. Either NP swabs and/or blood samples (EDTA tube) were collected. Tests are performed at Sinochips Kansas LLC, Sinochips Diagnostics (CLIA number:17D2176068, CAP number: 8709463). The PCR test is performed with FDA authorized 2019-Novel Coronavirus (2019-nCoV) Real-Time RT-PCR Diagnostic Panel EUA. The Elecsys® Anti-SARS-CoV-2 (Roche Diagnostics) immunoassay was used to qualitative detection of antibodies to SARS-CoV-2 in human plasma. Results From 06/18/2020 to 12/18/2020, 861 participated in the study. 1095 tests were completed for SAR2-CoV-2 virus infection, and 918 were completed for antibody. Amount participants, 530 had both virus and antibody tested. 235 were tested more than once for viral infection and 166 were tested more than once for the antibody. Median age of participants was 39 years (IQR 32-51 years). Among these 84.7% were females, 84.4% white, 6.7% African American, 4.8% Asian and 84.7% non-Hispanic. The cumulative incidence of a positive test for the virus was 2.2% (16/712), and for the antibody test was 3.8% (26/679). 5 had both viral and antibody tests positive, with an average time of 4.1 weeks from viral testing positivity to detectable antibody among 3 cases and 2 cases with both viral infection and antibody detected at same time. There were 3 cases virus was detected more than once after turning positive. 2 remained positive at 16 and 22 days after initial test and one turned negative at 36 days as of last follow up. There were 7 cases where the antibody was tested more than once after turning positive and all 7 remained positive as of last follow up (range 7-103 days). Conclusion Prospective voluntary testing in asymptomatic medical and research staff who work in direct contact with cancer patients was feasible and resulted in identification of asymptomatic carriers who then placed in quarantine, thereby limiting exposure to cancer patients. Medical and research staff who work with cancer patients are general very cautious and the frequency of infections were significantly lower than general society. In addition, it seems that 1) virus and antibody may co-exist in the same person after exposure, and 2) the antibody may last for a relatively long time.

16.
Turkish Journal of Biochemistry ; 46(SUPPL 2):85, 2021.
Article in English | EMBASE | ID: covidwho-1770806

ABSTRACT

Laboratory Medicine has been showing its great Value during Covid-19 pandemic in the whole care process: diagnosis, screening, follow up and outcome of the disease. The diagnostic tools to date are able to dose viral RNA, and antibodies against viral proteins or viral proteins themselves. Even if the conventional RT-PCR has been the most widely used method, the greatest innovation in molecular diagnosis was reported by the so called CRISPR Community. The first serological tests to be introduced were rapid serological tests with direct reading (first generation) or with fluorescence reading (2nd generation) and microfluidic with fluorescent reading (3rd generation). Then conventional CLIA method have been introduced with better sensitivity and more recently a new kind of serological assay has been proposed able to detect anti SARS-Cov-2 serum antibodies throughout a competitive streptoavidin/biotin assay which utilize RBD as coated antigen and ACE-2 labelled with biotin as competitor molecule for serum antibodies. Until few months ago the harmonization between many methods produced by many manufacturers was impossible. Recently the WHO produced an international standard (pool of sera-total antibodies) able to permit a sort of harmonization. To date NGS return to be widely utilized in the effort to intercept new variants. Finally, pathophysiology and natural course of Post-acute Sequelae of COVID-19 (PASC) also called Long Covidis unclear, meriting further studies. Also in this almost still unknown field, Clinical Laboratory could contribute in diagnosis and monitoring.

17.
Genetics in Medicine ; 24(3):S331-S332, 2022.
Article in English | EMBASE | ID: covidwho-1768099

ABSTRACT

Introduction: The ACMG has recommended returning clinically relevant results for certain genes when identified in research or as secondary findings in diagnostic testing. Research studies have shown that genomic population screening detects patients with previously unrecognized and often actionable health risks or genetic conditions, with acceptably low levels of harm. Cascade testing of relatives at risk is enabled. Screening for recessive disorder carrier status with gene sequencing panels is common in clinical practice. Preventative screenings routinely occur in primary care settings. The cost of reliably sequencing of many genes in a clinically reliable fashion is approaching levels where offering genomic screening tests may be contemplated for entire populations, and the results used for preventative health purposes, including clinical correlation, early screening, and education. In anticipation of universal genome sequence-based screening, integrated with existing health risk screenings, we piloted a novel implementation of clinical genomic population screening in primary care, mostly family medicine clinics. Screening involved clinical sequencing and reporting of 431 genes where variants are associated with personal health risks or recessive disease carrier status. Methods: Interested primary care providers (PCPs) in two Family Medicine practice systems were invited to participate and given onboarding education. Adult patients with any health status were introduced to The Genomic DNA Test and provided test information by their PCPs in the context of preventative health assessment. Patient education materials included paper, online, and video information, a ‘hotline,’ and optional free genetic counseling. Patients completing a bespoke, health system-approved, written clinical consent provided blood or occasionally saliva samples that were NGS sequenced according to validated procedures in a commercial CLIA-certified genetic testing laboratory. Laboratory reports were returned to the PCP and patient after a local genetics professional added a 1-to-3-page messaging document, the Genomic Medicine Action Plan (GMAP). The PDF-format reports and GMAP were placed in the patient’s electronic health record. Only pathogenic (P) and likely pathogenic (LP) variants were reported. Variant classification was according to Sherloc, the performing laboratory’s system. Patients or providers could request free post-test genetic counseling locally, and the performing lab offered free family member testing and limited-cost partner testing for health risk panel genes and recessive disorder panel genes, respectively. Patients with health risk results were defined as being heterozygous for a P/LP variant for a dominant condition or for a recessive condition where some heterozygotes are symptomatic or co-dominant, hemizygous for a P/LP variant for an X-linked recessive condition, or bi-allelic and plausibly in trans for an autosomal (or X-linked in a female) recessive condition. Many such conditions that are common have reduced or low penetrance, and were characterized as increased risk compared to those not having those variants. When increased risk was identified, the GMAP recommended appropriate medical responses and/or patient education. As part of quality assessment of the pilot, the frequencies of reported results and certain events are monitored. Results: Between November 2019 and October 2021, 186 patients with a median age of 58 years were tested by 20 PCPs at no cost to patients or insurance. Testing volumes declined during the COVID-19 pandemic and when other health system events made high demands on PCPs and their staff. Only 13.3% of patients had no reportable variants in any of the 431 genes. Eighty point nine percent were carriers for at least one recessive disease. The most common recessive genes showing carrier status were HFE, SERPINA1, GALT, CFTR, BTD, F5, DHCR7, PC, GAA, GJB2, PMM2, PAH, and PKHD1. Twenty-six percent had at least one potential health risk result identified, 20% if the common thrombophilias are excluded. The most common category was hereditary cancer risk (7.5%), followed by F5, F2, and SERPINC1 thrombophilia variants (6.5%), hereditary hemochromatosis 1 (HFE) (4.3%), cardiovascular disorders, mostly cardiomyopathies (3.8%), alpha-1-antitrypsin deficiency or other pulmonary disorder (3.8%), familial Mediterranean fever heterozygotes (1.6%), G6PD deficiency (1.1%), and lipid disorder (0.5%). Two patients had health risks in two areas, and two in three areas. Interestingly, BRCA1 and BRCA2 variants were only identified in males. Thirteen patients, about 7%, had an amended report issued during the period. This happened when an unreported variant of uncertain significance was reclassified as LP or P, or when LP became P, and the performing laboratory issued an amended report. Surprisingly few patients took advantage of the free genetic counseling. No patient adverse events were reported by the participating PCPs despite ongoing outreach, nor by patients. Conclusion: Genomic population health screening can be successfully implemented in primary care settings with use of limited but essential genetic professional assistance, after careful planning and input from other medical specialties. A significant proportion of adults not selected for health status harbors germline genetic variants associated with increased health risk. In the absence of a culture where routine genomic screening is expected and where patient genomic competency is high, PCP capacity limits are a barrier to universality. Inclusion of genes for both health risk results with variable degrees of penetrance and for recessive carrier status, and multiple simultaneous results, dictates careful messaging of the implications, while doing so in a primary care setting begs a concise and efficient process. Rates of carrier detection were in-line with predictions based on general population frequencies. Rates of health risk detections were higher than earlier research programs because a larger number of genes with a much broader scope of health risk was included, including disorders with low penetrance yet meaningful clinical relevance and carefully-designed care pathways meant to optimize care while avoiding unnecessary additional testing. We conclude that genomic population health screening of primary care patients where large numbers of genes are clinically sequenced is feasible in a real-world health system, and that value exists for some tested patients now. Research to overcome certain technical limitations of current clinical genomic testing methods and to better stratify risk level in the context of incomplete penetrance should enhance the value of universally-offered genomic population health screening in the future.

18.
Infectious Diseases in Clinical Practice ; 30(3):6, 2022.
Article in English | Web of Science | ID: covidwho-1764690

ABSTRACT

Background There is limited evidence regarding seroprevalence during the first wave of COVID-19 in Thailand. The limited capacity of molecular laboratories in distant provinces may have resulted in fewer confirmed COVID-19 cases and possible undetected ongoing transmission, as suggested by a previously published seroprevalence study. Objectives This study aimed to assess the SARS-CoV-2 IgG and IgM seroprevalence among healthcare personnel and patients in Suddhavej Hospital and cross-reactivity of SARS-CoV-2 antibody assays with infectious and autoimmune diseases. Methods We conducted a cross-sectional study to determine seroprevalence among healthcare personnel and patients in Suddhavej Hospital, a secondary care hospital in Mahasarakham Province (population of 974,534 as of 2015). A chemiluminescence assay was used to test for IgG and/or IgM SARS-CoV-2 antibodies. Results The study included 112 healthcare personnel and 78 patients with a median age of 29 years (interquartile range, 25-40 years);35.8% were male. The study found an IgG seroprevalence of 3 of 190 (1.6%;95% confidence interval, 0.3%-4.5%). The 3 IgG-positive cases recalled possible exposure risk to COVID-19 infection outside the province. One case had a persistent elevated IgG level after 10 months of follow-up. No cross-reactivity was found among patients with a variety of infectious or immunologic diseases. Conclusions Our study suggests that there is a low seroprevalence among high-risk exposure groups. This evidence supports that the preventive measures used during the first wave of COVID-19 were effective in preventing asymptomatic transmission in a remote province with a low COVID-19 incidence rate.

19.
Open Forum Infectious Diseases ; 8(SUPPL 1):S541-S542, 2021.
Article in English | EMBASE | ID: covidwho-1746354

ABSTRACT

Background. New Jersey experienced a 64% decrease in HIV screening during the COVID-19 pandemic, hampering the Federal "End the Epidemic Initiative". From March 2020- May 2021, North Jersey Community Research Initiative, a community-based organization in Newark, NJ, noted a HIV seropositivity of 3.1% despite a decrease of 25% in testing. Qualitative interviews conducted virtually with community individuals and focus groups during that time period indicated that COVID-19 suggested clients were taking more risks due to feelings of isolation, depression and anxiety. NJCRI in collaboration with Robert Wood Johnson Medical School in Somerset, NJ and five other community-based partners in NJ wanted to assess if offering community combination COVID-19 screening and HIV screenings during the pandemic would increase community screening for HIV. Methods. CLIA Waived Screening for COVID-19 from two antigen assays, LumiraDx and BD Veritor was combined with a referenced laboratory based molecular screening from saliva Infinity Biologix under FDA emergency use authorization within CDC guidance with HIV Alere/Determine and INSTI in those individuals that identified as asymptomatic for COVID-19 but with high risk for HIV Results. NJCRI began the COVID-19 and HIV rapid screening to clients on January 4, 2021.Clients tested for COVID-19 (N=274), 3% tested positive for HIV and < 3% are self-reported HIV+ (94% of the sample tested negative for HIV). Overall, 92% of clients tested negative for COVID-19. Clients testing positive for COVID-19 (N=19), there was a 6% positivity rate utilizing COVID-19 Antigen by nasal swab. Those positive via COVID-19 Molecular (N=19) method, results indicate clients also tested positive 6% of the time using a saliva indicator. Approximately, 5% of the study sample are confirmed COVID-19 positives via both testing methods (separately 1% Antigen and < 2% Molecular). 19% of the sample (N=3) tested positive for both HIV and COVID-19. Conclusion. Newly diagnosed patients were treated the same day with antiretroviral therapy;linked to medical care, behavioral health and risk reduction services. Combining COVID-19 and HIV screening in a trusted community-based setting improved delivery of HIV care and linkage to care for newly diagnosed individuals in Newark, NJ.

20.
Molecular Genetics and Metabolism ; 132:S352-S353, 2021.
Article in English | EMBASE | ID: covidwho-1735109

ABSTRACT

Integration of genomics into health practice depends on successful implementation in non-research settings. We describe a medical home-centered implementation at the intersection of genomic medicine and population health in the UVM Health Network. In this clinical implementation, the hospital laboratory orchestrates a collaboration involving primary care providers (PCPs), patient and family advisors, health system administrators, clinical genetics services, oncologists and cardiologists, Vermont’s accountable care organization, and a commercial CLIA genomic testing laboratory. Phenotypically unselected adult primary care patients are offered “The Genomic DNATest” at no cost as part of their regular care. Testing is introduced by primary care providers and their staff using a brief animated video and printed decision aids with graded detail. Question resolution and pre- and post-test genetic counseling is offered at no cost using telephone, video, or in-person visits, and is coordinated bya single phone and email contact point, the Genomic Medicine Resource Center. 431 genes are sequenced for germline health risk and recessive carrier variants;only pathogenic and likely-pathogenic variants are reported. New reports are issued when reported and unreported variants are later reclassified. Test reports are reviewed by a clinical geneticist and genetic counselor. Two brief "action plans" are developed with PCP and patient focus in a single messaging document. This is prepended to the lab reports before release to the PCP, who reviews and then conveys them to the patient. PCPs and their staff receive initial training on the test and process and are invited to participate in an online community with monthly video case discussions. Among the first 72 patients tested, 17% had a health risk identified. This included dominantly inherited disorders and bi-allelic or hemizygous variants for common recessive disorders. Care pathways created in advance using multi-disciplinary expertise were activated for those. Free testing for blood relatives was made available. 76% of tested patients had at least one heterozygous recessive disease variant identified, and low-cost partner testingwas made available. Frequency of positive test results was in line with population frequency predictions. Pre- and post-test genetic counseling uptakewas lower than expected. This raised the question of unmet informational needs. A 2-page anonymous process quality survey mailed twice to the first 61 tested patients had a 31% return rate. Key findings included (1) pre-test engagement methods and decision aids were helpful;(2) the testing decision was influenced equally by value for the individual’s health, for their family’s health, and for researchers;(3) emotions during the ∼4-week time to results were neutral or excited, with none experiencing anxious feelings, and none reported the wait time as too long;(4) 21% reported contacting the Genomic Medicine Resource Center;(5) 16% reported referral to a specialist due to their result;(6) about half reported sharing the results with family members, but none reported any family members getting tested;(7) none indicated they were dissatisfied with the testing and result process, and only one responded they would not recommend others get the test;and (8) all agreed or somewhat agreed that the PCPs officewas the right place to do this testing.While this implementation was designed with scalability and a low management profile in mind, several systems-level barriers were encountered that contributed to lower engagement efforts and slower expansion than planned. This included lack of institutional information technology resources to surmount paper-based systems for requisitions, sample-routing, and consent forms;dependency of the patient engagement process during PCP visits on rooming and nursing staff during times of staffing shortages;susceptibility to practice model disruptions and priorities caused by the Covid-19 pandemic;and PCP time distraction resulting from user interface and polic changes in our EHR during the pilot. These barriers are targets for study and continuous process improvement activities. In summary, an example of clinical genomic population health testing using a medical-home focus has been successfully implemented in a non-research setting, supported by multi-disciplinary collaboration. This implementation depends on minimal staff, avoids financial barriers to access and genetic counseling, and offers a short, defined, test turnaround time as compared to similar biobank-based research programs. Tested patients find the program satisfactory, and meaningful test results are at least as common as in existing population health risk screening archetypes.

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