Are anti-SARS-CoV-2 S/N IgG/IgM antibodies always predictive of previous SARS-CoV-2 infection?

We planned this study to verify whether immunoassays for quantifying anti-SARS-CoV-2 IgG/IgM antibodies against both spike (S) and nucleocapsid (N) proteins may be used for identifying previous SARS-CoV-2 infections. The study population consisted of a cohort of fully vaccinated healthcare workers. All study subjects underwent regular medical visits and molecular testing for diagnosing SARS-CoV-2 infections every 2-4 weeks between 2020-2022. Venous blood was drawn for measuring anti-SARS-CoV-2 antibodies with MAGLUMI 2019-nCoV lgG/IgM CLIA Assays directed against both SARS-CoV-2 S and N proteins. Overall, 31/53 (58.5%) subjects had tested positive for SARS-CoV-2 by RT-PCR throughout the study (24 once, 7 twice). No positive correlation was found between anti-SARS-CoV-2 S/N IgM antibodies and molecular test positivity. In univariate regression analysis, both a molecular test positivity (r=0.33;p=0.015) and the number of positive molecular tests (r=0.43;p=0.001), but not vaccine doses (r=-0.12;p=0.392), were significantly correlated with anti-SARS-CoV-2 S/N IgG antibodies. These two associations remained significant in multiple linear regression analysis (p=0.029 and p<0.001, respectively) after adjusting for sex, age, body mass index, and vaccine doses. In ROC curve analysis, anti-SARS-CoV-2 S/N IgG antibodies significantly predicted molecular test positivity (AUC, 0.69;95% CI;0.55-0.84), with the best cutoff of 0.05 AU/mL displaying 67.9% accuracy, 0.97 sensitivity, and 0.27 specificity. Although anti-SARS-CoV-2 S/N IgG antibodies provide helpful information for identifying previous SARS-CoV-2 infections, a lower cutoff than that of sample reactivity should be used. Anti-SARS-CoV-2 S/N IgM antibodies using conventional cutoffs seem useless for this purpose. © 2023 the author(s), published by De Gruyter, Berlin/Boston.

Could body temperature be used as surrogate measure of mRNA-based vaccination efficacy in the general population?

Predicting the humoral, cellular and clinical response to coronavirus disease 2019 (COVID-19) vaccination remains a central aspect for efficiently tackling the ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Several current studies have focused on predicting the clinical response to COVID-19 vaccination by testing both immunological and cellular biomarkers. Nonetheless, this strategy is plagued by a number of drawbacks, so that a "biological marker" which may help predicting vaccine efficacy, efficiently surrogating laboratory-based tests, would be a valuable resource for optimizing vaccine delivery. A number of recent studies, summarized in this clinical practice review, have repeatedly emphasized the existence of a significant relationship between increased body temperature and humoral response after mRNA-based COVID-19 vaccination. Therefore, we put forward the idea that fever should be no longer considered only an adverse (almost undesirable) post-vaccination side effect, wherein its onset may actually reflect enhanced immunological response to vaccine, and its measurement could hence be used for screening at least mRNA-based vaccine immunogenicity in terms of humoral response up to 3 months after mRNA-based COVID-19 vaccination by using specifically validated algorithms incorporating the integrate assessment of body temperature and anti-SARS-CoV-2 antibodies.Copyright © Journal of Laboratory and Precision Medicine. All rights reserved.

The landscape of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomic mutations

Background: This article is aimed to provide an updated landscape of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomic mutations emerged since its first identification and sequencing. Method(s): We downloaded and analyzed all mutations within the SARS-CoV-2 RNA genome submitted up to February 8, 2022 to the website of the National Center for Biotechnology Information (NCBI), which contains all variants in Sequence Read Archive (SRA) records compared to the prototype SARS-CoV-2 reference sequence NC_045512.2. Result(s): Our search identified 26,005 different mutations. The largest number of mutations was located within the gene encoding for the Nsp3 protein (20.7%), followed by the gene encoding for the spike protein (14.6%). Overall, 17,948/26,005 (69.0%) of these mutations interested single nucleotide positions, thus spanning over ~62% of the entire SARS-CoV-2 genome. Of all mutations, 61.5% were non-synonymous, whilst 17.4% of those in the gene encoding for the spike protein involved the sequence of the receptor binding domain, 59.2% of which were non-synonymous. When the number of mutations was expressed as ratio to the gene size, the highest ratio was found in the sequence encoding for ORF7a (ratio, 2.25), followed by ORF7b (ratio, 1.85), ORF8 (ratio, 1.60) and ORF3a (ratio, 1.48). The gene encoding for RNA-dependent RNA polymerase accounted for only 0.1% of all mutations, with considerably low ratio with the gene size (i.e., ratio, 0.01). Conclusion(s): The results of our analysis demonstrate that SARS-CoV-2 has enormously mutated since its first sequence has been identified over 2 years ago.Copyright © 2022 AME Publishing Company. All rights reserved.

Longitudinal analysis of electrolyte prolife in intensive care COVID-19 patients

Introduction: According to a substantial body of research, electrolyte abnormalities are a common manifestation in coronavirus disease 2019 (COVID-19) patients and are associated with adverse outcomes. This study aimed to investigate electrolyte imbalances in COVID-19 patients and assess their relation to mortality. Method(s): Adult COVID-19 patients hospitalized in the Security Forces Hospital in Saudi Arabia from June 8th till August 18th, 2020 were enrolled in this retrospective observational study. We examined baseline characteristics, comorbidities, acute organ injuries, medications, and electrolyte levels including sodium, potassium, chloride, calcium, bicarbonate, phosphate, and magnesium on ICU admission, as well as every following day of ICU stay, until death or discharge. Patients were stratified according to survival, and differences in variables between groups were compared using Mann-Whitney's U test or Fisher's exact test. Longitudinal electrolyte profiles were modeled using random intercept linear regression models. Result(s): A total of 60 COVID-19 patients were enrolled. Compared to survivors, non-survivors had significantly higher sodium and phosphate on admission and death, higher potassium and magnesium at death, and significantly lower calcium at death. Abnormalities in admission levels of chloride and bicarbonate were also more frequently observed in non-survivors. Furthermore, in the deceased group, we observed a daily increase in potassium and phosphate levels, and a daily decrease in sodium and chloride. Finally, calcium increased in non-survivors over time, however, not as significantly as in the survivor group. Conclusion(s): Admission levels of electrolytes and changes over the course of ICU stay appear to be associated with mortality in COVID-19 patients.Copyright © 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

COVID-19 diagnostics and early phase clinical trials: challenges and risk mitigation in the Omicron variants era

The evolution of the coronavirus disease 2019 (COVID-19) pandemic and widespread community of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variants continues to present new challenges for early phase clinical trials and COVID-19 diagnostic strategies. Many regulatory agencies, including the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) continue to provide updated guidance on the operations of clinical trials during the pandemic. However, guidance is limited with respect to medical and scientific specific issues, such as COVID-19 diagnostics. Here we discuss, the challenges for early phase studies associated with COVID-19 diagnostics in the Omicron era and potential risk mitigation strategies in the face of continued widespread community transmission. We note how careful consideration and planning can help mitigating the risk of COVID-19 impacting the medical and scientific validity and patient safety in clinical trials. Clinical study design should consider mitigation strategies at the patient, investigator, and clinical research organization (CRO)/Sponsor level following evaluation of the overall for their specific study/investigational product and patient overall wellbeing. Specific language regarding COVID-19-related policies and procedures should be included in the study protocol. Special considerations should be taken for novel immunotherapeutics which may require interruption in the event of a subject developing COVID-19 or for investigative products that may have hazardous interactions with commonly prescribed anti-COVID-19 therapies. Moving forward, its essential for trials to remain adaptable to evolving nature of the pandemic. © Journal of Laboratory and Precision Medicine. All rights reserved.

COVID-19 in pregnancy: underestimated risk

The almost relentless worldwide diffusion of severe acute respiratory syndrome coronavirus (SARS-CoV-2) is deeply engaging the minds of many scientists, clinicians and laboratory professionals, who struggle to identify the possible short- and long-term consequences of coronavirus disease 2019 (COVID-19) in the general population, as well as in specific cohorts of individuals, who may display peculiar features of infection. Pregnant women represent one of these categories, since the biological implications of SARS-CoV-2 infection extend far beyond those caused to the mother, involving also the fetus. Several lines of evidence now attest that although mother-to-child SARS-CoV-2 transmission is relatively rare (<2% of all pregnancies), the consequences on maternal-fetal-neonatal interface of COVID-19 can be very serious. To this end, some important questions raise, such as "is COVID-19 a risk factor for complications in pregnancy?", "which laboratory tests are more predictable of unfavorable pregnancy outcomes?", "how efficacious is COVID-19 vaccination in pregnancy?" and, last but not least, "what evidence supports laboratory monitoring of COVID-19 vaccination immunogenicity in pregnancy?". In this opinion paper, we will attempt to provide an overview of the current biological, clinical and laboratory evidence of SARS-CoV-2 infection in pregnancy, trying also to provide reliable answers to the aforementioned questions. Copyright © 2022 Biomedia. All rights reserved.

Humoral response post-BNT162b2 single booster in pre-vaccination baseline SARS-CoV-2 seronegative and seropositive subjects

Background: we report here data on humoral immune response post-BNT162b2 primary vaccination and booster in pre-vaccination baseline severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seronegative and seropositive subjects. Method(s): the study population consisted in 51 baseline SARS-CoV-2 seronegative and 11 baseline SARS-CoV-2 seropositive subjects, who underwent primary mRNA-based BNT162b2 vaccination (two doses) followed by homologous booster administration (third dose). Venous blood was sequentially collected up to 1 months after vaccine booster administration, and humoral response was monitored by measuring anti-SARS-CoV-2 spike trimeric IgG antibodies. Result(s): the humoral response after the three doses of BNT162b2 displayed an overlapping trend in the two groups, although the baseline and post-primary vaccination concentration of anti-SARS-CoV-2 spike trimeric IgG were constantly higher in baseline SARS-CoV-2 seropositive than in baseline SARS-CoV-2 seronegative subjects (all p<0.001). Unlike before vaccine booster administration, the levels of anti-SARS-CoV-2 spike trimeric IgG, 1 month after receiving the third BNT162b2 dose were not significantly different between pre-vaccination baseline SARS-CoV-2 seropositive and seronegative subjects (7 430 versus 9 020 kBAU/L;p=0.232). In both cohorts, all recipients of vaccine booster displayed antibodies levels >264 kBAU/L. Conclusion(s): the results of this study demonstrate that although baseline SARS-CoV-2 seropositive subjects have magnified humoral response to primary BNT162b2 vaccination, vaccine booster generates anti-SARS-CoV-2 spike trimeric IgG values not different from those found in baseline SARS-CoV-2 seronegative subjects. Thus, this study provides evidence that a prior SARS-CoV-2 infection does not mitigate the need for additional vaccine boosters. Copyright © 2022 Biomedia. All rights reserved.

Cardiac biomarkers in COVID-19: a narrative review

The diagnosis and risk stratification of coronavirus disease 2019 (COVID-19) is primarily based on discretionary use of laboratory resources. Several lines of evidence now attest that cardiovascular disease not only is a frequent complication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but its pre-existence may increase the risk of morbidity, disability, and death in patients with COVID-19. To this end, routine assessment of biomarkers of cardiac injury (i.e., cardiac troponin I or T) and dysfunction (e.g., natriuretic peptides) has emerged as an almost essential practice in patients with moderate, severe, and critical COVID-19 illness. Therefore, this narrative review aims to provide an overview of cardiac involvement in patients with SARS-CoV-2 infection as well as the clinical background for including cardiac biomarkers within specific panels of laboratory tests for managing COVID-19 patients. © 2021 International Federation of Clinical Chemistry and Laboratory Medicine. All rights reserved.