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.

Personal protective equipment use among dental healthcare personnel during the coronavirus disease 2019 (COVID-19) pandemic and the impact of an educational video in clinical practice.

OBJECTIVE: Dental healthcare personnel (DHCP) are at high risk of exposure to coronavirus disease 2019 (COVID-19). We sought to identify how DHCP changed their use of personal protective equipment (PPE) as a result of the COVID-19 pandemic, and to pilot an educational video designed to improve knowledge of proper PPE use. DESIGN: The study comprised 2 sets of semistructured qualitative interviews. SETTING: The study was conducted in 8 dental clinics in a Midwestern metropolitan area. PARTICIPANTS: In total, 70 DHCP participated in the first set of interviews; 63 DHCP participated in the second set of interviews. METHODS: In September-November 2020 and March-October 2021, we conducted 2 sets of semistructured interviews: (1) PPE use in the dental community during COVID-19, and (2) feedback on the utility of an educational donning and doffing video. RESULTS: Overall, 86% of DHCP reported having prior training. DHCP increased the use of PPE during COVID-19, specifically N95 respirators and face shields. DHCP reported real-world challenges to applying infection control methods, often resulting in PPE modification and reuse. DHCP reported double masking and sterilization methods to extend N95 respirator use. Additional challenges to PPE included shortages, comfort or discomfort, and compatibility with specialty dental equipment. DHCP found the educational video helpful and relevant to clinical practice. Fewer than half of DHCP reported exposure to a similar video. CONCLUSIONS: DHCP experienced significant challenges related to PPE access and routine use in dental clinics during the COVID-19 pandemic. An educational video improved awareness and uptake of appropriate PPE use among DHCP.

Improving the effectiveness of Field Epidemiology Training Programs: characteristics that facilitated effective response to the COVID-19 pandemic in Uganda.

BACKGROUND: The global need for well-trained field epidemiologists has been underscored in the last decade in multiple pandemics, the most recent being COVID-19. Field Epidemiology Training Programs (FETPs) are in-service training programs that improve country capacities to respond to public health emergencies across different levels of the health system. Best practices for FETP implementation have been described previously. The Uganda Public Health Fellowship Program (PHFP), or Advanced-FETP in Uganda, is a two-year fellowship in field epidemiology funded by the U.S. Centers for Disease Control and situated in the Uganda National Institute of Public Health (UNIPH). We describe how specific attributes of the Uganda PHFP that are aligned with best practices enabled substantial contributions to the COVID-19 response in Uganda. METHODS: We describe the PHFP in Uganda and review examples of how specific program characteristics facilitate integration with Ministry of Health needs and foster a strong response, using COVID-19 pandemic response activities as examples. We describe PHFP activities and outputs before and during the COVID-19 response and offer expert opinions about the impact of the program set-up on these outputs. RESULTS: Unlike nearly all other Advanced FETPs in Africa, PHFP is delinked from an academic degree-granting program and enrolls only post-Master's-degree fellows. This enables full-time, uninterrupted commitment of academically-trained fellows to public health response. Uganda's PHFP has strong partner support in country, sufficient technical support from program staff, Ministry of Health (MoH), CDC, and partners, and full-time dedicated directorship from a well-respected MoH staff member. The PHFP is physically co-located inside the UNIPH with the emergency operations center (EOC), which provides a direct path for health alerts to be investigated by fellows. It has recognized value within the MoH, which integrates graduates into key MoH and partner positions. During February 2020-September 2021, PHFP fellows and graduates completed 67 major COVID-related projects. PHFP activities during the COVID-19 response were specifically requested by the MoH or by partners, or generated de novo by the program, and were supervised by all partners. CONCLUSION: Specific attributes of the PHFP enable effective service to the Ministry of Health in Uganda. Among the most important is the enrollment of post-graduate fellows, which leads to a high level of utilization of the program fellows by the Ministry of Health to fulfill real-time needs. Strong leadership and sufficient technical support permitted meaningful program outputs during COVID-19 pandemic response. Ensuring the inclusion of similar characteristics when implementing FETPs elsewhere may allow them to achieve a high level of impact.

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.

Assessment of dental health care personnel protocol deviations and self-contamination during personal protective equipment donning and doffing.

BACKGROUND: Dental health care personnel (DHCP) may be at increased risk of exposure to severe acute respiratory syndrome coronavirus 2, the virus that causes COVID-19, as well as other clinically important pathogens. Proper use of personal protective equipment (PPE) reduces occupational exposure to pathogens. The authors performed an assessment of PPE donning and doffing practices among DHCP, using a fluorescent marker as a surrogate for pathogen transmission. METHODS: Participants donned PPE (that is, disposable gown, gloves, face mask, and eye protection) and the fluorescent marker was applied to their palms and abdomen. DHCP then doffed PPE according to their usual practices. The donning and doffing processes were video recorded, areas of fluorescence were noted, and protocol deviations were assessed. Statistical analyses included frequency, type, and descriptions of protocol deviations and factors associated with fluorescence. RESULTS: Seventy DHCP were enrolled. The donning and doffing steps with the highest frequency of protocol deviations were hand hygiene (66% of donning and 78% of doffing observations involved a deviation) and disposable gown use (63% of donning and 60% of doffing observations involved a deviation). Fluorescence was detected on 69% of DHCP after doffing, most frequently on hands. An increasing number of protocol deviations was significantly associated with increased risk of fluorescence. DHCP with a gown doffing deviation, excluding doffing out of order, were more likely to have fluorescence detected. CONCLUSIONS: DHCP self-contamination was common with both donning and doffing PPE. PRACTICAL IMPLICATIONS: Proper use of PPE is an important component of occupational health.

Tourfor Diversity in Medicine & Pediatric Mentoring Circles: Bringing Pediatric Advising and Mentoring of Premedical Students to the Virtual World

Background: To strengthen the pathways for diverse applicants to health professional school, we need to rethink traditional strategies for providing outreach as current measures haven't met the growing needs. The Tour for Diversity in Medicine (T4D) was established as a grassroots effort to mediate pipeline leakiness through a mission to educate, inspire, and cultivate future health professionals of diverse racial and ethnic background. Coronavirus, though, changed the landscape of engaging with students. In April 2020, T4D conducted new virtual sessions beginning with Instagram live interview sessions. This progressed to a virtual mentorship conference, #VirtualT4D, which engaged with >1300 viewers over four days, including high school, undergraduate, and medical students from diverse backgrounds across the globe. To strengthen the pediatrician pipeline, T4D adapted its model to provide pediatric careerspecific mentorship virtually through the Pediatric Mentoring Circles (PMC) to trainees considered underrepresented in medicine and students from backgrounds considered disadvantaged. Methods: Student recruitment was conducted through T4D social media channels (Twitter, Instagram). This targeted premedical students from high school through postbaccalaureate level. Faculty included six pediatrician mentors from T4D, representing various training levels from residency to junior faculty with different specialty backgrounds. Monthly sessions were conducted from September-December 2020. Grant funding was obtained through the American Association of Pediatrics “Pediatric Pipeline Innovation Program” mechanism. Results: Fifty-five students were selected and divided into groups with the six T4D faculty mentors. Students represented 16 states with >90% representing underrepresented racial/ ethnic backgrounds. Importantly, 42% of students never previously attended a pipeline program, 65% are first generation college students, 75% will be the first healthcare worker in their family, and 100% would be the first physician in their family. Five topic areas were addressed (applying to medical school, goal setting and network development, pediatrics career opportunities, pediatrics leadership, and the impact of racism on child and adolescent health) through workshops utilizing different learning modalities. Students were provided pre and post workshop learning articles and tools for further developing their professional identity formation, through goal setting, network mapping, and personal reflections. Conclusion: T4D PMC increased exposure to pediatrics through a unique virtual model with scaffolded sessions based on the students' education level and a supportive environment to foster professional identity formation through pediatric-focused mentorship. Additionally, PMC provided introductory knowledge and skills for students regarding the medical school/ residency application process. Students appreciated the virtual model as it gave them a national tiered network of peers and mentors. Mentors empowered students to continue their journeys to pediatrics by embracing shared experiences through stories about successes and hardships. Next steps include long-term evaluation of student outcomes and partnering with organizations such as Association of Pediatric Program Directors as the next planned cohort targets medical students from diverse backgrounds.