Analytical evaluation of the novel Mindray high sensitivity cardiac troponin I immunoassay on CL-1200i.

OBJECTIVES: The current study was designed to evaluate the analytical performance of the new Mindray highly sensitive cardiac troponin I (hs-cTnI) chemiluminescent immunoassay on Mindray CL-1200i, as a thorough validation of novel hs-cTnI methods is required before introduction into clinical practice. METHODS: The evaluation of the analytical performance of this hs-cTnI immunoassay encompassed the calculation of the limit of blank (LOB), limit of detection (LOD), functional sensitivity, imprecision, linearity, 99th percentile upper reference limit (URL) and concordance with another previously validated hs-cTnI chemiluminescent immunoassay. RESULTS: The LOB and LOD were 0.32 and 0.35 ng/L, whilst the functional sensitivity (expressed as cTnI value with <10 % imprecision), was 0.35 ng/L. The linearity was excellent throughout a wide range of clinically measurable values (r=1.00 between 0.8 and 9,726.9 ng/mL). The intra-assay, inter-assay and total imprecision were 1.1-1.3 %, 5.5-8.1 % and 5.6-8.2 %, respectively. The 99th percentile URL calculated using residual plasma from 246 ostensibly healthy blood donors was 9.2 ng/L (4.3 ng/L in women vs. 12.3 ng/L in men). The Spearman's correlation between Mindray hs-cTnI and Access hs-TnI was 0.97, with mean bias of 7.2 % (95 % CI, 2.6-11.9 %). CONCLUSIONS: Although we failed to confirm the very optimistic analytical characteristics previously reported for this method, our evaluation of the novel Mindray hs-cTnI immunoassay on CL-1200i demonstrated that the overall performance is comparable to that of other commercially available hs-cTnI techniques, making it a viable alternative to other methods.

EFLM Task Force Preparation of Labs for Emergencies (TF-PLE) recommendations for reinforcing cyber-security and managing cyber-attacks in medical laboratories.

The healthcare systems are a prime target for cyber-attacks due to the sensitive nature of the information combined with the essential need for continuity of care. Medical laboratories are particularly vulnerable to cyber-attacks for a number of reasons, including the high level of information technology (IT), computerization and digitization. Based on reliable and widespread evidence that medical laboratories may be inadequately prepared for cyber-terrorism, a panel of experts of the Task Force Preparation of Labs for Emergencies (TF-PLE) of the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) has recognized the need to provide some general guidance that could help medical laboratories to be less vulnerable and better prepared for the dramatic circumstance of a disruptive cyber-attack, issuing a number of consensus recommendations, which are summarized and described in this opinion paper.

Red blood cell distribution width (RDW) reflects disease severity in patients with carbon monoxide poisoning: systematic literature review and meta-analysis.

No definitive prognostic biomarkers for carbon monoxide (CO) poisoning have been proposed. The aim of this study is to investigate, through a systematic literature review and pooled analysis, whether red blood cell distribution width (RDW) can predict disease severity in CO-poisoned patients. We performed an electronic search in Scopus and PubMed using the keywords: 'red blood cell distribution width' OR 'RDW' AND 'carbon monoxide' AND 'poisoning,' with no time or language restrictions (i.e. through August 2023) to find clinical studies that examined the value of RDW in patients with varying severity of CO poisoning. The analysis was performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 reporting checklist. We identified 29 articles, seven of which were included in our analysis, with a total of 1979 CO-poisoned patients, 25.9% of whom were severely ill. In all but one of the studies, the RWD mean or median value was higher in CO-poisoned patients with severe disease. The weighted mean difference (WMD) of RDW was 0.36 (95% confidence interval (CI), 0.26-0.47)%. In the three articles in which the severity of illness in CO-poisoned patients was defined as cardiac injury, the WMD of the RDW was 1.26 (95%CI, 1.02-1.50)%. These results suggest that monitoring RDW in CO-poisoned patients may help to determine the severity of disease, particularly cardiac injury.

In silico evaluation of the impact of Omicron variant of concern sublineage BA.4 and BA.5 on the sensitivity of RT-qPCR assays for SARS-CoV-2 detection using whole genome sequencing.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant of concern (VoC) Omicron (B.1.1.529) has rapidly spread around the world, presenting a new threat to global public human health. Due to the large number of mutations accumulated by SARS-CoV-2 Omicron, concerns have emerged over potentially reduced diagnostic accuracy of reverse-transcription polymerase chain reaction (RT-qPCR), the gold standard diagnostic test for diagnosing coronavirus disease 2019 (COVID-19). Thus, we aimed to assess the impact of the currently endemic Omicron sublineages BA.4 and BA.5 on the integrity and sensitivity of RT-qPCR assays used for coronavirus disease 2019 (COVID-19) diagnosis via in silico analysis. We employed whole genome sequencing data and evaluated the potential for false negatives or test failure due to mismatches between primers/probes and the Omicron VoC viral genome. METHODS: In silico sensitivity of 12 RT-qPCR tests (containing 30 primers and probe sets) developed for detection of SARS-CoV-2 reported by the World Health Organization (WHO) or available in the literature, was assessed for specifically detecting SARS-CoV-2 Omicron BA.4 and BA.5 sublineages, obtained after removing redundancy from publicly available genomes from National Center for Biotechnology Information (NCBI) and Global Initiative on Sharing Avian Influenza Data (GISAID) databases. Mismatches between amplicon regions of SARS-CoV-2 Omicron VoC and primers and probe sets were evaluated, and clustering analysis of corresponding amplicon sequences was carried out. RESULTS: From the 1164 representative SARS-CoV-2 Omicron VoC BA.4 sublineage genomes analyzed, a substitution in the first five nucleotides (C to T) of the amplicon's 3'-end was observed in all samples resulting in 0% sensitivity for assays HKUnivRdRp/Hel (mismatch in reverse primer) and CoremCharite N (mismatch in both forward and reverse primers). Due to a mismatch in the forward primer's 5'-end (3-nucleotide substitution, GGG to AAC), the sensitivity of the ChinaCDC N assay was at 0.69%. The 10 nucleotide mismatches in the reverse primer resulted in 0.09% sensitivity for Omicron sublineage BA.4 for Thai N assay. Of the 1926 BA.5 sublineage genomes, HKUnivRdRp/Hel assay also had 0% sensitivity. A sensitivity of 3.06% was observed for the ChinaCDC N assay because of a mismatch in the forward primer's 5'-end (3-nucleotide substitution, GGG to AAC). Similarly, due to the 10 nucleotide mismatches in the reverse primer, the Thai N assay's sensitivity was low at 0.21% for sublineage BA.5. Further, eight assays for BA.4 sublineage retained high sensitivity (more than 97%) and 9 assays for BA.5 sublineage retained more than 99% sensitivity. CONCLUSION: We observed four assays (HKUnivRdRp/Hel, ChinaCDC N, Thai N, CoremCharite N) that could potentially result in false negative results for SARS-CoV-2 Omicron VoCs BA.4 and BA.5 sublineages. Interestingly, CoremCharite N had 0% sensitivity for Omicron Voc BA.4 but 99.53% sensitivity for BA.5. In addition, 66.67% of the assays for BA.4 sublineage and 75% of the assays for BA.5 sublineage retained high sensitivity. Further, amplicon clustering and additional substitution analysis along with sensitivity analysis could be used for the modification and development of RT-qPCR assays for detecting SARS-CoV-2 Omicron VoC sublineages.

An overview of the most important preanalytical factors influencing the clinical performance of SARS-CoV-2 antigen rapid diagnostic tests (Ag-RDTs).

Due to the many technical limitations of molecular biology, the possibility to sustain enormous volumes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) diagnostic testing relies strongly on the use of antigen rapid diagnostic tests (Ag-RDTs). Besides a limited analytical sensitivity, the manually intensive test procedures needed for performing these tests, very often performed by unskilled personnel or by the patients themselves, may contribute to considerably impair their diagnostic accuracy. We provide here an updated overview on the leading preanalytical drawbacks that may impair SARS-CoV-2 Ag-RDT accuracy, and which encompass lower diagnostic sensitivity in certain age groups, in asymptomatic subjects and those with a longer time from symptoms onset, in vaccine recipients, in individuals not appropriately trained to their usage, in those recently using oral or nasal virucidal agents, in oropharyngeal swabs and saliva, as well as in circumstances when instructions provided by the manufacturers are unclear, incomplete or scarcely readable and intelligible. Acknowledging these important preanalytical limitations will lead the way to a better, more clinically efficient and even safer use of this important technology, which represents an extremely valuable resource for management of the ongoing pandemic.

Diagnostic accuracy of Siemens SARS-CoV-2 Antigen (CoV2Ag) chemiluminescent immunoassay for diagnosing acute SARS-CoV-2 infection: a pooled analysis.

BACKGROUND: This article provides a critical literature review and pooled analysis of diagnostic accuracy of the fully-automated Siemens SARS-CoV-2 Antigen (CoV2Ag) chemiluminescent immunoassay for diagnosis of acute SARS-CoV-2 infections. METHODS: An electronic search was conducted in Scopus, PubMed and medRxiv using the keywords ["Siemens AND CoV2Ag"] OR ["Siemens AND SARS-CoV-2 AND antigen"] for capturing studies that investigated the accuracy of Siemens CoV2Ag for diagnosing acute SARS-CoV-2 infection against a reference SARS-CoV-2 molecular test. The retrieved information was used for constructing a 2 × 2 table and for calculating pooled diagnostic sensitivity, specificity, Summary Receiver Operating Characteristic Curve (SROC) and Agreement. This study followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) reporting checklist. RESULTS: Four studies totalling 1,310 respiratory samples (612 with high viral load) were finally included in our analysis. The cumulative area under the curve, accuracy, sensitivity, specificity, were 0.964 (95% CI, 0.957-0.971), 86.9% (95% CI, 84.9-88.7%), 0.79 (95% CI, 0.76-0.82) and 0.98 (95% CI, 0.96-0.99), respectively. The negative (NPV) and positive (PPV) predictive values were 0.77 (0.74-0.79) and 0.98 (95% CI, 0.96-99), respectively. The diagnostic sensitivity in samples with high viral load (i.e., Ct<29-30) was 0.95 (95% CI, 0.93-0.97). CONCLUSIONS: The Siemens CoV2Ag fully-automated and high-throughput immunoassay approximates the minimum performance criteria for general SARS-CoV-2 antigen testing and displays excellent performance in samples with high viral load, thus representing a valuable screening solution for risk assessment in COVID-19 and for limiting viral spread.

Safety monitoring of drug-induced muscle injury and rhabdomyolysis: a biomarker-guided approach for clinical practice and drug trials.

Skeletal muscle tissue (SKM) may be damaged due to mechanical, metabolic, and exertional causes. However, drug-induced myopathy is among the most frequent causes of muscle disease. The clinical picture of drug-induced myopathies may be highly variable. It may present as asymptomatic or mild myalgias, with or without muscle weakness, which are likely underreported. However, it may also appear as chronic myopathy with severe weakness and, rarely, even as massive rhabdomyolysis with acute kidney injury (AKI). Unfortunately, the available biomarkers for SKM injury do not fully meet the needs for satisfactory detection of drug-induced damage, both in clinical and research settings, mainly due to their low sensitivity and specificity. Therefore, the present study proposes a strategy for drug safety monitoring using the available biomarkers of SKM injury. Moreover, we will discuss mechanisms of drug-induced SKM injury, traditional laboratory testing for SKM injury, and novel skeletal myocyte biomarkers under investigation. This can be incredibly useful in both clinical practice and for de-challenge/re-challenge investigational trials where the risk of drug-induced SKM injury is present.

Positivization time of a COVID-19 rapid antigen self-test predicts SARS-CoV-2 viral load: a proof of concept.

OBJECTIVES: This proof of concept study was aimed to validate the hypothesis that the time of positivization of SARS-CoV-2 self-performed rapid diagnostic tests (RDTs) may reflect the actual viral load in the specimen. METHODS: A SARS-CoV-2 positive sample with high viral load was diluted and concomitantly assayed with molecular assay (Xpert Xpress SARS-CoV-2) and RDT (COVID-VIRO ALL IN RDT). The (mean cycle threshold; Ct) values and RDT positivization times of these dilutions were plotted and interpolated by calculating the best fit. The parameters of this equation were then used for converting the positivization times into RDT-estimated SARS-CoV-2 Ct values in routine patient samples. RESULTS: The best fit between measured and RDT-estimated Ct values could be achieved with a 2-degree polynomial curve. The RDT-estimated Ct values exhibited high correlation (r=0.996) and excellent Deming fit (y=1.01 × x - 0.18) with measured Ct values. In 30 consecutive patients with positive RDT test, the correlation between RDT positivization time and measured Ct value was r=0.522 (p=0.003). The correlation of RDT-estimated and measured Ct values slightly improved to 0.577 (Deming fit: y=0.44 × x + 11.08), displaying a negligible bias (1.0; 95% CI, -0.2 to 2.2; p=0.105). Concordance of RDT-estimated and measured Ct values at the <20 cut-off was 80%, with 0.84 sensitivity and 0.73 specificity. CONCLUSIONS: This proof of concept study demonstrates the potential feasibility of using RDTs for garnering information on viral load in patients with acute SARS-CoV-2 infection.

Clinical assessment of SNIBE Maglumi SARS-CoV-2 antigen fully-automated chemiluminescent immunoassay.

OBJECTIVES: Given that SARS-CoV-2 antigen tests will represent a pillar for supporting or surrogating molecular testing in the endemic period, we report here the clinical performance of the new SNIBE Maglumi SARS-CoV-2 antigen fully-automated chemiluminescent immunoassay (MAG-CLIA SARS-CoV-2 Ag). METHODS: The study population consisted of 181 subjects (mean age 61 ± 21 years; 92 females) undergoing coronavirus disease 2019 (COVID-19) testing at the local diagnostic facility, from December 2022 to February 2023. Routine diagnostic practice involved the collection of a double nostril nasopharyngeal swab, analyzed in duplicate with SARS-CoV-2 antigen (MAG-CLIA SARS-CoV-2 Ag) and molecular (Altona Diagnostics RealStar SARS-CoV-2 RT-PCR Kit) tests. RESULTS: A significant Spearman's correlation was found between MAG-CLIA SARS-CoV-2 Ag and mean Ct values of SARS-CoV-2 E and S genes (r=-0.95; p<0.001). In all nasopharyngeal samples, the area under the curve (AUC) of MAG-CLIA SARS-CoV-2 Ag was 0.86 (95% CI, 0.81-0.90), with 0.71 sensitivity and 1.00 specificity at 7 ng/L cut-off, increasing to 0.98 (95% CI, 0.96-1.00) AUC and 0.96 sensitivity (with 0.97 specificity) in high viral load samples. When SARS-CoV-2 N protein concentration was replaced with raw instrumental readings (i.e., relative light units [RLU]), the AUC in all samples increased to 0.94. A RLU value of 945 was associated with 88.4% accuracy, 0.85 sensitivity, 0.95 specificity, 0.77 negative predictive value (NPV) and 0.97 positive predictive value (PPV), respectively. CONCLUSIONS: We found satisfactory analytical performance of MAG-CLIA SARS-CoV-2 Ag, which could be used as surrogate of molecular testing for identifying high viral load samples. Broadening the reportable range of values may generate even better performance.

Deciphering the role of monocyte and monocyte distribution width (MDW) in COVID-19: an updated systematic review and meta-analysis.

The SARS-CoV-2 infection is characterized by both systemic and organ hyper-thromboinflammation, with a clinical course ranging from mild up-to critical systemic dysfunction and death. In patients with coronavirus disease 2019 (COVID-19) the monocyte/macrophage population is deeply involved as both trigger and target, assuming the value of useful diagnostic/prognostic marker of innate cellular immunity. Several studies correlated morphological and immunophenotypic alterations of circulating monocytes with clinical outcomes in COVID-19 patients, concluding that monocyte distribution width (MDW) may retain clinical value in stratifying the risk of disease worsening. Through an electronic search in Medline and Scopus we performed an updated literature review and meta-analysis aimed to explore the association between increased MDW levels and illness severity in COVID-19 patients, deciphering role(s) and function(s) of monocytes in the harmful network underlining SARS-CoV-2 infection. We found that significantly elevated MDW values were frequently present in COVID-19 patients who developed unfavorable clinical outcomes, compounded by a significant association between monocyte anisocytosis and SARS-CoV-2 outcomes. These findings suggest that blood MDW index and its scatter plot could represent useful routine laboratory tools for early identification of patients at higher risk of unfavorable COVID-19 and for monitoring the progression of viral infection, clinical outcomes, and therapeutic efficacy throughout hospitalization. According to this evidence, therapeutic decisions in patients with SARS-CoV-2 infection could benefit from monitoring MDW value, with administration of drugs limiting thrombo-inflammation due to monocyte hyper-activation in patients with severe/critical COVID-19 disease.

Assessment of humoral and cellular immunity after bivalent BNT162b2 vaccination and potential association with reactogenicity.

OBJECTIVES: This study investigated the feasibility and clinical value of using a novel, automated and high-throughput SARS-CoV-2 Interferon Gamma Release Assay (IGRA), combined with total anti-SARS-CoV-2 antibodies assessment, for evaluating the immune response after bivalent BNT162b2 vaccination. METHODS: A cohort of healthcare workers, who already underwent primary vaccination and boosting with monovalent BNT162b2 vaccine, received a booster dose of the new BNT162b2 bivalent formulation. Blood samples were taken immediately before vaccination (T0) and 1 month afterwards (T1). Humoral and cellular immunity were assayed with Roche Elecsys Anti-SARS-CoV-2 and Roche Elecsys IGRA SARS-CoV-2, respectively. RESULTS: The study population consisted of 51 subjects (median age: 43 years; 51% females). Total anti-SARS-CoV-2 antibodies and IGRA SARS-CoV-2 values increased at T1 from 9,050 to 25,000 BAU/mL (p<0.001), and from 0.44 to 0.78 IU/mL (p=0.385), accounting for median increase of 2.0 and 1.6 folds, respectively. Increased T1 values of total anti-SARS-CoV-2 antibodies and IGRA SARS-CoV-2 were recorded in 100% and 68.6% subjects, respectively. In those with baseline values below the median, post-vaccine levels displayed larger increases of 3.3 and 5.1 folds for anti-SARS-CoV-2 total antibodies and IGRA SARS-CoV-2, respectively. The variation of total anti-SARS-CoV-2 antibodies was inversely associated with their T0 values (r=-0.97; p<0.001), whilst that of IGRA SARS-CoV-2 was inversely associated with its T0 value (r=-0.58; p<0.001). No other signifcant associations were found with demographical or clinical variables, including side effects. CONCLUSIONS: The bivalent BNT162b2 vaccine booster enhances humoral and cellular immunity against SARS-CoV-2, especially in recipients with lower baseline biological protection.

Estimating the worldwide burden of health loss due to hearing loss.

We planned this study to define the worldwide burden of health loss attributed to hearing impairment occurred during the past 10 years according to the 2019 Global Health Data Exchange (GHDx) database. The current worldwide burden of health loss due to all forms of hearing impairment is estimated at 43.4 million Years Lived with Disability (YLDs), representing 28% of cumulative YLDs due to all physical impairments in GHDx. The hearing loss-attributable YLDs have linearly increased (r = 0.997; P < 0.01) by 18.7% during the past 10 years. Reinforced policies are hence needed for preventing development of mild hearing impairment and/or progression toward more severe deficiencies.

Topographic anatomy of the submental artery and its clinical implications for reconstructive surgery.

Knowledge about the anatomy of the submental artery (SA) is of immense importance when performing plastic and reconstructive procedures. A retrospective study was performed to analyze the topographic anatomy of the SA. The measurements were performed on 80 consecutive patients who underwent head and neck computed tomography angiography (CTA). The SA was present in 131 out of 137 hemifaces (95.6%). The vessel originated from the facial artery in all cases (100.0%). Moreover, the SA was found to have 0-4 branches. However, most commonly, the said artery had no branches of considerable size (51.1%). Due to the high variability of the course of the said artery, the authors of the present study created a novel classification system presenting the most prevalent courses of the SA in the submental region. The current study utilized 131 hemifaces of 80 (CTA) to create a heat map of the SA, illustrating its precise origin and course in the submental region. The findings of this study could assist surgeons in developing a mental map of the arterial anatomy of the submental region, potentially improving the efficiency of localizing the SA and reducing the risk of complications during plastic and reconstructive procedures.

Coronavirus disease 2019, hypertension, and renin-angiotensin-aldosterone system inhibitors.

PURPOSE OF REVIEW: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mostly uses the angiotensin-converting enzyme 2 (ACE-2) as cellular receptor for entering the host cells. Some, but not all, animal studies have shown that renin-angiotensin-aldosterone system (RAAS) inhibitors can increase ACE-2 expression. On that premise, it was hypothesized that these agents could make it more likely to develop coronavirus disease 2019 (COVID-19). On the other hand, there was also evidence that being on these agents could lessen the severity of the lung injury in patients with severe SARS-CoV-2 infection. Herein, we review the available evidence on the role of RAAS inhibitors on SARS-CoV-2 and COVID-19 development. RECENT FINDINGS: Recent randomized controlled trials demonstrate that RAAS blockade or withdrawal does not influence the severity of COVID-19 in patients who are already on these medications. Currently, there is no evidence to support stopping RAAS inhibitors in patients hospitalized for COVID-19. Several questions still need to be addressed. Ongoing studies are currently evaluating the de novo use of RAAS inhibitors in patients with COVID-19. Another area that needs to be investigated is whether or not using these medications increase the risk of infection. SUMMARY: The wealth of evidence indicates that ACE inhibitors and angiotensin-receptor blocker administration has no harmful effects on hospitalizations and severity of COVID-19 in patients already on these medications and might even reduce mortality among hypertensive patients diagnosed with COVID-19. More evidence and data need to be collected, and at this time, these agents should not be discontinued.

Diagnostic performance of the fully automated Roche Elecsys SARS-CoV-2 antigen electrochemiluminescence immunoassay: a pooled analysis.

OBJECTIVES: Among the diagnostic tests that have recently become commercially available for diagnosing coronavirus disease 2019 (COVID-19), the fully-automated Roche Elecsys severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen electrochemiluminescence immunoassay (ECLIA) is one of the most widespread for its adaptability within a system of laboratory automation, rapidity and high-throughput. This article is aimed to provide the results of the first pooled analysis of its accuracy for diagnosing SARS-CoV-2 infections. CONTENT: We carried out an electronic search in Scopus and Medline, without language or date restrictions (i.e., up to January 18, 2022), to identify articles where the diagnostic performance of Roche Elecsys SARS-CoV-2 antigen ECLIA was compared with that of reference molecular diagnostic techniques. SUMMARY: Overall, 11 studies were identified, 10 of which (n=6,095 swabs) provided necessary data for inclusion in a pooled analysis. The pooled diagnostic sensitivity, specificity and area under the curve (AUC) in nasopharyngeal samples were 0.68 (95%CI, 0.66-0.70), 0.99 (95%CI, 0.99-0.99) and 0.958 (95%CI, 0.936-0.980), respectively. The cumulative observed agreement with reference molecular assays was 89.5% and the kappa statistic was 0.735 (95%CI, 0.716-0.754). The pooled diagnostic sensitivity in samples with high viral load (i.e., cycle threshold values <28-30) was 0.95 (95%CI, 0.92-0.97). OUTLOOK: The results of this pooled analysis confirm that the fully-automated Roche Elecsys SARS-CoV-2 antigen ECLIA has high diagnostic specificity and optimal diagnostic sensitivity for identifying nasopharyngeal samples with higher viral load, thus making it a reliable technique for mass screening and for supporting strategies based on shorten isolation and/or quarantine.

Artificial intelligence at the time of COVID-19: who does the lion's share?

OBJECTIVES: The development and use of artificial intelligence (AI) methodologies, especially machine learning (ML) and deep learning (DL), have been considerably fostered during the ongoing coronavirus disease 2019 (COVID-19) pandemic. Several models and algorithms have been developed and applied for both identifying COVID-19 cases and for assessing and predicting the risk of developing unfavourable outcomes. Our aim was to summarize how AI is being currently applied to COVID-19. METHODS: We conducted a PubMed search using as query MeSH major terms "Artificial Intelligence" AND "COVID-19", searching for articles published until December 31, 2021, which explored the possible role of AI in COVID-19. The dataset origin (internal dataset or public datasets available online) and data used for training and testing the proposed ML/DL model(s) were retrieved. RESULTS: Our analysis finally identified 292 articles in PubMed. These studies displayed large heterogeneity in terms of imaging test, laboratory parameters and clinical-demographic data included. Most models were based on imaging data, in particular CT scans or chest X-rays images. C-Reactive protein, leukocyte count, creatinine, lactate dehydrogenase, lymphocytes and platelets counts were found to be the laboratory biomarkers most frequently included in COVID-19 related AI models. CONCLUSIONS: The lion's share of AI applied to COVID-19 seems to be played by diagnostic imaging. However, AI in laboratory medicine is also gaining momentum, especially with digital tools characterized by low cost and widespread applicability.

What is the impact of circulating histones in COVID-19: a systematic review.

The infectious respiratory condition COVID-19 manifests a clinical course ranging from mild/moderate up-to critical systemic dysfunction and death linked to thromboinflammation. During COVID-19 infection, neutrophil extracellular traps participating in cytokine storm and coagulation dysfunction have emerged as diagnostic/prognostic markers. The characterization of NET identified that mainly histones, have the potential to initiate and propagate inflammatory storm and thrombosis, leading to increased disease severity and decreased patient survival. Baseline assessment and serial monitoring of blood histone concentration may be conceivably useful in COVID-19. We performed a literature review to explore the association among increased circulating levels of histones, disease severity/mortality in COVID-19 patients, and comparison of histone values between COVID-19 and non-COVID-19 patients. We carried out an electronic search in Medline and Scopus, using the keywords "COVID-19" OR "SARS-CoV-2" AND "histone" OR "citrullinated histones" OR "hyperhistonemia", between 2019 and present time (i.e., June 07th, 2022), which allowed to select 17 studies, totaling 1,846 subjects. We found that substantially elevated histone values were consistently present in all COVID-19 patients who developed unfavorable clinical outcomes. These findings suggest that blood histone monitoring upon admission and throughout hospitalization may be useful for early identification of higher risk of unfavorable COVID-19 progression. Therapeutic decisions in patients with SARS-CoV-2 based on the use of histone cut-off values may be driven by drugs engaging histones, finally leading to the limitation of cytotoxic, inflammatory, and thrombotic effects of circulating histones in viral sepsis.

Ad interim recommendations for diagnosing SARS-CoV-2 infection by the IFCC SARS-CoV-2 variants working group.

This document, endorsed by the IFCC Working Group on SARS-CoV-2 Variants, aims to update previous indications for diagnosing acute SARS-CoV-2 infection, taking into consideration the evidence that has emerged after the origin and spread of new lineages and sub-lineages of the virus characterized by mutated genetics and altered biochemical, biological and clinical characteristics. These indications encompass the use of different diagnostic strategies in specific clinical settings, such as high risk of SARS-CoV-2 infection (symptomatic patients), low risk of SARS-CoV-2 infection (asymptomatic subjects) at hospital admission/contact tracing, testing in asymptomatic subjects, in epidemiologic surveys and/or population screening, along with tentative indications for identification of new lineages and/or sub-lineages of SARS-CoV-2.

Effect of BNT162b2 booster dose on anti-SARS-CoV-2 spike trimeric IgG antibodies in seronegative individuals.

OBJECTIVES: We provide here an updated analysis of an ongoing serosurveillance study, presenting data on the effect of a third dose of Pfizer/BioNTech BNT162b2 vaccine on serum anti-SARS-CoV-2 IgG antibodies. METHODS: We tested baseline SARS-CoV-2 seronegative healthcare workers undergoing primary vaccination with the mRNA-based COVID-19 Comirnaty vaccine, followed by administration of homologous vaccine booster (third dose). Venous blood was collected before either dose of primary vaccination, at 1, 3 and 6 months afterwards, as well as before and 1 month after receiving the vaccine booster. The serum concentration of anti-SARS-CoV-2 IgG was assayed with DiaSorin Trimeric spike IgG immunoassay. RESULTS: The final study population included 53 SARS-CoV-2 seronegative healthcare workers (median age 46 years; 60% females). A first peak of anti-SARS-CoV-2 spike trimeric IgG values was reached 1 month after completing primary vaccination, after which the levels gradually declined until before receiving the vaccine booster. A second peak of anti-SARS-CoV-2 spike trimeric IgG concentration was observed 1 month after receiving the vaccine booster dose (8,700 kBAU/L), which was 39-fold higher than before receiving the vaccine booster (221 kBAU/L; p<0.001), but was also nearly threefold higher compared to values seen at the first peak (2,990 kBAU/L; p<0.001). The rate of subjects with protective anti-SARS-CoV-2 spike trimeric IgG values (i.e., >264 kBAU/L) increased from 47.2% to 100% after 1 month from vaccine booster. CONCLUSIONS: These results support current policies fostering COVID-19 vaccine boosters to reinforce humoral immunity against SARS-CoV-2.

Blood lactate concentration in COVID-19: a systematic literature review.

Coronavirus disease 2019 (COVID-19) is an infectious respiratory condition sustained by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which manifests prevalently as mild to moderate respiratory tract infection. Nevertheless, in a number of cases the clinical course may deteriorate, with onset of end organ injury, systemic dysfunction, thrombosis and ischemia. Given the clinical picture, baseline assessment and serial monitoring of blood lactate concentration may be conceivably useful in COVID-19. We hence performed a systematic literature review to explore the possible association between increased blood lactate levels, disease severity and mortality in COVID-19 patients, including comparison of lactate values between COVID-19 and non-COVID-19 patients. We carried out an electronic search in Medline and Scopus, using the keywords "COVID-19" OR "SARS-CoV-2" AND "lactate" OR "lactic acid" OR "hyperlactatemia", between 2019 and present time (i.e. October 10, 2021), which allowed to identify 19 studies, totalling 6,459 patients. Overall, we found that COVID-19 patients with worse outcome tend to display higher lactate values than those with better outcome, although most COVID-19 patients in the studies included in our analysis did not have sustained baseline hyperlactatemia. Substantially elevated lactate values were neither consistently present in all COVID-19 patients who developed unfavourable clinical outcomes. These findings suggest that blood lactate monitoring upon admission and throughout hospitalization may be useful for early identification of higher risk of unfavourable COVID-19 illness progression, though therapeutic decisions based on using conventional hyperlactatemia cut-off values (i.e., 2.0 mmol/L) upon first evaluation may be inappropriate in patients with SARS-CoV-2 infection.