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Approximately 15%-20% of patients infected with SARS-CoV-2 coronavirus (COVID-19) progress beyond mild and self-limited disease to require supplemental oxygen for severe pneumonia; 5% of COVID-19-infected patients further develop acute respiratory distress syndrome (ARDS) and multiorgan failure. Despite mortality rates surpassing 40%, key insights into COVID-19-induced ARDS pathology have not been fully elucidated and multiple unmet needs remain. This review focuses on the unmet need for effective therapies that target unchecked innate immunity-driven inflammation which drives unchecked vascular permeability, multiorgan dysfunction and ARDS mortality. Additional unmet needs including the lack of insights into factors predicting pathogenic hyperinflammatory viral host responses, limited approaches to address the vast disease heterogeneity in ARDS, and the absence of clinically-useful ARDS biomarkers. We review unmet needs persisting in COVID-19-induced ARDS in the context of the potential role for damage-associated molecular pattern proteins in lung and systemic hyperinflammatory host responses to SARS-CoV-2 infection that ultimately drive multiorgan dysfunction and ARDS mortality. Insights into promising stratification-enhancing, biomarker-based strategies in COVID-19 and non-COVID ARDS may enable the design of successful clinical trials of promising therapies.

Coronavirus disease 2019 (COVID-19), caused by an infection with the novel coronavirus SARS-CoV-2, has resulted in a global pandemic and poses an emergency to public health systems worldwide. COVID-19 is highly infectious and is characterized by an acute respiratory illness that varies from mild flu-like symptoms to the life-threatening acute respiratory distress syndrome (ARDS). As such, there is an urgent need for the development of new therapeutic strategies, which combat the high mortality in severely ill COVID-19 patients. Glucocorticoids are a frontline treatment for a diverse range of inflammatory diseases. Due to their immunosuppressive functions, the use of glucocorticoids in the treatment of COVID-19 patients was initially regarded with caution. However, recent studies concluded that the initiation of systemic glucocorticoids in patients suffering from severe and critical COVID-19 is associated with lower mortality. Herein we review the anti-inflammatory effects of glucocorticoids and discuss emerging issues in their clinical use in the context of COVID-19.

Background Geriatric patients with coronavirus disease (COVID‐19) are at high risk of developing cardiac injury. Identifying the factors that affect high‐sensitivity cardiac troponin I may indicate the cause of cardiac injury in elderly patients, and this could hopefully assist in protecting heart function in this patient population. Methods One hundred and eighty inpatients who were admitted for COVID‐19 were screened. Patients older than 60 years were included in this study, and the clinical characteristics and laboratory results of the cohort were analyzed. The correlation between cardiac injury and clinical/laboratory variables was statistically analyzed, and further logistic regression was performed to determine how these variables influence cardiac injury in geriatric patients. Results Age (p, Our study explored potential risk factors related to cardiac injury in elderly patients with COVID‐19. The results suggest that age and inflammatory factors influence cardiac injury in elderly patients. Interfering with inflammation in this patient population may potentially confer cardiac protection.

Objective To explore the clinical value of serum IgM and IgG to SARS‐CoV‐2 in COVID‐19. Methods 105 COVID‐19 patients were enrolled as the disease group. 197 non‐COVID‐19 patients served as the control group. Magnetic chemiluminescent immunoassay (MCLIA) was used to detect the IgM and IgG. Results The peak of positive rates of SARS‐CoV‐2 IgM was about 1 week earlier than that of IgG. It reached to peak within 15–21 days and then began a slowly decline. The positive rates of IgG were increased with the disease course and reached the peak between 22 and 39 days. The differences in sensitivity of the three detection modes (IgM, IgG, and IgM + IgG) were statistically significant. The largest group of test cases (illness onset 15–21 days) showed that the positive rate of IgG was higher than IgM. Also, the sensitivity of IgM combined with IgG was higher than IgM or IgG. IgM and IgG were monitored dynamically for 16 patients with COVID‐19, the results showed that serological transformation of IgM was carried out simultaneously with IgG in seven patients, which was earlier than IgG in four patients and later than IgG in five patients. Conclusion The detection of SARS‐CoV‐2 IgM and IgG is very important to determine the course of COVID‐19. Nucleic acid detection combined with serum antibody of SARS‐CoV‐2 may be the best laboratory indicator for the diagnosis of SARS‐CoV‐2 infection and the phrase and predication for prognosis of COVID‐19., Antibody response to SARS‐CoV‐2 in 105 COVID‐19 patients. (A) The positive rate of SARS‐CoV‐2 antibody in 105 patients. (B) The changes of antibody titers to SARS‐CoV‐2 in 105 patients.

Background The emergence and rapid spread of the deadly novel coronavirus disease caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is a swiftly evolving public health crisis worldwide. SARS‐CoV‐2 infection is characterized by the development and progression of inflammatory responses. Hematological parameters, such as white blood cells (WBCs) and their subpopulations, red cell distribution width, platelet count, mean platelet volume, plateletcrit, and derived markers such as neutrophil‐to‐lymphocyte ratio (NLR), platelet‐to‐lymphocyte ratio (PLR), and lymphocyte‐to‐monocyte ratio, are established biomarkers of inflammatory responses. We aimed to investigate associations between hematological parameters and disease severity in patients with SARS‐CoV‐2 infection. Methods We retrospectively analyzed data from 68 patients with confirmed SARS‐CoV‐2 infection. Twenty‐two patients had mild illness, and 46 had moderate or severe illness at the time of admission. Univariate and multivariate regression analyses were used to identify correlates of disease severity. The areas under receiver operating characteristic curves were calculated to estimate and compare the predictive values of different diagnostic markers. Results Mean lymphocyte and monocyte counts were lower while WBC counts, neutrophil counts, NLR, and PLR were higher in patients with severe disease compared with those with mild disease (all P, ROC curves showing the relative diagnostic performance of age and hematological parameters for prediction of disease severity in patients with SARS‐CoV‐2 infection. Abbreviations: WBC, white blood cell; NLR, neutrophil‐to‐lymphocyte ratio; PLR, platelet‐to‐lymphocyte ratio; LMR, lymphocyte‐to‐monocyte ratio; PSI, Pneumonia Severity Index.

Le champ de l’épidémiologie mathématique a connu, au cours de la pandémie de Covid-19, une production doublée d’une médiatisation exceptionnelle de ses travaux. Alors même que les données et les connaissances sur la maladie émergente étaient parcellaires, une grande diversité de modèles a été développée et appliquée dans des délais inédits, dans l’objectif d’estimer le nombre de reproduction, la date de début de l’épidémie ou l’incidence cumulée, mais aussi afin d’explorer différents scénarios d’interventions non pharmaceutiques. Leurs résultats ont largement contribué à l’épidémiosurveillance et éclairé la prise de décisions relatives aux politiques de santé publique.

Highlights • Saliva is an eligible matrix for SARS-CoV-2 molecular detection and IgA measurement. • Saliva collection offers several advantages: safe, non-invasive and self-collection. • Positive molecular testing results were associated with disease duration. • The presence of salivary IgA was associated with pneumonia and CRP values., Aim This study aims to verify whether standardized saliva collection is suitable for SARS-CoV-2 molecular detection and IgA measurement. Methods 43 COVID-19 inpatients and 326 screening subjects underwent naso-pharyngeal (NP)-swab and saliva collection (Salivette). Inpatients also underwent repeated blood collections to evaluate inflammation and organs involvement. In all patients and subjects, SARS-CoV-2 (gene E) rRT-PCR was undertaken in saliva and NP-swabs. Salivary IgA and serum IgA, IgG, IgM were measured on inpatients’ samples. Results NP-swabs and saliva were both SARS-CoV-2 positive in 7 (16%) or both negative in 35 (82%) out of 43 patients successfully included in the study. NP-swabs and saliva results did not perfectly match in one patient (saliva positive, NP-swab negative). Positive molecular results were significantly associated with disease duration (p = 0.0049). 326/326 screening subjects were SARS-CoV-2 negative on both NP-swabs and saliva. Among the 27 saliva samples tested for IgA, 18 were IgA positive. Salivary IgA positivity was associated with pneumonia (p = 0.002) and CRP values (p = 0.0183), not with other clinical and molecular data, or with serum immunoglubulins. Conclusions A standardized saliva collection can be adopted to detect SARS-CoV-2 infection in alternative to NP-swabs. Preliminary data on salivary IgA support the use of saliva also for patient monitoring.

This essay aims to discuss some aspects of blood transfusion in the perspective of the changes that occurred over time as well as modifications of the paradigms that transformed the activities and the organization of blood transfusion services. Without specific knowledge, pioneers envisioned precision and personalized medicine, rendering transfusion medicine operational. Transfusion medicine is like The Picture of Dorian Grey: always young despite being old and sometimes appearing old-fashioned. Over the years, the transfusion medicine discipline has evolved, and major progress has been achieved, despite some troublesome periods (for example, the tainted blood scandal, and-at the time being-the offending plasma market and the selling of human parts). Transfusion medicine has at all times implemented the rapidly developing biomedical technologies to secure blood components. The safety of blood components has now reached an exceptional level in economically wealthy countries, especially compared to other health care disciplines. Strengthening of the safety has mandated that blood donors and recipients are unrelated, an issue which has eased preservation and fractionation practices; blood is no longer arm-to-arm transfused and neither is whole blood, the commonest component. However, it is interesting to note that a revival is occurring as whole blood is back on stage for certain specific indications, which is one among the many paradoxes encountered while studying this discipline.

Highlights • We evaluated the Ansh Laboratories SARS-CoV-2 IgG and SARS-CoV-2 IgM ELISA semi-quantitative immunoassays as part of an orthogonal testing algorithm recommended by the CDC. • The IgG and IgM ELISA assays showed acceptable precision, were robust to analytical interference and did not exhibit cross reactivity with specimens positive for common respiratory viruses. Both assays exhibited 95% agreement with a primary screening serological assay utilized at our institution as well as with a reference laboratory semi-quantitative method. Concordance with RT-PCR was excellent >6 days after symptom onset (100%)., Background While the diagnosis of SARS-CoV-2 infection is primarily based on detection of viral RNA, the detection of SARS-CoV-2 antibodies is useful for assessing past prevalence of the disease, and in corroborating a current infection in challenging cases. Sensitive and specific immunoassays provide the ability to identify exposure to SARS-CoV-2, to determine seroconversion, to confirm eligibility for donation of convalescent plasma as well as play an essential part in epidemiological studies. We report on the validation of the Ansh Laboratories SARS-CoV-2 IgG and SARS-CoV-2 IgM ELISA immunoassays. These assays were evaluated for detection of anti-SARS-CoV-2 IgG and IgM antibodies for clinical use in our hospital as part of an orthogonal testing algorithm recommended by the CDC. Methods Diagnostic specificity and sensitivity of the IgG and IgM ELISA assays were tested using samples confirmed to be negative or positive for COVID-19 by RT-PCR. We also evaluated precision, analytical interference, and cross-reactivity with known cases of infection with other viruses. Additionally, we validated concordance with molecular and other serological testing and evaluated seroconversion in our patient population. Results The IgG and IgM ELISA assays showed acceptable precision, were robust to analytical interference and did not exhibit cross reactivity with specimens positive for common respiratory viruses. Both assays exhibited 95% agreement with a primary screening serological assay utilized at our institution as well as with a reference laboratory semi-quantitative method. Concordance with RT-PCR was excellent >6 days after symptom onset (100%). Conclusions The Ansh SARS-CoV-2 ELISA assays have good analytical performance suitable for clinical use.

Cadmium pollution has become a serious environmental issue due to its toxicity and frequent entrance into environment components such as soil, water, and air via many anthropogenic sources. Over the last two decades, whole-cell bacterial bioreporters have been acknowledged as bio-sentinels for the determination of toxic heavy metals. Herein a sensitive and quite specific bacterial bioreporter was developed to cope with the need for the rapid and simple determination of cadmium. The construction and characterization of a fluorescence-based whole-cell cadmium bioreporter strain, Escherichia coli MG1655 (pBR-PzntA), was described which is based on the expression of green fluorescent protein under the control of the zntA gene promoter of heavy metal resistance determinant. The developed bioreporter was able determine cadmium at 5 mu g/L after 3.5 hours of induction in a defined medium while the cadmium detection limit was improved to 2 mu g/L after 1.5 hours by the use of an inorganic phosphate-limiting defined medium. Drastic changes in cadmium sensitivity were obtained between bioreporter cells induced at different growth phases. The maximum fluorescence performance was obtained for early exponential growth phase cells. This cadmium bioreporter was found to be more sensitive and specific to cadmium ions than to a wide range of heavy metals and was sensitive to only cadmium at drinking water quality standard concentrations. These findings will lead to future studies including integration of the bioreporter cells into a portable device to assess bioavailable cadmium levels in environmental samples which will provide a rapid and practical field detection technique.

ObjectiveWith the COVID-19 pandemic, there have been supply challenges necessitating that laboratories must prepare their own viral transport medium (VTM), which provides stability for clinical specimens for diagnostic viral testing.MethodsWithin a veteran affairs medical center clinical laboratory, VTM was prepared with a Hanks Balanced Salt Solution (HBSS) 500 mL bottle with phenol red, sterile heat-inactivated fetal bovine serum (FBS), gentamicin sulfate (50 mg/mL), and amphotericin B (250 μg/mL). An antimicrobial mixture was made of 50 mL each of amphotericin B and gentamicin sulfate. Ten mL of FBS and 2 mL of the antimicrobial mixture were mixed into the HBSS bottle, from which 3 mL aliquots were made. Sterility and efficacy check were assessed. These preparations were conducted at our VAMC’s clinical laboratory to assure adequate VTM supply during the COVID-19 shortage.ResultsThe VTM was successfully prepared in-house, supporting uninterrupted testing for the facility and other affiliated medical facilities/centers and community living centers.ConclusionThis quality assurance/improvement report represents the first published manuscript on feasible VTM preparation exclusively within a clinical microbiology laboratory during the COVID-19 pandemic.

Highlights • To summarize the blood CD4+ or CD8+ T cell count in COVID-19 patients. • The first meta-analysis on blood CD4+ or CD8+ T cell count between mild and severe COVID-19 patients. • The lower blood CD4+ or CD8+ T cell count could predict worse prognosis in COVID-19 patients., This study mainly focused on the very serious COVID-19 epidemic situation at present and provided a new insight for the treatment and monitor of patients with COVID-19. Through this meta-analysis, we could draw a conclusion that less expression of blood CD4+ and CD8+ T cells count might reflect the severity of infection and often accompanied by a poor prognosis. Hence, we inferred blood CD4+ and CD8+ T cells count could be a promising biomarker for disease assessment and monitor of patients with COVID-19.

Cases of coronavirus disease 2019 (COVID-19) have been breaking out around the world recently. However, the dynamic changes in the clinical symptoms and prognosis of COVID-19 patients remain unknown. According to the onset time of initial clinical symptoms, 843 COVID-19 patients admitted between Jan 22 and Feb 14, 2020 were divided into three groups: group A (Jan 21 to Jan 25, n = 324), group B (Jan 26 to Jan 31, n = 358) and group C (Feb 1 to Feb 10, n = 161). Data on the demographics, symptoms, first laboratory results, treatments and outcomes (within 12 days of hospitalization) were collected. The results showed that the median duration from symptom onset to admission shortened over time (13, 10 and 5 days, respectively, p

Objective During the current pandemic, COVID-19 has been detected in patients using real-time reverse transcriptase-polymerase chain reaction (RT-PCR) that confirms the presence of SARS-CoV-2 RNA. The demand for increased testing, particularly for asymptomatic individuals required alternative approaches to single-patient RT-PCR testing, such as pooling. Methods This study explored the impact of dilution on the detectability of SARS-CoV-2 in asymptomatic patients using RT-PCR and demonstrated that pooling can be effective in low prevalence populations. Results The RT-PCR results for the 3:1, 5:1, and 7:1 aliquot samples showed little differences in CT values, confirming detection capability at these dilutions. Conclusion Based on the results of the present study, a pooled approach with up to 5:1 sample aliquots and using the current RT-PCR methodology likely will detect SARS CoV2 RNA among asymptomatic patients.

Highlights • Laboratory medicine fulfill a great assistance to early detection of SARAS-CoV-2. • Laboratory abnormalities could discriminate between severe and non-severe COVID-19 patients. • Abnormal laboratory parameters mirror the evolution of COVID-19 toward an unfavorable outcome. • Lymphopenia and increased D-dimer, LDH, ALT, AST reflect poor prognosis in COVID-19., Background Since its first description, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), formerly known as 2019-nCoV, has attracted tremendous attention in a short period of time as the death toll and number of confirmed cases grows unceasingly. Methods To provide a better understanding of the importance of abnormal laboratory findings in COVID-19 diagnosis and prognosis, we searched the Scopus, PubMed, and Web of Science medical databases and selected 19 articles (totaling 2988 patients, 484 of whom [16.1%] had severe disease) that reported panels of laboratory examinations in patients with COVID-19. Results Although in vitro diagnostics, primarily using PCR- and ELISA-based methods, efficiently contribute to the etiological identification of SARS-CoV-2 infection, we suggest that laboratory medicine may also be of significant assistance when differentiating between severe and non-severe COVID-19. Conclusion When we wrote this article, our ability to provide a definitive conclusion may have been adversely affected by some limitations, such as the low sample size, differently applied methods, dissimilar reference ranges, non-synchronized representations of results, and variety of the patients’ panels. Despite the limitations, the analysis of the current scientific literature demonstrates the value of laboratory parameters as simple, rapid, and cost-effective biomarkers in COVID-19 patients.

Quatre coronavirus sont responsables chez l’homme d’infections respiratoires fréquentes et le plus souvent bénignes, il s’agit des HCoV-OC43, HCoV-229E, HCoV-NL63 et HCoV-HKU 1. À côté de ces coronavirus humains endémiques, trois nouveaux coro-navirus d’origine zoonotique ont émergé dans la population humaine ces vingt dernières années. Il s’agit du Sars-CoV(-l) apparu en 2003, du Mers-CoV apparu en 20l2, et du Sars-CoV-2 apparu en 20l9. Ces trois coronavirus sont responsables d’un syndrome respiratoire sévère. L’épidémie de syndrome respiratoire aigu sévère due au Sars-CoV-l a touché environ 8 000 individus et occasionné environ 800 décès mais a été jugulée en quelques mois. Le Mers-CoV a occasionné plus de 2 500 cas depuis 20l2 avec une mortalité de l’ordre de 35 %. Le Sars-CoV-2 est actuellement responsable d’une pandémie majeure avec une mortalité importante chez les sujets âgés ou présentant des co-morbidités.

The entire spectrum of diagnostic testing, from reagent supply to test performance, has been a major focus during the coronavirus disease 2019 (COVID-19) pandemic. The hope for serologic testing is that it will provide both epidemiologic information about seroprevalence as well as individual information about previous infection. This information is particularly helpful for high-risk individuals who may be outside of the viral shedding window, such as children with suspected multisystem inflammatory syndrome. It is not yet understood whether serologic testing can be interpreted in terms of protective immunity. These concerns must be addressed using highly sensitive and specific tests.

Reverse transcription (RT)-PCR, the principal diagnostic method applied in the world-wide struggle against COVID-19, is capable of detecting a single molecule of a viral genome. Correctly designed and practiced RT-PCR assays for SARS-CoV-2 should not cross react with similar but distinct viral pathogens, such as the coronaviruses associated with the common cold, and should perform with very high analytical sensitivity. This analytical performance is predicated on the ability of the method to detect the presence of the selected nucleic acid target, without detection of a false positive signal.

SARS-CoV-2 (also known as COVID-19) has been an unprecedented challenge in many parts of the medical field with blood banking being no exception. COVID-19 has had a distinctly negative effect on our blood collection nationwide forcing blood banks, blood centers, and the US government to adopt new policies to adapt to a decreased blood supply as well as to protect our donors from COVID-19. These policies can be seen distinctly in patient blood management and blood bank operations. We are also faced with developing policies and procedures for a nontraditional therapy, convalescent plasma; its efficacy and safety is still not completely elucidated as of yet.

Aims To investigate the eosinophil cell (EC) expression in peripheral blood of patients infected with severe acute respiratory syndrome coronavirus 2(SARS‐CoV‐2) and its clinical significance of diagnosis and prognosis. Methods 95 patients, whose nucleic acid test of SARS‐CoV‐2 was positive to make a definite diagnosis of COVID‐19, were selected as the study group. They were admitted at the Chengdu Public Health Clinical Medical Center from January 21 to March 2, 2020. Another 95 healthy subjects and 95 non‐infectious fever patients during the same period were selected as the control group. The BC‐6900 blood cell analyzer was used to continuously observe and detect ECs in 95 patients with COVID‐19 and the control group. The differences in expression levels of ECs in peripheral blood were analyzed. Results ECs were significantly decreased in 95 (75.8%) COVID‐19 patients (P, Continuous observation and detection of the eosinophil cell (EC) in patients with COVID‐19 showed that ECs decreased significantly in this group. When the condition improved, the ECs returned to normal, while the ECs of the patients who did not improve continued to decline. It is suggested that ECs have clinical significance in the diagnosis and prognosis of covid‐19, and may be a useful index in the early warning of acute infectious diseases. In addition, the decrease of ECs in three kinds of diseases caused by coronavirus, COVID‐19, Middle East respiratory syndrome and severe acute respiratory syndrome, suggests that coronavirus may damage the immune function of human body and cause immune damage syndrome by attacking the cells in bone marrow.

Background We aimed to evaluate the analytical performance of five commercial RT‐PCR kits (Genekey, Daan, BioGerm, Liferiver, and Yaneng) commonly used in China, since such comparison data are lacking. Methods A total of 20 COVID‐19 confirmed patients and 30 negative nasopharyngeal swab specimens were analyzed by five kits. The detection ability of five RT‐PCR kits was evaluated with 5 concentration gradients diluted by a single positive sample. The limit of detection was evaluated by N gene fragment solid standard. Two positive clinical specimens were used to evaluate the repeatability and imprecision. Finally, we used six human coronaviruses plasmid and four respiratory pathogens plasmid to check for cross‐reactivity. Results The positive detection rate was 100% for Genekey, Daan, and BioGerm,and 90% for Liferiver and Yaneng in 20 clinical SARS‐CoV‐2 infection. The coincidence rate of five kits in 10 negative samples was 100%. The detection rate of target genes for Daan, BioGerm, Liferiver, and Yaneng was 100% from Level 1 to Level 3. In Level 4, only Daan detection rate was 100%. In Level 5, five kits presented poor positive rate. The limit of detection declared by each manufacturer was verified. The repeatability for target genes was less than 5% and so did the total imprecision. There is no cross‐reactivity of five kits with six human coronaviruses and four respiratory pathogens for ORF1ab and N gene. Conclusions Five RT‐PCR kits assessed in this study showed acceptable analytical performance characteristics and are useful tools for the routine diagnosis of SARS‐CoV‐2., In the work, we presented the analytical performance evaluations of five RT‐PCR kits using nasopharyngeal swabs samples from patients with confirmed SARS‐CoV‐2 infection, and negative nasopharyngeal swabs samples (Figure 1). A total of 20 COVID‐19 confirmed patients and 30 negative nasopharyngeal swab specimens were analyzed by five kits. The detection ability of five RT‐PCR kits was evaluated with 5 concentration gradients diluted by a single positive sample. The limit of detection was evaluated by N gene fragment solid standard. Two positive clinical specimens were used to evaluate the repeatability and imprecision. Finally, we used six human coronaviruses plasmid and four respiratory pathogens plasmid to check for cross‐reactivity

The deadly pandemic, coronavirus disease 2019 (COVID‐19), caused due to the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), has paralyzed the world. Although significant methodological advances have been made in the field of viral detection/diagnosis with 251 in vitro diagnostic tests receiving emergency use approval by the US‐FDA, little progress has been made in identifying curative or preventive therapies. This review discusses the current trends and potential future approaches for developing COVID‐19 therapeutics, including repurposed drugs, vaccine candidates, immune‐modulators, convalescent plasma therapy, and antiviral nanoparticles/nanovaccines/combinatorial nanotherapeutics to surmount the pandemic viral strain. Many potent therapeutic candidates emerging via drug‐repurposing could significantly reduce the cost and duration of anti‐COVID‐19 drug development. Gene/protein‐based vaccine candidates that could elicit both humoral and cell‐based immunity would be on the frontlines to prevent the disease. Many emerging nanotechnology‐based interventions will be critical in the fight against the deadly virus by facilitating early detection and enabling target oriented multidrug therapeutics. The therapeutic candidates discussed in this article include remdesivir, dexamethasone, hydroxychloroquine, favilavir, lopinavir/ritonavir, antibody therapeutics like gimsilumab and TJM2, anti‐viral nanoparticles, and nanoparticle‐based DNA and mRNA vaccines., In view of what is known so far about the SARS‐CoV‐2 structure, its pathophysiology, life cycle, and related immunological responses, key steps are envisaged where nanotechnologists and nanotechnology could play a pivotal part in designing advanced biomimetic approaches and engineered nanomaterials having versatile chemical functionalities against COVID‐19 prophylaxis, diagnosis, and treatment.

Introduction: Cell population data (CPD) are background optical signals measured during complete blood count analysis on hematology analyzers that reflect structural and morphological characteristics of leukocytes. Our aim was to assess the value of CPD obtained on Sysmex XN-1000 in the differential diagnosis of coronavirus disease 2019 (COVID-19) at the early stage of the disease. Methods: This retrospective study included 114 COVID-19 confirmed cases and 88 negative patients presenting with respiratory flu-like symptoms for whom laboratory analysis was performed at hospital admission. Results of leukocyte count, including CPD, and C-reactive protein (CRP) were compared between the two groups. Results: All CPD except lymphocyte internal complexity (LY-WX) and monocyte nucleic acid content (MO- WY) were significantly different in COVID-19 compared to non-COVID-19 cases (P

Background The ongoing coronavirus disease 19 (COVID‐19) is posing a threat to the public health globally. Serological test for SARS‐CoV‐2 antibody can improve early diagnosis of COVID‐19 and serves as a valuable supplement to RNA detection. Method A SARS‐CoV‐2 IgG/IgM combined antibody test strip based on colloidal gold immunochromatography assay was developed, with both spike protein and nucleocapsid protein of SARS‐CoV‐2 antigen used for antibody detection. From 3 medical institutions across China, serum or plasma of 170 patients with confirmed COVID‐19 diagnosis and 300 normal controls were collected and tested with the strip. Sensitivity, specificity, kappa coefficient, receiver operating characteristic (ROC) curve, and area under the curve (AUC) were analyzed. Positive rates in different medical centers, age group, gender, and different disease course were compared. Results 158 out 170 samples from confirmed COVID‐19 patients had positive results from the test, and 296 out of 300 samples from normal controls had negative results. The kit was 92.9% sensitive and 98.7% specific. The positive rate was 77.3% during the first week after disease onset, but reached 100% since day 9. AUC and kappa coefficient were 0.958 and 0.926, respectively, which showed the consistency of the test results with the standard diagnosis. Age or gender caused little variations in the kit sensitivity. Conclusion The rapid, easy‐to‐use SARS‐CoV‐2 IgG/IgM combined antibody test kit has a superior performance, which can help with accurate diagnosis and thus timely treatment and isolation of COVID‐19 patients, that contributes to the better control of the global pandemic., A SARS‐CoV‐2 IgG/IgM combined antibody test strip based on immunochromatography assay was developed with both spike protein and nucleocapsid protein used for detection. With clinical assessment from 3 medical centers from across China, the kit was 92.9% sensitive and 98.7% specific. The positive rate was 77.3% during the first week after disease onset and reached 100% since day 9.

We report an artificial molecular machine that moves along a track, iteratively joining building blocks to form an oligomer of single sequence with a continuous backbone of carbon-carbon bonds. The rotaxane features a macrocycle bearing an aldehyde-terminated chain and an axle containing different phosphonium ylides separated by rigid spacers. Each ylide is large enough to block the passage of the macrocycle, trapping the ring between the stopper at the terminus of original threading and the next ylide along the track. Once a building block is reachable, it is removed from the track through a Wittig reaction that adds it to the terminus of the growing chain. Operation on a four-barrier tetra(phosphonium salt) track produces a tetra(diphenylpropane) of single sequence linked through alkene bonds. The prototype extends the principle for molecular machines that build polymers by moving along tracks to the synthesis of sequence-encoded chains with continuous carbon backbones. Sequence is crucial in the molecular world. Proteins are built from a common set of 20 amino acids, but different sequences afford materials as diverse as snake venom, muscle, and spider silk. However, the synthesis of artificial sequence polymers remains challenging. Biology uses molecular machines (e.g., ribosomes) for such tasks, inspiring the invention of artificial systems that move along tracks, picking off and joining building blocks in sequence. To date, such small-molecule machines have used amide formation to join building blocks, the same bonds the ribosome uses to make peptides. Here, we report on the design, synthesis, and operation of a track-based molecular machine that assembles a single-sequence oligomer with a continuous backbone of carbon-carbon bonds. This new class of de novo molecular synthesizer utilizes chemistry and reactivity patterns unavailable to biological machines. The long-term goal is for such molecular assemblers to ultimately be able to play significant roles in molecular construction. Molecular machines, such as ribosomes, are ubiquitous in biology. These natural systems are inspiring artificial systems that move along tracks, picking off and joining building blocks in sequence. To date, such small-molecule machines have used amide formation to connect building blocks, much like the ribosome. Here, the design, synthesis, and operation of a track-based molecular machine that iteratively forms a continuous backbone of carbon-carbon bonds is described. This new class of de novo molecular synthesizer utilizes chemistry and reactivity patterns unavailable to biological machines.

Systemic delivery of therapeutics for treatment of lung diseases has several limitations including poor organ distribution of delivered payload with relatively low accumulation of active substances in the lungs and severe adverse side effects. In contrast, nanocarrier based therapeutics provide a broad range of opportunities due to their ability to encapsulate substances with different aqueous solubility, transport distinct types of cargo, target therapeutics specifically to the deceased organ, cell, or cellular organelle limiting adverse side effects and increasing the efficacy of therapy. Moreover, many nanotherapeutics can be delivered by inhalation locally to the lungs avoiding systemic circulation. In addition, nanoscale based delivery systems can be multifunctional, simultaneously carrying out several tasks including diagnostics, treatment and suppression of cellular resistance to the treatment. Nanoscale delivery systems improve the clinical efficacy of conventional therapeutics allowing new approaches for the treatment of respiratory diseases which are difficult to treat or possess intrinsic or acquired resistance to treatment. The present review summarizes recent advances in the development of nanocarrier based therapeutics for local and targeted delivery of drugs, nucleic acids and imaging agents for diagnostics and treatment of various diseases such as cancer, cystic fibrosis, and coronavirus., Targeted delivery of nanotherapeutics specifically to diseased lungs, pulmonary cells, and/or specific organelles offers distinct advantages over systemic delivery by enhancing efficacy of the treatment and limiting severe adverse side effects. Nanoscale based systems can transport various types of payload, simultaneously carry out several distinct tasks and perform multiple function in diagnosis, treatment, and suppression of cellular resistance.

Author(s): Singh, Kunwar; Mittal, Sasha; Gollapudi, Sumanth; Butzmann, Alexandra; Kumar, Jyoti; Ohgami, Robert S | Abstract: BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2), known to be the causative agent of COVID-19, has led to a worldwide pandemic. At presentation, individual clinical laboratory blood values, such as lymphocyte counts or C-reactive protein (CRP) levels, may be abnormal and associated with disease severity. However, combinatorial interpretation of these laboratory blood values, in the context of COVID-19, remains a challenge.MethodsTo assess the significance of multiple laboratory blood values in patients with SARS-CoV-2 and develop a COVID-19 predictive equation, we conducted a literature search using PubMed to seek articles that included defined laboratory data points along with clinical disease progression. We identified 9846 papers, selecting primary studies with at least 20 patients for univariate analysis to identify clinical variables predicting nonsevere and severe COVID-19 cases. Multiple regression analysis was performed on a training set of patient studies to generate severity predictor equations, and subsequently tested on a validation cohort of 151 patients who had a median duration of observation of 14ndays.ResultsTwo COVID-19 predictive equations were generated: one using four variables (CRP, D-dimer levels, lymphocyte count, and neutrophil count), and another using three variables (CRP, lymphocyte count, and neutrophil count). In adult and pediatric populations, the predictive equations exhibited high specificity, sensitivity, positive predictive values, and negative predictive values.ConclusionUsing the generated equations, the outcomes of COVID-19 patients can be predicted using commonly obtained clinical laboratory data. These predictive equations may inform future studies evaluating the long-term follow-up of COVID-19 patients.

Highlights • Heating-activation at 56 °C for 30 min does not impair the antibodies of SARS-CoV-2. • Heating-activation would not decrease the diagnostic efficacy of SARS-CoV-2 IgM or IgG antibodies (ELISA-immunoassay). • Sera inactivated by heating should be recommended to minimize the risk of virus contamination of laboratory staff., Background To establish a safe and accurate method for detecting SARS-CoV-2 IgM and IgG, we assessed the impact of sera after heat-inactivation on the SARS-CoV-2 IgM and IgG levels measured by ELISA-immunoassay. Methods The serum samples of 62 patients with COVID-19 and 18 healthy controls were collected in Hankou’s Hospital of Wuhan from February 27 to March 6, 2020. Before and after the samples were inactivated, the levels of IgM and IgG antibodies were measured. Results The indexes of antibodies after inactivated were significantly higher than those in fresh sera, while the positive rates in all participants or in patients with COVID-19 did not change. The positive coincidence rate, negative coincidence rate and total coincidence rate of IgM antibodies before and after inactivation were 100.00% (55/55), 96.00% (24/25) and 98.75% (79/80), respectively (κ = 0.971, P

Highlights • Laboratory diagnostic parameters in symptomatic Covid19 disease patients. • Monocyte distribution width and monocyte modification in infection disease and sepsis. • SARS COV2 infection, prognosis in severe respiratory failure with multiple organ failure, clinical and laboratory finding., Introduction Interesting results regarding the contribution of MDW (Monocyte Distribution Width) in the Infectious Disease Unit have been reported. An observational study is ongoing at San Donato Hospital with the aim to evaluate the contribution of MDW in the diagnostic pathway in adult patients entering in the ED setting and tested for SARS-CoV-2. Material and method COVID-19 symptomatic and paucisymptomatic patients presenting to ED (Emergency Department), have been enrolled consecutively. Whole blood venous samples have been collected on K2 EDTA for MDW determination, at the same time a nasopharyngeal swab for SARS-CoV-2 RNA detection have been collected. Results One hundred six patients were negative for SARS-CoV-2 with MDW mean value of 20.3 ± 3.3, while forty-one were positive for SARS-CoV-2 with higher MDW mean value of 27.3 ± 4.9 (P

Efficient and rapid detection of viruses plays an extremely important role in disease prevention, diagnosis, and environmental monitoring. Early screening of viral infection among the population has the potential to combat the spread of infection. However, the traditional methods of virus detection being used currently, such as plate culturing and quantitative RT-PCR, give promising results, but they are time-consuming and require expert analysis and costly equipment and reagents; therefore, they are not affordable by people in low socio-economic groups in developing countries. Further, mass or bulk testing chosen by many governments to tackle the pandemic situation has led to severe shortages of testing kits and reagents and hence are affecting the demand and supply chain drastically. We tried to include all the reported current scenario-based biosensors such as electrochemical, optical, and microfluidics, which have the potential to replace mainstream diagnostic methods and therefore could pave the way to combat COVID-19. Apart from this, we have also provided information on commercially available biosensors for detection of SARS-CoV-2 along with the challenges in development of better diagnostic approaches. It is therefore expected that the content of this review will help researchers to design and develop more sensitive advanced commercial biosensor devices for early diagnosis of viral infection, which can open up avenues for better and more specific therapeutic outcomes.

To manage the COVID-19 pandemic, development of rapid, selective, sensitive diagnostic systems for early stage β-coronavirus severe acute respiratory syndrome (SARS-CoV-2) virus protein detection is emerging as a necessary response to generate the bioinformatics needed for efficient smart diagnostics, optimization of therapy, and investigation of therapies of higher efficacy. The urgent need for such diagnostic systems is recommended by experts in order to achieve the mass and targeted SARS-CoV-2 detection required to manage the COVID-19 pandemic through the understanding of infection progression and timely therapy decisions. To achieve these tasks, there is a scope for developing smart sensors to rapidly and selectively detect SARS-CoV-2 protein at the picomolar level. COVID-19 infection, due to human-to-human transmission, demands diagnostics at the point-of-care (POC) without the need of experienced labor and sophisticated laboratories. Keeping the above-mentioned considerations, we propose to explore the compartmentalization approach by designing and developing nanoenabled miniaturized electrochemical biosensors to detect SARS-CoV-2 virus at the site of the epidemic as the best way to manage the pandemic. Such COVID-19 diagnostics approach based on a POC sensing technology can be interfaced with the Internet of things and artificial intelligence (AI) techniques (such as machine learning and deep learning for diagnostics) for investigating useful informatics via data storage, sharing, and analytics. Keeping COVID-19 management related challenges and aspects under consideration, our work in this review presents a collective approach involving electrochemical SARS-CoV-2 biosensing supported by AI to generate the bioinformatics needed for early stage COVID-19 diagnosis, correlation of viral load with pathogenesis, understanding of pandemic progression, therapy optimization, POC diagnostics, and diseases management in a personalized manner.

Highlights • Serological assays for SARS-CoV-2 are widely available. • Data on diagnostic sensitivity, specificity and likelihood ratio are needed. • The identification of reliable thresholds improves diagnostic accuracy. • The negative predictive value is a valuable clinical information., Background The evaluation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) specific antibody (Ab) assay performances is of the utmost importance in establishing and monitoring virus spread in the community. In this study focusing on IgG antibodies, we compare reliability of three chemiluminescent (CLIA) and two enzyme linked immunosorbent (ELISA) assays. Methods Sera from a total of 271 subjects, including 64 reverse transcription-polymerase chain reaction (RT-PCR) confirmed SARS-CoV-2 patients were tested for specific Ab using Maglumi (Snibe), Liaison (Diasorin), iFlash (Yhlo), Euroimmun (Medizinische Labordiagnostika AG) and Wantai (Wantai Biological Pharmacy) assays. Diagnostic sensitivity and specificity, positive and negative likelihood ratios were evaluated using manufacturers’ and optimized thresholds. Results Optimized thresholds (Maglumi 2 kAU/L, Liaison 6.2 kAU/L and iFlash 15.0 kAU/L) allowed us to achieve a negative likelihood ratio and an accuracy of: 0.06 and 93.5% for Maglumi; 0.03 and 93.1% for Liaison; 0.03 and 91% for iFlash. Diagnostic sensitivities and specificities were above 93.8% and 85.9%, respectively for all CLIA assays. Overall agreement was 90.3% (Cohen’s kappa = 0.805 and SE = 0.041) for CLIA, and 98.4% (Cohen’s kappa = 0.962 and SE = 0.126) for ELISA. Conclusions The results obtained indicate that, for CLIA assays, it might be possible to define thresholds that improve the negative likelihood ratio. Thus, a negative test result enables the identification of subjects at risk of being infected, who should then be closely monitored over time with a view to preventing further viral spread. Redefined thresholds, in addition, improved the overall inter-assay agreement, paving the way to a better harmonization of serologic tests.

Since December 2019, an outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China, has spread throughout the world. Coagulation dysfunction is one of the major causes of death in patients with severe COVID-19. Several recent observations in Algeria and elsewhere maintain that a pulmonary embolism is frequent in patients with COVID-19 with a high incidence in intensive care. In addition, other studies have shown that many deceased patients have diagnostic criteria for disseminated intravascular coagulation (DIC) set by the International society of hemostasis and thrombosis (ISTH). The office of the Algerian society of transfusion and hemobiology composed of hemostasis and blood transfusion experts from Algerian hospitals on the epidemic front line have established a consensus on the issue through 4 axes: Indication of thromboprophylaxis, monitoring of hemostasis, indications of transfusion in the event of disseminated intravascular coagulation (DIC) and anticoagulant treatment after discharge.

COVID-19 is a systemic infection with a significant impact on the hematopoietic system and hemostasis. Lymphopenia may be considered as a cardinal laboratory finding, with prognostic potential. Neutrophil/lymphocyte ratio and peak platelet/lymphocyte ratio may also have prognostic value in determining severe cases. During the disease course, longitudinal evaluation of lymphocyte count dynamics and inflammatory indices, including LDH, CRP and IL-6 may help to identify cases with dismal prognosis and prompt intervention in order to improve outcomes. Biomarkers, such high serum procalcitonin and ferritin have also emerged as poor prognostic factors. Furthermore, blood hypercoagulability is common among hospitalized COVID-19 patients. Elevated D-Dimer levels are consistently reported, whereas their gradual increase during disease course is particularly associated with disease worsening. Other coagulation abnormalities such as PT and aPTT prolongation, fibrin degradation products increase, with severe thrombocytopenia lead to life-threatening disseminated intravascular coagulation (DIC), which necessitates continuous vigilance and prompt intervention. So, COVID-19 infected patients, whether hospitalized or ambulatory, are at high risk for venous thromboembolism, and an early and prolonged pharmacological thromboprophylaxis with low molecular weight heparin is highly recommended. Last but not least, the need for assuring blood donations during the pandemic is also highlighted.