Many individuals who survive tuberculosis disease face ongoing disability and elevated mortality risks. However, the impact of post-tuberculosis sequelae is generally omitted from policy analyses and disease burden estimates. We therefore estimated the global burden of tuberculosis, inclusive of post-tuberculosis morbidity and mortality.We constructed a hypothetical cohort of individuals developing tuberculosis in 2019, including pulmonary and extrapulmonary disease. We simulated lifetime health outcomes for this cohort, stratified by country, age, sex, HIV status, and treatment status. We used disability-adjusted life-years (DALYs) to summarise fatal and non-fatal health losses attributable to tuberculosis, during the disease episode and afterwards. We estimated post-tuberculosis mortality and morbidity based on the decreased lung function caused by pulmonary tuberculosis disease.Globally, we estimated 122  million DALYs due to incident tuberculosis disease in 2019, with 58 (38–83) million DALYs attributed to post-tuberculosis sequelae, representing 47% (95% UI 37–57) of the total burden estimate. The increase in burden from post-tuberculosis varied substantially across countries and regions, driven largely by differences in estimated case fatality for the disease episode. We estimated 12·1 DALYs (95% UI 10·0–14·9) per incident tuberculosis case, of which 6·3 DALYs (5·6–7·0) were from the disease episode and 5·8 DALYs (3·8–8·3) were from post-tuberculosis. Per-case post-tuberculosis burden estimates were greater for younger individuals, and in countries with high incidence rates. The burden of post-tuberculosis was spread over the remaining lifetime of tuberculosis survivors, with almost a third of total DALYs  accruing 15 or more years after incident tuberculosis.Post-tuberculosis sequelae add substantially to the overall disease burden caused by tuberculosis. This hitherto unquantified burden has been omitted from most previous policy analyses. Future policy analyses and burden estimates should take better account of post-tuberculosis, to avoid the potential misallocation of funding, political attention, and research effort resulting from continued neglect of this issue.National Institutes of Health. Tuberculosis was estimated to cause 1·4 million deaths in 2019.The term post-tuberculosis describes the range of pathological conditions experienced by tuberculosis survivors. Pulmonary tuberculosis, the commonest disease presentation, causes progressive destruction of lung tissue, and this damage might not fully resolve after treatment.Evidence before this studyA growing number of cross-sectional and longitudinal studies have described chronic lung disease, long-term disability, and elevated mortality among individuals surviving tuberculosis disease. However, these post-tuberculosis sequelae are omitted from disease burden estimations and policy analyses that quantify the health losses caused by tuberculosis.Added value of this studyWe quantified the global burden of disease caused by incident tuberculosis in 2019, inclusive of post-tuberculosis morbidity and mortality over the lifetime of tuberculosis survivors. The results of this analysis demonstrate that post-tuberculosis burden adds considerably to the health losses caused by incident tuberculosis—globally, we estimated 122  million disability-adjusted life-years (DALYs) due to tuberculosis occurring in 2019, with 58 (38–83) million DALYs attributed to post-tuberculosis sequelae, representing 47% (37–57) of the total burden estimate.Implications of all the available evidenceWhen post-tuberculosis sequelae are considered, the disease burden caused by tuberculosis is substantially greater than conventional tuberculosis burden estimates. Accounting for post-tuberculosis in burden estimates and policy analyses will probably lead to revisions in the estimated impact of tuberculosis control efforts.Historically, post-tuberculosis has not been a major focus of the tuberculosis control agenda. However, the health-care needs of tuberculosis survivors are drawing increasing attention,Disease burden estimates shape the health research agenda and funding landscape, and they also determine how interventions are prioritised within disease control budgets. By excluding post-tuberculosis, current burden estimates might substantially underestimate the health losses caused by tuberculosis, which could lead to misallocation of funding, political attention, and research effort. Burden estimates for individual settings have provided initial evidence of the biases from omitting post-tuberculosis burden: an analysis estimating tuberculosis burden for India with and without post-tuberculosis found that total DALYs increased by 62% when post-tuberculosis was included.We constructed a hypothetical cohort of individuals developing tuberculosis in 2019, including pulmonary and extrapulmonary disease, who were stratified by factors related to the burden of tuberculosis or consequences after tuberculosis cure, and for whom sufficient data were available . We synthesised evidence describing quality of life and mortality among individuals with tuberculosis, during the disease episode and over their remaining life. Using this evidence, we simulated lifetime health outcomes for the cohort developing tuberculosis disease in 2019. We used DALYs to summarise the total health losses attributable to tuberculosis.The WHO Global TB Programme reports annual estimates of the population developing tuberculosis disease, stratified by country, sex, and age group.We adopted WHO estimates of tuberculosis case fatality in 2019.Tuberculosis disability weights were based on current Global Burden of Disease Study (GBD) valuationsIndividuals surviving tuberculosis disease face elevated mortality risks. A recent meta-analysis reported a standardised mortality ratio of 2·91 (95% CI 2·21–3·84) for tuberculosis survivors, compared with individuals without previous tuberculosis.1%), and assumed that tuberculosis induced a downward shift of this distribution. For each country, the reduction in FEV1% among tuberculosis survivors was estimated to match the ORs for chronic respiratory disease in tuberculosis survivors, which was defined as an FEV1% lower than 80%. To model the association between FEV1% and mortality we fitted a quadratic function to mortality rate ratios (RRs) reported for different FEV1% impairment levels,1% distribution compared with the distribution without post-tuberculosis. Country-level mortality RRs estimated for post-tuberculosis varied between 1·02 and 1·34, with a median of 1·14  and years lived with disability (YLDs).We specified probability distributions to represent uncertainty in model parameters , and we The mortality RR for post-tuberculosis used in the main analysis is conservative, as it only captures one of several mechanisms through which tuberculosis affects future mortality risks. As a sensitivity analysis, we recalculated results using a mortality risk ratio for post-tuberculosis of 1·78 (95% CI 1·61–1·98), based on a retrospective cohort study of individuals with and without post-tuberculosis, controlling for multiple demographic and clinical risk factors for mortality.The funder of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report.DALYs attributable to post-tuberculosis have not been included in past tuberculosis burden estimates, and their inclusion substantially increases burden estimates, by 91% (95% UI 59–132) globally. The increase in total DALYs produced by considering post-tuberculosis varied substantially by region, from 60% in Africa to 267% in the Western Pacific. The proportional increase in YLDs  was 383% (154–755), reflecting the extended duration of post-tuberculosis relative to the tuberculosis disease episode. The proportional increase in YLLs was 71% (47–104). Reductions in survival represent the majority (73% [68–79]) of DALYs from the post-tuberculosis period. We also estimated the DALYs from tuberculosis disease and post-tuberculosis for the 30 high-tuberculosis-burden countries identified by WHO . In thesTotal and per-person DALY estimates varied by individual-level and country-level factors . The aveThe The To our knowledge, this study is the first to estimate the global burden of tuberculosis inclusive of post-tuberculosis morbidity and mortality. Even with conservative assumptions, the inclusion of post-tuberculosis substantially increased the total burden estimate. For the 8·5 million individuals surviving incident tuberculosis in 2019, we estimated that 58 million post-tuberculosis DALYs will accrue over the remaining lifetime, representing almost half of the 122 million DALYs estimated for tuberculosis.Our burden estimate was approximately twice the GBD estimate for tuberculosis DALYs in the same year.The primary disease burden tabulations produced by GBD are calculated to be categorical, such that the sum of DALYs for each individual disease equals the total DALYs from all diseases. However, users of disease burden estimates commonly interpret them to be the burden caused by a given disease, in the sense that they summarise the death and disability avertable through global elimination of that disease. If our results are correct, the causal interpretation of current GBD estimates for tuberculosis disease burden substantially undervalues the potential impact of tuberculosis control efforts. Appropriate valuation of post-tuberculosis disease burden might also lead to reprioritisation within the tuberculosis control portfolio. This could include greater attention to programmatic activities that can prevent tuberculosis from occurring in the first place, to active case-finding that may accelerate diagnosis, and to interventions that can prevent, mitigate, or repair lung damage from tuberculosis. These changes are consistent with a broader definition of treatment success, beyond simply sterilising the causative pathogen. This could include a greater role for end-of-treatment assessments of pathological damage and functional deficits in order to implement interventions that meet the health-care needs of tuberculosis survivors, who in any given year represent a much larger group than the individuals newly developing tuberculosis.The magnitude of post-tuberculosis disease burden also has implications for new research. In particular, further research is needed on the mechanisms of post-tuberculosis impairment, the range of conditions experienced by tuberculosis survivors, and how the extent of impairment changes over time.Our analysis has several limitations. First, our results might represent an underestimate of post-tuberculosis burden, as we only considered one pathway through which tuberculosis affects future health outcomes. Tuberculosis disease has deleterious effects on multiple organ systems, and some tuberculosis survivors experience respiratory symptoms even in the absence of clinically impaired lung function.Many individuals who survive tuberculosis disease face ongoing disability, despite achieving microbiological cure. For these tuberculosis survivors, post-tuberculosis sequelae limit opportunities and enjoyment of life, and increase the risk of early death. Our analysis has quantified these health losses, demonstrating that post-tuberculosis adds substantially to the global disease burden caused by tuberculosis. Future analyses should take better account of post-tuberculosis, to avoid the potential misallocation of funding, political attention, and research effort that would be produced by continued neglect of this issue.Analytic code and data inputs are available upon request to the corresponding author (nmenzies@hsph.harvard.edu).We declare no competing interests.


Development of novel antibodies to combat the novel SARS-CoV-2 virus is ongoing. Importantly, particular subgroups are more prone to severe disease, namely patients with poor immune responses. This includes cancer patients with solid and haematological disease, solid organ transplant (SOT) patients and those with congenital or acquired immunodeficiency. Outcomes for patients with poor immune responses receiving antibody therapy for underlying disease and SARS-CoV-2 severe infection are undergoing investigation. The objective of this study was to perform a search on patients with poor immune responses with severe SARS-CoV-2 infection, to assess if antibody therapy is beneficial in such populations. We performed searches using PubMED and medrXiv up to May 2021 of patients with solid and hematologic malignancy, SOT patients and acquired or congenital immunodeficiency. The primary outcome was to assess if antibody therapy was included during SARS-CoV-2 infection and the clinical outcomes of such treatment in this population. Here we find that there is a repurposing of monoclonal antibodies to target cytokine release syndrome, along with the use of convalescent plasma (CP). Despite CP demonstrating promising results, we reiterate evidence that CP forces mutational escape and subsequent variant development. Repurposing of antibody therapies (such as Tocilizumab) proved effective, especially in SOT patients. This also potentially opens an avenue for the use of anti-SARS-CoV-2 spike protein neutralizing monoclonal antibodies; however, studies have yet to focus on patients with poor immune responses as a subpopulation. Its gloFurther, those with solid malignancy , solid organ transplant (SOT) or on chronic immunosuppressive disease modifying treatment had increased risk of severe outcomes such as secondary bacterial/fungal superinfection, higher ICU admissions, mechanical ventilation with intubation and overall mortality . Althoug+ T cell count (lymphopenia) and pathogenic TH1 cells resulting in increased cytokine parameters. Overall, a lymphopenic and hypercytokinaemia profile definitively suggests a severe SARS-CoV-2 infection with poor prognosis and these inflammatory parameters are now used to guide treatment Patients with poor immune responses owing to underlying disease and/or immunosuppressive therapy are at increased risk for severe infection, often coupled with Cytokine Release Syndrome (CRS). CRS is characterised by fever, hyperferritinemia and a cytokine storm . Importantly, Interestingly, this association between SARS-CoV-2 infection and CRS has steered treatment towards immunosuppression via CRS specific mAbs benefiting patients by reducing proinflammatory reactivity and subsequently abating the storm. Additionally, a more preventative approach, especially significant in immunocompromised patients, might include Neutralizing mAbs (NMAbs) that target the SARS-CoV-2 receptor binding domain (RBD) and prevent severe disease developing.Currently, several pharmaceutical companies are trialing repurposed mAbs that target the CRS and are under investigation in patients with poor immune responses . There iThe expansion of prophylactic therapy for SARS-CoV-2 in patients with poor immune responses is increasingly prudent. Poor vaccine immunogenicity and the growing threat of mutational escape globally is forcing the development of alternative targets in the form of immunotherapy as previously described. According to a recent review patients with haematological and solid cancers demonstrate reduced immunogenicity to SARS-CoV-2 vaccinations. This is a constant trend echoed amongst other vaccines, for example, acute lymphoblastic leukemia (ALL) patients had 10–27% immunogenicity after hepatitis B and meningococcal subunit vaccines . Further2In order to attain a large volume of literature on this topic, we utilised PubMed and medrXiv search databases for publications on the use of antibody therapies in SARS-CoV-2 patients with poor immune responses from January 1st, 2019 to May 1st, 2021, see PRISMA digram  which di2.1The process of creating a novel mAb is complex, composing of animal and human testing. Firstly the target is identified for the antibody. NMAbs inhibit SARS-CoV-2 through inhibiting the viral spike protein  . This isESCs are filtered and selected for desired genetic modifications. These are inserted into murine embryos at an early stage of development. This results in subsequent murine progeny having the ability to create novel antibodies. Next, the target protein can be introduced.One introduced, the target protein is identified and the new genome codes for the production of new antibodies. These are harvested and filtered via flow cytometry. Once viable antibodies are discovered, they are tested firstly in preclinical trials (safety and efficiency) and finally onto human trials.2.2Importantly, we recognize that immunosuppressive therapies have differing mechanisms of action on the immune system. A recent meta-analysis found no evidence of improvement of severe SARS-CoV-2 disease under treatment with TNF-blockers, IL-1 blockers or IL-6 blockers . This pe2.3As previously mentioned, data demonstrates patients with solid and haematological cancers are more prone to severe presentations, outcomes and higher mortality rates in comparison to general population . FurtherRnjak et al.  demonstrCurrently, there are few clinical trials investigating the effect of mAbs on SARS-CoV-2 infection in solid and haematological cancer patients. The C-SMART trial (NCT04534725) is evaluating the effect of Selinexor and Lenzilumab (vs Placebo) on the treatment of SARS-CoV-2 infection in cancer patient's with moderate and severe SARS-CoV-2 infection respectively. Selinexor inhibits nuclear export while Lenzilumab is a mAb that targets CSF2/GM-CSF. This is a multi-centre trial with four main arms, expecting to provide insight into the best practice for prevention and treatment of SARS-CoV-2 in cancer patients as emerging standard of care measures are not always suitable to this especially vulnerable population.Another multicenter randomised control study (NCT04333914) is investigating the efficacy of three mAbs: GNS561 (an autophagy inhibitor), Monalizumab (anti-NKG2A) and Avdoralimab (anti-C5aR), compared to the standard of care in patients with advanced or metastatic cancer and SARS-CoV-2 infection – results are expected toward the end of 2021. Finally, a recent phase two trial (NCT04370834) assessed the effect of Tocilizumab in reducing inflammation associated with CRS seen in severe SARS-COV-2 infection in cancer patients. However, recent randomised data no longer supported its continuation.Overall, despite the positive results in many case studies/case-reports, there is still a lack of data surrounding cancer patient use of monoclonal antibodies to treat SARS-CoV-2 proinflammatory CRS. Specifically, large randomised control trials are needed in order to draw more robust and reliable conclusions.2.4We have established patients lacking humoral response develop prolonged and a more severe course of infection. Since the onset of the pandemic, there is some evidence of the beneficial effects of mAbs and CP for patients with poor immune responses. Delgado-Fernandez et al.  report hA recent study published by Leelayuwatanakul et al.  observed2.5Due to transplant patient's increased frailty and immunosuppression in comparison to the general population, they are considered a high risk population . The useCP administration has demonstrated beneficial effects in SOT patients with improved therapeutic response to severe SARS-CoV-2 infection. MAbs have also demonstrated improved clinical outcome in SOT patients. A recent case study observed effect of tocilizumab in a series of kidney transplant patients with severe respiratory SARS-CoV-2 infection. Despite 4 of 6 patients eventually succumbing to their underlying condition, C-reactive protein was reduced in all patients without significant modification in LDH or D-Dimer. IL-6 was reduced in 4/6 patients. Furthermore, in the 2 surviving patients, a significant increase in lymphocyte count was observed, supporting the notion that restoring lymphocyte activity is critical for obtaining a favourable outcome . AnotherCurrently, a multicentric clinical trial is aiming to better understand the incidence, risk factors, etiology, clinical manifestations and outcome of SARS-CoV-2 infection in SOT patients (Multicentric Study of Coronavirus Disease 2019) (COVID-2019) in Solid Organ Transplant Recipients - Full Text View - 2.6Repurposed mAbs operate through the alteration of the cytokine chain, such as tocilizumab, an IL-6 inhibitor. The complexity of the cytokine chain provides opportunities for the discovery of novel treatments . ConversFirstly, direct reactions to the administered proteins can cause anaphylactic reactions or cytokine storms , both ofIndirect adverse events are more frequent and derived from the action of the antibody , the most frequent adverse events reported to the FDA have been nausea, dizziness, headache, pruritus, non-severe immediate hypersensitivity, diarrhea, and vomiting . BamlaniA safety concern related to the preventing the spread of SARS-CoV-2 is the emergence of viral escape mutations. Viral escape is when under the pressure of medication, the virus mutates in order to evade neutralization. As S-protein variants that resist neutralization are now present at low frequencies in circulating SARS-CoV-2 populations, monoclonal antibody combinations as opposed to polyclonal CP are favored to mitigate viral escape . The com3Here we review the latest data on monoclonal antibody therapy in patients with poor immune responses following severe SARS-CoV-2 infection. It is evident that the number of studies conducted is limited. Results from case reports and cohort studies in this review tell us how treatment regimens of underlying conditions are being altered on an individual basis in order to prevent the otherwise deleterious effects of complete treatment cessation.Tocilizumab appears to be leading SARS-CoV-2 mAb therapy, with ability to control CRS and reduce proinflammatory markers with subsequent resolution of severe disease. Despite inadequate data, CP also appears to prevent SARS-CoV-2 CRS. However, it is important to remain cautious due to increased mutational escape rates resulting from increased selective pressures .Currently, it seems that clinical trials are focused on the effect of SARS-CoV-2 infection in immunocompromised patients clinically  and their ability to mount an immune response to current vaccinations. Outcomes of such patients are improving owing to biological therapies that target immune response against malignant disease, as well as supportive care and cellular therapies seen in SOT patients. These same treatments are being used in patients with severe SARS-CoV-2 infection in order to control the CRS clinical picture. Importantly, alterations in immunosuppressive therapies could negatively impact primary disease outcomes in these patients.Overall, we recognize that the field surrounding this topic is rapidly evolving. With our discussion and conclusions based on case reports and cohort studies, we acknowledge the potential for accompanying biases. However, this will change as clinical data accumulates and more in-depth and large clinical trials are conducted within this subpopulation. Clinical trials should remain vigilant and continue to investigate the effect of MAbs for the treatment of severe SARS-CoV-2 infection in patients with poor immune responses.No funding support was provided for this study.William Migo: conducted online search studies, Formal analysis, Writing – original draft. Marko Boskovic: Writing – original draft. Robert Likic: devised and suggested the topic, advised on all parts of the manuscript.The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.


Unfortunately, the original version of this article  containeIn the analyses that were published, there were significant differences on Low Self-Esteem at follow-up favoring CBT+, but no other differences in both Emotional Dysregulation and Low Self-Esteem. With the correct scoring we found significant differences favoring CBT+ on Emotional Dysregulation at end of treatment and Self-Esteem at both end of treatment and follow-up. Our conclusion favoring CBT+ has not changed, but the evidence supporting this conclusion has strengthened.Abstract should report that:The Results: Overall, greater improvements were observed in CBT+. Differences in number of objective binge eating episodes, emotional dysregulation  and self-esteem (EDI-3 Low Self Esteem) at end of treatment, and eating disorder psychopathology  and self-esteem at follow-up reached statistical significance with small to medium effect sizes (Cohen’s d between 0.43 and 0.66). Of the patients in the CBT+ group, 69.9% reached clinically significant change at end of the treatment vs 65.0% at follow-up. Although higher, this was not significantly different from the patients in the DBT group (52.9% vs 45.8%).Plain English Summary: Greater improvements were observed in the CBT group regarding the number of objective binge eating episodes, emotional dysregulation and self-esteem at the end of treatment, and regarding global eating disorder psychopathology and self-esteem 6 months after treatment.Table Secondary Outcomes should report:The p = 0.038; d = 0.43). Also, the CBT+ group experienced greater reductions in EDI-3 Low Self-Esteem at both end of treatment  and at follow-up . Results of sensitivity analyses confirmed these findings at both end of treatment  and follow-up .Results of secondary outcome analyses are presented in Table Discussion should report:The Also, again contrary to our expectations, we did not detect any differences in favor of DBT-BED on measures related to emotion regulation. Indeed, at end of treatment, CBT+ outperformed DBT-BED on emotional dysregulation. This seems remarkable given the theoretical foundation of both therapies with DBT-BED targeting emotion regulation and CBT targeting dietary restraint and other behavior originating from the overvaluation of weight and shape. Possible reasons for failing to find differences may be related to limited statistical power or to increased treatment time in CBT+. Concurrently, to stay close to clinical practice we did not control for content and therefore conceptual overlap may have occurred. Differential effects of both therapies were possibly compromised because of this. However, it should be noted that most findings on the emotion regulation measures in this study are in line with Safer and colleagues [26] who found a consistent lack of differential impact with a broad range of emotion-regulation measures comparing DBT-BED to an active controlled for content comparison. Also, in individuals with bulimia nervosa, CBT has been found to produce decreases in emotion dysregulation [60]. This suggests that decreases in emotion dysregulation might not be attributable to the specific emotion regulation techniques used in DBT-BED, but to therapeutic elements shared across various treatments.


The emergence and development of aggregation induced emission (AIE) have attracted worldwide attention due to its unique photophysical phenomenon and for removing the obstacle of aggregation-caused quenching (ACQ) which is the most detrimental process thereby making AIE an important and promising aspect in various fields of fluorescent material, sensing, bioimaging, optoelectronics, drug delivery system, and theranostics. In this review, we have discussed insights and explored recent advances that are being made in AIE active materials and their application in sensing, biological cell imaging, and drug delivery systems, and, furthermore, we explored AIE active fluorescent material as a building block in supramolecular chemistry. Herein, we focus on various AIE active molecules such as tetraphenylethylene, AIE-active polymer, quantum dots, AIE active metal-organic framework and triphenylamine, not only in terms of their synthetic routes but also we outline their applications. Finally, we summarize our view of the construction and application of AIE-active molecules, which thus inspiring young researchers to explore new ideas, innovations, and develop the field of supramolecular chemistry in years to come. The recent development in the field of supramolecular chemistry, especially in chemo-/biosensing, biological cell imaging, and drug delivery systems, has gained a lot of attention due to its high quantum yield and good photostability ,2,3. HenN,N-dicyclohexyl-1,7-dibromo-3,4,9,10-perylenetetracarboxylic diimide (DDPD) as shown in Figure 2. There are other non-radiative decay processes such as restricted intramolecular vibration and rotational relaxation responsible in the AIE process. Many research groups have reported AIE-active molecules that can be used for chemical sensors [Figure 3.Luminescence is a spontaneous light emission process that comes from excited electronic states upon absorption of UV-vis light which has received great attention in various fields in chemistry, physics, material science, medicine and biology . Most of sensors ,19,20. A sensors ,22. The  sensors . This ch sensors ,27,28,29Although a few review articles were previously published on AIE-active molecules which describe their application in different fields separately, each review has only explored one type of application. Therefore, in this review, we decided to combine the AIE-active luminogens in biological oriented application such as such as sensing of different essential and non-/toxic ions, biological cell imaging, fluorescent biomarker markers and have further extended this to drug delivery systems for controlled release of a drug, which may attract more researchers in the field. +, K+, Ca2+, Zn2+ and Mg2+, Fe2+) and non-essential/toxic metals  and anions . Detection with a lower detection limit with quantification is very important for both the essential and non-essential metal ions due to their presencefrom a biological and environmental point of view. Among the wide range of applications of fluorescence techniques using fluorescent molecules of various cations and anions, is the most important and found to be a promising active platform in various areas.Metal ions play a very important role in various biological and physiological processes occurring in the body and are required by all life forms. Most of the metal ions participate in many biochemical processes, such as material transportation, energy conversion, information transmission, and metabolic regulation . The pre+ in plasma ranges from 3.5 to 5.5 mM; moreover, if the concentration increases to 7.0 mM then it may result in a complication [+ ion, Liu et al. synthesized molecular rotors for detection of K+ ion [+ ions. There are very few AIE active fluorescent probes that have been reported until now. In this regard, Wang and co-workers utilized an AIE strategy and constructed a highly sensitive and selective fluorescent OFF-ON probe via host-guest molecular recognition by functionalizing a novel crown ether on TPE derivative by the thiol via click reaction, yielding TPE-(SH)4 and maleimide-functionalized benzo-15-crown-5(B15C5). The probe TPE-(B15C5)4, consisted of TPE as the core moiety with four substituted B15C5 units. Its optical properties were studied via the AIE mechanism and found to be highly selective and sensitive towards K+ ions [+ ion. Furthermore, the probe was used for biological cell imaging [+ in water [Among cations, potassium ion is an essential component of the human body that plays a very important role in monitoring and regulating the various physiological functions, such as heart beat, muscle strength, regulates nervous and renal functions ,32. The lication . To quanf K+ ion  bearing  K+ ions . In addi imaging . Moreovein water . The str2+ may result in various diseases resulting in obesity and Alzheimer’s disease [2+ in the body may lead to several diseases’ cardiac arrhythmias, sarcoidosis, and tuberculosis. Therefore, sensing and monitoring extracellular and intracellular Ca2+ is important for diagnosis. In this regard, Gao and co-workers designed an AIE active probe for in situ detection of calcium. The probe SA-4CO2Na can distinguish efficiently between the normal and hypercalcemic calcium in the cell. The probe was synthesized by reacting 5-(chloromethyl)-2-hydroxybenzaldehyde with diethyl imino diacetate in the presence of hydrazine monohydrate to give SA-4CO2Et which was further reacted in presence of sodium methoxide affords to form SA-4CO2Na. The exact mechanism involved in the detection of Ca2+ is by the formation of highly emissive fibrillar aggregate via electrostatic and chelating interaction between the iminodiacetate groups and Ca2+ ion. Initially in the absence of calcium the probe shows very weak emission in aqueous solution while in the presence of calcium the formation of fibrillar takes place resulting in the enhancement in fluorescence, as shown in Calcium is another essential metal ion for various physiological functions such as muscle contraction, blood pressure, heart beats, vascular and nerve functioning at the same time calcium major component of the bone structure in the body . The int disease . The inc2+ using the criteria of AIE behavior. The probe consisted of a TPE moiety with a bidentate pyridine carboxylate unit. The probe showed a “turn-on” fluorescence response to Ca2+ with a lower detection limit of 51.2 nM. Importantly, the probe can also be recycled by addition of ethylenediamine tetra-acetic acid (EDTA) [2+ imaging. This gel consisted of polyacrylic acid (PAA) functionalized with TPE produces PAA-TPE, in which TPE acted as a pendant with an AIE-active property. Interestingly, crosslinking with gel (g-PAA-TPE) showed good selectivity towards Ca2+ [2+.In another report, Wang and coworkers designed AIE active polyarylene ether nitrile fluorescent nanoparticles acting as an excellent probe for intracellular imaging. The synthesized nanosphere showed excellent biocompatibility in presence of calcium with a 21% quantum yield . Moreoved (EDTA)  and furtrds Ca2+ . Figure +, K+ and Ca2+, Zn2+, plays a very important role in various biological and physiological functions such as the nervous system, gene transcription, immune functions, and mammalian reproduction. In fact, one of the most important applications is that the Zn2+ acts as an excellent catalytic cofactor and structural center in various enzymes, DNA, and proteins. Therefore, the need for studying and monitoring the Zn2+ is a major aspect in sensing applications. By taking advantage of AIE-activity of molecules, Sun and coworkers designed a TPE-based “turn-on” fluorescent probe for detection of Zn2+ ion in an aqueous medium. In this, co-ordination of Zn2+ to -N(CH2COO−)2 and intermolecular coordination of Zn2+ lead to aggregation resulting in an enhancement in fluorescence [2+ ions. This fluorescent probe can be employed for biological cell imaging and drug delivery systems [2+ and Hg2+ ion with 1.24 × 10−6 molL−1 and 2.55 × 10−9 mol L−1, respectively. The AIE activity of the fluorescent probe was analyzed using the THF-water fraction [3+ and Zn2+ detection [2+ ions [2+ with high selectivity and sensitivity exhibiting a low limit of detection of 38.9 nM. Thus due to its low cytotoxicity, the probe is applied for sensing of Zn2+ in live cells [2+ and three histidine residues. The probe showed strong fluorescence emission in presence of Zn2+. The observed limit of detection was 18.56 nM and it can be employed for biological cell imaging and intracellular detection of Zn2+ having low cytotoxicity and good stability [2+ ion. In the human body it is well known that after iron, zinc is the second most common transition metal ion. Along with Narescence . In anot systems . Anotherfraction . More reetection . Diana a[2+ ions . Moreoveve cells . In thistability . Figure 3+, Cr3+, Cd2+, Co2+, Mg2+, Hg2+, Sb3+, CN−, F−, Br−, Cl−, As3+, As5+, Cu2+. Therefore, there are several analytical tools have been employed for the detection of this metal ion and anion in the system such as atomic absorption spectroscopy, inductively coupled plasma mass spectrometry, and colorimetric methods. However, fluorescent chemosensors have gained a lot of advantages over all these methods for several reasons such as fast, cost-effective, simple and easy to handle, naked-eye detection, and low cost of instrumentation. However, few organic fluorescents suffer from aggregation-caused quenching thanks to the AIE phenomenon developed to overcome the difficulties faced due to ACQ. Therefore, here different AIE active fluorescent probes  in aqueous media [3+ to give a symmetrical As–(Cys-TPE)3 complex. Wen and group synthesized a novel AIE triphenylamine fluorophore used for sensing of Hg2+ and CN−. The probe showed excellent AIE active behavior and has potential application in biological cell imaging. However, the probe can be recycled and reused without any loss [2+ in aqueous media. The probe has good practical applicability in the preparation of test strips and detection of Hg2+ in a water sample [2+. The probe showed a very low limit of detection up to 7.93 nM and the probe was further used for test strip preparation, which is one of the best advantages for practical applicability [2+ and Al3+. Here, the probe showed quenching of fluorescence to Cu2+ and red-orange fluorescence for Zn2+ with 1:1 stoichiometry. However, the strong fluorescence of Bis-TPE+Cu2+ can be recovered by adding adenosine triphosphate (ATP) giving “turn-on” fluorescence similar to Bis-TPE+Zn2+ that can be quenched by adding Cu2+ which is then further recovered by adding ATP. The probe Bis-TPE can be employed for test strips sensing and biological cell imaging [2+. The probe possesses a good AIE active property and shows a “turn-on” fluorescence response towards Cd2+ ions. The limit of detection for the probe was found to be 0.01 μM. Interference studies in the presence of only Cd2+ showed a good response [Beglan et al. synthesized a derivative of TPE functionalized with cysteine as the fluorescent AIE active dye for the detection of Arsenic  prepared by NIPAM as a hydrophilic unit and tetraphenylethylene-spiropyran monomer (TPE-SP) employed for detection of cyanide in aqueous media. The unique property of this fluorescent probe is that in the presence of UV light the closed spiropyran (non-emissive) poly(NIPAM-co-TPE-SP) opens to give merocyanine (MC) (poly(NIPAM-co-TPE-MC) in an aqueous solution . In addiea probe . Similarea probe . In anotrobe [2− . AIE actrobe [2− , explosirobe [2− ,71,72, brobe [2− ,74, pathrobe [2− , food adrobe [2−  and so oThe various fundamental processes taking place in life can be very well studied and understood which can be achieved effortlessly using fluorescence technique. Fluorescence microscopy is an important tool that has now become most advantageous and launched in biological research for advance and a better understanding of various intracellular processes and dynamics at a cellular level. The field of fluorescence imaging is actively developing as this fluorescent tool plays a major role in monitoring the different analytes and helps in studying the biological events occurring in the intracellular environment. Fluorescence microscopy is one of the best techniques to have been used in the last few decades. Nowadays, there is great progress in instrumentation techniques which makes fluorescence imaging simple and also overcomes the drawbacks and challenges suffered in the past. Doing so, various advantages may be tackled such as minimal photodamage, high resolution, and penetration deep into tissues. Nevertheless, in fluorescence microscopy, two-photon fluorescence imaging has a greater advantage over one-photon fluorescence imaging .2. Interestingly, the Tat (transactivator of transpiration)-AIE dots demonstrated excellent imaging properties [In this regard, Li and co-workers designed organic far-red/near-infrared AIE active TPE substituted dots such as TPE-TPAFN and TPA-FN with excellent utility in long-term cellular tracing. Due to its excellent characteristics of high emission efficiency, large absorptivity, excellent biocompatibility, and also its photobleaching resistance, the fluorescent probe is a good candidate for in vitro as well as in vivo cellular tracing. The matrix used for fabrication is the mixture of polyethylene glycol (PEG) and lipid-PEG-NHoperties ,79. Wang et al. used “turn-on” fluorescence based on AIE active TPE in conjugation with chitosan to produce chitosan-TPE bioconjugate which can be used as “turn-on” fluorescence for long-term cellular tracing, which is very important for monitoring biological and therapeutic processes. This bioconjugate exhibits excellent AIE active property followed by internalization of aggregate take place in HeLa cells for further biological cell imaging. The HeLa culture was used and incubated for 24 h and the fluorescence images were recorded, and the cell imaging process was carried out until the 15th passage, In the fluorescent materials, far-red/near-infrared (FR/NIR) emissions higher than 640 nm are regarded as an excellent and promising candidate for fluorescence imaging. Using similar criteria, the Qin group synthesized selenium containing FR/NIR AIE active luminogen (TTSe dots) which is very rare; however, there are very few reports available on selenium-containing fluorescent probes for bioimaging application. The synthesized probe has excellent applications in imaging of the sentinel lymph node (SLN) mapping and finally in tumor imaging. In addition, this fluorescent luminogen is utilized for imaging the brain blood vessels of mice using a high-resolution two-photon imaging technique as shown in 2000 and DSPE-PEG2000 maleimide matrix. Furthermore, the obtained nanoparticle was modified with cysteine Tat-peptide (RKKRRQRRRC). The fluorescence quantum yield of the compound was found to be 23.5% with a lifetime of 5.37ns. Thus, the red emission made the AIE-Tat NPs a promising candidate for bioimaging of BMSCs cells; however, intense red emissions were observed in a confocal microscope. The results indicated 100% labeling efficiency and the concentration of AIE Tat does not affect the cell viability of BMCs cells [− in cells. The TPE unit being hydrophobic forms aggregate nanoparticles into micelle that emits red fluorescence. Therefore, the probe can be utilized for endogenous ClO− detection in live cells. To study the endogenous imaging of ClO−, the zebrafish was used as a sample because of their excellent transparency at the embryonic and larval stages. Zebrafishes were incubated with the fluorescent compound for 60min, and green fluorescence was observed however the green fluorescence enhanced with increasing incubation time. This result reveals that the probe can be employed well for in vivo ClO− detection and imaging applications [Similarly, Gao and coworkers developed AIE functionalized with Tat-peptide (AIE-Tat NPs) PITBT-TPE for tracing bone marrow mesenchymal stem cells (BMSCs). The fluorogens consisted of a mixture of DSPE-PEGCs cells . Huang eications . The Ma ications . Moreover, the Wan group prepared AIE-active fluorescent polymeric nanoparticle using the polysaccharides, as many of the fluorescent polymeric nanoparticles (FPNs) have increasing demand in theranostic application especially in drug delivery systems in ttreatment and diagnosis. In Wan group work, they utilized cost-effective naturally occurring polymer oxidized sodium alginate (OSA) obtained from marine seaweeds. The designed fluorescent AIE active OSA-Phe-OSA FPNs show red fluorescence with excellent photostability and biocompatibility. The biological cell imaging studies were conducted on L929 cells using OSA-Phe-OSA FPNs. They showed the cellular uptake of the fluorescent probe was effective with excellent biocompatibility. The strong fluorescence was observed after 3 h of incubation which suggests that the OSA-Phe-OSA has excellent staining performance. They concluded that these OSA-Phe-OSA AIE-active nanoparticles can be used in future for controlled drug delivery of cisplatin . Lipid droplets are the powerhouse of proteins and lipids responsible for various biological processes and diseases, for example virus infection, cancer, obesity and so on. Several approaches are being used earlier for visualization such as color staining, Raman microscopy, transmission electron microscopy. Amongst all these techniques near-infrared and two-photon excited fluorescence (TPEF) are more advantageous over other techniques due to their high-resolution imaging and low photodamage. Therefore, Gao et al. introduced AIE active triphenylamine (TPA) and indane-1,3-dione optical material. The compound showed good AIE activity and TICT effect hence can be used for lipid droplet specific imaging and thus making it easily available for biological applications. The biological cell imaging on HCC827 and A549 cells were carried out which suggested that upon incubation for 15 min the fluorescent probe IND-TPA shows excellent cellular uptake property . Another2 NPs are beneficial for long-term super-resolution bioimaging applications in future technology developments [Fluorescence microscopy is considered an important tool in the imaging of tissue. Due to optical diffraction limits, the spatial resolution is restricted up to nearly 200 nm which keeps the imaging unclear. After several decades numerous high-resolution methods were discovered. In this direction, Li and co-workers synthesized AIE active nanoparticle (NPs) of 2,3-Bisphenyl)amino)phenyl)fumaronitrile (TTF), which was fabricated with colloidal mesoporous silica to form AIE-active NPs which are used for cell imaging by utilizing the stimulated emission depletion nanoscopy  which is a super-resolution imaging technique as it gives a resolution of <50 nm that is more advantageous over other fluorescence imaging tool. Moreover, utilizing the long-term stimulated emission depletion (STED) nanoscopy TTF@SiO2 NP was investigated for imaging cancerous HeLa cells. lopments .Supramolecular interactions play a very important role and have been widely used for the fabrication of various fluorescent assembled nano- and micro-superstructures. In this regard, the Xu group fabricated AIE active fluorescent organic nanoparticles (FONs). The FONs were synthesized having an AIE active property exhibiting red emission, however they were fabricated through the supramolecular interaction between β-cyclodextrin (β-CD) and adamantine AIE active dye. Due to its AIE activity of Ph-Ad/β-CD and strong red emission, the FONs can be used for an imaging application. To check its biocompatibility cell viability studies were carried out using a CCK-8 assay. The 100 % cell viability was observed for A549 upon incubation with FON of cells for 24 h. Cell uptake studies for the FONs were evaluated and confirmed that due to low cytotoxicity the Ph-Ad/β-CD, FONs acts as an outstanding platform and thus can be utilized for further biological and biomedical application . AnotherGuan and coworkers synthesized AIE active non-conjugated polymer dots (Pdots) by fabricating amphiphilic PNIPAM with Eu (III) complex which self assembles in aqueous media as a four-arm star polymer TPE-tetraPNIPAM-Eu (III). The developed fluorescent material is employed for cancer cell imaging. The Pdots show dual fluorescence emission properties from TPE hydrophobic moiety and hydrophilic PNIPAM-Eu (III). Due to its dual emission property, blue light at 630 nm and red light at 395nm make it a promising candidate for cell imaging of HeLa cells, A549, and HepG2 cells upon incubation with AIE Pdots. The cytotoxicity studies revealed 90% cell viability Zhuang et al. synthesized AIE-active redox and pH-responsive polymeric micelles mPEG-P(TPE-co-AEMA). This synthesized polymeric micelle has excellent biocompatibility, it acts as a prominent nanocarrier for drug delivery system. The cellular imaging was carried out using a mPEG-P(TPE-co-AEMA) micelle for 4T1 cells and HeLa cells. Both the cells showed 100% cell viability indicating that the micelle has excellent biocompatibility. The confocal laser scanning microscopy (CLSM) images of 4T1 cells as represented in Zhang and coworkers designed amphiphilic TPE-based pyridinium salt with yellow emissive (TPE-MEM) with a unique AIE active phenomenon. The probe has good water solubility, biocompatibility, and cell membrane specificity. The cytotoxicity study revealed that the cells were viable to 20 μM with low toxicity. The cell imaging studies were undertaken by using cervical cancer HeLa cells which were incubated with TPE-MEM at room temperature with 5 μM. The excess of PBS buffer was removed by washing and the images were recorded as shown in o-Py, but as the Fe3+ was added the blue, as well as red, emission was illustrated. Upon incremental addition of Fe(III) red fluorescence intensity increases rapidly. Its excellent biocompatibility reveals that TPE-o-Py acts as an excellent boilable for Fe(III) in both Hela and MCF7 cells [3− and ClO4−. The fluorophores were used for mitochondrial targeting. To study the effect of alkyl substituent the HeLa cells and HEK-293T were selected for cytotoxicity, eventually investigated by CLSM and subsequently showing that TPEPy-1 and TPEPy-2 get accumulated and represent the yellow fluorescence; however, weak fluorescence was observed for TPEPy-3 and negligible fluorescence for TPEPy-4 fluorogens. Thus, they have concluded that the TPEPy-1 and TPEPy-2 due to suitable hydrophobicity accumulate well in the cell membrane while a very strong hydrophobic nature makes it impossible for fluorogens to penetrate deep in the tumor as well as the normal cells Feng et al. demonstrated a position-dependent substituent effect on another TPE-based AIE active fluorescent probe functionalized with pyridine moiety (TPE-o-Py) which displays high selectivity and sensitivity towards the Fe(III) ion. In addition, in vitro cellular imaging and selectivity of Fe(III) was carried and this fluorescent probe shows pronounced red-shift and is applicable in biological cell imaging. The HeLa and MCF7 cells were incubated with the fluorescent probe, and images were captured under confocal fluorescence microscopy. The HeLa cells exhibited blue emission upon incubation with TPE-F7 cells . In anotHowever, it is critically important for a cell viability study of therapeutic efficacy in biomedical applications. Therefore, Hu and co-workers designed and synthesized AIE active polymeric material with TPE and a negatively charged side chain of OEGs P(TPE-OEG) to study the viability of cells. AIE-active polymer demonstrates good tracking ability and excellent biocompatibility . The LinBy using the specific sugar–protein interaction strategy, Wang and coworkers developed a diketopyrrolopyrrole (DPPM) AIE-active probe with two mannose groups and diketopyrrolopyrole (DPP) core. They further studied the effect of an increasing number of sugar groups on the DPPM two DPPF-M (with four mannose units) and DPPS-M (with six mannose units). All three DPPM, DPPF-M, and DPPS-M fluorophores showed AIE activity which was further employed for the detection of lectin. The fluorescence of the DPP unit increased upon the addition of lectin. Interestingly, the probe showed low cytotoxicity towards MCF-7 and MDA-MB cells and had greater capacity for recognition of sugar ligands and glycoproteins cellular imaging of cancer cells which overexpressed mannose receptors through a specific sugar–protein interaction. In which, DPPS-G was used as a reference without any mannose unit for comparative cell imaging study with DPPF-M and DPPS-M probe. The laser scanning confocal microscopy (LSCM) results show that upon incubation of cells with DPPS-M and DPPF-M, units showed red fluorescence to cancer cells while no fluorescence to normal cells. In addition, they noticed that cells upon incubation with DPPM had very weak red fluorescence, and with DPPS-G showed no red fluorescence. This indicated that only the mannose functionalized DPP-based AIE-active compounds with a greater number of mannose groups comprising a greater number of binding sites are responsible for cellular uptake resulting in its utilization in a biological cell imaging application .2H4∙H2O in living cells. The HeLa cells were incubated with probes C1 and C2. The results indicated that upon incubation with hydrazine there was the disappearance of fluorescence under a fluorescence microscope, suggesting that the presence of hydrazine makes the probe C1 and C2 applicable for the detection of hydrazine in live cells [Yan et al. synthesized di(2-picolyl)amine(DPA) which was highly selective towards the Zn(II) metal ion. The modified DPA to form 3-amino-9-ethyl carbazole with salicylaldehyde was prominently utilized for detecting the Zn (II) ion in aqueous media. The probe applied for biological cell imaging. Initially, cytotoxicity studies were undertaken to study the viability which revealed low toxicity with 97.7% viability. Thus the probe was used for recognizing Zn(II) ion in HeLa cells . Wang’s ve cells . Tarai and co-workers synthesized two cyano functionalized ICT and AIE active probes for cytotoxicity and cell imaging applications. The molecules with substitution effect on AIE-1 and AIE-2 were investigated. The AIE-1 without substitution showed yellow color with weak charge transfer whereas AIE-2 showed strong charge-transfer absorption with yellowish-orange color. In both AIE-1 and AIE -2, indole moiety acts as an electron donor and the cyan-functionalized group acts as an electron acceptor unit. Furthermore, both the probes were investigated for cell imaging by using the HeLa cells as the model system for cellular uptake. The toxicity studies revealed good cell viability to 90% even after increasing cell incubation period. Furthermore, the HeLa cells were incubated with AIE-1 and AIE-2 for 24 h and at 37 °C. The images were captured by a confocal microscope under bright and greenfield as illustrated in Thermoresponsive polymeric AIE active -benzene-b-N-isopropyl acrylamide micelles were developed very recently by Ma and co-worker by reversible addition-fragmentation chain transfer polymerization of 1-ethenyl-4--benzene (TPEE) and N-isopropylacrylamide (NIPAM). The polymer PTPEE-Pns possesses a good AIE-active property. As the polymeric micelle showed excellent stability and bright fluorescent emission, the micelle was further explored for cell imaging. Before cell imaging, the micelle was subjected to a cytotoxicity study which revealed low cytotoxicity with 95% cell viability. The micelle exhibited blue fluorescence upon incubation and blue fluorescence was observed in the cytoplasm rather than the nucleus. Thus, it was considered a promising candidate for cellular imaging . +). The TPE-NIM+ was used for staining of different cell lines acting as an excellent fluorescent marker [Various biological and cell functions are accompanied via the plasma membrane which is the important building block of a cell. In this regard, Sayed et al. reported photostable AIE active probe for a plasma membrane imaging study comprising of tetraphenylethylene naphthalimide  [In the last few decades, several nanocarrier molecules were used as drug delivery vehicles and considered as an excellent platform to carry different nucleic acids, antibodies, photosensitizers, imaging agents, and anticancer drugs that help in diagnosis and therapeutics . There a2) ,120,121 2) , functio2) , cyclode2) ,125 and 2) . However2) ,127. Man2) ,129. The2) .hyd-TPE via conjugation with TPE consisting of acid cleavable hydrazone bonds. Further micelle was loaded with DOX forming the hydrophobic interaction, as shown in hyd-TPE-DOX micelle in 24 h. The self-assembled TPE micelle disassembled itself under acid conditions through bond cleavage as the DOX release increased. Thus, this suggests that the micelle acts as an excellent candidature for drug release under an acidic condition in tumor cells. In addition, the micelle was utilized for cell imaging.In this regards, Li et al. prepared TPE functionalized organophosphonic acid, bis)-bis(methylene diphosphonic acid (PATPE) with excellent AIE activity . The molIn vivo drug release monitoring by using AIE-active thermogelling polymer was carried out by Liow et al.  The self7 polymer was fabricated by further self-assembling into vesicles and micelles which consists of hydrophobic TPE fluorophore connected by Schiff base bonds. The molecule maintains structural integrity at normal physiological pH but under the acidic condition the aggregated molecules lose their identity. It is noteworthy that caged-shaped POSS improves the AIE effect by restricting the intramolecular rotation of TPE. The polymeric micelle is further encapsulated with antitumor DOX which maintains stability and protects leakage in blood circulation, however, at the same time the rapid release of DOX takes place due to protonation of Schiff base as it gets internalized at the tumor site on the process of drug release mechanism [co-HD)-ss-P(TPE-co-HD)-PAEMA-PMPC copolymer exhibiting an AIE-active imaging property and charge conversion for chemotherapy and bioimaging application. The imine conjugated with DOX becomes cleaved under an acidic condition which is combined with a hydrophobic core along with the glutathione (GSH) disulfide bond as shown in Hyaluronic acid (HA) is a naturally occurring polysaccharide found mostly in the extracellular matrix, epithelial connective tissue widely used in biomedical applications especially in drug delivery, tissue engineering, and molecular imaging. HA is considered as a prodrug nanocarrier in combination with DOX, paclitaxel, and mitomycin Cor siRNA for cancer therapy. In this regard, Wang’s group modified HA with phosphorylcholine in conjugation with AIE active moiety and DOX system. Usually, the HA forms micelles which are internalized into cancer cells and the fluorescent ability of AIE active makes it more possible for the drug delivery process and helps to locate the micelles. However, the hydrazone bond cleavage takes place in an acidic environment releasing DOX at the targeted site . They haechanism . Hao andechanism . Nanodiaechanism . As discWang et al. reported two color-tunable AIE active conjugated polymers which were synthesized by Pd-catalysis by the Suzuki coupling polymerization reactions P-1 and P-2, with P-1 exhibiting intramolecular FRET pair with clear green colored AIE fluorescence and P-2 with TPE and DTBT moiety turning from green to red fluorescence. This AIE-active polymer can form stable conjugated polymer nanoparticle which acts as drug carrier of paclitaxel (PTX) and showed good cytotoxicity on HeLa and A549 cells which internalize in the cells located with green or red AIE fluorescence. Therefore, this type of AIE-active CPN acts as a drug carrier of PTX which has a self-indicating property with intramolecular FRET pairs . Herein,2+ which is considered a multifunctional candidate for cell imaging, drug loading, and delivery as well as acting as a “turn-on” sensor for detection of Zn2+ ion [. The structure of the polymeric material is shown in Besides the pH-responsive systems, Shamsipur and coworkers designed dual emissive fluorescent silver nanoclusters (AgNCs) capped with hemoglobin exhibiting features such as NC oxidation and AIE enhancement used for drug delivery and cell imaging. The oxidation and AIE-active nature resulted in ligand to metal charge transfer of the NC in presence of oxygen, sulfur, and nitrogen that converts Ag(I) ions to Ag(0)@Ag(I)-Hb core-shell NCs. However, the hyaluronic acid (HA) on the surface of the Hb forms an excellent platform for doxorubicin drugs such as DOX/HA/AgNCs. This system can be used in imaging, gene delivery, biosensing, photocatalysis, and electrochemical applications . Metal-oZn2+ ion . NanomatZn2+ ion . In addiAnother light activable and AIE-active polymeric nanoparticle for investigation of drug release mechanism. Wu and coworkers employed Pt (IV) prodrug with AIE active fluorophore which was embedded in PtAIECP and DOX further encapsulated with nanoparticle to give PtAIECP@DOX NP. This nanocarrier activated the prodrug Pt (IV) to Pt(II) thus releasing the DOX into the cell via the fluorescence “turn-on” approach resulting in the cleavage of the polymeric linkage. Thus, considered a good platform for Pt (II) as an anticancer and DOX for intracellular drug release at a particular site. This polyprodrug acts as a dual drug release mechanism in combination with AIE active phenomenon. In the reported work, initially upon irradiation a reduction activation process takes place in which Pt(IV) is converted to Pt(II) which further promotes the Pt(II) and DOX to be dissociated. In 1 hour of pre-irradiation, 30% of the Pt and DOX were released making it impossible for the nanocarrier to release the drug in dark conditions. Accordingly, it represents the switch ON/OFF effect in the presence of light and dark conditions. Therefore, the drug release can be investigated by using fluorescent nanoparticles .Dong et al. constructed AIE active self-assembled nanostructure pH/redox with FRET effect that can be utilized for monitoring the drug delivery and release at a specific site. The molecule was synthesized by polyamide amine (H-PAMAM) and polyethylene glycol (PEG) bridged at the periphery by dipropionic acid. Furthermore, this AIE active molecule was loaded with the anticancer drug DOX. It was observed that H-PAMAM shows strong fluorescence, while the AIE effect and FRET between H-PAMAM and DOX help in monitoring the drug release mechanism. As the release of the drug takes place, the FRET process between the carrier and loaded drug completely disappears. Thereafter, the host–guest interaction between the PEG and cyclodextrin (α-CD) forms the nanocarrier as H-PAMAM-ss-mPEG/α-CD abbreviated as (HG/CD) effectively shows both AIE as well as the FRET process. The rapid and selective release of the drug was well monitored by using the pH/redox dual-responsive material carrying excellent biocompatibility enabled the drug carrier tracing, drug release, and chemotherapy .The design and synthesis of multicolored drug carriers have shown significant importance which helps in a self-illuminating drug delivery system. Recently in 2019 Wang and coworkers developed donor-acceptor conjugated polymer exhibiting AIE activity. In this work, the conjugated polymers P1, P2, and P3 were synthesized by using AIE active tetraphenylethylene moiety and donor–acceptor moiety (D-A). The fluorescence characteristics of all three P1, P2, and P3 can be changed from ACQ to AIE by varying the donor moiety N,N-dimethylaminoaniline salicylaldehyde Schiff-base with different substituents for an intracellular fluorescence assay, imaging, and drug delivery system. The functionalized DSS-4-DEA exhibits high cell-penetrating capacity, which was found to be a more promising fluorescent material. In addition, the DSS-4-DEA fluorescent probe acts as a transmembrane carrier for enhancing the internalization of DSS-5-Cl. Furthermore, the DSS-4-DEA is considered an excellent platform for drug delivery. Here, the fluorescent material is loaded with the anticancer drug curcumin (Cur). The Cur has excellent medical effects including anti-inflammatory and antiproliferative. Since DSS-4-DEA forms the aggregate it can thus be loaded with Cur. Therefore, the DSS-4-DEA displayed multiple bio applications [Blink-DA) with an AIE-active property was synthesized. This fluorescent molecule has potential application in bioimaging and can be used for theranostic applications. The PEI contains the polyethyleneimine linkage, dimethyl maleic anhydride (DA), and polyethylene glycol (PEG) which is a bridge to the PEI chain via benzoyl imine linkage. This polymeric micelle was further loaded with DOX exhibiting a prolonged-release drug mechanism with bioimaging, and hence considered as an excellent candidate for enhanced chemotherapeutics delivery [Li and group designed multifunctional AIE active 4-ications . Ma and delivery .2O2 or dithiothreitol (DTT). However, the following polymeric gel was encapsulated with DOX and can be used as a good drug carrier with controlled drug delivery and sensing application. Since the redox process is faster in tumor cells, the drug release is explained well under redox conditions as the polymeric gel is well utilized as diselenide bond cleavage takes place for redox stimulus in the tumor environment. Hence, the SeSey-PAA-TPEx can be used for loading and release [3+ agent which was considered to be highly active as an anticancer agent. Thereafter, the transferrin (Tf) was coated outside the Gd3+ which made the nanoparticle nontoxic for cells. However, charge reversion in lysosomes Tf protein being released makes the nanoparticle toxic and helps in killing the cancerous cells. Thus, this is considered an excellent candidature for theranostic application, There are several traditional multifunctional drug delivery systems (DDS) with a fluorescent dye and targeted unit that were synthesized but due to instability and manufacturing problems as well as low drug is entrapped. Therefore, in 2020 Ma and coworkers constructed multifunctional DDSs via amphiphilic conjugated β-D-galactose with tetraphenylethylene  micromolecules. Here, TPE acts as a hydrophobic chromophore while the Gal species acts as a targeting ligand which self assembles and helps in loading water-insoluble paclitaxel (PTX) as well water-soluble DOX anticancer drugs. Thus pH/b-D-galactosidase DOX loaded TPE-Gal@DOX has good antitumor efficacy compared to free DOX . Additio release . Recentl3 were synthesized by using fluorescent core and oligo ethylene glycol (OEG) chain with azide group which self-assemble into a nanoparticle. Moreover, these soft AIE active dots were loaded with unmethylated cytosine-phosphate-guanine (CpG) that induces the immunostimulatory effect of RAW264.7 cells. Here, TPA-TPE acts as a hydrophobic core, wherein the OEG azide acts as a hydrophilic substitute, and -N3 via a click reaction reacts to the drug. Therefore, the synthesized probe is an excellent platform for the drug delivery system [There are several AIE/AIEE possessing luminophore which has extended its application in biomedical applications. So herein Kumar and co-workers have demonstrated different TPE derivative which has wide application in bioimaging and utilized further for drug delivery process . Recently system . Interesy system .The recent developments in the fluorescent materials in solid and aggregated forms have shown importance in the different scientific and technological fields, especially in biomolecular and environmental applications. There are several organic fluorescent molecules but they suffer from the detrimental phenomenon known as aggregation-caused quenching. To overcome the ACQ process, the Tang group developed another phenomenon known as AIE which is now commonly and widely used in many fields. The AIE phenomenon has become an excellent platform for sensing, biological cell imaging, and drug delivery systems. TPE is the most frequently used luminogen upon functionalization for various purposes to its AIE phenomenon and mechanochromic properties. Nevertheless, AIEgens have been widely used in green energy devices and environmental monitoring. Furthermore, the application can be explored in food safety and quality control which is a major focus in terms of public health.Despite remarkable advancement and development in the AIEgens in sensing, cell imaging, and drug delivery, some challenges should be addressed to find solutions to remaining hurdles. There are a few disadvantages attributed to them such as multiple-step synthesis, non-specific features due to binding sites, and non-targeted drug delivery.To overcome these small issues, the rational design of AIEgens should comprise specific binding sites, which can be used as receptor/binding sites for high selectivity, sensitivity towards the particular analyte, along with easy and simple synthetic routes for design the AIEgens. One more aspect to keep in mind is that the photostability and solubility for a specific application, thus, there is a need for simple and cost-effective strategies to be employed. Therefore, given these facts fluorescent materials need more attention in terms of good stability with varying functionalities.In conclusion, we have focused on the most recent AIEgens and their potential application in the field of sensing, cell imaging, and biomedical application, especially in drug delivery systems. Although several luminogens have been successfully employed limits to their application remain and they are yet to be exploited. In this review, we have described briefly the different AIE-active molecules especially TPE, pyrene, salicylaldehyde organic dye, metal-organic framework, polymeric micelles for sensing of essential, non-/toxic metal ions, and anions. This review also describes AIE luminogens for cell imaging and drug delivery systems. Selectivity and specificity are most important factors considered in biomedical application which can be achieved by combining the target-specific moiety to AIE active chromophore. Thus, distinct properties of AIEgens make them available for sensing, cell imaging and theranostic application. However, more insightful research in the field of AIE-active materials is required for further application in the field of supramolecular chemistry.Even though AIEgens has extended its application in cell imaging and drug delivery systems, there are many problems still to overcome, for example, short wavelengths absorption, non-optimized emission, and broad emission spectrum which restricts its usage in biomedical applications. To overcome the aforementioned problems, the multiphoton absorption, harmonic generation, and up-conversion methods should be constantly employed.


TC) value. Rapid antigen detection tests using self-collected anterior nasal swabs proved to be as sensitive as and more tolerable than professionally collected nasopharyngeal swabs for TC values up to 30 determined by RT-PCR. This finding illustrates the reliability of tests obtained by adequate self-collected anterior nasal specimen. Sensitivity was dependent upon the TC value for each sampling method. While the main advantage of rapid antigen detection tests is the immediate availability of results, PCR should be preferred in crucial settings wherever possible.The objective of our study was to evaluate the sensitivity and specificity of rapid antigen detection tests versus those of reverse transcriptase PCR (RT-PCR) using oral, anterior nasal, and nasopharyngeal swabs. The underlying prospective, diagnostic case-control-type accuracy study included 87 hospitalized and nonhospitalized participants in a positive and a negative sample cohort between 16 March and 14 May 2021 in two hospitals in Vienna. SARS-CoV-2 infection status was confirmed by RT-PCR. Participants self-performed one oral and one anterior nasal swab for the rapid antigen test, immediately followed by two nasopharyngeal swabs for the rapid antigen test and RT-PCR by the investigator. Test results were read after 15 min, and participants completed a questionnaire in the meantime. Test parameters were calculated based on the evaluation of 87 participants. The overall sensitivity of rapid antigen detection tests versus that of RT-PCR with oral, anterior nasal, and nasopharyngeal samples was 18.18% , 63.04% (95% CI 47.55% to 76.79%), and 73.33% (95% CI 58.06% to 85.4%), respectively. All sampling methods had a test specificity of 100% regardless of the cycle threshold (IMPORTANCE Rapid antigen detection devices for SARS-CoV-2 represent a valuable tool for monitoring the spread of infection. However, the reliability of the tests depends largely on the test performance and the respective sampling method. Nasopharyngeal swabs mark the gold standard for sample collection in suspected respiratory tract infections but are unsuitable for widespread application, as they must be performed by medically trained personnel. With the underlying study, the head-to-head test performance and the usability of self-collected samples for SARS-CoV-2 detection using rapid antigen detection devices were evaluated. The results confirm similar sensitivity of self-collected anterior nasal swabs to that of professionally collected nasopharyngeal swabs for patients with a TC of < 30 determined by RT-PCR. The SARS-CoV-2 pandemic is an ongoing threat that requires effective measures, such as rapid and accurate testing methods, to contain its spread. Rapid antigen detection (RAD) tests are highly valued in the detection of potentially infectious patients, as they can provide prompt results in a cost-effective manner , 2. HoweNasopharyngeal (NP) swabs are typically preferred for sample collection in suspected respiratory tract infections. However, to ensure reliable results, the swab must be performed by trained medical professionals, which limits its widespread use in the general population. Moreover, NP swabs are commonly perceived as unpleasant or even painful due to the sensitivity of the nasal and nasopharyngeal mucosa. Even though complications are rare, individual preconditions or improper execution of the swab carry the risk of complications . As a coSwab samples collected from the oral or anterior nasal (AN) cavity offer a less invasive alternative and may improve compliance and testing frequency. As they are easy to obtain, individuals may self-collect samples, thus eliminating the need for health care professionals and reducing the risk of virus transmission. Self-testing presents a major advance in infection control and saves costly resources in the health care sector.Reverse transcriptase-PCR (RT-PCR) is the gold standard for laboratory diagnosis of viral respiratory infections, including SARS-CoV-2. Several studies have confirmed the reliability of saliva and samples from the AN cavity for the detection of SARS-CoV-2 RNA with PCR –11.–Oral swabs might offer an alternative when saliva production is impaired. However, the viral load of oral swabs obtained from SARS-CoV-2-infected children was found to be lower than that of NP swabs . This fiIn view of these results, the use of self-collected AN and oral samples for RAD devices is promising due to their easy collection. However, data regarding the reliability of self-collected samples for RAD devices remain limited –17, and –Demographic data are displayed in TC) values are listed in TC values for all swabbing methods. This decline was particularly pronounced for oral samples, whose sensitivity declined from 100% for a TC of <15 to 33.33% for a TC of 15 to <20  cases, compared to 32 of 46 (69.57%) cases in oral swabs . Support was provided in 15 of 46 (32.61%) and 25 of 46 (54.35%) cases for AN and oral swabs, respectively .No adverse event was reported for any sampling method.TC of <30, RAD tests using self-collected AN swabs were similarly sensitive to RAD devices using professionally collected NP swabs.In participants with a TC values are below 25 but becomes increasingly unlikely when they exceed 30, which goes in hand with infectivity  and negative percentage agreement (NPA) of RAD devices using oral swabs were 24% and 100%, which is well comparable to the test performance of saliva samples reported by Agulló et al., thus rendering oral swabs unsuitable for SARS-CoV-2 RAD devices .Based on the above evidence, RAD tests require considerable viral loads to deliver reliable results. While positive test results thus detect an infection with a high degree of certainty, negative results must not be interpreted as ruling out an infection.In addition, the course of viral load and that of antigen response are variable and dynamic throughout the course of infection . As a coCurrently, RT-PCR is the most sensitive diagnostic method, allowing the detection of small amounts of the viral genome, and thus has potential to confirm infection at any stage of the disease. Because of this property, RT-PCR may be the preferred method in critical settings, such as health facilities and nursing homes. RAD devices, on the other hand, should be considered complementary, high-threshold tools that play their strengths especially in patients with a high pretest probability, i.e., symptomatic patients or close contacts of infected patients.Usability of self-collected samples for SARS-CoV-2 detection using RAD devices has been addressed by few studies , 25. SimA difference in sampling quality of hospitalized and healthy participants was observed, which is also reflected by the number of hospitalized participants that required support by the supervising investigator.Considering that hospitalized and healthy participants received identical instructions, one possible explanation for this discrepancy could be the abnormal situation of hospitalization. In addition, the age difference between the study groups might also have contributed to these differences. Nevertheless, clear instructions are essential to obtain high-quality samples, which in turn form the basis for reliable test results.According to the questionnaire, participants showed a greater willingness to perform AN swabs regularly than to perform NP swabs. For this reason, AN swabs might be a more beneficial screening method despite the slightly lower sensitivity of RAD tests using AN swabs compared to that of RAD tests using NP swabs.A limitation of this study is the moderate sample size for the evaluation of test specificity.Also, participants were supported if they were unable to perform the swab correctly, opposing a real-life-scenario. However, this intervention was necessary to assess the test performance, which was the primary aim of this study.Additionally, the mean age difference between the study groups may have influenced the performance and quality of the swabs. Older age and multimorbidity are undoubtedly among the greatest risk factors for severe SARS-CoV-2 infection requiring hospitalization, which resulted in a higher average age in the patient population but did not affect the primary endpoint –30.–We also acknowledge the difficulties in objectively assessing factors such as perception of swabs and willingness to frequently repeat sampling.Conclusion. Self-collected AN swabs demonstrated sensitivity similar to that of professionally collected NP swabs in participants with TC of <30, illustrating the reliability of RAD tests obtained by using adequate self-collected AN specimens.TC of <15.Self-collected AN and oral swabs were found to be more tolerable and less painful than NP swabs. Although RAD tests using self-collected oral swabs were perceived to be most tolerable and least painful, they were sensitive only in participants with However, RAD test results are highly dependent on the particular swabbing method and are inferior to RT-PCR in terms of sensitivity, limiting its advantages of rapid and cost-effective results to patients with increased pretest probability.This prospective, diagnostic case-control-type accuracy study was conducted in accordance with the ICH-GCP guidelines, the current version of the Declaration of Helsinki (October 2013), and the Austrian Medical Devices Act . Ethical approval for this study was obtained from the Ethics Committee of the Medical University of Vienna. The study was conducted at the General Hospital, Vienna and Clinic Favoriten, Vienna in Austria.The study included 46 hospitalized participants in a positive sample group with active SARS-CoV-2 infection and 41 healthy participants in a negative sample group, both confirmed by RT-PCR in a consecutive series. Participants were enrolled at the Medical University of Vienna and the Clinic Favoriten, Vienna, between 16 March and 14 May 2021, after giving oral and written informed consent to participate.Oral and AN swabs were self-collected by study participants after they received written instructions. Additional explanations were provided only if a participant had difficulties performing the sampling procedure correctly. All swabs were performed at least 30 min after eating, drinking, or brushing teeth.Oral samples were obtained by swabbing between the gums and the inside of the cheeks, collecting saliva and mucosa from either side of the oral cavity. Nasal swabs were self-collected from both nostrils by gently twisting and pushing the swab against the inner wall of the nasal vestibule. NP swabs for RAD devices and RT-PCR tests were performed by the investigating physician immediately after by slightly tilting the participant’s head back and inserting the swab through the nostril parallel to the palate. The swab was then gently rotated at the wall of the nasopharyngeal cavity to absorb secretions before being removed in a rotating motion. At the time the index tests were performed, reference test results were not available to the investigators.50)/mL for SARS-CoV-2 was used. This lateral flow assay is based on colloidal gold immunochromatography using the double-antibody-sandwich method.For RAD devices, the Medomics SARS-CoV-2 antigen test device  with a limit of detection (LoD) of 10 50% tissue culture infective doses  was then dropped into the sample well of the antigen testing device. A visible red test and control line indicated a positive result. RAD test results were read after 15 min and were then photodocumented using Scarletred Vision medical device software .TC), with a test positivity cutoff of TC less than 35.For RT-PCR testing, NP swabs were performed by the investigators immediately after self-collection of oral and AN swabs. The collected material was diluted in 2 mL of physiologic saline solution and was immediately sent to the study site’s virological laboratory for RT-PCR testing. Samples were analyzed by the laboratory without knowledge of the participant’s infectious status. RT-PCR was performed on the fully automated CE/IVD-certified Roche Cobas 6800 RT-PCR system  with the CE/IVD-certified Cobas SARS-CoV-2 assay, according to the manufacturer’s instructions. The Cobas SARS-CoV-2 assay targets highly conserved open reading frame 1a/b (ORF-1a/b) and E-gene regions and uses 400 µL of sample processing volume. Viral load was determined in a semiquantitative manner expressed by the number of PCR cycles needed to amplify RNA to a detectable level, termed cycle threshold  and Microsoft Excel Version 2016 .The sample size consideration is based on exact binomial 95% confidence intervals (95% CI) for the estimated diagnostic test sensitivity of 87%. To yield a lower bound of the confidence interval above 74%, 46 reference test positive individuals needed to be included.Sensitivity and specificity of the index tests, i.e., RAD tests using oral, AN, and NP swabs, are based on comparison to RT-PCR results acting as the reference standard. In this study, sensitivity describes the RAD test’s ability to identify participants whose RT-PCR result confirms SARS-CoV-2 infection. Analogously, specificity refers to the RAD test’s ability to identify participants with negative RT-PCR test results. Positive (PPV) and negative predictive value (NPV) indicate the probability of SARS-CoV-2 infection in participants with a positive test result and no SARS-CoV-2 infection in participants with a negative test result, respectively.For comparison to a test that is not considered the reference standard, positive (PPA) and negative percentage agreements (NPA) are appropriate instead of sensitivity and specificity; however, calculations are identical. Accordingly, percentage agreements were used to describe the test performance of RAD tests using self-collected oral and AN swabs compared to that of RAD tests using professionally collected NP swabs.Accuracy describes the test’s ability to discriminate healthy and infected participants correctly with regard to the reference standard. If the index test is compared to a test that is not the reference standard, the overall rate of agreement (ORA) is used as an equivalent for accuracy.Test performance parameters were calculated according to the following equations:Wilcoxon signed rank test was applied for ordinally scaled paired variables retrieved from the questionnaires, in particular information on discomfort, pain, and willingness to frequently perform a sampling method. The two-sided significance level α was set at 0.05.


Minor neurological symptoms such as anosmia are relatively common manifestations of coronavirus disease 2019 (COVID-19). However, severe affection of the central nervous system (CNS) occurs in a minority of cases and its treatment and pathophysiology is not yet well understood. It has been described that encephalitis due to COVID-19 may be caused by the proinflammatory state due to the cytokine storm or direct invasion of the virus in the CNS. Here we present a case of a 66-year-old man with bipolar disorder and moderate respiratory COVID-19 symptoms who presented to the emergency department with a decreased level of consciousness. Brain computerized tomography (CT) showed no acute pathology. A thorough investigation of other possible causes of CNS affection was negative. The patient was treated with pulse therapy with methylprednisolone and presented a significant improvement of his neurological condition, being discharged with a complete neurological recovery five days after the start of the treatment. This case illustrates the importance of a high index of suspicion in diagnosing severe CNS impairment in mild respiratory COVID-19 cases. Also, this case corroborates with previous reports of glucocorticoid response in CNS impairment associated with COVID-19, although more robust studies are required to confirm this relation.  The coronavirus disease 2019 (COVID-19) pandemic that has hit the world since the end of 2019 has now caused more than 180 million cases of infection around the globe according to the World Health Organization . NeuroloA 66-year-old male with bipolar disorder and hypertension presented to the Emergency Room due to decreased level of consciousness 14 days after a COVID-19 diagnosis through real-time reverse-transcriptase polymerase chain reaction. He had been discharged from the hospital two days ago due to an atrial flutter and mild respiratory COVID-19 symptoms, with lung imaging showing 10-20% of ground-glass opacities. Vital signs at the present admission were 84 beats per minute with a sinus rhythm, blood pressure of 128/80 mmHg, and 94% oxygen saturation on room air. On physical examination, the patient was afebrile, with a Glasgow Coma Scale of 14, not oriented in time and space, with hyperreflexia and globally decreased strength. He presented no signs of meningism, no abnormal gait, no focal deficit, and no signs of respiratory distress nor hemodynamic instability. Laboratory testing revealed leukocytosis with normal differential, normal electrolytes, normal d-dimers, C-reactive protein of 5.9 mg/dl, creatinine of 3.49 mg/dl, urea of 175 mg/dl and serum lithium of 2.3 mEq/L, which was suspected to be the cause of his obnubilation. Brain computerized tomography (CT) only showed signs of microangiopathy, with no acute process explaining his mental state alteration , with normal anti-thyroid peroxidase (TPO), T3 and T4. Cerebrospinal fluid (CSF) showed no evidence of infection in the central nervous system (CNS). CSF analysis was clean, with glucose of 85 mg/dl, proteins of 10 mg/dl and normal leukocytes with predominant mononuclear cells. CSF testing was negative for tuberculosis, cryptococcosis and syphilis. There were identical IgG oligoclonal bands in CSF and plasma serum indicated systemic inflammation. Electroencephalogram (EEG) showed moderate cortical encephalopathy. Magnetic resonance imaging (MRI) revealed discrete ectasia of the supratentorial ventricular system, associated with slight erasure of the paramedian brain gyri, which may be associated with some degree of normal pressure hydrocephalus and also mild to moderate cerebral volumetric reduction Figure . FurtherBy the fifth day after admission, the patient was hemodynamically stable, recovered his renal function and was breathing comfortably in room air. Despite the improvement of his general condition, his neurological status kept declining. Considering that other causes of primary CNS affection  were excluded, it was hypothesized that the patient’s impaired neurological status was due to a COVID-19-related encephalopathy. Based on previous studies reporting improvement of neurological condition of COVID-19 patients after corticosteroid treatment, pulse therapy with methylprednisolone 500 mg IV for three days was started on day five after admission. A significant improvement in his neurological condition was seen on the first day of therapy. He was discharged five days after the start of methylprednisolone with a complete recovery of his mental status. In an outpatient consult two weeks post-discharge, the patient remained with significant neurological improvement, but complaining of transitory aphasias and lapses of memory, happening three times a week and lasting for a few seconds. His new EEG had no abnormalities.Encephalopathy is a pathobiological process in the brain that usually develops over hours to days and can manifest as changed personality, behaviour, cognition, or consciousness . AlthougThere are multiple and independent theoretical mechanisms implicated in neurological impairment in COVID-19. These include direct virus invasion, systemic dysfunction due to cardiorespiratory distress and proinflammatory state with cytokine storm . NeuroimDiagnostic criteria for COVID-19-related encephalopathy are not well established in the literature . PossiblOur patient presented a dramatic response to three-day intravenous methylprednisolone 500mg, being discharged from the hospital five days after the beginning of the pulse therapy without neurological abnormalities. Even though the MRI, CSF analysis and EEG had no characteristic findings, the immense response to steroid treatment and the exclusion of other causes supports SARS-CoV-2 encephalopathy theoretical pathophysiological mechanisms. Similar cases of COVID-19-related encephalopathy responsive to high-dose glucocorticoids are being reported around the globe . FurtherEncephalopathy is a potentially severe COVID-19 manifestation that is usually seen in severe presentations of the disease and is associated with great morbimortality. Because of its highly variable presentation, the diagnosis of encephalopathy related to COVID-19 requires a high index of suspicion. Here, we described a patient with mild COVID-19 symptoms who developed an encephalopathy highly responsive to glucocorticoids. This report complements the current literature on CNS affection due to COVID-19, and it corroborates with previous studies suggesting a potential role of glucocorticoids in the treatment of COVID-related CNS affection. More robust studies must be conducted to evaluate the best treatment in COVID-19 patients.