Emerging nanophotonic biosensor technologies for virus detection

Highly infectious viral diseases are a serious threat to mankind as they can spread rapidly among the community, possibly even leading to the loss of many lives. Early diagnosis of a viral disease not only increases the chance of quick recovery, but also helps prevent the spread of infections. There is thus an urgent need for accurate, ultrasensitive, rapid, and affordable diagnostic techniques to test large volumes of the population to track and thereby control the spread of viral diseases, as evidenced during the COVID-19 and other viral pandemics. This review paper critically and comprehensively reviews various emerging nanophotonic biosensor mechanisms and biosensor technologies for virus detection, with a particular focus on detection of the SARS-CoV-2 (COVID-19) virus. The photonic biosensing mechanisms and technologies that we have focused on include: (a) plasmonic field enhancement via localized surface plasmon resonances, (b) surface enhanced Raman scattering, (c) nano-Fourier transform infrared (nano-FTIR) near-field spectroscopy, (d) fiber Bragg gratings, and (e) microresonators (whispering gallery modes), with a particular emphasis on the emerging impact of nanomaterials and two-dimensional materials in these photonic sensing technologies. This review also discusses several quantitative issues related to optical sensing with these biosensing and transduction techniques, notably quantitative factors that affect the limit of detection (LoD), sensitivity, specificity, and response times of the above optical biosensing diagnostic technologies for virus detection. We also review and analyze future prospects of cost-effective, lab-on-a-chip virus sensing solutions that promise ultrahigh sensitivities, rapid detection speeds, and mass manufacturability.

COVID-19 and hemolysis, elevated liver enzymes and thrombocytopenia syndrome in pregnant women - association or causation?

Pregnant women are among the high-risk population for severe coronavirus disease 2019 (COVID-19) with unfavorable peripartum outcomes and increased incidence of preterm births. Hemolysis, the elevation of liver enzymes, and low platelet count (HELLP) syndrome and severe preeclampsia are among the leading causes of maternal mortality. Evidence supports a higher odd of pre-eclampsia in women with COVID-19, given overlapping pathophysiology. Involvement of angiotensin-converting enzyme 2 receptors by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for the entry to the host cells and its downregulation cause dysregulation of the renin-angiotensin-aldosterone system. The overexpression of Angiotensin II mediated via p38 Mitogen-Activated Protein Kinase pathways can cause vasoconstriction and uninhibited platelet aggregation, which may be another common link between COVID-19 and HELLP syndrome. On PubMed search from January 1, 2020, to July 30, 2022, we found 18 studies on of SARS-COV-2 infection with HELLP Syndrome. Most of these studies are case reports or series, did not perform histopathology analysis of the placenta, or measured biomarkers linked to pre-eclampsia/HELLP syndrome. Hence, the relationship between SARS-CoV-2 infection and HELLP syndrome is inconclusive in these studies. We intend to perform a mini-review of the published literature on HELLP syndrome and COVID-19 to test the hypothesis on association vs causation, and gaps in the current evidence and propose an area of future research.

Effect of Urinary Trypsin Inhibitor (Ulinastatin) Therapy in COVID-19.

Purpose: End-organ damage in coronavirus disease-2019 (COVID-19) is linked to "cytokine storm" and excessive release of inflammatory mediators. Various novel therapies have been used in COVID-19 including urinary trypsin inhibitor therapy. This study explores the efficacy of ulinastatin in COVID-19. Materials and methods: We retrieved the medical records of patients admitted during one month and did a propensity score analysis to create matched treatment and control groups. We analyzed these groups and the outcomes were presented with appropriate statistics. Survival curve was prepared to compare the survival effect of ulinastatin therapy at the end of hospitalization, among both the groups. Results: A total of 736 patients were admitted, and after adjusting the data with propensity score matching, 55 cases were selected by the system. On the final outcome analysis, we found that intensive care unit (ICU) length of stay [median (interquartile range) days 3 (3.5-7.8) vs 2 (0-4); p-value 0.28] in control vs intervention groups, and in hospital mortality (odds ratio: 0.491, CI 95%: 0.099-2.44, p-value 0.435) were not statistically different among the groups. In survival plot analysis also, there was no statistical difference (p-value 0.414) among both the groups.Conclusion: In this retrospective study, we conclude that the final outcome of the ICU length of stay, and overall, in hospital mortality were not different among both the groups. Hence, adequately powered randomized control trials are urgently required to confirm any benefit of ulinastatin therapy in COVID-19 treatment. How to cite this article: Jain A, Kasliwal R, Jain SS, Jain R, Gupta D, Gupta P, et al. Effect of Urinary Trypsin Inhibitor (Ulinastatin) Therapy in COVID-19. Indian J Crit Care Med 2022;26(6):696-703.

Expert Consensus Statements on the Use of Corticosteroids in Non-severe COVID-19.

INTRODUCTION: There is strong evidence for the use of corticosteroid in the management of severe coronavirus disease-2019 (COVID-19). However, there is still uncertainty about the timing of corticosteroids. We undertook a modified Delphi study to develop expert consensus statements on the early identification of a subset of patients from non-severe COVID-19 who may benefit from using corticosteroids. METHODS: A modified Delphi was conducted with two anonymous surveys between April 30, 2021, and May 3, 2021. An expert panel of 35 experts was selected and invited to participate through e-mail. The consensus was defined as >70% votes in multiple-choice questions (MCQ) on Likert-scale type statements, while strong consensus as >90% votes in MCQ or >50% votes for "very important" on Likert-scale questions in the final round. RESULTS: Twenty experts completed two rounds of the survey. There was strong consensus for the increased work of breathing (95%), a positive six-minute walk test (90%), thorax computed tomography severity score of >14/25 (85%), new-onset organ dysfunction (using clinical or biochemical criteria) (80%), and C-reactive protein >5 times the upper limit of normal (70%) as the criteria for patients' selection. The experts recommended using oral or intravenous (IV) low-dose corticosteroids (the equivalent of 6 mg/day dexamethasone) for 5-10 days and monitoring of oxygen saturation, body temperature, clinical scoring system, blood sugar, and inflammatory markers for any "red-flag" signs. CONCLUSION: The experts recommended against indiscriminate use of corticosteroids in mild to moderate COVID-19 without the signs of clinical worsening. Oral or IV low-dose corticosteroids (the equivalent of 6 mg/day dexamethasone) for 5-10 days are recommended for patients with features of disease progression based on clinical, biochemical, or radiological criteria after 5 days from symptom onset under close monitoring. HOW TO CITE THIS ARTICLE: How to cite this article: Nasa P, Chaudhry D, Govil D, Daga MK, Jain R, Chhallani AA, et al. Expert Consensus Statements on the Use of Corticosteroids in Non-severe COVID-19. Indian J Crit Care Med 2021;25(11):1280-1285.

Infection control in the intensive care unit: expert consensus statements for SARS-CoV-2 using a Delphi method.

During the current COVID-19 pandemic, health-care workers and uninfected patients in intensive care units (ICUs) are at risk of being infected with SARS-CoV-2 as a result of transmission from infected patients and health-care workers. In the absence of high-quality evidence on the transmission of SARS-CoV-2, clinical practice of infection control and prevention in ICUs varies widely. Using a Delphi process, international experts in intensive care, infectious diseases, and infection control developed consensus statements on infection control for SARS-CoV-2 in an ICU. Consensus was achieved for 31 (94%) of 33 statements, from which 25 clinical practice statements were issued. These statements include guidance on ICU design and engineering, health-care worker safety, visiting policy, personal protective equipment, patients and procedures, disinfection, and sterilisation. Consensus was not reached on optimal return to work criteria for health-care workers who were infected with SARS-CoV-2 or the acceptable disinfection strategy for heat-sensitive instruments used for airway management of patients with SARS-CoV-2 infection. Well designed studies are needed to assess the effects of these practice statements and address the remaining uncertainties.

Delphi methodology in healthcare research: How to decide its appropriateness.

The Delphi technique is a systematic process of forecasting using the collective opinion of panel members. The structured method of developing consensus among panel members using Delphi methodology has gained acceptance in diverse fields of medicine. The Delphi methods assumed a pivotal role in the last few decades to develop best practice guidance using collective intelligence where research is limited, ethically/logistically difficult or evidence is conflicting. However, the attempts to assess the quality standard of Delphi studies have reported significant variance, and details of the process followed are usually unclear. We recommend systematic quality tools for evaluation of Delphi methodology; identification of problem area of research, selection of panel, anonymity of panelists, controlled feedback, iterative Delphi rounds, consensus criteria, analysis of consensus, closing criteria, and stability of the results. Based on these nine qualitative evaluation points, we assessed the quality of Delphi studies in the medical field related to coronavirus disease 2019. There was inconsistency in reporting vital elements of Delphi methods such as identification of panel members, defining consensus, closing criteria for rounds, and presenting the results. We propose our evaluation points for researchers, medical journal editorial boards, and reviewers to evaluate the quality of the Delphi methods in healthcare research.

Air leak with COVID-19 - A meta-summary.

INTRODUCTION: There are various reports of air leaks with coronavirus disease 2019 (COVID-19). We undertook a systematic review of all published case reports and series to analyse the types of air leaks in COVID-19 and their outcomes. METHODS: The literature search from PubMed, Science Direct, and Google Scholar databases was performed from the start of the pandemic till 31 March 2021. The inclusion criteria were case reports or series on (1) laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, (2) with the individual patient details, and (3) reported diagnosis of one or more air leak syndrome (pneumothorax, subcutaneous emphysema, pneumomediastinum, pneumoperitoneum, pneumopericardium). RESULTS: A total of 105 studies with 188 patients were included in the final analysis. The median age was 56.02 (SD 15.53) years, 80% males, 11% had previous respiratory disease, and 8% were smokers. Severe or critical COVID-19 was present in 50.6% of the patients. Pneumothorax (68%) was the most common type of air leak. Most patients (56.7%) required intervention with lower mortality (29.1% vs. 44.1%, p = 0.07) and intercostal drain (95.9%) was the preferred interventional management. More than half of the patients developed air leak on spontaneous breathing. The mortality was significantly higher in patients who developed air leak with positive pressure ventilation (49%, p < 0.001) and required escalation of respiratory support (39%, p = 0.006). CONCLUSION: Air leak in COVID-19 can occur spontaneously without positive pressure ventilation, higher transpulmonary pressures, and other risk factors like previous respiratory disease or smoking. The mortality is significantly higher if associated with positive pressure ventilation and escalation of respiratory support.

Expert consensus statements for the management of COVID-19-related acute respiratory failure using a Delphi method.

BACKGROUND: Coronavirus disease 2019 (COVID-19) pandemic has caused unprecedented pressure on healthcare system globally. Lack of high-quality evidence on the respiratory management of COVID-19-related acute respiratory failure (C-ARF) has resulted in wide variation in clinical practice. METHODS: Using a Delphi process, an international panel of 39 experts developed clinical practice statements on the respiratory management of C-ARF in areas where evidence is absent or limited. Agreement was defined as achieved when > 70% experts voted for a given option on the Likert scale statement or > 80% voted for a particular option in multiple-choice questions. Stability was assessed between the two concluding rounds for each statement, using the non-parametric Chi-square (χ2) test (p < 0·05 was considered as unstable). RESULTS: Agreement was achieved for 27 (73%) management strategies which were then used to develop expert clinical practice statements. Experts agreed that COVID-19-related acute respiratory distress syndrome (ARDS) is clinically similar to other forms of ARDS. The Delphi process yielded strong suggestions for use of systemic corticosteroids for critical COVID-19; awake self-proning to improve oxygenation and high flow nasal oxygen to potentially reduce tracheal intubation; non-invasive ventilation for patients with mixed hypoxemic-hypercapnic respiratory failure; tracheal intubation for poor mentation, hemodynamic instability or severe hypoxemia; closed suction systems; lung protective ventilation; prone ventilation (for 16-24 h per day) to improve oxygenation; neuromuscular blocking agents for patient-ventilator dyssynchrony; avoiding delay in extubation for the risk of reintubation; and similar timing of tracheostomy as in non-COVID-19 patients. There was no agreement on positive end expiratory pressure titration or the choice of personal protective equipment. CONCLUSION: Using a Delphi method, an agreement among experts was reached for 27 statements from which 20 expert clinical practice statements were derived on the respiratory management of C-ARF, addressing important decisions for patient management in areas where evidence is either absent or limited. TRIAL REGISTRATION: The study was registered with Clinical trials.gov Identifier: NCT04534569.