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.

Role of high dose vitamin C in management of hospitalised COVID-19 patients: A minireview.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged as one of the most dreadful viruses the mankind has witnessed. It has caused world-wide havoc and wrecked human life. In our quest to find therapeutic options to counter this threat, several drugs have been tried, with varying success. Certain agents like corticosteroids, some anti-virals and immunosuppressive drugs have been found useful in improving clinical outcomes. Vitamin C, a water-soluble vitamin with good safety profile, has been tried to reduce progression and im-prove outcomes of patients with coronavirus disease 2019 (COVID-19). Because of its anti-oxidant and immunomodulatory properties, the role of vitamin C has expanded well beyond the management of scurvy and it is increasingly been employed in the treatment of critically ill patients with sepsis, septic shock, acute pancreatitis and even cancer. However, in spite of many case series, observational studies and even randomised control trials, the role of vitamin C remains ambiguous. In this review, we will be discussing the scientific rationale and the current clinical evidence for using high dose vitamin C in the management of COVID-19 patients.

Air leaks in COVID-19.

Coronavirus disease 2019 (COVID-19) continues to create havoc and may present with myriad complications involving many organ systems. However, the respiratory system bears the maximum brunt of the disease and continues to be most commonly affected. There is a high incidence of air leaks in patients with COVID-19, leading to acute worsening of clinical condition. The air leaks may develop independently of the severity of disease or positive pressure ventilation and even in the absence of any traditional risk factors like smoking and un-derlying lung disease. The exact pathophysiology of air leaks with COVID-19 remains unclear, but multiple factors may play a role in their development. A significant proportion of air leaks may be asymptomatic; hence, a high index of suspicion should be exercised for enabling early diagnosis to prevent further deterioration as it is associated with high morbidity and mortality. These air leaks may even develop weeks to months after the disease onset, leading to acute deterioration in the post-COVID period. Conservative management with close monitoring may suffice for many patients but most of the patients with pneumothorax may require intercostal drainage with only a few requiring surgical interventions for persistent air leaks.

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.

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.

Effectiveness of convalescent plasma in Indian patients with COVID-19.

BACKGROUND: Convalescent plasma (CP) is being used as a treatment option in hospitalized patients with COVID-19. Till date, there is conflicting evidence on efficacy of CP in reducing COVID-19 related mortality. OBJECTIVE: To evaluate the effect of CP on 28-day mortality reduction in patients with COVID-19. METHODS: We did a multi-centre, retrospective case control observational study from 1st May 2020 to 31st August 2020. A total of 1079 adult patients with moderate and severe COVID-19 requiring oxygen, were reviewed. Of these, 694 patients were admitted to ICU. Out of these, 333 were given CP along with best supportive care and remaining 361 received best supportive care only. RESULTS: In the overall group of 1079 patients, mortality in plasma vs no plasma group was statistically not significant (22.4% vs 18.5%; p = 0.125; OR = 1.27, 95% CI: 0.94--1.72). However, in patients with COVID-19 admitted to ICU, mortality was significantly lower in plasma group (25.5% vs 33.2%; p = 0.026; OR = 0.69, 95%CI: 0.50-0.96). This benefit of reduced mortality was most seen in age group 60 to 74 years (26.7% vs 43.0%; p = 0.004; OR = 0.48, 95% CI: 0.29-0.80), driven mostly by females of this age group (23.1% vs 53.5%; p = 0.013; OR = 0.26, 95% CI: 0.09-0.78). Significant difference in mortality was observed in patients with one comorbidity (22.3% vs 36.5%; p = 0.004; OR = 0.50, 95% CI: 0.31-0.80). Moreover, patients on ventilator had significantly lower mortality in the plasma arm (37.2% vs 49.3%; p = 0.009; OR = 0.61, 95% CI: 0.42-0.89); particularly so for patients on invasive mechanical ventilation (63.9% vs 82.9%; p = 0.014; OR = 0.37, 95% CI: 0.16-0.83). CONCLUSION: The use of CP was associated with reduced mortality in COVID-19 elderly patients admitted in ICU, above 60 years of age, particularly females, those with comorbidities and especially those who required some form of ventilation.

Basic Critical Care for Management of COVID-19 Patients: Position Paper of Indian Society of Critical Care Medicine, Part-I.

With more than 23 million infections and more than 814,000 deaths worldwide, the coronavirus disease-2019 (COVID-19) pandemic is still far from over. Several classes of drugs including antivirals, antiretrovirals, anti-inflammatory, immunomodulatory, and antibiotics have been tried with varying levels of success. Still, there is lack of any specific therapy to deal with this infection. Although less than 30% of these patients require intensive care unit admission, morbidity and mortality in this subgroup of patients remain high. Hence, it becomes imperative to have general principles to guide intensivists managing these patients. However, as the literature emerges, these recommendations may change and hence, frequent updates may be required. How to cite this article: Juneja D, Savio RD, Srinivasan S, Pandit RA, Ramasubban S, Reddy PK, et al. Basic Critical Care for Management of COVID-19 Patients: Position Paper of Indian Society of Critical Care Medicine, Part-I. Indian J Crit Care Med 2020;24(Suppl 5):S244-S253.

Basic Critical Care for Management of COVID-19 Patients: Position Paper of the Indian Society of Critical Care Medicine, Part II.

In a resource-limited country like India, rationing of scarce critical care resources might be required to ensure appropriate delivery of care to the critically ill patients suffering from COVID-19 infection. Most of these patients require critical care support because of respiratory failure or presence of multiorgan dysfunction syndrome. As there is no pharmacological therapy available, respiratory support in the form of supplemental oxygen, noninvasive ventilation, and invasive mechanical ventilation remains mainstay of care in intensive care units. As there is still dearth of direct evidence, most of the data are extrapolated from the experience gained from the management of general critical care patients. How to cite this article: Juneja D, Savio RD, Srinivasan S, Pandit RA, Ramasubban S, Reddy PK, et al. Basic Critical Care for Management of COVID-19 Patients: Position Paper of the Indian Society of Critical Care Medicine, Part II. Indian J Crit Care Med 2020;24(Suppl 5):S254-S262.