Noninvasive Respiratory Assist Devices in the Management of COVID-19-related Hypoxic Respiratory Failure: Pune ISCCM COVID-19 ARDS Study Consortium (PICASo).

Objective: To determine whether high-flow nasal oxygen (HFNO) or noninvasive ventilator (NIV) can avoid invasive mechanical ventilation (IMV) in COVID-19-related acute respiratory distress syndrome (ADRS), and the outcome predictors of these modalities. Design: Multicenter retrospective study conducted in 12 ICUs in Pune, India. Patients: Patients with COVID-19 pneumonia who had PaO2/FiO2 ratio <150 and were treated with HFNO and/or NIV. Intervention: HFNO and/or NIV. Measurements: The primary outcome was to assess the need of IMV. Secondary outcomes were death at Day 28 and mortality rates in different treatment groups. Main results: Among 1,201 patients who met the inclusion criteria, 35.9% (431/1,201) were treated successfully with HFNO and/or NIV and did not require IMV. About 59.5% (714/1,201) patients needed IMV for the failure of HFNO and/or NIV. About 48.3, 61.6, and 63.6% of patients who were treated with HFNO, NIV, or both, respectively, needed IMV. The need of IMV was significantly lower in the HFNO group (p <0.001). The 28-day mortality was 44.9, 59.9, and 59.6% in the patients treated with HFNO, NIV, or both, respectively (p <0.001). On multivariate regression analysis, presence of any comorbidity, SpO2 <90%, and presence of nonrespiratory organ dysfunction were independent and significant determinants of mortality (p <0.05). Conclusions: During COVID-19 pandemic surge, HFNO and/or NIV could successfully avoid IMV in 35.5% individuals with PO2/FiO2 ratio <150. Those who needed IMV due to failure of HFNO or NIV had high (87.5%) mortality. How to cite this article: Jog S, Zirpe K, Dixit S, Godavarthy P, Shahane M, Kadapatti K, et al. Noninvasive Respiratory Assist Devices in the Management of COVID-19-related Hypoxic Respiratory Failure: Pune ISCCM COVID-19 ARDS Study Consortium (PICASo). Indian J Crit Care Med 2022;26(7):791-797.

The Second- vs First-wave COVID-19: More of the Same or a Lot Worse? A Comparison of Mortality between the Two Waves in Patients Admitted to Intensive Care Units in Nine Hospitals in Western Maharashtra.

BACKGROUND: India, along with the rest of the world, faced the challenging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. The second wave in India lagged behind that in the Western world, due to different timing of seasons. There is scarce data about the differences between the two waves, for intensive care unit (ICU) patients. We present the data of 3,498 patients from 9 ICUs of western Maharashtra. MATERIALS AND METHODS: We collected prospective data of hospitalized, RT-PCR confirmed, coronavirus-2019 (COVID-19) patients, from nine tertiary centers, after institutional ethics committee (IEC) approval. Then, we segregated and analyzed the data of patients admitted to the ICU, for comorbidities, high-resolution computed tomography (HRCT) score, ventilatory support, etc. The primary outcomes were ICU and hospital mortality. We also performed multivariable analysis for predictors of ICU mortality. RESULTS: Overall, there were 3,498 ICU patients. In the first wave, 1,921 patients needed ICU admission, while in the second wave, 1,577 patients. Patients in the second wave had significantly higher ICU (26.1 vs 13.4%, p <0.001) and hospital mortality (29.9 vs 18.2%, p <0.001) and need for ventilatory support of any type. More patients received steroids during the second wave. On multivariable regression, male gender, ICU admission during the second wave, increasing HRCT score, and need for intubation and mechanical ventilation were significant predictors of ICU mortality. CONCLUSION: ICU patients admitted during the two waves were of the similar age, but there were more females, and more patients had comorbidities during the second wave. The ICU and hospital mortality were significantly higher during the second wave. HOW TO CITE THIS ARTICLE: Zirpe KG, Dixit S, Kulkarni AP, Pandit RA, Ranganathan P, Prasad S, et al. The Second- vs First-wave COVID-19: More of the Same or a Lot Worse? A Comparison of Mortality between the Two Waves in Patients Admitted to Intensive Care Units in Nine Hospitals in Western Maharashtra. Indian J Crit Care Med 2021; 25(12):1343-1348.

Increasing the Safety of Percutaneous Dilatational Tracheostomy in COVID-19 Patients.

How to cite this article: Bhosale SJ, Khatib KI. Increasing the Safety of Percutaneous Dilatational Tracheostomy in COVID-19 Patients. Indian J Crit Care Med 2021;25(6):610-612.

Itolizumab Treatment for Cytokine Release Syndrome in Moderate to Severe Acute Respiratory Distress Syndrome Due to COVID-19: Clinical Outcomes, A Retrospective Study.

BACKGROUND: Hyperinflammation, hypercoagulation and multi-organ dysfunction are life-threatening complications needing immediate attention in moderate-tosevere COVID-19 patients. We present our real world experience with Itolizumab, a repurposed immunomodulatory monoclonal antibody, administered in COVID-19 patients. METHODOLOGY: Data from 25 confirmed moderate-to-severe COVID-19 patients, with high levels of pro-inflammatory markers and pulmonary function worsening on best supportive care and Itolizumab were included in this analysis. Patients requiring invasive mechanical ventilation were excluded. Clinical parameters (oxygen requirement) and laboratory parameters (ferritin, interleukin [IL]-6, C-reactive protein [CRP] and absolute lymphocyte count [ALC]) were studied preand post-treatment. Average total length of stay in hospital and ICU, percentage of patients requiring ICU admission and average time taken for weaning off oxygen for all patients were also reported. RESULTS: All Patients were in the range of 30-78 years of age, with majority being male (76%). Most prevalent comorbid conditions were diabetes (64%) and hypertension (28%). Median IL-6 value showed a decline by 85.4%. Significant reduction in median CRP (86.96%) and Ferritin (55.61%) was observed post- Itolizumab compared to pre-dose values. Median ALC improved from 1605 cells/ mm3 (pre-dose) to 2462.5 cells/mm3 (post-dose). Average recovery time, defined as time from Itolizumab infusion to discharge was 9.28 ± 4.04 days. Average duration of hospitalization and ICU admission was 14.24 ± 4.15 and 8.27 ± 4.47 days, respectively, with 76% patients recovered and discharged. Median oxygen saturation improved from 88 % (pre-dose) to 96 % (post-dose). All patients were weaned off oxygen within Avg + SD : 6.53 ± 2.09 days post-Itolizumab treatment. One and two point reduction in ordinal scale was observed in 88% and 76% patients, respectively. Three patients (12%) did not show improvement in ordinal sore of which two patients died because of complications due to pre-existing comorbidities. The all-cause mortality of 8%; was considered not related to Itolizumab. One infusion related event reported abated with infusion period extension. INTERPRETATION AND CONCLUSION: A single dose of Itolizumab accelerated recovery in adult patients with COVID-19 by controlling immune hyperactivation. The clinical improvement was demonstrated by reduction in inflammatory markers, weaning off oxygen, reduced length of hospital stay and improvement of ordinal score. Itolizumab was well tolerated and when administered in the early phase of the inflammatory cascade is an efficient therapeutic option for treatment of cytokine release syndrome in moderate to severe COVID-19 patients.

Pathophysiological Mechanisms and Neurological Manifestations in COVID-19.

With increasing knowledge of the coronavirus disease-2019 (COVID-19), we now understand that COVID-19 presents with various extrapulmonary manifestations with multi-organ involvement. Involvement of the central nervous system (CNS) occurs probably via transsynaptic spread or transfer across the blood-brain barrier. Hypoxia, immune-mediated injury, and vascular damage are the potential mechanisms for the CNS manifestations. Headache, dizziness, chemosensory disturbances, such as loss of smell, taste, encephalopathy, stroke, etc., are among the commonly encountered neurological presentations. Headache is identified as one of the red flag symptoms for COVID-19. Sudden onset of loss of smell and/or taste in the absence of nasal congestion can help in COVID-19 case identification and testing prioritization. Both hemorrhagic and ischemic brain injury is common in patients developing stroke. Besides these, COVID-19-associated CNS involvement demands more careful attention toward patients with existing neurological disorders especially that are managed with immunosuppressant agents. In all, neurological involvement in COVID-19 is not uncommon and may precede, occur concomitantly or after the respiratory involvement. It may also be the sole presentation in some of the patients necessitating high vigilance for COVID-19. In this review, we briefly discussed the pathogenesis of CNS involvement and some important neurological manifestations in COVID-19. How to cite this article: Zirpe KG, Dixit S, Kulkarni AP, Sapra H, Kakkar G, Gupta R, et al. Pathophysiological Mechanisms and Neurological Manifestations in COVID-19. Indian J Crit Care Med 2020;24(10):975-980.

Anticoagulation in COVID - 19: An Update.

The novel coronavirus disease, 2019 (COVID - 19) evolved as an unprecedented pandemic. The severe acute respiratory syndrome-corona virus-2 (SARS-CoV-2) infection has been associated with significantly deranged coagulation parameters and increased incidence of thrombotic events. Deranged coagulation parameters, such as D-dimers and fibrin degradation products, can indicate a poor prognosis, and their measurement will help stratify the patients according to the disease severity, need of intensive care unit admission, and prediction of the clinical course. Gaps in understanding the natural history of the disease cause difficulties in tailoring therapies and optimizing the management of patients. Lack of specific treatment further complicates this situation. While thrombotic events can cause significant morbidity and mortality in patients, a focused approach to the prevention and treatment of venous thromboembolism (VTE) can, to a great extent, decrease the disease burden caused by thrombotic diseases. Pharmacological prophylactic anticoagulants and mechanical therapies such as pneumatic compression devices can help prevent venous thromboembolism and other thrombotic events. Thrombotic events due to COVID-19, their prevention and management, are the focus of this paper, with the prospect of providing insights into this relatively unexplored area.

Current Approaches to COVID-19: Therapy and Prevention.

The coronavirus disease-2019 (COVID-19) pandemic has affected millions of people worldwide. As our understanding of the disease is evolving, our approach to the patient management is also changing swiftly. Available new evidence is helping us take radical decisions in COVID-19 management. We searched for inclusion of the published literature on treatment of COVID-19 from around the globe. All relevant evidences available till the time of submission of this article were briefly discussed. Once advised as blanket therapy for all patients, recent reports of hydroxychloroquine with or without azithromycin indicated no potential benefit and use of such combination may increase the risk of arrhythmias. Clinical evidence with newer antivirals such as remdesivir and favipiravir is promising that can hasten the patient recovery and reduce the mortality. With steroids, evidence is much clear in that it should be used in low dose and for short period not extending beyond 7 days in moderate to severe hospitalized patients. Low-molecular-weight heparin should be initiated in all hospitalized COVID-19 patients and dose should be based on the coagulation profile and risk of thromboembolism. Immunomodulatory drugs such tocilizumab may be considered for severe and critically ill patients to improve the outcomes. Though ulinastatin can be a potential alternative immunomodulator, there is lack of clinical evidence on its usage in COVID-19. Convalescent plasma therapy can be potentially lifesaving in critically ill patients. However, there is need to generate further evidence with various such therapies. Though availability of a potent vaccine is awaited, current treatment of COVID-19 is based on available therapies, which is guided by the evidence. In this review, we discuss the potential treatments available around the globe with current evidence on each of such treatments. How to cite this article: Dixit SB, Zirpe KG, Kulkarni AP, Chaudhry D, Govil D, Mehta Y, et al. Current Approaches to COVID-19: Therapy and Prevention. Indian J Crit Care Med 2020;24(9):838-846.