Co-infection and ICU-acquired infection in COIVD-19 ICU patients: a secondary analysis of the UNITE-COVID data set.

BACKGROUND: The COVID-19 pandemic presented major challenges for critical care facilities worldwide. Infections which develop alongside or subsequent to viral pneumonitis are a challenge under sporadic and pandemic conditions; however, data have suggested that patterns of these differ between COVID-19 and other viral pneumonitides. This secondary analysis aimed to explore patterns of co-infection and intensive care unit-acquired infections (ICU-AI) and the relationship to use of corticosteroids in a large, international cohort of critically ill COVID-19 patients. METHODS: This is a multicenter, international, observational study, including adult patients with PCR-confirmed COVID-19 diagnosis admitted to ICUs at the peak of wave one of COVID-19 (February 15th to May 15th, 2020). Data collected included investigator-assessed co-infection at ICU admission, infection acquired in ICU, infection with multi-drug resistant organisms (MDRO) and antibiotic use. Frequencies were compared by Pearson's Chi-squared and continuous variables by Mann-Whitney U test. Propensity score matching for variables associated with ICU-acquired infection was undertaken using R library MatchIT using the "full" matching method. RESULTS: Data were available from 4994 patients. Bacterial co-infection at admission was detected in 716 patients (14%), whilst 85% of patients received antibiotics at that stage. ICU-AI developed in 2715 (54%). The most common ICU-AI was bacterial pneumonia (44% of infections), whilst 9% of patients developed fungal pneumonia; 25% of infections involved MDRO. Patients developing infections in ICU had greater antimicrobial exposure than those without such infections. Incident density (ICU-AI per 1000 ICU days) was in considerable excess of reports from pre-pandemic surveillance. Corticosteroid use was heterogenous between ICUs. In univariate analysis, 58% of patients receiving corticosteroids and 43% of those not receiving steroids developed ICU-AI. Adjusting for potential confounders in the propensity-matched cohort, 71% of patients receiving corticosteroids developed ICU-AI vs 52% of those not receiving corticosteroids. Duration of corticosteroid therapy was also associated with development of ICU-AI and infection with an MDRO. CONCLUSIONS: In patients with severe COVID-19 in the first wave, co-infection at admission to ICU was relatively rare but antibiotic use was in substantial excess to that indication. ICU-AI were common and were significantly associated with use of corticosteroids. Trial registration ClinicalTrials.gov: NCT04836065 (retrospectively registered April 8th 2021).

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.

Cerebral Venous Sinus Thrombosis (CVST) as a Complication of SARS-COV2 Infection

Background and Purpose:Severe acute respiratory syndrome coronavirus 2 (SARS-COV2) infection induces a prothrombotic state frequently associated with arterial ischemic strokes. Cerebral venous sinus thrombosis (CVST) is also reported with corona virus disease-19 (COVID-19) but a large cohort study is lacking. Our aim was to study the characteristics, treatment response, and outcomes of CVST occurring in association with COVID-19 (COVID-CVST) and the causal relationship with COVID-19.Methods:Data of 34 patients admitted in COVID facility and suffering from CVST and SARS-COV2 infection was studied with respect to their clinic-radiological and lab features, predisposing factors, treatment, and outcome.Observations and Results:15 patients with CVST were detected positive for COVID but remained asymptomatic for the same. 14 patients had CVST along with symptoms of COVID, whereas 5 had CVST after recovery from COVID, at an average of 18 days after COVID-19. 4 patients were on aspirin as prophylaxis against thrombo-embolic events. The number of males exceeded females (22:12), conventional risk factors were seen in only 8 patients (postpartum state-3, alcohol abuse-2 and anemia-3), whereas the majority (26/34) showed none of them. The mean serum homocysteine level was normal and antiphospholipid antibody was tested normal in the assessed subjects. D-dimer and C reactive protein were elevated in all. 4 symptomatic patients who suffered from severe pneumonia died because of systemic complications.Conclusion:COVID-19 predisposes to CVST and the outcome is related to the severity of COVID pneumonia. CVST related to COVID occurs during or after a few weeks of COVID pneumonia and can also be seen in asymptomatic SARS-COV2 infection. COVID-19 can occur independently or in association with traditional thrombotic risk factors which increase the risk and severity of CVST in COVID. If recognized early, CVST associated with COVID can usually be treated effectively to achieve a very good outcome.

Intravenous Methylene Blue as a Rescue Therapy in the Management of Refractory Hypoxia in COVID-19 ARDS Patients: A Case Series.

Objectives: To describe the clinical outcomes of hypoxic coronavirus disease 2019 (COVID-19) patients treated with intravenous methylene blue (MB) in a tertiary care hospital. Materials and methods: We conducted a case series of 50 patients with hypoxic COVID-19 treated with intravenous MB admitted to our hospital between June 01 and September 10, 2020. Intravenous MB was administered as rescue therapy in dosage of 1 mg/kg body weight, with a maximum of five doses, to patients with high oxygen requirements (SpO2/FiO2 <200) apart from the standard of care after obtaining G6PD levels. Data were abstracted from multiple electronic data sources or patient charts to provide information on patient characteristics, clinical and laboratory variables and outcomes. Results: The median age of the patients was 53.3 (range 25-74 years) and most patients (74%) were men. About 68% of patients had pre-existing comorbidity. Median SpO2/FiO2 ratio progressively improved from 132.5 (predose) to 284 before the terminal event (death or discharge), ventilator-free days, and decrease in the proinflammatory biochemical parameter was significantly higher after the second dose of MB. A total of six patients out of 50 required invasive mechanical ventilation (IMV). Thirty patients were discharged with a recovery rate of 60%, while 20 patients succumbed to the illness. There was no major side effect or adverse event reported in any of the patients. Conclusion: MB due to its polypharmacological action against SARS-CoV-2, an inexpensive and widely available drug with minimal side effects, has a significant potential in the treatment of COVID-19. How to cite this article: Mahale N, Godavarthy P, Marreddy S, Gokhale SD, Funde P, Rajhans PA, et al. Intravenous Methylene Blue as a Rescue Therapy in the Management of Refractory Hypoxia in COVID-19 ARDS Patients: A Case Series. Indian J Crit Care Med 2021;25(8):934-938.

The Surviving Sepsis Campaign: Research Priorities for Coronavirus Disease 2019 in Critical Illness.

OBJECTIVES: To identify research priorities in the management, pathophysiology, and host response of coronavirus disease 2019 in critically ill patients. DESIGN: The Surviving Sepsis Research Committee, a multiprofessional group of 17 international experts representing the European Society of Intensive Care Medicine and Society of Critical Care Medicine, was virtually convened during the coronavirus disease 2019 pandemic. The committee iteratively developed the recommendations and subsequent document. METHODS: Each committee member submitted a list of what they believed were the most important priorities for coronavirus disease 2019 research. The entire committee voted on 58 submitted questions to determine top priorities for coronavirus disease 2019 research. RESULTS: The Surviving Sepsis Research Committee provides 13 priorities for coronavirus disease 2019. Of these, the top six priorities were identified and include the following questions: 1) Should the approach to ventilator management differ from the standard approach in patients with acute hypoxic respiratory failure?, 2) Can the host response be modulated for therapeutic benefit?, 3) What specific cells are directly targeted by severe acute respiratory syndrome coronavirus 2, and how do these cells respond?, 4) Can early data be used to predict outcomes of coronavirus disease 2019 and, by extension, to guide therapies?, 5) What is the role of prone positioning and noninvasive ventilation in nonventilated patients with coronavirus disease?, and 6) Which interventions are best to use for viral load modulation and when should they be given? CONCLUSIONS: Although knowledge of both biology and treatment has increased exponentially in the first year of the coronavirus disease 2019 pandemic, significant knowledge gaps remain. The research priorities identified represent a roadmap for investigation in coronavirus disease 2019.

A Retrospective Observational Study of Hypoxic COVID-19 Patients Treated with Immunomodulatory Drugs in a Tertiary Care Hospital.

OBJECTIVES: To describe the demographics and evaluate the clinical outcomes of hypoxic coronavirus disease-2019 (COVID-19) patients treated with different immunomodulatory (IM) drugs in a resource-limited setting. MATERIALS AND METHODS: We conducted a retrospective cohort study of these patients admitted to our hospital between March 22 and May 31, 2020. Data were abstracted from multiple electronic data sources or patient charts to provide information on patient characteristics, clinical, laboratory variables, and outcomes. RESULTS: A total of 134 patients met the inclusion criteria and were followed up till June 7, 2020. The median age of the patients was 55.6 years (range 20-89 years) and 68% were men. At least one comorbidity was seen in 72% of the patients with diabetes (44%) and hypertension (46%) being the most common. At triage, fever (82%), shortness of breath (77%), and cough (61%) were the most common presenting symptoms. A PaO2/FiO2 ratio less than 300 was seen in 60%, and 4.5% required invasive mechanical ventilation within 72 hours of hospital admission. Five immunomodulatory agents (hydroxychloroquine, methylprednisolone, colchicine, etoricoxib, and tocilizumab) were administered in different combinations. Overall, in-hospital mortality was 26.9%, and 32% required mechanical ventilation. Around 69% of patients were discharged home. Five variables (SpO2, PaO2/FiO2 ratio, leucocytosis, lymphopenia, and creatinine) on admission were found to be significant in the patients who died. CONCLUSION: Our study provides the characteristics and outcomes of hypoxic COVID-19 patients treated with IM drugs in varied combination. Five independent variables were strong predictors of mortality. HOW TO CITE THIS ARTICLE: Mahale N, Rajhans P, Godavarthy P, Narasimhan VL, Oak G, Marreddy S, et al. A Retrospective Observational Study of Hypoxic COVID-19 Patients Treated with Immunomodulatory Drugs in a Tertiary Care Hospital. Indian J Crit Care Med 2020;24(11):1020-1027.

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.

Preparedness of Acute Care Facility and a Hospital for COVID-19 Pandemic: What We Did!

BACKGROUND AND AIM: India is facing the pandemic of coronavirus disease (COVID-19) just like the whole world. The private sector is the backbone of a healthcare facility in India. Presently, only a few major hospitals in the country are actively dealing with the COVID-19 patients while others are facing troubles due to lack of manpower, management, and required experience to face the pandemic. Despite the lockdown, the cases are ever increasing and each and every hospital in the country should be prepared to face this pandemic the world has never seen before. As one of the largest multispecialty hospitals and a designated COVID center, we have developed and adopted some strategies for better preparedness to face the surge of this pandemic. We would like to share our experience and hope that the strategies laid down and adopted by us will help many other acute care facilities in many parts of India. MATERIALS AND METHODS: Different strategies are adopted to deal with the crisis situation of the COVID-19 pandemic. Our adopted strategies were directed to mitigate the challenges of administration, hospital space organization, management of staff and supplies, maintenance of standard of care, and specific COVID care and ethics during this pandemic. RESULTS: Based on strategies adopted by us, we feel more confident and prepared to deal with COVID-19 pandemic. CONCLUSION: Our approach for preparing for the COVID-19 pandemic may not be the best one but we believe that the basic managerial principles we adopted will guide many other institutions to find their path in tackling the pandemic in the best possible way. HOW TO CITE THIS ARTICLE: Jog S, Kelkar D, Bhat M, Patwardhan S, Godavarthy P, Dhundi U, et al. Preparedness of Acute Care Facility and a Hospital for COVID-19 Pandemic: What We Did! Indian J Crit Care Med 2020;24(6):385-392.