Factors associated with mortality among moderate and severe patients with COVID-19 in India: a secondary analysis of a randomised controlled trial.

OBJECTIVE: Large data on the clinical characteristics and outcome of COVID-19 in the Indian population are scarce. We analysed the factors associated with mortality in a cohort of moderately and severely ill patients with COVID-19 enrolled in a randomised trial on convalescent plasma. DESIGN: Secondary analysis of data from a Phase II, Open Label, Randomized Controlled Trial to Assess the Safety and Efficacy of Convalescent Plasma to Limit COVID-19 Associated Complications in Moderate Disease. SETTING: 39 public and private hospitals across India during the study period from 22 April to 14 July 2020. PARTICIPANTS: Of the 464 patients recruited, two were lost to follow-up, nine withdrew consent and two patients did not receive the intervention after randomisation. The cohort of 451 participants with known outcome at 28 days was analysed. PRIMARY OUTCOME MEASURE: Factors associated with all-cause mortality at 28 days after enrolment. RESULTS: The mean (SD) age was 51±12.4 years; 76.7% were males. Admission Sequential Organ Failure Assessment score was 2.4±1.1. Non-invasive ventilation, invasive ventilation and vasopressor therapy were required in 98.9%, 8.4% and 4.0%, respectively. The 28-day mortality was 14.4%. Median time from symptom onset to hospital admission was similar in survivors (4 days; IQR 3-7) and non-survivors (4 days; IQR 3-6). Patients with two or more comorbidities had 2.25 (95% CI 1.18 to 4.29, p=0.014) times risk of death. When compared with survivors, admission interleukin-6 levels were higher (p<0.001) in non-survivors and increased further on day 3. On multivariable Fine and Gray model, severity of illness (subdistribution HR 1.22, 95% CI 1.11 to 1.35, p<0.001), PaO2/FiO2 ratio <100 (3.47, 1.64-7.37, p=0.001), neutrophil lymphocyte ratio >10 (9.97, 3.65-27.13, p<0.001), D-dimer >1.0 mg/L (2.50, 1.14-5.48, p=0.022), ferritin ≥500 ng/mL (2.67, 1.44-4.96, p=0.002) and lactate dehydrogenase ≥450 IU/L (2.96, 1.60-5.45, p=0.001) were significantly associated with death. CONCLUSION: In this cohort of moderately and severely ill patients with COVID-19, severity of illness, underlying comorbidities and elevated levels of inflammatory markers were significantly associated with death. TRIAL REGISTRATION NUMBER: CTRI/2020/04/024775.

A Prospective Study of the Course and Outcome of COVID-19 Patients with Acute Kidney Injury Admitted in an Intensive Care Unit.

BACKGROUND: COVID-19, caused by SARS-COV-2, has been a health emergency of great concern throughout the world. Acute Kidney Injury was reported in a considerable amount of patients suffering from COVID-19, especially in those admitted in the ICU setting. This study was undertaken to study the clinical profile, incidence, severity, requirement of renal replacement therapy, and the outcomes of COVID-19 patients with Acute Kidney Injury admitted in the Intensive Care Unit. MATERIALS AND METHODS: A prospective observational study was conducted at a tertiary hospital recognized as Dedicated COVID Hospital during the period of May 2020 to September 2020. 218 patients hospitalised in the Intensive Care Unit during this period were monitored for the development of Acute Kidney Injury. The clinical profile, laboratory findings, requirement of invasive ventilation and renal replacement therapy, and outcomes of such patients were recorded. Data was analysed using the SPSS software. RESULTS: Among all the patients enrolled in the Intensive Care Unit during the study period, 27.06% developed Acute Kidney Injury. 67.79% of these patients developed AKI during the first five days of hospitalisation. 76.27% of the patients with AKI required invasive mechanical ventilation, while 28.81% required renal replacement therapy. There was a significant association between the development of Acute Kidney Injury and the requirement of invasive mechanical ventilation (p = 0.0000015). 44.68% of the deaths among the 218 patients were associated with COVID-19 related AKI (p = 0.0000003). CONCLUSION: Acute Kidney Injury was found to be common among the hospitalised COVID-19 patients in our Intensive Care Unit. AKI occurs early, often in a temporal association with respiratory failure, and portends a dire prognosis.

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.

Hereditary HaemorrhagicTelangiectasia--A Rare Cause of Severe Anaemia.

Hereditary Haemorrhagic Telangiectasia also known as Osler-Rendu-Weber disease is a rare autosomal dominant disorder affecting small vessels of skin and mucosa, usually misdiagnosed because of its non specific symptomatology. This disease usually presents as epistaxis, gastrointestinal bleeding and visceral arteriovenous malformations. Although the epistaxis and gastrointestinal blood loss can result in anaemia, patients with hereditary haemorrhagic telangiectasia rarely presents as severe anaemia. Herein, we report a case of a 60 year-old man with severe anaemia resulting in congestive cardiac failure who ultimately was diagnosed as hereditary haemorrhagic telangiectasia with recurrent epistaxis as a cause of his severe anaemia.

High risk for occupational exposure to HIV and utilization of post-exposure prophylaxis in a teaching hospital in Pune, India.

BACKGROUND: The risk for occupational exposure to HIV has been well characterized in the developed world, but limited information is available about this transmission risk in resource-constrained settings facing the largest burden of HIV infection. In addition, the feasibility and utilization of post-exposure prophylaxis (PEP) programs in these settings are unclear. Therefore, we examined the rate and characteristics of occupational exposure to HIV and the utilization of PEP among health care workers (HCW) in a large, urban government teaching hospital in Pune, India. METHODS: Demographic and clinical data on occupational exposures and their management were prospectively collected from January 2003-December 2005. US Centers for Diseases Control guidelines were utilized to define risk exposures, for which PEP was recommended. Incidence rates of reported exposures and trends in PEP utilization were examined using logistic regression. RESULTS: Of 1955 HCW, 557 exposures were reported by 484 HCW with an incidence of 9.5 exposures per 100 person-years (PY). Housestaff, particularly interns, reported the greatest number of exposures with an annual incidence of 47.0 per 100 PY. Personal protective equipment (PPE) was used in only 55.1% of these exposures. The incidence of high-risk exposures was 6.8/100 PY (n = 339); 49.1% occurred during a procedure or disposing of equipment and 265 (80.0%) received a stat dose of PEP. After excluding cases in which the source tested HIV negative, 48.4% of high-risk cases began an extended PEP regimen, of whom only 49.5% completed it. There were no HIV or Hepatitis B seroconversions identified. Extended PEP was continued unnecessarily in 7 (35%) of 20 cases who were confirmed to be HIV-negative. Over time, there was a significant reduction in proportion of percutaneous exposures and high-risk exposures (p < 0.01) and an increase in PEP utilization for high risk exposures (44% in 2003 to 100% in 2005, p = 0.002). CONCLUSION: Housestaff are a vulnerable population at high risk for bloodborne exposures in teaching hospital settings in India. With implementation of a hospital-wide PEP program, there was an encouraging decrease of high-risk exposures over time and appropriate use of PEP. However, overall use of PPE was low, suggesting further measures are needed to prevent occupational exposures in India.