Analysis of predictors and outcomes of COVID-19 patients requiring ICU admission from COVID 19 (preprint)

BackgroundSevere Corona virus disease (COVID-19) is associated with high mortality. Although single centre intensive care units (ICU) have reported clinical characteristics and outcomes, no large scale multicentric study from India has been published. The present retrospective, multi-centre study was aimed to describe the predictors and outcomes of COVID-19 patients requiring ICU admission from COVID-19 Registry of Indian council of Medical Research (ICMR), India.MethodsProspectively collected data from multiple participating institutions was entered in the electronic National Clinical Registry of COVID 19. We enrolled patients aged>18 years with COVID-19 pneumonia requiring ICU admission between March 2020 and August 2021. Exclusion criteria were negative RT PCR, death within 24 hours of ICU admission, or patients with incomplete data in the registry Their demographic characteristics, laboratory variables, ICU severity indices, treatment strategies and outcomes were analysed.ResultsA total of 5865 patients, with mean age 56±15 years, with 3840/5865 (65.4%) men, were enrolled in the ICMR registry.. Overall mortality was 2535/5865 (43.5%). Non-survivors were older than survivors (58.2±15.4 years vs 53.6 ±14.7 years; P=0.001). Non-survivors had multiple comorbidities (n=1951, 52.9%) with hypertension (47.2%) and diabetes (45.6%) being the most common, higher creatinine (1.6 ± P=0.001, high D-dimer (1.56 vs 1.37, P=0.001), higher CT severity index (16.8±5.2 vs 13.5 ±5.47 ) compared to  survivors. Non survivors had longer hospital and ICU stay (P=0.001). On multivariate regression analysis, high NLR (HR 1.017, 95% CI 1.005- 1.029, P=0.001), high CRP (HR 1.008, 95% CI 1.006- 1.010, P=0.001), high D dimer ((HR 1.089, 95% CI 1.065- 1.113, P=0.001) were associated with mechanical ventilation while younger age, (HR 0.974, CI 0.965-0.983, p=0.001), high D dimer (HR-1.014, CI 1.001-1.027, P=0.035) and use of prophylactic LMWH (HR 0.647, CI 0.527-0.794, p=0.001) were independently associated with mortality. ConclusionIn this large retrospective study of 5865 critically ill COVID 19 patients admitted to ICU, overall mortality was 2535/5865 (43.5%). Age, high D dimer, CT Severity score and use of prophylactic LMWH were independently associated with mortality. 

Impact of body mass index on critically ill COVID-19 patients admitted in a tertiary care hospital: A retrospective observational study

Background: Increased body mass index (BMI) is a known risk factor for respiratory infection and is being recognized as a predisposing factor in the COVID‐19 pandemic caused by the severe acute respiratory syndrome coronavirus‐2. Aims and Objectives: This study aimed to assess the impact of BMI on critically ill COVID-19 patients. Secondary outcomes include development of respiratory failure, shock, acute cardiac injury, acute kidney injury, acute liver injury, secondary infection and sepsis. Materials and Methods: This retrospective study of 6 months included the laboratory-confirmed COVID-19 patients admitted to an ICU of a tertiary care academic health-care organization. The medical records were reviewed at least 14 days after admission. Results: A total of 484 patients were included, and BMI data were available for 306 patients. About 40.19% had a normal weight, 26.79% were overweight, 17.97% had BMI 30–34.9 Kg/m², and 15.03% had BMI ≥35 Kg/m². Overall, 58 patients (18.95%) died within 14 days of ICU admission, 50.98% were discharged alive or referred from the hospital within 14 days, and 30.06% remained hospitalized at 14 days. After controlling for all covariates, there was a significantly increased risk of mortality in the patients with obesity Class I (RR 2.03, 95% CI 1.07–3.85, P=0.030) and patients with obesity Classes II and III (RR 2.83, 95% CI 1.54–5.22, P<0.001) compared with those with normal BMI. Conclusion: Obesity was associated with an unfavorable outcome among patients with COVID-19. Patients with obesity should be more closely monitored when hospitalized for COVID-19 as there is increasing evidence of relation of severity of COVID-19 and obesity which appears to be a factor in the health risks. [ FROM AUTHOR] Copyright of Asian Journal of Medical Sciences is the property of Manipal Colleges of Medical Sciences and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Efficacy of Two Siddha Poly herbal Decoctions, Nilavembu Kudineer and Kaba Sura Kudineer, along with Standard Allopathy Treatment in the Management of Mild to Moderate Symptomatic COVID-19 Patients -a Double-Blind, Placebo Controlled, Clinical Trial (preprint)

Background & Aim: Globally, the ongoing pursuit in exploring an effective drug to combat severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus has not met with significant success till date. Indian traditional medicines, especially poly herbal formulations like Nilavembu Kudineer (NVK) and Kaba Sura Kudineer (KSK) of the Siddha system of medicine have been used as public health interventions for controlling viral epidemics like dengue and Chikungunya. These traditional therapies have been found safe, effective, and widely accepted. The current study evaluates the comparative efficacy of NVK and KSK as opposed to the placebo, in the management of mild to moderate COVID-19 disease. Methods: The study was a double blind, placebo controlled comparative clinical trial, with the primary objective of determining the efficacy of KSK and NVK. Patients (n=125) diagnosed with mild to moderate COVID-19 symptoms were enrolled in the study over a period of 4 months (Aug 2020 – Dec 2020). Participants were randomised into 3 arms; placebo-decaffeinated tea in Arm 1; NVK in Arm II and KSK in Arm III. Each arm received 60 ml of the respective treatment twice a day, post morning and evening meals, along with standard Allopathy treatment for a maximum of 10 days. The main outcome measures of the study were the reduction in SARS-CoV-2 viral load, hospital stay, and time taken by the patients to become asymptomatic from symptomatic. Efficacy assessments included clinical symptoms (fever, cough and breathlessness) each day and real-time reverse transcription-polymerase chain reaction (RT-PCR),liver function test (LFT), renal function test (RFT) and electrolytes and electrocardiogram (ECG) at baseline (Day 0), Day 3, 6 and 10. Post treatment, participants were followed up for 30 days via phone for adverse effects if any. Effects of drugs on inflammatory markers (IL6,) at the end of treatment were also recorded. Adverse events (AE) were monitored throughout the study. Results: The results revealed that when compared to patients in placebo arm, those in NVK and KSK arms showed a statistically significant reduction in hospital stay time, reduction in viral load of SARS-CoV-2, and the time taken to become symptomatic from asymptomatic. Out of 125 COVID-19 patients recruited, 120 completed the study; two from the placebo group developed severe symptoms and were shifted to intensive care unit (ICU) and three patients from arms II and III withdrew from the study. The mean age of females (n=60) and males (n=60) enrolled was between 40.2 and 44.3 years respectively. Results were more promising for all the patients in NVK and KSK arms as all enrolled participants (100%) under this group got discharged by day 6 as compared to only 42.5% (n=17) from placebo groupon that day. The hospital stay time for patients in Arm I, was significantly longer (Mean [SD]=8.4 [2.0] days) as compared to the Arm II and III (Mean [SD]=4.7 [1.5] and 4.2 [1.5] days respectively (Kruskal Wallis test, p=0.0001).Patients in the three groups took a significantly different number of days to become asymptomatic. While Arm II and III patients took mean 2.5 and 1.7 days respectively, Arm I, patients took a mean of 4.2 days (Kruskal Wallis test, p=0.0001). In all, two adverse events were recorded, one for vomiting and one for diarrhoea lasting a day in Arm I & Arm II respectively. Mean value of interleukin-6 (IL6) was significantly different in comparison to the placebo-decaffeinated tea arm (NVK=2.6 and KSK=2.2, Placebo=4.0, p=0.02).The other blood biochemical parameters like C-Reactive Protein (CRP), Lactate Dehydrogenase (LDH), Ferritin and D-Dimer that were analysed at the baseline and at the time of discharge from hospital, were not significantly different in the three arms. Conclusion: NVK and KSK arms showed a statistically significant reduction in hospital stay time, reduction in viral load of SARS-CoV-2 and time taken for patients to become asymptomatic from symptomatic, when compared to the placebo (decaffeinated tea).The primary outcome measures of KSK arm were significantly better than that in the NVK arm. 

Convalescent plasma in the management of moderate COVID-19 in India: An open-label parallel-arm phase II multicentre randomized controlled trial (PLACID Trial) (preprint)

ObjectivesConvalescent plasma (CP) as a passive source of neutralizing antibodies and immunomodulators is a century-old therapeutic option used for the management of viral diseases. We investigated its effectiveness for the treatment of COVID-19. DesignOpen-label, parallel-arm, phase II, multicentre, randomized controlled trial. SettingThirty-nine public and private hospitals across India. ParticipantsHospitalized, moderately ill confirmed COVID-19 patients (PaO2/FiO2: 200-300 or respiratory rate > 24/min and SpO2 [≤] 93% on room air). InterventionParticipants were randomized to either control (best standard of care (BSC)) or intervention (CP + BSC) arm. Two doses of 200 mL CP was transfused 24 hours apart in the intervention arm. Main Outcome MeasureComposite of progression to severe disease (PaO2/FiO2< 100) or all-cause mortality at 28 days post-enrolment. ResultsBetween 22nd April to 14th July 2020, 464 participants were enrolled; 235 and 229 in intervention and control arm, respectively. Composite primary outcome was achieved in 44 (18.7%) participants in the intervention arm and 41 (17.9%) in the control arm [aOR: 1.09; 95% CI: 0.67, 1.77]. Mortality was documented in 34 (13.6%) and 31 (14.6%) participants in intervention and control arm, respectively [aOR) 1.06 95% CI: -0.61 to 1.83]. InterpretationCP was not associated with reduction in mortality or progression to severe COVID-19. This trial has high generalizability and approximates real-life setting of CP therapy in settings with limited laboratory capacity. A priori measurement of neutralizing antibody titres in donors and participants may further clarify the role of CP in management of COVID-19. Trial registrationThe trial was registered with Clinical Trial Registry of India (CTRI); CTRI/2020/04/024775.