A Combination of Inflammatory and Hematological Markers is Strongly Associated with the Risk of Death in Both Mild and Severe Initial Disease in Unvaccinated Individuals with COVID-19 Infection

Background Inflammatory and hematological markers are used extensively for early prognostication and monitoring in COVID-19. We aimed to determine whether routinely prescribed laboratory markers can predict adverse outcome at presentation in COVID-19. Methods This retrospective observational study was performed on 401 samples collected between July to December 2020 from COVID-19 positive subjects, admitted at All India Institute of Medical Sciences, Delhi, India. Clinical details and laboratory investigations within 3 days of COVID-19 positivity were obtained. Clinical outcomes were noted from patient medical records, till discharge or death. Laboratory parameters, with individually defined cut-offs, were used, either singly or in combination to distinguish survival and death for those having severe and non-severe disease at initial presentation. Findings Total Leukocyte count, Absolute neutrophil count, Neutrophil to Lymphocyte ratio, C-Reactive Protein (CRP), Interleukin-6 (IL-6), Lactate Dehydrogenase, Ferritin and Lymphocyte to CRP ratio (LCR) were significantly altered at presentation in severe COVID-19 as compared to non-severe cases;and, also in those who died due to COVID-19 compared to those who survived. A combination of four markers, CRP (≥3.9mg/dL);IL-6 (≥45.37pg/ml);Ferritin (≥373ng/mL);1/LCR ≥0.405 was found to strongly predict mortality in cases with non-severe presentation as also in severe cases. Conclusion and Interpretation The combination of routinely used markers, CRP, IL-6, Ferritin and 1/LCR can be used to predict adverse outcomes, even in those presenting with mild to moderate disease. This would identify subset of patients who would benefit from closer monitoring than usual for non-severe disease.

Recasting Biomedical Waste Management Strategies during COVID-19 Pandemic in Dental Practice

A rise in the COVID-19 pandemic has led to increase in biomedical waste (BMW) all over the globe that leads to the perilous situation. Hence, this review has made an attempt to gather all the guidelines for appropriate BMW management in dental practice during COVID-19 pandemic. The keywords such as Biomedical waste management guidelines, COVID-19, dental waste management, and India were used in the literature search engines such as PubMed, Scopus, Web of Science, and Google Scholar along with the various guidelines provided by international, national agencies and verified government websites with a focus on the BMW management in dentistry during COVID-19. The result enumerated that Biomedical Waste Management Rules, 2016, categorizes the bio-medical waste generated from the health-care facility into four categories based on the segregation pathway and color code. These guidelines were reshaped in 2018, 2019, and in 2020 for COVID-19 pandemic. Collection and segregation of biomedical waste separately before handling it to the Common Bio-medical Waste Treatment and Disposal Facility was highly recommended that should be labeled with "COVID-19” both in medical and dental waste management guidelines. This review revealed that BMW management guidelines should be followed by all the health-care fraternities including oral health professionals as they are at a heightened risk of COVID-19, it is vital that they are informed of the most up-to-date protocols for BMW disposal in this pandemic.

High seroprevalence against SARS-CoV-2 in non-vaccinated patients with inflammatory bowel disease from Northern India.

BACKGROUND: The information on seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among patients with inflammatory bowel disease (IBD) and its comparison to healthy controls is sparse. We compared the seroprevalence rates in patients with IBD and healthy controls (HCs). METHODS: Patients with IBD and HCs (contact of patients) underwent SARS-CoV-2 antibody testing (chemiluminescent immunoassay: Siemens kit IgG against antigen-S1RBD) between July 2020 and April 2021. Information on demography, disease characteristics, drug history and past history of SARS-CoV-2 infection were noted. Patients on 5-aminosalicylic acid or no treatment were considered not on immunosuppressants and those who had received steroids, thiopurines or methotrexate within six months of inclusion were considered being on immunosuppressants. RESULTS: A total of 235 patients (51.9%, males; mean age, 38.7 ± 12.4 years; median disease duration, 60 months [interquartile range, IQR: 36-120]) (ulcerative colitis [UC]: 69.4%, Crohn's disease [CD]: 28.9%, IBD unclassified [IBDU]: 1.7%) and 73 HCs (mean age, 39.6 ± 10.9 years, 80% males) were enrolled. Of the 235 patients, 128 (54.5%) patients were on immunosuppressants and 107 (45.5%) were not on immunosuppressants. Seventy-four (31.5%) patients were seropositive, of which two (0.9%) had previous history of SARS-CoV-2 infection and none received coronavirus disease-19 (COVID-19) vaccine. Seroprevalence between IBD patients and HCs (32% vs. 27%, p > 0.05) and between patients with and without immunosuppressants (28.1% vs. 36%, p > 0.05) was similar. Age, gender, disease type, duration and activity in the last six months; and medication use were similar between patients with positive and negative serology. There was a progressive increase in seroprevalence from July 2020 to April 2021. CONCLUSION: Up to 1/3rd of patients with IBD were seropositive for immunoglobulin G (IgG) SARS-Cov-2 antibody indicating high seroprevalence in patients with IBD from Northern India.

The Effectiveness of SARS-CoV-2 Vaccination in Preventing Severe Illness and Death - Real-world Data from a Cohort of Patients Hospitalized with COVID-19.

Background: While long-term studies on the correlates of protection, vaccine effectiveness, and enhanced surveillance are awaited for SARS-CoV-2 vaccine, studies on breakthrough infections help understand the nature and course of this illness among vaccinated individuals and guide in public health preparedness. This study aims to compare the differences in the hospitalization outcomes SARS-CoV-2 infection of fully vaccinated individuals with with those of unvaccinated and partially vaccinated individuals. Materials and Methods: Single institution observational cohort study. This study compared the differences in clinical, biochemical parameters and the hospitalization outcomes of 53 fully vaccinated individuals with those of unvaccinated (1464) and partially vaccinated (231) individuals, among a cohort of 2,080 individuals hospitalized with SARS-CoV-2 infection. Descriptive statistics and propensity-score weighted multivariate logistic regression analysis adjusting for clinical and laboratory parameters were used to compare the differences and to identify factors associated with outcomes. Results: Completing the course of vaccination protected individuals from developing severe COVID-19 as evidenced by lower proportions of those with hypoxia, abnormal levels of inflammatory markers, requiring ventilatory support, and death compared to unvaccinated and partially vaccinated individuals. There were no differences in these outcomes among patients who received either vaccine type approved in India. Conclusions: Efforts should be made to improve the vaccination rates as a timely measure to prepare for the upcoming waves of this highly transmissible pandemic. Vaccination rates of the communities may also guide in the planning of the health needs and appropriate use of medical resources.

Does HPWS amplify employees' change readiness for digital transformation? A study through the “work-from-anywhere” prism

PurposeThis study intends to advance the research on the relationship between high-performance work systems (HPWS) and change readiness by examining the mediating role of positive employee outcomes. Therefore, the streams of strategic human resource management (SHRM) and change management are studied in the context of digital transformation in the post-COVID-19 pandemic scenario.Design/methodology/approachPrimary responses from 409 Information Technology (IT) employees were analysed to investigate the mediating relationship between HPWS, positive employee outcomes and employee readiness to change. Researchers used statistical techniques to analyse the data, such as confirmatory factor analysis, correlations, regression and bootstrapping. In addition, sequential mediation was examined using "PROCESS Macro" and syntax for SPSS.FindingsResults of the study revealed that implementation of HPWS through extensive training and development, performance-based appraisal and compensation, participation in decision-making, flexible work arrangements and rigorous recruitment and staffing results in enhanced employee-level outcomes. Thereby conclusively impacting their readiness to change for digital transformations.Practical implicationsThis study revisits the elements of HPWS in the post-pandemic work-from-anywhere (WFA) scenario. Thus, it provides adequate indications that investment in designing bundles of change-oriented human resource (HR) practices amplifies the chances of success of a change initiative by creating a favourable mindset and attitude among IT employees in India.Originality/valueThis study is among the earliest to link two major streams of SHRM and change management by establishing HPWS as an essential antecedent of a change-related outcome by introducing multiple mediators in the sequence. This sequence provides new insights for enhancing the probability of organisational change directives succeeding.

Association of anxiety with oral health-related quality of life among Kashmiri Residents

Introduction: Along with other healthcare indicators, psychological well-being of the population worldwide has been greatly affected after outbreak of covid-19. Almost all states in India including Jammu and Kashmir suffered during COVID-19. Thus this study was planned to determine the association of anxiety and its impact on oral health-related quality of life (14-item Oral Health Impact Profile [OHIP-14]) among residents of four districts of Jammu and Kashmir state during COVID-19. Materials and Methods: A self-administered questionnaire consisting of OHIP-14 along with a 7-item Generalized Anxiety Disorder Scale (GAD-7 Scale) was distributed among the residents of Kashmir via e-mails, WhatsApp groups, and Facebook using Google Forms. Results: Majority of the participants were males (53%) over 18 years of age. The most frequently experienced problems were discomfort during eating food (75%) and physical pain in the mouth such as aching in the mouth (60%). A highly statistically significant negative correlation was found between OHIP-14 and GAD among painful aching in the mouth (−0.044) (0.154**) **p<0.001. Half (50%) of the participants reported minimal anxiety. Conclusion: There is an unmet and immediate need to escalate the mental health services in Jammu and Kashmir state of India, which consisted of community participation, awareness programs, and mental health rehabilitation services.

Bendamustine in combination with pomalidomide and dexamethasone in relapsed/refractory multiple myeloma: A phase II trial.

Treatment of patients with resistant/refractory multiple myeloma (MM) is an unmet need. In this phase II study, we evaluated the role of bendamustine, pomalidomide and dexamethasone combination in this setting. Between February 2020 and December 2021, 28 patients were recruited. Patients received bendamustine 120 mg/m2 day 1, pomalidomide 3 mg days 1-21, and dexamethasone 40 mg days 1, 8, 11, 22, regimen given for a maximum of six cycles. The median (range) age of the patients was 54 (30-76) years and 15 (53.6%) were males. Patients had received a median (range) of three (two-six) prior lines and 85.7% were refractory to both lenalidomide and bortezomib. The primary end-point was the overall response rate (ORR) defined as ≥partial response after at least three cycles. Secondary objectives were toxicity, progression-free survival (PFS), time to progression and overall survival (OS). An intent-to-treat analysis was done. An ORR of 57.6% was achieved. Patients with extramedullary myeloma had a better response rate. At a median follow-up of 8.6 months, the median PFS and OS were 6.2 and 9.7 months respectively. Toxicity was manageable; mainly haematological (neutropenia, 46.4%; anaemia, 42.8%; and thrombocytopenia, 7.1%). Bendamustine, pomalidomide and dexamethasone could be a novel combination for the heavily pretreated, lenalidomide-refractory myeloma population.

Statin and aspirin as adjuvant therapy in hospitalised patients with SARS-CoV-2 infection: a randomised clinical trial (RESIST trial).

BACKGROUND: Statins and aspirin have been proposed for treatment of COVID-19 because of their anti-inflammatory and anti-thrombotic properties. Several observational studies have shown favourable results. There is a need for a randomised controlled trial. METHODS: In this single-center, open-label, randomised controlled trial, 900 RT-PCR positive COVID-19 patients requiring hospitalisation, were randomly assigned to receive either atorvastatin 40 mg (Group A, n = 224), aspirin 75 mg (Group B, n = 225), or both (Group C, n = 225) in addition to standard of care for 10 days or until discharge whichever was earlier or only standard of care (Group D, n = 226). The primary outcome variable was clinical deterioration to WHO Ordinal Scale for Clinical Improvement ≥ 6. The secondary outcome was change in serum C-reactive protein, interleukin-6, and troponin I. RESULTS: The primary outcome occurred in 25 (2.8%) patients: 7 (3.2%) in Group A, 3 (1.4%) in Group B, 8 (3.6%) in Group C, and 7 (3.2%) in Group D. There was no difference in primary outcome across the study groups (P = 0.463). Comparison of all patients who received atorvastatin or aspirin with the control group (Group D) also did not show any benefit [Atorvastatin: HR 1.0 (95% CI 0.41-2.46) P = 0.99; Aspirin: HR 0.7 (95% CI 0.27-1.81) P = 0.46]. The secondary outcomes revealed lower serum interleukin-6 levels among patients in Groups B and C. There was no excess of adverse events. CONCLUSIONS: Among patients admitted with mild to moderate COVID-19 infection, additional treatment with aspirin, atorvastatin, or a combination of the two does not prevent clinical deterioration. Trial Registry Number CTRI/2020/07/026791 ( http://ctri.nic.in ; registered on 25/07/2020).

A Comparative Study of the Patterns of Mortality in COVID-19 Patients in Juxtaposition with Non-COVID-19 Mortality in the First and Second Waves of the Pandemic.

BACKGROUND AND OBJECTIVES: The Coronavirus disease 2019 (COVID-19) pandemic has posed an unprecedented challenge to the public healthcare system worldwide like none before, producing far-reaching global economic, humanitarian, and social crises. It is estimated to have affected more than 1.8 million people worldwide. India has faced two phases of the pandemic, being the country with 2nd most number of deaths with varying mortality patterns across the two waves. In this study, we compare the patterns of mortality between the two phases of pandemics in association with COVID-19 and non-COVID-19 deaths. MATERIALS AND METHODS: A retrospective observational study at a tertiary care center in Central India was carried out. Demographic patterns of mortality have been studied in each of the groups, and a comparative analysis was done between COVID-19 and non-COVID-19 mortality patterns in each phase of the study, that is, from 20th March 2020 to 19th September 2020 and from 20th September 2020 to May 2021, as well as between the two phases. RESULTS: The case fatality rate of COVID-19 positive patients in the second phase of the study was 22.04%, whereas the those of non-COVID-19 patients in the second phase were found to be 15.95%. A maximum number of COVID-19 positive deaths during the first wave of the pandemic occurred in September 2020 and during the second wave in April 2021. In the first phase of the study, 69.6% of patients who died were males, and 30.3% were females, whereas in the second phase among COVID-19 positive subjects, 65% deaths were among males, and 35% deaths were among females. COVID-19 positive mortality in the second phase showed, 26.53% to be hypertensive, while 13.8% were diabetic. CONCLUSION: It was found that most of the deaths in both phases of COVID-19 amongst COVID-19 positive patients and non-COVID patients were amongst the elderly population (>60 years) with male predominance. Most deaths in both populations occurred during the first 3 days of admission whereas it was relatively less in the second phase. Noncommunicable diseases like systemic hypertension, and DM had a significant influence on all-cause mortality and morbidity in both COVID-19 positive and non-COVID-19 patients in the first and second waves of COVID-19. Noncommunicable diseases thus played a major role in mortality among both the populations under study.

Silent Hypoxia in Coronavirus disease-2019: Is it more dangerous? -A retrospective cohort study.

Background: Hypoxia in patients with COVID-19 is one of the strongest predictors of mortality. Silent hypoxia is characterised by the presence of hypoxia without dyspnoea. Silent hypoxia has been shown to affect the outcome in previous studies. Methods: This was a retrospective study of a cohort of patients with SARS-CoV-2 infection who were hypoxic at presentation. Clinical, laboratory and treatment parameters in patients with silent hypoxia and dyspnoeic hypoxia were compared. Multivariate logistic regression models were fitted to identify the factors predicting mortality. Results: Among 2080 patients with COVID-19 admitted to our hospital, 811 patients were hypoxic with SpO2 <94% at the time of presentation. Among them, 174 (21.45%) did not have dyspnoea since the onset of COVID-19 symptoms. Further, 5.2% of patients were completely asymptomatic for COVID-19 and were found to be hypoxic only on pulse oximetry. The case fatality rate in patients with silent hypoxia was 45.4% as compared to 40.03% in dyspnoeic hypoxic patients (P = 0.202). The odds ratio of death was 1.1 (95% CI: 0.41-2.97) in the patients with silent hypoxia after adjusting for baseline characteristics, laboratory parameters, treatment and in-hospital complications, which did not reach statistical significance (P = 0.851). Conclusion: Silent hypoxia may be the only presenting feature of COVID-19. As the case fatality rate is comparable between silent and dyspnoeic hypoxia, it should be recognised early and treated as aggressively. Because home isolation is recommended in patients with COVID-19, it is essential to use pulse oximetry in the home setting to identify these patients.

Impact of various hematological and biochemical parameters on mortality in coronavirus disease 2019 (COVID-19): A single-center study from North India.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS CoV-2), which causes coronavirus disease 2019 (COVID-19), has rapidly evolved into a pandemic, affecting more than 90 million people and more than 1.9 million deaths worldwide. Despite extensive study, the prognostic role of various hematological and biochemical parameters remains unclear. Methods: This study was carried out at a COVID care facility in Delhi. The demographic and clinical information, laboratory parameters (hematological, biochemical, and inflammatory), and the treatment of admitted COVID-19 patients during first wave were collected from electronic medical records and were subsequently analyzed. Results: Between March 2020 and November 2020, a total of 5574 patients were admitted to hospital due to COVID-19. Majority (77.2%) were male and had a mean (standard deviation [SD]) age of 38.9 (14.9) years. The mean (SD) duration of hospital stay was significantly higher in nonsurvivors. Out of the entire cohort, 8.7% of the patients had comorbidities, whereas 47.1% of the patients were asymptomatic at presentation. Compared to the survivors, the nonsurvivors had a significantly higher proportion of comorbidities and were more likely to be symptomatic. Patients who died during hospital stay had significantly higher relative neutrophil percent and neutrophil-lymphocyte ratio and lower lymphocyte percent. The patients who died had significantly higher levels of ferritin, D-dimer, and fibrinogen. Conclusions: Analysis of various hematological and inflammatory parameters can provide useful prognostic information among COVID-19-affected patients. It can also help in identifying patients who merit aggressive institutional care and thereby potentially mitigate the mortality.

Molecular signature of postmortem lung tissue from COVID-19 patients suggests distinct trajectories driving mortality.

To elucidate the molecular mechanisms that manifest lung abnormalities during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, we performed whole-transcriptome sequencing of lung autopsies from 31 patients with severe COVID-19 and ten uninfected controls. Using metatranscriptomics, we identified the existence of two distinct molecular signatures of lethal COVID-19. The dominant 'classical' signature (n=23) showed upregulation of the unfolded protein response, steroid biosynthesis and complement activation, supported by massive metabolic reprogramming leading to characteristic lung damage. The rarer signature (n=8) that potentially represents 'cytokine release syndrome' (CRS) showed upregulation of cytokines such as IL1 and CCL19, but absence of complement activation. We found that a majority of patients cleared SARS-CoV-2 infection, but they suffered from acute dysbiosis with characteristic enrichment of opportunistic pathogens such as Staphylococcus cohnii in 'classical' patients and Pasteurella multocida in CRS patients. Our results suggest two distinct models of lung pathology in severe COVID-19 patients, which can be identified through complement activation, presence of specific cytokines and characteristic microbiome. These findings can be used to design personalized therapy using in silico identified drug molecules or in mitigating specific secondary infections.

Variants of concern responsible for SARS-CoV-2 vaccine breakthrough infections from India.

Emerging reports of SARS-CoV-2 breakthrough infections entail methodical genomic surveillance for determining the efficacy of vaccines. This study elaborates genomic analysis of isolates from breakthrough infections following vaccination with AZD1222/Covishield and BBV152/Covaxin. Variants of concern B.1.617.2 and B.1.1.7 responsible for cases surge in April-May 2021 in Delhi, were the predominant lineages among breakthrough infections.

Clinical features, demography, and predictors of outcomes of SARS-CoV-2 infection at a tertiary care hospital in India: A cohort study.

BACKGROUND: The "second wave" of the COVID-19 pandemic hit India from early April 2021 to June 2021. We describe the clinical features, treatment trends, and baseline laboratory parameters of a cohort of patients with SARS-CoV-2 infection and their association with the outcome. METHODS: This was a retrospective cohort study. Multivariate logistic regression models were fitted to identify clinical and biochemical predictors of developing hypoxia, deterioration during the hospital stay, and death. RESULTS: A total of 2080 patients were included. The case fatality rate was 19.5%. Among the survivors, the median duration of hospital stay was 8 (5-11) days. Out of 853 (42.3%%) of patients who had COVID-19 acute respiratory distress syndrome at presentation, 340 (39.9%) died. Patients aged >45 years had higher odds of death as compared to the 18-44 years age group. Vaccination reduced the odds of death by 40% (odds ratio [OR] [95% confidence interval [CI]]: 0.6 [0.4-0.9], P = 0.032). Patients with hyper inflammation at baseline as suggested by leukocytosis (OR [95% CI]: 2.1 [1.5-3.1], P < 0.001), raised d-dimer >500 mg/dL (OR [95% CI]: 3.2 [2.2-4.7], P < 0.001), and raised C-reactive peptide >0.5 mg/L (OR [95% CI]: 3.7 [2.2-13], P = 0.037) had higher odds of death. Patients who were admitted in the 2nd week had lower odds and those admitted in the 3rd week had higher odds of death. CONCLUSION: This study shows that vaccination status and early admission during the inflammatory phase can change the course of illness of these patients. Improving vaccination rates and early admission of patients with moderate and severe COVID-19 can improve the outcomes.

Single-dose oral ivermectin in mild and moderate COVID-19 (RIVET-COV): A single-centre randomized, placebo-controlled trial.

INTRODUCTION: Ivermectin is an antiparasitic drug which has in-vitro efficacy in reducing severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) viral load. Hence, Ivermectin is under investigation as a repurposed agent for treating COVID-19. METHODS: In this pilot, double blind, randomized controlled trial, hospitalized patients with mild-to-moderate COVID-19 were assigned to a single oral administration of an elixir formulation of Ivermectin at either 24 mg or 12 mg dose, or placebo in a 1:1:1 ratio. The co-primary outcomes were conversion of RT-PCR to negative result and the decline of viral load at day 5 of enrolment. Safety outcomes included total and serious adverse events. The primary outcomes were assessed in patients who had positive RT-PCR at enrolment (modified intention-to-treat population). Safety outcomes were assessed in all patients who received the intervention (intention-to-treat population). RESULTS: Among the 157 patients randomized, 125 were included in modified intention-to-treat analysis. 40 patients each were assigned to Ivermectin 24 mg and 12 mg, and 45 patients to placebo. The RT-PCR negativity at day 5 was higher in the two Ivermectin arms but failed to attain statistical significance (Ivermectin 24 mg, 47.5%; 12 mg arm, 35.0%; and placebo arm, 31.1%; p-value = 0.30). The decline of viral load at day 5 was similar in each arm. No serious adverse events occurred. CONCLUSIONS: In patients with mild and moderate COVID-19, a single oral administration of Ivermectin did not significantly increase either the negativity of RT-PCR or decline in viral load at day 5 of enrolment compared with placebo.