Role of Matrix Degradation, Oxidative Stress, Inflammation & Trace Elements in COVID-19 Patients: A Multivariate Study from India.

The interrelationship between matrix degradation, oxidative stress, inflammation and trace elements can be speculated in COVID-19. The objective of the study was to evaluate the oxidative stress, inflammation and matrix degradation markers and trace elements in COVID-19 positive patients. A group of confirmed severe COVID-19 positive patients (n = 30) along with COVID-19 negative patients (n = 30) with similar symptoms were included. Both group of patients were assessed for oxidative stress markers, inflammatory cytokines, matrix metalloproteinase (MMP)s and their inhibitors along with trace elements in blood. All the data were subjected to univariate as well as multivariate analysis including PCA, PLS-DA, OPLS-DA. Diagnostic accuracy was tested by ROC curve analysis. Further relationship with Neutrophil/ lymphocyte (N/L) ratio was established if any. Increased oxidative stress, inflammation and matrix degradation is evidenced by significant rise in oxidative markers, inflammatory cytokines and MMP9/TIMP-1 ratio. Decreased Cu/Zn ratio is also observed in COVID-19 positive patients. Multivariate analysis identified SOD, Cu/Zn ratio, IL-6 and TOS, as effective discriminant among the two groups of patients. Further, accuracy was confirmed by ROC curves. Neutrophil/ lymphocyte (N/L) ratio, shows significant negative association with SOD (r= -0.75, p < 0.005) and Cu/Zn ratio (r = -0.88, p < 0.005). These data suggest the attributes of these biomarkers in disease severity. The potential use of these blood-based laboratory markers in disease prognosis seems promising and warrants further attention. Given by the symptoms and severity of the disease, it will be promising to monitor Cu/Zn ratio along with other prognostic indicators.

Effect of treatment regimens in severe COVID pneumonia at an Indian tertiary care hospital: An observational, real-world study.

Background: Corticosteroids have attracted attention as a treatment option for severe Coronavirus disease (COVID-19). However, published data on steroid therapy is debatable, and real-world data is lacking. This study evaluated the effect of treatment regimens, especially Pulse steroid therapy (Injection Methyl Prednisolone 250 mg iv once a day for three days) in severe-COVID-19 pneumonia at an Indian tertiary care hospital. Methods: This observational cross-sectional study included severe COVID-19 pneumonia patients aged >18 years, requiring assisted ventilation. As part of the hospital protocol, patients received either pulse steroid therapy, remdesivir or tocilizumab in addition to the recommended steroid doses i.e., injection of dexamethasone 6 mg iv once a day. The association of factors and treatment regimens to patient outcomes was evaluated. Results: Data of eighty-three patients were assessed, majority being above 60 years (n = 30, 36.14%) and males (n = 45/83, 54.21%). The commonest comorbidities were hypertension (n = 26), diabetes (n = 23) and obesity (n = 19), fifty-five patients (66.26%) reported at least one comorbidity. Sixty-one patients (73.49%) had received pulse steroid regimen, forty-eight patients (57.83%) were administered remdesivir-based regimen while twelve patients (14.46%) had received tocilizumab treatment. 54.1% patients managed with pulse steroid regimens were discharged after treatment, statistically similar to remdesivir-managed subgroup (62.5%, p > 0.05). On sub-group analysis, pulse steroids showed better outcomes in young males with no comorbidities. No comorbidity had significant relationship with patient outcomes (p > 0.05). Conclusion: Pulse steroid therapy is an effective therapy in management of patients with severe COVID-19 pneumonia in a real-world setting, with better outcomes in young males without comorbidities. Pulse steroids can be considered a viable option for severe-COVID-19 pneumonia management.

Disease profile and patient outcomes in vaccinated COVID-19 patients at a tertiary care Indian hospital: An observational, real-world study.

Background: There is a lack of real-world evidence evaluating the disease outcomes and patient features in vaccinated coronavirus disease (COVID-19) cases. This study aimed to address this scientific need gap and also compare characteristics between the partially vaccinated and fully vaccinated COVID-19 patients in India. Methods: This observational cross-sectional study included data of adult patients diagnosed with COVID-19 at a tertiary care Indian hospital with a history of at least single-dose COVID-19 vaccination. Overall evaluation of patient features and disease characteristics was done. Patients were segregated into two groups based on vaccination status (partial or fully vaccinated), and characteristics were compared between these two groups along with COVID-19 outcomes. Results: Data of 403 vaccinated patients treated for breakthrough COVID-19 infection postvaccination was evaluated. The mean age was 47.7 ± 15.3 years (range: 19-87 years), with the majority being males (73.94%); 54.1% of evaluated cases were fully vaccinated; 74.93% of cases were asymptomatic. The majority of the symptomatic cases (60.39%) suffered from only mild-moderate symptoms; 72.7% of cases needed only home isolation, while only 1.99% died. A significantly higher number of partially vaccinated COVID-19 patients had severe COVID-19 pneumonia vs. fully vaccinated ones (14.59% vs. 5.96%, p < 0.05). The relative risk (RR) for the development of severe COVID-19 infection was 0.32 for the fully vaccinated subgroup, which was a significant finding (CI: 0.19-0.55, p < 0.05). Conclusion: The majority of vaccinated COVID-19 patients are asymptomatic or suffer from mild clinical features, which can be managed with home isolation. Fully vaccinated patients have a lower risk of developing severe COVID-19 infection in comparison to partially vaccinated cases.

A single-center experience in use of tocilizumab in COVID-19 pneumonia in India.

BACKGROUND: IL-6 receptor antagonist tocilizumab (TCZ) has been used in several reported studies in the treatment of COVID-19 pneumonia and pieces of evidence are still emerging. METHODS: All patients with COVID-19 pneumonia showing features of hyperinflammatory syndrome receiving TCZ at a tertiary care center in India were included in the study and a retrospective descriptive analysis was done. RESULTS: Between May 2020 to August 2020, 21 patients received TCZ out of which 13 survived and 8 died. All non-survivors had longer duration (median 12 days, minimum 9, maximum 15 days compared to median 6 days, minimum 3 and maximum 14 days in survivors) of symptoms and severe disease requiring mechanical ventilation at the time of TCZ administration. Among survivors, 8 patients had severe disease, 3 had moderate disease, and 2 patients had mild disease. Six out of 8 (75%) among non-survivors and 8 out of 13 (62%) among survivors had preexisting medical comorbidities. The non-survivors had higher baseline neutrophil-to-leukocyte ratio (10.5 vs 8.8), serum ferritin (960 ng/ml vs 611 ng/ml), lactate dehydrogenase (795 IU/L vs 954 IU/L), and D-dimer (5900 µg/ml vs 1485 mg/ml) levels. No drug-related serious adverse effect was noted among the patients. CONCLUSION: In a scenario of emerging evidence for the role of TCZ in the management of severe COVID-19, our study provides useful data on its use in the Indian scenario. Deliberate patient selection and timing initiation of TCZ at a crucial stage of the disease may be beneficial in COVID-19 pneumonia with good safety returns.

A Study on the Safety of Percutaneous Tracheostomy in Patients with Severe Acute Respiratory Syndrome Novel Corona Virus 2 (SARS-nCoV2) Infection: A Single-Center Observational Cohort Study in a CoVID Intensive Care Unit.

BACKGROUND: We studied the safety of percutaneous dilatational tracheostomy (PCDT) in severe acute respiratory syndrome novel coronavirus 2 (SARS-nCoV2). PATIENTS AND METHODS: From 01 March 20 to 30 November 2020, 1635 required hospital admission of which 145 (9%) required intensive (ICU) care. The primary outcomes are mortality and secondary outcomes were duration of invasive mechanical ventilation (IMV), length of stay (LOS) in ICU and hospital, and days required for decannulation. RESULTS: Out of the 145 (9%), 107 (73.7%) were males (mean 61.4 years, median body mass index (BMI) of 28.2 kg/m2), and 38 (26.2%) were females (mean 58.10 years, median BMI of 31.2 kg/m2). In the cohort of 80 (55.17%) requiring IMV, 19 (23.7%) died within 72 hours and were not included in the study, 37 (group "NT") and 24 (group "T") had a median duration of ventilation of 9 d (IQR, 6-11) and 12 d (IQR, 11-17.25) respectively. Patients in group "T" underwent PCDT based on clinical criteria (fraction of inspired oxygen (FiO2) of ≤ 50% with positive end-expiratory pressure (PEEP) of ≤ 10 cms of H2O with stable hemodynamics), and 16 (66.7%) had survived. The reverse transcription-polymerase chain reaction (RT-PCR) does not need to be negative, and none of the health care workers (HCW's) were infected. The Cox-hazard ratio [HR] is 0.19, 95% confidence interval [CI] (0.09, 0.41) with a P-value of <0.001, 83 (57.2%) were discharged with a mortality of 42.8%. CONCLUSIONS: PCDT is safe and effective in patients anticipated in need of prolonged mechanical ventilation.

Cerebral Venous Thrombosis in Acute Lymphoblastic Leukemia with Severe COVID-19: a Case Report.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has brought an unprecedented upheaval in our health-care systems. Amongst the many challenges posed by the disease, increased risk of thromboembolism has presented a distinct new front for increased mortality and morbidity. While there are multiple documented evidences for the same, the exact mechanism, knowledge of groups at-risk, and mitigation strategies are evolving. We present a case of a young individual who was diagnosed with acute lymphoblastic leukemia (ALL), was started on appropriate chemotherapy, and subsequently developed severe COVID-19 pneumonia. He was treated for COVID-19 pneumonia and recovered from the illness. However, his recovery from COVID-19 was further complicated by cortical venous sinus thrombosis (CVT). Contrast enhanced magnetic resonance imaging (CEMRI) brain and magnetic resonance venography (MRV) revealed the diagnosis of CVT with hemorrhagic parenchymal changes. He was managed with therapeutic anticoagulation and cerebral decongestants and was subsequently shifted to oral anticoagulant therapy. While the case was managed at a tertiary care setting, it opened up the question of identifying the high-risk groups and to formulate guidelines for extended thromboprophylaxis in these patients.

Diabetes Mellitus and Hypertension Increase Risk of Death in Novel Corona Virus Patients Irrespective of Age: a Prospective Observational Study of Co-morbidities and COVID-19 from India.

Elderly people and people with co-morbidities have emerged as the most vulnerable group at risk of developing complications and succumbing to novel coronavirus (COVID-19) infection. We recorded the baseline demographic profile, baseline clinical and laboratory parameters, and prevalence of various co-morbidities and their effect on the prognosis of COVID-19 cases. We conducted a prospective observational study and analyzed baseline clinical and laboratory parameters and co-morbidities and their effect on severity and mortality in 710 COVID-19 cases. Seven hundred ten patients with laboratory-confirmed COVID-19 were recruited from the 28th of March to the 31st of August 2020. The mean age was 48.4 ± 16.4years. A total of 530 (74.6%) patients were male. Overall, the mean length of hospital stay was 12.7 days. In total, 645 patients(90.8%) were mild to moderate cases and did not require initial ICU care. Sixty-five (9.2%) cases required initial intensive care unit care. Fifty (7%) admitted patients succumbed to the illness. Diabetes mellitus and hypertension increased the risk of death in COVID-19 patients irrespective of age. Increasing age and co-morbidities adversely affect the prognosis of patients of COVID-19. Diabetes mellitus and hypertension increase the risk of death in COVID-19 patients and negate the incremental effect of age on death in these patients.

Reinfection or Reactivation of Coronavirus-19 in Patients with Hematologic Malignancies: Case Report Series.

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been relentless. We are into the 10th month of the pandemic, and we are still getting surprised every day. Although neutralizing antibodies are generated in response to coronavirus disease-19 (COVID-19), these antibodies do not appear to confer lifelong immunity, as lately there have been reports from various parts of the world of reinfection with the virus, starting from Hong Kong, Belgium, and the USA. The Indian Council of Medical Research (ICMR) has been on-record claiming three cases of reinfection in India. Herein, we report three patients of hematologic malignancy who most probably had reinfection with SARS-CoV-2, after complete documented recovery from first infection. All three patients were immunocompromised owing to their primary hematologic malignancy coupled with ongoing therapy, and the second infection was documented to be severe in all the three cases from the first episode.

Clinical Triaging in Cough Clinic Alleviates COVID-19 Overload in Emergency Department in India.

The importance of this study is the efficacy of "symptoms only" approach at a screening clinic for coronavirus disease 2019 (COVID-19) diagnosis in low- and middle-income countries (LMIC) setting. The objective of this study was to assess how efficiently primary care physicians at the screening clinic were able to predict whether a patient had COVID-19 or not, based on their symptom-based assessment alone. The current study is a cross-sectional retrospective observational study. This study was conducted at a single-center, tertiary care setting with a dedicated COVID-19 facility in a metropolitan city in eastern India. Participants are all suspected COVID-19 patients who presented themselves to this center during the outbreak from 1 August 2020 to 30 August 2020. Patients were referred to the Cough Clinic from the various outpatient departments of the hospital or from smaller satellite centers located in different parts of the city and other dependent geographical areas. The main outcome(s) and measure(s) is to study whether outcome of confirmatory test results can be predicted accurately by history taking alone. From 01 August 2020 to 30 Aug 2020, 511 patients with at least one symptom suggestive of COVID-19 reported to screening clinic. Out of these, 65.4% were males and 34.6% were females. Median age was 45 years with range being 01 to 92 years. Fever was seen in 70.4% while cough was present in 22% of cases. Overall positivity for SARS-CoV-2 during this period in this group was 54.21%. At 50% pre-test probability, the sensitivity of trained doctors working at the clinic, in predicting positive cases based on symptoms alone, was approximately 74.7%, and specificity for the same was 58.12%. The positive predictive value of the doctors' assessment was 67.87%, and the negative predictive value was 66.02%. Rapid triaging for confirmatory diagnosis of COVID-19 is feasible at screening clinic based on history taking alone by training of primary care physicians. This is particularly relevant in LMIC with scarce healthcare resources to overcome COVID-19 pandemic.