Unraveling antiviral efficacy of multifunctional immunomodulatory triterpenoids against SARS-COV-2 targeting main protease and papain-like protease.

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may be over, but its variants continue to emerge, and patients with mild symptoms having long COVID is still under investigation. SARS-CoV-2 infection leading to elevated cytokine levels and suppressed immune responses set off cytokine storm, fatal systemic inflammation, tissue damage, and multi-organ failure. Thus, drug molecules targeting the SARS-CoV-2 virus-specific proteins or capable of suppressing the host inflammatory responses to viral infection would provide an effective antiviral therapy against emerging variants of concern. Evolutionarily conserved papain-like protease (PLpro) and main protease (Mpro) play an indispensable role in the virus life cycle and immune evasion. Direct-acting antivirals targeting both these viral proteases represent an attractive antiviral strategy that is also expected to reduce viral inflammation. The present study has evaluated the antiviral and anti-inflammatory potential of natural triterpenoids: azadirachtin, withanolide_A, and isoginkgetin. These molecules inhibit the Mpro and PLpro proteolytic activities with half-maximal inhibitory concentrations (IC50 ) values ranging from 1.42 to 32.7 µM. Isothermal titration calorimetry (ITC) analysis validated the binding of these compounds to Mpro and PLpro. As expected, the two compounds, withanolide_A and azadirachtin, exhibit potent anti-SARS-CoV-2 activity in cell-based assays, with half-maximum effective concentration (EC50 ) values of 21.73 and 31.19 µM, respectively. The anti-inflammatory roles of azadirachtin and withanolide_A when assessed using HEK293T cells, were found to significantly reduce the levels of CXCL10, TNFα, IL6, and IL8 cytokines, which are elevated in severe cases of COVID-19. Interestingly, azadirachtin and withanolide_A were also found to rescue the decreased type-I interferon response (IFN-α1). The results of this study clearly highlight the role of triterpenoids as effective antiviral molecules that target SARS-CoV-2-specific enzymes and also host immune pathways involved in virus-mediated inflammation.

Respiratory support in patients with severe COVID-19 in the International Severe Acute Respiratory and Emerging Infection (ISARIC) COVID-19 study: a prospective, multinational, observational study.

BACKGROUND: Up to 30% of hospitalised patients with COVID-19 require advanced respiratory support, including high-flow nasal cannulas (HFNC), non-invasive mechanical ventilation (NIV), or invasive mechanical ventilation (IMV). We aimed to describe the clinical characteristics, outcomes and risk factors for failing non-invasive respiratory support in patients treated with severe COVID-19 during the first two years of the pandemic in high-income countries (HICs) and low middle-income countries (LMICs). METHODS: This is a multinational, multicentre, prospective cohort study embedded in the ISARIC-WHO COVID-19 Clinical Characterisation Protocol. Patients with laboratory-confirmed SARS-CoV-2 infection who required hospital admission were recruited prospectively. Patients treated with HFNC, NIV, or IMV within the first 24 h of hospital admission were included in this study. Descriptive statistics, random forest, and logistic regression analyses were used to describe clinical characteristics and compare clinical outcomes among patients treated with the different types of advanced respiratory support. RESULTS: A total of 66,565 patients were included in this study. Overall, 82.6% of patients were treated in HIC, and 40.6% were admitted to the hospital during the first pandemic wave. During the first 24 h after hospital admission, patients in HICs were more frequently treated with HFNC (48.0%), followed by NIV (38.6%) and IMV (13.4%). In contrast, patients admitted in lower- and middle-income countries (LMICs) were less frequently treated with HFNC (16.1%) and the majority received IMV (59.1%). The failure rate of non-invasive respiratory support (i.e. HFNC or NIV) was 15.5%, of which 71.2% were from HIC and 28.8% from LMIC. The variables most strongly associated with non-invasive ventilation failure, defined as progression to IMV, were high leukocyte counts at hospital admission (OR [95%CI]; 5.86 [4.83-7.10]), treatment in an LMIC (OR [95%CI]; 2.04 [1.97-2.11]), and tachypnoea at hospital admission (OR [95%CI]; 1.16 [1.14-1.18]). Patients who failed HFNC/NIV had a higher 28-day fatality ratio (OR [95%CI]; 1.27 [1.25-1.30]). CONCLUSIONS: In the present international cohort, the most frequently used advanced respiratory support was the HFNC. However, IMV was used more often in LMIC. Higher leucocyte count, tachypnoea, and treatment in LMIC were risk factors for HFNC/NIV failure. HFNC/NIV failure was related to worse clinical outcomes, such as 28-day mortality. Trial registration This is a prospective observational study; therefore, no health care interventions were applied to participants, and trial registration is not applicable.

Disseminated Intravascular Coagulation Score and Sepsis-induced Coagulopathy Score in Prediction of COVID-19 Severity: A Retrospective Analysis.

BACKGROUND: The novel disseminated intravascular coagulation (DIC) score (platelet count, prolonged prothrombin time, D-dimer, and fibrinogen) and sepsis-induced coagulopathy (SIC) score (platelet count, international normalized ratio, and sequential organ failure assessment score) are markers of coagulopathy, which, for the first time, are explored in line with the coronavirus disease-2019 (COVID-19) disease outcomes. The correlation of D-dimer with these findings is also studied. MATERIALS AND METHODS: A retrospective analysis of hospital-based records of 168 COVID-19 patients was done. Data including D-dimer, routine investigations, DIC, and SIC scorings (all within 3 days of admission) were collected and correlated with the outcomes. The study was conducted in a tertiary care center catering to North India's population. RESULTS: Higher DIC score (1.59 ± 1.18 vs 0.96 ± 1.18), SIC score (1.60 ± 0.89 vs 0.63 ± 0.99), and D-dimer titers (1321.33 ± 1627.89 vs 583·66 ± 777.71 ng/mL) were significantly associated with severe COVID-19 disease (p <0.05). DIC score and SIC score ≥1, and D-dimer ≥1315 ng/mL for severe disease; DIC score ≥1, SIC score ≥2, and D-dimer ≥600 ng/mL for pulmonary embolism (PE); and DIC score and SIC score ≥1, and D-dimer level ≥990 ng/mL for mortality were the respective cutoff values we found from our study. CONCLUSION: Higher DIC scores, SIC scores, and D-dimer values are associated with severe COVID-19 disease, inhospital mortality, and PE risk. They can serve as easily accessible early markers of severe disease and prioritize hospital admissions in the presently overburdened scenario and may be used to develop prognostic prediction models. HOW TO CITE THIS ARTICLE: Kapoor M, Panda PK, Saini LK, Bahurupi Y. Disseminated Intravascular Coagulation Score and Sepsis-induced Coagulopathy Score in Prediction of COVID-19 Severity: A Retrospective Analysis. Indian J Crit Care Med 2021;25(12):1357-1363.

Intracranial Aspergillosis in an Immunocompetent Young Woman.

Intracranial aspergillosis (ICA) is very rare in the immunocompetent individuals, usually misdiagnosed as a tumor or an abscess. A high index of clinical suspicion is required in patients who present with focal neurological deficits, headache, or seizures. We report the case of a 25-year-old immunocompetent female, who presented with a 15-month history of headache, seizures, left-sided proptosis and ophthalmoplegia, and right hemiparesis. Recovery from the symptoms and decrease in the lesion size seen on the radiological assessment were achieved through two decompressive craniotomies followed by prolonged combined systemic antifungal therapies. Although the initial neuroimaging suggested a mitotic pathology, the surgical sample confirmed ICA. Now the patient is on single antifungal therapy (Tab. voriconazole, 200 mg twice daily) and doing her daily activities, but with a reduced intelligent quotient. We report a challenging case of ICA where multiple courses of combined antifungal therapies and repeat surgeries paved the way for a good prognosis.

Dyskeratosis Congenita with Acute Myeloid Leukemia, Cryptogenic Liver Fibrosis and Portal Hypertension.

Dyskeratosis Congenita (DC), a 100-year-old known rare hereditary entity, has recently changed its definition as per the pathogenetic model in the last decade. Now it is well known as one of the telomeropathies, pathognomonically characterized by a triad of reticulate pigmentation of the skin, nail dystrophy, and mucosal leukoplakia. It is a progressive systemic disorder which usually presents with involvement of several family members. Malignancies are increasingly reported. Clinical diagnosis is simple once there is a suspicion, but nowadays genetic diagnosis is advocated. Treatment is symptomatic and organ-oriented. We hereby report an adolescent male who presented with the classical mucocutaneous triad of DC with pancytopenia for four months. Bone marrow examination later revealed evolution of acute myeloid leukemia (AML). Liver function tests, imaging, and liver biopsy showed cryptogenic fibrosis with portal hypertension. Chemotherapy was started since hematopoietic stem cell transplantation was not feasible; however, he died very early due to repeated infections before completion of the treatment. AML and liver disease are increasingly reported independently in DC; however, coexistence of both complications in a single patient at first presentation has never been reported earlier. Early age onset of AML is noticeable too.

An Interventional Quality Improvement Study to Assess the Compliance to Cardiopulmonary Resuscitation Documentation in an Indian Teaching Hospital.

BACKGROUND: Cardiopulmonary resuscitation (CPR) should be performed as per the international guidelines; however, compliance to these guidelines is difficult to assess. This study was conducted to determine the compliance to American Heart Association (2010) guideline on CPR documentation by among resident physicians before and after resident training (two arms). METHODS: This pre-postinterventional quality improvement study was conducted in a referral center, North India. Data of hospitalized in-hospital CPR patients were collected in the form of quality indicators (checklists) as defined by the guideline and compared between two arms of before-after resident training. Residents were given appropriate training in CPR technique as per the guideline. The compliance of CPR documentation was assessed pre- and post-intervention. RESULTS: The baseline arm compliance of various components of CPR documentation was low. The postintervention arm compliances of all components significantly increased (baseline, 2.5% to postintervention, 15.11%, P = 0.03). Individual components assessed were documentation of assessment of responsiveness (65% to 77.9%, P = 0.19), assessment of breathing (37.5% to 58.1%, P = 0.03), assessment of carotid pulse (62.5% to 79%, P = 0.05), rate of chest compressions (20% to 39.5%, P = 0.04), airway management (62.5% to 82.5%, P = 0.02), and compressions to breaths ratio (12.5% to 31.4%, P = 0.02). Documentation of chest compression rate compared to nondocumentation (12 of 42 vs. 11 of 84, P = 0.04) was independently associated with a higher rate of return of spontaneous circulation. The study however did not show any survival benefits. CONCLUSIONS: This study establishes that the compliance to CPR documentation is poor as assessed by CPR documentation content and quality, which improves after physician training, but not up to the mark level (100%) that may be due to busy Indian hospital settings and human behavioral factors. Due to ethical constraints of live CPR assessment, this document checklist approach may be considered as an internal quality assessment method for CPR compliance. Furthermore, correct instruction in CPR technique along with proper documentation of the procedure is required, followed up with periodic re-education during the residency period and beyond.

Unique Triad of 'Pregnancy, Kala Azar and Hemophagocytic Lymphohistiocytic Syndrome from a Non-Endemic Region'.

India and neighboring Nepal, Bangladesh along with Sudan and Brazil are the four largest foci of visceral leishmaniasis and account for 90% of the world's visceral leishmaniasis (VL) burden, with India being the worst affected. High degree of suspicion is usually based on patient presenting from endemic area with features of pancytopenia hepatosplenomegaly. Hemophagocytic lymphohistiocytic (HLH) syndrome also presents with similar clinical features. Visceral leishmaniasis leading to secondary HLH syndrome is in itself a rare entity while both of these presenting in pregnant patient, to the best knowledge of the authors, is yet to be described in literature.

Pseudomonas and aspergillus symbiotic coinfections in a case of chronic obstructive pulmonary disease and diabetes mellitus.

Coinfection of Pseudomonas and Aspergillus has not been previously reported in patients with chronic obstructive pulmonary disease (COPD). A middle-aged, thinly built woman (Body Mass Index: 18.1 kg/m²) who smokes bidi (a type of tobacco) and has a history of exposure to open log fires for cooking, has been suffering from COPD for the last 4 years. She has been taking inhaled betamethasone and tiotropium. Additionally, she had uncontrolled diabetes for a few months. She presented with fever, productive cough, shortness of breath and chest pain for 5 days. She required non-invasive ventilation support for type-2 respiratory failure. Chest X-ray and CT confirmed pneumonia, cavities and abscesses in both lungs. Repeated sputum and bronchoalveolar lavage confirmed coinfections with Pseudomonas aeruginosa and Aspergillus fumigatus, respectively. Along with supportive therapy, she was treated with tablet levofloxacin and injection amikacin for 6 weeks based on culture sensitivity reports, and capsule itraconazole for 6 months. She recovered completely to her baseline COPD and diabetes status. This case study confirms that coinfections can occur in COPD and diabetes, highlighting the need for clinicians to be vigilant for the possibility of such symbiotic coinfections.

Community-acquired multidrug-resistant pneumonia, bacteraemia, and infective endocarditis: A case report.

BACKGROUND: The prevalence of multidrug-resistant (MDR) bacteria has increased globally, with extensive drug-resistant (XDR) bacteria posing a threat to patients. CASE SUMMARY: This case report describes a young man admitted for suspected tropical fever infections who experienced rapid deterioration in health. Despite negative results for tropical fever infections, he had neutrophilic leucocytosis, acute kidney injury, and chest imaging findings suggestive of bilateral consolidations. On day two, he was diagnosed with infective endocarditis with possible rheumatic heart disease and MDR methicillin-resistant Staphylococcus aureus bacteraemia, and community-acquired pneumonia. Despite treatment with broad-spectrum antibiotics, he did not respond and succumbed to death on day five. CONCLUSION: This case highlights that clinicians/public should be aware of MDR community-acquired pneumonia, bacteraemia, and endocarditis which ultimately culminate in high rates of morbidity and mortality. Early identification of pathogenic strain and prompt antibiotic treatment are a mainstay for the management and prevention of early fatalities. Simultaneously, route cause analysis of community-acquired MDR/XDR pathogens is a global need.

Burkholderia-associated polymyositis.

A diagnosis of polymyositis can readily be made when there is a typical history of proximal muscle weakness together with clinical findings, and there is corroboratory evidence in the form of elevated creatine kinase lactate dehydrogenase, aldolase, and serum glutamic-oxaloacetic transaminase (aspartate aminotransferase). A muscle biopsy usually helps in making the confirmatory diagnosis. A female in her 50s presented with non-healing multiple deep necrotic ulcers with muscle weakness. The initial possibility of vasculitis ulcers remained. Later, this proved to be a case of polymyositis with mildly elevated creatine kinase (which is usually not the case), atypical skin manifestations (usually there is no skin involvement), and negative extended myositis specific antibody panel with the growth of Burkholderia cepacia (perhaps the triggering factor). Hence, polymyositis can present with a myriad of atypical findings. Thus, thorough clinical examination and an integrated approach are necessary for early identification and treatment of the disease.

Amoxicillin Induced Fever, Rash, and Catatonia - A Case Study.

INTRODUCTION: Adverse drug reactions (ADR) are defined as any harmful or unpleasant events or injuries resulting from the use of any particular drug. Among those antibiotics that cause adverse reactions, amoxicillin is one of them. Catatonia and vasculitic rash are its rare adverse effects. CASE PRESENTATION: A 23-year-old postpartum female, with a history of taking empirical Amoxiclav (amoxicillin-clavulanic acid 625 mg) injection and oral tablets for episiotomy wound, presented with altered sensorium and fever followed by maculopapular rash. On examination, she had generalized rigidity with waxy flexibility that improved by lorazepam challenge and was diagnosed as catatonia. On evaluation, amoxicillin was found to be precipitating catatonia in this patient. CONCLUSION: Since the diagnosis of catatonia is often missed, any cases with clinical presentation of fever, rash, altered sensorium, and generalized rigidity should also be suspected for druginduced ADR and the precipitating factor should be searched for.

Characteristics and outcomes of COVID-19 patients admitted to hospital with and without respiratory symptoms.

Background: COVID-19 is primarily known as a respiratory illness; however, many patients present to hospital without respiratory symptoms. The association between non-respiratory presentations of COVID-19 and outcomes remains unclear. We investigated risk factors and clinical outcomes in patients with no respiratory symptoms (NRS) and respiratory symptoms (RS) at hospital admission. Methods: This study describes clinical features, physiological parameters, and outcomes of hospitalised COVID-19 patients, stratified by the presence or absence of respiratory symptoms at hospital admission. RS patients had one or more of: cough, shortness of breath, sore throat, runny nose or wheezing; while NRS patients did not. Results: Of 178,640 patients in the study, 86.4 % presented with RS, while 13.6 % had NRS. NRS patients were older (median age: NRS: 74 vs RS: 65) and less likely to be admitted to the ICU (NRS: 36.7 % vs RS: 37.5 %). NRS patients had a higher crude in-hospital case-fatality ratio (NRS 41.1 % vs. RS 32.0 %), but a lower risk of death after adjusting for confounders (HR 0.88 [0.83-0.93]). Conclusion: Approximately one in seven COVID-19 patients presented at hospital admission without respiratory symptoms. These patients were older, had lower ICU admission rates, and had a lower risk of in-hospital mortality after adjusting for confounders.

Study on good clinical practices among researchers in a tertiary healthcare institute in India.

BACKGROUND: Good clinical practice (GCP) is put in place to protect human participants in clinical trials as well as to ensure the quality of research. Non-adherence to these guidelines can produce research that may not meet the standards set by the scientific community. Therefore, it must be ensured that researchers are well-versed in the GCP. But not much is known about the knowledge and practices of the GCP in the medical colleges of North India. AIM: To assess the knowledge and practices of researchers about GCP and analyze these with respect to the demographics of participants. METHODS: This is a cross-sectional study. A self-structured questionnaire about GCP, after expert validations, was circulated among researchers, at a tertiary healthcare institute, All India Institute of Medical Sciences (AIIMS), Rishikesh. A total of 59 individuals, who were selected by universal sampling, participated in the study. All healthcare workers who have been investigators of Institutional Ethics Committee-approved research projects, except residents and faculty, and are still a part of the institute have been included in the study. The study was approved by the Institutional Ethics Committee of AIIMS, Rishikesh. We used descriptive analysis and the Chi-squared test to analyze data. P value < 0.05 was considered significant. RESULTS: Out of 59 participants, only 11 (18.6%) were certified for GCP. Most of the participants (64.4%) had "Average" knowledge, 33.9% had "Good" knowledge and 1.7% had "Poor" knowledge. Only 49% of participants had satisfactory practices related to GCP. There was a significant difference in the knowledge based on the current academic position for the items assessing knowledge of institutional review board (P = 0.010), confidentiality & privacy (P = 0.011), and participant safety & adverse events (P < 0.001). There was also a significant difference in knowledge of research misconduct (P = 0.024) and participant safety & adverse events (P = 0.011) based on certification of GCP. There was a notable difference in the practices related to recruitment & retention on the basis of current academic position (P < 0.001) and certification of GCP (P = 0.023). We also observed a considerable difference between the knowledge and practices of GCP among the participants (P = 0.013). CONCLUSION: Participants have basic knowledge of GCP but show a lack thereof in certain domains of GCP. This can be addressed by holding training sessions focusing on these particular domains.

Ground level utility of Access, Watch, Reserve classification: Insights from a tertiary care center in North India.

BACKGROUND: The overuse and misuse of antimicrobials contribute significantly to antimicrobial resistance (AMR), which is a global public health concern. India has particularly high rates of AMR, posing a threat to effective treatment. The World Health Organization (WHO) Access, Watch, Reserve (AWaRe) classification system was introduced to address this issue and guide appropriate antibiotic prescribing. However, there is a lack of studies examining the prescribing patterns of antimicrobials using the AWaRe classification, especially in North India. Therefore, this study aimed to assess the prescribing patterns of antimicrobials using the WHO AWaRe classification in a tertiary care centre in North India. AIM: To study the prescribing patterns of antimicrobials using WHO AWaRe classification through a cross-sectional study in All India Institute of Medical Sciences Rishikesh. METHODS: A descriptive, cross-sectional study was conducted from July 2022 to August 2022 at a tertiary care hospital. Prescriptions containing at least one antimicrobial were included in the study. Data on prescriptions, including patient demographics, departments, types of antimicrobials prescribed, and duration of treatment, were collected. A questionnaire-based survey was also conducted to assess the knowledge and practices of prescribing doctors regarding the utility of AWaRe classification. RESULTS: The study involved a total of 123 patients, each of whom received at least one antimicrobial prescription. Most prescriptions were for inpatients, evenly distributed between Medicine (Internal medicine, Pediatrics, Dermatology) and Surgical departments (General surgery and specialties, Otorhinolaryngology, Ophthalmology, Obstetrics and Gynecology). Metronidazole and ceftriaxone were the most prescribed antibiotics. According to the AWaRe classification, 57.61% of antibiotics fell under the Access category, 38.27% in Watch, and 4.11% in Reserve. Most Access antibiotics were prescribed within the Medicine department, and the same department also exhibited a higher frequency of Watch antibiotics prescriptions. The questionnaire survey showed that only a third of participants were aware of the AWaRe classification, and there was a lack of knowledge regarding AMR and the potential impact of AWaRe usage. CONCLUSION: This study highlights the need for better antimicrobial prescribing practices and increased awareness of the WHO AWaRe classification and AMR among healthcare professionals. The findings indicate a high proportion of prescriptions falling under the Access category, suggesting appropriate antibiotic selection. However, there is a significant difference between the WHO Defined Daily Dose and the prescribed daily dose in the analysed prescriptions suggesting overuse and underuse of antibiotics. There is room for improvement and educational interventions and antimicrobial stewardship programs should be implemented to enhance knowledge and adherence to guidelines, ultimately contributing to the containment of AMR.

Hyper-Eosinophilic Syndrome with Myocarditis after Inactivated SARSCoV- 2 Vaccination - A Case Study.

INTRODUCTION: COVID-19 vaccine-induced serious adverse reactions are rare. Hypereosinophilia syndrome with myocarditis has not been reported earlier following BBV152 vaccine administration. CASE PRESENTATION: A young man without any co-morbidities presented with persistent periorbital swelling along with itchy swelling over fingers, resting tachycardia, and exertional breathlessness following the first dose of an inactivated SARS-CoV-2 vaccine (BBV152, COVAXIN). On investigation, the patient had elevated blood eosinophils (maximum 21.5% with an absolute eosinophil count of 2767/mm3) and myocarditis (Lake Louise Criteria). He was successfully treated with steroids and supportive treatment. CONCLUSION: This is the first reported case of hyper-eosinophilia syndrome after COVAXIN administration. Prior history of the allergic disease may be a predisposing factor in this case. Hypereosinophilia can present with variable symptoms. In the current case, myocarditis was present with persistent resting tachycardia and dyspnea. Steroid and antiallergic drugs may be successful for the treatment of vaccine-induced hyper-eosinophilia with myocarditis. Increased vigilance is needed for such adverse events.

Convalescent Plasma the Experience and Journey from Blockbuster to Incognito: A Single Centre Experience.

BACKGROUND: Convalescent plasma has been used to provide passive immunotherapy to patients with COVID-19 with a high level of safety. Very few efficacy studies were available, and due to COVID being a relatively new disease, its exact therapeutic role was unclear. This observational study on the impact of COVID convalescent plasma (CCP) on clinical outcomes attempts to evaluate the effectiveness of convalescent COVID-19 plasma therapy in the treatment of COVID-19 patients at the tertiary care center in the Uttarakhand state of India. METHODS: CCP was collected by plasmapheresis/whole blood from willing COVIDrecovered donors who underwent pre-donation testing including ABO and RhD grouping, mandatory blood screening tests for HIV, HBV, HCV, syphilis and Malaria, Haemoglobin estimation and COVID IgG assay. Hospitalized patients with severe COVID-19 pneumonia who received these CCP units were followed up and the outcome (Recovery/death) was observed. RESULTS: A total of 63 patients who received CCP were included in the study. Out of the total, 13 (20.7%) were females and 50 (79.3%) were males and their ages ranged from 24 to 80 years with a median age of 53 years. The period between the start of symptoms and hospitalization ranged from 1 to 14 days with an average duration of 4.7 days. Symptoms on presentation included Fever 53/63 (84.1%), Tachypnoea 60/63 (95.2%) and Cough 42/63 (66.7%). Among these patients, 22/63 (34.9%) were on non-invasive ventilation (NIV), 6/63 (9.5%) on non-rebreather mask (NRBM) and 32/63 (50.8%) were on Ventilator support. The infused convalescent plasma had a Mean IgG value of 57.3 AU with a range of (10-142 AU). A total of 37 (58.7%) patients were lost to COVID-19 infection and 26 (41.3%) were discharged from the hospital in a healthy state. CONCLUSION: The use of convalescent plasma in addition to standard treatment in our study on patients with severe pneumonia due to COVID-19 did not demonstrate reduced mortality of COVID-19 patients amidst numerous variables. The results showed that the use of convalescent plasma as a treatment option in the present conditions needs a serious re-evaluation. Studies on a strictly defined recipient group and transfusion of CCP units, with adequate antibody titer and/or neutralization activity, must be analyzed for future works.

Correlation of serum SARS-CoV-2 IgM and IgG serology and clinical outcomes in COVID-19 patients: Experience from a tertiary care centre.

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has become a pandemic for the last 2 years. Inflammatory response to the virus leads to organ dysfunction and death. Predicting the severity of inflammatory response helps in managing critical patients using serology tests IgG and IgM. AIM: To investigate the correlation of the serology (IgM and IgG) with reverse transcriptase polymerase chain reaction (RT-PCR) status, disease severity [mild to critical], intensive care unit (ICU) admission, septic shock, acute kidney injury, and in-hospital mortality. METHODS: We conducted a longitudinal study to correlate serum SARS-CoV-2 immunoglobulin M (IgM) and immunoglobulin G (IgG) serology with clinical outcomes in coronavirus disease 2019 (COVID-19) patients. We analyzed patient data from March to December 2020 for those who were admitted at All India Institute of Medical Sciences Rishikesh. Clinical and laboratory data of these patients were collected from the e-hospital portal and analyzed. A correlation was seen with clinical outcomes and was assessed using MS Excel 2010 and SPSS software. RESULTS: Out of 494 patients, the mean age of patients was 48.95 ± 16.40 years and there were more male patients in the study (66.0%). The patients were classified as mild-moderate 328 (67.1%), severe 131 (26.8%), and critical 30 (6.1%). The mean duration from symptom onset to serology testing was 19.87 ± 30.53 d. In-hospital mortality was observed in 25.1% of patients. The seropositivity rate (i.e., either IgG or IgM > 10 AU) was 50%. IgM levels (AU/mL) (W = 33428.000, P ≤ 0.001) and IgG levels (AU/mL) (W = 39256.500, P ≤ 0.001), with the median IgM/ IgG levels (AU/mL), were highest in the RT-PCR-Positive group compared to RT-PCR-Negative clinical COVID-19. There was no significant difference between the two groups in terms of all other clinical outcomes (disease severity, septic shock, ICU admission, mechanical ventilation, and mortality). CONCLUSION: The study showed that serology levels are high in RT-PCR positive group compared to clinical COVID-19. However, serology cannot be useful for the prediction of disease outcomes. The study also highlights the importance of doing serology at a particular time as antibody titers vary with the duration of the disease. In week intervals there was a significant correlation between clinical outcomes and serology on week 3.

Characteristics and outcomes of an international cohort of 600 000 hospitalized patients with COVID-19.

BACKGROUND: We describe demographic features, treatments and clinical outcomes in the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) COVID-19 cohort, one of the world's largest international, standardized data sets concerning hospitalized patients. METHODS: The data set analysed includes COVID-19 patients hospitalized between January 2020 and January 2022 in 52 countries. We investigated how symptoms on admission, co-morbidities, risk factors and treatments varied by age, sex and other characteristics. We used Cox regression models to investigate associations between demographics, symptoms, co-morbidities and other factors with risk of death, admission to an intensive care unit (ICU) and invasive mechanical ventilation (IMV). RESULTS: Data were available for 689 572 patients with laboratory-confirmed (91.1%) or clinically diagnosed (8.9%) SARS-CoV-2 infection from 52 countries. Age [adjusted hazard ratio per 10 years 1.49 (95% CI 1.48, 1.49)] and male sex [1.23 (1.21, 1.24)] were associated with a higher risk of death. Rates of admission to an ICU and use of IMV increased with age up to age 60 years then dropped. Symptoms, co-morbidities and treatments varied by age and had varied associations with clinical outcomes. The case-fatality ratio varied by country partly due to differences in the clinical characteristics of recruited patients and was on average 21.5%. CONCLUSIONS: Age was the strongest determinant of risk of death, with a ∼30-fold difference between the oldest and youngest groups; each of the co-morbidities included was associated with up to an almost 2-fold increase in risk. Smoking and obesity were also associated with a higher risk of death. The size of our international database and the standardized data collection method make this study a comprehensive international description of COVID-19 clinical features. Our findings may inform strategies that involve prioritization of patients hospitalized with COVID-19 who have a higher risk of death.

Predictors of Mortality among Patients Hospitalized with COVID-19 during the First Wave in India: A Multisite Case-Control Study.

Severe acute respiratory syndrome coronavirus 2 disease (COVID-19) has caused more than 6 million deaths globally. Understanding predictors of mortality will help in prioritizing patient care and preventive approaches. This was a multicentric, unmatched, hospital-based case-control study conducted in nine teaching hospitals in India. Cases were microbiologically confirmed COVID-19 patients who died in the hospital during the period of study and controls were microbiologically confirmed COVID-19 patients who were discharged from the same hospital after recovery. Cases were recruited sequentially from March 2020 until December-March 2021. All information regarding cases and controls was extracted retrospectively from the medical records of patients by trained physicians. Univariable and multivariable logistic regression was done to assess the association between various predictor variables and deaths due to COVID-19. A total of 2,431 patients (1,137 cases and 1,294 controls) were included in the study. The mean age of patients was 52.8 years (SD: 16.5 years), and 32.1% were females. Breathlessness was the most common symptom at the time of admission (53.2%). Increasing age (adjusted odds ratio [aOR]: 46-59 years, 3.4 [95% CI: 1.5-7.7]; 60-74 years, 4.1 [95% CI: 1.7-9.5]; and ≥ 75 years, 11.0 [95% CI: 4.0-30.6]); preexisting diabetes mellitus (aOR: 1.9 [95% CI: 1.2-2.9]); malignancy (aOR: 3.1 [95% CI: 1.3-7.8]); pulmonary tuberculosis (aOR: 3.3 [95% CI: 1.2-8.8]); breathlessness at the time of admission (aOR: 2.2 [95% CI: 1.4-3.5]); high quick Sequential Organ Failure Assessment score at the time of admission (aOR: 5.6 [95% CI: 2.7-11.4]); and oxygen saturation < 94% at the time of admission (aOR: 2.5 [95% CI: 1.6-3.9]) were associated with mortality due to COVID-19. These results can be used to prioritize patients who are at increased risk of death and to rationalize therapy to reduce mortality due to COVID-19.