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 Covid-recovered 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.

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.

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.

Comparing India's second COVID wave with the first wave - a single-center experience.

Background The COVID-19 pandemic has resurfaced in India in the form of a hard-hitting second wave. This study aims to compare the clinical profile of the first wave (April-June 2020) and the second wave (March-May 2021) of the severe acute respiratory syndrome coronavirus-2 pandemic (SARS-CoV-2) in a single tertiary care center of India. Methods In this retrospective observational study, we examined the demographic profile, symptoms at presentation, the severity of illness, baseline investigations, treatments received, underlying comorbidities, and outcomes of the COVID-19 patients belonging to the first (W1) and the second wave (W2) of the pandemic in India. Results The age group affected most in the W2 is 50.5 (17.7) versus 37•1 (16•9) years for W1. The baseline oxygen saturation is lower in W2, being 84•0 (13•4) % compared with 91•9 (7•4) % in W1 [SpO2 <90% OR 14.3 (6.1-33), P<0.0001]. 70.2 % of the cases belonged to the severe category in W2 compared to 37.5% in W1. W2 has worse outcomes. Incidence of acute respiratory distress syndrome (ARDS) [48.7% v/s 6.45%; OR 15.4 (6.5-35.7), P<0.0001], Acute Kidney Injury (AKI) [18% v/s 2.4%; OR 6 (1.7-22.2), P=0.005], Acute Liver Injury (transaminitis) [12.8% v/s 6.4%, OR 7.3 (3.7-14.3), P<0.0001], and deaths (29% v/s 9.6%, standardized mortality ratio 3.5) is higher in W2. Similarly, the CT severity score for W2 [29.5 (6.7)] was higher than W1 [23•2 (11•5), P<0.05]. The proportion of patients requiring oxygen [81.8% v/s 11.2%; OR 125 (40-333.3), P<0.0001], high flow nasal cannula (HFNC) (11.4% v/s 5.6%), Non-Invasive Ventilation (NIV) (41.2% v/s 1.5%), invasive ventilation [24.5% v/s 0.9%; OR 22.72 (2.94-166.6), P=0.003], as well as ICU/HDU admissions [56.4% v/s 12.0%; OR 10.5 (5.3-21.2), P<0.0001] was higher for W2 as compared with W1. Cough, invasive ventilation, inotrope requirement, and ARDS are significantly related to higher mortality in the W2 than W1. Conclusion Higher age, oxygen requirement, ventilator requirement, ICU admission, and organ failure are more prevalent in the admitted COVID-19 cases during the second wave that hit India than the first wave and are associated with more fatalities. Strategy for another wave should be planned accordingly.

Hyper-eosinophilic syndrome with myocarditis after inactivated SARS-CoV-2 vaccination - a case study.

INTRODUCTION: COVID-19 vaccine induced serious adverse reactions are rare. Hyper-eosinophilia 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 first dose of an inactivated SARS-CoV-2 vaccination (BBV152, COVAXIN). On investigation, patient had elevated blood eosinophils (maximum 21.5% with absolute eosinophil count of 2767/mm3) and myocarditis (Lake Louise Criteria). He was successfully treated with steroid and supportive treatment. CONCLUSION: This is the first reported case of hyper-eosinophilia syndrome after COVAXIN administration. Prior history of allergic disease may be a predisposing factor in this case. Hyper-eosinophilia can present with variable symptoms. In the current case, myocarditis was present with presentation as persistent resting tachycardia and dyspnea. Steroid and antiallergic drugs may be successfully used for the treatment of vaccine induced hyper-eosinophilia with myocarditis. Increased vigilance is needed for such adverse events.

Utility of IL-6 in the Diagnosis, Treatment and Prognosis of COVID-19 Patients: A Longitudinal Study.

COVID-19 has caused devastating effects worldwide ever since its origin in December 2019. IL-6 is one of the chief markers used in the management of COVID-19. We conducted a longitudinal study to investigate the role of IL-6 in diagnosis, treatment, and prognosis of COVID-19-related cytokine storm. Patients with COVID-19 who were admitted at AIIMS Rishikesh from March to December 2020 were included in the study. Patients with no baseline IL-6 value at admission and for whom clinical data were not available were excluded. Clinical and laboratory data of these patients were collected from the e-hospital portal and entered in an excel sheet. Correlation was seen with other inflammatory markers and outcomes were assessed using MS Excel 2010 and SPSS software. A total of 131 patients were included in the study. Of these, 74.8% were males, with mean age 55.03 ± 13.57 years, and mean duration from symptom onset being 6.69 ± 6.3 days. A total of 82.4% had WHO severe category COVID-19, with 46.56% having severe hypoxia at presentation and 61.8% of them having some comorbidity. Spearman rank correlation coefficient of IL-6 with D-dimer was 0.203, with LDH was -0.005, with ferritin was 0.3, and with uric acid was 0.123. A total of 11 patients received Tocilizumab at a mean duration from symptom onset of 18.09 days, and 100% mortality was observed. Deaths were reported more in the group with IL-6 ≥ 40 pg/mL (57.1% vs. 40.2%, p = 0.06). ICU admissions and ventilator requirement were higher in the IL-6 ≥ 40 pg/mL group (95.9% vs. 91.4%, p = 0.32 and 55.1% vs. 37.8%, p = 0.05). The study showed that IL-6 can be used as a possible "thrombotic cytokine marker". Higher values of IL-6 (≥40 pg/mL) are associated with more deaths, ICU admissions, and ventilator requirement.

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.

Impact of Pregnancy on Susceptibility and Severity of COVID-19: A Hospital-Based Prospective Observational Study.

OBJECTIVE:  Pregnancy is a transient state of immunosuppression. The objective of this study was to ascertain whether pregnant women are more susceptible to coronavirus disease 2019 (COVID-19) than non-pregnant women and the impact of pregnancy on the severity of COVID-19 and associated morbidity and mortality. METHODS:  A prospective observational study was performed at All India Institute of Medical Sciences (AIIMS) Rishikesh for a period of two months. A total of 42 and 33 COVID-19 positive women were included in the obstetric and non-obstetric cohorts respectively. RESULTS:  Baseline characteristics were similar in both groups. Approximately 48% of the obstetric cohort had no COVID-19-related symptoms. Whereas, 100% of the non-obstetric cohort was symptomatic and had a significantly higher number of patients presenting with fever, cough, and breathlessness. The obstetric cohort had a significantly higher incidence of mild disease (p=0.009). In the obstetric cohort, the mean gestational age was 32.59 ± 2.57 weeks, with patients spread across all trimesters. Most of the patients with severe disease were in their second trimester. There was no difference in intensive care unit (ICU) admission, duration of ICU stay, duration of hospital stay, and mortality among both groups. A significantly smaller number of patients in the obstetric cohort required ventilatory support (p=0.0002). The maternal mortality rate was 16.67%. All of them had severe diseases requiring ICU admission. The cause of death was attributed to severe COVID pneumonia with septic shock in all cases. The mortality rate was comparatively higher (27.27%) in the non-obstetric group. CONCLUSION:  Pregnancy, unlike other immunocompromised conditions, does not seem to affect the prognosis of COVID-19 in terms of disease severity or mortality.

Mixed invasive fungal infections among COVID-19 patients.

Background and Purpose: The healthcare system in India collapsed during the second wave of the COVID-19 pandemic. A fungal epidemic was announced amid the pandemic with several cases of COVID-associated mucormycosis and pulmonary aspergillosis being reported. However, there is limited data regarding mixed fungal infections in COVID-19 patients. Therefore, we present a series of ten consecutive COVID-19 patients with mixed invasive fungal infections (MIFIs). Materials and Methods: Among COVID-19 patients hospitalized in May 2021 at a tertiary care center in North India, 10 cases of microbiologically confirmed COVID-19-associated mucormycosis-aspergillosis (CAMA) were evaluated. Results: All patients had diabetes and the majority of them were infected with severe COVID-19 pneumonia (6/10, 60%) either on admission or in the past month while two were each of moderate (20%) and mild (20%) categories of COVID-19; and were treated with steroid and cocktail therapy. The patients were managed with amphotericin-B along with surgical intervention. In total, 70% of all CAMA patients (Rhizopus arrhizus with Aspergillus flavus in seven and Aspergillus fumigatus complex in three patients) survived. Conclusion: The study findings reflected the critical importance of a high index of clinical suspicion and accurate microbiological diagnosis in managing invasive dual molds and better understanding of the risk and progression of MIFIs among COVID-19 patients. Careful scrutiny and identification of MIFIs play a key role in the implementation of effective management strategies.

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.

Serum ferritin as a predictive biomarker in COVID-19. A systematic review, meta-analysis and meta-regression analysis.

Ferritin is a known inflammatory biomarker in COVID-19. However, many factors and co-morbidities can confound the level of serum ferritin. This current metaanalysis evaluates serum ferritin level in different severity levels in COVID-19. Studies evaluating serum ferritin level in different clinical contexts (COVID-19 vs. control, mild to moderate vs. severe to critical, non-survivor vs. survivor, organ involvement, ICU and mechanical ventilation requirement) were included (total 9 literature databases searched). Metaanalysis and metaregression was carried out using metaphor "R" package. Compared to control (COVID-19 negative), higher ferritin levels were found among the COVID-19 patients [SMD -0.889 (95% C.I. -1.201, -0.577), I2 = 85%]. Severe to critical COVID-19 patients showed higher ferritin levels compared to mild to moderate COVID-19 patients [SMD 0.882 (0.738, 1.026), I2 = 85%]. In meta-regression, high heterogeneity was observed could be attributed to difference in "mean age", and "percentage of population with concomitant co-morbidities". Non-survivors had higher serum ferritin level compared to survivors [SMD 0.992 (0.672, 1.172), I2 = 92.33%]. In meta-regression, high heterogeneity observed could be attributed to difference in "mean age" and "percentage of male sex". Patients requiring ICU [SMD 0.674 (0.515 to 0.833), I2 = 80%] and mechanical ventilation [SMD 0.430 (0.258, 0.602), I2 = 32%] had higher serum ferritin levels compared to those who didn't. To conclude, serum ferritin level may serve as an important biomarker which can aid in COVID-19 management. However, presence of other co-morbid conditions/confounders warrants cautious interpretation.

Fear, Anxiety, Stress, and Depression of Novel Coronavirus (COVID-19) Pandemic Among Patients and Their Healthcare Workers - A Descriptive Study.

PURPOSE: Disease pandemics are known to cause psychological distress. The ensuing mental health issues are not only restricted to the patients and their relatives/friends but affect the healthcare workers (HCWs) as well. Our study aims to assess these psychological trends during the COVID-19 pandemic between the two most affected population groups, that is, patients and frontline healthcare workers. PATIENTS AND METHODS: A survey questionnaire, including scales to assess fear, anxiety, stress, depression - PSS 10, and DASS 21, was distributed and sent to all COVID-19 suspected/confirmed individuals and healthcare workers at a tertiary care center along with a second visit after 14 days of answering the first questionnaire and this continued as follow-up. Data were analyzed with the SPSS version 23 using various tests of significance. RESULTS: In the community, COVID-19 patients in the age group 41-50 with respiratory tract symptoms and those who were home isolated/quarantined experienced a greater tendency of mental health problems. Healthcare workers posted in COVID-19 designated areas of the hospital displayed higher levels of stress, anxiety, and depression. CONCLUSION: The high degree of uncertainty associated with novel pathogens has a profound effect on the psychological state of suspected/confirmed cases as well as healthcare workers. Within the community, individuals suspected of having COVID-19 display a significant mental health burden, while HCWs also experience an unprecedented amount of stress, anxiety, depression and fear during such enduring situations.

Antiviral Combination Clinically Better Than Standard Therapy in Severe but Not in Non-Severe COVID-19.

PURPOSE: Definitive antiviral treatment is not available for COVID-19 infection, with the exception of remdesivir, which still evokes many doubts. Various monotherapy or combination therapies with antivirals or other agents have been tried. The present study aims to evaluate the therapeutic potential of hydroxychloroquine and lopinavir-ritonavir in combination with ribavirin in mild-severe COVID-19. PATIENTS AND METHODS: A single-center, open-label, parallel-arm, stratified randomized controlled trial evaluated the therapeutic potential of combination antiviral therapies. Enrolled patients in the severe category were randomized into three groups: (A) standard treatment, (B) hydroxychloroquine+ribavirin+standard treatment, or (C) lopinavir+ritonavir+ribavirin+standard treatment; while the non-severe category comprised two groups: (A) standard treatment or (B) hydroxychloroquine+ribavirin. Combination antivirals were given for 10 days and followed for 28 days. The primary endpoints were safety, symptomatic and laboratory recovery of organ dysfunctions, and time to SARS-CoV-2 RT-PCR negative report. RESULTS: In total, 111 patients were randomized: 24, 23, and 24 in severe categories A, B, and C, respectively, and 20 in each of the non-severe groups. Two patients receiving ribavirin experienced drug induced liver injury, and another developed QT prolongation after hydroxychloroquine. In the severe category, 47.6%, 55%, and 30.09% in A, B, and C groups, respectively, showed symptomatic recovery, compared to 93.3% and 86.7% in A and B groups, respectively, in the non-severe category at 72 hours (P>0.05). CONCLUSION: Though the results failed to show statistical superiority of the antiviral combination therapies to that of the standard therapy in both the severe and non-severe categories in symptomatic adult patients of COVID-19 due to very small sized trial, clinically hydroxychloroquine+ribavirin therapy is showing better recovery by 7.4% than standard therapy in the former category. However, results do indicate the benefit of standard therapy in the non-severe category by 6.6%. Furthermore, the dose of ribavirin needs to be reconsidered in the Indian population.

Febrile neutropenia due to COVID-19 in an immunocompetent patient.

While lymphopenia has been a common finding in COVID-19 infection, particularly in severe cases, febrile neutropenia has been very rarely reported in immunocompetent patients with COVID-19. Herein, we report the case of a 76-year-old hypertensive and diabetic man who was hospitalised with severe COVID-19 infection and developed delayed-onset severe neutropenia with neutropenic fever, which responded to treatment with antibiotics and granulocyte colony-stimulating factor. This case highlights the importance of identifying a rare complication (febrile neutropenia on the fifth week) of COVID-19 infection in hospitalised patients by intensive monitoring and aggressive management for favourable outcomes.

Steroid harms if given early in COVID-19 viraemia.

COVID-19 is a biphasic illness with an initial viraemia phase and later effective adaptive immune phase, except in a minority of people who develop severe disease. Immune regulation is the key target to treat COVID illness. In anticipation, an elderly man self-medicated himself with dexamethasone on the day of symptom onset of a flu-like illness, took other symptomatic measures and was tested positive for SARS-CoV-2. His condition deteriorated with each passing day resulting in hospitalisation. He demanded oxygen and declared as severe COVID. With supportive treatment, he recovered after the 20th day of illness. Immunosuppression and anti-inflammation are likely to benefit when the immune response is dysregulated and turning into a cytokine storm. A medication that has saved many could be the one predisposing to severity if taken as a preventive measure, too early in the disease course, especially the viraemia phase.