Outcomes of High-Dose Vitamin C Therapy on Patients Diagnosed with COVID-19 Associated ARDS in Intensive Care Units: Multi-Center Retrospective Study

Background and Aim: The new type of Severe Acute Respiratory Syndrome Coronavirus 2 (Coronavirus 2019-COVID-19) infection is the largest pandemic in the last decade. Acute respiratory distress syndrome is the complication with the highest mortality rate of this infection and there is no adequate treatment with proven efficacy to reduce mortality. This multi-center, retrospective study aimed to determine the effect of high-dose vitamin C on survival and other endpoints in invasively ventilated ARDS patients. Method(s): This multi-center, observational retrospective cohort study was performed at five ICU centers between March 2020 and July 2020. Patients with ARDS due to COVID-19 who required IMV were included. High-dose vitamin C group was defined as patients who were treated with vitamin C over 200 mg/kg for four days. Patients who were not given vitamin C treatment were defined as the control group by using propensity score match analysis, as well. The groups were compared about the effects of high-dose vitamin C treatment on ICU mortality. Result(s): A total of 86 patients with a mean age of 67.85 +/- 10.38 were included in the study. 72.1% of the patients were male. Forty-two (49%) patients were in the high dose vitamin C group, and 44 (51%) were in the control group. The mean PaO2/FiO2 at the time of admission to the ICU was 128.27+/-58.69 mmHg (133.63+/-56.51 mmHg in the control group, 122.36+/-61.18 mmHg in the study group, p=0.389). The mortality rate of high dose vitamin C group was lower than the control group (73.8% vs. 90.9%, p = 0.037,respectively). Conclusion(s): As an adjunctive therapy in invasively ventilated patients with COVID-19-associated ARDS, high doses of vitamin C may reduce mortality and development of organ damage. Prospective, randomized controlled studies with larger numbers of patients are needed to confirm these findings.Copyright © 2023, Society of Turkish Intensivists. All rights reserved.

Immune responses to COVID-19 booster vaccinations in intensively anti-CD38 antibody treated patients with ultra-high-risk multiple myeloma: results from the Myeloma UK (MUK) nine OPTIMUM trial.

Multiple myeloma (MM) and anti-MM therapy cause profound immunosuppression, leaving patients vulnerable to coronavirus disease 2019 (COVID-19) and other infections. We investigated anti-severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) antibodies longitudinally in ultra-high-risk patients with MM receiving risk-adapted, intensive anti-CD38 combined therapy in the Myeloma UK (MUK) nine trial. Despite continuous intensive therapy, seroconversion was achieved in all patients, but required a greater number of vaccinations compared to healthy individuals, highlighting the importance of booster vaccinations in this population. Reassuringly, high antibody cross-reactivity was found with current variants of concern, prior to Omicron subvariant adapted boostering. Multiple booster vaccine doses can provide effective protection from COVID-19, even with intensive anti-CD38 therapy for high-risk MM.

Comparison of Efficacy and Safety of Low-Dose Versus High-Dose Dexamethasone in Hospitalized COVID-19 Patients: A Meta-Analysis.

The aim of this study is to compare the efficacy and safety of low-dose and high-dose dexamethasone in hospitalized coronavirus disease 2019 (COVID-19) patients. The current meta-analysis was conducted in compliance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A comprehensive literature search was carried out using PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL), and Embase. Outcomes assessed in the current meta-analysis included 28-day mortality, intensive care unit (ICU) admission, mechanical ventilation, length of ICU admission (days), and length of hospital stay (days). For safety, we compared hypoglycemia and the incidence of infection between the high-dose dexamethasone group and the low-dose dexamethasone group. A total of four studies fulfilled the inclusion criteria and were included in this meta-analysis. No significant difference was found between the two groups in terms of ICU admission (risk ratio (RR): 0.72, 95% confidence interval (CI): 0.41-1.28, p-value: 0.27), length of stay in ICU in days (mean difference (MD): -0.05, 95%CI: -3.96-3.87, p-value: 0.98, I-square: 94%), length of hospital stay in days (MD: -0.94, 95%CI: -1.94-0.06, p-value: 0.07), need of mechanical ventilation (RR: 0.72, 95%CI: 0.36-1.48, p-value: 0.38), and 28-day mortality (RR: 0.90, 95% CI: 0.50-1.64, p-value: 0.74). The current study showed that higher doses of dexamethasone failed to enhance efficacy compared to low-dose dexamethasone. Thus, based on the findings of this meta-analysis, low-dose dexamethasone can be recommended for these patients.

Oral high-dose acetylcysteine: Effective against the Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)?

The Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a high rate of transmission and it exhibits immune escape characteristics. N-acetyl-L-cysteine (NAC) is a precursor of reduced glutathione (GSH), which can enter cells to play an antioxidant role, so it is better than glutathione. Patients tolerate NAC well, and adverse reactions are rare and mild, so this type of drug with multiple actions is considered to be a mucolytic agent as well as a drug for the prevention/treatment of various diseases, including COVID-19. Previous studies indicated that the clinical effectiveness of NAC is dose-dependent. Low-dose NAC (0.2 g tid for adults) is a mucolytic expectorant, high-dose NAC (0.6 g bid or tid) has expectorant action as well as antioxidant action, and extreme-dose NAC (300 mg/kg.d) is used for detoxification in cases of an acetaminophen overdose. Presumably, orally administered high-dose NAC (0.6 g tid for adults and 10 mg/kg tid for children) could be used as an adjuvant to treat an Omicron infection. It should reduce the time to negative conversion and prevent severe COVID-19, reducing the duration of hospitalization and increasing the bed turnover rate.

High-dose Intravenous Vitamin C in Early Stages of Severe Acute Respiratory Syndrome Coronavirus 2 Infection: A Double-blind, Randomized, Controlled Clinical Trial.

Objective: Based on previous studies in the sepsis population, Vitamin C could prevent injuries when administered in high doses and before the damage is established. This study aimed to evaluate the protective potentials of high-dose Vitamin C in the progression of coronavirus disease 2019 (COVID-19). Methods: A double-blind, placebo-controlled clinical trial was conducted. Patients with moderate-to-severe disease severity based on the World Health Organization definition were enrolled and received 12 g/d Vitamin C (high-dose intravenous Vitamin C [HDIVC]) or placebo for 4 days. Sequential Organ Failure Assessment (SOFA) score as a primary outcome, National Early Warning Score, Ordinal Scale of Clinical Improvement, and cytokine storm biomarkers were recorded on days 0, 3, and 5. Survival was also assessed on day 28 after enrollment. Findings: Seventy-four patients (37 patients in each group) were enrolled from April 5, 2020, to November 19, 2020, and all patients completed follow-up. A lower increase in SOFA score during the first 3 days of treatment (+0.026 vs. +0.204) and a higher decrease in this parameter in the last 2 days (-0.462 vs. -0.036) were observed in the treatment group. However, these differences did not reach a significance level (P = 0.57 and 0.12, respectively). Other indices of clinical and biological improvement, length of hospitalization, and intensive care unit admission days were the same between the two groups. Treatment did not affect the 28-day mortality. Conclusion: Among patients with moderate-to-severe disease of COVID-19, the use of HDIVC plus standard care resulted in no significant difference in SOFA score or 28-day mortality compared to the standard care alone.

Evidence for the Efficacy of a High Dose of Vitamin D on the Hyperinflammation State in Moderate-to-Severe COVID-19 Patients: A Randomized Clinical Trial.

Background and Objectives: Vitamin D supplementation plays a key effect in lowering cytokine storms among COVID-19 patients by influencing the activity of the renin-angiotensin system and the production of the angiotensin-2 converting enzyme. The study was conducted to explore the effect of high-dose intramuscular vitamin D in hospitalized adults infected with moderate-to-severe SARS-CoV-2 in comparison with the standard of care in the COVID-19 protocol. Materials and Methods: Two groups of patients were compared in this prospective randomized controlled trial as the vitamin D was administered orally to group 1 (alfacalcidol 1 mcg/day) and intramuscularly to group 2 (cholecalciferol 200,000 IU). One hundred and sixteen participants were recruited in total, with fifty-eight patients in each group. Following the Egyptian Ministry of Health's policy for COVID-19 management, all patients received the same treatment for a minimum of five days. Results: A significant difference was recorded in the length of hospital stay (8.6 versus 6.8 days), need for high oxygen or non-invasive mechanical ventilator (67% versus 33%), need for a mechanical ventilator (25% versus 75%), clinical improvement (45% versus 55%), the occurrence of sepsis (35% versus 65%), and in the monitored laboratory parameters in favor of high-dose vitamin D. Moreover, clinical improvement was significantly associated with the need for low/high oxygen, an invasive/non-invasive mechanical ventilator (MV/NIMV), and diabetes, while mortality was associated with the need for MV, ICU admission, atrial fibrillation, chronic obstructive pulmonary disease, asthma, and the occurrence of secondary infection. Conclusions: Our study showed that high-dose vitamin D was considered a promising treatment in the suppression of cytokine storms among COVID-19 patients and was associated with better clinical improvement and fewer adverse outcomes compared to low-dose vitamin D.

Camostat Mesylate Versus Lopinavir/Ritonavir in Hospitalized Patients With COVID-19-Results From a Randomized, Controlled, Open Label, Platform Trial (ACOVACT).

Background: To date, no oral antiviral drug has proven to be beneficial in hospitalized patients with COVID-19. Methods: In this randomized, controlled, open-label, platform trial, we randomly assigned patients ≥18 years hospitalized with COVID-19 pneumonia to receive either camostat mesylate (CM) (considered standard-of-care) or lopinavir/ritonavir (LPV/RTV). The primary endpoint was time to sustained clinical improvement (≥48 h) of at least one point on the 7-category WHO scale. Secondary endpoints included length of stay (LOS), need for mechanical ventilation (MV) or death, and 29-day mortality. Results: 201 patients were included in the study (101 CM and 100 LPV/RTV) between 20 April 2020 and 14 May 2021. Mean age was 58.7 years, and 67% were male. The median time from symptom onset to randomization was 7 days (IQR 5-9). Patients in the CM group had a significantly shorter time to sustained clinical improvement (HR = 0.67, 95%-CI 0.49-0.90; 9 vs. 11 days, p = 0.008) and demonstrated less progression to MV or death [6/101 (5.9%) vs. 15/100 (15%), p = 0.036] and a shorter LOS (12 vs. 14 days, p = 0.023). A statistically nonsignificant trend toward a lower 29-day mortality in the CM group than the LPV/RTV group [2/101 (2%) vs. 7/100 (7%), p = 0.089] was observed. Conclusion: In patients hospitalized for COVID-19, the use of CM was associated with shorter time to clinical improvement, reduced need for MV or death, and shorter LOS than the use of LPV/RTV. Furthermore, research is needed to confirm the efficacy of CM in larger placebo-controlled trials. Systematic Review Registration: [https://clinicaltrials.gov/ct2/show/NCT04351724, https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-001302-30/AT], identifier [NCT04351724, EUDRACT-NR: 2020-001302-30].

The adverse effects of high-dose corticosteroid on infectious and non-infectious sequelae in renal transplant recipients with coronavirus disease-19 in India.

INTRODUCTION: The corticosteroid dosing modulation in renal transplant recipients (RTRs) with coronavirus disease-19 (COVID-19) is not well defined. We aimed to analyze the outcomes and infectious and non-infectious sequelae in RTR with COVID-19 with reference to corticosteroid dosing and the first and second pandemic waves of COVID-19. MATERIALS AND METHODS: This study included RTRs admitted during two pandemic waves between March 25, 2020, and July 31, 2021. Patients were categorized into mild, moderate, and severe COVID-19. The outcomes and predictors of survival at 4 weeks were analyzed. The survivors were also followed for 6 months and were studied for mortality, readmission rates, and infectious and non-infectious sequelae with reference to high-dose and standard-dose corticosteroids. RESULTS: A total of 251 RTRs, 104 during the first wave and 147 during the second wave, were treated. Overall mortality was 15.1% (11.5% in the first wave vs. 17.5% in the second wave, p = .23). The use of high-dose steroids was also significantly high in non-survivors (85.8% vs. 11.3%, p = .001). On multivariate analysis, the severity of COVID-19, graft dysfunction, and high dose of corticosteroid therapy were associated with increased odds of mortality. Among survivors, 6-month mortality (17.3% vs. 0.5%, p = .001), readmission rate (91.3% vs. 23.7%, p = .001), fungal infection (30.4% vs. 2.2%, p < .001), and post-COVID lung sequelae (21.7% vs. 4.4%, p = .008) were significantly higher in the high-dose corticosteroid group than in the standard-dose group. CONCLUSION: High-dose corticosteroid dosing in RTRs with COVID-19 was associated with increased infections, particularly fungal infections, and non-infectious sequelae with higher mortality on subsequent follow-up.

A Case of COVID-19 With Myasthenic Crisis.

Coronavirus disease 2019 (COVID-19) infection can increase the risk of myasthenic crisis. Dexamethasone has been widely used to manage severe COVID-19 infection. Paradoxically, steroids are effective for treating myasthenia gravis; however, when they are started in high doses, there is an associated risk of steroid-induced exacerbation. This case report describes an 86-year-old male with seropositive generalised myasthenia gravis, whose course had been stable for years. At the time of his COVID-19 diagnosis, he was on pyridostigmine and prednisolone 10 mg daily. He was treated with IV dexamethasone 6 mg daily, remdesivir, and antibiotics. On day 10 of admission, he had a sudden deterioration with a Glasgow Coma Scale (GCS) score of 3. Arterial blood gas (ABG) showed a new type 2 respiratory failure suggesting myasthenic crisis. Although his ABG improved after commencing bilevel positive airway pressure (BiPAP), his condition continued to deteriorate and he died the next day. A decision not to intubate and ventilate had been made given his poor clinical state and low chance of recovery. His myasthenic crisis was likely precipitated by the COVID-19 infection, although steroids, azithromycin, and doxycycline also have the potential to cause the worsening of myasthenia gravis. Further studies are needed to evaluate the efficacy and risk of steroid use in this patient population. Ventilatory failure may occur insidiously and is often difficult to detect, especially in elderly and delirious patients in whom performing a neurological examination can be difficult. Regular ABG and bedside measures of forced vital capacity may be considered to monitor the development of type 2 respiratory failure.

Immune globulin therapy and kidney disease: Overview and screening, monitoring, and management recommendations.

PURPOSE: This report calls attention to the potential risks of diminished kidney function when administering immune globulin (IG). The goal is to increase awareness of chronic kidney disease (CKD) and kidney function impairment in patients receiving IG and provide recommendations for screening, monitoring, and management to promote risk prevention and mitigation. SUMMARY: Human IG preparations for intravenous (IVIG) or subcutaneous (SCIG) administration are the mainstay of treatment in patients with primary immunodeficiency diseases. Increasingly, IVIG at high doses (1,000 to 2,400 mg/kg) is also used as a treatment for a variety of autoimmune and inflammatory conditions. Although some autoinflammatory disorders respond to a single course of IVIG therapy, the majority of patients require long-term, regular infusions, thereby increasing the overall risks. Often, both patients and physicians treating adults with IG are unaware of underlying CKD or kidney function impairment. This lack of awareness constitutes a major risk factor for potential worsening, particularly when using high doses of IVIG. Therefore, screening of all patients for CKD and kidney function impairment before the use of IG is essential. Identification of the cause of kidney impairment is strongly encouraged, as IG therapy may need to be modified. CONCLUSION: As detailed here, there are potential risks to patients with impaired kidney function with administration of IG, particularly at high doses. Product selection, volume, route of administration, and rate of infusion may impact those with compromised kidney function. Therefore, screening of all patients for CKD and kidney function impairment before the use of IVIG and SCIG, as well as ongoing monitoring and management, is critical. As with all potential adverse drug reactions, the best approach is to prevent them.

Treatment of vaccine-induced immune thrombotic thrombocytopenia (VITT).

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a novel prothrombotic disorder characterized by thrombosis, thrombocytopenia, and disseminated intravascular coagulation identified in hundreds of recipients of ChAdOx1 nCoV-19 (Oxford/AstraZeneca), an adenovirus vector coronavirus disease 2019 (COVID-19) vaccine. VITT resembles heparin-induced thrombocytopenia (HIT) in that patients have platelet-activating anti-platelet factor 4 antibodies; however, whereas heparin typically enhances platelet activation by HIT antibodies, VITT antibody-induced platelet activation is often inhibited in vitro by pharmacological concentrations of heparin. Further, the thrombotic complications in VITT feature much higher frequencies of atypical thrombosis, most notably cerebral vein thrombosis and splanchnic vein thrombosis, compared with HIT. In this review, we outline the treatments that have been used to manage this novel condition since its recognition in March 2021, including anticoagulation, high-dose intravenous immune globulin, therapeutic plasma exchange, corticosteroids, rituximab, and eculizumab. We discuss the controversial issue of whether heparin, which often inhibits VITT antibody-induced platelet activation, is harmful in the treatment of VITT. We also describe a case of "long VITT," describing the treatment challenges resulting from platelet-activating anti-PF4 antibodies that persisted for more than 9 months.

Prognostic accuracy of time to sputum culture conversion in predicting cure in extensively drug-resistant tuberculosis patients: a multicentre retrospective observational study.

BACKGROUND: There was a lack of information about prognostic accuracy of time to sputum culture conversion (SCC) in forecasting cure among extensively drug-resistant tuberculosis (XDR-TB) patients. Therefore, this study evaluated the prognostic accuracy of SCC at various time points in forecasting cure among XDR-TB patients. METHODS: This retrospective observational study included 355 eligible pulmonary XDR-TB patients treated at 27 centers in Pakistan between 01-05-2010 and 30-06-2017. The baseline and follow-up information of patients from treatment initiation until the end of treatment were retrieved from electronic nominal recording and reporting system. Time to SCC was analyzed by Kaplan-Meier method, and differences between groups were compared through log-rank test. Predictors of time to SCC and cure were respectively evaluated by multivariate Cox proportional hazards and binary logistic regression analyses. A p-value < 0.05 was considered statistically significant. RESULTS: A total of 226 (63.6%) and 146 (41.1%) patients respectively achieved SCC and cure. Median time to SCC was significantly shorter in patients who achieved cure, 3 months (95% confidence interval [CI]: 2.47-3.53), than those who did not (median: 10 months, 95% CI: 5.24-14.76) (p-value < 0.001, Log-rank test). Patient's age > 40 years (hazards ratio [HR] = 0.632, p-value = 0.004), baseline sputum grading of scanty, + 1 (HR = 0.511, p-value = 0.002), + 2, + 3 (HR = 0.523, p-value = 0.001) and use of high dose isoniazid (HR = 0.463, p-value = 0.004) were significantly associated with early SCC. Only SCC at 6 month of treatment had statistically significant association with cure (odds ratio = 15.603, p-value < 0.001). In predicting cure, the sensitivities of SCC at 2, 4 and 6 months were respectively 41.8% (95%CI: 33.7-50.2), 69.9% (95%CI: 61.7-77.2) and 84.9% (95%CI: 78.1-90.3), specificities were respectively, 82.8% (95%CI: 76.9-87.6), 74.6% (95%CI: 68.2-80.4) and 69.4% (95%CI: 62.6-75.5) and prognostic accuracies were respectively 65.9% (95%CI: 60.7-70.8), 72.7% (95%CI: 67.7-77.2) and 75.8% (95%CI: 71.0-80.1). CONCLUSION: In forecasting cure, SCC at month 6 of treatment performed better than SCC at 2 and 4 months. However, it would be too long for clinicians to wait for 6 months to decide about the regimen efficacy. Therefore, with somewhat comparable prognostic accuracy to that SCC at 6 month, using SCC at 4 month of treatment as a prognostic marker in predicting cure among XDR-TB patients can decrease the clinicians waiting time to decide about the regimen efficacy.

Favourable outcome of severe COVID-19 patients in hyperinflammatory phase with high dose dexamethasone pulse therapy: A series of 10 cases.

The hyperinflammatory phase of COVID-19 occurring because of cytokine storm is the leading cause of mortality and morbidity in the affected patients. Various drugs with no definite cure are being tried to tackle the cytokine storm. Recently high dose corticosteroids are being used to arrest the surge of cytokines. In the current case series, we will be discussing the outcome of high dose dexamethasone pulse therapy in 10 cases of COVID-19 in hyperinflammatory phase who were cured of the disease along with improvement in laboratory parameters without any complications to the therapy.

Successful Treatment with High-dose Steroids for Acute Exacerbation of Idiopathic Pulmonary Fibrosis Triggered by COVID-19.

We herein report a case of acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) triggered by COVID-19. An 87-year-old woman tested positive for COVID-19 on a polymerase chain reaction test, and computed tomography revealed ground-glass opacity (GGO) superimposed on a background pattern consistent with usual interstitial pneumonia. Considering these data, we diagnosed her with AE-IPF. She experienced worsening of dyspnea and expansion of the GGO. Therefore, we introduced high-dose steroids (methylprednisolone 250 mg/day for 3 days). After the treatment, the pulmonary infiltrates improved. She was discharged from our hospital without severe disability. High-dose steroids can be a viable treatment option for AE-IPF triggered by COVID-19.

High-Dose Dexamethasone Versus Tocilizumab in Moderate to Severe COVID-19 Pneumonia: A Randomized Controlled Trial.

Background and objectives Recent randomized controlled trials (RCTs) have indicated potential therapeutic benefits with high-dose dexamethasone (HDD) or tocilizumab (TCZ) plus standard care in moderate to severe coronavirus disease 2019 (COVID-19) with acute respiratory distress syndrome (ARDS). No study has compared these two against each other. We aimed to compare the efficacy and safety of HDD against TCZ in moderate to severe COVID-ARDS. Methods Patients admitted with moderate to severe COVID-19 ARDS with clinical worsening within 48 hours of standard care were randomly assigned to receive either HDD or TCZ plus standard care. The primary outcome was ventilator-free days (VFDs) at 28 days. The main secondary outcomes were 28-day all-cause mortality and the incidence of adverse events. Our initial plan was to perform an interim analysis of the first 42 patients. Results VFDs were significantly lower in the HDD arm (median difference: 28 days; 95% confidence interval (CI): 19.35-36.65; Cohen's d = 1.14;p < 0.001). We stopped the trial at the first interim analysis due to high 28-day mortality in the HDD arm (relative risk (RR) of death: 6.5; p = 0.007; NNT (harm) = 1.91). The incidence of secondary infections was also significantly high in the HDD arm (RR: 5.5; p = 0.015; NNT (harm) = 2.33). Conclusions In our study population, HDD was associated with a very high rate of mortality and adverse events. We would not recommend HDD to mitigate the cytokine storm in moderate to severe COVID-19 ARDS. TCZ appears to be a much better and safer alternative.

High-Dose Intravenous Immunoglobulin in Severe Coronavirus Disease 2019: A Multicenter Retrospective Study in China.

BACKGROUND: The effective treatment of coronavirus disease 2019 (COVID-19) remains unclear. We reported successful use of high-dose intravenous immunoglobulin (IVIg) in cases of severe COVID-19, but evidence from larger case series is still lacking. METHODS: A multi-center retrospective study was conducted to evaluate the effectiveness of IVIg administered within two weeks of disease onset at a total dose of 2 g/kg body weight, in addition to standard care. The primary endpoint was 28-day mortality. Efficacy of high-dose IVIg was assessed by using the Cox proportional hazards regression model and the Kaplan-Meier curve adjusted by inverse probability of treatment weighting (IPTW) analysis, and IPTW after multiple imputation (MI) analysis. RESULTS: Overall, 26 patients who received high-dose IVIg with standard therapy and 89 patients who received standard therapy only were enrolled in this study. The IVIg group was associated with a lower 28-day mortality rate and less time to normalization of inflammatory markers including IL-6, IL-10, and ferritin compared with the control. The adjusted HR of 28-day mortality in high-dose IVIg group was 0.24 (95% CI 0.06-0.99, p<0.001) in IPTW model, and 0.27 (95% CI 0.10-0.57, p=0.031) in IPTW-MI model. In subgroup analysis, patients with no comorbidities or treated in the first week of disease were associated with more benefit from high-dose IVIg. CONCLUSIONS: High-dose IVIg administered in severe COVID-19 patients within 14 days of onset was linked to reduced 28-day mortality, more prominent with those having no comorbidities or treated at earlier stage.

Comparing efficacy and safety of different doses of dexamethasone in the treatment of COVID-19: a three-arm randomized clinical trial.

BACKGROUND AND OBJECTIVES: Corticosteroids are commonly used in the treatment of hospitalized patients with COVID-19. The goals of the present study were to compare the efficacy and safety of different doses of dexamethasone in the treatment of patients with a diagnosis of moderate to severe COVID-19. METHODS: Hospitalized patients with a diagnosis of moderate to severe COVID-19 were assigned to intravenous low-dose (8 mg once daily), intermediate-dose (8 mg twice daily) or high-dose (8 mg thrice daily) dexamethasone for up to 10 days or until hospital discharge. Clinical response, 60-day survival and adverse effects were the main outcomes of the study. RESULTS: In the competing risk survival analysis, patients in the low-dose group had a higher clinical response than the high-dose group when considering death as a competing risk (HR = 2.03, 95% CI: 1.23-3.33, p = 0.03). Also, the survival was significantly longer in the low-dose group than the high-dose group (HR = 0.36, 95% CI = 0.15-0.83, p = 0.02). Leukocytosis and hyperglycemia were the most common side effects of dexamethasone. Although the incidence was not significantly different between the groups, some adverse effects were numerically higher in the intermediate-dose and high-dose groups than in the low-dose group. CONCLUSIONS: Higher doses of dexamethasone not only failed to improve efficacy but also resulted in an increase in the number of adverse events and worsen survival in hospitalized patients with moderate to severe COVID-19 compared to the low-dose dexamethasone. (IRCT20100228003449N31).

Comparison of Tocilizumab and High-dose Methylprednisolone Pulse on Outcomes in Severe Corona Virus Disease-2019: TAME-COVID, a Retrospective Multicentric Study.

BACKGROUND: India recently encountered fierce second wave of coronavirus disease (COVID-19), and scarcity of novel medications added to the management challenges. Various studies have highlighted the effectiveness of tocilizumab and high-dose steroids in severe COVIDs, but none has compared their efficacy. MATERIALS AND METHODS: This retrospective multi-centric analysis compares intravenous tocilizumab (8 mg/kg/day, maximum dose-800 mg), and intravenous Methylprednisolone Pulse (MPS-1 g/day for 3 days) in severe COVID-19. Both the groups had additionally received the standard of care COVID treatment as per protocol. Outcomes were assessed at 30 days. RESULTS: A total of 336 patients, with 249 receiving MPS and 87 receiving tocilizumab were compared. Majority of these were males (72.9%) with a mean age of 57.4 ± 13.6 years. Diabetes was the most common comorbidity. Patients in both groups had comparable age distribution, comorbidities, presenting mean-arterial pressures, d-Dimer levels, serum ferritin, serum leukocyte-dehydrogenase, and procalcitonin. However, the tocilizumab group had more number of males, higher incidence of coronary artery disease, more tachypnea and leukocytosis, more number of patients with severe acute respiratory disease syndrome (PaO2/FiO2 ratio <100), and higher C-reactive protein levels at presentation. Both groups had comparable adverse events' profile. Tocilizumab group had lesser requirement of invasive ventilation than MPS group (17% vs. 29%, P = 0.038), however mortality at the end of 30 days follow-up was similar (36% vs. 34% respectively; P = 0.678). CONCLUSIONS: Tocilizumab decreased the need for invasive ventilation in severe COVID-19; however, it did not translate to improved survival. A planned prospective randomized study is recommended in this respect to compare their efficacy.

Immune Thrombocytopenia Exacerbation After COVID-19 Vaccination in a Young Woman.

The coronavirus disease 2019 (COVID-19) pandemic is one of the greatest health concerns worldwide. Safe and effective COVID-19 vaccines are urgently needed and have been rapidly approved. COVID-19 vaccine-induced thrombocytopenia was reported as a rare adverse effect in the Vaccine Adverse Events Reporting System. A 25-year-old woman, who was previously diagnosed with immune thrombocytopenia (ITP, stage I), had exacerbated severe thrombocytopenia (platelet count of 6,000/µL) with a headache, joint pain, general fatigue, and bleeding tendency three days after receiving her second dose of the Pfizer BioNTech COVID-19 vaccine. Pulsed high-dose dexamethasone therapy rapidly ameliorated the ITP. Although it is difficult to confirm a causal association between Pfizer BioNTech COVID-19 vaccination and ITP exacerbation, abrupt onset of ITP exacerbation after vaccination suggests that the ITP may be vaccination-induced thrombocytopenia exacerbation. Rare but severe adverse events such as ITP may be observed, depending on increased numbers of individuals who receive COVID-19 vaccines worldwide. Further investigation is needed to clarify the mechanisms of COVID-19 vaccine-induced ITP.

Encephalopathy in COVID-19 Patients.

The clinical presentation of coronavirus disease 2019 (COVID-19) has a wide spectrum, ranging from asymptomatic patients to severe presentations with acute respiratory distress syndrome (ARDS), kidney injury, stroke, electrolyte imbalance, and multi-organ failure. Encephalopathy and encephalitis are devastating severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus-associated central nervous system complications. We reported a case of a 67-year-old male who was admitted to the hospital for the management of COVID-19 pneumonia. Due to worsening hypoxia, the patient was transferred to ICU and was intubated. On examination, he was aphasic and noted to have right-sided hemiplegia with left-sided hemiparesis on day 4. CT scan of the head without contrast and MRI findings were suggestive of acute necrotizing encephalopathy secondary to intracranial cytokine storm caused by viral infection. The patient was treated with intravenous immunoglobulin (IVIG), and high dose corticosteroids, with clinical improvement in the right-sided hemiparesis on day 5. A repeat MRI brain revealed decreased edema. The pathogenesis of encephalopathy associated with COVID-19 may be multifactorial. Postulated mechanisms include hypoxic/metabolic changes produced by the intense inflammatory response due to cytokine storm and neurotropism. Cytokine storm causes hypoxia and metabolic insults that result in global dysfunction of the brain. Altered consciousness, ranging from mild confusion, delirium, to deep coma, are some of the cardinal clinical features. The most common imaging finding on MRI T2-weighted fluid-attenuated inversion recovery (MRI T2/FLAIR) includes symmetric, multifocal lesions with invariable thalamic involvement. Other commonly involved locations include the brainstem, cerebral white matter, cortical and subcortical white matter, and cerebellum. In a few case reports, cerebrospinal fluid (CSF) analysis has shown the presence of the virus. Management of encephalopathy in COVID-19 patients involves supportive care including supplemental oxygen therapy and immune modulators. Immune modulation therapy including high-dose corticosteroids and IVIG have been shown to improve outcomes in these patients.