Comparative study of tocilizumab versus itolizumab in coronavirus disease 2019-infected patients: a randomized controlled trial

Objective We aimed to compare the effect of tocilizumab and itolizumab in terms of PaO2/FiO2 ratio (P/F ratio), interleukin 6 (IL-6) level, serum ferritin, C-reactive protein, and a reduction in mortality. Our primary objective was to compare P/F ratio at various time intervals: baseline (before administering the drug), 12 h after drug administration, once a day for the next 7 days, and on the 14th day. Our secondary objective was to evaluate serum level of biomarkers like IL-6, ferritin, and C-reactive protein before start of drug infusion and following drug infusion at 72 h and on 7th day. Patients and methods A total of 50 patients, age between 18 and 60 years, having moderate Acute Respiratory distress syndrome (ARDS) following coronavirus disease 2019 infection were recruited. Patients of group I received a single dose of injection of tocilizumab 8 mg/kg intravenously (i.v.) via infusion over 1–2 h. Group II patients received premedication with hydrocortisone 100 mg and pheniramine 30 mg and a single dose of injection itolizumab 1.6 mg/kg dissolved in 250 ml of 0.9% normal saline infusion over 5–6 h. Results We observed significantly higher P/F ratio in the itolizumab group (239.18±97.31) than in the tocilizumab group (104.87±75.25) on the 3rd day following drug administration (P<0.001). Similarly, the IL-6 level was lower in the itolizumab group (72±100) in comparison with the tocilizumab group (682±1360), and the differences were statistically significant (P<0.05). We identified adverse effects of the drugs in 10 patients who have received itolizumab. Conclusion We observed an increasing trend in P/F ratio on the 3rd day following itolizumab administration in comparison with tocilizumab, and the difference was statistically significant (P<0.001).

Interim Analysis of Impact of Adding Low Dose Pulmonary Radiotherapy to Moderate COVID-19 Pneumonia Patients: IMpaCt-RT Study.

Background: Treatment for coronavirus disease 2019 (COVID-19) pneumonia remains largely supportive till date and multiple clinical trials took place within the short span of time to evaluate the role of investigational therapies. The anti-inflammatory effect of low dose whole lung radiation in treating pneumonia has been documented earlier. This clinical trial analyzed the effect of low dose radiation therapy (LDRT) in a moderately affected COVID-19 pneumonia patient cohort and has evaluated its effect in stopping the conversion of moderate disease into severe disease. Methods: Patients with moderate COVID-19 pneumonia as characterized by the Ministry of Health and Family Welfare (MOHFW), Government of India, were randomized (1:1) to low dose whole lung radiation versus no radiation. All treatment of patients was concurrently being given as per institutional protocol. Patients were followed up with clinical and laboratory parameters monitored on Days 1, 3, 7, and 14. Computed tomography scan (CT scan) of thorax was performed on Days 1 and 7. Patients were evaluated for conversion of moderate into severe disease as per National Early Warning Score-2 (NEWS-2 score) as the primary end point. The secondary endpoints included changes in ratio between peripheral capillary oxygen saturation and fraction of inspired oxygen (SpO2/FiO2), biochemical markers, 25-point CT severity score, and radiation induced acute pulmonary toxicities. Findings: At the interim analysis, there were seven patients in the radiation arm and six in the control. A whole lung LDRT improved the outcome of SpO2/FiO2 at Day 3; however it did not convert into a statistically significant improvement for the NEWS-2 score. The serum levels of LDH, CRP, Ferritin and D-dimer were significantly reduced on 14 days in the LDRT arm in comparison to the baseline value but were not significant between the two groups. Interpretation: LDRT seems to have the potential to prevent moderate COVID-19 pneumonia from a deteriorating to severe category. However, further randomized clinical trial with an adequate number of such patients is warranted to establish the definitive role of LDRT in the management of COVID-19 pneumonia. Funding: An intramural research project bearing code: I-27/621, was sanctioned from the All India Institute of Medical Sciences, Patna, India. Clinical Trial Registration: Clinical Trials Registry-India (CTRI/2021/06/033912, 25th May 2021) ctri.nic.in/Clinicaltrials/login.php.

Does Long-term Oxygen Therapy and Noninvasive Ventilation Predispose Rhino-orbital-cerebral Mucormycosis in COVID-19 Patients?

How to cite this article: Kumar A, Kumar A, Kumar N, Kumar A, Sinha C, Singh PK. Does Long-term Oxygen Therapy and Noninvasive Ventilation Predispose Rhino-orbital-cerebral Mucormycosis in COVID-19 Patients? Indian J Crit Care Med 2022;26(9):1063-1064.

An Epidemiological Investigation to evaluate the link between hypovitaminosis D and COVID-19.

Background: The COVID-19 pandemic has become a global threat, with an inexplicable course of action and suboptimal response to the multitudes of therapies being tried. Vitamin D's pleiotropic effects (immunomodulatory, anti-inflammatory, and antiviral) have lately received considerable attention in the scientific community, and it has been shown to be helpful in the defense against viral respiratory infections. Aim: To find out the association between vitamin D and COVID-19. Methods: Overall, 360 (156 COVID-19 +ve and 204 COVID-19 -ve) subjects were investigated in this hospital-based case-control study. The study participants were taken from the COVID-19 wards and Flu clinic of a dedicated COVID hospital between August 1 and September 15, 2020. The demographics and clinical data including alcohol and smoking history along with serum vitamin D levels were recorded. Binary logistic regression analysis was performed to assess the association between age, gender, alcohol intake, smoking history, vitamin D status, and COVID-19. Results: There was no significant difference in the mean vitamin D levels between cases and controls. Bivariate analysis of predictors and COVID-19 revealed that predictors such as advanced age, BMI, alcohol intake, smoking habit, diabetes, hypertension, and vitamin D deficiency were significantly associated with COVID-19. Conclusions: This study showed that serum vitamin D status might be able to reduce the impact of COVID-19, although more studies are required to establish clear causality.

Interim Analysis of Impact of Adding Low Dose Pulmonary Radiotherapy to Moderate COVID-19 Pneumonia Patients: IMpaCt-RT Study

Background Treatment for coronavirus disease 2019 (COVID-19) pneumonia remains largely supportive till date and multiple clinical trials took place within the short span of time to evaluate the role of investigational therapies. The anti-inflammatory effect of low dose whole lung radiation in treating pneumonia has been documented earlier. This clinical trial analyzed the effect of low dose radiation therapy (LDRT) in a moderately affected COVID-19 pneumonia patient cohort and has evaluated its effect in stopping the conversion of moderate disease into severe disease. Methods Patients with moderate COVID-19 pneumonia as characterized by the Ministry of Health and Family Welfare (MOHFW), Government of India, were randomized (1:1) to low dose whole lung radiation versus no radiation. All treatment of patients was concurrently being given as per institutional protocol. Patients were followed up with clinical and laboratory parameters monitored on Days 1, 3, 7, and 14. Computed tomography scan (CT scan) of thorax was performed on Days 1 and 7. Patients were evaluated for conversion of moderate into severe disease as per National Early Warning Score-2 (NEWS-2 score) as the primary end point. The secondary endpoints included changes in ratio between peripheral capillary oxygen saturation and fraction of inspired oxygen (SpO2/FiO2), biochemical markers, 25-point CT severity score, and radiation induced acute pulmonary toxicities. Findings At the interim analysis, there were seven patients in the radiation arm and six in the control. A whole lung LDRT improved the outcome of SpO2/FiO2 at Day 3;however it did not convert into a statistically significant improvement for the NEWS-2 score. The serum levels of LDH, CRP, Ferritin and D-dimer were significantly reduced on 14 days in the LDRT arm in comparison to the baseline value but were not significant between the two groups. Interpretation LDRT seems to have the potential to prevent moderate COVID-19 pneumonia from a deteriorating to severe category. However, further randomized clinical trial with an adequate number of such patients is warranted to establish the definitive role of LDRT in the management of COVID-19 pneumonia. Funding An intramural research project bearing code: I-27/621, was sanctioned from the All India Institute of Medical Sciences, Patna, India. Clinical Trial Registration Clinical Trials Registry-India (CTRI/2021/06/033912, 25th May 2021) ctri.nic.in/Clinicaltrials/login.php

Painful Blisters of Left Hand Following Extravasation of Remdesivir Infusion in COVID-19.

How to cite this article: Kumar N, Kumar A, Pradhan S, Kumar A, Singh K. Painful Blisters of Left Hand Following Extravasation of Remdesivir Infusion in COVID-19. Indian J Crit Care Med 2021;25(2):240-241.

Acute Exacerbation of Cough as a Precipitating Cause of Hypoxia in COVID-19 Patients.

Kumar A, Kumar A, Kumar A, Sinha C, Kumar N, Singh PK. Acute Exacerbation of Cough as a Precipitating Cause of Hypoxia in COVID-19 Patients. Indian J Crit Care Med 2021;25(11):1324-1325.

The COSEVAST Study Outcome: Evidence of COVID-19 Severity Proportionate to Surge in Arterial Stiffness.

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection affects the cardiovascular system at many levels. It initially infects endothelial cells, inducing marked endothelial damage and inflammation. However, there was no empirical evidence of functional compromise of arterial walls. AIMS AND OBJECTIVE: Our primary objective was to study functional arterial damage in coronavirus disease 2019 (COVID-19) and establish the noninvasive measurement of arterial stiffness as an independent marker of disease severity. MATERIALS AND METHODS: We recorded the arterial stiffness of 23 mild, 21 moderate, and 20 severe COVID-19 patients grouped on the latest National Institute of Health (NIH) severity criteria. We observed arterial stiffness of COVID-19 patients with standard parameters like noninvasive estimated carotid-femoral pulse wave velocity (cfPWV), age-normalized increase in cfPWV (ANI_cfPWV), age-normalized increase in aortic augmentation pressure (ANI_AugP), and heart rate-normalized augmentation index (HRN_ AIx). All the parameters were also corrected for statistically significant confounding factors. RESULTS: Moderate and severe COVID-19 patients have extremely significantly elevated arterial stiffness than mild patients. In mild patients, cfPWV (829.1 ± 139.2 cm/second) was significantly lower than both moderate (1067 ± 152.5 cm/second, p <0.0001) and severe (1416 ± 253.9 cm/second, p <0.0001) patients. ANI_cfPWV in moderate and severe patients was significantly higher than mild patients (mild: 101.2 ± 126.1 cm/second; moderate: 279 ± 114.4 cm/second; severe: 580.1 ± 216.4 cm/second; intergroup p <0.0001). The results even after correction for significant confounding factors did not show any considerable change in the increasing trend of arterial stiffness. CONCLUSION: This study establishes the functional deterioration of arteries in proportion to the severity of COVID-19. HOW TO CITE THIS ARTICLE: Kumar N, Kumar S, Kumar A, Bhushan D, Kumar A, Kumar A, et al. The COSEVAST Study Outcome: Evidence of COVID-19 Severity Proportionate to Surge in Arterial Stiffness. Indian J Crit Care Med 2021;25(10):1113-1119.

Repackaging of Malfunctioning High-flow Nasal Cannula as a Rescue Oxygen Therapy: An Innovation amid COVID-19 Crisis.

Oxygen supplementation is required for approximately 14% of the patients diagnosed of having COVID-19 infection. Despite the use of conventional oxygen therapy, 5% among these require treatment in the intensive care unit (ICU). Here, we are describing a situation in which oxygen therapy was delivered to the patients by making an assembly of oxygen tubing, three-way stopcock, and high-flow nasal cannula (HFNC) present in the hospital setting following the malfunction of air blender of HFNC machine (Fig. 1). This assembly might be useful as rescue oxygen therapy during a malfunction of HFNC machine and in resource-limited settings where HFNC machine is not available. The mechanisms of action could be (1) washout of anatomic dead space due to medium oxygen flow, (2) improved gas mixing in large airways, and (3) increased oxygen concentration inside the conducting airway. How to cite this article: Kumar A, Kumar A, Kumar N, Kumar A, Singh V, Kumar S, et al. Repackaging of Malfunctioning High-flow Nasal Cannula as a Rescue Oxygen Therapy: An Innovation amid COVID-19 Crisis. Indian J Crit Care Med 2021;25(8):948-949.

Second-degree Heart Block Caused by Itolizumab-induced Infusion Reaction in COVID-19.

How to cite this article: Kumar A, Kumar N, Lenin D, Kumar A, Ahmad S. Second-degree Heart Block Caused by Itolizumab-induced Infusion Reaction in COVID-19. Indian J Crit Care Med 2021;25(4):474-475.

Multiple Peaked Cytokine Storm: Is Multiple Exposures to the COVID-19 Virus a Possible Cause?

Severe acute respiratory syndrome coronavirus 2 is the pathogen that causes coronavirus disease-2019 (COVID-19). Recent studies have shown that the "cytokine storm" (high concentration of proinflammatory cytokines) may contribute to the mortality of COVID-19. Repeated exposure to the virus can lead to a dose-dependent immune response that may be associated with more disease severity and higher mortality. Sudden deterioration/increased oxygen consumption after initial improvement may be due to multiple surges of cytokines storm within a short period, the possible cause may be due to multiple exposures within the incubation period. We hypothesize that multiple surges in cytokines storm in some patients may be due to multiple exposures of the same patient within the incubation period, sepsis, or other inflammatory lesions inside the body. In our cases, sepsis as a cause of cytokine storm was ruled out by doing the procalcitonin test, which was within the normal limit. HOW TO CITE THIS ARTICLE: Kumar A, Kumar A, Kumar A, Kumar N, Sinha C, Singh V. Multiple Peaked Cytokine Storm: Is Multiple Exposures to the COVID-19 Virus a Possible Cause? Indian J Crit Care Med 2021;25(4):463-464.

Off-label Use of Itolizumab in Patients with COVID-19 ARDS: Our Clinical Experience in a Dedicated COVID Center.

Severe acute respiratory syndrome coronavirus 2 has affected millions of people worldwide. This pandemic requires newer medical management strategies to control the morbidity and mortality associated with the disease. Several approaches, including global targeting of inflammation or neutralizing a single key inflammatory mediator, are being employed to cope with cytokine storms in coronavirus disease-2019 (COVID-19). The role of anti-inflammatory biologics, such as acalabrutinib, tocilizumab, anakinra, and itolizumab can become relevant. Itolizumab is a humanized recombinant immunoglobulin G1 monoclonal antibody. It targets the extracellular, scavenger receptor cysteine-rich (SRCR) distal domain 1 of CD6 and is responsible for priming, activation, and differentiation of T-cells. Itolizumab has been approved by the Drug Controller General of India for the treatment of COVID-19 in India. Here, we shared our clinical experience of 20 patients having moderate acute respiratory distress syndrome (ARDS) due to COVID-19 on treatment with itolizumab. We observed the mortality benefit with single-dose itolizumab (1.6 mg/kg) in patients having moderate COVID-19 ARDS. HOW TO CITE THIS ARTICLE: Kumari P, Kumar A, Sinha C, Kumar A, Singh PK, Arun SK. Off-label Use of Itolizumab in Patients with COVID-19 ARDS: Our Clinical Experience in a Dedicated COVID Center. Indian J Crit Care Med 2021;25(4):467-469.

Dual Oxygen Therapy in COVID-19 Patient: A Method to Improve Oxygenation.

Approximately 5-6% of patients diagnosed to have COVID-19 infection present with severe hypoxemia requiring invasive ventilation or non-invasive ventilation (NIV). Additional oxygen to patients on NIV can be given by nasal prong or by connecting oxygen tubing directly to the O2 pick-off port of the NIV mask or by connecting oxygen tubing to the single-limb circuit in between ventilator and patient. Dual oxygen therapy improves oxygenation in COVID-19 patients on NIV. This method may make the patient more comfortable, increase tolerance to NIV, increase the usefulness of NIV for moderate and severe COVID-19 acute respiratory distress syndrome (ARDS). How to cite this article: Kumar A, Kumar A, Sinha C, Kumar N, Singh K, Singh PK. Dual Oxygen Therapy in COVID-19 Patient: A Method to Improve Oxygenation. Indian J Crit Care Med 2021;25(2):231-233.