Comparative Safety and Efficacy of Remdesivir Versus Remdesivir Plus Convalescent Plasma Therapy (CPT) and the Effect of Timing of Initiation of Remdesivir in COVID-19 Patients: An Observational Study From North East India.

Introduction As per the COVID-19 treatment guidelines of India, remdesivir and convalescent plasma therapy (CPT) are indicated in moderate and severe patients. In this study, we have evaluated the comparative safety and efficacy of remdesivir versus remdesivir CPT combination and effect of early versus late initiation of remdesivir. Materials and methods A hospital-based observational study was conducted among hospitalized moderate and severe COVID-19 patients treated with either remdesivir and/or CPT as per national guidelines. Response to therapy was evaluated in terms of mortality, mechanical ventilation requirement, ICU requirement, and safety. Results and observations A total of 95 moderate and severe COVID-19 patients on remdesivir (n=35) or remdesivir + CPT combination (n=60) were included. Both the remdesivir and remdesivir + CPT groups were comparable in terms of baseline characteristics, however, proportion of patients with baseline serum creatinine >1.5 was higher in the remdesivir group. No difference was seen between both the groups in terms of mortality, mechanical ventilation requirement, ICU requirement, and safety parameters in the overall moderate and severe COVID-19 populations and when each of these severity categories (moderate and severe) were analyzed separately. Early initiation (<9 days from symptom onset) of remdesivir was associated with better treatment outcome in terms of mortality and requirement of ICU. Post-therapy shortness of breath and LFTs (liver function tests) elevation was more in the late initiation of remdesivir group, which may be due to the lack of efficacy and subsequent disease progression or a direct effect of the drug. The beneficial effect of remdesivir was maintained even after adjustment for important prognostic factors and baseline imbalances (age, sex, disease severity, CPT use, and serum creatinine level). Conclusions Early initiation of remdesivir was associated with clinical benefit in terms of mortality and mechanical ventilation requirement. However, addition of convalescent plasma therapy as an additional therapeutic modality to remdesivir was not found to be beneficial.

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.

An Uncommon Cause of Acute Transverse Myelitis Following Acinetobacter Baumannii-Associated UTI, Which Responded to Intravenous Pulse Methylprednisolone Alone.

Acute transverse myelitis (ATM) is a non-compressive localized inflammation involving one or more levels of the spinal cord due to various etiologies characterized by motor weakness, sensory impairments, and autonomic dysfunction. It can be idiopathic or primary or secondary due to infection, autoimmune disorder, connective tissue disorder, and uncommonly after vaccination which came to the limelight during the ongoing massive vaccine drive against coronavirus disease 2019 (COVID-19). We report a case of a 21-years-old male who presented with gradually progressive weakness of both lower limbs following urinary tract infection (UTI) with a history of similar illness in the family which improved with high dose methylprednisolone and antibiotic therapy followed by physical rehabilitation. A diagnosis of long segment ATM possibly following UTI was suggested after ruling out other secondary causes and was confirmed by magnetic resonance imaging (MRI) of the spinal cord. Asymmetric symptoms and signs with small lesions involving

Yogic Neti-Kriya Using Povidone Iodine: Can it have a Preventive Role Against SARS-CoV-2 Infection Gateway?

During this COVID-19 pandemic, except steroid, none of the therapeutic measures have showed any evidence of efficacy. Traditionally jala-neti using lukewarm salted water remains a yogic way of maintaining upper airway hygiene. Saline irrigation decreases the concentration of inflammatory mediators (e.g. histamine, leukotriene etc.) in nasal secretions, reduces the severity and frequency of sinusitis, reduce need of antibiotic therapy and restores competency of nasal mucosa. Jala-neti is an integral part of six cleansing techniques of yogic kriyas practised in India since thousands of years. Jala-neti can clean the upper airways, prevents colonization of infectious agents, removes foreign bodies, prevents stasis of mucous and subsequently enhances the drainage of paranasal sinuses and maintain health. Regular practice of Jala neti improves nasal symptoms and overall health status of patients with sinusitis. Jala-neti sample can even be used for COVID-19 diagnosis. Povidone iodine (PVP-I) has been utilized as a time tested antimicrobial agent with broad spectrum coverage against wide range of bacteria and viruses. Anti-SARS-CoV-2 action of PVP-I was seen at a concentration as low as 0.45%. PVP-I is generally well tolerated upto 5%, however nasal ciliotoxicity is reported at this concentration, however, this toxicity is not reported with lower concentrations(1.25% and 0.5%). So, theoretically, by using neti-kriya with povidone iodine (0.5-1%) as irrigation solution can combine and enhance the protection against COVID-19 and this can be an important armor in the fight against COVID-19. However, this hypothesis needs to be validated in real life clinical trial scenario before implementing.

Rhino-orbital-cerebral-mucormycosis in COVID-19: A systematic review.

Since the onset of COVID-19 pandemic, parallel opportunistic infections have also been emerging as another disease spectrum. Among all these opportunistic infection, mucormycosis has become a matter of concern with its rapid increase of cases with rapid spread as compared to pre-COVID-19 era. Cases have been reported in post-COVID-19-related immune suppression along with the presence of comorbidity which adds on the deadly outcome. There is no systematic review addressing the issue of COVID-19-associated mucormycosis. This is the first systematic review of published studies of mucormycosis associated with COVID-19. The aim was to analyze the real scenario of the disease statement including all the published studies from first November 2019 to 30th June to analyze the contemporary epidemiology, clinical manifestations, risk factor, prognosis, and treatment outcome of COVID-19 associated rhino-orbito-cerebral-mucormycosis. A comprehensive literature search was done in following databases, namely, PubMed, Google Scholar, Scopus, and EMBASE using keywords mucormycosis, rhino orbital cerebral mucormycosis, COVID-19, and SARS-CoV-2 (from November 01, 2019 to June 30, 2021). Our study shows that, while corticosteroids have proved to be lifesaving in severe to critical COVID-19 patients, its indiscriminate use has come with its price of rhino-orbito-cerebral mucormycosis epidemic, especially in India especially in patients with preexisting diabetes mellitus with higher mortality. Corticosteroid use should be monitored and all COVID-19 patients should be closely evaluated/monitored for sequelae of immunosuppression following treatment.

Study of Hearing Status in COVID-19 Patients: A Multicentered Review.

To evaluate the hearing status of COVID-19 patients and compare with control group. Prospective study carried out in 9 institutes. The pure tone audiogram and impedance audiometry of COVID-19 patients performed initially and at 3 months follow up. The control group consisted COVID-19 negative individuals with no history of ear related diseases. The average of air and bone conduction threshold (AC and BC) were compared between the COVID-19 patients and control group using independent t-test with a p value of less than 0.05 considered significant. Total of 331 patients, age 32 ± 4.3 years, 66.7% males and 33.3% females were included in the study. There were 80 individuals in the control group. Aural symptoms were, tinnitus in 1.8%, aural fullness in 1.4%, hearing loss in 3. 9%, and ear ache in 1.8% were present initially, resolved at 3 months follow up. The impedance audiometry demonstrated type B and type C curve in 5.1% and 1.15% ears, and out of these 64.7% and 40% improved at 3 months follow up respectively. No significant difference observed between the average AC and BC of the COVID-19 patients and control group. The COVID-19 infection may present with aural symptoms; however, it was concluded that there was no significant difference in the hearing status of the COVID-19 positive patients in comparison to the control group. The presence of some changes in the normal functioning of the eustachian tube and middle ear in the COVID-19 infection was also highlighted.

Smell and Taste Disturbance in COVID-19 Patients: A Prospective Multicenteric Review.

To study the incidence of the smell and taste disturbance in the COVID-19 patients and a follow up at 4 months to observe for the duration of resolution of these symptoms. This is a multicentric prospective study carried out in 3 different countries, from April, 2020 to January, 2021. The COVID-19 positive patients, aged between 15 and 60 years, were inquired about the presence of any smell or taste related symptoms. The same patients were followed up with the telephonic interview after 2 months and then after 4 months, respectively. The duration of resolution of the smell and taste disturbance symptoms was noted. Total of 188 COVID-19 positive patients, average age 33.1 ± 1.7 years, 54.2% males and 45.8% female were included in the study. The smell disturbance was present in 60.6% (hyposmia 36.1%, anosmia 20.2%, and parosmia 4.2%) and taste disturbance in 28.7% of patients (hypogeusia 20.2%, ageusia 6.9%, and parageusia 1.6%). There was improvement of anosmia by 97.4, hyposmia by 95.6%, parosmia by 100%, ageusia by 100%, hypogeusia 94.8%, and parageusia by 66.7%, at 4 months follow up. The present study concludes that the smell and taste disturbances are one of the main early presenting features of the COVID-19 infection. The temporary effect of the COVID-19 infection on the olfactory and gustatory pathway was also highlighted with more than 95% patients improving at 4 months of follow up.