Post-COVID Syndrome: The Stranger Ghost of Culprit COVID-19.

BACKGROUND: Post-COVID syndromes are the most abundant sequel of coronavirus disease of 2019 (COVID-19) infection, which affects millions of people around the whole world. There is a significant difference observed during the acute phase as well as during the post-COVID period between patients hospitalized with (alpha, delta, or omicron) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant. In the present scenario, when most people are vaccinated, COVID-19 disease is less likely, but the remnants of previous COVID-19 infections are still a vast health burden. MATERIALS AND METHODS: This prospective, observational, comparative, and analytical study included a total of 3,840 COVID-19-infected patients who visited the hospital. We included 1,150 patients of alpha variants, 1,845 patients of delta variants, and 815 patients of omicron variants, from June 2020 to November 2020, March 2021 to July 2021, and January 2022 to May 2022, respectively. All medical data of the study population, including hospital stay and vaccination status, were collected, and all patients were followed up for 6 months of duration. All collected data were compiled and analyzed to compare the post-COVID thrombotic and other events among different variants of COVID-19. RESULTS: Patients infected during the delta variant are the most symptomatic at onset (higher prevalence of fever, dyspnea, cough, myalgia, headache, or gastrointestinal problems) than those infected with the alpha or omicron variant (p < 0.01). A total of 2,830 patients (7.48%) [1,520 (82.38%) of delta variant, 598 (73.37%) of omicron variant, and 712 (60.34%) of omicron variant] developed post-COVID syndrome during their follow-up period out of 3,220 enrolled patients and the difference was statistically significant when compared among variants (p < 0.05). In this study, the highly prevalent post-COVID syndrome was mucormycosis (11.41%), followed by new-onset diabetes (9.89%), pulmonary fiosis (7.67%), ischemic heart disease (6.46%), ain stroke (3.29%), and other thromboembolic disorders (2.37%). CONCLUSION: COVID-19-associated onset symptoms during the delta variant were more severe and highly prevalent, while neurological symptoms (aguesia and anosmia) were more common during the alpha variant. Patients infected with the delta variant of COVID-19 are more prone to develop post-COVID-associated complications with minimal risk in the omicron variant and intermediate risk in the alpha variant. Long COVID-19 requires specific attention for management, irrespective of the SARS-CoV-2 variant.

Correction to "SARS-CoV-2 accelerated clearance using a novel nitric oxide nasal spray (NONS) treatment: A randomized trial".

[This corrects the article DOI: 10.1016/j.lansea.2022.100036.].

Effectiveness of budesonide formoterol fixed-dose combination MDI in reducing cough symptoms in COVID-19 patients: A real-world evidence study.

Background: Cough is a wearisome and exasperating symptom affecting the daily life of the infected patient. Cough due to coronavirus disease 2019 (COVID-19) causes excessive morbidity in human populations globally. Apart from the morbidity associated with cough, it also enhances the transmission of this viral infection through droplets. Therefore, curbing cough is crucial to limit its spread. Patients often administer over-the-counter products and antitussive agents, which have no proven benefit. The present study was undertaken to find out if cough associated with COVID-19 and other indicative clinical outcomes is alleviated with a budesonide/formoterol fixed-dose combination (FDC) metered-dose inhaler (MDI). Materials and Methods: A prospective observational study was conducted in mild COVID-19 patients who presented with a cough score ≥8 at presentation. Patients who were initiated on ICS-LABA MDI were observed as group A and those who were not initiated on MDI were observed as Group B. Cough symptom score (at baseline and on day 3 and day 7), the incidence of hospital admission and/or death, and need for mechanical ventilation were documented. Prescribing patterns of anti-cough medications were also noted and analysed. Results: Compared to group B, a higher mean cough score reduction was noted for group A patients at day 3 and day 7 when compared to the baseline, and this was significant at P < 0.001. A significant negative correlation was also observed between mean latency of MDI initiation from the symptom onset and mean cough score reduction. Analysis of the proportion of patients prescribed medications to treat cough showed that overall, 10.78% did not require these, with a greater proportion in group A compared to group B. Conclusion: Patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) COVID-19 who were treated with ICS-LABA MDI along with usual care benefitted significantly in terms of symptom reduction compared to usual care.

Efficacy and safety of pegylated interferon-α2b in moderate COVID-19: a phase 3, randomized, comparator-controlled, open-label study.

OBJECTIVE: To evaluate the efficacy and safety of pegylated interferon alpha-2b (PEG IFN-α2b) administered in conjunction with the standard of care (SOC) in subjects with moderate coronavirus disease-19 (COVID-19). METHODS: In this study, adult subjects with confirmed moderate COVID-19 were randomized in a 1:1 ratio to receive either PEG IFN-α2b + SOC or SOC alone. The primary endpoint was a two-point improvement in clinical status on Day 11, measured by the World Health Organization's seven-point ordinal scale. RESULTS: Of 250 subjects, 120 were randomized to the PEG IFN-α2b + SOC arm and 130 were randomized to the SOC arm. The results for the PEG IFN + SOC arms vs the SOC arm for the proportion of subjects with a two-point improvement in the seven-point ordinal scale were 80.36% vs 68.18% (P=0.037) on Day 8, 91.60% vs 92.56% (P=0.781) on Day 11, and 94.12% vs 95.93% (P=0.515) on Day 15. There was a time-dependent decrease in the biomarkers in both arms, and no clinically significant changes in laboratory parameters. The safety profile was similar in both arms. CONCLUSION: PEG IFN-α2b induced early viral clearance, improved the clinical status, and decreased the duration of supplemental oxygen. It provides a viable treatment option and can limit the spread of severe acute respiratory syndrome coronavirus-2.

SARS-CoV-2 accelerated clearance using a novel nitric oxide nasal spray (NONS) treatment: A randomized trial.

Background: Additional outpatient therapies which are readily accessible will be essential to reduce COVID-19 illness progression in high risk individuals. Especially as the virus continues to mutate with greater transmissibility despite increased global vaccination. Methods: A randomized, double-blind, multicentre, parallel group, placebo-controlled phase III clinical trial evaluated the ability of nitric oxide (NO) to rapidly eradicate nasal SARS-CoV-2 RNA. Adults (18-70 years) with mild symptomatic COVID-19 were randomized, confirmed by laboratory SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) nasal swab. Randomisation was 1:1, NONS (N = 153) vs placebo (N = 153). NO generated by a nasal spray (NONS) was self-administered six times daily as two sprays per nostril (0⋅45 mL of solution/dose) for seven days. Patients at high risk of illness progression, defined as unvaccinated, ≥ 45 years of age or having comorbidities, were the primary analysis population. Findings: Overall, mean SARS-CoV-2 RNA concentrations (6·96 log10 copies/mL in the NONS group and 7·16 log10 copies/mL in the placebo group) were comparable at baseline. Primary endpoint mean treatment difference SARS-CoV-2 RNA change from baseline to the end of treatment (EOT) was -0·52 copies/mL (SE 0·202, 95% CI -0·92 to -0·12; p = 0·010) with NONS compared to placebo. Secondary endpoint assessments demonstrated a greater proportion of patients receiving NONS (82·8%) cleared SARS-CoV-2 (RT-PCR negative) by EOT compared to placebo (66·7%, p = 0·046), with no virus RNA detected a median of four days earlier compared to placebo (three vs seven days; p = 0·044). Interpretation: Use of NONS in patients recently infected with SARS-CoV-2 accelerates nasal virus clearance. Funding: Funding provided by Glenmark Pharmaceuticals Limited. Study medication provided by SaNOtize.

Efficacy and Safety of Aspirin, Promethazine, and Micronutrients for Rapid Clinical Recovery in Mild to Moderate COVID-19 Patients: A Randomized Controlled Clinical Trial.

Introduction In the present study, the combination of two tablets, one with Aspirin and Promethazine and the other with vitamin D3, C, and B3 along with zinc and selenium supplementation was proposed as an intervention (APMV2020). The ingredients in the formulation represent a precise, tailored therapy for the symptoms of COVID-19, combined with natural constituents to help the body itself build immunity to recover from infection. The present study was conducted to clinically validate the safety and efficacy of the APMV2020 tablets. Trial design The present trial is a randomized, multicentric, controlled clinical trial involving 260 mild to moderate COVID-19 patients. The treatment duration was of 10 days. Methodology The subjects were randomized to receive either the control intervention (clinical management protocol for COVID-19 advocated by the Indian Council of Medical Research (ICMR) or the test intervention (treatment with APMV2020 tablets along with the standard control treatment. The assessment days were baseline, days five and 10. Results APMV2020 significantly (<0.05) improved symptoms of COVID-19 like cough, myalgia, headache, and anosmia as compared to the control group. APMV2020 treatment also reduced inflammatory markers like lactate dehydrogenase (LDH), ferritin, and C-reactive protein (CRP). Conclusion APMV2020 can prove as a good candidate to be integrated into the COVID-19 management protocol. As it can offer speedy clinical recovery to reduce the burden on healthcare infrastructure, second, the combination shows significant anti-inflammatory potential to improve prognosis, and lastly, the immunomodulatory properties offer long-term protection that can help in combating long COVID symptoms and complications.

Real-World Experience with Favipiravir for the Treatment of Mild-to-Moderate COVID-19 in India.

Background: Favipiravir, an RNA-dependent RNA polymerase inhibitor (RdRp), is a broad-spectrum oral antiviral agent approved in India under emergency use authorization, for the treatment of mild-to-moderate coronavirus disease (COVID-19). The present study was planned to evaluate the effectiveness and safety of favipiravir in real-world clinical practice. Materials and Methods: This was a multicentric, retrospective, single-arm study conducted across four centres in India, after obtaining permission from the independent ethics committee. Medical records were analysed to evaluate effectiveness and safety of patients who were prescribed favipiravir. Results: The medical records of a total of 360 patients met the inclusion criteria, with 358 of them available for the final analysis. Males made up 58.46% of the study population. The average age of enrolled patients was 51.80 ± 16.45 years. The most common symptoms were fever, cough, and myalgia-fatigue. The median time to clinical cure and fever relief was five and four days, respectively. The average length of stay in the hospital was six days. In total, 8% of the patients experienced adverse events. Hepatic enzyme elevation, diarrhoea, decreased appetite, headache, fatigue, and giddiness were the common symptoms. Conclusion: In our real-world study, favipiravir was found to have a clinical cure rate of more than 90% in mild-to-moderate COVID-19 patients. This supports the use of favipiravir in the treatment of COVID-19. Favipiravir was well tolerated, with only minimal side effects, which were transient in nature.

Efficacy and Safety of a Phytopharmaceutical Drug Derived from Cocculus hirsutus in Adults with Moderate COVID-19: a Phase 2, Open-label, Multicenter, Randomized Controlled Trial.

INTRODUCTION: There is an urgent need for an effective, oral therapy for COVID-19. Purified aqueous extract of Cocculus hirsutus (AQCH) has shown robust antiviral activity in in vitro studies. We aimed to evaluate the efficacy and safety of AQCH plus standard of care in hospitalized patients with moderate COVID-19. METHODS: In an open-label, multicenter, randomized controlled trial conducted in India, eligible patients (aged 18-75 years) were randomized (1:1) to receive AQCH 400 mg orally three times a day plus standard of care (AQCH group) or standard of care alone (control group) for 10 days. Primary endpoint was the proportion of patients showing clinical improvement by day 14. Time to clinical improvement, time to viral clearance, and duration of hospitalization were secondary endpoints. RESULTS: A total of 210 patients were randomized. By day 14 most patients in both groups showed clinical improvement [difference - 0.01 (95% CI - 0.07 to 0.05); p = 1.0]. Median time to clinical improvement was 8 days (IQR 8-11) in the AQCH group versus 11 days (IQR 8-11) in the control group [HR 1.27 (95% CI 0.95-1.71); p = 0.032]. Time to viral clearance and duration of hospitalization were also significantly shorter in the AQCH group (p = 0.0002 and p = 0.016, respectively). AQCH was well tolerated, with no safety concerns identified. CONCLUSIONS: AQCH significantly reduced time to clinical improvement, time to viral clearance, and duration of hospitalization. In a pandemic, this has significant potential to decrease healthcare resource utilization and increase hospital bed availability. Further investigation of the therapeutic potential of AQCH in patients with COVID-19 is warranted. TRIAL REGISTRATION: Clinical Trials Registry - India (CTRI/2020/05/025397).

Clinical characteristics of AY.4 infections are similar to B.1.617.2 infections: a preliminary study

Background: The SARS-CoV-2 Delta variant (B.1.617.2) was first detected in India in late 2020 and soon became the predominant lineage owing to its high transmissibility. Over time, the virus has acquired mutations and has evolved into many new sub-lineages. AY.4 is one such sub-lineage that grew in frequency globally. Therefore, we aimed to compare the severity of infection due to Delta sub-lineages to Delta infections in Pune, Maharashtra, India. Material and Methods: Whole-genome sequencing and analysis of 255 SARS-CoV-2 positive samples, collected between 1st August to 1st September 2021, by BJ Government Medical College, Pune, was carried out at the Indian Institute of Science Education and Research (IISER), Pune and the Council of Scientific and Industrial Research-Institute of Genomics and Integrative Biology (CSIR-IGIB), New Delhi. Individual-level data on these patients were collected from ICMR COVID-19 Data Portal. Additional information regarding the presence of any symptoms, comorbidities, hospitalization, international travel history within 14 days and vaccination status was collected by telephonic interview with each patient by the BJGMC Sequencing Team.

COVID-19 associated mucormycosis: A Descriptive Multisite Study from India.

BACKGROUND AND AIMS: Mucormycosis is an invasive fungal infection and carries a significant morbidity and mortality. A number of cases of mucormycosis have been reported in association with COVID-19. In this study, a consortium of clinicians from various parts of India studied clinical profile of COVID-19 associated mucormycosis (CAM) and this analysis is presented here. METHODS: Investigators from multiple sites in India were involved in this study. Clinical details included the treatment and severity of COVID-19, associated morbidities, as well as the diagnosis, treatment and prognosis of mucormycosis. These data were collected using google spreadsheet at one centre. Descriptive analysis was done. RESULTS: There were 115 patients with CAM. Importantly, all patients had received corticosteroids. Diabetes was present in 85.2% of patients and 13.9% of patients had newly detected diabetes. The most common site of involvement was rhino-orbital. Mortality occurred in 25 (21.7%) patients. On logistic regression analysis, CT scan-based score for severity of lung involvement was associated with mortality. CONCLUSION: Universal administration of corticosteroids in our patients is notable. A large majority of patients had diabetes, while mortality was seen in ∼1/5th of patients, lower as compared to recently published data.

Absence of Case of Mucormycosis (March 2020-May 2021) under strict protocol driven management care in a COVID-19 specific tertiary care intensive care unit.

AIMS: With a sudden increase in cases of mucormycosis seen in Covid -19 patients, we conducted a retrospective analysis of all admitted patients in a tertiary care covid-19 hospital looking at incidence of mucormycosis. METHODS: Intensive care unit daily rounds data stored in an electronic format was retrieved by one of the consultants, looking for incidence of mucormycosis, diabetes mellitus, adherence to protocol for steroid use, glycemic control and use of monoclonal antibodies. Also, patients follow up data base of post covid Outpatients Department was searched for cases of mucormycosis. RESULTS: A total of 5248 patients were admitted between March 2020 to May 2021, of which 1027 were in ICU and 4221 in wards. Of the 1027 patients admitted in Intensive care unit, 915 received steroids and 417 had diabetes as existing co-morbidity. No case of mucormycosis was reported during the stay in the hospital and during immediate outpatient department follow up. The low dose steroids were administered as per state government protocol for treating COVID 19, a nurse driven strict glycemic control regime (blood glucose level was maintained between 140 and 180 mg/dl through the admission in ICU and was achieved consistently in 842 (82%) patients, followed along with minimal use of other immunomodulatory like monoclonal antibodies. CONCLUSION: A strict adherence to protocol of low dose steroids coupled with strict glycemic control helped in eliminating the risk and incidence of mucormycosis in a tertiary care dedicated covid-19 hospital.

Mucormycosis in COVID-19: A systematic review of cases reported worldwide and in India.

BACKGROUND AND AIMS: There are increasing case reports of rhino-orbital mucormycosis in people with coronavirus disease 2019 (COVID-19), especially from India. Diabetes mellitus (DM) is an independent risk factor for both severe COVID-19 and mucormycosis. We aim to conduct a systematic review of literature to find out the patient's characteristics having mucormycosis and COVID-19. METHODS: We searched the electronic database of PubMed and Google Scholar from inception until May 13, 2021 using keywords. We retrieved all the granular details of case reports/series of patients with mucormycosis, and COVID-19 reported world-wide. Subsequently we analyzed the patient characteristics, associated comorbidities, location of mucormycosis, use of steroids and its outcome in people with COVID-19. RESULTS: Overall, 101 cases of mucormycosis in people with COVID-19 have been reported, of which 82 cases were from India and 19 from the rest of the world. Mucormycosis was predominantly seen in males (78.9%), both in people who were active (59.4%) or recovered (40.6%) from COVID-19. Pre-existing diabetes mellitus (DM) was present in 80% of cases, while concomitant diabetic ketoacidosis (DKA) was present in 14.9%. Corticosteroid intake for the treatment of COVID-19 was recorded in 76.3% of cases. Mucormycosis involving nose and sinuses (88.9%) was most common followed by rhino-orbital (56.7%). Mortality was noted in 30.7% of the cases. CONCLUSION: An unholy trinity of diabetes, rampant use of corticosteroid in a background of COVID-19 appears to increase mucormycosis. All efforts should be made to maintain optimal glucose and only judicious use of corticosteroids in patients with COVID-19.

A two-arm, randomized, controlled, multi-centric, open-label phase-2 study to evaluate the efficacy and safety of Itolizumab in moderate to severe ARDS patients due to COVID-19.

Objective: Efficacy and safety of Itolizumab, an immunomodulatory mAb, in treating moderate-to-severe acute respiratory distress syndrome (ARDS) due to cytokine release in COVID-19 patients was evaluated in a multi-centric, open-label, two-arm, controlled, randomized, phase-2 study.Methods: Patients were randomized (2:1) to Arm-A (best supportive care [BSC]+Itolizumab) and Arm-B (BSC). Primary outcome of interest was reduction in mortality 30-days after enrollment.Results: Thirty-six patients were screened, five treated as first-dose-sentinels and rest randomized, while four patients were screen-failures. Two patients in Arm-A discontinued prior to receiving one complete infusion and were replaced. At end of 1-month, there were three deaths in Arm-B, and none in Arm-A (p = 0.0296; 95% CI = -0.3 [-0.61, -0.08]). At end of study, more patients in Arm-A had improved SpO2 without increasing FiO2 (p = 0.0296), improved PaO2 (p = 0.0296), and reduction in IL-6 (43 vs 212 pg/ml; p = 0.0296) and tumor necrotic factor-α (9 vs 39 pg/ml; p = 0.0253) levels. Transient lymphopenia (Arm-A: 11 patients) and infusion reactions (7 patients) were commonly reported treatment-related safety events.Conclusion: Itolizumab is a promising, safe and effective immunomodulatory therapy for treatment of ARDS due to cytokine release in COVID-19 patients, with survival and recovery-benefit.

Role of favipiravir in the treatment of COVID-19.

The coronavirus disease-2019 (COVID-19) outbreak all over the world has led the researchers to strive to develop drugs or vaccines to prevent or halt the progression of this ailment. To hasten the treatment process, repurposed drugs are being evaluated. Favipiravir is one such oral drug that was approved for new and reemerging pandemic influenza in Japan in 2014 and has shown potent in vitro activity against severe acute respiratory syndrome coronavirus-2. It has a wide therapeutic safety margin indicated by a wide CC50/EC50 ratio for a high dose. From the clinical studies in COVID-19, it has shown rapid viral clearance as compared to lopinavir/ritonavir (LPV/RTV) and superior recovery rate than umifenovir. Overall, favipiravir has shown promising results in clinical studies in China, Russia, and Japan, and more trials are underway in multiple countries, including USA, UK, and India. Recently, treatment guidelines from many countries and some states from India have included favipiravir in the treatment protocol. This review provides insights into the evidence-based evolving role of favipiravir in the management of COVID-19 infection with emphasis on benefits of initiating an early antiviral therapy with special focus on favipiravir, its pharmacodynamic, pharmacokinetic, in vitro, clinical data, and inclusion in the treatment protocols of COVID-19.

Coronavirus disease 2019 and thyroid disease: Position statement of Indian Thyroid Society

About Coronavirus and Coronavirus Disease 2019 Coronavirus belongs to a large family of single-stranded RNA viruses. Elderly people, and those with medical conditions such as hypertension, cardiac problems or diabetes, chronic obstructive airway disease, are more likely to develop serious illness.[[2]] Thyroid Disorders in India Thyroid diseases are common worldwide. The prevalence of hypothyroidism in T2DM and hypertension in India was found to be about 33%.[[6]] Hypothyroidism and Coronavirus Disease 2019 There is no information on how it affects individuals with hypothyroidism. [Extracted from the article] Copyright of Thyroid Research & Practice is the property of Wolters Kluwer India Pvt Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Itolizumab, an anti-CD6 monoclonal antibody, as a potential treatment for COVID-19 complications.

INTRODUCTION: The globally rampant SARS CoV-2 pandemic requires novel medical strategies to control the severity of disease and death due to complications. Of the 15-20% patients that develop pulmonary symptoms, a sub-set develops an acute respiratory distress syndrome (ARDS) rapidly progressing into a critical condition. Marked elevation of cytokines/chemokines is observed with elevation of additional markers of inflammation, coagulation, and organ damage such as CRP, D-dimer, LDH, Ferritin and Troponin-I. This hyperinflammation leads to worsening of oxygen saturation due to pulmonary infiltration and exudation, organ damage, and dysfunction of coagulation pathway and may lead to multi-organ failure. AREAS COVERED: The role of anti-inflammatory monoclonal antibodies such as Itolizumab, in cytokine storm. EXPERT OPINION: Itolizumab, an anti-CD6 humanized IgG1 mAb, binds to domain-1 of CD-6 that is responsible for priming, activation, and differentiation of T-cells. Itolizumab significantly reduces T-cell proliferation along with substantial downregulation of the production of cytokines/chemokines. Approved for moderate to severe chronic plaque psoriasis in 2013 it is currently being studied for addressing COVID-19 related cytokine storm and its complications. This article reviews its use in COVID-19 infections; its dose, administration protocol, contra-indications, and safety in treating moderate-to-severe ARDS by preventing and treating the cytokine storm and its complications.