Delta Variant of Concern in COVID-19

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The Delta variant is the most recently designated variant of concern (VOC), as classified by the World Health Organization (WHO). This variant is now seen across the world, though it may have geographic origins in India. It is essentially the B.1.617.2 lineage and has likely contributed to the fast spreading and now the faster recovering Indian second wave. It seems to have high transmissibility but appears to be less virulent (lower case fatality, but there is a need for better documentation for a better evidence base). There was an explosion of cases due to its cluster spreading nature, which had overwhelmed the health care system. The symptoms may be more severe and include gastrointestinal issues such as nausea, diarrhea, abdominal pain and loss of appetite, as well as hearing loss, gangrene and blood clotting. A better natural history data is still awaited. The public health and the clinical approaches to the Delta variant cases appear to be similar to that of standard COVID-19 treatments.

The biggest concern with the Delta VOC is the immune escape it may have with the Oxford-AstraZeneca/Covishield and the Pfizer-BioNTech mRNA vaccines.

Aziz Sheikh et al, on behalf of Public Health Scotland and the EAVE II Collaborators, recently wrote in The Lancet about the impact of the Delta strain on the Scottish population. They wrote on May 19, 2021 that the Delta VOC has rapidly become the dominant strain of SARS-CoV-2 in Scotland replacing the Alpha VOC, which had earlier been the dominant strain.

EAVE II is a Scotland-wide COVID-19 surveillance platform that has been used to track and forecast the epidemiology of COVID-19, inform risk stratification and investigate vaccine effectiveness and safety. They used the EAVE II platform to undertake a cohort analysis to describe the demographic profile of COVID-19 patients, investigate the risk of hospital admission for COVID-19 and also estimate vaccine effectiveness in preventing COVID-19 hospital admissions in S gene-positive cases. Their analysis covered the period from April 1 to June 6, 2021, for the demographic distribution of cases.

By April 1, 2021, 44.7% of the population in Scotland had received one dose of the COVID-19 vaccine, and 7.6% had received two doses. Among people aged 65 years or older, the percentages were 91.2% and 15.9%, respectively. By the end of the study period (i.e., June 6, 2021), 59.4% had received one dose and 39.4% two doses; the corresponding proportions were 91.7% and 88.8%, respectively for those aged 65 years or older.

The researchers concluded that the Delta VOC in Scotland was found mainly in younger, more affluent groups. Compared to patients with Alpha VOC (B.1.1.7 lineage), the risk of hospital admission was approximately doubled in those with the Delta VOC; patients with five or more relevant comorbidities in particular were more likely to be hospitalised.

While both the Oxford-AstraZeneca and Pfizer-BioNTech COVID-19 vaccines were effective in reducing the risk of SARS-CoV-2 infection and COVID-19 hospitalization in people with the Delta VOC, these effects on infection appeared to be diminished when compared to those with the Alpha VOC. The numbers of hospital admissions to compare between vaccines in this respect were insufficient. The Oxford–AstraZeneca vaccine appeared less effective than the Pfizer–BioNTech vaccine in preventing SARS-CoV-2 infection in those with the Delta VOC. Since these are observational data, estimates of vaccine effectiveness need to be interpreted with caution.

Source: Sheikh A, et al on behalf of Public Health Scotland and the EAVE II Collaborators. SARS-CoV-2 Delta VOC in Scotland: demographics, risk of hospital admission, and vaccine effectiveness. The Lancet. Published June 14, 2021. DOI: https://doi.org/10.1016/S0140-6736(21)01358-1

11th World Congress of Diabetes India is underway virtually this year

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The 11th World Congress of Diabetes India started yesterday. Stalwarts of diabetes have joined hands with the International Associations and Bodies like ADA, EASD and International Hypoglycemia etc. on a virtual platform to discuss the latest happenings in diabetes across the globe.

Diabetes India was initiated by (Late) Dr Sadikot in 2002 with a group of Key opinion leaders and seniors with the sole purpose of carrying out National Level epidemiological research in the field of Diabetes. He was the Founder President of DiabetesIndia, who used to collaborate with International bodies and bring International faculty to India to exchange ideas.

Diabetes India with its Vision of “Accessible, Affordable & Accountable treatment for all people with Diabetes” worked as a common platform for various stakeholders to come together. Apart from regular CMEs at all levels, Zonal meetings were also regularly conducted across India.

The Prevalence of Diabetes in India study (PODIS) was a true effort of DiabetesIndia and Dr Sadikot led the team of researchers across India to come out with the first national level prevalence data on diabetes in India. The International Diabetes Federation (IDF) adopted the data to be incorporated into the IDF Atlas.

Diabetes India began holding its Annual meetings once in 2 years starting in the year 2002 and invited the best from across the world as faculty.  This was a clear changing phenomenon in India.  An International faculty of more than 25 has never been seen in the past. This trend continues even today and the 11th edition has over 60 foreign faculties.  DiabetesIndia also collaborated with many International groups like IDF, EASD, ISPAD, Atherosclerosis Society and many more.

DiabetesIndia believes in national level epidemiological studies that can change diabetes treatment across the country. The CINDI 2 study published in 2016 is an example. It plans to do many more studies in the years to come.

The meeting this year is unique in so many ways. The meeting has been arranged in a virtual platform due to the existing Covid situation. Highest number of international faculty that too in top positions are participating in this unique conference. The Dr Sadikot Oration and Dr Siddharth Shah Oration would be delivered by Top faculty from India. More than 4000 delegates across the Globe have been registered for this conference.

The official journal of Diabetes India “Diabetes and Metabolic Syndrome: Clinical Research and Reviews (Elsevier)” was started in 2004 and continues to have great readership. Dr Anoop Misra is the Editor-in-Chief of the journal.

We assure that all participants would enjoy this feast of knowledge exchange from national and international faculties.

We look forward to getting more people registered and be benefitted by this conference.

Dr SR Aravind, President, DiabetesIndia

Dr Banshi Saboo, Hon. Secretary, DiabetesIndia

HCFI Round Table Expert Zoom Meeting on “COVID 19 & Mucormycosis”

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HCFI Dr KK Aggarwal Research Fund

15th and 22nd May, 2021, 11am-12pm

Key points from discussion

  • Many cases of mucormycosis are being reported during the second wave. Earlier there were sporadic cases. But then a spurt of cases was reported from Maharashtra, Gujarat and even Delhi. The speed at which it is spreading in the country is very alarming.
  • More than 1000 cases have been detected in a month and most of them are in medical colleges or big private hospitals.
  • It is not seen in other parts of the world. Risk factors are climate, genetic, large number of diabetic population, steroid overuse.
  • Mucormycosis is a fungal disease. Fungal spores are present in the environment – in the air and in the soil. Although rare, it is a serious disease. Hence, it is important to discuss its prevention and early detection.
  • Risk factors include poorly controlled diabetes, hematopoietic malignancy, prolonged neutropenia, solid or stem cell transplant. Use of unsterilized water in oxygen humidifier is another risk factor. Prediabetic persons may be at risk if they are prescribed steroids.
  • It presents as rhino-orbital-cerebral-mucormycosis, which involves the nose, paranasal sinuses, eyes and the brain. Pulmonary (most common); GI and cutaneous or disseminated mucormycosis are other forms of the disease. GI mucormycosis is common in children.
  • Initial symptoms include fever, perinasal and periorbital pain, congestion, nasal discharge. In advanced disease, nasal ulceration or necrotic lesion can occur.
  • Most patients present with unilateral sinusitis; in the later stage, the disease becomes bilateral. It can be diagnosed by color changes in the nasal mucosa, nasal endoscopy, be watchful in the third/fourth week after discharge, especially if the patient has diabetes. Sympathetic ophthalmitis is very rare.
  • Microscopy is the confirmatory diagnostic test. Crust or deep tissue material is required for diagnosis. In some hospitals in Maharashtra, KOH smears are done as a routine at discharge, for any patient who is hospitalized for more than 21 days.
  • First treatment option is intense medical treatment; surgery should be the last option.
  • Surgical removal of mucormycosis is a big challenge; surgery itself is associated with high morbidity, especially in the immunocompromised persons.
  • Prevention is the best treatment for this disease; proper oral and personal hygiene, wearing shoes, long trousers, full sleeve shirts and gloves when handling soil, good oral and nasal hygiene (povidone iodine), appropriate use of antibiotics and antifungals, tight glycemic control for first 3 months post Covid, optimised steroid use (use in right doses for the right time) and use of clean and sterile water in humidifier and oxygen therapy. Many ENT surgeons use amphotericin irrigation. Hydrogen peroxide irrigation can also be done; it is more economical.
  • There is no medical need for water in oxygen supplementation system; it only indicates continuous flow of oxygen. If sterile/distil water is not available, then at least boiled water should be used. The bottle should be cleaned every day.
  • Remove possible sources of fungus infection in hospitals such as oxygen humidifiers.
  • Don’t miss warning signs. Detect it early and start treatment at the earliest. Manifestations picked up in the nose are critical to saving the eyes. There is no role of prophylaxis.
  • Shortage of liposomal amphotericin is a challenge.  It is the drug of choice, but it is also a very nephrotoxic drug. Posaconazole, another drug can be used; it is supposed to be kidney safe. Avoid variconazole.
  • All case of blocked noses should not be considered as bacterial sinusitis. Be aggressive for microscopy, KOH and culture.
  • Good ENT examination at the time of discharge (nasal endoscopy) “with all safety measures”, probably when the patient is Covid-negative may be considered.
  • There should be robust data, which is regionally representative, on mucormycosis as it needs to be re-looked at, especially in Covid time, with regard to factors such as difference in clinical presentation etc.
  • There is a need to sensitise all healthcare workers on this issue.
  • There are now dedicated mucor wards in many tertiary care referral centers. Nursing care of high risk patients should be done very carefully.
  • Careful monitoring and management of diabetes should be given equal importance as Covid treatment in those Covid patients who have comorbid diabetes. This may be key to reducing the number of cases of mucormycosis.
  • There is a need to build up a referral mechanism and insist on good pharmacy and prescription practices.
  • Effective implementation of Drugs and Cosmetics Rules is required.
  • Strengthening of the primary healthcare is the need of the hour. Proper diagnostic facilities should be available in all PHCs and Health & Wellness Centers.
  • The cost of medicines is presently prohibitive.
  • There is an urgent need to follow preventive measures. Prevention of Covid-19 will automatically prevent mucormycosis.
  • A presentation on “Covid-19 associated Rhino-orbital-cerebral-mucormycosis (ROCM)” was given by Dr AK Grover, Chairman, Dept. of Ophthalmology, Sir Ganga Ram Hospital and Chairman, Vision Eye Centres, Siri Fort Road and West Patel Nagar, New Delhi
  • ROCM is a huge problem almost exclusive to India. In a review of published cases (up to May 13), out of total 101 cases, 82 were from India. 80% of patients had pre-existing diabetes and 76% patients had received steroids. Rhinological symptoms were the most common symptoms reported by almost 89% of patients.
  • Factors predisposing to RCOM include: diabetes/hyperglycemia, steroids, immunodeficiency, malignancy, stem cell transplantation and iron overload.
  • Lowering of innate immunity by Covid, lowered immunity due to use of steroids/tocilizumab, hyperglycemia aggravated by steroids, oxidative stress, high ferritin levels, zinc and use of antibiotics facilitating breakthrough infections may cause covid-associated ROCM. Not much is still known, except hyperglycemia is certainly an important contributory factor.
  • Diagnosis of ROCM has been divided into possible, probable and proven.
  • Possible ROCM: typical signs and symptoms in the clinical setting of recently (≤6 weeks) treated Covid-19, diabetes, immunosuppression, use of systemic steroids/tocilizumab, mechanical ventilation or oxygen supplementation
  • Probable ROCM: supportive evidence clinically and on diagnostic nasal endoscopy and/or contrast enhanced MRI/CT scan. No evidence on direct microscopy or culture or histopathology with special stains or molecular diagnostics
  • Proven ROCM: supportive evidence clinically and on diagnostic nasal endoscopy and/or contrast enhanced MRI/CT scan. Confirmation on direct microscopy or culture or histopathology with special stains or molecular diagnostics
  • Patient examination involves rhinological, ophthalmic and neurological examination in addition to systemic examination.
  • Ocular signs and symptoms of ROCM are periocular or facial edema, conjunctival congestion, sudden ptosis/double vision or motility restriction, proptosis and even sudden loss of vision.
  • Early presentation is lid edema and congestion; lid edema and motility restriction or ocular motility restriction and ptosis may also occur. In advanced stage, there is proptosis and formation of a large black eschar. The disease may become bilateral with necrosis. Cerebral involvement may occur in severe disease.
  • Along with medical therapy, sinus debridement surgery is done; sometimes exenteration requires to be done if there is more than two-quarter involvement of the orbit. This is a dilemma.
  • General signs and symptoms are regional/facial pain, fever, worsening headache, facial palsy, focal seizures.
  • Microscopic examination of tissue from nose (KOH) showing non septate hyphae, angioinvasion  is important for diagnosis. Direct microscopy has a sensitivity of 90%.
  • Contrast enhanced MRI is the imaging modality of choice.
  • There is tenting of the globe in the later stage. There may be bilateral optic nerve involvement.
  • Imaging is very important in assessment to find out the extent of involvement.
  • A multidisciplinary approach is critical for management.
  • Treatment is IV liposomal amphotericin, strict metabolic control and monitoring of renal function or IV posaconazole/isavuconazole. Aggressive debridement of PNS is required; turbinectomy/palatal wall/orbital wall resection may need to be done.
  • In the first wave, Sir Gangaram Hospital (SGRH) had 31 cases of mucormycosis; of these 29 had diabetes while in the second wave, there have been 89 cases (till 26th May); 72 had long-standing diabetes, while 17 had recently been diagnosed as having diabetes; 40 patients were hypertensive. Predominantly males were more affected than females. Most patients required oxygen supplementation.
  • A 6-weekly follow up is done for 3-6 months to assess regression or stabilization of disease, both clinically and via imaging.
  • Several reasons have been put forth for the epidemic of mucormycosis in India. To name a few: tropical climate, more dust/environment with spores, poor metabolic control and contamination of oxygen delivery.
  • Covid-associated ROCM can be prevented and can be treated adequately to prevent its devastating impact.
  • Recognise the red flags: purulent nasal discharge with or without epistaxis with sinusitis, decreased sensation inside the nose, nasal ulceration and necrosis, grey or reddish mucosa, black eschar in the nasal septum, palate, eyelid, face or orbital areas, facial pain on one side, swelling or numbness.
  • Prevention measures include education of the general public and medical community, strict glycemic control, rational use of steroids, use of distilled water in oxygen delivery systems, isotonic saline nasal spray at least twice daily.

Participants

Dr AK Agarwal

Dr Suneela Garg

Dr Ashok Grover

Dr Mahesh Verma

Dr Girdhar Gyani

Dr Anita Chakravarti

Dr Alex Thomas

Dr Ashok Gupta

Dr Sumit Mrig

Dr DR Rai

Dr Jayakrishnan Alapet

Mr Bejon Misra

Ms Balbir Verma

Mrs Upasana Arora

Dr Anuradha Sapra

Dr Reena Arora

Dr Promod Kumar

Dr Russell D’Souza, Australia

Dr KK Kalra

Dr Anil Kumar

Ms Ira Gupta

Dr S Sharma

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