Day: 04/19/2022

Covid-19: What do we know about the delta omicron recombinant variant?

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A combination of the delta (AY.4) and BA.1 omicron variants has been named by the World Health Organization as the BA.1 x AY.4 recombinant. First detected in France in January 2022, it has since picked up the nickname “deltacron”1—Elisabeth Mahase finds out more

How does a recombinant emerge?

Recombinants can emerge when multiple variants infect the same person at the same time, allowing the variants to interact during replication, mix up their genetic material, and form new combinations. These events become more likely when cases are higher—an important consideration, as covid-19 cases worldwide have once again started to rise after several weeks of decline.2

Maria Van Kerkhove, the World Health Organization’s covid-19 technical lead, said in a post on social media,3 “[This is] what happens when we allow the virus to circulate at such an intense level. The virus continues to evolve and more variants are expected. Recombinants are also expected . . . as we have been explaining for a very long time.”

She emphasised that vaccines alone could not be used to control the SARS-CoV-2 pandemic but that other measures were also needed, while testing and sequencing around the world were vital.

What do we know about “deltacron”?

So far, very little. The literature on deltacron is sparse, although a perspective published by the Chinese Center for Disease Control and Prevention has provided some insight.4 The researchers have reported that the recombinant is very similar to the delta (AY.4) variant except when it comes to the region encoding the spike gene, which is similar to BA.1. Of the 36 amino acid mutations found in the spike protein, 27 were found in BA.1 and five in AY.4, while four were found in both.

The authors have also highlighted that while this is not the first recombination event identified in SARS-CoV-2, and while some have even seen a small amount of community transmission, no previous events have involved such large genomic fragments. As such, the authors said that the emergence of the BA.1 x AY.4 recombinant could be a cause for concern.

They warned, “Although the emergence and subsequent spread of variants of concern has had a huge impact on global health and economy, it may not have been the worst case until now, as recombination (a major mechanism bringing genetic diversity to coronaviruses) has not really emerged on a large scale and shown its power before the emergence of ‘deltacron.’

“The emergence of ‘deltacron’ is therefore a ‘grey rhino’ [an obvious threat that has been ignored or played down] rather than ‘black swan’ [an unlikely but extremely serious] event . . . With the advent of ‘deltacron,’ further concerns are coming.”

On the other hand, a preprint released through medRxiv suggested that delta and omicron coinfections and recombination events were still rare.5 Researchers sequenced 29 719 positive samples taken from November 2021 to February 2022, when delta and omicron were co-circulating in the US. They found 20 coinfections and two independent cases of infection by a delta-omicron recombinant virus. They concluded that these recombinants were rare and that there was currently no evidence that those identified in this study were more transmissible than the omicron lineages already circulating (BA.1, BA.2).

Shishi Luo, lead author and a senior bioinformatics scientist at the genomics company Helix, told The BMJ, “We haven’t seen any evidence for concern for either of the recombinants reported in our study. However, given that other recombinants are being identified at around the same time around the world, we should definitely be increasing our ability to monitor and track them.”

Speaking to The BMJ, Eric Topol, professor of molecular medicine at the Scripps Research Institute in California, echoed the message that while this recombinant may not pose a threat, it could be a warning of what is to come.

“There have been at least three different ‘deltacron’ variants identified now,” he said. “Our concern about them is tempered by lack of evidence that any of these have spread potential or signs of increased virulence. But their appearance emphasises the potential for these recombinant, fusion, hybrid occurrences.

“At the same time, more simultaneous coinfections of variants are being recognised, and there’s also the potential of these occurring in animal reservoirs, or like with bird flu-influenza, a recombinant between humans and animals harbouring SARS-CoV-2.”

This article is made freely available for personal use in accordance with BMJ’s website terms and conditions for the duration of the covid-19 pandemic or until otherwise determined by BMJ. You may download and print the article for any lawful, non-commercial purpose (including text and data mining) provided that all copyright notices and trade marks are retained.https://bmj.com/coronavirus/usage

References

  1. ↵European Centre for Disease Prevention and Control. SARS-CoV-2 variants of concern as of 17 March 2022. Mar 2022. https://www.ecdc.europa.eu/en/covid-19/variants-concern
  2. ↵
    1. Mahase E. Covid-19: Is the UK heading for another omicron wave?BMJ2022;376:o738.pmid:35304409FREE Full TextGoogle Scholar
  3. ↵Van Kerkhove M. Twitter. https://twitter.com/mvankerkhove
  4. ↵Wang L, Gao GF. The “wolf” is indeed coming: recombinant “deltacron” SARS-CoV-2 detected. China CDC Weekly 2022 Mar. https://weekly.chinacdc.cn/fileCCDCW/journal/article/ccdcw/newcreate/CCDCW220051.pdf
  5. ↵Bolze A, White S, Basler T, et al. Evidence for SARS-CoV-2 delta and omicron co-infections and recombination. medRxiv 2022.03.09.22272113 [preprint]; doi:https://doi.org/10.1101/2022.03.09.22272113. https://www.medrxiv.org/content/10.1101/2022.03.09.22272113v1Google Scholar

Source: BMJ

What is the current status of the COVID-19 XE variant?

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Worldwide COVID-19 cases have started to rise once again after several weeks of decline. When multiple variants of the virus infect the same person simultaneously, the variants can interact during replication, mix up their genetic material and form recombinants.1 In January 2022, the COVID-19 XE variant was identified in the United Kingdom, and more than 600 samples of the XE variant have since been collected in several countries. According to the U.K. Health Security Agency (UKHSA), the XE variant of COVID-19 is a “recombinant”, which is a mutant hybrid of BA.1 and BA.2 Omicron strains. 

  • According to the World Health Organisation (WHO), given the current high rate of transmission worldwide, more variations, including recombinants, are likely to emerge.
  • Early estimations imply that the XE variant of COVID-19 is 10% more contagious than BA.2 (Omicron). However, this finding requires further confirmation.
  • The clinical presentation of the XE variation is not different than that of BA.[1] or BA.2. 
  • According to the WHO, the XE variant belongs to the Omicron variant until significant differences in transmission and disease characteristics, including severity, are reported.

The first incidence of the XE variant of COVID-19 in India was reported on 6th April 2022. The Brihanmumbai Municipal Corporation (BMC) announced that a 50-year-old woman having a travel history to South Africa have been infected with the ‘XE’ variant. The announcement about this discovery raised concern about the risk of a fresh wave of infections in India, although no critical global signal of concern is there as of now. This woman is totally asymptomatic, and the RTPCR result revealed negative on repeat testing. However, according to the Union Health Ministry, New Delhi, the sample identified as the ‘XE’ variant was thoroughly examined by genome experts from the Indian severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Genomics Consortium (INSACOG), who concluded that the genomic constitution of this variant did not match that of the XE variant.

WHO continues to closely monitor and analyse the public health risk posed by SARS-CoV-2 variants and will provide updates once new evidence becomes available.

How to manage vomiting in children?

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Vomiting is a common problem in the paediatric population. Acute gastritis and gastroenteritis (AGE) are mostly responsible for acute vomiting in children. It is essential to detect the underlying cause of vomiting. The initial evaluation should be directed at assessment of airway, breathing and circulation, evaluation of hydration status and red flag signs in cases of bilious or bloody vomiting, inconsolable cry or excessive irritability, severe dehydration, altered sensorium, toxic/septic/apprehensive look, concern for symptomatic hypoglycaemia, severe wasting, Bent-over posture, etc. to rule out more severe underlying conditions. 

Management of vomiting includes:

  • treatment of dehydration
  • stoppage of oral fluids/feeds
  • decompression of the stomach with a nasogastric tube (for patients with bilious vomiting)

Low osmolarity ORS may reduce the incidence of vomiting in children with acute gastroenteritis. Most children with vomiting can be managed with regular small sips (5-10 ml) of ORS. 

Antiemetics should be used for children in whom the vomiting is severe, recurrent, and interferes with ORS intake. Ondansetron and Domperidone are the commonly used antiemetics indicated for use in children. Ondansetron, a serotonin antagonist, is approved for the treatment of vomiting in children unable to take orally due to persistent vomiting, postoperative vomiting, chemotherapy-induced vomiting, cyclic vomiting syndrome, and acute mountain sickness. Ondansetron doses recommended in children include:

  • oral- 0.2 mg/kg 
  • parenteral- 0.15 mg/kg
  • maximum- 4 mg 

Domperidone, a dopamine antagonist, is also effective in the management of vomiting. Domperidone is used at a dose of 0.1-0.3 mg/kg/dose.   

Clinical trials reported that Ondansetron is more efficacious than Domperidone in the cessation of vomiting associated with AGE in children aged 3 months to 5 years; no or mild to moderate dehydration is reported in this age group. Ondansetron is thus considered effective for the emergency management of vomiting.[1] 

Other antiemetic drugs used for the management of vomiting in patients with AGE include Promethazine, Prochlorperazine, and Metoclopramide.

Citation

  1. ^ Hanif H, Jaffry H, Jamshed F, et al. Oral Ondansetron versus Domperidone for Acute Gastroenteritis Associated Vomiting in Young Children. Cureus. 2019;11(9):e5639. doi:10.7759/cureus.5639.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6822884/

What is the comparison between the use of antitussives and mucolytics in the management of cough?

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AntitussivesMucolytics
Antitussive drugs act in the central nervous system (CNS) and increase the threshold of the cough centre or act peripherally in the respiratory tract to decrease tussal impulses or both these actions.Mucolytic drugs act on the mucous layer of the respiratory tract to enhance its clearance. These medications break down the polymer bonds within the secretions.
Antitussives are recommended for:dry non-productive cough unduly tiring coughsleep disturbing coughhazardous cough (piles, hernia, cardiac disease, ocular surgery).Mucolytics are recommended to manage mucus hypersecretion and its sequelae like recurrent infection in patients suffering from:cystic fibrosischronic obstructive pulmonary disease (COPD)bronchiectasis.
As per the Clinical Practice Guidelines for Diagnosis and Management of Cough by the Chinese Thoracic Society (CTS) Asthma Consortium- central or peripheral acting antitussive agents are recommended for patients with severe dry cough.As per the Clinical Practice Guidelines for Diagnosis and Management of Cough by the Chinese Thoracic Society (CTS) Asthma Consortium- mucolytics can improve cough in patients with difficulty expectorating sputum. 
As per the Belgian Guidelines, antitussives are contra-indicated in paediatric patients (age < 6 years). Their use is also not recommended in patients between 6 to 12 years.As per the Belgian Guidelines, mucolytics are contra-indicated in patients (age < 2 years). Guaifenesin is contra-indicated in children below 6 years. Mucolytics are also not recommended in children between 6 to 12 years.
According to the Indian guideline, central antitussives are recommended in early onset of whooping cough, haemoptysis and post-surgery, and dry cough with sleep disturbance and pain. Dextromethorphan is the preferred central antitussive drug.[1] Peripheral antitussive – Levodropropizine is recommended in non-productive cough.[1]According to the Indian guideline, mucolytics can be used to facilitate mucus clearance in children with chronic cough.
Codeine is an opioid (antitussive drug) used for the symptomatic treatment of acute cough in children (aged >12 years). However, clinical studies do not substantiate the effectiveness of this drug in the management of acute cough. Moreover, the side effects of Codeine restrict the use of this drug for cold and cough in children younger than 18 years of age.A study in India reported that Dextromethorphan and Codeine are mostly recommended for the management of cough in paediatric patients. The commonly prescribed mucolytics include Bromhexine, Ambroxol, Acetyl cysteine, Carbocysteine.Erdosteine, a mucolytic drug, is used for the treatment of chronic obstructive pulmonary disease. A clinical study tried to determine the effect of Erdosteine used in combination with an antibiotic (Amoxicillin) for the treatment of cough in children. Significant cough reduction was documented in the group treated with Erdosteine and Amoxicillin.Letosteine used at a dose of 25 mg 3 times daily for 10 days in children (age 2 to 12 years) with acute febrile bronchitis was also effective in alleviating acute cough.  Clinical studies claimed that Guaifenesin, another mucolytic drug, was effective in the management of symptoms in children (age 12 years and above) suffering from upper respiratory tract infection.[2]

Citation

  1. a, b Paramesh H, Mohanty NC, Kumar R, Kumar P, Sivabalan S, et al. Airway Disease Education & Expertise (ADEX) NEXT working group recommendations-persistent (Chronic) cough in pediatric practice. Journal of the Pediatrics Association of India. 2017 Oct 1;6(4):230.https://nijp.org/wp-content/uploads/2018/01/v6n4-p230-243.pdf
  2. ^ Marseglia GL, Manti S, Chiappini E, et al. Acute cough in children and adolescents: A systematic review and a practical algorithm by the Italian Society of Pediatric Allergy and Immunology. Allergol Immunopathol (Madr). 2021;49(2):155-169. doi:10.15586/aei.v49i2.45 https://www.all-imm.com/index.php/aei/article/view/45/229#figures

What are the differences among Biguanide, SGLT-2I, GLP-1A, DPP-4I, sulfonylureas, and thiazolidinediones?

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CharacteristicsBiguanidesSodium-glucose cotransporter-2 (SGLT2) inhibitorsGlucagon-like peptide-1 (GLP-1) agonistsDipeptidyl peptidase 4 (DPP- 4) inhibitorsSulfonylureasThiazolidinediones
IndicationsType 2 diabetes mellitusGestational diabetesManagement of antipsychotic-induced weight gainType 2 diabetes preventionPolycystic ovary syndrome (PCOS)Pre-diabetesType 2 diabetes HypertensionCongestive heart failure[1]Non-alcoholic fatty liver disease (NAFLD)ObesityType 2 diabetes ObesityType 2 diabetes Type 2 diabetes Type 2 diabetes Polycystic ovary syndrome (PCOS)Nonalcoholic steatohepatitis (NASH)1
Contraindicationshypersensitivity to the drug.severe renal dysfunction (eGFR less than 30 mL/minute/1.73 m2).metabolic acidosis, including diabetic ketoacidosis.hypersensitivity to the drug.end-stage renal disease (ESRD).patients on dialysis.hypersensitivity to the drugpregnancygastrointestinal diseases, such as gastroparesis and inflammatory bowel disease.a personal or family history significant for multiple endocrine neoplasia 2A, multiple endocrine neoplasia 2B, or medullary thyroid cancerpatients with a history of pancreatitis.Dose adjustment required for Saxagliptin in patients with eGFR < 45 mL/min/1.73 m2 with the dose of 2.5 mg once daily.[2]For Sitagliptin, a low dose of 25 mg daily administered in patients with a creatinine clearance of less than 30 ml/min/1.73 m2 and contraindicated in patients on haemodialysis or peritoneal dialysis. No dose adjustment necessary for Linagliptin.Hypersensitivity to the drug or Sulfonamide derivatives.type 1 diabetes mellitusdiabetic ketoacidosisHypersensitivity to the drug.New York Heart Association Class III or IV heart failure.serious hepatic impairment.bladder cancer.history of macroscopic haematuria.pregnancy
ExamplesMetforminDapagliflozinCanagliflozinExenatideLixisenatideLiraglutideSitagliptinSaxagliptinVildagliptinLinagliptinGlipizideGliclazideGlimepirideRosiglitazonePioglitazone

Citation

  1. ^ Ganesan K, Rana MBM, Sultan S. Oral Hypoglycemic Medications. [Updated 2021 May 15]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. https://www.ncbi.nlm.nih.gov/books/NBK482386/
  2. ^ Collins L, Costello RA. Glucagon-like Peptide-1 Receptor Agonists. [Updated 2021 Jun 25]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. https://www.ncbi.nlm.nih.gov/books/NBK551568/

How to manage heatstroke victims in the emergency department of tertiary care centre?

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Heatstroke is the most serious complication of heat-related illnesses. Early detection and prompt management are essential to avoid fatal consequences. The National Action Plan on heat-related Illnesses is developed by the National Centre for Disease Control, Ministry of Health and Family Welfare, Government of India under the National Programme on Climate Change and Human Health.[1] This guideline outlines the management protocol for heatstroke victims at the tertiary health care centre. The protocol is as follows:

  • Primary triage is essential to confirm the heatstroke.
  • Airway, breathing, and circulation should be reassessed. IV access is ensured. Emergency investigations are conducted.
  • Definitive airway protection should be provided if required.
  • Active cooling measures:
    • All unnecessary clothing needs to be removed (while maintaining the patient’s dignity).
    • The patient should be covered with a thin wet cloth sheet. Alternatively, cool water can be sprayed.
    • Ice packs should be placed at the neck, axillary regions, groin, and head.
    • Mist fan or evaporative method should be employed.
    • Tepid sponging or cool blankets are used if available.
    • Paracetamol or non-steroidal anti-inflammatory drugs (NSAIDs) should be avoided.
    • Gastric lavage must be performed with cold saline.
  • IV fluids should be administered judiciously. Healthcare providers should be cautious about patients’ premorbid status. The development of pulmonary oedema should be checked.
  • Close monitoring of the following is essential:
    • Temperature every 15-30 minutes (should not be less than 38 degrees C)
    • Vital signs (blood pressure/heart rate/SpO2), altered cardiac rhythms (through ECG), altered mental status (through Glasgow Coma Scale/GCS)
    • Complications of treatment like:
      • Acute pulmonary oedema
      • Hypothermia
    • Seizure (should be treated with benzodiazepines)
    • Prevention of shivering (by paralysing patient if intubated)
    • Signs of coagulopathy
    • Regular screening of arterial blood gas (ABG) for metabolic acidosis
    • CT scan of the brain to detect complications or rule out intracranial pathology
  • Management should be continued, and the patient should be referred to the intensive care unit if required.
  • The patient’s relatives should be informed regarding the condition and prognosis of the patient.

Citation

  1. ^ National Action Plan on heat-related Illnesses. National Programme on Climate Change and Human Health, National Centre for Disease Control, Ministry of Health and Family Welfare, Government of India. July 2021.https://ncdc.gov.in/WriteReadData/linkimages/NationActionplanonHeatRelatedIllnesses.pdf