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RSSDI 28 March 2020
Introduction
The coronavirus has derived it’s name because of resemblance of its shape to a crown or solar corona when imaged using an electron microscope.
The three deadly human respiratory coronaviruses so far:
People with diabetes do face a higher chance of experiencing serious complications from COVID-19:
In general, people with diabetes are more likely to experience severe symptoms and complications when infected with a virus. If diabetes is well-managed, the risk of getting severely sick from COVID-19 is about the same as the general population.
When people with diabetes do not manage their diabetes well and experience fluctuating blood sugars, they are generally at risk for a number of diabetes-related complications. Having heart disease or other complications in addition to diabetes could worsen the chance of getting seriously ill from COVID-19, like other viral infections, because your body’s ability to fight off an infection is compromised. But if glucose control is poor, severity of viral illness and risk of complications will increase because of impairment of immunity.
Viral infections can also increase inflammation, or tissue oedema in people with diabetes. This is also caused byabove-target blood sugars, and both could contribute to more severe complications.
People with diabetes do face an increased risk of DKA (diabetic ketoacidosis) and or Hypoglycemia. DKA is commonly experienced by people with type 1 diabetes.
COVID-19 risk for people with type 1 versus type 2 diabetes:
Terms | Definitions |
SARI | An ARI with history of fever or measured temperature ≥38 C° and cough; onset within the last~10 days; and requiring hospitalization. |
Surveillance case definitions for SARI | 1. SARI in a person, with history of fever and cough requiring admission to hospital, with no other etiology that fully explains the clinical presentation1 (clinicians should also be alert to the possibility of atypical presentations in patients who are immune-compromised); and any of the following: a) A history of international travel in 14 days prior to symptom onset; or b) the disease occurs in a health care worker who has been working in an environment where patients with severe acute respiratory infections are being cared for, without regard to place of residence or history of travel; or c) the person develops an unusual or unexpected clinical course, especially sudden deteriora- tion despite appropriate treatment, without regard to place of residence or history of travel, even if another etiology has been identified that fully explains the clinical presentation 2. A person with acute respiratory illness of any degree of severity who, within 14 days before onset of illness, had any of the following exposures: a) close physical contact with a confirmed case of COVID - 19 infection, while that patient was symptomatic; or b) a healthcare facility in a country where hospital-associated COVID - 19 infections have been reported |
Uncomplicated illness | Patients with uncomplicated upper respiratory tract viral infection, may have non-specific symptoms such as fever, cough, sore throat, nasal congestion, malaise, headache. The elderly and immunosuppressed may present with atypical symptoms. These patients do not have any signs of dehydration, sepsis or shortness of breath. |
Mild pneumonia | Patient with pneumonia and no signs of severe pneumonia. Child with non-severe pneumonia has cough or difficulty in breathing/ fast breathing: (fast breathing - in breaths/min): |
When should a Diabetologist suspect COVID-19?
Cold | Flu | Corona Virus | |
Time between catching the virus and beginning to show symptoms | 1-3 days | 1-4 days | 2-14 days |
Symptom onset | Gradual | Abrupt | Gradual |
How long do symptoms last | 7-12 days | 3-7 days | Mild cases: approx 2 weeks.Severe or critical disease: 3-6 weeks |
Fever | Sometimes | Common | Common |
Runny nose | Common | Sometimes | Less Common |
Sore throat | Common Sometimes Less Common | Sometimes | Less Common |
Cough | Common | Sometimes | Common |
Body Ache | Rare; if occurs mild | Common | Less Common |
Difficulty breathing | Rare | Rare | Common |
In adults, emergency warning signs include:
How to implement infection prevention and control measures for patients with suspected or confirmed COVID - 19 infection:
1) At triage:
2) Apply droplet precautions:
Precautions to be taken in diabetics:
Investigations:
Laboratory Markers In COVID-19 Patients:
Most Frequent:
In SEVERE COVID-19:
Specimen collection:
Responsibilities:
Selection of patient:
Specimen labelling and processing:
Specimen type | Collection materials | Transport to laboratory | Storage till testing | Comment |
Nasopharyngeal and oropharyngeal | swab Dacron or polyester flocked swabs* | 4 °C | ≤5 days: 4 °C>5 days: -70 °C | The nasopharyngeal and oropharyngeal swabs should be placed in the same tube to increase the viral load. |
Bronchoalveolarlavage | sterile container* | 4 °C | ≤48 hours: 4 °C>48 hours: –70 °C | There may be some dilution of pathogen, but still a worthwhile specimen |
Tracheal aspirate, nasopharyngeal aspirate or nasal wash | sterile container* | 4 °C | ≤48 hours: 4 °C>48 hours: –70 °C | Not applicable |
Sputum | sterile container* | 4 °C | ≤48 hours: 4 °C>48 hours: –70 °C | Ensure the material is from the lower respiratory tract |
Tissue from biopsy or autopsy including from lung | sterile container with saline | 4 °C | ≤24 hours: 4 °C>24 hours: –70 °C | Autopsy sample collection preferably to be avoided |
Serum (2 samples - acute and convalescent) | Serum separator tubes (adults: collect 3-5 ml whole blood) | 4 °C | ≤5 days: 4 °C >5days: –70 °C | Collect paired samples:• acute – first week of illness• convalescent - 2 to 3 weeks later |
*For transport of samples for viral detection, use VTM (viral transport medium) containing antifungal and antibiotic supplements. Avoid repeated freezing and thawing of specimens.
Treatment:
Drugs | Types | Mechanisms of action | Past evidences |
Chloroquine | 4-aminoquinoline | Not clearly known, changes the pH of endosomes and believed to prevent viral entry, transport and post-entry events | Inhibits infection of cells by SARS-CoV-2 in vitro, approved for malaria treatment and prophylaxis |
Hydroxychloroquine | 4-aminoquinoline | Not clearly known, changes the pH of endosomes and believed to prevent viral entry, transport and post-entry events | Inhibits infection of cells by SARS-CoV-2 in vitro, approved for malaria prophylaxis and autoimmune disease (e.g. rheumatic diseases). Approved for treatment of T2DM in India |
Remdesivir | Adenosine nucleotide analogues | Inhibits viral application | Effective against SARS and MERS |
Ribavirin | Nucleoside analogue | Inhibits viral RNA synthesis and mRNA capping | No evidence in SARS (potential harm) and MERS |
Ribavirin plus Interferon | Inhibits viral replication | Mixed result against MERS | |
Camostat Mesilate | Protease inhibitors | Blocks viral maturation andentry to cells | Effectively blocked SARS-CoV-2 in lung cells in vitro |
Lopinavir/Ritonavir | Protease inhibitors | Blocks viral cellular entry | Effective against SARS-CoV-1 both in vitro and human studies, approved for HIV-1 treatment |
Darunavir/Cobicistat | Protease inhibitors | Blocks viral cellular entry | Established anti-HIV medication. No activity against coronavirus- es or other respiratory viruses. No in vitro or clinical data |
Favipiravir | RNA polymerase inhibitors | Inhibits viral RNA-dependent polymerase | Broad-spectrum anti-viral- against influenza, arenavirus, bunyavirus and filovirus |
Umifenovir | Fusion inhibitor | Inhibits fusion between viral and cellular membrane | Antiviral against other Corona viruses |
Interferon-ß1 | Cytokines | Stimulate innate antiviral immunity | MERS-CoV appears to be more sensitive than SARS-CoV in vitro studies. Anti-MERS-CoV action noted in animal studies. |
Interferon beta plusLopinavir/Ritonavir | Interferon beta inhibits viral replication | Ongoing study for SARS-Cov-2 and MIRACLE trial for MERS | |
Aerosolized interferon α | Cytokines | Stimulate innate antiviral immunity | Case report suggested benefit in MERS |
Oseltamivir | Neuraminidase inhibitor | Inhibits viral replication | No effect in SARS in vitro studies. No evidence in SARS and MERS |
Baloxivir marboxil | Viral endonuclease inhibitor | Inhibits influenza virus multiplication | Approved for uncomplicated influenza only. Oral route. |
Tocilizumab, Sarilumab Eculizumab | Monoclonal antibody | IL-6 inhibitor, blocks cytokine storm. | No data on SARS or MERS. Tocilizumab reduced fever and oxygen requirement inCOVID-19, approved for rheumatoid arthritis. |
SARS-Cov-2 specific protease drug candidate | Protease inhibitors | Blocks viral infectivity | No data available |
SARS-Cov-2 specificantibodies | Antibody | Binds to virus and block infection, binds to infected cells and change the immune system | Inhibits SARS-CoV-2 entry into cells in vitro |
SARS- severe acute respiratory syndrome, MERS- Middle-East respiratory syndrome, HIV- Human Immunodeficiency syndrome, T2DM – type 2 diabetes, COVID-19- Corona virus disease 19.
As of 21/03/20, the following guidelines10 have been recommended by various centres and organisation
Study/Guidelines/Country | Dose (adults) |
Expert consensus from Department of Science and Technology and Health Commission of Guangdong province, China21 | Chloroquine phosphate 500 mg BID for 10 days. |
Central Clinical Task Force, Korea22 | Moderate to severe COVID-19: Lopinavir 400mg/Ritonavir 100mg BID or Chloroquine 500mg orally per day or Hydroxychloroquine 400mg orally per day for 7-10 days |
Centre for Disease Control and Prevention, Atlanta, MICC Version 1 (March 12, 2020)23 | URTI plus positive PCR: • Chloroquine phosphate 500 mg BID for 5 days. • Oseltamivir 150 mg BID for 5 days. COVID-19 Pneumonia: • Chloroquine phosphate 500 mg BID for 5 days plus Darunavir 800 mg/Cobicistat 150 mgOD for 2 weeks. • Atazanavir 400 mg OD for 2 weeks plus Oseltamivir 150 mg BID for 5 days. |
The Dutch Center of Disease Control24 | 600 mg of Chloroquine base followed by 300 mg after 12 h on day 1, then 300 mg × 2/day per person on days 2-5. |
Italian Society of Infectious and Tropical Diseases (Lombardy Section)25 | Mild to moderate COVID-19: Lopinavir/ritonavir plus Chloroquine 500 mg × 2/day or Hydroxychloroquine 200 mg perday for 10 days. Severe or critical COVID-19: Remdesivir plus Chloroquine 500 mg × 2/day or Hydroxychloroquine 200 mg per day for10-20 days. |
Mount Sinai Health System, Canada26 | Mild to moderate COVID-19: Hydroxychloroquine 400 mg BID x 2 doses then 12 hours later start 400 mg OD for 5-10 days. |
Surviving Sepsis Campaign, The Society of Critical Care Medicine and the European Society of Intensive Care Medicine.27 | Insufficient evidence to issue a recommendation on the use of chloroquine or hydroxychloroquine in critically ill adults with COVID-19 at this point of time. |
Clinical guidance for patients with suspected or confirmed COVID-19 in Belgium28 | Mild/Moderate/Severe COVID-19: Hydroxychloroquine 400 mg at diagnosis, 400 mg 12 hour later, followed by 200 mg BID for 5 days, |
Or, Chloroquine 600 mg at diagnosis and 300 mg 12 hour later followed by 300 mg BID for 5 days (Consider lopinavir 400 mg/ritonavir 100 mg BID for 14 days as a second choice only if HCQ and chloroquine is contraindicated, provided it can be administered within 10 days after onset of symptoms) Critical COVID-19: Remdesivir 200 mg loading dose i.v within 30 minutes followed by 100 mg OD for 2-10 days (Hydroxychloroquine is second option if Remdesivir is unavailable) | |
Clinical guidance for patients with suspected or confirmed COVID-19 in Netherland28 | Mild/moderate/severe COVID-19: Chloroquine 600 mg on day 1, then 300 mg BID for 5 days (lopinavir/ritonavir as second option) Critical COVID-19: Remdesivir for 10 days plus chloroquine for 5 day |
Gautret et al, Marseille, France19 | Hydroxychloroquine 200 mg TID for 10 days. |
OD- once daily, BID- twice daily, TID- thrice daily, URTI- upper respiratory tract infection, PCR- polymerase chain reaction, i.v - intravenous
Is there a role for Chemoprophylaxis? The following data is available
Other data available based on experimental and 2 human studies10
Timing of intervention | Proposed |
Chemoprophylaxis | • No conclusive evidence so far; however, chloroquine or HCQ could be researched as a prophylactic agent in endemic areas. Recent guidelines from Indian Council of Medical Research recommend it as a prophylactic agent (see reference 42 for indication and dose). • Note: HCQ can be used as an adjunct to control glycemia in adult patients with type 2 diabetes (approved for treatment in India). However, role of such adjunctive treatment for testing its potential role as prophylaxis of COVID-19 in diabetes has not been researched but could be attempted (in view of above) considering a higher mortality in patients with diabetes, as compared to non-diabetic subjects with COVID-19. |
Confirmed COVID-19 | A. Chloroquine phosphate: @$
B. Hydroxychloroquine: @$ Loading dose: 400 mg BID day 1, then Maintenance dose: 200 mg BID for 5-10 days. C. Monitor and watch for side effects* |
@ watch for hypoglycemia in diabetes especially with concurrent use of lopinavir/ritonavir,
$ should not be used concurrently with lopinavir/ritonavir and remdisivir due to increased QTc prolongation,
*complete blood count, renal, hepatic profile and ECG – watch for QTc prolongation, URTI- upper respiratory tract infection, LRTI- lower respiratory tract infection, HCQ- hydroxychloroquine, BID – twice daily
Administration of Lopinavir/ Ritonavir:**
Administration of Lopinavir/ Ritonavir to be considered in Laboratory confirmed cases of COVID – 19 when the following criteria are met:
** It should be noted however, that a recent RCT conducted with Lopinavir/Ritonavir failed to show any benefit in 199 case of COVID-19and drug was stopped at day 13 due to adverse events.11
NOTE: A large fast-tracked pragmatic open-label RCT (n=3200) is already underway named SOLIDARITY trial on behalf of WHO comparing standard of care head-on with 4 drug (HCQ vs. Remdesivir vs. Lopinavir/Ritonavir vs. Lopinavir/Ritonavir plus Interferon Beta) and is expected to report its result within a month. This trial expected to be a final nail in the coffin to show which drug is most effective against COVID-19.12
Drugs to be avoided in COVID-19:
Status of Vaccination
“ Let’s keep our hopes alive and our attitude positive!
Remember, even the darkest clouds have a silver lining.”
The complete document is available on www.rssdi.in
This document has been prepared by experts from Research Society for
Study of Diabetes in India (RSSDI)
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