With input from Dr Monica Vasudev

1226: Nearly half of Singapore’s migrant workers, i.e., 152,000 individuals, were infected with the coronavirus this year, states new government data. The rest of the population recorded less than 4,000 cases. (Source: NY Times)

1227: Colchicine in patients with stable coronary artery disease: For patients with chronic coronary disease receiving other secondary preventive strategies, colchicine 0.5 mg (or 0.6 mg) daily should be added to the medical regimen (Grade 2B).

Chronic inflammation is a risk factor for coronary artery disease events, such as myocardial infarction, and colchicine is known to have anti-inflammatory effects.

In the LoDoCo2 trial, more than 5500 patients with chronic coronary disease were randomized to receive 0.5 mg of colchicine once a day or placebo. After a median follow-up of around two and half years, those receiving colchicine had a decreased risk of myocardial infarction (3.0 versus 4.2 percent) and ischemia-driven coronary artery revascularization (4.9 versus 6.4 percent) in comparison with the control group. Treatment was well tolerated except for a small increase in myalgias.

Uptodate suggests adding colchicine 0.5 mg (or 0.6 mg) once daily to other secondary preventive strategies in patients with stable coronary artery disease. 

Trial

The LoDoCo2 trial randomly assigned 5522 patients, 85% men, with chronic coronary disease to 0.5 mg of colchicine once per day or placebo.

After a median follow-up of around two and half years, the risk of MI was 30% lower in the colchicine group (3.0 versus 4.2 percent), and there was a 25% lower risk of ischemia-driven coronary artery revascularization (4.9 versus 6.4 percent).

The difference between the two groups in the risk of death from any cause (2.6 versus 2.2 percent, respectively) was insignificant. Except for a somewhat greater rate of myalgia with colchicine (21.2 versus 18.5 percent), no other significant adverse events were seen. 

 (Source: UpToDate; N Engl J Med. 2020;383(19):1838. Epub 2020 Aug 31.)

1228: Effect of colchicine on hs-CRP

1. Among patients with stable CAD, raised levels of biomarkers of inflammation, including high-sensitivity C-reactive protein (hs-CRP) > 2.0 mg/L, predict future vascular events.
2. Long-term low-dose colchicine is safe and effective for dampening inflammation.
3. An open-label pilot study evaluated whether colchicine could significantly lower hs-CRP in patients with stable CAD having hs-CRP was > 2.0 mg/L, despite taking both aspirin and high-dose atorvastatin therapy.
4. Plasma hs-CRP level was measured in 200 patients with clinically stable coronary artery disease taking aspirin and atorvastatin.
5. In 64 patients, hs-CRP was > 2.0 mg/L.
6. In 20 of these patients, hs-CRP was measured again at 2 weeks (no treatment group), and in 44 patients, hs-CRP was measured again after 4 weeks of colchicine 0.5 mg twice daily (treatment group).
7. In the no treatment group, mean baseline hs-CRP did not decrease significantly, (4.28 +/- 2.03 mg/L at baseline and 3.70 +/- 2.30 mg/L after repeated measurement;mean change 11.0%).
8. hs-CRP appeared to decrease in all patients given colchicine treatment (mean baseline hs-CRP decreasing from 4.58 +/- 2.05 to 1.78 +/- 1.38 mg/L (p <0.001), absolute decrease of 2.80 mg/L and a relative decrease of 60%).
9. In 28 patients (64%) in this group, the decrease in hs-CRP was >50% from baseline, and in 31 patients (70%), hs-CRP decreased to <2.0 mg/L.
10. There were no significant side effects.

Low-dose colchicine (0.5 mg twice daily) has the potential to effectively decrease hs-CRP in patients with clinically stable coronary artery disease and increased hs-CRP independent of aspirin and atorvastatin use.

(Source: American Journal of Cardiology 2007; 99(6):805-7) 

1229: Colchicine is an anti-inflammatory drug, indicated for the treatment of pericarditis or gout.In the COLCOT trial, 4745 patients with MI within 30 days who were receiving optimal medical therapy were randomized to colchicine 0.5 mg daily or placebo

After a median follow-up of about two years, the risk of primary composite endpoint (death from cardiovascular causes, resuscitated cardiac arrest, MI, stoke, or urgent hospitalization for angina leading to coronary revascularization) was found to be lower in the colchicine group.

 This result was largely guided by lower risks of angina and stroke. Adverse events were generally similar in the two groups.

While the results of COLCOT appear promising, treatment with colchicine is not given on account of the absence of improvement in hard endpoints such as cardiovascular death or MI and a relatively high discontinuation rate (about 18.5% in both groups). (Source: N Engl J Med. 2019;381(26):2497.) 

1230:  In non ICU patients, day 2 blood sugar of over 250 or less than 70 associated with poor outcomes in patients with COVID-19:  Both hyperglycemia and hypoglycemia were found to be associated with poor outcomes in patients with COVID-19, in a study published in Diabetes Care.

An analysis of 1,544 patients with COVID-19 from 91 hospitals in 12 states revealed that glucose level at admission was a robust predictor of death among the 360 patients directly admitted to ICU and severe hyperglycemia after admission strongly predicted death among the 1,184 patients admitted to a non-ICU setting. Of the patients, 279 (18.1%) died in the hospital. The mortality for ICU patients (31%) appeared to be nearly twice that in non-ICU patients (16%).

Among non-ICU patients, severe hyperglycemia (blood glucose >250 mg/dL]) on days 2 to 3 had an independent association with high mortality compared with patients with blood glucose <140 mg/dL. This relationship was not significant for admission glucose.

In patients who were admitted directly to the ICU, severe hyperglycemia on admission was tied to increased mortality. This relationship was not significant on day 2. Hypoglycemia (blood glucose <70 mg/dL) was also found to be linked with increased mortality.

(Reference: https://care.diabetesjournals.org/content/diacare/early/2020/12/08/dc20-1857.full.pdf SOURCE: Diabetes Care)

1231: Are Old Vaccines Helpful Against COVID-19?

Vaccines stimulate broad, innate immune response, which plays a vital role in fighting COVID-19. Can this approach bridge the time until entire populations are vaccinated, particularly against SARS-CoV-2?

Three vaccines are dominating the discussion -

1. BCG has been tied to milder courses of infection for respiratory syncytial virus, human papillomavirus, herpes simplex, and influenza. Fifteen clinical trials are evaluating it for COVID-19; however, a drawback is the 1% rate of adverse events.
2. OPV has also been associated with milder infections for decades. It decreases the morbidity from influenza 3.8-fold.
3. MMR drew the focus in the spring when 955 sailors aboard the U.S.S. Roosevelt tested positive for COVID-19, while only one was hospitalized. As recruits routinely receive MMR, re-vaccination of others might prevent the fatal inflammation of COVID-19.

A virus that enters the body comes across the complex cascade of defensive proteins that make up innate immunity. This includes cytokines, present in mucosal sites in the lungs, nose, and genitals, and that recruit immune cells. Complement proteins also kill the viruses. Being non-specific responses, theyre called innate. Cells of innate immunity include macrophages, neutrophils, and natural killer cells, and the epithelial and endothelial cells that interface the circulation. If innate immunity is unable to contain an infection, the adaptive immune system starts work: T cells, B cells, and antibodies bring specificity and memory. Adaptive immunity also hikes cytokine and complement secretion.

A cytokine storm is the turn to the dark side of the innate response.

An RNA virus delays interferon (a cytokine) production, blocks signals, and escapes natural killer cells, and replicates explosively until it invades the bloodstream. A wave of inflammation goes through linings and lymphoid tissues as the adaptive response pours out more cytokines. This scenario would not happen if the innate immune system is trained to make interferon early and get ahead of the virus. It will recruit cells to clear the damage so that the adaptive immunity isnt kicked into overdrive. The virus will be controlled, or at least slowed, and the patient will be better.

Children have a strong innate immune system because they dont have pre-existing antibodies and T cells, because they havent seen the pathogens. Children have enough innate response to SARS-CoV-2 even if viral loads in the nose are high. But they dont get as sick with respect to the respiratory tract, developing pneumonia.  Innate immunity is even intact in MIS-C (multisystem inflammatory syndrome in children), which points to a delayed impairment of adaptive immunity.

(Source: Medpage Today)

Dr KK Aggarwal

President CMAAO, HCFI and Past National President IMA