Risk factors for severe disease - Revision history

Bosmana at 14:47, 6 April 2020

2020-04-06T14:47:20Z

Bosmana at 14:24, 3 April 2020

2020-04-03T14:24:47Z

Bosmana: /* What is already known */

2020-04-03T14:13:38Z

‎What is already known

Bosmana: /* Rumours about interaction with medicines */

2020-04-03T14:11:29Z

‎Rumours about interaction with medicines

Bosmana: /* Analysis and interpretation */

2020-03-22T15:54:31Z

‎Analysis and interpretation

Bosmana: /* Consequences for action */

2020-03-22T15:50:22Z

‎Consequences for action

Bosmana: /* Analysis and interpretation */

2020-03-22T15:47:28Z

‎Analysis and interpretation

Bosmana: /* Analysis and interpretation */

2020-03-22T15:45:11Z

‎Analysis and interpretation

Bosmana at 15:24, 22 March 2020

2020-03-22T15:24:01Z

Bosmana: /* Observations */

2020-03-22T14:55:25Z

‎Observations

← Older revision		Revision as of 14:47, 6 April 2020
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	* Relevant evidence based guidance can be found at the [https://www.cebm.net/covid-19/ Oxford COVID-19 Evidence Service].		* Relevant evidence based guidance can be found at the [https://www.cebm.net/covid-19/ Oxford COVID-19 Evidence Service].
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		+	=Infectious Dose=
		+	==What is already known==
		+	* The evidence suggests an association of viral dose with the severity of the disease. However, the evidence of the relationship is limited by the poor quality of many of the studies, the retrospective nature of the studies, small sample sizes and the potential problem with selection bias. <Ref>SARS-CoV-2 viral load and the severity of COVID-19. The Centre for Evidence-Based Medicine (CEBM) Oxford. March 26, 2020. </ref>
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		+	==Observations==
		+	==Analysis and interpretation==
		+	==Consequences for Action==
		+

	=Discussions about 'replaced mortality'=		=Discussions about 'replaced mortality'=

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 * Additional studies to find supporting evidence (or refuting) are needed for both topics (ACE-inhibitors and Ibuprofen)
 * Clinicians should take note of the study of Fang et al., and make decisions on a case by case basis
 =References=

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 =What is already known=
 * Case fatality of COVID19 increases with age. This is a consistent observation world wide.
-−
 {| class="wikitable"
 ! Age-group (years)
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 |}
 Table 1: Current estimates of the severity of cases. The IFR estimates from Verity et al. have been adjusted to account for a non-uniform attack rate giving an overall IFR of 0.9% (95% credible interval 0.4%-1.4%). Hospitalisation estimates from Verity et al. were also adjusted in this way and scaled to match expected rates in the oldest age-group (80+ years) in a GB/US context. <ref name="Ferguson">Ferguson, Neil M., et al. "Impact of non-pharmaceutical interventions (NPIs) to reduce COVID-19 mortality and healthcare demand."</ref>
 =Discussions about 'replaced mortality'=

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 =Rumours about interaction with medicines=
 ==Observations==
 *  Recent studies suggest that ACE2 expression is increased in diabetes and treatment with ACE inhibitors and ARBs increases ACE2 expression. Consequently, the increased expression of ACE2 would facilitate infection with COVID-19. This observation makes some researchers hypothesize that diabetes and hypertension treatment with ACE2-stimulating drugs increases the risk of developing severe and fatal COVID-19. <ref name="Fang2020">Fang, Lei, George Karakiulakis, and Michael Roth. "Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection?." The Lancet Respiratory Medicine (2020).</ref>
 * "Ibuprofen should not be used for managing symptoms", say some doctors. <Ref name="Day17-0302020">Michael Day. Covid-19: ibuprofen should not be used for managing symptoms, say doctors and scientists BMJ 2020;368:m1086 doi:10.1136/bmj.m1086 (Published 17 March 2020)</ref>
-* In the Netherlands, rumors circulate (and are even discussed at National Television) that Ibuprofen and NSAID in general increase the rik of severe COVID19 disease outcome.
+* In the Netherlands, rumours circulate (and are even discussed at National Television) that Ibuprofen and NSAID in general increase the risk of severe COVID19 disease outcome.
-* In Greece, the same rumors have led to a shortage of paracetamol in the pharmacies. The representative of the Ministry of Health said that there is not enough evidence thus it would be good when people have symptoms to prefer paracetamol.
+* In Greece, the same rumours have led to a shortage of paracetamol in the pharmacies. The representative of the Ministry of Health said that there is not enough evidence thus it would be good when people have symptoms to prefer paracetamol.
 ==Analysis and interpretation==
 * The study of Fang et al. is relevant and credible. However, the study alone does not (yet) constitute convincing evidence that ACE2-inhibitors are risk factors for COVID19 and severe outcome. The association is plausible, yet requires more study to generate supporting evidence.
 * Notwithstanding the above, it is important to take note of the study of Fang et al. The observation deserves consideration, especially by clinicians treating patients who are in known risk groups for severe COVID19
-* The news item in the BMJ by Michael Day on Ibuprofen, seems to support the rumors that are observed in some countries. This is still at the level of case reports and observations, without explanatory study results.
+* The news item in the BMJ by Michael Day on Ibuprofen, seems to support the rumours that are observed in some countries. This is still at the level of case reports and observations, without explanatory study results.
 * After the news item in BMJ by Michael Day, the WHO places an announcement that they have no indication to recommend against ibuprofen.

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 ==Analysis and interpretation==
 * The Spiegelhalter blog uses the table of Ferguson et al (see Table 1 above), and interprets this (erroneously) as COVID19 mortality.
-** Case fatality is a risk percentage: risk of death ''due to a disease'' per 100 patients (no specific time period). Mortality is rate: the risk of death per population (usually 100k or 1M) ''over a certain period of time'''''Bold text''' (usually 12 months). Comparing both directly is like comparing apples and chewing gum. The only similarity between the two, is that you can put it in your mouth.
+** Case fatality is a risk percentage: risk of death ''due to a disease'' per 100 patients (no specific time period). Mortality is rate: the risk of death per population (usually 100k or 1M) '''''over a certain period of time''''' (usually 12 months). Comparing both directly is like comparing apples and chewing gum. The only similarity between the two, is that you can put it in your mouth.
 ** Better comparison would be to look at the case fatality RATE (that is, the percentage of COVID19 patients dying of COVID19 over a certail period of time. Let's say 1 month.) and compare that with the age-specific mortality rate in the general population over the same time period (so 1 month, not 12).
 ** If we do that, we get the following table:

← Older revision		Revision as of 15:50, 22 March 2020
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	==Consequences for action==		==Consequences for action==
		+	* Blogs such as that of Spiegelhalter must be contradicted clear and widely, in order to avoid that the misconception takes hold that COVID19 mortality is simply replacing regular age-specific mortality. The suggestion that 'these old and weak people would have died anyway' is completely against everything we currently know about COVID19, and must be refuted before it settles in the minds of some decision makers.

	=Rumours about interaction with medicines=		=Rumours about interaction with medicines=

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 ==Consequences for action==