Establishing Prognosis and Outcomes of Novel Coronavirus

What is the case fatality rate (CFR) of Novel Coronavirus infection?

A key indicator of the severity of disease caused by SARS-CoV-2 is CFR, calculated by dividing the number of deaths by the number of confirmed cases (1). Cases can either constitute 'closed' cases (recovered or deceased) or total cases (all ongoing) which each introduce different biases (2). According to the latest COVID-19 data published by the WHO, the current estimated CFR is 4.4% (as of 14th July). 

CFR varies between different countries, being affected by the availability of tests, criteria for testing, reporting on death certificates, delivery of healthcare, public health measures and demographics of the population.  All of these, and other factors, will introduce biases and true differences accounting for variability (1).

Additionally, it has been noted in other pandemics that CFR tends to get lower over time as the most serious cases are noted at the beginning (2).

What about the infection fatality rate (IFR) in COVID-19?

This includes unreported, asymptomatic and unconfirmed cases, meaning it is less subject to selection bias of severe presentations. IFR can be indicated from seroprevalence studies, which tend to indicate much lower fatality rates of <1%.  A useful case study of IFR is the Diamond Princess Cruise ship, an isolated and tested population, which had an IFR of 0.85% (1).

What does this mean for prognosis of individual COVID-19 patients?

Of course, these are overall figures for populations. An individuals risk of fatality will depend on factors including their age, co-morbidities, smoking status, sex and ethnicity (1). Again, numbers vary from study to study and country to country.

Chinese CDC reported mortality varied by age from 0·2% for those 11–19 years, to 14·8% for those ≥80 years, as well as sex differences (2·8% for men vs 1·7% for women) (3).

The most common cause of death in COVID-19 is ARDS. Multi-organ failure, myocardial damage and renal and hepatic dysfunction are other adverse effects associated with cases of COVID-19 mortality. Critical care patients have around a 50% mortality (1,4).  Mechanically ventilated patients from a series of 5700 in New York had an 88% mortality (5).  Figures from other regions have been lower. Read a summary of Outcomes in Intensive Care Admissions throughout England, Wales and Northern Ireland.

What is known is that the following factors provided by Fowler, Fletcher and Beeching are associated with higher morbidity and mortality in COVID-19 (1):


Adverse prognostic indicators:

Demographic

  • Over 65 years old

  • Male

  • Smoker

  • Comorbidity: hypertension, diabetes, cardiovascular or cerebrovascular disease, respiratory disease, obesity

Signs and symptoms

  • Breathlessness

  • Low oxygen

Blood results

  • Low lymphocyte count

  • High white cell count

  • Low platelets

  • Ratio of neutrophils to lymphocytes raised

  • Hypoalbuminaemia

  • High blood glucose

  • Renal or hepatic dysfunction

  • High lactate dehydrogenase

  • Raised inflammatory markers (C-reactive protein, procalcitonin)

  • High cardiac troponin I

  • High D-dimer

  • High serum amyloid A

  • Low CD3+, CD4+, or CD8+ T cells

  • High interleukin-6

Existing Scores

  • Elevated Sequential Organ Failure Assessment (SOFA) or Acute Physiology and Chronic Health Evaluation II (APACHE II) score.

What about published predictive models?

Many new models for predicting risk of hospital admission and prognosis in COVID-19 exist in the literature. However, a recent systematic review found high levels of researcher bias in these models, meaning that their predicted accuracy is likely to be overestimated.  The review cautioned the use of such models, which could potentially be detrimental, until they have been correctly evaluated (6).

References

1. Fowler R, Fletcher TE, Beeching NJ. BMJ Best Practice: Coronavirusdisease 2019 (COVID-19), Follow-up, Prognosis. [Online] Available from: https://bestpractice.bmj.com/topics/en-gb/3000168/prognosis [Accessed 9.6.20]

2. Spychalski P, Błażyńska-Spychalska A, Kobiela J. Estimating case fatality rates of COVID-19. Lancet, March 2020. [epub ahead of print] https://doi.org/10.1016/S1473-3099(20)30246-2

3. Ruan S. Likelihood of survival of coronavirus disease 2019. Lancet, 20 (6); 630-631. [epub ahead of print] https://doi.org/10.1016/S1473-3099(20)30257-7

4. ICNARC. ICNARC report on COVID-19 in critical care 27 March 2020. Available from: https://www.icnarc.org/About/Latest-News/2020/03/27/Report-On-775-Patients-Critically-Ill-With-Covid-19 [Acessed 30.3.20]

5. Richardson, Safiya et al. “Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area.” JAMA, 323 (20) 2052–2059. 22 Apr. 2020, doi:10.1001/jama.2020.6775

6. Wynants, Laure et al. “Prediction models for diagnosis and prognosis of covid-19 infection: systematic review and critical appraisal.” BMJ (Clinical research ed.) 369, 1328. 7 Apr. 2020, doi:10.1136/bmj.m1328

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