Epidemiology and clinical characteristics

Update March 2021 – what’s new?

 Updated figures for asymptomatic patients, pre-symptomatic patients, and infection
fatality ratio.

The mean incubation period for COVID-19 is 4-5 days. Patients may be infectious for 2-3 days
prior to the onset of symptoms however.

The strongest risk factor for severe disease is advanced age. Other risk factors include
cardiopulmonary comorbidities, obesity, HIV, and diabetes mellitus.

The spectrum of COVID-19 clinical presentations includes asymptomatic infection, a respiratory

tract infection that may range from mild to severe, and atypical manifestations such as
diarrhoea, skin manifestations, hyperglycaemic syndromes and large vessel strokes.

SARS-CoV-2 is a betacoronavirus closely related to SARS-CoV and MERS-CoV. It is an enveloped, non-

segmented, positive sense RNA virus. It is thought to have originated in bats but the animal
responsible for transmission to humans remains unknown.

Epidemiology
The median incubation period for COVID-19 is estimated to be 4-5 days, with an interquartile range of
2-7 days. Based on patients’ viral shedding patterns and on epidemiological modelling, patients appear
to be infectious for 2-3 days prior to the onset of symptoms, and the contribution of pre-symptomatic
infections to the overall pandemic may be substantial.1-7 The basic reproductive number for the virus
is approximately 2.2 (meaning that on average each person spread the infection to two others).8 A
male preponderance of cases has been noted globally both in terms of absolute case numbers, and in
severe disease.9-11 Risk factors for severe disease include older age, cardiopulmonary comorbidities,
obesity, HIV, and diabetes mellitus. Very few cases which required hospitalisation have been reported
among children under the age of 15 years (~1%).

Clinical characteristics – what to look for

Truly asymptomatic COVID-19 patients (as distinguished from pre-symptomatic patients) comprise
approximately 20% of COVID-19 cases.12-14 Around half the patients who are asymptomatic at the time
of diagnosis are actually pre-symptomatic however.15,16 Among symptomatic patients in China, 81%
developed mild disease, an estimated 14% developed severe disease (with hypoxaemia, marked
tachypnoea and extensive lung infiltrates), while 5% became critically ill (with respiratory failure,
septic shock and/or multiorgan dysfunction).17 Because of the strong effect of age on disease severity,
the proportions of mild, severe, and critical cases seen in a country will partially depend on that
country’s population age structure.

The most common presenting symptom has been fever in approximately 90%, but importantly this
may only be present in a minority of patients on admission.11,18 A cough is present in two-thirds of
patients, but sputum production is only reported by one third of patients, as is dyspnoea. Myalgia, a
sore throat, nausea, vomiting, and diarrhoea are all present in less than one fifth of cases. 11,18,19
Anosmia (loss of sense of smell) and dysgeusia (alteration of the sense of taste) have also emerged as
relatively common, early, and moderately specific symptoms.20,21 Atypical manifestations are
increasingly being recognised, including large vessel strokes in young patients, diabetic
ketoacidosis/hyperglycaemic hyperosmolar syndrome, unexplained abdominal pain and various
dermatological manifestations.22,23

Abnormalities are visible on chest X-ray in at least 60% of hospitalised COVID-19 patients, with chest
CT scans being more sensitive.11,18,24 These are typically bilateral patchy ground glass opacities, though
other patterns have been described.11,25 However, a normal chest X-ray or chest CT scan does not rule
out COVID-19. This is especially true of patients with mild disease, in whom a majority of chest X-rays
may be normal.26

Outcomes and prognosis

The vast majority of cases will make a full recovery, although this may take several weeks, particularly
in severe cases. In a minority of cases, COVID-19 has been associated with rapid progression to acute
respiratory distress syndrome (ARDS), multiple organ failure and sometimes death. Internationally,
the case fatality ratio has ranged between 0.7-7%, and is partially determined by the particular
population’s age distribution, the pandemic’s burden on the healthcare system at the time, and the
extent to which mild or asymptomatic cases are diagnosed.9,27 The infection fatality ratio (which
includes both asymptomatic and symptomatic patients) is estimated at around 0.8% overall, though
again there is substantial age-related variability, from <1 per 10,000 cases in those less than 30 years
to 12% in those over 80 years of age.28 Full recovery from COVID-19 may take several weeks, and in a
minority, symptoms can persist for >1 month (now often referred to as “long-COVID”, see module 11).
A multisystem inflammatory syndrome resembling Kawasaki disease has also been described,
occurring almost exclusively in patients aged <21 years (“MIS-C syndrome”), and typically appearing
2-3 weeks after the primary infection.29

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