Coronavirus disease (COVID-19) technical guidance by WHO Investigation protocol for COVID-19 | Page 4

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Background
The detection and spread of an emerging respiratory pathogen are accompanied by uncertainty over
the key epidemiological and serologic characteristics of the novel pathogen and particularly its
ability to spread in the human population and its virulence (case-severity). This is the case for the
COVID-19 virus, first detected in Wuhan city, China in December 2019 (1).
To date initial surveillance has focused primarily on patients with severe disease, and, as such, the
full spectrum of the disease, including the extent and fraction of mild or asymptomatic infections
that do not require medical attention are not clear. Estimates of the case fatality ratio, and other
epidemiological parameters, will likely be lower than current crude mortality estimates once the full
spectrum of disease is able to be included in the denominator. In addition, the role of asymptomatic
or subclinical infections in human-to-human transmission of COVID-19 virus is not well understood
and it is not yet clear whether those who are reported as asymptomatic may be able to transmit the
virus to other individuals.
With a novel coronavirus, initial seroprevalence in the population is assumed to be negligible due to
the virus being novel in origin. Therefore, surveillance of antibody seropositivity in a population can
allow inferences to be made about the extent of infection and about the cumulative incidence of
infection in the population.
The following protocol has been designed to investigate the extent of infection, as determined by
seropositivity in the general population, in any country in which COVID-19 virus infection has been
reported. Each country may need to tailor some aspects of this protocol to align with public health,
laboratory and clinical systems, according to capacity, availability of resources and cultural
appropriateness. However, using a standardized protocol such as this one below, epidemiological
exposure data and biological samples can be systematically collected and shared rapidly in a format
that can be easily aggregated, tabulated and analyzed across many different settings globally for
timely estimates of COVID-19 virus infection severity and attack rates, as well as to inform public
health responses and policy decisions. This is particularly important in the context of a novel
respiratory pathogen, such as COVID-19 virus.
Comments for the user’s consideration are provided in purple text throughout the document as the
user may need to modify methods slightly because of the local context in which this study will be
carried out.
1.1 Objectives
There are two primary objectives for this seroepidemiological investigation:
1. To determine the extent of infection in the general population and age-specific infection
cumulative incidence, as determined by seropositivity
2. To determine the fraction of asymptomatic or subclinical infections
Seroepidemiological investigations provide the opportunity to evaluate secondary objectives, such
as, but not limited to:
1. To determine risk factors for infection by comparing the exposures of infected and non-
infected individuals
2. To more accurately determine the case fatality ratio
COMMENT: Little is currently known about COVID-19 virus antibody kinetics. Asymptomatic infected
persons may clear the virus more quickly than do symptomatic patients and antibody titers in the
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