China had 232k coronavirus cases in first wave, four times more than official count: Study
At least 232,000 people may have been infected in the first wave of coronavirus pandemic in China, which is four times the official figure, according to a new study. While China officially reported at least 55,000 cases as of February 20, researchers say that the true number would have been higher if the definition of a COVID-19 case that was later used had been applied from the start of the outbreak.
According to a research team, the case definition was initially narrow and was gradually broadened to allow detection of more cases as knowledge increased, particularly milder cases and those without epidemiological links to Wuhan, China, or other known cases. Experts say the narrow case definition at the start of the pandemic likely resulted in the inability to detect ongoing community transmission for weeks before it was first reported.
The team says that changes in case definitions or laboratory testing capacity should be accounted for when analyzing an epidemic curve. "In China, broadening the case definitions over time allowed a greater proportion of infections to be detected as cases. These changes should be taken into account when making inferences on epidemic growth rates and doubling times, and therefore on the reproductive number, to avoid bias," says the research team from the WHO Collaborating Centre for Infectious Disease Epidemiology and Control, School of Public Health, Li Ka Shing Faculty of Medicine and The University of Hong Kong.
The analysis, published in The Lancet, comes at a time when many countries, including the US, suspect that the number of people who have taken ill and have died in the COVID-19 pandemic could be much higher in China than what is being officially reported.
Case definitions changed 7 times
When a new infectious disease emerges, appropriate case definitions are important for clinical diagnosis and public health surveillance. Tracking case numbers over time is important to establish the speed of spread and the effectiveness of interventions. Accordingly, the researchers wanted to evaluate whether changes in case definitions affected inferences on the transmission dynamics of COVID-19 in China.
The research team found that from January 15 to March 3, seven versions of the case definition for COVID-19 were issued by the National Health Commission in China. Before January 15, the researchers were unable to identify the case definition that was used in Wuhan to recognize the earliest 41 confirmed cases.
The first national guideline for diagnosis and treatment was issued on January 15 and required six specific criteria to be met for a patient to be a confirmed case of COVID-19.
Notably, patients needed to have an epidemiological link to Wuhan or a wet market in Wuhan and had to fulfill four clinical conditions indicative of viral pneumonia to be identified as suspected cases. They then had to have a respiratory specimen tested by full genome sequencing showing a "close homology with SARS-CoV-2 for the final confirmation of COVID-19". In the following days and weeks, several revisions were made to the case definitions, allowing gradually greater sensitivity in the criteria required for case confirmation, the analysis shows.
"The second edition of the case definitions removed the requirement for the failure of antibiotic treatment to identify suspected cases and allowed PCR confirmation in addition to whole-genome sequencing. There was no change in case definitions in the third edition, but classifications of severe and critical cases were modified and clarified. The fourth edition allowed patients to have an epidemiological link to other areas with reported cases, instead of being restricted to Wuhan, and suspected cases required only two, instead of all three, types of clinical manifestations in addition to an epidemiological link," says the study.
The greatest change was in the fifth edition, which introduced a new category of cases (that is, clinically confirmed cases), specifically for Hubei province, which was the epicenter of the outbreak and had the largest number of cases identified in the country. Here, clinically confirmed cases were patients that met clinical criteria and had radiological evidence of pneumonia with or without a certain epidemiological link but did not need to have a virological confirmation of infection.
In the sixth edition, this criterion for the diagnosis of clinically confirmed cases was removed and no distinction was made between cases inside or outside Hubei province. In the seventh edition, serology was added as an additional option for laboratory confirmation, says the team.
The results
The researchers found that the changes in case definitions had a clear and substantial effect on the proportion of infections that were identified and counted as confirmed cases, and therefore also had a considerable effect on the epidemic curve.
As of February 20, there were 55,508 confirmed cases in China, among which 27,000 were from Wuhan, 16,000 were from the rest of Hubei province and 13,000 were from the rest of China, official numbers show.
The researchers estimated that when the case definitions were changed, the proportion of infections being detected as cases increased by 7.1 times from version 1 to 2, 2.8 times from version 2 to 4, and 4.2 times from version 4 to 5. "If the fifth version of the case definition had been applied throughout the outbreak with sufficient testing capacity, we estimated that by February 20, there would have been 232,000 confirmed cases in China as opposed to the 55,508," says the team in their findings published in the Lancet.
Of these 232,000 estimated cases, 127,000 cases were from Wuhan, 55,000 were from the rest of Hubei province excluding Wuhan, and 50,000 were from the rest of China, excluding Hubei, shows the analysis.
The researchers, however, say that the number of individuals who were infected is likely to be greater than 232,000 because many mild cases were not tested or confirmed, and some infections were asymptomatic. "The true number of infections could still be higher than that currently estimated considering the possibility of under-detection of some infections, particularly those that were mild and asymptomatic, even under the broadest case definitions," says the team.
As of April 26, China's National Health Commission had received reports of 82,830 confirmed cases and 4,633 deaths, according to the April 27 update from the Commission.