Undetected Cases Speed COVID-19 Spread and a Potential Second Wave

submerged iceberg

Professor of Biostatistics and Statistics Xihong Lin along with a team of scientists from Huazhong Science and Technology University in Wuhan, including the co-corresponding author Chaolong Wang, a former Biostats postdoctoral fellow, recently published a paper in the journal Nature that suggests that about 87%  of virus infections went undetected in Wuhan. Moreover, the study found that undetected infections — from sources including people who were asymptomatic or had only mild symptoms — likely played a substantial role in the fast spread of COVID-19, and may lead to a high chance of resurgence if all control measures are lifted after reopening.

The paper builds on the researchers’ earlier work, released on a preprint server in early March and published in the journal JAMA in April. With the new study, researchers decided to look at the full transmission dynamics of the virus in Wuhan to better understand how easily the virus spreads, the number of undetected cases, their effects during an outbreak, the efficacy of containment measures, and the chance of resurgence when reopening by lifting control measures.

The researchers examined 32,583 laboratory-confirmed coronavirus cases from Dec. 8, 2019, until March 8, 2020. They divided the dates into five time periods based on key events and interventions, such as the implementation of mandatory centralized isolations and quarantines of people infected or suspected of being infected.

Using statistical and epidemiological modeling to reconstruct the outbreak, the team found that transmission rates during the earliest period in the absence of intervention could have been as high as 3.54 infections per single case. The multi-faceted interventions implemented at the time successfully controlled the outbreak by reducing the effective reproduction number to 0.27 by March 8.

The study showed the virus is highly covert and that about 87 percent of cases in the city during the study period may have gone undetected. Many of these undetected/unascertained cases were likely to be asymptomatic and mildly symptomatic, suggesting that the detected cases are the tip of the iceberg. The stringent interventions that were implemented by the city helped block the transmission by these undetected asymptomatic and mildly symptomatic cases.

Their results of the study were consistent with several serological studies in Wuhan, US and other parts of the world, including the CDC serological study in 10 sites, which found the total numbers of COVID-19 cases were likely 6 to 24 times higher than were reported using the PCR test. The two features of COVID-19: high transmissibility and high covertness makes combat COVID-19 much more challenging compared to SARS and MERS.

In the paper, the scientists also used their model to predict the likelihood of a second wave of infections if all restrictions are lifted 14 days after the first day on which no cases are reported. In this case they found a 97 percent chance of resurgence that would likely begin around day 34, owing largely to undetected infections.

In discussing the implications of the study, the researchers suggest that undetected transmission could become one of the leading factors for a possible second wave of infections if restrictions are lifted too early, and emphasize the effectiveness of vigorous and multifaceted containment efforts such as wearing face masks, social distancing, and quarantining close contacts.

According to Lin “Even though they are undetected, they are still infectious. It’s important to avoid reopening too early without vigilant control measures, because when the number of detected cases is not low, the numbers of undetected cases, or unascertained cases, are not low either. They are even bigger.”

For more on the study results and methodology, see the recent review on the research in the Harvard Gazette.