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Monday, April 13, 2020

COVID-19 Study Predicts Lockdown Is Difficult to Remove Safely

By Peter M. Goodwin

However attractive a prompt return to "business as usual" may seem for countries in the grip of the global pandemic of COVID-19, this may turn out to be advisable only by adopting strict measures that are guided by stringent and difficult-to-meet criteria.

"Without herd immunity against COVID-19, cases could easily resurge as businesses, factory operations, and schools gradually resume and increase social mixing—particularly given the increasing risk of imported cases from overseas as COVID-19 continues to spread globally," said Joseph T. Wu BS, PhD, FFPH, Professor of Epidemiology and Biostatistics at the University of Hong Kong who co-led the research reported in The Lancet (2020;

Wu said the stringent control measures adopted in China appeared to have reduced the number of infections to very low levels. But the study forecast that achieving a return to normal life could be fraught with difficulties.

Transmissibility Below 1.0

The research model incorporated data on transmissibility of the virus, as measured by the reproductive number (the average number of secondary cases of infection generated by each person primarily infected) in China since the outbreak of the pandemic. A number less than 1.0 implied that the epidemic had receded, whereas a reproductive number greater than 1.0 implied that it was still growing.

"Although control policies such as physical distancing and behavioral change are likely to be maintained for some time, proactively striking a balance between resuming economic activities and keeping the reproductive number below one is likely to be the best strategy until effective vaccines become widely available," noted Wu.

By simulating the impact of relaxing current control measures, the study found that premature lifting of these interventions could lead to transmissibility exceeding 1.0 again, resulting in a second wave of infection. 

Delicately Balanced Approach

To avoid a resurgence of case numbers, the researchers concluded there needed to be a delicately balanced approach to withdrawal from lockdown—involving real-time monitoring of COVID-19 transmissibility and severity—so as to "fine-tune" control strategies and offer the best chance to minimize a second wave of infection in mainland China, outside Hubei province—and by implication in any country affected by the pandemic.

Although the initial outbreak seemed to have been contained in China by the reduction of social interactions plus isolation of cases (identified by reverse transcriptase polymerase chain reaction (RT-PCR) testing for the viral genome), there remained a risk of a second wave of the pandemic, which threatened to be harder to contain, the researchers warned.


Fatality Rates Variability

The study found a six-fold difference in the "case fatality rate" (the probability of dying faced by patients with confirmed COVID-19) between different regions of China. Outside Hubei, the fatality rate was 0.98 percent, but in Hubei 5.91 percent of patients infected went on to die. There was a big variation between different provinces that appeared to be associated with economic development and the availability of health care resources. Fatality ranged from 0 percent in prosperous regions like Jiangsu to 1.76 percent in less developed provinces such as Henan.

The pandemic could potentially swamp the "surge capacity" of health services everywhere. "Even in the most prosperous and well-resourced megacities like Beijing and Shanghai, health care resources are finite and services will struggle with a sudden increase in demand," said senior author Gabriel M. Leung, MD, FRCP, Dean of Medicine, Professor in Population Health and Chair of Public Health Medicine at the University of Hong Kong. "Our findings highlight the importance of ensuring that local health care systems have adequate staffing and resources to minimize COVID-related deaths."

Study Details

The study analyzed local Health Commission data of confirmed COVID-19 cases between mid-January and February 29, 2020, to estimate the transmissibility and severity of COVID-19 in four big cities (Beijing, Shanghai, Shenzhen, Wenzhou) and the 10 provinces outside Hubei with the highest number of confirmed COVID-19 cases. The number of new daily imported and local cases was used to assess epidemic dynamics for each location and incorporated in the modeling to calculate weekly reproduction numbers. The research also modeled the potential impact of relaxing control measures after the first wave of infection. 

The implication was that in regions outside Hubei, control measures should only be lifted gradually so that the resulting reproductive number did not exceed 1.0. The model suggested that, once elevated, simply tightening control interventions again could not reduce the burden back to its original level, and would require extra effort to drive the reproductive number below 1.0 to revert to the pre-relaxation level.

"We are acutely aware that, as economic activity increases across China in the coming weeks, local or imported infection could lead to a resurgence of transmission," said co-lead author Kathy Leung, PhD, MPhil, BS, Research Assistant Professor in Epidemiology and Biostatistics at the University of Hong Kong. "Real-time monitoring of the effect of increased mobility and social mixing on COVID-19 transmissibility could allow policymakers to fine tune control measures to interrupt transmission and minimize the impact of a possible second wave of infections," she said.

Factors Affecting Fatality, Risk

In a linked comment to the study reported in The Lancet, Shunqing Xu, MD, PhD, from the School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan in China wrote that case fatality rate (CFR) had been one of the important unknowns of COVID-19.

"Leung and colleagues found the confirmed CFR was correlated with provincial per capita gross domestic product and the availability of hospital beds per 10,000. In Wuhan, the CFR was up to 5.08 percent by March 28, 2020. The remarkable difference in the CFR between these locations and Wuhan might be attributed to the difference in the degrees of health care capacity. Therefore, consideration should be given to the variations in health care capacity when implementing interventions."

The study investigators wrote of their concern that cases of COVID-19 in China—and by implication anywhere—could increase exponentially if the transmissibility of the virus (as measured by the reproductive number) rose above 1.0 in the wake of relaxation of lockdown epidemic mitigation measures.

"The findings from our modeling impact assessment suggest that the comprehensive package of non-pharmaceutical interventions China undertook, including social distancing and population behavioral change, has substantially reduced transmissibility of COVID-19 across the country. The daily number of local COVID-19 cases has dropped substantially to nearly zero in areas outside Hubei since late February."

But they insisted that a second wave of COVID-19 transmission could overtake China because of viral reintroduction, particularly from other countries where cases had been exponentially increasing since March 2020. It was also likely that viral transmissibility might rebound with the gradual resumption of economic activities leading to normal levels of social mixing.

"Close monitoring of the instantaneous effective reproduction number and real-time tuning of policy interventions to ensure a manageable second wave remains the overriding public health priority," the researchers concluded.

They warned that early detection of cases was essential. They reported that Guangdong province did more than 320,000 RT-PCR tests on patients who had attended fever clinics and hospitals over 30 days between January and February 2020: about 10 times baseline testing capacity for routine influenza-like illness surveillance during the influenza season of 2018. "Such a level of testing should be maintained, if not increased, to monitor the real-time point prevalence of COVID-19, so that any possible reintroduction of infected cases could be swiftly identified and isolated, and their contacts traced and quarantined."

The study authors stated that proactively striking a balance between resuming economic activities and keeping the reproductive number below 1.0 was likely to be the optimal strategy until effective vaccines became widely available, and that control policies—including social distancing, behavioral change, and public awareness—would probably need to be maintained for "some time."

They concluded that, although the interventions China implemented in response to the COVID-19 outbreak had a real and dramatic effect on interrupting transmission in all areas outside of Hubei, vigilance was needed. Real-time assessment (by monitoring the instantaneous effective reproduction number as economic activity continued to resume) was necessary to allow policymakers to "tune" relaxation decisions to keep transmissibility below the self-sustaining threshold of 1.0.

Peter M. Goodwin is a contributing writer.