People are feeling more and more anxious as we see news coverage of COVID-19 pneumonia taking away the lives of celebrities or of many severely ill patients connected to ventilators. As I wrote in a previous post in this section before, reports indicate that children tend to remain in a relatively mild condition (although severe cases among infants have been reported), while adults can develop a severe condition including the younger generation, even in their 20s. At the same time, asymptomatic cases have been reported where people are infected but do not develop symptoms at all.

Then, what is the proportion of asymptomatic infections among adults, or those who overcome the virus without developing symptoms at all? Learning about the subclinical cases among adults may help in preventing children's infections.

Different countries are taking different measures to combat SARS-CoV-2, something which is provoking wide international debate. The current internal and external criticism leveled against Japan is the insufficient number of PCR tests. Japan was also criticized for the measures taken against infection within the cruise ship docked at Yokohama port, in Kanagawa Prefecture. The accurate data of the behavioral pattern, symptoms, and results of PCR tests collected from the numerous passengers on this cruise ship is now attracting attention from researchers throughout the world as quite precious material in the study of public health.

One of them is the answer to the question about the percentage of subclinical cases among the infected.

Asymptomatic patients do not exhibit symptoms even though they test positive in PCR tests. However, that alone does not determine they are truly asymptomatic. They may not display symptoms at first, but there is a high degree of possibility they are in the incubation period, which means they may become symptomatic in anything from a few days to two weeks. Asymptomatic infection can only be confirmed when they do not develop symptoms after the two-week incubation period after testing positive in PCR tests.

Since asymptomatic patients do not exhibit symptoms, the only way to find out is to conduct PCR tests on people without symptoms or conduct a blood test to find antibodies to SARS-CoV-2. Furthermore, you need to test numerous people without symptoms after the SARS-CoV-2 infection has ended--i.e. no new patients with symptoms or PCR test positive patients are found for a certain period, such as a longer period than the incubation period--to ascertain the proportion of asymptomatic patients infected with the virus among those who exhibit no symptoms.

Suppose the SARS-CoV-2 infection ended in an area (country). Residents in the area (country) can then be categorized into one of the following for SARS-CoV-2 infection.

1. Deceased
2. Recovered after developing symptoms of fever, cough, pneumonia, etc. (symptomatic patient)
3. Recovered without developing any symptoms (asymptomatic patient)
4. Uninfected

It is easy to find 1 and 2, but you cannot distinguish between 3 and 4 even if you conduct PCR tests after the epidemic ends because both of them would test negative. In order to tell them apart, you need to regularly give PCR tests on everyone before the epidemic ends or conduct antibody tests. Asymptomatic patients would have a high degree of antibody titer. The intention of specialists insisting on performing PCR tests on those not exhibiting symptoms, is to gain information about the infection in addition to isolating asymptomatic patients and those who are in the incubation period. But in order to do so, you must give PCR tests on everyone in the area (country) or conduct a large number of random PCR tests. What's more, as no country or area has yet defeated the SARS-CoV-2 infection, it is impossible to figure out the proportion of asymptomatic infection at this point. Currently there is a plan in the United States to conduct antibody tests on the asymptomatic population. The purpose is to ascertain the proportion of asymptomatic infection cases.

However, there was one single place in the world where the proportion of asymptomatic infection could reliably be ascertained--the cruise ship that was anchored at Yokohama Port.

Almost all the passengers on board received PCR tests, including some who were tested multiple times. Of course, clinical symptoms such as fever and pneumonia were recorded in detail. The passengers were allowed to leave the ship only after no new infected patients were confirmed. So, the SARS-CoV-2 infection on board has ended. A group of researchers noticed the importance of such records and succeeded in ascertaining the proportion of asymptomatic infection cases by data analysis.

Skipping the precise details of the research method, 3,063 PCR tests were given to 3,711 passengers and crew on the ship, of which 634 tested positive. In addition, 306 developed symptoms of fever, cough and pneumonia, etc. by February 21 when the quarantine period ended. The total of asymptomatic cases at the time of intermediate counting, conducted six times, was 320. This 320 is the total of those who exhibited no symptoms until the end and those who developed symptoms later. The estimated total of truly asymptomatic patients is 113 judged by the incubation period, etc., or 17.9% of those who tested positive in PCR tests. Many passengers on the cruise ship were in their 60s to 70s, so you cannot directly apply the results to any particular area or country. Moreover, the conditions related to the spread of SARS-CoV-2 infection vary among countries or areas. That said, a rough percentage of asymptomatic infection of COVID-19 in an area or a country was obtained for the first time in the world.

This proportion of asymptomatic cases is a quite useful item of data for measures against SARS-CoV-2 infection in the future. For example, if 10,000 people exhibit COVID-19 symptom(s), in an area or a country, it means that in reality there are about 12,195 (10,000÷(1.00-0.179) infected cases. Some claim there are several times more COVID-19 patients than those reported, but that number is based on speculation and has no scientific grounding.

Another important fact emerging from this research was that the majority of people were infected before the quarantine started on February 5, judging by the onset of symptoms in the infected patients. So the criticism from some infectious disease experts, that the infection prevention system on board after quarantine was insufficient, is in fact groundless.

Regrettably, the outbreak of COVID-19 on the cruise ship claimed the lives of 12 passengers. Still, it provided useful and precious data for measures to deal with any future pandemic.

Reference:

• Mizumoto Kenji, Kagaya Katsushi, Zarebski Alexander, Chowell Gerardo. Estimating the asymptomatic proportion of coronavirus disease 2019 (COVID-19) cases on board the Diamond Princess cruise ship, Yokohama, Japan, 2020. Euro Surveill. 2020;25(10):pii=2000180.
  https://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2020.25.10.2000180