After coexisting with the new coronavirus, do we still need to monitor the virus?

Coexistence with COVID-19 needs to be based on understanding it rather than ignoring it.

Written by Zhou Yebin

On December 25, the National Health Commission issued a statement: "From now on, no daily epidemic information will be released." As large-scale nucleic acid testing has withdrawn from the stage, the number of confirmed cases reported by the authorities based on nucleic acid testing can no longer reflect the actual infection situation. More and more people are diagnosed through antigen self-testing, and many people have symptoms but do not have antigen test kits to come for testing. Some people will also say that most infected people have mild or no symptoms anyway, and they will take cold medicine if they are tested, and they will take cold medicine if they are not tested, so is there any point in testing for the virus?

Some people think that "opening up means lying down" and "no need to care about the existence of the new coronavirus". But this is absolutely not the case. Countries and regions that lifted a large number of epidemic prevention measures before China are still maintaining the detection and epidemic monitoring of the new coronavirus. my country can also learn from their successful practices to avoid being passive in understanding the direction of the epidemic and formulating targeted measures.

1

Coexisting with the virus does not mean ignoring its existence

Although the inherent toxicity of the Omicron virus strain currently prevalent is weaker than some previous strains, and since the vast majority of people in China have been vaccinated, many people who are infected only have mild symptoms or are asymptomatic, so there is no need to be too afraid. However, the threat of Omicron to high-risk groups cannot be underestimated. For example, data from Hong Kong showed that among unvaccinated people over 80 years old, the mortality rate of Omicron infection was still as high as 14.6%, and the mortality rate after three doses of inactivated vaccine was still 2% [1].

From the perspective of protecting high-risk groups, we need to have good monitoring of the new coronavirus infection situation so that we can adjust the prevention and control plan in a targeted manner. In addition, the transmission ability of Omicron is too strong. In the United States, Singapore, Hong Kong, Taiwan and other places, 20-30% of the population were infected in the first wave of Omicron epidemic within two or three months. This situation of a large number of people being infected in a short period of time will also have an impact on the normal operation of society. Now many medical staff in China have been tested positive and insist on working. Necessary monitoring of the infection situation can also enable us to make necessary preparations in various aspects such as medical resource allocation and social services.

In addition, the development of the epidemic means that the virus is also constantly replicating, and each replication of the virus corresponds to the risk of mutation. Today, many people are worried about the risk of secondary infection. Generally speaking, the risk of secondary infection within three months is very low, but once a new mutant with enhanced immune escape appears, the risk of secondary infection will increase significantly. Without testing for the new coronavirus, it is naturally impossible to detect the mutation of the virus, let alone warn and prevent potential new mutants.

2

The amount of nucleic acid testing has decreased. How to judge the trend of the epidemic?

In the past few years, China has used large-scale nucleic acid testing to find almost every case of infection, and further found most of the close contacts, isolated and managed them, and blocked transmission. However, this level of prevention and control will cost extremely high manpower and material resources, and as the number of infections increases, it is becoming increasingly unsustainable. Now that the epidemic has already broken out, it is impossible for us to pursue the use of nucleic acid testing to find every case of infection. However, this does not mean that nucleic acid testing is useless. We can still provide key information on the trend of the epidemic through certain tests.

Nucleic acid testing can provide two pieces of information. One is the number of positive cases. This directly provides information on the infection situation, and it was the only point we focused on before. However, when a certain amount of nucleic acid tests are aggregated, another data can be provided: the "positive detection rate", that is, the number of people tested who are positive. If the same number of nucleic acid tests is done, the more serious the community transmission, the less this amount of testing will be, and the higher the positive detection rate will be.

Combining the number of positive cases with the positive detection rate can provide certain information about the epidemic trend. Insufficient nucleic acid testing is a long-standing problem in many countries, so there is also international experience in adding the positive detection rate to judge the community transmission situation. For example, the community transmission status assessment standard launched by the US CDC combines the number of new cases with the positive detection rate [2]:

U.S. CDC community transmission criteria

The combination of new infections per 100,000 people per week and the nucleic acid positive detection rate, whichever indicator corresponds to a higher risk of transmission, indicates the level of transmission risk. Although routine nucleic acid testing has been withdrawn, there are still certain nucleic acid tests in special places such as hospitals. The testing in these places can be regarded as sampling of local communities to a certain extent. Incorporating the positive detection rate into the epidemic analysis can provide a more accurate trend of the epidemic.

Of course, more and more people may turn to self-testing with antigens. These data are more difficult to compile than nucleic acid tests that are ultimately completed in the laboratory. In this regard, we can refer to Hong Kong and Singapore, both of which provide residents with an online window to report positive antigen test results [3-4]. Although this self-reporting is bound to underestimate the actual number of positive cases, it is still helpful to judge the trend of the epidemic. For example, let's look at the changes in the epidemic in Singapore since 2022 [5]:

Changes in the Omicron epidemic in Singapore

Although the specific number of cases is likely to be underestimated because many antigen-positive cases may not be reported, the overall trend at least reflects the impact of several different Omicron substrains. Such data can help public health departments make better epidemic prevention recommendations, and also allow the public to understand the current situation of the epidemic and do a good job of personal health management.

3

Monitoring the impact of COVID-19 can be done “behind the scenes”

Nucleic acid testing and antigen testing are traditional COVID-19 testing methods, and the data is specific to each individual who takes the test. Even if we provide more extensive testing opportunities and collect as many test results as possible, we will still encounter situations where someone has not taken the test or has not uploaded the antigen test results. As we coexist with COVID-19 for a long time, the motivation for people to take the test may also decrease. Therefore, in addition to these traditional testing methods, we should also consider some more "behind-the-scenes" actions to ensure the integrity of epidemic monitoring.

One approach worth considering is to monitor the novel coronavirus in domestic sewage. For example, the United States has established a National Wastewater Surveillance System (NWSS), and all regions can participate in the NWSS. Currently, there are 1,304 sampling points for monitoring the amount of novel coronavirus in wastewater across the United States[6].

The principle of NWSS is that there will be a certain amount of COVID-19 in the domestic wastewater of COVID-19 infected people (it may just be dead virus, not necessarily contagious). When a community's domestic wastewater is collected at the corresponding wastewater treatment plant, samples can be taken and then the samples can be tested for viral genomes to determine whether COVID-19 is present, what strain it is, and how much virus there is[7]. This is equivalent to monitoring the epidemic situation of the entire community.

If we refer to the current NWSS test results[6], we can find that many monitoring stations show that the number of local COVID-19 cases is increasing. This is equivalent to telling public health departments that the COVID-19 outbreak is not slowing down, but that there is a lack of testing when personal testing is reduced.

NWSS COVID-19 surveillance results

When the epidemic develops to a certain stage, we may pay more attention to the extent to which the medical system is affected by the new crown, rather than just the number of infected cases. In this regard, we can refer to the current US CDC new crown community risk index [8]:

CDC COVID-19 Community Risk Indicators

These indicators can show how many new COVID-19 hospitalizations are added to hospitals when new cases increase, and what proportion of beds are occupied by COVID-19 patients? These data combined can better reflect the impact of the disease burden of the epidemic on society, and can also reflect the pressure on the medical system in a specific region.

4

Monitoring COVID-19 mutations is critical

After coexisting with the new coronavirus, detecting the new coronavirus requires not only understanding the epidemic trend and the pressure on the medical system, but also monitoring the changes in the new coronavirus itself, that is, the evolution of mutant strains.

In the three years since the outbreak of the COVID-19 pandemic, major changes in the direction of the epidemic have been accompanied by the emergence of new mutants. At the end of 2020, the emergence of the Alpha mutant accelerated the spread of the COVID-19 around the world; in the summer of 2021, the emergence of Delta brought a new peak of the epidemic; and then at the end of 2021, the emergence of Omicron changed the direction of the epidemic. Even though the entire 2022 was caused by Omicron, the changes in various substrains within Omicron also brought repeated outbreaks in different regions.

For example, in the changes in the epidemic in Singapore that we have seen before, from BA.1 to BA.5 to XBB, the three peaks correspond to three Omicron substrains. The immune escape ability of these three substrains continues to increase. BA.5 has immune escape from BA.1, and XBB can escape from BA.5 to a certain extent. This difference in immune escape has led to the rise of the next Omicron substrain after the previous Omicron substrain epidemic has come to an end.

It can be said that understanding the evolution of COVID-19 mutants during the epidemic is extremely important for us to predict the trend of the epidemic. The rapid changes of the Omicron substrain make it even more important to monitor the viral genome in a timely manner. For example, the mainstream Omicron substrain in the United States has changed almost every 3-4 months this year, which is significantly faster than the previous Alpha Delta dominance for half a year [9]:

Figure: Evolution of mainstream coronavirus strains in the United States

Therefore, on the basis of detecting the new coronavirus, we also need to sample the test samples and select a sample size sufficient to represent the current epidemic situation in various places to conduct full genome sequencing of the virus in order to identify the virus strain.

As the domestic epidemic develops, tracking the viral genome will become increasingly important because it is also related to the confirmation of the effectiveness of vaccines and therapeutic drugs. For example, the increasingly mainstream virus strains BQ.1 and XBB abroad have made all the monoclonal antibody drugs on the market ineffective, which fully demonstrates that understanding the current popular virus strains is directly related to the choice of therapeutic drugs.

At the press conference of the Joint Prevention and Control Mechanism of the State Council on December 20, experts from the CDC stated that China is establishing a national SARS-CoV-2 genome database. According to the “Work Plan for Monitoring Variants of SARS-CoV-2 in the Chinese Population”, each province is required to select three cities, each city to select one sentinel hospital, and each sentinel hospital to collect samples from 15 outpatient and emergency cases, 10 severe cases, and all deaths per week for genome sequencing and analysis, and upload the sequencing data within one week to establish a national SARS-CoV-2 genome database[10].

This is a very important step, but judging from the amount of testing, it is probably far from being representative of the actual virus strains in the country. First of all, this sampling method will be concentrated in the central hospitals of large cities, and cannot represent small and medium-sized cities, let alone towns and rural areas. Secondly, excluding deaths, there are only 25 sequencing cases per hospital per week, and 75 cases per province. This is a very small amount for the national epidemic. Nowadays, rumors about various mutant strains are constantly circulating on the Internet. For example, the virus strain in the north is more serious than that in the south, and there is even speculation that some infections are Delta. If there is perfect viral genome monitoring, these rumors that may cause panic can also be avoided.

The standard set by the United States in early 2021 is to sequence 5% of confirmed cases[11]. In California, 15% and 13% of COVID-19 cases were sequenced in September and October 2022, respectively[12]. Considering that a large number of infected cases will not be reported, only by sequencing the whole genome of a higher proportion of nucleic acid test samples can there be enough data to represent the actual prevalence of the current virus strain.

The new coronavirus genome monitoring we need should be able to reflect the proportion of various virus strains currently prevalent in the country and also have a certain predictive function. Referring to the changes in the new coronavirus strains in the United States summarized by the US CDC [13], we can see that the highest proportions in the United States are BQ.1 and BQ.1.1, but XBB is also rising, and the proportion may further expand in the future. BA.1, which previously dominated the mainstream, is already a minority and will further decline. At the same time, BA.4.6 and BF.7 did not gain an advantage in the competition with BQ.1 and BQ.1.1. This information will help us judge the future trend of the epidemic and determine which drugs will be affected in terms of effectiveness.

Changes in the U.S. Coronavirus Strains

Coexisting with the new coronavirus is not our own choice, but an inevitable reality. But coexistence does not mean that the new coronavirus is no longer a virus that threatens our health. After all, Omicron has only reduced its pathogenicity and has not become a probiotic. Therefore, from many perspectives, such as understanding the trend of the epidemic, formulating corresponding prevention and control plans, and facilitating people to make self-prevention judgments, we need to continue to monitor the new coronavirus and be more accurate in the release of relevant data. In addition, considering the extremely fast mutation rate of the new coronavirus, this monitoring also needs to have a certain "depth" to detect changes in the virus strain in a timely manner.

In short, coexistence with COVID-19 is based on understanding it rather than ignoring it, and continuous and effective monitoring of COVID-19 is the cornerstone of this understanding.

References

[1] https://www.covidvaccine.gov.hk/pdf/death_analysis.pdf

[2] https://www.cdc.gov/coronavirus/2019-ncov/science/science-briefs/indicators-monitoring-community-levels.html

[3] https://www.chp.gov.hk/ratp/#

[4] https://www.sync.gov.sg/

[5] https://www.moh.gov.sg/covid-19/statistics

[6] https://covid.cdc.gov/covid-data-tracker/#wastewater-surveillance

[7] https://www.cdc.gov/healthywater/surveillance/wastewater-surveillance/wastewater-surveillance.html#how-wastewater-surveillance-works

[8] https://www.cdc.gov/coronavirus/2019-ncov/science/science-briefs/indicators-monitoring-community-levels.html

[9] https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2022-09-01/07-COVID-Swanson-508.pdf

[10] http://wsjkw.hebei.gov.cn/html/zwyw/20221221/392832.html

[11] https://www.science.org/content/article/us-rushes-fill-void-viral-sequencing-worrisome-coronavirus-variants-spread

[12] https://www.cdph.ca.gov/Programs/CID/DCDC/Pages/COVID-19/COVID-Variants.aspx

[13] https://covid.cdc.gov/covid-data-tracker/#variant-proportions

Produced by: Science Popularization China

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