H1N1 and Norovirus also have "COVID-19 sequelae"? Will it become more terrible?

The influenza A and norovirus viruses that have recently caused some schools to close have actually existed in human society for thousands of years. After the COVID-19 pandemic, their epidemic manifestations will be temporarily different from the past, but they will eventually return to normal. In the past, we were able to coexist with these common infectious diseases, and in the future, we are likely to coexist at a lower cost.

Written by Zhou Yebin

Recently, schools in many places have suspended classes or adopted online teaching measures because some students were infected with the new coronavirus or influenza. Having just experienced the peak of the new coronavirus epidemic, many people are still in fear and are more wary of various infectious diseases, worrying about whether a second wave of the new coronavirus epidemic will come or whether other viruses will impact our lives.

In fact, there are many infectious diseases that have existed in our lives for a long time, and COVID-19 will probably join them and become a common disease that we coexist with. In the post-COVID era, which is gradually emerging from the pandemic, we should not only pay attention to the possibility that some infectious diseases that have been ignored in the past few years may reappear, but also look rationally at the actual risks of various common viruses and take reasonable but not excessive response measures.

1

Human society has always coexisted with pathogens

Three years after the COVID-19 outbreak, the general public has developed a very deep impression of the word "virus", and even fear of it. Therefore, when hearing that a child in a school has been infected with influenza A or that there is an outbreak of norovirus in a certain place, many people feel a chill on their backs, fearing that a new epidemic is coming. In fact, human society has been coexisting with many common pathogens, including influenza A and norovirus, which have been in the news recently. They are common pathogens and can be regarded as our long-term "companions". These viruses may sound unfamiliar, but when it comes to common symptoms, such as suddenly catching a "severe cold" in winter or having diarrhea due to "eating bad things", most people have similar experiences in their lives. We don't take these "minor illnesses" too seriously, but if we really want to dig up the root of the problem, these "minor illnesses" are likely to be the viruses that have been in the news recently and made us worried.

The full name of H1N1 is influenza A virus. There are many types of influenza A viruses, some of which mainly infect birds or other mammals. For example, the H5N1 that has been spreading around the world since the end of the 20th century is a highly pathogenic avian influenza that mainly infects birds. It is also classified as influenza A virus. But the influenza A reported in the news that the children were infected with refers to the seasonal influenza A. That is, the influenza virus that has existed in our society for a long time, is more prevalent in winter, and has formed seasonal characteristics.

Seasonal influenza viruses are mainly caused by two influenza A strains, H1N1 and H3N2, and two influenza B strains, Victoria and Yamagata. Generally speaking, influenza A is the mainstream of seasonal influenza, but the proportion of influenza B in children is generally slightly higher than that in adults. The specific prevalent virus strains also change each year. But in general, it is normal to see a large number of influenza A cases in winter. For example, the U.S. Centers for Disease Control and Prevention (CDC) estimates that from 2010 to 2020, seasonal influenza will cause symptomatic illnesses ranging from 9 million to 40 million cases each year, which can be said to be very common [1].

Another virus that has been in the news recently is the norovirus, which is the most common pathogen causing infectious gastroenteritis[2]. The symptoms caused by the norovirus are also known as winter vomiting disease abroad, reflecting its tendency to break out in cold weather. Another common respiratory infectious disease that also likes to appear in winter is the respiratory syncytial virus (RSV), and the symptoms are often similar to the common cold.

It is not difficult to see that many viruses seem to regard winter as a comfort zone. This is actually related to the behavioral patterns of their hosts, that is, us humans. In cold seasons, we spend more time indoors, which gives these viruses more opportunities to spread and easily cause outbreaks. This is true for respiratory viruses such as influenza and RSV. Even those that cause gastroenteritis, such as norovirus, are mainly transmitted from person to person, such as through aerosols after the infected person vomits. Therefore, outbreaks are more likely to occur in winter when more people gather.

2

In the post-COVID era, common infectious diseases are also emerging from the epidemic

Many people may find it strange that experts often say that infectious diseases such as influenza A are common, but we haven’t heard of them in recent years. What’s going on?

First, many common infectious disease viruses have been ignored by us for a long time. This can be seen from the history of the discovery of some viruses. For example, RSV virus was not discovered by scientists until 1956. At first, it was named "chimpanzee upper respiratory pathogen" because it was found in chimpanzees. Later, scientists realized that this respiratory virus infection was extremely common in the human population. Almost everyone was infected before the age of three. Those infected chimpanzees were infected by the breeders. Therefore, it was renamed "human respiratory syncytial virus" [3]. The same is true for Norovirus. It was named after an outbreak in an elementary school in Norwalk, Ohio, USA in 1968. In fact, a similar outbreak was also recorded in Denmark in the 1930s. From the genome analysis of different strains, several strains had parted ways one or two thousand years BC. These viruses may have been with us before human civilization [4].

It can be seen that some viruses that have existed in human society for a long time have also been ignored by us, and it is normal that the general public has not heard of them. Even seasonal influenza, an infectious disease that causes a large number of hospitalizations and even deaths every year, is likely to be confused with a cold by people who pay less attention to infectious diseases or public health. However, after the COVID-19 pandemic, the public has a profound experience of the threat of infectious diseases, and the media will report more cases of various infectious diseases, which naturally gives people the feeling that there are suddenly more viruses.

Secondly, we should also note that as human society gradually emerges from the shadow of the COVID-19 pandemic, some common infectious diseases are also "returning to normal." In the previous article, an important factor in the outbreak of infectious diseases in winter is human behavior patterns. People gather more in cold seasons, which provides the best opportunity for the virus to spread. However, during the COVID-19 pandemic in the past three years, human behavior patterns around the world have undergone short-term drastic changes, which have also affected the incidence of many common infectious diseases.

Refer to the changes in seasonal influenza test positivity rates in the United States in recent years [5]:

Figure 1. Changes in influenza test positivity rates in the United States since the 2015/16 influenza season (Source, citation [5])

2020/21 is the first flu season after the global pandemic of the new crown, but the influenza virus was almost extinct that year. It can be said that there was no flu season at all that year. The disappearance of influenza is precisely due to the huge change in people's behavior patterns that year. In the 2021/22 flu season, as the vaccination rate of the new crown vaccine increased, the United States gradually relaxed various new crown epidemic controls, and the flu also recovered slightly, but the number of cases was still far lower than usual, and a rare double peak appeared: there were not many peak cases in the winter of that year, and another small peak appeared in the spring. What happened in the winter of 2021/22? It was when the first wave of the Omicron epidemic hit the world. At this time, people's behavior was difficult to recover due to the epidemic, and influenza, a traditional respiratory infectious disease, was naturally affected.

But in the 2022/23 flu season, which began last winter, many parts of the world have begun to coexist with the new crown, and people's behavior patterns are getting smaller and smaller than before the new crown pandemic: visiting relatives and friends during the holidays, watching the World Cup, the audience seats are full... As human society and human behavior return to normal, the common infectious disease of influenza has also begun to return to "normal". For example, in the United States, the positive detection rate at the peak of infection is not much different from that before the new crown epidemic.

Not only influenza, RSV has also experienced a similar "disappearance and return" in Europe and the United States. Different countries and regions have different times for epidemic control adjustments, so the recovery of these traditional epidemics will also be different. China did not adjust its COVID-19 prevention measures until the end of 2022, and we may only be facing the "recovery" of viruses such as influenza now. After not seeing these "old friends" who have existed in human society for three years, it is inevitable that there will be a feeling that more viruses have suddenly appeared when we meet them again. However, the truth is not that new viruses suddenly appeared, but that old viruses, like our society, have begun to recover.

3

Pre-existing immunity and the virus's "post-COVID sequelae"

Although infectious diseases such as influenza have also begun to recover from the impact of the COVID-19 pandemic, judging from the situation in Europe and the United States, there will still be a transition period. In the short term, we will also see some abnormal manifestations of traditional epidemics.

For example, the 2022/23 flu season in the United States, in terms of disease peak, is similar to previous flu seasons, but it occurred much earlier than in the past, starting in the 40th week of 2022, in October, nearly two months earlier than in most previous years. This is also reflected in the number of flu hospitalizations [5]:

Figure 2. Number of influenza hospitalizations per 100,000 people per week in the United States over the past six influenza seasons (from reference [5])

Judging from the number of influenza hospitalizations per 100,000 people per week, the peak of the 2022/23 flu season in the United States is around 50 to 60 people per 100,000, similar to the 2018/19 and 2019/2020 seasons, which is within the normal range and lower than the particularly severe 2017/18 flu season. However, the peak came two months earlier than in the past.

At the same time, this flu came early and went early in the United States. The number of infections dropped sharply in February 2023. If there is no rebound afterwards, it means that the flu epidemic would have ended at the peak of previous flu epidemics.

Since human society and other viruses are emerging from the shadow of COVID-19, why is there such an "abnormality"? Because the return of human behavior patterns may not be consistent with seasonal patterns. In the short term, the activity patterns of these viruses will be closer to the time of human behavior changes, and it will take some time to return to the original seasonality. But another factor that cannot be ignored is that humans have just gotten rid of the COVID-19 pandemic, and their pre-existing immunity to many common viruses has not yet returned to normal.

Similar to the new coronavirus, the severity of the epidemic caused by viruses such as influenza in human society is also affected by two factors: the pathogenicity of the virus and the immune foundation of the population. For example, the influenza virus is constantly mutating, and most of the mutations are subtle, which are just small changes in antigens for the human immune system, that is, antigenic drift. In this case, after repeated infections in multiple flu seasons, people will have a better immune foundation for influenza, limiting the impact of influenza. However, when influenza undergoes major changes and antigenic shift occurs, the pre-existing immunity accumulated by the immune system from repeated infections in the past is limited in effect, and severe flu seasons are prone to occur.

Under the influence of the epidemic in the past three years, the epidemic patterns of common viruses such as influenza and RSV have been abnormal for several consecutive epidemic seasons, which has also caused our pre-existing immunity to deviate from normal levels. The "abnormality" of pre-existing immunity also makes it more likely that the virus will behave "abnormally".

For example, RSV usually peaks in winter, just like influenza. However, in the summer of 2021, the United States experienced its first RSV peak since the COVID-19 pandemic[6]:

Figure 1. The United States experienced an unusual peak in RSV infection in August 2021 (blue curve) (from citation [6])

Since October 2022, RSV infection in young children in the United States has also surged, with an abnormal peak not seen in previous years[7]. The high-risk groups for RSV are at both ends of the age structure: one is newborns, who have never been infected and have no immune basis, so they are relatively vulnerable; the other is the elderly, who are physically weak and also have a certain risk of severe illness. In the past, children had basically been infected with RSV after the age of 2, and since then, relying on the immune basis of previous infections, RSV infections were often mild. However, in the years when the RSV epidemic disappeared, many children did not have pre-existing immunity even after the age of 2, which led to the abnormal manifestations of RSV in terms of time or severity.

Similarly, although norovirus infection manifests as acute gastroenteritis with diarrhea and vomiting, increased social distance and wearing masks during the COVID-19 pandemic will inhibit the spread of the virus. Therefore, many countries and regions rarely experienced norovirus outbreaks in the early stages of strict epidemic prevention and control [8-9]. On the other hand, while norovirus spreads among communities, it also accumulates corresponding immunity at the population level. Therefore, after COVID-19 control, the population's immune reserve decreases, and norovirus may rebound more strongly than before. This is also a phenomenon observed in the United Kingdom, the United States and other countries [10].

From this perspective, common viruses are also experiencing "post-COVID sequelae" and will need an adaptation period before they can fully recover from their past epidemics. Some viruses may experience more severe "post-COVID sequelae". For example, the Yamagata strain, one of the two common influenza B virus strains of seasonal influenza, has rarely been detected since the outbreak of the COVID-19 pandemic. Even in the 2022/23 flu season, when influenza as a whole has recovered, this strain is still hard to find. We cannot rule out the possibility that this strain has become extinct in the past three years due to a lack of a host[11].

4

Rational response to common viruses in recovery

Having just experienced the peak of the COVID-19 pandemic, it is normal to have some degree of worry when facing the "return" of various common viruses. However, as "H1N1" and "Norovirus" frequently become hot words today, we can still refer to the scientific experience accumulated in dealing with these common viruses in the past, face them rationally and reduce anxiety.

First of all, in the short term, we must be prepared for some common viruses to behave abnormally. As mentioned earlier, after European and American countries began to coexist with the new crown, both influenza and RSV have shown different performances from previous epidemic patterns. This is because both human behavior patterns and pre-existing immunity have not fully returned to normal. China's epidemic prevention policy has not been adjusted for long, and it is likely to encounter similar anomalies. The large-scale travel and circulation of people just resumed at the end of 2022, which may lead to the rising period of influenza only now, while the influenza epidemic in the United States is nearing its end.

The “abnormal” manifestations of common epidemics in China as it enters the post-COVID era do not mean that common viruses will change drastically. It is just a manifestation of the transitional period in which everything is gradually returning to normal. We do not need to be overly afraid.

Secondly, some deficiencies in pre-existing immunity can be compensated artificially. Lower than normal pre-existing immunity may make us more vulnerable to some common viruses, but it is by no means irreversible. For example, the recent influenza A virus that caused some schools to change their teaching plans, according to the tracking of the 2022/23 influenza season in Europe and the United States, the influenza vaccine of the current influenza season has a better protective effect [12]. Getting the influenza vaccine as soon as possible can make up for the lack of pre-existing immunity caused by the previous COVID-19 pandemic to a certain extent, and may also better cope with the resurgence of the influenza virus.

Thirdly, those common viruses still have their own characteristics, and their pathogenicity will follow the original rules. As common viruses, influenza A, RSV, norovirus, etc. have relatively stable pathogenicity, and there are corresponding high-risk groups, most of which are concentrated in infants and the elderly. We can fully prepare for such laws. For example, the medical system can be prepared for the possibility of an increase in high-risk groups seeking medical treatment. And take additional protective measures in places where high-risk groups gather, such as schools and nursing homes, and appropriately improve indoor ventilation in cold seasons, which will reduce some threats from influenza and RSV. Norovirus can also be prevented by personal attention to hand hygiene, strengthening the hygiene conditions of schools, restaurants and other places, and other measures.

Finally, science and medicine are constantly improving, so even if common viruses will not disappear from our lives, we will have more and more ways to deal with them. For example, with breakthroughs in vaccine antigen structure design (the same technology is also used in some of today's highly effective COVID-19 vaccines), two RSV vaccines for the elderly may soon be available [13]. In the past, these common viruses did not prevent our human society from moving forward, and in the future, our methods of dealing with these viruses will only become better as technology develops. In the past, we were able to coexist with these common infectious diseases, and in the future, we are likely to coexist at a lower cost.

References

[1] https://www.cdc.gov/flu/about/burden/past-seasons.html

[2] https://www.cdc.gov/hai/organisms/norovirus.html

[3] https://pubmed.ncbi.nlm.nih.gov/23575961/

[4] https://pubmed.ncbi.nlm.nih.gov/30619155/

[5] https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2023-02/slides-02-22/influenza-02-Grohskopf-508.pdf

[6] https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2022-06-22-23/03-RSV-McMorrow-508.pdf

[7] https://www.cnn.com/2022/10/21/health/rsv-hospitals-what-to-know-wellness/index.html

[8] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8662166/

[9] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8888229/

[10] https://www.vox.com/health/2023/2/17/23603035/norovirus-stomach-flu-vomiting-nausea-diarrhea-outbreak-norwalk

[11] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9524051/

[12] https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2023-02/slides-02-22/influenza-03-Olson-Lewis-Tenforde-508.pdf

[13] https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2023-02/slides-02-23/RSV-Adults-04-Melgar-508.pdf

This article is supported by the Science Popularization China Starry Sky Project

Produced by: China Association for Science and Technology Department of Science Popularization

Producer: China Science and Technology Press Co., Ltd., Beijing Zhongke Xinghe Culture Media Co., Ltd.

Special Tips

1. Go to the "Featured Column" at the bottom of the menu of the "Fanpu" WeChat public account to read a series of popular science articles on different topics.

2. Fanpu provides a function to search articles by month. Follow the official account and reply with the four-digit year + month, such as "1903", to get the article index for March 2019, and so on.

Copyright statement: Personal forwarding is welcome. Any form of media or organization is not allowed to reprint or excerpt without authorization. For reprint authorization, please contact the backstage of the "Fanpu" WeChat public account.