The strongest "transmissible" strain XBB.1.5 has struck! Can it cause severe diarrhea? Fear of secondary infection? How should our country respond?

Interestingly, this week the CDC revised the transmission data for different subtypes of the new coronavirus: the actual proportion of XBB.
1.
5 subtypes last week was 18.
3%, and this week it rose to 27.
6%.

Although not as scary as the previously provided data, the weekly increase of close to 60% shows the speed at which this new strain is
spreading.

In contrast, as early as last year, China has detected XBB and XBB.
1 cases, but they are imported
from abroad.
Recently, 369 new Chinese local new coronavirus sequencing results added to the Global Influenza Sharing Database (GISAID) showed that of the 25 XBB families monitored in Shanghai, 3 imported cases were XBB.
1.
5, which has not caused large-scale local transmission
.

Super high transmissibility, super immune escape ability?

"Covid forecasters" discover the secret behind XBB.
1.
5

With such a high spreading power, it is indeed somewhat appalling
.

In fact, every new strain that wants to surpass the previous "poison" and "poison" head is nothing more than two things: faster transmission and stronger immune escape ability
.
Tried and tested, so did the new Omicron subtype XBB.
1.
5
.

Cao Yunlong, a researcher from Peking University, who was evaluated as a "new crown predictor" by Nature magazine, and his team, found that "XBB.
1.
5 The mystery behind the "ultra-high transmissibility" - this strain shows a stronger binding affinity with angiotensin-converting enzyme 2 (hACE2) receptors in the human body, and the ability
of neutralizing antibodies similar to XBB.
1 to escape.

https://doi.
org/10.
1101/2023.
01.
03.
522427

To assess the immune evasion capacity of the new strain, the researchers calculated the neutralization titer of XBB.
1.
5 using plasma from people who had received 3 doses of Sinovac vaccine but were still exposed to breakthrough infection (BTI) with BA.
1, BA.
5 or BF.
7 variants
.

The results showed that compared with the B.
1 variant, the plasma of the recovered patients had a significant decrease in the 50% neutralization titers (NT50) for XBB.
1 and XBB.
1.
5, so they were better able to avoid the detection of the "guards" in the human body
.

Specifically, the plasma plasma of BA.
5 breakthrough infected patients who received a booster dose of Sinovac vaccine had a neutralizing activity of 29 times for XBB.
1.
5, which was 40 times lower than NT50 for B.
1; similarly, the plasma of a breakthrough infection with BF.
7 who received a booster dose of Sinovac vaccine had a neutralizing activity of 35 for XBB.
1.
5, which was 27 times
lower than NT50 for B.
1.
Of course, a similar trend
is observed even if mRNA vaccines were administered before breakthrough infection.

XBB.
1.
5 exhibits strong neutralizing antibody avoidance

Further, the researchers monitored the Ser486Pro mutation
on the spike protein (S protein) of XBB.
1.
5 that was different from XBB.
1.
What kind of "superpowers" does the mutation give the new variant?

Deep mutation scanning showed that the equilibrium dissociation constant KD of XBB.
1.
5 and hACE2 was 3.
4 nM, far exceeding XBB.
1 (KD=19 nM) and BQ.
1.
1 (KD=8.
1 nM).

In fact, a smaller KD value means a weaker dissociation ability, i.
e.
a stronger
affinity with ACE2 receptors.

ACE2 binding affinity for different variants

In other words, the possible reason why XBB.
1.
5 has a growth advantage over XBB.
1 is that the Ser486Pro mutation gives the XBB.
1.
5 subtype a stronger ACE2 binding affinity, and the hACE2 protein is a receptor for the new coronavirus to invade human cells, which also explains why "'Gripsio' is more susceptible to the human body"
.

In fact, as early as December last year, Professor He Dayi, a virus epidemiologist who discovered the super ability of XBB and XBB.
1.
5 subtypes, to escape neutralizing antibodies, which was published in the top journal Cell
.

This study is to find out the additional mutation of the new strain and the "advantage" it brings - Omicron variant XBB.
1.
5 with its stronger ACE2 binding affinity and higher immune evasion ability, rapid spread in many countries around the world, or replace BQ.
1.
1 as the dominant strain
in the near future.

Jesse Bloom researcher from HHMI (Howard Hughes Medical Institute) said that the current transmission coefficient (Rt) of XBB.
1.
5 exceeds 1.
6, breaking the balance between the immune barrier/public health measures established by previous infection or vaccination in the United States in the past six months and the spread of the virus.
At this stage, XBB.
1.
5 can spread rapidly throughout the United States" is an important reason
.

Are "Cerberus" really poison kings?

Rumors are self-defeating in the face of real data

At the beginning of the emergence of the Omicron variant XBB.
1.
5, it rushed to the hot search more than once - causing severe diarrhea, quickly go to stock up on medicine; Strong immune evasion ability, unable to avoid secondary infection; The pathogenicity is stronger, and it is possible to usher in a new wave of hospitalization peaks.
.
.
For a time, rumors were everywhere, and it was difficult to distinguish the true from the false
.

Is the "Eagle Lion" really the new poison king as the legend?

Let's start with a set of data: the XBB strain has been the first to cause a wave of infections in Singapore, and peaked in November last year (XBB accounted for the highest proportion of 77%, another 12% BA.
2 and its lineage, 8% BA.
5 and its lineage, 3% BQ.
1, etc.
).

From the perspective of the number of new infections, the peak caused by the XBB subtype did not exceed the previous strain; Similarly, there was no significant increase in severity (hospitalizations and deaths); In terms of secondary infection, the mortality and severe disease rates of XBB secondary infection were 4/100,000 and 232/100,000, respectively, lower than 35/100,000 and 282/100,000
for the first infection.

Singapore has new coronavirus infections and deaths

At this stage, the situation in the United States also has certain reference significance
.

XBB.
1.
5 is in a period of rapid growth in the United States, with the proportion of infections rising
rapidly.
In addition to the high rate of transmission mentioned above, it is undeniable that XBB.
1.
5 did trigger a wave of hospitalizations in the United States, far exceeding the previous BQ.
1 and earlier BA.
5, and even close to about
half of the first wave of Omicron BA.
1 epidemic.

Is it really that "Eagle Head" XBB.
1.
5 has stronger toxicity?

From data from India and Singapore, the new strain XBB.
1.
5 did not cause very serious disease, and the main symptom of infection was still respiratory infection
.
Therefore, the main reason for the recent increase in hospitalization rates in the United States is not increased toxicity, but its ultra-high immune evasion ability
.

In detail, even if infected with the variant that previously caused the peak of the epidemic in the United States, it has almost no protective effect on XBB.
1.
5, and the "population immunity window" gives XBB.
1.
5 an opportunity; in contrast, the BA.
2.
75 strain previously circulating in South Asia will have a certain immune neutralizing effect on XBB and even XBB.
1.
5 after infection, so the symptoms caused are not serious
.

In addition, the latest bivalent mRNA vaccines have a weak protective effect against XBB.
1.
5, and the very low percentage of vaccination in the US population has also led to a relatively severe wave of
hospitalizations.

Hospitalizations due to new coronavirus infection in many places in the United States

In summary, rather than calling XBB.
1.
5 the "poison king", "the king" would be more accurate - according to the current data, the "Gripper" does have a strong transmission power, but there is no indication that XBB.
1.
5 is more deadly than the previously popular variant and does not induce serious gastrointestinal diseases
.

In fact, as the main receptor of new coronavirus binding cells, ACE2 is not only expressed in the lungs, but also in the intestines
.
Dr.
Li Tongzeng of the Department of Respiratory and Infectious Diseases of Beijing You'an Hospital said in an interview that each variant of the new coronavirus will infect intestinal mucosal cells, but due to individual differences, it will determine whether intestinal clinical symptoms
will occur.

Some people had diarrhea symptoms in the previous "yang" process, but at that time, XBB had not yet spread on a large scale in China, so the new strain could not carry this "black pot"
.
There is also no evidence that XBB.
1.
5 is more likely to cause severe diarrhea or other gastrointestinal symptoms than other strains, and it is not necessary to stock up on too many "diarrhea" drugs
.

From the infection situation in countries where XBB variants have been circulated, the vast majority of patients have symptoms similar to the current BF.
7 and BA.
5.
2, and common symptoms include headache, sore throat, nasal congestion, fever, fatigue, cough, and body pain
.

The mutation process of different new crown strains

I believe that the last question is also what everyone is very concerned about now - with such a high immune escape ability, will XBB.
1.
5 enter the country cause serious "secondary infection"?

It is undeniable that XBB.
1.
5 does have a strong immune evasion ability, and repeated infection is a possible situation
.
But there is no need to worry too much, as infectious disease expert Professor Xu Jianqing emphasized in an interview, XBB.
1.
5 has few opportunities in China
.

"The symptoms of this round of infection in China are relatively serious, and the immunity of people who have experienced this round of infection will not be low, and at the same time they have established an immune response of the system and mucosa, with T cell immunity and a good level
of neutralizing antibodies.
" After this round of viral infection, the pathogenicity of the new coronavirus in China in the future should be similar
to that of Singapore now.
”

Other experts believe that immunocompetent people who have been previously vaccinated have a low risk of reinfection in a short period of time (3-6 months), and symptoms after infection are usually milder
than the first time.

Of course, due to the strong escape ability of XBB.
1.
5 against neutralizing antibodies, the immunity currently generated is not very protective against the new strain and cannot be taken lightly
.
At the same time, individual differences are a big problem and the protection of the elderly and vulnerable groups is still very necessary
.

It is clear that XBB.
1.
5 will not be the last Omicron variant, and the pathogenic capacity of the new strain depends more on the immune background
of the population.
Wang Nianshuang, a doctor and senior scientist at Tsinghua University, said, "After the population establishes universal immunity, the new variant will roughly show a steady state in terms of pathogenic ability, and there will be ups and downs, but just like seasonal influenza, there will be no particularly big changes.
.
.
The war between mankind and the new crown virus is decided
.
”