when most people become "Yang Guo", to sort out the basic plate of the new crown.

new coronavirus is another of the most serious global epidemics since the 1918 influenza pandemic, and as an RNA virus, it is very easy to genetically evolve, and there are currently five main variants.

started in China in December 2019, when a wild-type new coronavirus was found in Wuhan. In September 20, the UK discovered the variant Alpha, which has increased its transmission capacity, lethality and serious illness rate. In December, South Africa discovered the variant Beta, a K417N with the same immune escape capability superimposed on Alpha, and its one-shot vaccine effectiveness dropped from 85 per cent to 16.9 per cent.

January 21, Brazil discovered the variant Gamma, which has 2-4 times stronger transmission and lethal ability. In March, Britain discovered the variant Delta super strain, which was 97% stronger than Gamma and quickly occupied the world. In November, the variant Omicron was discovered in Botswana. Subsequently, Omicjon became the main strain sweeping the world. Its aggressiveness to the bronchus is stronger, its transmission is stronger, and its immune escape ability surpasses Beta.

but the good news is, as the virus mutates,Omicjon's pathogenicity and lethality are far weaker than all the previous strains, most of the infected people for mild illness, its fatality rate has been reduced to less than 1 ‰, only 90% of the flu, the new crown has become a "large flu".

Figure 1: Global variation and time course of neo-crown strains

the overall risk of sequelae is lower, but it is more toxic to the nervous system.According to a June 2022 willow knife study, 4-5% of cases during the peak of Omicjon infection experienced a long new crown, half as low as Delta's 8-10%. However, a study in the September 2022 issue of Nature Medicine found that after the acute phase of COVID-19, there will be an increased risk of a range of neurological sequelae, known as "brain fog", including ischemic and hemorrhagic strokes, cognitive and memory disorders, peripheral nerve disorders, mental disorders, encephalitis or encephalopathy.

reinfection leads to an increased risk of all-cause mortality.During the epidemic period of the virus, due to the genetic variability of the virus, there is no protection against the strains that have been infected, and the probability of re-infection of people who have been infected is also increasing. According to a study published in Nature Medicine in December 22,superinfection was associated with a 117 percent increased risk of death and a 232 percent increased risk of hospitalization. In addition, it also increases the risk of sequelae including lung disease, cardiovascular disease, blood disease, diabetes, gastrointestinal disease, kidney disease, mental disease, musculoskeletal disease and neurological disease, with the increase rate ranging from 60% to 255.And, this increased risk is significant regardless of vaccination.

Figure 2: Risk of sequelae and burden of disease with and without repeat infection

data source: Nature Medicine

sequelae increases with the number of infections.Compared with those who have never been infected, the risk of at least one sequela in patients who have been infected once, twice and three times is increased by 37%, 107% and 135 respectively, and the disease burden within one year is also increased by 305 ‰ from 109 ‰. Therefore, it is still necessary to follow the epidemic prevention rules for uninfected people, and for those who have been infected, they need to be vigilant to reduce the risk of repeated infection.

Figure 3: Cumulative Risk and Sequela Burden of Uninfected and Repeated Infections

data source: Nature Medicine

don't blame the vaccine for not giving force, but the virus is too able to escape.vaccines are a very effective preventive tool against epidemic diseases, but because adaptive mutations in the genome of the new coronavirus can change the pathogenic potential of the virus, even a single amino acid exchange can greatly affect the virus's ability to evade the immune system. However, the state still calls on everyone to inject the third or even the fourth injection to strengthen, after the fourth injection, can activate the immune system in a short period of time, to regain a high level of neutralizing antibodies against the new coronavirus variant strain.

vaccines has also been upgraded from traditional inactivated vaccines to genetically engineered vaccines, including DNA/mRNA vaccines, recombinant protein subunit vaccines, viral vector vaccines, etc., but it has not yet been achieved to defeat the new crown, and it is important to continue to develop vaccines against multiple new crown variants.

Figure 4: Progress in vaccine research and development by domestic enterprises

Data source: Pharmaceutical Rubik's Cube (only shows the R & D pipeline of enterprises, except universities and hospitals)

data as of December

oral medicine domestic research and development progress can be expected.from the current new crown pneumonia treatment drug market, small molecules are the focus of attention, China's research and development pipeline has more than 10, but the domestic market oral drugs only Pfizer Paxlovid and real biological Azvudine 2.taking into account Pfizer's limited production capacity, high pricing and supply chain security and stability, domestic new crown oral medicine will still have a huge market. According to the price of 300 yuan for one course of domestic drugs, the 0.264 billion of the elderly population aged 60 and above in China will reach 16.6 billion yuan, assuming 70% infection rate and 30% utilization rate.

, we also mentioned in our August article that the rapid progress at present includes VV116 of Junshi Biology and Favelavir of Haizheng Pharmaceutical. The SIM0417 of Simcere Pharmaceutical is expected to go public in February 23 at the earliest.

Figure 5: New Crown Oral Drug Latest Clinical Research Progress in China

Data Source: Medical Rubik's Cube, ClinicalTrials, Data as of November

Paxlovid designated generic drug manufacturers benefit from this?the current global demand gap for Pfizer's new crown cure is huge. According to its annual report, the annual output is expected to reach 0.12 billion courses in 22 years. Paxlovid sales in the first half of the year were $9.6 billion and are expected to reach $22 billion for the whole year. At present, the market is still in short supply and there is an urgent need to increase production capacity.

March 22, the Geneva Pharmaceutical Patent Pool (MPP) signed agreements with 36 companies to allow the production of generic drugs for Pfizer's new crown oral drug, Nematvir tablets, including five Chinese pharmaceutical companies.Shanghai Diseno, Huahai Pharmaceuticals, Plo Pharmaceuticals, Fosun Pharmaceuticals, Jiuzhou Pharmaceuticals.these generic drug manufacturers will not be able to supply their products to the market for at least 23 years. First of all, the drug is a new drug and is still in the patent period. Licensed enterprises may not be able to imitate it successfully and mass produce it. Secondly, even if it enters the list of Pfizer's original research drug suppliers, it may not necessarily get large-scale orders. In the end, Pfizer may only choose two or three of them as suppliers.

with the Paxlovid volume, domestic designated manufacturers and some CDMO enterprises are expected to usher in incremental performance due to increased orders, but will not show the same explosive collective momentum as the new crown testing reagents or vaccines., if Botten received a $0.681 billion order from Pfizer at the beginning of the year, the incremental value of the new crown cure to domestic CDMO companies will exceed $1 billion in 2022.

the new coronavirus continues to mutate and may remain a threat for years or even decades to come, leading to the possible emergence of new mutant strains with more immune escape capabilities. There is therefore an urgent need for a strategy that can produce a more durable new coronavirus vaccine that covers a wide range of mutant strains, reduce the spread of the new coronavirus, and reduce the number of people infected or re-infected. Additional pharmacological and non-pharmacological interventions are also needed to reduce the risk of superinfection and its adverse health consequences.

in the first half of 2022, the new crown-related drugs occupied three seats, Pfizer's vaccine Comirnaty became the new drug king, half-year sales of $22.1 billion, contributing 41% of Pfizer's revenue. Modena's vaccine Spikevax followed closely, ranking sixth in Paxlovid, which shows the short-term performance outbreak brought to the industry by this pandemic.

Chart 6: Top 10 Global Best-Selling Drugs Forecast in 2023

data source: Nature Reviews Drug Discovery

January 2023, the WHO Emergency Committee will meet to discuss the criteria for judging that the new crown no longer constitutes a global health emergency. On December 26, the National Health Commission also officially renamed it "new crown virus infection", and starting from January 8 next year, the prevention and control measures for Class A infectious diseases will be lifted and Class B management will be implemented. This marks the normalization of the three-year epidemic.

as the vaccination rate increases, the demand for vaccination will gradually "fade" in the future, and in the forecast of heavy varieties in 2023,New Crown-related drugs, while sales may have declined year-over-year, remain among the best-selling drugs in the world. Domestic vaccine growth will also slow down, while domestic new crown drugs are expected to increase market capacity.