Future prospects
It is expected that the COVID-19 pandemic will be halted to the maximum extent under the help of vaccination. China has set an example due to the practice of “ISISI” strategies for the COVID-19 pandemic. So far, there are more than 1.2 billions of Chinese residents who received the whole vaccination, and it’s still continuing coverage among non-adults from 3 to 17-year-old. We expect that the pandemic will be effectively halted by not only powerful candidate vaccines but also continuing the “ISISI” barriers which cover antiviral drugs (Molnupiravir, Paxlovid, Chinese combination of BRII-196/BRII-198) (4-7), traditional Chinese medicine, small molecules and plant-derived anti-SARS-CoV-2 agents. It’s happy to see a living WHO guideline on drugs to prevent COVID-19 (25). And it’s believed that people will combat the COVID-19 pandemic sooner or later under the help of these comprehensive strategies.
After rigorous clinical trial design, current vaccination by receiving developed candidate vaccines is a reliable strategy for against SARS-CoV-2 infection and transmission, and control of COVID-19 in the globe. Both animal models and clinical trials confirmed the protective roles elicited by vaccination of multiple safe and effective vaccines, such as two doses of the mRNA-1273 COVID-19 vaccine (26), StriFK-FH002C (27), the AS03-adjuvanted preS dTM vaccine (28), ChAdOx1 nCoV-19/AZD1222 (29), Two doses of the SARS-CoV-2 BNT162b2 vaccine (30), COVID-19 mRNA vaccines (31), Ad26.COV2.S vaccination (32), AZD1222/ChAdOx1 nCoV-19 vaccination (33). Newly, GRAd-COV2, a candidate vaccine against COVID-19, is safe and immunogenic in younger and older adults (34). However, there are still many challenges since current Omicron variant appear to diminish the protection conferred by pre-existing immunity.
There was historically high excess mortality during the COVID-19 pandemic in some European countries since the beginning of the 20th century (35), but telemedicine service may reduce infection-related mortality (36). Although there are rare adverse events (myocarditis, carditis, thrombosis) in some cases (37-39), vaccination (40) and history of infection (41) have a protection against reinfection and variants (42). And vaccination in organ transplant recipients may increase neutralizing antibody response against SARS-CoV-2 variants (43). In conclusion, on the one hand, we need to rapidly develop novel efficacious vaccines against SARS-CoV-2 and its major variants (Delta and Omicron) since human immunity and early non-neutralizing antibody responses are associated with COVID-19 severity (1, 44); On the other hand, we should rigidly control Omicron variant for restriction of infection and transmission in the globe by the comprehensive “ISISI” strategies.
Currently, megadose vitamin C (45) can be used as a potential treatment, unfractionated heparin (UFH) can directly inhibit binding of spike protein to the human ACE2 protein receptor (46), and protease-activated receptors (PARs) blockers may fight against cytokine release syndrome and COVID-19-associated coagulopathy (47), the options to target complement may halt disease progression and death (48). All in all, a polypharmacology approach or multi-drug treatment (49, 50) may help improve clinical outcomes since there are acute kidney injury (AKI) and fibroproliferative changes in the lung, heart and kidney in COVID-19 cases. Because mass vaccination cannot quickly end the pandemic, it is suggested to adopt an influenza-like vaccination strategy (51). In conclusion, the prevention and control of COVID-19 needs the comprehensive “ISISI” strategies.