The Omicron variant is driving caseloads to record highs, filling up hospitals, and streams of breakthrough infections over the winter gave rise to skepticism about the efficacy of COVID-19 vaccines. Nevertheless, real-world data showed more than 80% effectiveness against the severity of the disease and hospitalization rates. Current vaccines against SARS-CoV-2 that target the spike protein are a decisively initial step toward developing antiviral therapeutics and next-generation vaccines. As the SARS-CoV-2 virus has rapidly evolved, researchers are eager to assess the feasibility of using a combination of multiple spike protein variants or viral antigens in the next-generation vaccine design.




Multiple research teams recently proposed another unique feature of the Omicron: the variant prefers entering cells by an endosomal route, similar to SARS-CoV, rather than driving receptor-dependent syncytium formation, catalyzed by surface TMPRSS2 protease. Some data indicate Omicron alternatively uses a lysosomal protease such as cathepsin B/L to cleave the spike protein and gain access to the host cell. Respiratory tract cells lacking TMPRSS2 protease are shown to have reduced lung pathology following SARS-CoV infection. In ex vivo experiments of human cell explant cultures, Omicron replicated substantially quicker in the upper conducting airways (nose, throat, and trachea) than in both the wild-type strain and the Delta variant, but the reverse is true for the deep pulmonary tissue in which the replication was ten times slower. This may be a probable explanation for why Omicron causes milder symptoms in the lungs.


Compared to its Delta predecessor, preliminary data state that the Omicron variant does not seem to infiltrate the lungs, produce moderate symptoms in the upper respiratory tract, and therefore, have fewer risks of hospitalizations and deaths. The World Health Organization (WHO), however, warned against describing such a variant as mild. Experts explained that the highly contagious Omicron may be deadly to those who remain unvaccinated as the comparatively lower rate of hospitalizations and deaths so far is attributed to widespread vaccination, especially in vulnerable groups, such as those over 65 years of age and those with underlying medical conditions.


There are still uncertain factors affecting the illness of infected individuals. For example, cases of long-hauler symptoms, including “brain fog (an undefined cognitive dysfunction)”, persistent fatigue, and breathlessness are piling up. Roughly one-fourth of the people who had resolved acute Omicron infection suffer long-term health problems. Scientists attempt to clarify mechanistic links between the respiratory virus and cognitive disturbance. Thus, although the Omicron intrinsically causes a milder airway disease, it somehow commits other detrimental effects elsewhere in the human body.


COVID-19 is unlikely to be eradicated, but societies in the past have learned to live with diseases. Although it is inevitable that the perennial appearance of new viral strains carry unfavorable mutations, it is reassuring that most scientists agree that the COVID-19 pandemic will end, and that the virus will return back into an endemic. During its frenetic spread around the world, numerous sublineages have already been identified, including three major spinoffs: BA.1, BA.2, and BA.3. The standard Omicron is currently the most common subvariant, now referred to as BA.1/B.1.1.529.1. BA.2, and it gets most of the media’s attention ever since its outbreak in Denmark, the United Kingdom, and India, and its transmission rate seems to overtake other former sublineages. The third, BA.3, is yet to take off globally, only accounting for several hundred cases at the most. BA.1, BA.2, and BA.3 differ from one another just as much as the Alpha, Beta, Gamma, and Delta variants differ from one another. Likewise, several mutations also differ between the BA.1, BA.2, and BA.3, so it is crucial that we study the varied characteristics of all three sublineages carefully.


To combat the next surge of infections fueled by other variants, the “Swiss cheese strategy” seems to provide useful guidance for flattening out the epidemic curve and returning to a “new normal life” that coexists with SARS-CoV-2. The “Swiss cheese model”, initiated by James T. Reason and Rob Lee in the 1990s, is a systems approach that recognizes human fallibility and builds layers of defense. Its operative concept can be summarized in a single phrase: minimizing the probability of adverse outcomes and metaphorically being visualized as multiple stacked cheese slices. As applied to COVID-19, this model argues the additive odds of using multiple preventive interventions to mitigate the risk of infection. We know various interventions can significantly lower the chance of being exposed to an infectious titer of viruses, but considering that each one has inherent weaknesses or limitations (like holes on cheese slices), in particular circumstances, errors may leave room for viral transmission. It is above all important to note that while the newer variants of concern behave differently, no measure is perfect. When diverse public health measures and personal hygiene are combined, the holes are much less likely to align, thus providing the population with optimal defense.



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