Amsterdam institute for Immunology and Infectious diseases

Four years ago, panic gripped the nation upon the discovery of the first COVID-19 case in the Netherlands on February 27, 2020. Since then, the virus has presented unforeseen challenges, prompting a relentless race between its mutations and our defenses. In this article Dr. Van der Hoek, virologist and associate professor at Amsterdam UMC, and her counterparts at Erasmuc MC, and Utrecht University/RIVM share their vision.

And it was scarcely conceivable during the intelligent lockdown that followed, but a few weeks later experts predicted: this virus will become an endemic disease. It will become part of the fixed package of respiratory viruses that circulate every winter, including four mild COVID-viruses and the flu virus. These viruses are not a major problem for most people, only for vulnerable elderly and sick individuals.

So, how is SARS-CoV-2, the 'novel corona-virus, four years after that first coronavirus infection?

As we reflect on the four-year journey since the emergence of the first COVID-19 infection, the pressing question arises: How has SARS-CoV-2, commonly known as the 'novel corona virus,' evolved over time? Has it reached a level of comparability with other respiratory viruses? Have we emerged victorious in the battle against it, or do we still face the looming threat of dangerous variants?

One thing stands out: the emergence of the Omicron variant and its numerous subvariants currently in circulation has led to a notable decrease in the severity of illness among infected individuals. Hospitalization rates have plummeted, with less than 2 percent of all deaths attributed to COVID-19, a stark contrast to the 14 percent observed in 2020, as reported by CBS. However, the scientific community remains divided on whether this decline stems from inherent characteristics of the variant itself, or if it is primarily a result of widespread immunity acquired through vaccinations and prior infections.

The Evolution of SARS-CoV-2: From Alpha to Omicron

As the pandemic unfolded, the virus swiftly adapted to its human host, undergoing mutations that enhanced its transmissibility and stability. The original strain, which emerged from Wuhan in late 2019, was soon supplanted by the Alpha variant (dubbed the 'British variant') in December 2020. This variant proved significantly more contagious, requiring fewer virus particles to initiate infection. Subsequently, variants Beta (originating in South Africa) and Gamma (from Brazil) emerged, sharing similar mutations in the spike protein, the gateway through which the COVID-19 virus enters human cells.

Concurrently, the race to develop vaccines intensified. The Netherlands administered its first vaccine dose on January 8, 2021, marking a pivotal moment in the fight against the virus. However, the emergence of the Delta variant, originating in India at the end of 2020, posed a new challenge. Delta quickly eclipsed Alpha in terms of contagiousness, setting the stage for further waves of infection.

Yet, just as Delta seemed dominant, Omicron emerged at the end of 2021, swiftly outpacing its predecessors. Since the onset of 2022, various subvariants of Omicron have proliferated worldwide, with iterations such as BA.1 to BA.5 and novel combinations like the XBB variants. Presently, the JN.1 subvariant holds sway in the Netherlands, underscoring the ongoing evolution and complexity of the virus.

A Game-Changing Variant

The emergence of Omicron caught the world off guard, boasting a spike protein adorned with a multitude of mutations, surpassing all previous variants combined. "That marked the virus's first significant immune escape," notes Haagmans, virologist at Erasmus MC, Rotterdam. "It was anticipated, given the rising global immunity by the end of 2021."

Promptly, manufacturers pivoted to develop tailored vaccines to counter both the original strain and Omicron. These adapted vaccines were swiftly deployed in the fall of 2022. Initial data suggests that Omicron may penetrate less deeply into the lungs, with a reduced incidence of loss of taste and smell compared to Delta infections. Moreover, the risk of long-term symptoms diminished after an Omicron infection. However, Haagmans attributes this milder impact primarily to the widespread immunity now prevalent. "In Hong Kong, where stringent measures held the virus at bay until February 2022 and vaccination rates lagged, the Omicron BA.2 subvariant led to significant mortality."

Redefining SARS-CoV-2: Is it becoming a common cold virus?

Dr. Van der Hoek, a virologist at Amsterdam UMC, suggests that SARS-CoV-2 might now be akin to the milder viruses that have circulated for centuries, causing common colds every winter. "There used to be four, now there are five. I hardly see any difference."

While some virologists share this view, others remain cautious, noting that SARS-CoV-2 is still adapting to its human host. Dr. Van der Hoek's team discovered one of the prior four coronaviruses, NL63, in 2003, highlighting the potential severity of such seasonal coronaviruses.

Research into these milder coronaviruses is now thriving, providing insights into long-term immunity. Dr. Van der Hoek's recent study followed 44 individuals for seventeen years, revealing that immunity against these coronaviruses persists over time, even as antibody levels wane.

Insights into immunization

Dr. Van der Hoek's research sheds light on questions surrounding immunization. She explains, "An increase in antibodies indicates recent infection, but whether one experiences symptoms upon re-infection does not solely rely on antibody presence. Rather, the cellular immune response of T cells and B cells, forming immune memory, may be more crucial."

Her findings challenge assumptions about seasonal virus exposure, suggesting that regular infections may not significantly impact symptom severity over time. However, she cautions that SARS-CoV-2 immunity, acquired predominantly in adulthood, may differ from that of childhood-acquired immunity against endemic coronaviruses.

Dr. Haagmans, her colleague in Rotterdam, notes that SARS-CoV-2 variants remain more pathogenic than endemic coronaviruses, particularly affecting elderly and vulnerable individuals. Unlike common respiratory viruses, SARS-CoV-2 can cause severe organ damage and long-term complications, underscoring the importance of vaccination efforts.

Booster shot strategy

The ongoing necessity of vaccinations, particularly for high-risk groups, is a subject of annual consideration by the Health Council. Their recommendation in June 2023 underscored the importance of booster shots, especially for individuals aged 60 and above and those with underlying health conditions. These booster shots, tailored to combat the Omicron subvariant XBB.1.5, have demonstrated remarkable efficacy in reducing severe Covid-19 cases, with a protection rate exceeding 70% against hospitalization or intensive care admission, as evaluated by the RIVM.

Boosters play a crucial role in fortifying immunity across various fronts. They bolster the body's first line of defense by strengthening mucosal antibodies in the upper respiratory tract, vital in preventing viral penetration into deeper airway regions. However, the frequency and necessity of administering adjusted coronavirus shots annually remain uncertain.

Dr. Cécile van Els, a vaccinologist from Utrecht University and the RIVM, acknowledges the ongoing challenges in predicting the need for yearly vaccinations. While vaccination currently offers substantial protection to at-risk individuals, the rapidly evolving nature of the virus and the complexities of long-term immunity necessitate continued vigilance and research.

Unlike the flu, which benefits from a well-established global monitoring system guiding annual vaccine adjustments, the coronavirus lacks such a framework. Dr. Van Els emphasizes the need for vigilant surveillance to track variant trajectories and assess the potential need for vaccine modifications, recognizing the unique dynamics of the coronavirus compared to the flu virus.

The threat of new variants

International recommendations for vaccine updates are disseminated by an independent advisory group of the World Health Organization (WHO). In May 2023, they urged vaccine manufacturers to adapt their formulations to target the XBB1.5 subvariant, prompting swift adjustments from many manufacturers.

Despite ongoing vigilance, the emergence of a new, highly pathogenic variant remains a primary concern. While the spike protein undergoes continuous changes, mutations in the virus's internal proteins could potentially enhance its pathogenicity. However, virologist Haagmans remains optimistic, citing minimal variation in internal proteins across variants, which preserves cellular immunity, particularly T cell immunity crucial for combating infections deep within the lungs.

Haagmans further downplays the risk of heightened pathogenicity in variants emerging from other animal reservoirs or individuals with compromised immune systems. He attributes our ability to effectively manage the virus to the immunity we have acquired. Even during periods of rapid viral proliferation, such as observed in December, the virus's impact unexpectedly waned, indicating a level of resilience conferred by existing immunity.

Dr. van der Hoek shares this sentiment, anticipating that SARS-CoV-2 will maintain its mildness. The virus's survival hinges on its ability to sustain transmission without incapacitating hosts entirely. Therefore, while symptomatic, severe cases may prompt individuals to isolate, the virus is unlikely to evolve into a symptomless state.

Overall, the prevailing consensus suggests that the threat posed by SARS-CoV-2 has diminished significantly. Any future challenges are more likely to arise from novel viruses, though Haagmans expresses hope that familiarity with managing SARS-CoV-2 will better prepare us for future outbreaks.

Source: this article is a revised version of an article originally published in Dutch on NRC, authored by Niki Korteweg. Access the original piece here.