In a stark reflection of the post-pandemic era’s shifting health priorities, biotech giant Moderna (MRNA) has overtaken all other S&P 500 constituents to claim the unwelcome title of the most shorted stock, with investors betting heavily against its recovery amid plummeting demand for COVID-19 vaccines. As of late October 2025, approximately 18.29% of Moderna’s public float—equivalent to 63.66 million shares—remains sold short, a figure that dwarfs competitors across the index. This surge in bearish wagers comes as U.S. vaccination rates for the latest COVID boosters hit historic lows, signaling widespread “jab fatigue” among the public.
A Stock Under Siege: Record Short Interest Levels
Short selling, where investors borrow shares to sell high and buy back low, has long been a barometer of market skepticism. For Moderna, the strategy has proven prescient. Data from S3 Partners, a leading analytics firm, reveals that short sellers have racked up unrealized profits of about $622 million on their Moderna positions so far in 2025 alone. The company’s shares closed at $23.72 on Friday, a staggering 43% decline from the start of the year, erasing much of the windfall gains from its pandemic-era highs.
Moderna’s short interest ratio stood at 17.62% as of October’s end, down slightly from 18.66% in September but still the highest in the S&P 500. Within the healthcare sector, it remains unchallenged: Short bets on S&P 500 health stocks rose to 2.00% overall in October, yet Moderna’s exposure towers above peers like Pfizer or Johnson & Johnson. Analysts at GuruFocus noted that this positions Moderna as the outright leader in short interest across the entire index for the month.
The trend persisted into November, with Moderna retaining its crown as the most shorted healthcare name in the S&P 500, even as sector-wide short interest ticked up modestly from October. This isn’t a fleeting blip—Moderna has held this dubious distinction for much of 2025, underscoring deep-seated doubts about its pivot beyond COVID-19 revenue streams.
Vaccine Hesitancy Takes Center Stage: The Jab Skip Epidemic
At the heart of the sell-off lies a sobering reality: Americans are increasingly opting out of COVID-19 boosters. The Centers for Disease Control and Prevention (CDC) reports that just 13.8% of adults aged 18 and older have received the 2025-26 formulation, a figure that lags far behind even the already dismal uptake from prior seasons. For context, only about 23% of U.S. adults got a COVID shot during the 2024-25 season—compared to 47% who opted for flu vaccines—highlighting a stark divergence in public health priorities.
This decline traces back to late 2024, when adult booster uptake stalled at around 21% by December, marking the lowest rate since the pandemic’s onset. Factors abound: Vaccine fatigue after years of mandates and messaging, conflicting guidance from health authorities, and a perception that COVID-19 has become a “manageable” illness rather than an existential threat. A KFF Health News analysis points to immigration-related policy shifts and mixed signals on booster necessity as further eroding trust.
For Moderna, whose fortunes were forged in the fire of mRNA technology and its blockbuster Spikevax vaccine, the implications are dire. COVID-related sales, once projected to fuel billions in annual revenue, have cratered as boosters gather dust on pharmacy shelves. The company’s pivot to other mRNA candidates—like treatments for flu, RSV, and cancer—remains promising on paper but unproven at scale, leaving investors wary. Morningstar recently slashed its fair value estimate for Moderna from $40.30 to $37.32, citing these headwinds.
Broader Ripples: A Cautionary Tale for Biotech
Moderna’s plight isn’t isolated. The broader biotech sector grapples with a post-COVID recalibration, where hype around rapid vaccine development has given way to scrutiny over sustainability. Short interest in healthcare stocks broadly climbed in November, reflecting bets on overvaluation in a cooling demand environment. Yet Moderna’s outsized exposure—tied so inextricably to a single product line—amplifies the pain.
Analysts urge caution rather than capitulation. “Hold” ratings dominate, with firms like those cited in BioSpace advising investors to weather the storm as Moderna’s pipeline matures. A recent NEJM study underscored boosters’ effectiveness in slashing severe outcomes among the vaccinated, potentially reigniting interest if public health campaigns adapt. Still, with uptake mired in the low teens, the path to redemption looks arduous.
As winter looms and respiratory viruses circle, Moderna’s story serves as a poignant reminder: In the marketplace of health, innovation alone doesn’t guarantee immortality. Short sellers, flush with gains, are betting on a world that’s moved on from the jabs that once saved millions. Whether Moderna can reinvent itself—or if the bears’ feast continues—remains the biotech blockbuster of 2025.