For more than two years, the coronavirus disease 2019 (COVID-19) has turned the world upside-down. According to data from the World Health Organization (WHO), more than 486 million cases of COVID-19 had been reported, as of April 1, 2022, leading to over 6.1 million cumulative deaths. Nearly 973,000 of those deaths have occurred in the United States. 

Even though the worst of the pandemic appears to be in the rearview mirror, there's a real likelihood that COVID-19 becomes an endemic illness. This means initial inoculation campaigns, booster shots, and research into combination vaccines, is almost certain to continue -- and Wall Street knows it.

Based on the highest issued price targets from Wall Street analysts, the following three COVID-19 stocks offer monster upside over the next 12 months ranging from a "low" of 246% to as much as 355%.

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Novavax: Implied upside of 257%

The first COVID-19 play that offers drool-worthy upside, at least according to one Wall Street analyst, is biotech stock Novavax (NVAX 0.57%). Despite a $50 price-target reduction in February, B. Riley analyst Mayank Mamtani still believes Novavax can reach $265 a share.  This represents a cool 257% upside from where shares ended last week.

Mamtani's aggressive price target is based on a few factors. For instance, he believes that concerns over Novavax's near-term manufacturing struggles are overblown. Mamtani explained months ago that Novavax was nearing its monthly manufacturing target of around 150 million doses, and would likely be exporting more than 100 million monthly doses out of India, where it's working with the Serum Institute of India to produce NVX-CoV2373 vaccines. 

Mamtani also views the U.S. and European Union as core long-term sales opportunities for Novavax. Even though a substantial percentage of the population in these developed markets have already received their initial inoculations, the mutability of the SARS-CoV-2 virus that causes COVID-19 offers recurring revenue opportunities via boosters and combination vaccines. Novavax is one of a handful of companies currently developing a combination influenza/COVID-19 vaccine.

Something else to consider is that NVX-CoV2373 has been among the most effective vaccine candidates. Among U.S. and EU treatments that have received approval or emergency-use authorization (EUA), only three have managed to reach the 90% vaccine efficacy (VE) plateau. Novavax is one of those three, with the company's large-scale study in the U.S./Mexico (announced in June 2021) hitting a 90.4% VE. This should allow Novavax to easily supplant other COVID-19 vaccines with lower VEs, such as those from Johnson & Johnson and AstraZeneca.

Based on Wall Street's worst-case scenario for 2022, Novavax looks to be on track for a little over $4 billion in sales (the company recorded $1.15 billion in revenue last year) and over $13 in earnings per share. This would put Novavax's stock at less than six times Wall Street's most-pessimistic profit forecast in 2022.

While I don't expect Mamtani's lofty price target to hit over the next 12 months, I do believe $265 remains in the picture down the line if Novavax continues to execute and innovate.

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Vaxart: Implied upside of 246%

A second COVID-19 stock that offers monster upside over the next 12 months is clinical-stage drug developer Vaxart (VXRT -1.64%). Analyst Yasmeen Rahimi of Piper Sandler holds the high-water price target on Vaxart of $18 a share. If this figure were to become a reality, shareholders would enjoy a 246% gain from where Vaxart's stock ended this past week.

Rahimi's optimism is primarily tied to Vaxart's proprietary drug development technology known as "Vector-Adjuvant-Antigen Standardized Technology," or VAAST. While traditional vaccines aim to produce a systemic response, VAAST is intended to produce both a systemic and mucosal response. This dual approach is believed to provide better protection against airborne viruses. In Rahimi's view, VAAST's success has been demonstrated in previous clinical trials, which somewhat de-risks Vaxart's development platform. 

Another unique aspect of Vaxart's pipeline is that its COVID-19 candidate is an oral tablet and not a jab in the arm. An effective oral COVID-19 treatment would completely change the game globally. It would make distribution substantially easier (i.e., no medical professionals needed to administer shots), and there's a good likelihood that people would be more willing to swallow a pill than receive a vaccine.

Last year, early stage data from Vaxart's COVID-19 oral treatment demonstrated mixed results. Although it did generate an immune response, the level of neutralizing antibodies observed in clinical trials was notably lower than in patients who'd received a traditional COVID-19 vaccine.

Following this study, Vaxart ran a preclinical trial specifically targeting the S-protein, which is involved in receptor viral attachment and entry into host cells. The initial results of this study, which were released in late February, demonstrated "robust neutralizing antibody responses in mucosal sites" for non-human primates. 

Though these very early stage results are encouraging, Vaxart's oral S-only COVID-19 candidate, as well as its remaining pipeline, looks to be a long ways off from generating any recurring revenue. This makes Rahimi's $18 price target unlikely to be hit in 12 months, if ever.

A physician administering a vaccine into the upper-left arm of a patient.

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Ocugen: Implied upside of 355%

However, the crème-de-la-crème of upside opportunity among COVID-19 stocks happens to be small-cap clinical-stage biotech company Ocugen (OCGN -3.90%). If Robert LeBoyer of Noble Financial is correct with his price target of $15 a share for Ocugen, investors would enjoy a 355% ride higher over the coming 12 months.

Since this list is all about COVID-19 stocks, it shouldn't be a surprise that LeBoyer's optimism has almost everything to do with Covaxin, which is an experimental COVID-19 vaccine Ocugen has commercially licensed from India's Bharat Biotech.

In 2021, Bharat Biotech conducted a large-scale study involving Covaxin with 25,800 participants in India. This clinical trial produced a VE of 78% that ultimately was the basis for Covaxin getting the green light from the WHO. In LeBoyer's view, Covaxin offers competitive advantages over other available COVID-19 vaccines in North America. 

But there's a really big asterisk that investors need to be aware of. Ocugen's commercial licensing of Covaxin only pertains to the U.S. and Canada. Covaxin could theoretically be approved for use in every market around the world except the U.S. and Canada, and Ocugen wouldn't see a dime. While the U.S. and Canada are generally lucrative markets for brand-name drugs, both countries have already invested heavily in COVID-19 treatments and may not have room on pharmacy shelves for a vaccine that produced "only" a 78% VE.

The other big problem for Ocugen is that its quick path to revenue was yanked away by the U.S. Food and Drug Administration (FDA) one month earlier. On March 4, the FDA declined Ocugen's EUA request for pediatric patients aged 2 to 18. This means Covaxin's U.S. audience will only be adults, and Covaxin will have to go through the standard (i.e., slower) route of drug approval with the FDA. 

Although Ocugen's eye-disease-related pipeline could one day be worthwhile, it's hard to see this company getting anywhere near $15 with minimal use for Covaxin in the U.S. and Canada.