When Pfizer (PFE -1.01%) reports its second-quarter earnings on July 28, there's a good chance it'll be setting the tone for its stock performance for the rest of the year. Amid a highly unpredictable macroeconomic and epidemiological backdrop, investors will be on the lookout for any signs of weakness -- or of unexpected strength.

Especially if you're considering making an investment or selling your shares, it'll be helpful to know which issues to pay attention to in the earnings release. So let's run down the three most important questions the company will be addressing in detail.

1. Are Paxlovid sales above expectations, or below them?

The first question on investors' minds is likely to be about sales of Pfizer's antiviral pill for coronavirus infections, Paxlovid. Management's guidance for 2022 holds that the company will bring in $22 billion from the drug's global sales, spread across an estimated 120 million doses. So far, that schedule looks like it's on track based on the materials that the pharma has published and the comments made by its leaders. 

But there are also signs that could point to trouble. Health analytics company Airfinity says clinics have been slower to prescribe Paxlovid than initially expected, a sentiment that other industry commentators have echoed. And an analysis published by Reuters says demand for the pills in the European Union and Asia has been particularly slow to ramp up.

At the same time, some healthcare providers in the U.S. are reporting an increase in the number of prescriptions for the antiviral. So investors will get the final word on the topic when they see the earnings release. 

2. What's likely to happen with coronavirus product sales in 2023?

The twin successes of Paxlovid and Pfizer's vaccine for coronavirus, Comirnaty, are noteworthy. Paxlovid alone is responsible for 7.2% of its total revenue in the first quarter. Comirnaty is anticipated to make $32 billion in revenue in 2022, accounting for a 65.2% share of its total revenue in the first quarter. The two medicines' combined share of revenue raises a very important issue: How long can these two products continue to grow the top line? 

Pfizer will be keen to manage the market's expectations as accurately as possible. If the pandemic becomes less of a reason for government purchases of coronavirus medicines, 2023 could see a very sharp falloff in the company's top line. That would do some serious damage to its stock price, even if the drop-off is caused by its products being so effective at keeping case counts lower that they make themselves less necessary.

On the other hand, if innovation in Pfizer's variant-specific vaccine efforts leads to a more effective candidate that's capable of preventing people from getting infected, it would likely spur a new round of mass purchases, at least for a while.

3. Will R&D spending increase, and if so, when?

As a pharmaceutical business, research and development (R&D) is Pfizer's lifeblood. Last year, it spent more than $13.8 billion to advance its myriad clinical and pre-clinical programs on top of a steady beat of forging collaborations with -- or acquiring -- promising biotechs and smaller pharma companies.

But over the last five years, its quarterly R&D spending has fallen as a share of its revenue, indicating a lower priority for investment in new growth from its own pipeline projects. 

Still, it also claims that new R&D investments are a pillar of its capital allocation, separate from what it expects to make via partnerships and acquisitions.

Announcements of new medicines in development aren't going to be enough to move the needle unless they're significantly higher in number than usual. Instead, investors should be on the lookout for mentions of fresh research divisions dedicated to specific disease areas, or mentions of building new platforms for therapy development. Either would imply significant new R&D spending, and they would likely be a favorable sign for Pfizer's long-term performance.