The conflict between Israel and the Palestinians took another catastrophic turn Tuesday, when hundreds of people were reportedly killed in a blast at a Gaza City hospital. 

It came within a day of President Biden’s anticipated arrival in Israel.

Hamas has blamed the massive explosion on an Israeli airstrike. The Israel Defense Forces (IDF) have claimed rockets fired by Islamic Jihad were responsible. Neither version of events has been independently verified.

Even before the latest tragedy, about 2,800 Palestinians had been killed in reprisals for a surprise Hamas attack on Oct. 7, which claimed the lives of about 1,400 Israelis. At least 30 U.S. citizens have been killed.

The explosion Tuesday in Gaza City made an already bleak situation in the region even darker.

Biden was to fly overnight to Israel in a show of support for the key U.S. ally. White House press secretary Karine Jean-Pierre has said the trip is intended “to demonstrate his steadfast support for Israel in the face of Hamas’s brutal terrorist attack.”

Biden had been scheduled to later meet in Jordan with King Abdullah II, Egyptian President Abdel Fattah al-Sisi and Palestinian President Mahmoud Abbas. However, Abbas withdrew after news broke of the explosion at the hospital. Soon afterward, it was announced that Biden would no longer travel to Jordan.

Here are five big questions confronting Biden.

Does Israel hold off on a ground invasion while he’s there?

The trip holds some political risks for Biden, even if it is also an opportunity to show solidarity with Israel and command the world stage.

It is widely assumed Israel will launch a ground invasion of Gaza very soon.

But it also seems likely that an invasion will not take place while Biden is there, given the near certainty that the operation would be bloody and brutal.

Still, if an invasion commenced as soon as Biden left Israel, it could still pose political problems for the president. 

In particular, it would be potentially damaging if he appears to have rubber-stamped an Israeli plan that goes terribly wrong.

How strongly does Biden call for restraint?

One of the most difficult questions for Biden will be how to calibrate his message.

The White House does not seriously question Israel’s right to strike back with overwhelming force in the aftermath of what Biden on Saturday called “the worst massacre of Jewish people since the Holocaust.”

But Israel has already killed roughly twice as many people as were killed in the original attack. Save the Children has estimated more than 1,000 Palestinian children have died.

The huge and mounting death toll caused by Israel’s counterstrikes is already inflaming public opinion in Europe as well as the Middle East, though the American public tends to be more sympathetic to Israel. 

During a weekend visit, Senate Majority Leader Chuck Schumer (D-N.Y.)  said that while he supported Israel “eliminating the threat of Hamas, once and for all,” he also believed it was imperative for democracies to “hold themselves to a higher standard” than armed groups.

Defense Secretary Lloyd Austin said at a meeting with his Israel counterpart last Friday that it was “a time for resolve and not revenge.”

Beyond the Palestinian deaths, there is also a grave humanitarian crisis in Gaza, with water, food and fuel all in scarce supply.

How do Hamas, Hezbollah or Iran react to his trip?

A big worry in the current situation is a broader regional conflict. 

Iran is a longtime sponsor of Hamas, though the U.S. and Israeli governments have both said they do not have direct evidence that Tehran had prior knowledge of the Oct. 7 attack. 

Iran is also a patron of Hezbollah, the militant group whose stronghold is in southern Lebanon, abutting Israel’s northern border.

There has been fighting between Hezbollah and the IDF at the northern border in recent days but at a somewhat muted scale, relative to the capabilities of both sides.

It seems at least plausible that Hezbollah or Hamas could seek a show of defiance during Biden’s visit.

Iran’s foreign minister, Hossein Amirabdollahian, warned on Monday that “new fronts will be opened” unless Israel stops killing civilians in Gaza.

How much focus does he put on the plight of hostages?

One of the most vexing challenges facing Biden is the hostages taken by Hamas.

Israeli authorities on Monday increased their estimate of the number of people taken hostage to 199, up from around 150. 

Thirteen U.S. citizens are unaccounted for. The Biden administration has implicitly acknowledged some are likely to be in captivity, though the specifics are still shrouded in uncertainty.

Biden late last week held a virtual call with the families of those Americans whose whereabouts remain unknown.

But getting any hostages out will be extraordinarily difficult, given the nature of the conflict and the possibility that many of the hostages taken by Hamas are likely to be held underground.

The president won’t want to ignore the plight of the hostages, but he may be reluctant to say a lot in public, given that other members of his administration have said there are sensitive talks underway with third-party countries to try to win the hostages’ release. 

How does the trip play at home?

Biden’s short-term response to the violence in Israel and Gaza has not met with much direct criticism at home so far, in part because both major parties are united in their horror at the Hamas assault.

Still, some Republicans and their allies in conservative media have alleged that Biden has been too soft in his dealings with U.S. adversaries, including Iran, in a way that has emboldened bad actors.

A deal in recent months by which five Americans were released by Iran in return for the unfreezing of $6 billion in Iranian funds has come under particular criticism. Those funds have now been, in effect, refrozen.

On the other hand, Biden could benefit at home from being seen as statesmanlike — and as the personification of American support and sympathy for Israel in the wake of the Oct. 7 attack.