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It is the first attack of its kind in the Syrian capital since forces toppled longtime ruler Bashar Al-Assad in December, as security remains one of the greatest challenges for the country's new authorities.
The correspondents at the scene saw first responders transporting people from the site, with destruction at the church including shattered wood from fittings and pews, icons strewn on the ground and pools of blood.
The interior ministry said in a statement that "a suicide attacker affiliated with the terrorist organisation Daesh entered the Saint Elias church in the Dwelaa area of the capital Damascus where he opened fire then blew himself up with an explosive belt".
Syrian civil defence said in a statement that the attack killed "more than 15 people and a number of wounded, according to a preliminary toll".