The coronavirus crisis is a new threat in the Amazon where a surge in deforestation under far-right President Jair Bolsonaro already threatens isolated tribes.
"Today, the feast of Pentecost, we call on the Holy Spirit to grant light and strength to the Church and to society in Amazonia, which has been harshly tested by the pandemic," the Argentine pope said, recalling his Synod for poverty-stricken Amazon communities last October.
"There are so many infected and dead people, including among the indigenous peoples, who are particularly vulnerable," he said, urging that no one be without medical assistance.
According to the Association of Indigenous Peoples of Brazil, the virus has already spread through 40 native groups with 537 cases of infection and 102 fatalities.
The latest census from 2010 found nearly 800,000 indigenous people in 300 tribes living in Brazil.
The pope addressed Catholics from his window overlooking the square for the first time since March 10 as the city state further eases its virus lockdown.
For weeks his traditional Angelus prayer had been live-streamed each weekend to the world from inside the Apostolic Palace.