Our findings revealed for the first time that the common mtDNA variants at C5178a (ND2) and A249d (D-loop)/T6392C (CO1)/G10310A (ND3) contributed to resistance to COVID-19 development, whereas A4833G (ND2), A4715G (ND2), T3394C (ND1) and G5417A (ND2)/C16257a (D-loop)/C16261T (D-loop) variants may be risk factors, providing evidence that the gene-environment interactions exist in COVID-19 progression. Here, MT-ND3 is linked to COVID-19.