To the editor: We appreciate the response to our paper made by Dr. Mak and colleagues, whose data from Hong Kong SAR appear to be in good agreement with what we have seen in Norway. In our original study, we observed a significantly higher frequency of D222G in patients with severe outcomes (including fatal) compared to patients with mild dis-ease. In fact, in both our data set and the Hong Kong data, mutant viruses were not found among several hundred mild cases. Furthermore, as can be seen from our published data, the frequency may be higher also in fatal outcomes (eight of 27 cases) versus severe non-fatal outcomes (three of 34 cases). Comparing these frequencies results in p=0.078 with Fisher's exact test (two-sided) and p=0.046 with the Mid-P Exact test (two-sided). It would be interesting to know if the new data from Hong Kong SAR can corroborate this obser-vation. Mak et al. report four fatal D222G cases and five non-fatal severe D222G cases, but one would also need to know the total number of fatal cases versus non-fatal severe cases analysed to make the compari-son. Hopefully, this information can be obtained. D222G substitution in virus isolates only and not in the original clinical specimens was found in one case in Hong Kong and 14 cases reported by the United States (US) Centers for Disease Control and Prevention [1]. We have also seen this virus culture artefact in one case with mild disease. This case was counted as wild type in our data set. This further underscores the impor-tance to perform the sequence analysis of the primary specimen.