RESEARCH COMMUNICATIONS CURRENT SCIENCE, VOL. 119, NO. 3, 10 AUGUST 2020 535 *For correspondence. (e-mail: gangan_prathap@hotmail.com) The H1N1 factor and inverse correlation between death rates due to COVID-19 and influenza–pneumonia Ajit Haridas 1 and Gangan Prathap 2, * 1 42 Vrindavan Gardens B, Thiruvananthapuram 695 004, India 2 A. P. J. Abdul Kalam Technological University, Thiruvananthapuram 695 016, India In an earlier study, we had observed an inverse corre- lation between death rates due to COVID-19 and in- fluenza, suggesting cross-immunity. We examine virus surveillance data further to identify the key subtype of influenza virus that seems to give such cross- immunity. This is identified as the H1N1 strain and we show that a country where this strain was recently dominant has much lower COVID-19 mortality rates. It is possible to argue that many countries which already have a high burden of influenza and pneumo- nia-related deaths, may have a substantial fraction of the population immune to the SARS-CoV-2 virus and hence experience lower mortality rates at the peak typical of exponentially growing epidemics. This has implication on policies appropriate for managing the epidemic. Keywords: COVID-19, death rates, H1N1 subtype, influenza, pneumonia. IN a recent unrefereed study, Haridas and Prathap 1 showed that there is a strong and discernible inverse cor- relation between COVID-19 death rates and those due to influenza in many countries. An important implication is that several countries, including tropical countries like India with an already high burden of influenza and pneu- monia-related deaths, would be less affected by the SARS-CoV-2 virus. Another important takeaway is that, if COVID-19 death rates are indeed inversely related to those due to influenza–pneumonia, then there is the factor of ‘cross-immunity’ or ‘cross-protection’ to be consi- dered, that prior infection with one virus affords protec- tion against closely related ones. Unlike the COVID-19 pandemic, the 2009 H1N1 pandemic affected younger adults. This has been attributed to cross-immunity from infection by the prior 1950 H1N1 influenza strain 2 . Im- munological cross-reactivity of dengue virus antibodies to Zika virus (ZIKV) has been reported 3 . Cross-protection between successive waves of the 1918 Spanish flu pan- demic has been elucidated from epidemiological data 4 . Morales et al. 5 carried out a modelling study to identify factors contributing to country-wise variation in mortality in case of the 2009 H1N1 pandemic. They found that age structure contributed 40% of the variation. Mortality was prominently impacted by co-circulating influenza sub- types H3N2 and influenza B. There was a protective ef- fect to the 2009 pandemic in countries where H3N2 dom- inated in 2008. Interestingly, they found no association between pandemic mortality in 2009 and factors such as antiviral stockpiling, medical and economic factors (e.g. health expenditure), international air travel, previous circulation of seasonal H1N1, or pandemic timing in a country – the start and the peak 5 . In a major review of the lessons learnt from the 1918 influenza pandemic, Short et al. 6 remark that pre-existing immunity is likely to contri- bute to a more accurate prediction of viral severity even before the influenza virus in question becomes esta- blished as a pandemic. Skountzou et al. 2 studied cross-protection against the pandemic swine-origin 2009 H1N1 influenza virus A/California/04/09 provided by H1N1 influenza viruses that circulated in the human population from 1930 to 2000. They showed that mice exposed to the 1947 virus, A/FM/1/47, or the 1934 virus, A/PR/8/34, survived a lethal challenge with the 2009 virus. Conversely, mice exposed to the 2009 H1N1 virus were protected against a lethal challenge with mouse-adapted 1947 or 1934 H1N1 viruses. In addition, exposure to the 2009 H1N1 virus induced broad cross-reactivity against H1N1 as well as H3N2 influenza viruses. Finally, they showed that vacci- nation with the older H1N1 viruses, particularly A/FM/1/47, conferred protective immunity against the 2009 pandemic H1N1 virus. Their data offered an expla- nation for the decreased susceptibility of the elderly to the 2009 pandemic. Priyamvada et al. 3 addressed the issue of cross- reactivity between dengue virus (DENV) and ZIKV by testing sera and plasmablast-derived monoclonal anti- bodies from dengue patients against ZIKV. They showed that both acute and convalescent dengue sera potently bind and neutralize ZIKV. The cross-reactivity was evident at the monoclonal level. Their findings that pre-existing dengue antibodies may modulate immune responses to ZIKV infection are highly relevant as major- ity of regions experiencing Zika virus epidemics are endemic for dengue. The statistical inverse correlations seen between COVID-19 deaths and H1N1 infections and deaths suggest that there is a factor of cross-protection or pre- existing immunity involved, and this points the way to better interventions at the level of public health. As done in our earlier study 1 , we obtained influenza and pneumonia-related death rates per 100,000 of popula- tion for a cohort of 147 countries from the portal https:// www.worldlifeexpectancy.com/cause-of-death/influenza- pneumonia/by-country/ We obtained the count of deaths from COVID-19 as of 16 April 2020 for the same cohort of 147 countries from https://www.worldometers.info/coronavirus/ . Influenza and pneumonia are a natural cause of death in old age in many countries, irrespective of the quality of health care,