SARS-CoV-2 infection in India bucks the trend: Trained innate immunity?

SARS-CoV-2, the causative agent of COVID-19 pandemic caught the world unawares by its sudden onset in early 2020. Memories of the 1918 Spanish Flu were rekindled raising extreme fear for the virus, but in essence, it was the host and not the virus, which was deciding the outcome of the infection. Age, gender, and preexisting conditions played critical roles in shaping COVID-19 outcome. People of lower socioeconomic strata were disproportionately affected in industrialized countries such as the United States. India, a developing country with more than 1.3 billion population, a large proportion of it being underprivileged and with substandard public health provider infrastructure, feared for the worst outcome given the sheer size and density of its population. Six months into the pandemic, a comparison of COVID-19 morbidity and mortality data between India, the United States, and several European countries, reveal interesting trends. While most developed countries show curves expected for a fast-spreading respiratory virus, India seems to have a slower trajectory. As a consequence, India may have gained on two fronts: the spread of the infection is unusually prolonged, thus leading to a curve that is "naturally flattened"; concomitantly the mortality rate, which is a reflection of the severity of the disease has been relatively low. I hypothesize that trained innate immunity, a new concept in immunology, may be the phenomenon behind this. Biocultural, socioecological, and socioeconomic determinants seem to be influencing the outcome of COVID-19 in different regions/countries of the world.