COVID-19 pandemic more than a century after the Spanish flu

Eskild Petersen and colleagues published a relevant comparison of the novel coronavirus outbreak with past influenza pandemics.¹ Here we comment on fatality rates, considering evidence for the pathogenesis of these two respiratory viruses.

If introduced in our contemporary world, the influenza strain that caused the 1918 Spanish flu would probably not repeat the same scenario. Autopsy series have revealed that the majority of deaths at any age resulted from bacterial coinfections with common species of the upper respiratory tract, including Streptococcus pneumoniae.² Thus, antibacterial interventions and pneumococcal immunisation have substantially reduced the morbimortality of flu³ and probably explain the attenuation of influenza pandemic excess mortality during the past century.¹

Severe acute respiratory syndrome coronaviruses (SARS-CoVs) have a different pattern of disease. Autopsies during the 2002–03 SARS-CoV outbreak showed desquamative viral bronchio-alveolitis, but also interlobular and alveolar capillaritis and multiorgan vasculitis with associated thrombotic phenomena mostly in venules.⁴ In patients who died from SARS-CoV-2, anatomopathological analyses have highlighted small and medium arterial endothelial lesions with cytoplasm vacuolisation, cell detachment, and platelet plus fibrin aggregates.⁵ It appears then that, unlike influenza, severe and fatal SARS-CoV infections do not result from the combined occurrence of viral and bacterial pneumonia but are due to a secondary vascular and inflammatory disease in which immune responses dysregulation and host factors have a role.

Likewise, the age-specific patterns during influenza epidemics have been hypothesised to be driven by the immune history of the hosts, with a kind of imprinting induced by the influenza viruses encountered in life. Thus, the highest fatality rate in 1918 could have occurred in young adults because individuals older than 40 years had probably acquired a relative pre-immunity to influenza strains circulating before 1878. In 1977–78, the low proportion of influenza-related deaths among the group aged 20–65 years was linked with antibodies previously acquired against H1N1 viruses circulating before 1957. Similarly, this event might have thereafter reduced the attack rates of the 2009 H1N1 influenza virus in elderly people.⁶ To date, whether relative pre-immunity against SARS-CoVs exists is unknown. SARS-CoV-2 affects mainly older people, and access to high-quality health care probably explains in part disparities in SARS-CoV-2 mortality rates in people younger than 65 years. Partial protection against, or on the contrary antibody-dependent enhancement of, coronavirus disease could be conferred by previous exposure to antigenically related strains. However, specific antibodies against endemic coronaviruses are inconstantly acquired and of short duration.⁷

Thus, coronavirus infections have specificities that remain to be investigated. Availability of preventive and therapeutic tools against viral infections and their related complications is a determining factor for their disaster risk assessment.