Correspondence
COVID-19 pandemic
more than a century
after the Spanish flu
Eskild Petersen and colleagues pub­
lished 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
www.thelancet.com/infection Published online August 11, 2020 https://doi.org/10.1016/1473-3099(20)30650-2 1
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 Lancet Infect Dis 2020
inconstantly acquired and of short Published Online
duration.7 August 11, 2020
https://doi.org/10.1016/
Thus, coronavirus infections S1473-3099(20)30650-2
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.
We declare no competing interests.
*Emilie Javelle, Didier Raoult
emilie.javelle@gmail.com
Laveran Military Teaching Hospital, Marseille,
France (EJ); IHU-Méditerranée Infection, 13005
Marseille, France (EJ, DR); and Aix-Marseille
Université, IRD, AP-HM, SSA, MEPHI, and VITROME,
Marseille, France (EJ, DR)
1 Petersen E, Koopmans M, Go U, et al.
Comparing SARS-CoV-2 with SARS-CoV and
influenza pandemics. Lancet Infect Dis 2020;
published online July 3. https://doi.
org/10.1016/S1473-3099(20)30484-9.
2 Morens DM, Taubenberger JK, Fauci AS.
Predominant role of bacterial pneumonia
as a cause of death in pandemic influenza:
implications for pandemic influenza
preparedness. J Infect Dis 2008; 198: 962–70.
3 Chien Y-W, Levin BR, Klugman KP.
The anticipated severity of a “1918-like”
influenza pandemic in contemporary
populations: the contribution of antibacterial
interventions. PLoS One 2012; 7: e29219.
4 Ding Y, Wang H, Shen H, et al. The clinical
pathology of severe acute respiratory
syndrome (SARS): a report from China.
J Pathol 2003; 200: 282–89.
5 Varga Z, Flammer AJ, Steiger P, et al.
Endothelial cell infection and endotheliitis
in COVID-19. Lancet 2020; 395: 1417–18.
6 Morens DM, Taubenberger JK, Harvey HA,
Memoli MJ. The 1918 influenza pandemic:
lessons for 2009 and the future. Crit Care Med
2010; 38: e10–20.
7 Dandekar AA, Perlman S. Immunopathogenesis
of coronavirus infections: implications for
SARS. Nat Rev Immunol 2005; 5: 917–27.