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Which viruses are the most dangerous?

Tania Louis
Tania Louis
PhD in biology and Columnist at Polytechnique Insights
Key takeaways
  • Several criteria need to be considered to determine how dangerous a virus is, including its lethality, the number of people infected and its mode of transmission.
  • How dangerous a virus is also depends on the long-term after-effects it leaves behind, such as Lassa fever, which causes deafness and myocarditis.
  • Until it was eradicated in 1979, smallpox was probably the worst pandemic, with a mortality rate of 30% and 300 million victims over the last century.
  • The Covid-19 pandemic may have caused more than 18 million deaths in just two years, around thirteen times more than HIV over the same period.
  • Vaccines and treatments can considerably reduce the lethality of various viruses, but their availability remains extremely unequal around the world.

They have shaped our evo­lu­tion and can be promis­ing med­ical tools, but virus­es are above all asso­ci­at­ed with the notion of dis­ease. They even take their name from the Latin word for poi­son… Let’s take a look at the most dan­ger­ous spec­i­mens in the viral menagerie.

The most deadly viruses

The first thing that comes to mind when we talk about how dan­ger­ous a virus is gen­er­al­ly its lethal­i­ty: if a per­son is infect­ed, what is the risk of them dying? Some virus­es are par­tic­u­lar­ly wor­ry­ing from this point of view. The rabies virus, which affects the ner­vous sys­tem, is almost 100% fatal once symp­toms appear. The best defense against this dis­ease is vac­ci­na­tion. Use­ful before or after expo­sure to the virus, it can be used in humans but also in ani­mals like­ly to con­t­a­m­i­nate them, main­ly domes­tic dogs1

HIV, the Human Immun­od­e­fi­cien­cy Virus, is also fatal in almost 100% of cas­es if left untreat­ed. Less than one per­cent of patients seem to be able to spon­ta­neous­ly con­trol the virus and avoid the devel­op­ment of Acquired Immun­od­e­fi­cien­cy Syn­drome (AIDS)2. For­tu­nate­ly, cur­rent treat­ments can con­trol HIV so effec­tive­ly that infect­ed peo­ple may no longer have symp­toms, no longer be con­ta­gious and no longer die because of the viral infec­tion. Despite the absence of a vac­cine, effec­tive pre­ven­tive approach­es do exist, notably pre-expo­sure pro­phy­lax­is, or PreP. How­ev­er, access to these ther­a­pies remains unequal across the world, and there is no treat­ment that can be used on a large scale to cure HIV.

3D recon­struc­tion of a filovirus.

The exam­ples of rabies and HIV show that the intrin­sic lethal­i­ty of a virus can be great­ly reduced when effec­tive means of pre­ven­tion or treat­ment are avail­able. Progress is being made in these areas with anoth­er type of par­tic­u­lar­ly lethal virus: filovirus­es. This is the fam­i­ly of virus­es that includes Ebo­la and Mar­burg, which do not cause dis­ease in some African bats but do cause hem­or­rhag­ic fevers in humans. The aver­age fatal­i­ty rate is around 50%, but varies accord­ing to epi­dem­ic and strain, and has already exceed­ed 80%3. The WHO now rec­om­mends two mon­o­clon­al anti­body-based treat­ments for the most dan­ger­ous strain of Ebo­la4, as well as two vac­cines, although research is still under­way to deter­mine the best vac­cine reg­i­mens5

We can reduce lethal­i­ty of var­i­ous virus­es thanks to vac­cines and treat­ments. But we must not for­get that they are extreme­ly uneven­ly avail­able around the world, and vary accord­ing to geo­graph­i­cal area, geopo­lit­i­cal sit­u­a­tion, or finan­cial resources. Not all pop­u­la­tions have the same oppor­tu­ni­ties when faced with the same infec­tious agent6.

From theoretical lethality to actual mortality

Some virus­es become par­tic­u­lar­ly dan­ger­ous when they trig­ger spe­cif­ic dis­eases: the severe form of yel­low fever or the pul­monary syn­drome caused by cer­tain Han­tavirus­es, trans­mit­ted by rodents7, can exceed 50% lethal­i­ty. For­tu­nate­ly, how­ev­er, these clin­i­cal forms are rel­a­tive­ly rare. This illus­trates anoth­er para­me­ter to be con­sid­ered when assess­ing the dan­ger of a virus: the num­ber of peo­ple it infects and makes ill. The Crimean-Con­go hem­or­rhag­ic fever virus, trans­mit­ted by ticks, is a cause for con­cern, with a fatal­i­ty rate of around 40%. It is there­fore being mon­i­tored and stud­ied, but although it has been present for decades and is endem­ic in some coun­tries, few­er than 20,000 cas­es have been record­ed in total8.

To assess the real impact of a virus, it seems rel­e­vant to look at the num­ber of deaths it has actu­al­ly caused. From this point of view, HIV, with its 40 mil­lion deaths over forty years, remains the main scourge of the present day, but SARS-CoV­‑2 has affect­ed so many peo­ple and had so many indi­rect impacts that the Covid-19 pan­dem­ic may have caused more than 18 mil­lion deaths in just two years, i.e. around thir­teen times more than HIV over the same peri­od9. This con­sid­er­able num­ber is still low­er than the con­se­quences of the Span­ish flu, which is thought to have claimed at least 50 mil­lion lives in 1918 and 1919, in a con­text com­pli­cat­ed by the First World War10. This pan­dem­ic is con­sid­ered to be one of the worst ever expe­ri­enced by humanity.

World­wide dis­tri­b­u­tion of Crimean-Con­go fever virus (CCHFV)11.

How­ev­er, the fur­ther back we go, the more dif­fi­cult it is to make esti­mates, and com­par­isons lose their rel­e­vance if we don’t con­sid­er the increase in the num­ber of humans liv­ing togeth­er on our plan­et. If we exclude plagues caused by bac­te­ria, the worst pan­dem­ic is prob­a­bly that caused by small­pox. With a mor­tal­i­ty rate of around 30%, major after-effects in some of the sur­vivors, thou­sands of years of prop­a­ga­tion and 300 mil­lion vic­tims in the twen­ti­eth cen­tu­ry alone, it’s enough to make you shud­der12. This dis­ease, brought to Amer­i­ca by the con­quis­ta­dors, is even thought to have played a fun­da­men­tal role in the con­quest of the New World, because the native pop­u­la­tion had no immu­ni­ty at all13. But small­pox is also one of human­i­ty’s great­est suc­cess­es: since 1979, it is the only human dis­ease to have been offi­cial­ly erad­i­cat­ed thanks to vaccination.

Different reasons for concern

The mor­tal­i­ty rate of a virus is inevitably a sig­nif­i­cant fac­tor, but it is far from the only para­me­ter to be tak­en into account when assess­ing how dan­ger­ous it is. For exam­ple, the impact may be con­sid­ered more seri­ous when it affects cer­tain pop­u­la­tions, such as chil­dren. Rotavirus­es, for exam­ple, do not appear to pose much of a threat if they are pre­sent­ed as the cause of gas­tro-enteri­tis. But they par­tic­u­lar­ly affect chil­dren under the age of five, in whom they can cause severe dehy­dra­tion lead­ing to hos­pi­tal­i­sa­tion. More than 180,000 chil­dren died from them in 2017, main­ly in low- and mid­dle-income coun­tries14.

Fur­ther­more, how dan­ger­ous a virus is depends very much on its rate and modes of trans­mis­sion. Measles is par­tic­u­lar­ly impres­sive in this respect: one infect­ed per­son can infect around fif­teen oth­ers, mak­ing this dis­ease very dif­fi­cult to con­trol. It is so con­ta­gious that its spread can only be stopped if 95% of the pop­u­la­tion is immu­nised. How­ev­er, vac­ci­na­tion cov­er­age is far from reach­ing this lev­el every­where in the world, includ­ing Europe15. As a result, no coun­try has man­aged to rid itself of this dead­ly dis­ease, which remains a cause for con­cern for health agen­cies16.

Num­ber of deaths due to rotavirus per 100,000 chil­dren aged under 5 years in dif­fer­ent coun­tries, in 201617.

The three coro­n­avirus­es that have caused prob­lems over the last twen­ty years illus­trate the impor­tance of con­ta­gious­ness in the dan­ger posed by a virus. MERS-CoV, which appeared in Sau­di Ara­bia in 2012, seems wor­ry­ing with its case-fatal­i­ty rate of around 35%, but it has caused few­er than 1,000 deaths in total because it is very dif­fi­cult to trans­mit between humans: most cas­es result from con­tact with drom­e­daries car­ry­ing the virus18. Con­verse­ly, SARS-CoV­‑2 has a fair­ly low case-fatal­i­ty rate (which is dif­fi­cult to esti­mate at the moment because it varies depend­ing on the vari­ant, age, lev­el of immu­ni­sa­tion, etc.), but it has caused many more deaths because it has infect­ed more people. 

For its part, SARS-CoV­‑1, which appeared in 2002 and was respon­si­ble for SARS (Severe Acute Res­pi­ra­to­ry Syn­drome), was as con­ta­gious as SARS-CoV­‑2 at the start of the pan­dem­ic, and had sim­i­lar modes of trans­mis­sion. How­ev­er, this virus, which is lethal in almost 10% of cas­es, was stopped in just a few months, where­as its more recent cousin became uncon­trol­lable… Because car­ri­ers of SARS-CoV­‑1 were only con­ta­gious when they were symp­to­matic. It was there­fore easy to set up effec­tive quar­an­tines. SARS-CoV­‑2, on the oth­er hand, can be trans­mit­ted by peo­ple who show no symp­toms, mak­ing it much more dif­fi­cult to stop. The con­ta­gious­ness of asymp­to­matic peo­ple is there­fore also a dan­ger fac­tor. It also part­ly explains the spread of HIV, where car­ri­ers can be con­t­a­m­i­nat­ed for up to ten years before devel­op­ing symptoms.

More than just deaths 

Final­ly, to assess how dan­ger­ous a virus is, we need to con­sid­er all its con­se­quences, which, as the Covid-19 pan­dem­ic clear­ly showed, are not lim­it­ed to mor­tal­i­ty. Hos­pi­tal­i­sa­tion, which can over­whelm a health­care sys­tem, and long-term after-effects, which have health impli­ca­tions as well as social and eco­nom­ic ones, can also be sig­nif­i­cant. This was the case with small­pox, which caused scars, par­tic­u­lar­ly on the face, but could also lead to blind­ness. Polio, which has almost dis­ap­peared thanks to vac­ci­na­tion but is still cir­cu­lat­ing in Pak­istan and Afghanistan, can cause per­ma­nent paral­y­sis19. And Las­sa fever, endem­ic in West Africa, caus­es deaf­ness and myocardi­tis20

Papil­lo­mavirus­es can cause can­cer not only of the cervix, but also of the vagi­na, vul­va, anus, penis and oral cav­i­ty. Vac­ci­na­tion against cer­tain strains can now dras­ti­cal­ly reduce these risks.

The list of virus­es whose con­se­quences per­sist over time is a long one: we could add to it those that pro­mote the devel­op­ment of can­cers, such as papil­lo­mavirus­es or hepati­tis B and C virus­es21, those like­ly to cause more severe symp­toms when reac­ti­vat­ed after the orig­i­nal infec­tion (such as the chick­en­pox virus, also respon­si­ble for shin­gles) or those which, ini­tial­ly per­ceived as fair­ly harm­less, actu­al­ly appear to be linked to seri­ous ill­ness­es. The most recent exam­ple is the Epstein-Barr virus, a her­pes present in 90% of the pop­u­la­tion, which is clear­ly asso­ci­at­ed with the devel­op­ment of mul­ti­ple scle­ro­sis22.

Once all these fac­tors have been tak­en into account, it seems illu­so­ry to iden­ti­fy THE most dan­ger­ous virus. But hav­ing them in mind enables us to know which virus­es to keep a close eye on, and to con­sid­er ways of mak­ing each of them as safe as pos­si­ble, in par­tic­u­lar by abol­ish­ing the inequal­i­ties in access to treat­ment and pre­ven­tion tools that still divide the world. Obvi­ous­ly, this debate must be extend­ed to non-viral infec­tious agents: bac­te­ria, fun­gi, and oth­er par­a­sites, such as the Plas­mod­i­um respon­si­ble for malar­ia. The One Health approach is also a reminder that humans are part of ecosys­tems and that health issues must be con­sid­ered on an envi­ron­men­tal scale23.

3https://​www​.who​.int/​f​r​/​n​e​w​s​-​r​o​o​m​/​f​a​c​t​-​s​h​e​e​t​s​/​d​e​t​a​i​l​/​e​b​o​l​a​-​v​i​r​u​s​-​d​i​sease et https://​www​.who​.int/​f​r​/​n​e​w​s​-​r​o​o​m​/​f​a​c​t​-​s​h​e​e​t​s​/​d​e​t​a​i​l​/​m​a​r​b​u​r​g​-​v​i​r​u​s​-​d​i​sease

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