Is monkeypox the new COVID?

By Jasper Kan

Recently, the rise of monkeypox cases worldwide alarmed the COVID-19- recovering world. The lessons learnt from the coronavirus pandemic resulted in increased caution to prevent another outbreak. However, the question arose as to whether it is as big a threat as COVID was. 

Humans can be infected with monkeypox by either direct contact with other mammals or human-to-human transmission, which is achieved through respiratory excretions and saliva, or lesion exudates. A typical patient initially develops a fever, a headache and fatigue. Then, lymph nodes swell and become firm, tender, and painful. Rash development then follows, which first appears on the face and oral cavity, mainly spreading to proximal parts of the body. At this point, patients have difficulty swallowing as well. The time periods and clinical symptoms of monkeypox largely resembles that of smallpox, part from it causing a milder fever and the swelling lymph nodes.¹

The monkeypox virus belongs to the Orthopoxvirus genus and is closely related to the notorious smallpox virus. Monkeypox was first discovered in monkeys in 1958 (hence the namesake). In 1970, there was the first human case in the Democratic Republic of the Congo (DRC).² It was historically a West African disease which spread to Central Africa in the 1980s. Compared to its western counterparts, the Central African variant has mutated to prevent T-lymphocyte (part of adaptive immunity reacting with non-self-antigens) activation via their receptors and stops inflammatory cytokine production. Additionally, this variant inhibits complement enzymes that enhance the ability of antibodies and phagocytic cells to clear the virus; and downplay apoptotic responses (a programmed cell death of infected cells).¹ This elevates its mortality rate to 10.6% compared with West Africa’s 3.6%.²

Even before the global outbreak, there were increased speculations of such happening. Over the past 4-5 decades, rodents were reported as a new intermediate host in Ghana as well,  showing that monkeypox has developed the alarming ability to transmit between species. Increased monkeypox cases were also reported further and further away from their West African origin through increased global travelling and human-to-human close contact. Local transmission was already shown to have epidemic potential (R-number >1).² In early May 2022, the surge came in developed countries and the figure has reached 550 by June 1, 2022. Among them, nearly 200 were confirmed in the UK.³

The smallpox eradication in 1980 could be attributed to a drastic drop in routine smallpox vaccination, which also gives approximately 85% protection against monkeypox. Vaccination rates in countries with confirmed cases was only 0-21%, whereas 80-96% of all cases were unvaccinated. This makes local transmission easier since the virus enjoys a longer latent period for transmission before eventual elimination. As more and more new-borns were unvaccinated, the age range of unvaccinated people widens and creates more room for transmission. Rapid genetic evolution was also seen in monkeypox. In an area roughly the size of Iceland (within the DRC), there were 4 distinct lineages in 60 monkeypox samples, showing widespread virus genome diversity.²

Unsurprisingly, COVID-19 also shares similar characteristics, for example, many COVID variants rise and fall in a year – from α in late 2020 to β and δ, and finally omicron in late 2021, creating multiple surges and decreasing effectiveness of treatment due to its specificity to a variant. Also, unvaccinated communities suffer from a quicker transmission compared with vaccinated ones.⁴ Without widespread vaccinations of monkeypox-specific jabs, monkeypox could be difficult to contain, just as COVID-19 in early 2020. 

Although there are some similarities between the viruses, both viruses belong to different families and are treated differently. Thanks to its longer history, there are already many proposed treatments for monkeypox – one of them is tecovirimat (ST-246). ST-246 targets a highly conserved F13L gene in Orthopoxviruses and prevents viral egression, therefore prevents intracellular production and release of Orthopoxviruses. This was tested in macaques with ST-246 orally prescribed three days after an initial lethal-dose infection, followed by a same dose re-infection 2 months post-recovery. ST-246 was shown to control initial infections, which was measured by a shortened period of viraemia (virus in blood, correlated to survival probability), a reduced maximum of viral load (viral genome copies in blood). ST-246 also prevented re-infections, as subjects were asymptomatic while viral genome was undetectable.⁵ For COVID, one of the most effective drugs is remdesivir, a nucleoside analogue to inhibit RNA-dependent RNA polymerase (RdRp), stalling RNA synthesis. This is achieved in remdesivir’s monophosphate (RMP), which possesses a side chain truncating an amino acid and inactivating RdRp. RMP also forms a gene translocation barrier, which prevents suitable gene segments from contacting the viral gene for the latter’s inclusion. A patient trial proves its effect on improving clinical outcomes such as mortality rate and hospitalisation time. Thus, it is widely used by patients of different severities.^6,7

The trauma brought by COVID coupled with monkeypox’s relations to an eradicated serial killer unforeseeably alarms the world – which seems an overreaction considering monkeypox’s lower range and chance of transmission (mainly by close contact of body fluids). Nonetheless, ostracization and resentment towards Asians (thought as COVID carriers) appeared again, this time against Africans and LGBT groups based on ‘carrying monkeypox’ — even though there is no proof of correlation between same-gender sexual activities and monkeypox. These vicious labels discourage the discriminated to seek medical help and undermine cooperation against disease.^8,9,10  Just like COVID-19, widespread fear incited by monkeypox hindered sanity and rational thinking among the public. This ultimately backfires, making it harder to heal the diseased as well as social division. Thus, whether monkeypox could evolve to the COVID monstrosity depends on everyone. Apart from maintaining personal hygiene and appropriate social distancing, a lesson learnt from COVID, it is high time to lend a hand instead of pointing a finger. Solidarity is the only way out to fight pandemics.

References:

1. Andrea M. McCollum, Inger K. Damon, Human Monkeypox, Clinical Infectious Diseases, Volume 58, Issue 2, 15 January 2014, Pages 260–267, https://doi.org/10.1093/cid/cit703
2. Article Source: The changing epidemiology of human monkeypox—A potential threat? A systematic review
   Bunge EM, Hoet B, Chen L, Lienert F, Weidenthaler H, et al. (2022) The changing epidemiology of human monkeypox—A potential threat? A systematic review. PLOS Neglected Tropical Diseases 16(2): e0010141. https://doi.org/10.1371/journal.pntd.0010141
3. MedicalNewsToday. Monkeypox outbreak: Global cases rise to more than 550. https://www.medicalnewstoday.com/articles/what-to-know-about-monkeypox-and-the-latest-cases [Accessed 13 June 2022]
4. Stokel-Walker C. What do we know about covid vaccines and preventing transmission? BMJ 2022; 376 :o298 doi:10.1136/bmj.o298
5. Berhanu A, Prigge JT, Silvera PM, Honeychurch KM, Hruby DE, Grosenbach DW. Treatment with the smallpox antiviral tecovirimat (ST-246) alone or in combination with ACAM2000 vaccination is effective as a postsymptomatic therapy for monkeypox virus infection. Antimicrob Agents Chemother. 2015 Jul;59(7):4296-300. doi: 10.1128/AAC.00208-15. Epub 2015 Apr 20. PMID: 25896687; PMCID: PMC4468657.
6. Gottlieb, Robert L, Vaca, C. E., Paredes, R., Mera, J., Webb, B. J., Perez, G., Oguchi, G., et al. “Early Remdesivir to Prevent Progression to Severe Covid-19 in Outpatients.” The New England journal of medicinevol. 386,4 (2022): 305-315. doi:10.1056/NEJMoa2116846
7. Kokic, G., Hillen, H.S., Tegunov, D. et al. Mechanism of SARS-CoV-2 polymerase stalling by remdesivir. Nat Commun 12, 279 (2021). https://doi.org/10.1038/s41467-020-20542-0
8. Kozlov M. Monkeypox goes global: why scientists are on alert. Nature. 2022 [doi: 10.1038/d41586-022-01421-8] 
9. Joint United Nations Programme on HIV/AIDS. UNAIDS warns that stigmatizing language on Monkeypox jeopardises public health. https://www.unaids.org/en/resources/presscentre/pressreleaseandstatementarchive/2022/may/20220522_PR_Monkeypox. [Accessed: 14 Jun 2022]
10. National Institutes of Health. People from racial, ethnic, and other groups report frequent COVID-19–related discrimination. https://www.nih.gov/news-events/news-releases/people-racial-ethnic-other-groups-report-frequent-covid-19-related-discrimination. [Accessed: 14 Jun 2022]

Article written in June, 2022