6 June 2022 Episode 265: Monkeypox and COVID continued

Episode 265: Monkeypox and COVID continued

Dear colleagues,

In this episode, I will highlight some additional info on Monkeypox, provided by Patrick Smits, Wim Vandamme and Geert Molenberghs and I will discuss new data on long-term consequences of COVID, treatment options and the exciting possibility to monitor and even predict the epidemic via virus load and sequencing in wastewater.

PAR 1 MONKEYPOX

Ep 265-1: Situation update by WHO 4 June 2022

Clinical picture in these “Northern” cases is NOT classical:

• Common presenting symptoms include genital and peri-anal lesions, fever, swollen lymph nodes, and pain when swallowing.

• The initial presentation of a genital or peri-anal rash in many cases suggests close physical contact as the likely route of transmission during sexual contact:
  1. Face-to-face, skin-to-skin, mouth-to-mouth, mouth-to-skin contact including during sex. 
  2. Mucocutaneous ulcers, respiratory droplets (and possibly short-range aerosols), or contact with contaminated materials (e.g., linens, bedding, electronics, clothing).
  3. Simultaneous sexually transmitted infections such as herpes simplex virus, syphilis or N. gonorrhoea
  4. .
• West-African variant, but only few cases directly linked to West-Africa (i.e. Nigeria).
• Hospitalization because of adequate pain management and to treat secondary infections.
• No mortality until now

In Africa, mortality is higher, may be up to 10 % in Central African form.

Reason of death often bacterial super-infections. 

Animal reservoir includes rope squirrels, tree squirrels, Gambian pouched rats, dormice, non-human primates.

NO cases of domestic animals with MPX

INTERESTING PODCAST with Wim Vandamme: description of an unusual epidemic of 500 cases with 50 deaths in Maniema province of DRC https://podcasts.apple.com/be/podcast/health-check/id261779764?i=1000563892915

Ep 265-2 CASE REPORT

A case of monkeypox in an HIV-positive individual receiving antiretroviral therapy (normal CD4+ T cells and suppressed viral load):

• Presented with a genital rash in Melbourne, Australia after return from Europe in May 2022.
• Subsequently developed systemic illness and disseminated rash and
• 11 days after symptom onset, hospitalised to manage painful bacterial cellulitis of the genital area.

Ep 265-3: Potential vaccines

1. Dryvax-like = ACAM-2000 = classical cowpox-derived vaccine with quite some potential side effects

1. 1. Myocarditis and/or pericarditis, ischemic heart disease and non-ischemic dilated cardiomyopathy.
   2. Encephalitis, encephalomyelitis, encephalopathy, progressive vaccinia (vaccinia necrosum), generalized vaccinia, severe vaccinial skin infections, erythema multiforme major (including Stevens-Johnson syndrome), eczema vaccinatum, fetal vaccinia and fetal death.
   3.  Ocular vaccinia and blindness. (5.3)

These risks, including risks of severe disability and/or death, are increased in vaccinees with:

• Cardiac disease

• Eye disease treated with topical steroids.  

• Congenital or acquired immune deficiency disorders.

• History or presence of eczema and other skin conditions.

• Infants < 12 months of age.

• Pregnancy

ACAM2000 is a live vaccinia that can be transmitted to persons who have close contact with the vaccine

SAFER ALTERNATIVES

2. Modified Vaccinia Ankara-Bavarian Nordic: in Canada and Europe

MVA-BN is injected like other modern vaccines rather than Dryvax which is pricked into the skin with a bifurcated needle. While the MVA-BN virus is highly attenuated and is thus incapable of replicating in the body, it is still capable of eliciting a potent immune response and does so without producing the post-vaccination complications associated with traditional smallpox vaccines.

3. LC16-KAKETSUKEN is a Japanese live-attenuated derivative from the original Dryvax, which has been reported to be equally immunogenic as Dryvax but without the side effects.

Ep 265-4: Overview by Jon Cohen in Science 1 June

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Reasons for the rise?

• Vaccination against smallpox stopped in the seventies
• People are invading the forest and have more contact with animal reservoirs

Why only West-African variant “escapes” from Africa: it circulates also in West-African cities, while Central-African variant remains contained to remote areas.

Ep 265-5: Recent epidemics in Europe in Eurosurveillance June 2022

1. 1. UK: 86 cases, with only 1 contact in Nigeria and 66 MSM

Clear evidence of human-to-human transmission through close contacts, including in sexual networks

1. 2. Portugal: 96 cases, of which 27 confirmed

Most cases were neither part of identified transmission chains, nor linked to travel or had contact with symptomatic persons or with animals, suggesting the possible previously undetected spread of monkeypox.

1. 3. Italy: 4 cases in MSM with viral DNA in seminal fluid and anal, penile and skin lesion. 

Finally, Geert Molenberghs estimates the following doubling time (in days), based on confirmed cases until June 3rd (with 95 % confidence interval)

World: 6.2 [5.2;7.7]

Spain: 7.6 [5.2;14.3]

Portugal 7.5 [5.4;11.9]

Canada 4.7 [2.8;14.9]

UK 5.3 [4.2;7.2]

PAR 2 LONG-TERM CONSEQUEBCES of COVID

Episode 265-6: WHO corrected death toll 2020-2021 Nature June 2022

Death toll has been underestimated in many countries (e.g. Russia, India, Brazil, Egypt…) → real death toll is estimated to be approx. 2.5 X higher than officially reported, totaling  13.3-16.6 million deaths Jan 20- Dec 2021

IHME = The Institute for Health Metrics and Evaluation is an independent global health research center at the University of Washington.

Two ways of expressing excess death: either per 100,000 or above the norm expected

Ep 265-7: Uusküla in Lancet Reg Health shows that a 3 X increased mortality persists even in subjects recovered from COVID during the next year, as compared to those who remained uninfected.  It is mainly present in older people (> 65), those who required hospitalization  and includes  respiratory, cardiovascular, cancer and other reasons.   

Ep 265-8: Banerjee in Primary Diabetes Care conducts a meta-analysis on incidence of type 2 diabetes within 4 months after COVID.

• 59 % increased risk as compared to healthy controls
• 52 % increased risk as compared to other respiratory illness of similar severity (e.g. Flu)

However: several limitations (incl retrospective set-up) warrant proper prospective studies.

PAR 3: FOLLOW-UP on TREATMENT

Ep 265-9: Arbel Res Square: Benefit of Nirmatrelvir is selective in older patients with risk factors.

During the omicron variant surge, nirmatrelvir  reduced Covid-19 hospitalizations rates by 67 % and mortality by 81 % in adults aged > 65 years with pre-existing high risk, both in patients with and without prior Covid-19 immunity.

The absolute benefit of therapy was substantially higher in patients without prior immunity.

However, no significant benefit was shown in the younger cohort.

Ep 265-10:  Sullivan medRxiv 27 May evaluates 20 randomized controlled trials with either (high tittered) COVID- convalescent plasma (CCP), various monoclonal Ab or small molecules for their efficacy to reduce COVID-19 hospitalizations

See table 1 for demographics:

• Medial age below 65 in most trials
• Increased risk for most included patients

Overall result:   

Several CCP and most monoclonal therapies show positive effect

The antivirals remdesivir and nirmatrelivir have a clear benefit.  Molnupiravir has a marginal effect.

Repurposed drugs fluvoxamine, ivermectin, colchicine and hydroxychloroquine: no significant effect.

Peginterferon lambda is beneficial

Evolution of efficacy with new variants:

• Monoclonal antibodies gradually lose their efficacy, especially against omicron, where only Evusheld maintains partial efficacy.
• Also CCP risk to lose activity.
• The antivirals remdesivir, molnupiravir and nirmatrelvir keep their activity high against VOC.

PAR 4: USEFUL INFORMATION FROM WASTEWATER

Ep 265-11: Follow-up of COVID viral load and type in wastewater is predictive of the local epidemic.

Ep 265-12: Gregory medRxiv 3 June 2022: Wastewater sequencing may reveal mutations that (much) later become evident in new VPC in patients.

These “cryptic” lineages (which were found in wastewater but not yet in patients) contained between 4 to 24 amino acid substitutions in the RBD ….. Many of the amino acid substitutions in these lineages occurred at residues

also mutated in the Omicron variant of concern (VOC).

Explanation:  wastewater is an unbiased sample of all viruses from its capture area, while sequencing in patients is only done sporadically.

Ep 265-13:  Van Boven medRxiv 30 May 2022 shows that a nationwide sewage surveillance program in the Netherlands describes the epidemic, with viral loads in sewage water closely correlating with hospitalisations.