10 dec 2021 Episode 200 : COVID – HIV and OMICRON

Dear colleagues,

I will first “revisit” the relation between HIV and COVID.  There is a clear interaction !

And next, I will update the omicron news, which is quite disturbing.   

COVID-HIV

1. Clinical aspects

Episode 200-1 : Incidence in San-Francisco Feb-March 2021 (AIDS Dec 2021)

• Incidence of SARS-CoV-2 lower in PLWH: because better adherence to NPI?
• Higher risk of severe COVID (RR 1.84): in population with low CD4 T count.

Episode 200-2: D’Souza JAIDS Jan 2022: this study based on MACS cohort in US finds a higher SARS-CoV-2 positivity rate amongst PLWH (9.4%) as compared to HIV sero-negatives (SN) (4.8 %) over the several “waves” in 2020, despite similar behavior.  Symptoms were similar, but only in a very small sample (see Table 3)

Episode 200-3: Review by Yexin Yang in Current HIV/AIDS Reports  Nov 2021:

• Cohort studies suggest similar risk of SARS-CoV-2 infection, but increased risk of severe disease in PLWH
• Various HIV-related mechanisms could be active: low CD4 T count, impaired type 1 interferon, “exhausted” CD8 T cell activity or ‘immune overactivation”.
• In addition, PLWH have increased levels of co-morbidities (hypertension, diabetes…) as compared to age-matched  SN.
• Early reports suggested that some HIV anti-virals (e.g. the reverse transcriptase inhibitor Tenofovir and  the protease inhibitor Lopinavir) could be active against SARS-CoV-“, but there is no clinical evidence for that.
• There have been small studies with mRNA vaccines in PLWH, which show efficacy and no increased risk of side effects.
• The use of Adenovirus-5 vectors (as in the Sputnik  and the Cansino vaccine) has a certain risk of increasing the susceptibility for HIV infection (see the Step and Pamphili trials https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32156-5/fulltext)   

Ep 200-4: Lakatos in HIV Medicine Nov 2021 warns for drug-drug interactions between HIV-antiretroviral therapy  or ART (reverse transcriptase, protease and integrase inhibitors) and drugs, used for COVID (Remdesivir, favipiravir, dexamethasone and chloroquine). See Table 2 p. 5.  

Ep 200-5: Peluso in Curr HIV AIDS Rep of Nov 2021 asks the question whether PLWH would be more vulnerable to central nervous system (CNS) complications when co-infected with SARS-CoV-2. The review does not provide an answer, but discusses the topic

• In COVID-19, most obvious CNS complications occur in elderly and those with severe illness, with 2/3 presenting agitation and confusion and 1/3 remaining mental problems at discharge, including headache, sleep disorders, vertigo-tinnitus, dysgeusia-anosmia, mood and cognitive disorders.  There is also a tenfold increased risk of cerebrovascular incident as compared to severe influenza.
• Importantly, several of these complications have also been described in young people with milder disease.
• The HIV-associated neurocognitive disorder (HAND) may impact up to 1/3 of PLWH on ART: while many symptoms are similar to those described in acute and pos-acute COVID, HAND occurs more gradually.

The authors provide a research agenda to investigate the interaction between both CNS syndromes in PLWH.

Ep 200-6: Case report of concomitant acute HIV and SARS-CoV-2 infection  

Ep 200-7: Another case of HIV patient with originally mild COVID-19, but then complicated with neuro-toxoplasmosis and prolonged SARS-CoV-2, which evolved with multiple immune escape mutations, under pressure of convalescent plasma therapy.

2. Vaccination

Ep 200-8: Peter Bergman in EBioMedicine Nov 2021: Comparison of Pfizer in 5 groups of immunocompromised patients:

• Side effects higher than in control with 1 person who died. (see table 2 p 6)
• Seroconversion rate of HIV patients almost identical to controls also with CD4 T < 300   

Ep 200-9: Heftdal in J Int Med Dec 2021 shows that concentrations of IgG antibodies were lower in PWH than controls at three weeks and two months (p=0.025 and p<0.001), respectively. The IgG titers in PWH with a humoral response at two months were 77.9% (95% CI: 62.5-97.0%, age and sex-adjusted p=0.027) of controls.

Ep 200-10: Spinelli CID dec 2021: also clearly lower neutralization titers to mRNA vaccines.  More no or low response to Pfizer than Moderna.

Ep 200-11: PLWH also show lower neutralization responses to the Chinese inactivated vaccines.  

3. Africa

Ep 200-12: Msomi in Nature 2  Dec 2021: Tackle HIV and COVID together in Subsaharan Africa:

• In 3.5 million people from the Western Cape with 500,000  HIV-positive,
  • people with HIV were 2 X as likely to die from COVID-19,
  • uncontrolled or advanced HIV, the risk of dying from COVID-19 4 X higher
• Prolonged COVID-19 infection in immunocompromised could lead to the emergence of a variant that is more transmissible even than the Delta variant, or that renders current COVID-19 vaccines less effective = prophetic !!!
• Nov 2021 vaccination worldwide was 40 %, but only 7 % in Africa.  Elderly are prioritized,
  • But 80 % of PLWH is under 50 !!
  • Only 17.3 million of the estimated 25.3 million African PLWH (68 %) are on ART.  

Ep 200-12: Mandala Front Immunology further substantiates the argument for prioritizing PLWH for COVID vaccination.

Ep 200-13:  Anjorin in PLoSOne reports on COVID vaccine hesitancy in Africa: about 5400 particpants from Cameroon, Ghana, Nigeria,Egypt, South Africa, Democratic Republic of Con/go and Sudan:

• 50 % were active in health related fields
• 63 % were prepared to take the vaccine
• 79 % had concerns on side effects and 39 % had concerns about vaccine-associated infection!

OMICRON (again many thanks to Patrick Smits ! )

Ep 200-14: A very interesting website

https://sars2.cvr.gla.ac.uk/cog-uk/

See model of variant Spikes s in attachment: the number of omicron-associated mutations (in red) is really spectacular.    

Ep 200-15: Prediction on activity of human monoclonal antibodies in clinical use against VOC, based on susceptibility/resistance profile for single mutant viruses (from the same site).

• Casivirimab and Imdevimab (together the Regeneron cocktail) are predicted to have problems with K417N and N440K mutations respectively, which are present in omicron. Alexander Wilhelm et al have indeed show that Regeneron is inactive against omicron (see Ep 199-6).
• Etesivimab (in the Lilly combination) has also a problem with K417N
• Sotrovimab is active against all major mutations but may have a problem with G339D of omicron.

Ep 200-16: Cathcard in medRxiv show that Sotrovimab (or Vir 7831) is a superior mAb

• VIR7831 was derived from a SARS-CoV-1 patient (cross-neutralizing with SARS-CoV-2!)
• It has a very stable in vitro neutralizing value (EC50) against all VOC, known up to Nov 2021 (Table 2 p. 41)
• Retains full in vitro neutralizing activity against an omicron pseudovirus. 
• Pretreatment of hamsters with high dose of VIR 7831 and challenged with first USA isolate of March 2020 strongly reduces viral load in lung and all signs of pathology
• This mAb has also a lot of FcR mediated functions (e.g. activation of complement, macrophages, NK cells etc.    

Ep 200-17: Gupta NEJM 30 Oct Preliminary evidence of clinical activity of Sotrovimab

Comparing 290 high risk COVID treated with a singly 500 mg infusion of Sotrovimab with 290 placebo:

• Three in Sotro versus 27 in placebo had to be hospitalized.
• None of Sotro vs 5 placebo to IC
• None of Sotro vs 1 in placebo died
• No safety concern.

Ep 200-18: Grabowski in medRxiv 9 Dec 2021: Rapid omicron spread despite herd immunity to delta

• Exponential growth of the Omicron Gauteng in the four‐week period from November 8 to December 5, 2021, with the doubling time equal 3.38 day [CI 95%: 3.18–3.61 day].
• Before the Omicron outbreak, the Delta variant was the dominant strain in Gauteng, and between July and October the COVID‐19 epidemic was receding without significant mobility reduction, suggesting that the population of Gauteng has reached herd immunity to Delta.

Ep 200-18: Reduction of in vitro neutralization is very important, even by serum from subjects who recently received a third dose of mRNA vaccine, irrespective whether compared with original, alpha or delta variant, in assays with either pseudovirus or live virus.    

So, taking into account:

• the very high transmissibility;
• the many “escape” mutations, with significant reduction of protection by either previous infection or vaccination;  
• the fact that omicron has already been “seeded” over the world;  
• the public fatigue with all kind of non-pharmacological interventions (NPI), including face masks, telework, social distance etc.  
• and the holiday season, when people will mix all over and relax NPI anyway;

Can we expect anything else than quickly heading towards the next big wave very early next year?

Nevertheless, I wish you all a quiet pleasant WE

Take care,

Guido