27 March 2023 Episode 324: Status of the present epidemic and the latest on long COVID

Episode 324:  Status of the present epidemic and the latest on long COVID

Par 1 European epidemiology

Ep 324-1: Latest bi-weekly report from ECDC 13-19 March 2023

We seem to evolve towards “endemicity” with presently a dominance of omicron XBB.1.5 recombinant

1. Clearly downward trend in most epidemiological COVID parameters

2. Over the last 12 months: several waves, but with a general downwards trend

3. Variants: XBB1.5 = 54 % >>>  BA.2.75 = 17 % > XBB (recombinants other than WBB.1.5) = 14 % > BQ.1 = 12 %.  BA.2; BA.4 and BA.5 each less than 2 %.  

Par 2 Long COVID during Omicron

Ep 324-2 Jennifer Couzin-Frankel Science Insider 21 Marc 2023 : People who catch Omicron are less likely to get Long Covid

Par 2.1 Cancer patients

Ep 324-3 John Willan Br J Haemat Feb 2023 Mortality and long COVID have reduced in haematological patients during Omicron

Prospective study in 128 patients in one center with various hematological cancers over time

• Mortality at 90 days reduced from 42 → 9 →2 % during original/alpha, delta and omicron wave:
• Long COVID ( = 12 weeks after diagnosis):  46→ 35 →14 % during original/alpha, delta and omicron wave:

Both omicron and 3 + vaccinations protect against long COVID, but difficult to determine if both are independent (since all pt received many vaccines)

In any case: should these patients still maintain strict self-isolation?

Ep 324-4 Alessio Cortellini Lancet Oncol. March 2023 post-acute COVID lower in cancer patients, infected with omicron and decreasing with each vaccination.

Multicenter study on 1900 patients with either solid cancer or hematological cancer.

Post-acute COVID = only median 39 days (= 6/7 weeks) after diagnosis

• No difference between original/alpha and delta, but clear decrease in omicron period
• Clear tendency for protective effect of vaccination in both periods.  

Authors interpretation:

Despite the tendency of omicron to elude vaccinal protection against infection, our study provides original evidence to suggest that previous immunisation is protective against omicron-related COVID-19 sequelae, further highlighting the importance of universal vaccination in reducing long-term consequences from COVID-19, maintaining optimal delivery of systemic therapy, and preserving optimal oncological care throughout the evolving phases of the pandemic  

Par 2.2. General population

Ep 324-5:Michela Antonelli Lancet June 2022 Lower risk for long COVID with Omicron in general population

Case control observational study in general UK population: over 40,000 in Delta and over 56,000 in early Omicron (Dec 21- March 22) with post-acute COVID > 4 weeks after COVID diagnosis.   

Omicron cases were less likely to experience long COVID for all vaccine timings, with an odds ratio

ranging from 0·24 (0·20–0·32) to 0·50 (0·43–0·59).

These results were also confirmed when the analysis was stratified by age group.

The difference was most pronounced in subjects with a vaccine > 6 months ago.

Ep 324-6: Christian Kahlert Feb 2023 CID Feb 2023: Post-acute COVID sequelae in 2900 Swiss HCW

Cross-sectional study: median 18.3 months after Alpha/Delta infection and 3 months after Omicron

Means and 95% CI of post-acute sequelae of SARS-CoV-2 in relation to vaccine doses received before positive swab.

Left: Participants after infection in Delta period (1 July 1st to December 31th 2021).

Right: Participants after infection in Omicron BA.1 period (January 1st to June 30th 2022).

Asterisks above bars indicate statistical significance in reference to unvaccinated participants infected in the same period, respectively, as obtained through Wald tests on coefficients of negative binomial models with group "none" as reference (*, p < 0.05; ns, p ≥ 0.05).

Conclusion:

Previous infection with pre-Omicron variants was the strongest risk factor for PASC symptoms among HCW.

Apparently these PASC symptoms after alpha-delta were very long lasting (18 months!

Vaccination prior to Omicron BA.1 infection was not associated with a clear protection against PASC symptoms

Other risk factors:

• BMI > 30
• Co-morbidity
• Any medication

Ep 324-7: UK Office for National Statistics 23 Feb 2023 https://www.ons.gov.uk/peoplepopulationandcommunity/healthandsocialcare/conditionsanddiseases/bulletins/newonsetselfreportedlongcovidaftercoronaviruscovid19reinfectionintheuk/23february2023 irus (COVID-19) reinfection in the UK: 23 February 2023

Likelihood of long COVID 12-20 weeks after infection

• If first infection: 4 % for adults (> 16 yrs) versus 1 % for children (2-15 yrs)
• If second infection: 2.4 for adults and 0.6 % for children

Par 2.3. Prevention of long COVID

Ep 324-8: Eric Topol Ground Truth 23 March 2023: How to prevent long-COVID

1. Not getting infected =of course most efficient

2. Vaccination as prevention:Ep 324-8.1 Meta-analysis JAMA Int Med about Risk factors

Increased risk

• female sex (OR, 1.56; 95%CI, 1.41-1.73),
• age (OR, 1.21; 95%CI, 1.11-1.33),
• high BMI (OR, 1.15; 95%CI, 1.08-1.23),
• smoking (OR, 1.10; 95%CI, 1.07-1.13)
• Comorbidities (OR, 2.48; 95%CI, 1.97-3.13
• and previous hospitalization  or ICU admission  OR, 2.37; 95%CI, 2.18-2.56, respectively)

Decreased risk = vaccination: (OR, 0.57; 95%CI, 0.43-0.76).

3. PAXLOVID as early treatment: Ep 324-8.2 Yan Xie JAMA Int Med March 2023

For over 35,000 individuals treated within 5 days compared with246,000 controls there was a 26% reduction of Long Covid (Post-Covid Condition, PCC). Importantly, this benefit was across multiple organ system outcome as shown below (no effect seen for reducing liver disease or diabetes).

4. Metformin as early treatment Ep 324-8.3:Caroline Bramante SSRN March 2023

Adults  within 3 days of SARS-CoV-2 diagnosis with increased risk (overweight) and pregnant women NOT excluded.

Receiving metformin for 14 days versus placebo: throughout various variants waves, including omicron.

→ 42 % reduction of long COVID at day 300. (10.6 %  placebo vs 6.3% metformin)

No such effect with either Fluvoxamine or Ivermectin.

Possible explanation ?

• Direct antiviral effect?
• Anti-inflammatory or anti-oxidative effect?

Limitations:

• Does not indicate if still effective if started at the time of hospitalization, Intensive care or after acute symptoms have disappeared.

SOME CONCLUSIONS

Omicron evolves with regard to immune escape, but severity of the acute phase decreases  (with immune compromised patients remaining vulnerable)

Long COVID is less frequent in omicron infected subjects (and after reinfection).

Most evidence points to a preventive effect by vaccination before infection or by early treatment with Paxlovid (in a large study) or with Metformin (1 study only).