Covid: BA.2 severe in unvaccinated kids

 In the current surge of omicron BA.2 in Hong Kong, unvaccinated children did worse when compared to prior SARS-CoV-2 variants, or to influenza or parainfluenza (see covid omicron BA2 worse in kids hongkong lancetpreprint2022 in dropbox, or https://papers.ssrn.com/sol3/papers.cfm?abstract_id=4063036 )

Details:

-- data from the HK territory-wide CDARS database of hospitalizations in all public hospitals, comparing BA.2 outcomes in those 0-11 years old to 737 children with prior SARS-CoV-2 variants (Jan to Nov 2021), as well as 32,212 children with influenza, and 16,423 with parainfluenza, (both from Jan 2015 to Jan 2020)

    -- from 5February to 28February2022, 1147 children 0-11yo were hospitalized during the Omicron wave: 920 were aged 0-5

-- none with known prior Covid infections or vaccination

--outcomes measured: comparative fatalities, ICU admissions, and neurologic and respiratory complications

Results:

-- Deaths:

    -- Omicron BA.2: 4 deaths (0.35%), in kids aged 11 months, 3 yo, 4yo, 9yo; the 3 youngest in good health, the oldest had Duchenne muscular dystrophy, all unvaccinated

    -- other SARS-CoV-2 variants: 0 deaths

    -- influenza: 0.05%

    -- parainfluenza: 0.04%

-- ICU admissions, comparing Omicron BA.2 (21 admissions, 8 requiring mechanical ventilation, 1.83%) vs:

    -- other SARS-CoV-2 variants (total of 1 admission, not requiring mechanical ventilation): OR 18.50 (2.42-140.70), p=0.005

    -- influenza (254 admissions, 0.79%): OR 2.32 (1.48-3.64), p1.48-3.64), p<0.002

    -- parainfluenza (270 admissions, 1.64%): no significant difference

-- neurologic complications (for febrile seizures, the most common issue) comparing Omicron BA.2 (14.91% (171 of 1147 patients) vs:

    -- other SARS-CoV-2 variants: no febrile seizures

    -- influenza: OR 1.75 (1.48-2.08), p<0.001

    -- parainfluenza: OR 2.06 (1.74-2.46), p<0.001

    -- encephalitis/encephalopathy (only 5 cases with BA.2): none found with other SARS-CoV-2 variants, but twice as many vs influenza (not statistically significant), and 4-fold that of parainfluenza (p=0.005)

-- croup (laryngotracheobronchitis), 61 or 1147 (5.32%) , comparing Omicron BA.2 vs:

    -- other SARS-CoV-2 variants (2 of 737, 0.27%): OR 11.47 (2.77-47.46), p=0.001

    -- influenza: OR 2.08 (1.58-2.74), p<0.001

    -- parainfluenza: no significant difference 

Commentary:

-- As background, there have been >6 million deaths from Covid globally, and 0.4% were estimated to be in children <18yo

-- this study in Hong Kong found Omicron BA.2 to be highly transmissible (1147 children hospitalized in 23 days vs 737 with prior SARS-CoV-2 infections in 22 months) and was NOT a mild disease in unvaccinated children, having higher fatality and severe complications than prior SARS-CoV-2 variants, influenza and parainfluenza (higher death rates, ICU admissions, use of mechanical ventilation/oxygen use); also more neurologic and respiratory complications

-- in populations where Omicron appeared to be much milder, the majority seemed to have been protected by prior Covid infections and/or vaccination

-- Hong Kong avoided many of the earlier Covid outbreaks (waves) attributed to their strict social distancing policies, universal masking, contact tracing, intermittent business closures and widespread school suspensions (from Jan 2020 to March 2020 school attendance decreased from 400 to 300 days, and when reopening, students were allowed to attend only half-days), so their data on the effects of Omicron are not confounded so much by either prior infection, or vaccination (these were children, and, at the time of the Hong Kong study above, vaccination was not done in those 0-11 yo: the 5-11yo group started vaccination mid-January 2022)

    -- seroprevalence data suggested that only 1% of Hong Kong's population had had Covid infections

    -- and the BA.2 variant is so highly contagious that there were 900,000 cases from 31December2021 to 15March2022, vs 14,197 cases for the prior 2 years

-- and, a similar situation seems to be happening in the huge current BA.2 outbreak in Shanghai... see https://www.nytimes.com/2022/04/01/world/asia/china-covid-shanghai.html?referringSource=articleShare

-- in the US, a large retrospective cohort study of 881,473 patients with Covid (including 147,964 with Omicron) found the highest infection rate in those <5yo (see https://pubmed.ncbi.nlm.nih.gov/35233579/ or https://www.medrxiv.org/content/10.1101/2022.02.21.22271300v1). As compared to Delta variant, there were fewer ED visits (10.2% vs 14.6%), hospitalizations (2.6% vs 4.4%), ICU admissions (0.47% vs 1.00%) and mechanical ventilation (0.08% vs 0.3%). BUT, BA.2 is much more transmissible, and many people in the US had had prior infections and/or vaccinations. so, even the smaller percentages translate to lots of kids

    -- which seems to say that Omicron BA.2 may not really be a milder variant, but that prior vaccination or infection may have blunted the response in lots of people. however, those unvaccinated and naive to the virus itself might still have terrible outcomes

    -- which means that we should not necessarily be lulled into believing the BA.2 is pretty benign (though might be so more specifically in those with prior infection or vaccination). It is not, in and of itself, a benign disease

-- and, laryngotracheobronchitis (croup) has been reported to be more common with Omicron than past SARS-CoV-2 and with significant mortality (see https://pubmed.ncbi.nlm.nih.gov/35257175/ )

-- a UK study also found no difference in severe hospital admission with the BA.1 Omicron (the initial one) vs Delta in those <10yo (ie, BA.1 was also considered a "milder" disease overall, but not so for younger kids)

-- one interesting angle here is that because of the stringent mitigation strategies used in Hong Kong, those <5yo had less exposure to the 4 recurrent mild seasonal coronaviruses in the prior 2 years so may have been more susceptible to BA.2 (ie, if the prior exposures to these mild seasonal coronaviruses conferred some immunity to our current blight)

-- by the way, it does seem that Paxlovid will work well for BA.2, at least in lab studies of neutralizing activity. And bamlanivimab (monoclonal antibody) works really well: see covid omicron BA2 antiviral agents NEJM2022 in dropbox, or DOI: 10.1056/NEJMc2201933

Limitations:

-- no specific genomic sequencing was recorded in the database, so not absolutely sure all were BA.2, though this was clearly the dominant strain (>60%); analysis done in March 2022 found that of the 130 covid deaths, genomic sequencing found that 117 were Omicron and 13 Delta

-- Hong Kong was able to avoid the intensity of several of the previous variants through their intense mitigation strategies, but are now succumbing to the more highly transmissible BA.2 variant (perhaps in part because the community there had less natural infection and the vaccines worked less well against BA.2??). so not sure how these Hong Kong results translate to countries with much less aggressive Covid reduction strategies (ie most of the rest of the world)

-- in Hong Kong, children <5yo with mild BA.2 were cared for at home, limiting the accuracy of the in-hospital covid rates above, but the overall database included 13,000 children 0-11 yo, still representing infection rate of 0.02% (vs 0.005% in the UK)

so, we may be underestimating the severity of the Omicron BA.2 variant in the US given the high rates of past infection and pretty high rates of vaccination. therefore, even though our overall numbers look good (but are now tracking worse), it may well be that certain groups (eg unvaccinated kids) actually do get more severe infections, as also suggested in above US and UK studies. This data should reinforce vaccinating all, but including kids >5yo, as a highly likely means to decrease severe Covid outcomes (see https://www.nejm.org/doi/full/10.1056/nejmoa2116298 for article on benefit of vaccination in kids 5-11yo).  

One other (pessimistic, unfortunately) note: though it may have appeared that the initial Omicron and the subsequent BA.2 outbreaks had "milder" disease, this study from Hong Kong (and it seems that Shanghai is on course for the same) suggest that these variants are not by nature milder but are only so in the context of some pre-existing immunity (eg vaccination or infection). And newer variants are likely, in time, to morph into viruses resistant to this pre-existing immunity (which did happen to some but limited extent in these Omicron variants).  Which means we really need to be on-guard for the future.  Which means having a very low threshold to masks/distancing, and the continued ability to ramp up production of new vaccines against new variants rapidly....

geoff

 

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