covid infection protective; new Omicron variant

 some good and some not-so-good news:

1. the good news: another study was published recently from Qatar, this one finding that a prior Covid infection afforded great protection from severe subsequent infections (https://www.nejm.org/doi/full/10.1056/NEJMc2108120 ).

Details:

-- Qatar had first wave of Covid-19 infections from March-June 2020 (resulting in 40% of the population having detectable SARS-CoV-2 antibodies), then a resurgence of the Alpha and Beta variants from Jan-May 2021

-- they have impressive, inclusive databases (at least that's what they say: "Using national, federated databases that have captured all SARS-CoV-2–related data since the onset of the pandemic") on demographics, lab results, vaccinations, covid cases, severity of cases

-- primary outcome: Covid reinfections in those with prior infection (PCR-positive) between Feb 28,2021 and Apr 28, 2021, excluding the 87,547 who had a record of vaccination (reinfection was defined as a positive PCR at least 90 days after the primary infection; with assessment of the severity of the reinfection

 -- median dime to reinfection: 277 days (intraquartile range: 179-315)

Results:

-- 1304 reinfections were found: 413 (32%) by the Beta variant, 57 (4%) by the Alpha variant, 213 (16%) by the wild-type SARS-CoV-2, and 621 (48%) unknown type

-- severity of reinfection results:

-- the 4 people who progressed to severe infection:

    -- a Qatari female 50-54yo, tested for "clinical suspicion", had underlying diabetes, and AKI

    -- a Filipino male 40-44 yo, tested for "clinical suspicion", had underlying asthma

    --a Bangladeshi male 40-44yo, tested for "clinical suspicion", did not have reported comorbidities

    -- a Filipino male aged 44-49, with PCR testing for a "survey", had underlying hypertension

Commentary:

-- Reinfection rates in those unvaccinated mirrored the severity found in those vaccinated but without prior covid infection: in this study 90% had lower odds of hospitalization (only 4 infections) and none lead to ICU necessity or death

-- this is very reassuring, though unclear how long the protection will last (as with vaccines)

-- a recent Qatar article noted that those vaccinated after a primary covid infection (mostly with the Pfizer vaccine) had significantly greater protection from reinfection than those who were vaccinated but had no prior covid, particularly if the interval between primary infection and vaccination exceeded 6 months; and they had much lower clinically severe reinfection rates (see http://gmodestmedblogs.blogspot.com/2021/11/covid-vaccine-post-infection-decreases.html ). this result suggests that (not surprisingly) vaccination after covid infection boosted the clinical effectiveness of the immune system (and adds more credence to the utility of booster vaccinations)

Limitations:

-- the timeframe of this study did not allow for information on protection from the Delta variant infection, just the Alpha and Beta variants

-- almost half of the reinfections had unknown SARS-CoV-2 lineage

-- the study was done in one location, Qatar, and may not be generalizable to other areas where there may be different demographics, socioeconomic factors, comorbidities, etc.

    -- e.g., Qatar has a particularly young population, with only 9% of its residents being at least 50 years old, and also 89% are ex-patriots residing in Qatar on work visas from more than 150 countries, mostly male. so, not so many co-morbidities, for example

so, though a study with above limitations, it does seem to confirm that reinfections are less severe than primary infections

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2. the probably not-so-good news:

as we all know, the new SARS-CoV-2 variant Omicron was discovered in South Africa, a variant which seems to have had many mutations in the spike protein (the target of the vaccines), seems to be spreading locally and internationally, and has some suggestive data that it may escape protection from the vaccine... (see https://www.nytimes.com/live/2021/11/25/world/covid-vaccine-boosters-mandates? )

here is s summary do far (will do a real blog on this once real data become available and evaluable), but the variant is already labeled a "variant of concern" by the WHO and causing global consternation

Details:

--After an increase in covid-19 cases near the Johannesburg area of South Africa (which is in Gauteng province), about a week ago South Africa's National Institute for Communicable Disease identified 22 cases of a new variant B.1.1.529 (Greek name: Omicron). and at about the same time last week there were 4 in Botswana and 1 in Hong Kong

    -- as of 11/26/21, there were 2858 new virus infections in 24 hours in South Africa, 80% in Gauteng province, a tripling of cases in a week (we need to wait on the genomic sequencing, but this increase did happen in the area of the first discovered Omicron)

        -- the variant seems to be spreading rapidly in South Africa (was up to 77 identified cases on 11/26 after the initial 22 cases)

        -- vaccination rates in South Africa are only around 24%. and of the 60 million people in South Africa, there have been 3 million recorded Covid infections (though, that, no doubt, is a low number, as in all countries). At that time there were 4 cases in Botswana, 1 in Hong Kong, and cases were reported in Israel and Belgium (see https://www.bbc.com/news/health-59418127  )

    --as of 11/29, there have been cases identified in South Africa, Botswana, Hong Kong, Israel,  Belgium, Italy, UK, Denmark, the Netherlands, Scotland, and an outbreak of 13 cases in a Portuguese soccer team), and likely many more in the near future

--many countries are limiting international travel (Britain, Israel, Singapore, US, UK, Australia, many in the EU, Japan, Morocco), and concerns about Omicron has been reflected in the financial markets

    -- although some countries are limiting restrictions of flights only from African countries, some are restricting all international travel for the next 14 days (Israel, Morocco, and Australia is delaying their opening for 2 weeks).

-- this variant is highly mutated, with 50 mutations overall and 30 on the spike protein (which is target of most vaccines), and 10 mutations in the receptor binding domain (vs 2 in the Delta variant and 3 in Beta)

    --and, the current vaccines were designed on the Wuhan virus, prior to this large amalgam of mutations over the past 2 years

from NY Times: https://www.nytimes.com/2021/11/26/health/omicron-variant-vaccines.html?unlocked_article_code=AAAAAAAAAAAAAAAACEIPuonUktbfqohlSVUZBSbVUNEjsh3Bgv3Oy6Y7gDrgJTKUQDBeivocCIOB_UrWI6p_Yt95lxKqeOh8Cp59Dvpj0r0YeEV3VwijppbDkcxVKX5l-I_2UG5q1deQVOhmtDa7NGD8Ib92zbTn50uLO2jhS7WfhSN6XHttppVvcl6v3n0alOySQqMuhI4Ijbp2DYt6RDwDeCGJo_Ltbh19M9iFZRvWgRIkD6AbAXqA2I7BtM9TNVlaGlnET3tg4W0j6Ns6ONsfOa73LR9Ia9NbzPH-c3TMs6xVVZkLhPdB&referringSource=articleShare 

Commentary:

--this is indeed a concerning development. and likely to be increasingly global. But, a few things:

    -- we really know very little about this variant so far: how transmissible is it? does vaccination protect people? and which vaccines work best? does prior infection moderate the severity of disease, as in Qatar study above (prior infection may elicit a broader antibody response than the targeted ones from the vaccine)?

    -- there has been a similarly very scary variant recently, C.1.2, though this has not panned out to be so bad, at least as far as i can find. For more specifics on this, see http://gmodestmedblogs.blogspot.com/2021/09/covid-troublesome-new-variant-lurking.html . this variant was really concerning for the same reasons they postulate that Omicron may be bad: high levels of mutations, the rate of mutations is way higher than with the original Wuhan virus mutating at 2/month (C.1.2 having between 44-59 mutations and a rate calculated of 42 mutations/year that is 1.7-fold faster than Wuhan);  many mutations were in important areas of the virus: N-terminal domain, receptor binding motif, furin-cleavage site (which seems to be responsible for viral infectivity/transmissibility) and the spike protein; early concern of increased transmissibility; early spread to other countries. But, nothing on the news about it since September, and not even a Greek name...

        -- the WHO decided already that Omicron is a "variant of concern", reflecting its potential badness, but such classification never happened with variant C.1.2. Will Omicron similarly disappear from the radar screen???

    -- there is concern that Omicron is spreading rapidly. But, perhaps Omicron has been around for a bit and spreading slowly? But right now, there is more testing and therefore more finding the variant. perhaps the increased cases found now merely reflect uncovering of already existing cases and not rapid spread??

        -- the cases in Gauteng province in South Africa, where the variant was first found, was in a university area with younger people. were they largely asymptomatic/mildly symptomatic, as is often the case in younger people, and perhaps the variant has been there awhile and actually not spreading so rapidly? or perhaps there was a single super-spreader event leading to a cluster there? (we have seen huge super-spreading events in the past: http://gmodestmedblogs.blogspot.com/2021/01/covid-biogen-superspreading-event-led.html ). who were the people who had the variant (what were their ages, comorbidities, past history of covid infection or vaccination)??? we need to wait to see if this variant is more transmissible or leads to more severe cases.

    -- all 4 initial people identified in Botswana with the variant had had prior vaccination (?which one ?when was it done). again, ?ascertainment bias that we just happened to find vaccinated individuals in this small number of cases in Botswana? maybe more widespread testing will find this to be a statistical fluke? or does the vaccine work less well with the variant?

-- it is also unclear if the new Merck/Pfizer pills will prevent severe Omicron outcomes... some more data suggests that these pills may be less effective in preventing serious disease even now (more like 30% vs initial estimates of 50+ %), and there are concerns about safety (toxicity and birth defects) see https://news.yahoo.com/fda-calls-merck-covid-19-174705927.html?fr=sycsrp_catchall . But no scientific paper has been published yet to scrutinize the findings.....  Similarly, we do not know at this point whether the monoclonal antibodies will work. what about fluvoxamine? (see http://gmodestmedblogs.blogspot.com/2021/11/covid-fluvoxamine-decreases.html )

-- fortunately, it seems that the current mRNA vaccine technology is leading to the pretty rapid ability to develop vaccines to cover this Omicron variant, and the mRNA makers are already working on Omicron boosters, projecting about 3 months until availability and global vaccination capability by the summer. the first genomes of the new variant were uploaded into the international database (GISAID) on November 22, within a day or so after its identification, with other genomes are being uploaded as the virus has spread

-- there is real concern that South Africa is being stigmatized and likely economically punished for being the first to identify the variant (fewer flights there, fewer global financial interactions). But:

    -- several of the new variants have been detected in South Africa because they have a robust system of identifying new variants earlier than most countries (including the US, which is also way behind the UK, for example). so, is much of Africa being punished because South Africa has better science than most other places? Maybe the variant actually started in the US (where several variants have occurred, including some found in New York and California): perhaps an infected student traveled to South Africa and that led to the Gauteng outbreak. and the variant was first found in Gauteng because of their more aggressive genomic testing????

    --and, what about the lack of global distribution of vaccines in South Africa, which were/are preferentially available in the richest countries? if this variant did start in South Africa, perhaps resource-rich countries are all to blame since vaccine went preferentially to us, leaving poorer countries in Africa and elsewhere more susceptible to variant evolution (seems a bit analogous to climate change issues: the resource-rich countries create emissions causing the global warning, but less affluent countries will likely suffer the most...)

    --also, when news first broke about this variant, resource-rich countries halted travel to many countries in Africa, yet several African countries have identified very few cases and sometimes fewer than in some of the European countries (i can find no cases reported in Mozambique, or Malawi, for example, though both are targeted with travel restrictions).  If we are all afraid of this variant (which is reasonable, given its profound destructive potential), maybe all international travel should be suspended? or at least from a large number of countries??

    -- one side issue: my understanding is that the WHO chose the Greek alphabet for the variants in order to de-stigmatize individual countries (previously, variants had cumbersome scientific names). Prior to this Greek letter nomenclature, these variants were often called the South African variant (eg Delta, which is B.1.617.2) or the UK variant (Alpha, which is B.1.1.7), etc

so, a few points:

-- Omicron may well be a bad problem globally. Not enough info about much of this variant's characteristics yet but clearly its evolution should be a further (and really strong) incentive to be more aggressive right now in mitigation strategies (masks, distancing, good ventilation, etc).

-- Though we do not know the effectiveness of vaccination against Omicron, it seems likely to be at least somewhat effective and should be done more aggressively now since it takes at least 2 weeks to be effective. ??maybe this outbreak and the potential need for aggressive restrictions about going to bars, restaurants, parties.... will help "convince" some vaccine-hesitant people???)

-- Omicron is a sobering reminder that other variants are likely to follow. Which is a real concern as we seem to be hurtling into a post-covid era a tad too early, with so much current non-masking, increased air travel, cruise ship travel (do people really forget how bad cruise ships can be: http://gmodestmedblogs.blogspot.com/2020/06/covid-asymptomatic-infections-and-viral.html ), etc.

i think all of us suffer from the past 1.5-2 years of social disruptions and have some PTSD about the prospects of more restrictions, lockdowns, inability to hang out with family/friends, etc, etc). But we know how bad Covid can be.  And we really do not want to go there.....

Hopefully we will be able to make more informed decisions soon.

geoff

 

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