covid: durability of antibody response in neonates

 

JAMA just published an article comparing the durability of anti-spike antibodies in infants born to women who either had natural Covid infection or vaccination (see covid durabil of infant Ab after matern infec jama2022, or doi:10.1097/AOG.0000000000004693)

 

Details:

-- 77 vaccinated pregnant women and 12 with symptomatic SARS-CoV-2 infection, both from weeks 20-32 gestation, evaluated in study done from July 21, 2021 to October 22, 2021

-- matched maternal and umbilical cord serum samples were collected at birth; infant capillary serum samples at two months after birth for infants of vaccinated mothers, and at six months for all

-- six-month samples: collected a mean of 170 days after birth from 28 infants of vaccinated mothers, and 207 days after birth from 12 infants of infected mothers

 

Results:

-- antibody titers, vaccinated versus natural infection:

    -- mothers: 2.03 (standard deviation 0.47) optical density (OD) versus 0.65 (SD 0.76) optical density, p<0.001

    -- cord blood at delivery: 2.17 (SD 0.50 OD ) versus 1.00 (SD 0.83), p<0.001

    -- infants of vaccinated mothers at two months: 98% (48 of 49) had detectable anti-spike IgG antibody, mean titer 1.29 (SD 0.53), mean titer was correlated with both maternal and cord blood titers at delivery

    -- infants at six months: 57% (16 of 28) from vaccinated mothers had detectable antibodies versus 8% from infected mothers, p=0.005; mean titer 0.33 (SD 0.46) versus zero (SD 0.01), p=0.004, though neither maternal nor cord blood titers were significantly correlated with these values

 

Commentary:

-- prior researchers found that anti-spike IgG antibodies in the umbilical cord blood correlated with maternal titers were are highest in the late second and early third trimesters of pregnancy

-- the imperative here is that this age group certainly can get significant SARS-CoV-2 infections, and there is no direct infant vaccine in the near future

    -- a systematic review of SARS-CoV-2 infections last year in infants (see https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7477627/pdf/main.pdf) found:

        -- from 1 November 2019 til 15 June 2020, published reports globally on laboratory-confirmed Covid in infants <3 mo old (range 5 days to <3 mo) uncovered 38 publications with total of 63 infants

        -- 58 (92%) of the infants were hospitalized, 13 (21%) were in intensive care, 2(3%) required mechanical ventilation, but no deaths

        -- most cases were mild-to-moderate

        -- symptoms included fever (in 73%), respiratory (66%), GI (14%), and neurologic (seizures in 3%)

        -- lab abnormalities included neutropenia (56%), lymphopenia (16%), increased inflammatory markers (19% increased CRP, 20% procalcitonin) and transaminases (82%, severe in only 1 infant) 

    -- but, there is also an attributable increase in infant deaths from the economic contraction associated with covid: one mathematical mortality study (see https://bmjopen.bmj.com/content/11/8/e050551 ), pooling birth histories in 83 low-income and middle-income countries between 1985-2018, projected 267,208 (112,000-422,415) excess infant deaths in 128 countries in 2020, a 6.8% (2.8%-10.7%) increase in the total number of infant deaths vs expected deaths without Covid

-- so, infant morbidity can be directly from SARS-CoV-2 infection, or indirectly through the huge socioeconomic disruptions from the pandemic

-- another recent article (https://pubmed.ncbi.nlm.nih.gov/34963127/ ), evaluating 1,359 vaccinated pregnant women before and throughout pregnancy, found detectable maternal anti-spike IgG levels at delivery regardless of the timing of vaccination in fully vaccinated women, and:

    -- early 3^rd trimester booster vaccine was associated with the highest IgG titers in maternal and cord blood samples

    -- those with history of Covid given a vaccine dose in early pregnancy had titers comparable to getting 3^rd trimester vaccination in those without covid history

    -- a booster does in the 3^rd trimester was associated with much higher anti-spike IgG levels than just 3^rd trimester vaccination in women with or without a history of covid (and, the presumption is that passive transfer of higher IgG titers to infants will last longer)

 

Limitations:

-- this study only measured anti-spike antibodies, which brings up a few issues:

    -- does the titer of this antibody correlate with actual protection against SARS-CoV-2, and specifically with clinical events? We do not know what titer might be associated with protection

    -- for example, there may well be other and more important components of the immune response, such as memory cells, that may efficiently respond to SARS-CoV-2 and provide clinical protection

    -- also, the mRNA vaccines target the spike protein, and elicit profound antibody response. But, perhaps a natural infection elicits a wider range of antibody responses from different areas of the virus? Are other antibodies associated with a natural, whole-virus infection important to protect the infants?

        -- It would be useful to have studies assessing this, ones which assess whether the serum from infants passively getting maternal antibodies from vaccination actually do effectively kill the virus as profoundly as those from natural infection (ie perhaps even low titers of IgG spike protein in infants from infected mothers might be very effective in combination with other antibodies generated by the infection???)

-- this was a very small study, limiting its generalizability

-- there was more delay in assessing serum antibody levels in those with natural infections (207 vs 170 days), and this is likely associated with decreasing titers in those infants from infected mothers

-- as with many Covid studies, the results reflect infection with prior variants that are no longer present. And, a bit unclear how the results will reflect the current situation: the effectiveness of either prior infection or vaccination suggested in this study may not translate well to the current or future variants

 

so, though there are no clinical data to support this, the above study does reinforce the likely importance of vaccination of pregnant women (and boosters might also help a lot), that there seems to be passive transfer of high and durable titers of the anti-spike antibodies to infants from vaccinated mothers (more so than conferred by  actual infection). But we do need actual clinical data on outcomes (which i cannot find at this time). a few points:

-- vaccination of pregnant women is really important, from our best guess now

-- when looking at the effects of infant infections, it is important to assess both the direct effects of the infection on the infants but also the indirect ones on the family and society

    -- direct effects: though they do not seem to be so, so bad and happen pretty uncommonly, having an infant with covid does lead to dramatic psychologic effects on the family (PTSD etc: see http://gmodestmedblogs.blogspot.com/2022/03/covid-ptsd-in-family-members.html ), and (who knows??) perhaps even long term effects on the infants development (eg, see http://gmodestmedblogs.blogspot.com/2022/02/covid-long-covid-longterm-effects-and.html which documents some of the long term changes found in adults)

    -- indirect effects: the huge economic burden from the ongoing covid scourge is affecting all but esp those in low- and middle-income countries. And there are also the indirect effects on families (eg from loss of work taking care of the infants, increasing stress, etc) and society overall from the profound disruptions associated with infant infections

--and, all of this reinforces, yet again, the importance of vaccination

 

geoff

 

If you would like to be on the regular email list for upcoming blogs, please contact me at gmodest@uphams.org

to get access to all of the blogs (2 options):

1. go to http://gmodestmedblogs.blogspot.com/ to see them in reverse chronological order

2. click on 3 parallel lines top left, if you want to see blogs by category, then click on "labels" and choose a category​

3. or you can just click on the magnifying glass on top right, then  type in a name in the search box and get all the blogs with that name in them

 

or: go to https://www.bucommunitymedicine.org/ , a website from the Community Medicine section at Boston Medical Center.  This site does have a very searchable and accessible list of my blogs (though there have been a few that did not upload over the last year or two). but overall it is much easier to view blogs and displays more at a time.

 

 

please feel free to circulate this to others. also, if you send me their emails, i can add them to the list