Covid: vaccine effectiveness in hospitalized patients

 Several important articles have come out recently on Covid vaccine effectiveness. Will divide this into two separate blogs: the first showing mRNA vaccination effectiveness in decreasing Covid hospitalizations and disease severity, the second assessing longer-term effectiveness of the vaccines

 

A multicenter US study found that vaccination with an mRNA vaccine was remarkably less likely in patients hospitalized with Covid-19 or with disease progression to death or mechanical ventilation; and the Moderna vaccine seem to edge out the Pfizer one (see covid mRNA vaccines dec severity of all variants JAMA2021 in dropbox, or doi:10.1001/jama.2021.19499 )

 

Details: 

-- data was from Influenza and Other Viruses in the Acutely Ill (IVY) Network, a collaboration of 21 US hospitals in 18 states as well as the CDC

--4513 patients (>18yo) were hospitalized at Network hospitals between March 11 and August 15, 2021, with 28-day outcome data on death and mechanical ventilation in those enrolled through July 14, 2021

-- median age 59, 49% women, 23% non-Hispanic Black/16% Hispanic/55% white, 10% current smoking

-- comorbidities: cardiovascular disease 60%, pulmonary disease 25%, diabetes 30%, obesity 50%,  immunocompromising condition 20% (includes solid organ cancer within the past six months, active hematologic cancer, HIV infection with or without AIDS, splenectomy, solid organ transplant, immunosuppressive meds, lupus, rheumatoid arthritis, psoriasis, scleroderma, inflammatory bowel disease)

    --vaccinated patients with breakthrough infections tended to be older (67 versus 53yo) more likely to be white (64% versus 43%), and more likely to be immunocompromised (41% versus 12%)

-- among 1700 fully vaccinated patients (including Covid cases and controls), 1036 (61%) received the Pfizer vaccine and 664 (39%) received the Moderna one

-- 730 Covid cases had SARS-CoV-2 lineage determined: 37% alpha variant, 46% delta variant, 21% other variants (the dominant variance shifted from alpha to delta in mid-June 2021)

-- multivariable analysis below was adjusted for admission date, age group (18-49, 50-64,>64yo), self-reported race/ethnicity

 

-- main outcomes: association between prior vaccination and either hospitalization for Covid-19 and control patients who were hospitalized for a different diagnosis, or disease progression in patients hospitalized for Covid-19

 

Results: 

-- 1197 patients were hospitalized with Covid infection between March 11 and July 14, 2021: 142 (12%) were vaccinated breakthrough cases and 1055 (88%) were unvaccinated

    -- vaccinated breakthrough cases were older and had more chronic medical conditions; but they were also less likely to receive ICU level care: 24.6% versus 40.1%, absolute difference of -15.5% (-23.1% to -7.8%), p<0.001

 

-- overall Covid hospitalization: 85% lower likelihood with vaccination, adjusted OR 0.15 (0.13-0.18)

    -- without prior immunocompromising conditions: 90% decrease, aOR 0.10 (0.09-0.13)

    -- with prior immunocompromising conditions: 51% decrease, aOR 0.49 (0.35-0.69)

        -- difference was statistically significant, with p<0.001

  

-- overall effect by mRNA vaccine type versus controls:

    -- Pfizer:  81% lower likelihood when vaccinated, 0.19 (0.16-0.23)

        -- 14-120 days since vaccination: 85% lower, aOR 0.15 (0.12-0.18)

        -- >120 days since vaccination: 64% lower, aOR 0.36 (0.27-0.49)

        -- median 140 days from vaccine dose to illness onset

    -- Moderna vaccine: 89% lower, aOR 0.11 (0.08-0.14)

        -- 14-120 days since vaccination: 91% lower, aOR 0.09 (0.07-0.13)

        -- >120 days since vaccination: 85% lower, aOR 0.15 (0.09-0.23)

        -- median 143 days from vaccine dose to illness onset

    -- of note, there was no statistical difference in time since vaccination for the Moderna vaccine, but a large difference in the Pfizer one. And, a lower aOR was found for the Moderna vaccine for patients with illness onset >120 days when restricting the analysis to patients without immunocompromising conditions or stratifying patients into those greater than versus less than 65 years old

 

-- hospitalization for Covid stratified by SARS-CoV-2 variant:

    -- alpha variant: 90% lower likelihood with vaccination, aOR 0.10 (0.06-0.16)

    -- delta variant: 86% lower likelihood, aOR 0.14 (0.10-0.21)

    -- i.e., no statistically significant difference between these variants (overlapping confidence intervals)

 

-- disease progression to death or invasive mechanical ventilation: 261 of 1055 (25%) patients who were unvaccinated versus 17 of 142 (12%) who were vaccinated, a 67% reduction in those who were vaccinated, aOR 0.33 (0.19-0.58)

-- deaths: 9 of 142 (6%) of vaccine breakthrough cases versus 91 of 1055 (9%) of unvaccinated patients with Covid, 59% lower likelihood of vaccination, a OR 0.41 (0.19-0.88)

-- by WHO Covid Clinical Progression Scale: the highest level of disease severity experienced was significantly lower among vaccine breakthrough cases then unvaccinated, 64% decrease, a OR 0.36 (0.25-0.51)

-- hospital discharge alive within 28 days of admission: 125 of 142 (88%) of vaccine breakthrough cases versus 814 of 1055 (77%) of unvaccinated cases, p=0.003; and those who were vaccinated had a shorter length of stay

 

Commentary: 

-- the researchers presented outcome data for the full hospitalization for those who had been vaccinated (as opposed to the original clinical trials showing just a decrease in the initial hospitalization)

-- this study documented the relative rarity of developing severe Covid infections after vaccination (severe “ breakthrough infections”). And when breakthrough infections did happen, they tended to be less severe, required less intensive intervention, had lower rate of death, lower severity scale overall, and shorter hospital length of stay

    -- breakthrough infections are bound to happen given that these vaccines are not 100% effective; the study did show that severe consequences are quite uncommon in those fully vaccinated, though those with immunocompromising conditions fared less well (still much better if vaccinated)

-- the study also found that especially beyond 120 days postvaccination, the Moderna vaccine did significantly better than the Pfizer one (though this was not a prespecified outcome, so is less statistically rigorous), and Moderna also had a statistically significant though small benefit for hospitalizations overall. of note, the Moderna vaccine is >3x more potent than the Pfizer one (100mcg vs 30mcg)

-- the study also provided more reassuring data that the delta virus does not seem to lead to worse outcomes than the alpha variant

 

Limitations:

-- as with pretty much all of the studies dealing with Covid vaccination, they did not take into account other important details that might affect getting disease or disease outcome, such as mitigation strategies used (masks, distancing, etc), medications taken, frailty, life stresses, housing conditions, other sociodemographic factors, etc.

--it is difficult to unscramble definitively the relationship between the vaccine and the alpha versus delta variants, since the delta variant happened later than the alpha one and therefore occurred at a time more distant from the vaccination (waning immunity). In addition, there may have been differences in patient Covid admission thresholds and treatment approaches that evolved over the several months when the different variants occurred. In this study there were non-statistically significant differences between the outcomes for these two variants with only a small trend to worse outcomes with delta, so this concern may not be significant

    -- and, overall, there may also have been conscious or unconscious bias to the threshold for hospitalization, based on whether the patient had been vaccinated or not

-- all this data is from patients who were hospitalized, without any information on those patients who had perhaps very symptomatic Covid infections but were not hospitalized

 

So, a very impressive study finding that vaccination (in this case with the mRNA vaccines) dramatically decreased the likelihood of hospitalization for Covid infections, and, when hospitalized, the patient outcomes were significantly better in those vaccinated. This was true across age groups, and was particularly true for the Moderna vaccine among those more than 120 days from completing their vaccination. The Moderna vaccine also seem to be somewhat more protective Pfizer one overall. (also see https://www.nytimes.com/interactive/2021/11/11/science/vaccine-waning-immunity.html?referringSource=articleShare ) A few points:

-- as the absolute number of people are vaccinated, there will be a larger total number of people with breakthrough infections, and even deaths (though the relative vaccine protection may well remain hugely beneficial)

-- the hurdle for us as clinicians is to put this in perspective for patients: the vaccine is not 100% effective (though quite close), there will therefore be a small percentage of people who are not sufficiently protected, we will hear about more bad outcomes (and these will likely be amplified in social media and certain news outlets) as more and more people are vaccinated, BUT the chances (relative risk) of having a severe Covid outcome is dramatically decreased by vaccination. And even those who are hospitalized seem to do much better.

-- immunocompromised patients did less well postvaccination, reinforcing the need for them to continue mitigation strategies (mass, distancing, etc.) and likely also the importance of booster vaccination

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Here is a graph from the CDC, showing that there is pretty remarkable benefit from by vaccination status in the top graph,  as well as for deaths in the bottom (see https://www.nytimes.com/interactive/2021/10/28/us/covid-breakthrough-cases.html?unlocked_article_code=AAAAAAAAAAAAAAAACEIPuonUyYiZ_tU1Gw5CRWySB4B991rf3b-VkPshnTj1KzaURXNI1ekcAJSA4UDQaqombNIo0i_dRMNENPVnYs1O-dJlHh4nTRi08NzDmZIZLj88op6yQG5xhpuUDO01-javMmPgeKIinebk-hiPYWn1CKeJ1Hcmcwg1pZUxZkjqjSJTvtrNFeB_3dZ72vYzVNstFXpbOn7877S_AA5-Od6Fchnf9gExPuhbUjnXltaXgKkSJEQQURmVCSMivhtvrY9UK9gVP67gLxY_e8qYgLwZCmNgLIfBFITIejdSKbYZMNnybIzIn2DJ&referringSource=articleShare ):

it should be pointed out that we do not have systematic testing or reporting for mild to moderate infections, let alone asymptomatic cases. not sure how this would affect the numbers. would those unvaccinated be more likely not to get Covid testing done (covid-deniers) if they had milder symptoms?  would those vaccinated not get testing done because they think covid is unlikely after vaccination and they only had mild to moderate symptoms? or would they be more likely to get tested to make sure they don't spread the virus around to others??  also, different individuals may well have very different thresholds for having themselves tested. and, we do not have any systematic numbers on asymptomatic people. so, the top graph may not really represent the accurate difference in weekly cases by vaccination status. Deaths, on the other hand, are probably pretty accurate.....

in terms of deaths, the CDC has found that age seems to be the prime predictor. though unvaccinated seniors have the highest death rate, vaccinated ones 80 years or older have higher death rates than unvaccinated people <50yo.

geoff

 

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