covid: vaccine effectiveness in outpatient and inpatient setting

 

An article assessed vaccine effectiveness for both mRNA vaccines and the J&J one against symptomatic Covid infection, including hospitalization, admission to the ICU, or ambulatory care in an emergency department or urgent care clinic (see covid vaccine effectiveness in outpt and inpt setting nejm2021 in dropbox, or DOI: 10.1056/NEJMoa2110362)

 

Details: 

-- 41,552 hospital admissions to 187 hospitals and 21,522 visits to 221 emergency departments or urgent care clinics, from January 1 through June 22, 2021, for adults at least 50 years old with a Covid-like illness

    -- this analysis was done through the CDC’s VISION Network, in collaboration with seven US healthcare systems having a total of 187 hospitals and research centers with integrated medical, laboratory, and vaccination records

    -- Covid-like illness was a defined as a clinical diagnosis of acute respiratory illness, or signs and symptoms that have been associated with Covid in previous studies

    -- Covid infection was defined as a positive PCR assay that occurred within 14 days before to less than 72 hours after a hospital admission, or an emergency department/urgent care clinical visit

-- vaccination status was documented in the electronic health record and immunization registries

-- among the vaccinated patients, 53% had received the Pfizer vaccine, 43% the Moderna vaccine, and 4% the J&J vaccine, with similar numbers for those who were hospitalized as those seen in outpatient setting

    -- the J&J vaccine was used in only five of the network partners, analyses included 11,468 hospitalizations and 8917 emergency department or urgent care visits

-- the median days from full vaccination to the index date of the Covid-like illness was similar for all three types of vaccine

-- primary outcome: odds of a PCR-positive Covid test among vaccinated versus unvaccinated patients

-- vaccine effectiveness was matched for propensity-for-vaccination score, and according to age, geographic region, calendar time from January 1 to the index medical visit, and local virus circulation, leading to the multi-variate adjustments below for vaccine effectiveness

-- secondary analysis: vaccine effectiveness estimated at 14-day intervals after each dose of vaccine

 

Results: 

-- 4321 hospitalized patients (10%) had laboratory-confirmed Covid infections among 41,552 patients; the remaining 37,231 hospitalized patients (90%) had discharge codes for Covid-like illness but were PCR-negative

-- 3251 of 21,522 patients visiting an emergency room or urgent care clinic (15%) had positive PCRs

-- these percentages varied considerably among the network partners involved in the study, related to the local infection rates

-- percentage of patients with PCR-positive infections was higher among unvaccinated patients and lower among those with chronic respiratory conditions

 

-- laboratory-confirmed Covid for mRNA vaccination at least 14 days after the second dose, as opposed to unvaccinated:

    -- hospitalization: 89% (87-91%) effective

       -- Moderna 91% effective against hospitalizations (89-93%) and Pfizer 87% (85-90%), with overlapping confidence intervals

    -- ICU admission: 90% (86-93%) effective (these outcomes were the combo from the 2 mRNA vaccines)

    -- emergency department or urgent care clinic visit: 91% (89-93%) effective

       --Moderna 92% effective against hospitalizations (89-94%) and Pfizer 89% (85-91%), also with overlapping confidence intervals

    -- so, these results were statistically similar for the Pfizer and Moderna vaccine

 

    -- mRNA vaccine effectiveness, in subgroup analysis (vaccine effectiveness not provided for the J&J vaccine, likely from too few people in the subgroups):

        -- those at least 85yo: 447 of 2960 unvaccinated were covid-positive (15.1%) vs 68 of 3306 (2.1%)  fully vaccinated were hospitalized, vaccine effectiveness (unadjusted) 88% (85-91%), if adjusted for calendar time, daily virus circulation, age, and geographic cluster was 83% (77-87%).

        --those with at least one chronic resp condition: 2359 of 13018 unvaccinated were covid-positive (18.1%) vs 152 of 10257 (1.5%) fully vaccinated were hospitalized, vaccine effectiveness (unadjusted) 93% (92-94%), if adjusted for calendar time, daily virus circulation, age, and geographic cluster was 90% (88-92%)

        --those with at least one chronic non-resp condition: 3043 of 18089 unvaccinated were covid-positive (16.8%) vs 240 of 13999 (1.7%) fully vaccinated were hospitalized, vaccine effectiveness (unadjusted) 91% (90-92%), if adjusted for calendar time, daily virus circulation, age, and geographic cluster was 88% (86-90%)

        -- and 86 to 90% for Black or Hispanic adults

 

    -- in patients who only received one dose of an mRNA vaccine at least 14 days before the index date (partially vaccinated):

        -- hospitalization: Pfizer vaccine 33% (18-46%) vs Moderna 68% (59-75%)

        -- ICU admission: Pfizer or Moderna vaccine 56% (35-70%), no breakdown by vaccine type

 

-- Emergency department and emergency room visits for mRNA vaccine recipients:

    -- full dose vaccination: Pfizer vaccine 89% (85-91%) vs Moderna 92% (89-94%)

    -- partial, only one-dose vaccination: Pfizer vaccine 58% (46-68%) vs Moderna 73% (64-79%)

    -- less than 14 days after the first dose: no protection

 

-- laboratory-confirmed Covid for J&J vaccine, vs unvaccinated:

    -- hospitalization: 68% (50-79%); no comment on ICU admissions

    -- emergency department or urgent care clinic visit: 73% (59-82%)

 

Commentary:

-- so quite impressive results in this real-world setting with roughly 88% effectiveness against Covid infection leading to hospitalization, 90% against infection leading to ICU admission, and 91% against infection leading to emergency department or urgent care clinic visit

    -- though the Moderna seemed a bit better than Pfizer, those having the full 2-shot series did similarly with overlapping confidence intervals. Those receiving only 1 dose, however, did better with Moderna (which actually is more potent)

    -- the J&J, on the other hand, did less well, though still provided considerable protection

        -- which raises the issue of whether it makes sense to do the mix-and-match if there is a booster vaccine (ie: giving an mRNA booster for those having had the J&J). this needs to be tested, though a prior study did suggest some benefit to giving the Pfizer booster to AstraZeneca, an adenovirus-vectored vaccine as is the J&J): see http://gmodestmedblogs.blogspot.com/2021/07/covid-mixing-and-matching-vaccines.html  

-- this study adds to the aggregate data we have accumulated, in that it is in a real-world setting, it included adults who were at least  85 yo and those with chronic medical conditions, it also included Black and Latinx adults, who for largely sociodemographic reasons do tend to have worse outcomes (effects of poverty, income equality, stress, multiple other social inequalities such as housing and access to good food, etc.) and as a group overall tend to be more distrustful of our systems, including the medical system (which have not served them well, as compared to other groups)

-- The study also showed that full dose vaccination had a durable effect for at least 112 days after the second dose (no difference in vaccine effectiveness against hospitalization if fully vaccinate in any 14-day interval from day 14 until those >112 days post dose-2)

-- And these results reinforce that the mRNA vaccines, though someone effective after a single dose, really require two doses to achieve the high levels of protection.

-- though not measured, it is highly likely that knowing antibody levels would have shown decline in this 4-month study (eg see http://gmodestmedblogs.blogspot.com/2021/08/covid-breakthrough-infections-and-assoc.html ), yet real-world clinical effectiveness was maintained, further supporting the importance of assessing clinical outcomes instead of the laboratory-measured immune response, at least until we have strong documentation of a specific antibody (or antibodies/other immune markers) and their required  levels as appropriate laboratory surrogate markers…)

 

Limitations:

-- this study only included patients who sought clinical care, with no bearing on those who were asymptomatic (though still may be susceptible to long Covid symptoms, and still may have transmissible virus)

-- not stated how representative these patients were for the US population overall: no assessment of socioeconomic status, if on Medicaid or Medicare, or other factors that might alter the risk for Covid, such as social distancing, mask wearing, living conditions, diet/exercise, specifics of chronic illnesses,... 

    -- as an observational study there may be unmeasured confounders including these, which limit generalizability of the results and render their conclusions only associations and not causal
-- there also might be important regional variations in who seeks clinical care different areas, with some people having less access to care for financial/sociopolitical reasons, some areas being more vaccine-hesitant for political reasons, etc.

-- this evaluation was prior to the Delta variant: during the time period of the study, the Alpha variant (B.1.1.7) was predominant in the geographic regions covered by the network, though no genetic analyses were done on those infected to document the specific variant involved or breakdown results by different variants

-- there are inherent differences in how the different clinical settings or individual clinicians may have had different clinical approaches, and may have tested for Covid with different thresholds for testing, again since this was an observational study without the rigor of a structured randomized control trial

--the percentage of Covid infections was lower in white, non-Hispanic patients, which is reasonably attributable to differences in sociodemographic situations

 

so, interesting real-world study with several possible lessons:

-- the mRNA vaccines were very effective, with some apparent small increased benefit of the Moderna one, with the J&J lagging behind

-- there was similar vaccine effectiveness in those at least 85yo vs the whole group (all being at least 50yo)

-- vaccination had a durable effect for close to 4 months after the second dose without evidence of decreasing effectiveness

-- it is abundantly clear that vaccination is indeed essential. one concern about those who are vaccine-hesitant but then decide that vaccination is important (perhaps after seeing someone get very sick), is that they may think that they will get immediate protection after vaccination. It should be clear that full protection requires approximately six weeks (at least two weeks after the second dose, with some suggestion that it might be even longer with the Delta variant) and that there is no protection at all for at least two weeks after the first shot of an mRNA vaccine

 

geoff

 

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