COVID: J&J vaccine; viral load after vaccine

 The formal study on safety and efficacy data were released for the single-dose Johnson & Johnson/Janssen Covid-19 vaccine (see covid vaccine J&J nejm2021 in dropbox, or DOI: 10.1056/NEJMoa2101544)

 

Details: 

-- international, randomized, double-blind, placebo-controlled trial with 19,630 SARS-CoV-2 negative participants who received the J&J vaccine and 19,691 placebo recipients, from September 21, 2020 to January 22, 2021

    -- this vaccine is a recombinant, replication-incompetent human adenovirus type 26 vector encoding full-length SARS-CoV-2 spike protein

-- median age 52 (67% 18-59yo, 34% >60yo), 45% female, BMI 27, 41% at least one coexisting condition, 59% white/20% Black/ indigenous South American/ Hispanic

-- 41% from Latin America (Brazil 17%, Colombia 10%, rest from Argentina, Chile, Mexico, Peru); 15% South Africa; 44% US

-- primary endpoints: vaccine efficacy against moderate to severe-critical Covid-19 with onset at least 14 days, and at least 28 days after administration in those who tested negative for SARS-CoV-2

-- safety/reactogenicity was assessed

-- median follow-up was 58 days, range 1-124; 55% had at least 8 weeks follow-up

 

Results: 

-- moderate to severe-critical Covid:

    -- at least 14 days after administration: 116 cases in the vaccine group, 348 in placebo: efficacy 66.9% (59.0-73.4%)

    -- at least 28 days after administration: 66 vs 193 cases, efficacy 66.1% (55.0-74.8%)

    -- review of their graph: cumulative incidence started to diverge around 16 days after vaccination, and plateaued after about 45 days

-- severe-critical Covid:

    -- at least 14 days after administration: vaccine efficacy 76.7% (54.6- 89.1%)

    -- at least 28 days after administration: vaccine efficacy 84% (54.2-96.9%)

    -- review of their graph showed divergence around 7 days and plateau at around 35 days with no further cases through126 days
-- deaths from Covid: none in vaccine group, 5 in placebo

-- overall efficacy was higher in the older age group (severity-adjusted symptomatic Covid at 14 days was 75% vs 66%)

-- overall vaccine efficacy increased with longer follow-up: 92.4% after day 42

-- asymptomatic infections: 18 identified in the vaccine group and 50 in the placebo group, vaccine efficacy of 65.5% (39.9-81.8%)

    --they tested all participants for asymptomatic infection at day 71, defined as a newly positive N-immunoassay

-- hospitalization: at least 14 days after administration: 2 in vaccine group, 29 in placebo, vaccine efficacy 93.1% (72.7-99.2%)

    -- after 28 days: no hospitalizations in the vaccine group and 16 in the placebo group

-- no evidence of different efficacy in those with or without coexisting condition

-- no evidence of waning efficacy in the 3000 people were followed for 11 weeks, or the 1000 people who were followed for 15 weeks

 

--- comparing different countries, vaccine efficacy:

    -- worldwide: moderate to severe-critical Covid: 14 days 66.3% (59.9-71.8%); 28 days 65.5% (57.2-72.4%)

        -- severe-critical: 14 days 76.3% (57.9-87.5%); 28 days 83.5% (54.2-96.9%)

    -- US: moderate to severe-critical 14 days: 74.4% (65.0-81.6%); 28 days 72.0% (58.2-81.7%)

        -- severe-critical: 14 days 78.0% (33.1-94.6%); 28 days 85.9% (-9.4 to 99.7%)

    -- Brazil: moderate to severe-critical 14 days 66.2% (51.0-77.1%); 28 days 68.1% (48.8-80.7%)

        -- severe-critical: 14 days 81.9% (17.0-98.1%); 28 days 87.6% (7.8-99.7%)

    -- South Africa: moderate to severe-critical: 52.0% (30.3-67.4%); 28 days 64.0 (41.2-78.7%)

        -- severe-critical: 14 days 73.1% (40.0-89.4%); 28 days 81.7% (46.2-95.4%)

       -- there were no hospitalizations for vaccine recipients at least 28 days after the administration

-- sequencing studies done on 512 PCR-positive samples (72% with SARS-CoV-2 infections):

    -- US: 96% Wuhan-Hu-1 virus including the D614G mutation

    -- South Africa: 95% B.1.351 variant

    -- Brazil: 31% Wuhan-Hu-1; 69% P.2 lineage (Wuhan-Hu-1 plus the E484K mutation)

 

-- safety:

     -- common ones: injection site pain was the most common (49%), headache (39%), fatigue (38%), myalgia  (33%), nausea (14%)

    -- 0.4% of those on vaccine as well as 0.4% on placebo had serious adverse events

        -- a few serious adverse events were considered to be related to the vaccine, comparing vaccine to placebo: DVT 6 vs 2, pulmonary embolism 4 vs 1, transverse sinus thrombosis 1 vs 0, seizure 4 vs 1.

            -- Most people with thromboembolic events had predisposing factors that might have contributed

        -- Deaths: 3 vs 16 (all felt to be unrelated to the trial intervention)

    -- more adverse events were reported in those 18-59 years old and those 60 or older

 

Commentary: 

-- another impressive study of vaccine efficacy, especially in decreasing moderate-to-severe cases and overall for patients who were hospitalized (though hospitalization criteria may be different in different countries, review of these cases by the central committee confirmed appropriateness of hospitalization)

--it is notable that the vaccine efficacy rates found in the different countries was effectively quite similar, with overlapping confidence intervals. This is despite the fact that there were significant differences in SARS-CoV-2 variants in these different countries, as noted above

    -- this is an important and really interesting finding, given concern about decreased neutralizing antibody response to the variants found in South Africa and Brazil, but there was still impressive vaccine efficacy (see http://gmodestmedblogs.blogspot.com/2021/04/covid-escape-mutant-virus.html for some of these concerns)

    -- and it raises the issue that other antibodies or T-cell responses may play an important role in preventing Covid (e.g. antibodies with Fc-mediated functions are induced by the SARS-CoV-2 virus in humans and do not show a decrease in potency against the new variants)

    -- though, there were questions about the AstraZeneca vaccine effectiveness with the B.1.351 variant in South Africa, see  http://gmodestmedblogs.blogspot.com/2021/03/covid-z-vaccine-not-seem-to-work-with.html )

-- this study formalizes the company’s FDA submission for EUA, with some more granular data (see http://gmodestmedblogs.blogspot.com/2021/03/covid-jjjanssen-vaccine-study.html )

-- one important point here is that is impossible to really compare J&J vaccine efficacy with the Moderna or Pfizer ones, given that these were not head-to-head comparisons at the same time and in the same places. The mRNA vaccines were done at a time of fewer virus variants of concern, and at a time of fewer Covid cases, and in fewer countries than the J&J vaccine

-- it was impressive that in post hoc analysis vaccine efficacy seemed to continue for 15 weeks. It is unclear how long a single dose of the mRNA vaccines would be effective. There are ongoing studies for different strengths of the J&J vaccine and the need for 2^nd doses, as noted in the FDA submission

-- there is concern about the J&J vaccine and cerebral venous thromboses, leading to the recent one-week pause in their availability. Of note these thromboses occurred only in younger women, and the incidence of these thromboses was actually much lower than their incidence in those having an actual Covid infection (see http://gmodestmedblogs.blogspot.com/2021/04/covid-vaccine-and-central-venous.html )

-- As a relevant aside, a new study from Israel found that after the Pfizer vaccine, breakthrough Covid infections had a reduced viral load (increased Ct) 12-37 days after the 1^st dose of vaccine (see covid pfizer vaccine israel dec viral load NatMed2021 in dropbox, or https://www.nature.com/articles/s41591-021-01316-7.pdf . This suggests that vaccinated people who do get a breakthrough infection are less likely to spread the virus to others (at least for the Pfizer vaccine as used in Israel, but likely the others).

Limitations:

-- short follow-up of the vaccine, limiting interpretation of long-term benefits, or the need for booster vaccines (though their data did not suggest any waning of protection)

-- there were very few cases of very severe Covid infections or hospitalizations or deaths in either group, limiting the precision of the estimates of vaccine efficacy

 

So, overall a very effective vaccine, especially for more severe cases and in older people, but also for asymptomatic infections. There is the issue of cerebral venous thromboses in younger women, which happen less with the mRNA vaccines. The J&J vaccine is better tolerated in terms of local and systemic reactions, however. And at this point it is just a single dose, which does have the huge benefit in terms of the ability of public health systems to vaccinate a community fully. Though it probably makes sense for young women to get one of the mRNA ones…

geoff

 

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