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Severe outcomes rare after two COVID jabs – CDC and NIH

Two COVID-19 vaccine studies published this week respectively identify risk factors for severe outcomes among adults given two doses and describe cancer patients’ antibody response to two or three doses.

A Morbidity and Mortality Weekly Report (MMWR) study by National Institutes of Health (NIH) and Centers for Disease Control and Prevention (CDC) researchers involved 1,228,644 American adults who completed their primary COVID-19 vaccination regimen from December 2020 to October 2021. The period was marked by the emergence of the more transmissible Delta variant.

The researchers used data from 465 healthcare facilities in the Premier Healthcare Database Special COVID-19 Release to evaluate the frequency of and risk factors for severe COVID-19 after two doses of the mRNA COVID-19 vaccines from Pfizer/BioNTech or Moderna or one dose of the Johnson & Johnson (J&J) vaccine 14 or more days before illness onset.

Of all vaccinees, 72,8% received Pfizer, 20% were given Moderna, 6,5% received J&J, and 0,8% received an unspecified vaccine.

Severe COVID-19 was defined as hospitalisation for acute respiratory failure, the need for non-invasive ventilation, intensive care unit (ICU) admission (including those needing invasive mechanical ventilation), or death (including release to hospice).

Adverse COVID-19 outcomes were rare, at 0,.015%, and the death rate was 0,003%. Of the 128,664 people who completed primary COVID-19 vaccination during the study period, 2,246 (18,0 per 10,000 vaccinated) were infected, and 189 (1,5/10,000) experienced a poor outcome, including 36 deaths (1,6%, 0,3 deaths/10,000 vaccinated).

Among infected patients, 24 (1,1%) survived and were admitted to an ICU, and 129 (5,7%) survived and were diagnosed with acute respiratory failure or needed non-invasive ventilation but were not admitted to an ICU.

Immunosuppression linked to poor outcomes

Risk factors for severe outcomes included age 65 years and older (adjusted odds ratio [aOR], 3,22), a suppressed immune system (aOR, 1,91), and at least one of six chronic conditions, including lung disease (aOR, 1,69), liver disease (aOR, 1,68), chronic kidney disease (aOR, 1,61), neurologic disease (aOR, 1,54), diabetes (aOR, 1, 47), and heart disease (aOR, 1,44). All patients with adverse outcomes had at least one of these risk factors, and 77,8% of those who died had at least four.

Relative to vaccinees who received the J&J vaccine, those given Pfizer had comparable odds of poor COVID-19 outcomes (aOR, 0,70), while Moderna recipients' odds were lower (aOR, 0,56).

Odds of adverse outcomes did not differ significantly by sex, race, time since primary vaccination, or whether infection occurred during the Delta variant surge. Previous COVID-19 illness was tied to reduced odds of severe outcomes (aOR, 0,27).

“Several factors could contribute to severe outcomes in populations who are at risk, including suboptimal response to vaccination, waning immunity, and predisposition to severe disease,” the researchers wrote. “People who might not have mounted a protective immune response after initial vaccination might benefit from an additional primary dose. Booster vaccination after primary vaccination has been demonstrated to further reduce the risk for infection, particularly severe COVID-19.”

While poor COVID-19 outcomes are rare after primary vaccination, people with the identified risk factors should receive targeted interventions, including chronic disease management, precautions to reduce exposure, more primary and booster vaccine doses, and effective drug treatments, the authors added.

Third dose raises immune response in cancer patients

In a single-centre observational study in JAMA Oncology, researchers at a French hospital evaluated the humoral immune response of 163 patients being treated for solid tumours after two or three doses of the Pfizer COVID-19 vaccine. Humoral immune response involves the production of antibodies by B lymphocytes, a kind of white blood cell.

Cancer patients with solid tumours are particularly at risk for COVID-19 infection and severe outcomes. In the study, active cancer was defined as solid cancer treatment within the previous six weeks or a plan to start treatment within the next two weeks.

From 1 February to 31 May 2021, cancer patients with a weak humoral immune response one month after receipt of the second COVID-19 dose were given a third dose. Median patient age was 66 years, 53% were men, 75% received chemotherapy, 9% received immunotherapy, and 16% received targeted therapies.

Twenty-two of 145 (15%) patients had anti-S immunoglobulin G (IgG) concentrations greater than the threshold of 1,000 arbitrary units per millilitre (AU/mL) at the time of the second COVID-19 vaccine dose, while 92 of 142 (65%) passed that threshold one month later.

Humoral immune response declined three months after the second dose. Of the 36 patients who received a third dose, 27 (75%) achieved a serologic response greater than the threshold value. Treatment type was linked to humoral response, but time between receipt of the vaccine and chemotherapy didn't alter the response.

No patient developed symptomatic COVID-19 after the second dose, and no serious adverse events were noted after the third.

“The results of this study suggest that a third dose of the SARS-CoV-2 vaccine could be needed at one month after the second dose in patients receiving active cancer treatment,” the authors concluded.

Study details 1

Risk Factors for Severe COVID-19 Outcomes Among Persons Aged ≥18 Years Who Completed a Primary COVID-19 Vaccination Series — 465 Health Care Facilities, United States, December 2020–October 2021

Christina Yek, Sarah Warner, Jennifer Wiltz, Junfeng Sun, Stacey Adjei, Alex Mancera, Benjamin Silk, Adi Gundlapalli, Aaron Harris, Tegan Boehmer, Sameer Kadri.

Published in Morbidity and Mortality Weekly Report (MMWR) on 1 January 2022

Summary

What is already known about this topic?
COVID-19 vaccines are highly effective against COVID-19–associated hospitalisation and death.

What is added by this report?
Among 1,228,664 persons who completed primary vaccination during December 2020–October 2021, severe COVID-19–associated outcomes (0.015%) or death (0.0033%) were rare. Risk factors for severe outcomes included age ≥65 years, immunosuppressed, and six other underlying conditions. All persons with severe outcomes had at least one risk factor; 78% of persons who died had at least four.

What are the implications for public health practice?
Vaccinated persons who are older, immunosuppressed, or have other underlying conditions should receive targeted interventions including chronic disease management, precautions to reduce exposure, additional primary and booster vaccine doses, and effective pharmaceutical therapy to mitigate risk for severe outcomes. Increasing vaccination coverage is a critical public health priority.

Study details 2

SARS-CoV-2 Antibody Response to 2 or 3 Doses of the BNT162b2 Vaccine in Patients Treated With Anticancer Agents

Charlotte Fenioux, Luis Teixeira, Slim Fourati, Giovanna Melica, Jean Daniel Lelievre, Sebastien Gallien, Gérard Zalcman, Jean Michel Pawlotsky, Christophe Tournigand,

Published in JAMA Oncology on 7 January 2022

Key Points
Question What is the immune humoral response to 2 or 3 doses of the BNT162b2 (BioNTech; Pfizer) vaccine in patients treated with anticancer agents for solid cancer?
Findings In this cohort study including 163 patients, a third vaccine dose strengthened the immune response in 75% of the patients treated with chemotherapy or targeted therapy presenting a weak humoral response after the second dose.
Meaning The data of this study appear to support the use of a third vaccine dose as a booster dose among patients with active cancer treatment for solid tumours.

Abstract

Importance Patients with solid cancer are more susceptible to develop SARS-CoV-2 infection and severe complications; the immunogenicity in patients treated with anticancer agents remains unknown.
Objective To assess the immune humoral response to two or three doses of the BNT162b2 (BioNTech; Pfizer) vaccine in patients treated with anticancer agents.

Design, Setting, and Participants A prospective observational cohort study was conducted between 1 February and 31 May 2021. Adults treated with anticancer agents who received two or three doses of vaccine were included; of these, individuals with a weak humoral response one month after the second dose received a third injection.

Interventions Quantitative serologic testing of antibodies specific for SARS-CoV-2 was conducted before vaccination and during follow-up.

Main Outcomes and Measures Humoral response was evaluated with a threshold of anti–SARS-CoV-2 spike protein antibody levels at 1000 arbitrary units (AU)/mL to neutralise less-sensitive COVID-19 variants.

Results Among 163 patients (median [range] age, 66 [27-89] years, 86 men [53%]) with solid tumors who received two or three doses of vaccine, 122 individuals (75%) were treated with chemotherapy, 15 with immunotherapy (9%), and 26 with targeted therapies (16%). The proportions of patients with an anti-S immunoglobulin G titer greater than 1000 AU/mL were 15% (22 of 145) at the time of the second vaccination and 65% (92 of 142) 28 days after the second vaccination. Humoral response decreased three months after the second dose. Treatment type was associated with humoral response; in particular, time between vaccine and chemotherapy did not interfere with the humoral response. Among 36 patients receiving a third dose of vaccine, a serologic response greater than 1000 AU/mL occurred in 27 individuals (75%).

Conclusions and Relevance The results of this cohort study appear to support the use of a third vaccine dose among patients with active cancer treatment for solid tumours.

CIDRAP article – Severe outcomes rare after two COVID vaccine doses (Open access)
https://www.cidrap.umn.edu/news-perspective/2022/01/severe-outcomes-rare-after-two-covid-vaccine-doses? _

MMWR article – Risk Factors for Severe COVID-19 Outcomes Among Persons Aged ≥18 Years Who Completed a Primary COVID-19 Vaccination Series — 465 Health Care Facilities, United States, December 2020–October 2021
https://www.cdc.gov/mmwr/volumes/71/wr/mm7101a4.htm?

JAMA Oncology article – SARS-CoV-2 Antibody Response to 2 or 3 Doses of the BNT162b2 Vaccine in Patients Treated With Anticancer Agents (Open access)
https://jamanetwork.com/journals/jamaoncology/fullarticle/2788011

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