Severe outcomes rare after two COVID vaccine doses

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

Adverse outcomes exceedingly rare

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 (B1617.2) 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 hospitalization for acute respiratory failure, the need for noninvasive 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 noninvasive 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. "Persons 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-center observational study in JAMA Oncology, researchers at a French hospital evaluated the humoral immune response of 163 patients being treated for solid tumors 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 tumors 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 6 weeks or a plan to start treatment within the next 2 weeks.

From Feb 1 to May 31, 2021, cancer patients with a weak humoral immune response 1 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 milliliter (AU/mL) at the time of the second COVID-19 vaccine dose, while 92 of 142 (65%) passed that threshold 1 month later.

Humoral immune response declined 3 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 1 month after the second dose in patients receiving active cancer treatment," the authors concluded.

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