Depressed seroconversion in immunocompromised COVID-19 vaccine recipients

The coronavirus disease 2019 (COVID-19) pandemic is a great risk to those with weakened immune systems, including both the immunocompromised and the elderly. While shielding tactics, social distancing, and other restrictions have attempted to keep immunocompromised people safe, as mass vaccination programs gain more and more traction, many governments are beginning to remove these measures.

Study: Efficacy of COVID-19 vaccines in immunocompromised patients: A systematic review and meta-analysis. Image Credit: Yuganov Konstantin/ Shutterstock

These vaccines have shown strong efficacy in immunocompetent individuals, with those approved in the EU showing between 70-90% protections following both doses. Unfortunately, vaccine trials rarely include immunocompromised people – both because many of them are incapable of receiving vaccines and the inherently increased risk in testing vaccines on those with weakened immune systems.

Theoretically, mRNA vaccines pose no threat of infection, but risks remain of allergic reactions and immune hypersensitivity. Researchers from the University Of Singapore have reviewed the data in post-vaccinated immunocompromised patients to examine the effectiveness of these vaccines in these patients.

A preprint version of the study is available on the medRxiv* server while the article undergoes peer review.

The study

The researchers took papers published between December 2020 and September 2021 and had two researchers screen them by title, abstract and full text, with any disagreements resolved by a third researcher. Only results from human subjects were included. Certain studies that did not report data in appropriate forms or included but did not report immunocompetent control groups were not included. Unfortunately, there were no randomized trials of COVID-19 vaccines in immunocompromised individuals. The researchers pooled risk ratios from studies and used DerSimonian random effects meta-analysis to examine associations, as well as performing sensitivity analysis and publication bias.

In total, 42 studies were eventually included in the review, from a total of 3283 before the screening. None were experimental trials – most observed seroconversion/seroprevalence in submitted blood samples. 88% of studies (37/42) showed seroconversion in both immunocompromised and control groups. Sixteen studies examined responses after the first dose, with the rest examining responses after the second. 83.3% of studies used mRNA vaccines, with two studies looking at CoronaVac and five examining both.

As expected, 17 studies showed significantly reduced seroconversion rates in immunocompromised individuals after the first dose, with the risk ratios (RR) at 0.27. Transplant recipients were at most risk, with an RR of 0.06, followed by hematological cancers, solid cancers, and then IMID patients. Another 30 studies showed the results of immunocompromised patients after the second dose.

Promisingly, the RR was much higher, with the total combined RR of immunocompromised individuals at 0.62, compared to 0.99 in healthy individuals. The immunocompromised patients at the greatest risk also changed following the second dose – although transplant patients were still the most endangered, followed by hematological cancers, IMID patients, and then solid cancers.

These results are backed up by previous studies showing lower vaccine protection in cancer patients for viruses such as influenza. The same trends were also seen in seroconversion rates and antibody titers, with some protection being offered but generally less than seen in healthy individuals.


The authors highlight that their study – the first meta-analysis of immunogenicity and serological titers in immunocompromised individuals who have taken the COVID-19 vaccine – further cements the importance of the second dose of the vaccine as well as strengthening the argument for booster shots, especially amongst the immunocompromised and at-risk groups such as the elderly. The second dose provided far more protection than the first dose, and in solid cancer patients raised the RR to levels approaching those seen in healthy patients.

The scientists also recommend that vaccine regimens be tailored to the level of risk and degree of immunocompromise. While governments already took this approach to a certain degree, the authors recommend going even further and providing booster doses with respect to factors such as the level of immunosuppression that certain drugs provide and the disease that caused the patient to become immunocompromised.

The researchers finally draw attention to the lack of information on the effects of the COVID-19 vaccines in certain populations, such as those suffering from HIV and AIDS, which are known to suffer lower vaccine response rates.

*Important notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information

Journal reference:
  • Lee, R. et al., (2021) Efficacy of COVID-19 vaccines in immunocompromised patients: A systematic review and meta-analysis. medRxiv. doi:

Posted in: Medical Science News | Medical Research News | Disease/Infection News

Tags: AIDS, Antibody, Blood, Cancer, Coronavirus, Coronavirus Disease COVID-19, Drugs, Efficacy, HIV, Hypersensitivity, Immunosuppression, Influenza, Pandemic, Traction, Transplant, Vaccine

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Written by

Sam Hancock

Sam completed his MSci in Genetics at the University of Nottingham in 2019, fuelled initially by an interest in genetic ageing. As part of his degree, he also investigated the role of rnh genes in originless replication in archaea.

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