Fourth doses, stealth variant, rapid tests focus of latest COVID-19 research

The effect and safety of a fourth dose of mRNA COVID-19 vaccine were– described in a letter published by the New England Journal of Medicine on March 16. It compared 154 Israeli health care workers who received the fourth dose of the Pfizer-BioNTech vaccine and 120 who received the Moderna vaccine to age-matched controls who had only gotten three shots of the Pfizer-BioNTech vaccine. Recipients of the fourth shot had increases in antibodies, but weekly testing showed an insignificant reduction in their risk of infection with the omicron variant (25.0% of controls, 18.3% with Pfizer-BioNTech, 20.7% with Moderna). Most of those infected reported negligible symptoms. “Our data provide evidence that a fourth dose of mRNA vaccine is immunogenic, safe, and somewhat efficacious (primarily against symptomatic disease),” said the authors, who concluded that a fourth shot for healthy young people “may have only marginal benefits.” They noted that older and vulnerable populations were not assessed.

Another letter published simultaneously looked at the BA.2, or stealth, omicron variant. Using antibody titers from a total of 32 patients, it found that neutralizing antibody titers against BA.2 were similar to those against the original omicron (BA.1) variant. “These findings have important public health implications and suggest that the increasing frequency of BA.2 in the context of the BA.1 surge is probably related to increased transmissibility rather than to enhanced immunologic escape,” the authors said.

The efficacy of a rapid antigen test at identifying infection with omicron was assessed in a study published by Annals of Internal Medicine on March 15. Nasal swabs from 731 people visiting a free testing site in San Francisco were simultaneously tested with the BinaxNOW rapid antigen test and reverse transcriptase polymerase chain reaction (RT-PCR). Overall, 40.5% had positive results on RT-PCR (almost all with the omicron variant). The rapid test detected 95.2% (95% CI, 91% to 98%) of persons who tested positive on RT-PCR with a cycle threshold (Ct) value below 30, 82.1% (95% CI, 77% to 87%) of those who tested positive on RT-PCR with a Ct value below 35, and 65.2% (95% CI, 60% to 71%) of all who were positive on RT-PCR. The study also included some use of the rapid test in the cheek and throat, finding that a cheek swab failed to detect 91% of specimens that were positive on a nasal swab and that throat swabs identified less than half of positive cases. The authors concluded that the rapid antigen test “is one important component of the diagnostic armamentarium for SARS-CoV-2,” adding that the results indicated cheek or throat swabs should not replace nasal swabs and that high-risk persons with an initial negative rapid result should be tested again.

Finally, a large European study found that Bell's palsy, encephalomyelitis, Guillain-Barré syndrome, and transverse myelitis were not associated with the COVID-19 vaccines. The study, published by The BMJ on March 16, included more than 4 million people who received the AstraZeneca vaccine, more than 3 million who received the Pfizer-BioNTech vaccine, 244,913 who received the Moderna vaccine, and 120,731 who received the Johnson & Johnson (Janssen) vaccine, along with 735,870 people who had COVID-19 and more than 14 million controls. Rates of these neurologic issues after vaccination were no higher than expected normally, but they were increased with COVID-19 infection. An accompanying editorial called the results “reassuring about the safety of the vaccines, particularly compared with the observed risks associated with SARS-CoV-2 infection.”