COVID-19 antibody levels vary widely in recovered patients

A study published yesterday in JAMA Internal Medicine of 175 patients who recovered from mild COVID-19 reveals wide variation in the levels of antibodies against the novel coronavirus, ranging from very high levels in 2 patients to undetectable levels in 10—but no significant difference in illness duration.

Researchers from Fudan University in Shanghai, China, measured antibody levels in COVID-19 patients released from Shanghai Public Health Clinical Center after being hospitalized from Jan 24 to Feb 26.

Of the 175 patients, 165 (94%) had significantly higher levels of COVID-19 antibodies than 13 uninfected controls in the convalescent phase of infection. Antibody levels were medium-low in 29 patients (17%), medium-high in 69 patients (39%), and high in 25 patients (14%).

Age, sex, inflammatory response

The investigators detected neutralizing antibodies in patients 4 to 6 days after symptom onset, and levels peaked 4 to 11 days later. Antibody levels were significantly higher in the 56 older (60 to 85 years) and 63 middle-aged subjects (40 to 59 years) than in 56 younger patients (15 to 39 years). The 10 patients with undetectable antibodies were younger (median age, 34 years), and 8 of them were women.

At hospital release, significantly higher antibody levels were found in 82 men (47%) than in 93 women (53%).

Among the 117 patients with 2-week follow-up data, the median antibody level was substantially lower than the median level at hospital release, and the 56 men (48%) still had significantly elevated antibody levels compared with the 61 women (52%). Antibody levels in patients with undetectable antibody levels at hospital release remained undetectable at follow-up.

At hospital admission, antibody levels were correlated with those of C-reactive protein (indicating inflammatory response) but not with lymphocyte counts (indicating immune response to infection). Low lymphocyte levels and high C-reactive protein levels have been associated with poor COVID-19 outcomes.

Compared with younger subjects, older and middle-aged patients had significantly lower lymphocyte counts and higher C-reactive protein levels at hospitalization, indicating weaker immune response and stronger inflammatory response to the coronavirus.

Role of convalescent plasma, vaccines in immunity

While neutralizing antibodies are considered important to infectious disease recovery and protection against future infection, whether they confer immunity against future COVID-19 infection and how long that immunity might last is unknown.

The use of convalescent plasma, or the transfer of blood plasma from recovered coronavirus patients to non-infected patients to confer immunity, is based on the premise that COVID-19 antibodies can provide protection against infection, but its durability is unknown.

The authors said that the variability of neutralizing antibody levels in recovered COVID-19 patients highlights the need to evaluate and adjust antibody levels in convalescent plasma before administration, should it prove efficacious.

They also pointed out that their finding that older COVID-19 patients tend to have higher antibody levels yet worse outcomes leads them to question the assumption that antibodies protect against future coronavirus infection. "The potential clinical implications of these findings for vaccine development and future protection from infection are unknown," they wrote.

In an editor's note in the same journal, Mitchell Katz, MD, of NYC Health + Hospitals, noted that older patients, men, and those with stronger inflammatory responses—who have typically had poor COVID-19 outcomes—had higher antibody levels than other subjects in the study, "suggesting that the higher titers of antibodies do not necessarily lead to higher recovery rate."

Katz called for research into whether certain groups of people need higher antibody levels to recover and whether higher levels of antibodies result in more protection against the virus in terms of vaccines.

"In this study, 10 of 175 patients had undetectable antibody levels despite documented infection," he wrote. "Are these patients susceptible to future infection, or do they have protection based on their infection sensitizing killer T cells or memory B cells? Answers to these pointed questions can lead to better protection when faced with this still largely unknown adversary."

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