Stable Levels of Antibodies Against Unrelated Toxoid Vaccines After COVID-19: COVID-19 Infection Does Not Affect Toxoid Vaccine Antibody Levels

Abstract

Background: Lymphopenia is common in COVID-19. This has raised concerns that COVID-19 could affect the immune system akin to measles infection, which causes immune amnesia and a reduction in protective antibodies.

Methods: We recruited COVID-19 patients (n = 59) in Helsinki, Finland, and collected plasma samples on 2 to 3 occasions during and after infection. We measured IgG antibodies to diphtheria toxin, tetanus toxoid, and pertussis toxin, along with total IgG, SARS-CoV-2 spike protein IgG, and neutralizing antibodies. We also surveyed the participants for up to 17 months for long-term impaired olfaction as a proxy for prolonged post-acute COVID-19 symptoms.

Results: No significant differences were found in the unrelated vaccine responses while the serological response against COVID-19 was appropriate. During the acute phase of the disease, the SARSCoV-2 IgG levels were lower in outpatients when compared to inpatients. SARS-CoV-2 serology kinetics matched expectations. In the acute phase, anti-tetanus and anti-diphtheria IgG levels were lower in patients with prolonged impaired olfaction during follow up than in those without.

Conclusions: We could not detect significant decline in overall humoral immunity during or after COVID-19 infection. In severe COVID-19, there appears to be a temporary decline in total IgG levels.

Keywords: Antibodies; COVID-19; Humoral; Immunity; Post-acute COVID-19 syndrome; Vaccines.

Figure 1.

Diphtheria, tetanus, and pertussis toxoid antibodies in peripheral blood. Vertical lines denote the range of minimum and maximum values, the box denotes 1st and 3rd quartile values, and the middle horizontal line denotes the median value. Black dots denote outlier values. A = acute (n = 55), B = convalescent (n = 50), C = recovered (n = 48). Figure 1A shows the distributions in all patients, and 1B shows outpatients and hospitalized patients separately.

Figure 2.

Total IgG, SARS-CoV-2 Spike protein IgG, and SARS-CoV-2 neutralizing antibody titers in peripheral blood. Vertical lines denote the range of minimum and maximum values, the box denotes 1st and 3rd quartile values, and the middle horizontal line denotes the median value. Black dots denote outlier values. A = acute, B = convalescent, C = recovered. Significance: * P< 0.05, ** P < 0.01 (paired Wilcoxon test). Figure 1A shows the distributions in all patients, and 1B shows outpatients and inpatients separately.

Figure 3.

Antibody levels for COVID-19 outpatients and hospitalized patients. Vertical lines denote the range of minimum and maximum values, the box denotes 1st and 3rd quartile values, and the middle horizontal line denotes the median value. Black dots denote outlier values. Outpatients (light purple bars) and hospitalized (dark purple), phases A = acute, B = convalescent, C = recovered. Significance: * P< 0.05, ** P < 0.01, *** P < 0.001 (Mann-Whitney U test).

Figure 4.

Antibody levels plotted with time since symptom onset (days). Red dots denote patients with no PASC (no impaired olfaction), and blue dots denote patients with PASC (impaired olfaction). Accordingly, the red line represents the local regression (as calculated with LOESS) in patients without PASC, and the blue line represents the moving average in patients with PASC.