key: cord-0889557-73rpgcgj
authors: Reicherz, Frederic; Golding, Liam; Lavoie, Pascal M; Abu-Raya, Bahaa
title: Decay of anti-Bordetella pertussis antibodies in women of childbearing age following COVID-19 non-pharmaceutical measures
date: 2022-05-11
journal: Vaccine
DOI: 10.1016/j.vaccine.2022.04.086
sha: ee2586e720fdae638e29c6979ef7db98ba96ed6a
doc_id: 889557
cord_uid: 73rpgcgj

BACKGROUND: Immunization against Bordetella pertussis during pregnancy reduces morbidity from severe pertussis in young infants via trans-placental transfer of anti-B. pertussis Immunoglobulin G (IgG). Studies have reported a near disappearance of respiratory pathogens including B. pertussis following implementation of mitigation strategies to control Coronavirus disease 2019 (COVID-19). We explored how immunity against B. pertussis changed in women of childbearing-age through the COVID-19 pandemic. METHODS: Paired blood samples from females of childbearing-age collected at the beginning (May-June 2020) and nearly one year into the COVID-19 pandemic (February-May 2021) in British Columbia (BC), Canada were tested for anti-B. pertussis IgG levels. To ascertain whether early-pandemic IgG levels in 2020 reflected levels in pregnant women early in gestation, 1(st) trimester sera collected from age-matched healthy pregnant women in 2018 and 2019 were tested for anti-B. pertussis IgG. Levels were compared by t tests. P-value of 0.05 was assigned and statistical significance was set as p<0.016 using Bonferroni correction. RESULTS: Annual provincial B. pertussis incidences per 100,000 in BC in 2020 (3/100,000) and 2021 (<1/100,000) approximated the lowest levels since 1990. In 2021 vs. 2020, anti-pertussis toxin (PT), filamentous hemagglutinin (FHA) and pertactin (PRN) IgG levels declined in women of childbearing-age: 6.8 IU/ml (95%CI, 4.2-10.9) vs. 8.4 IU/ml (5.1-13.9; p=0.004); 18.8 IU/ml (10.9-32.2) vs. 23.6 IU/ml (13.2-42.1; p<0.001); and 37.1 IU/ml (18.1-75.9) vs. 47.2 IU/ml (24.8-89.9; p=0.092), respectively. Although all values were slightly higher, anti-PT, FHA and PRN IgG levels in women of childbearing age did not significantly differ in 2020 compared with early-gestation pregnant women in 2018-2019, 8.4 IU/ml (95% CI, 5.1-13.9) vs. 5.4 IU/ml (95% CI, 3.8-7.7; p=0.166), 23.6 IU/ml (95% CI, 13.2-42.1) vs. 20.1 IU/ml (95% CI, 13.4-30.2; p=0.656), and 47.2 IU/ml (24.8-89.9) vs. 17.3 IU/ml (95% CI, 10.5-28.7; p=0.021), respectively. DISCUSSION: B. pertussis infections should be closely monitored during the relaxing of mitigation measures for COVID-19.

Young infants are at risk for severe pertussis (or "whooping cough") disease caused by the respiratory pathogen Bordetella pertussis [1] . In order to protect young babies from pertussis in early infancy, immunization with a tetanus-diphtheria-acellularpertussis (Tdap) vaccine is recommended during each pregnancy [2] . Two vaccines are available to protect from pertussis, the whole cell pertussis (wP) and acellular pertussis (aP) vaccines. The wP vaccine is composed of the whole inactivated B. Tdap administration during pregnancy boosts maternal pre-existing antibody levels against B. pertussis and increases trans-placental transfer to the newborn [3] [4] [5] . In the context of COVID-19 mitigation measures, countries have seen a profound decrease in clinical detection of B. pertussis infections in populations [6] [7] [8] [9] . In Canada, data from the province of Ontario showed that only 3 cases of pertussis were reported between January-June 2021, a significantly lower reported number compared to 193 5- year average year-to-date count [10] . This conjuncture offers an opportunity to study the trends of B. pertussis infections during the COVID-19 pandemic in another of one of Canada's larger provinces, British Columbia (BC), and the stability of preexisting antibody immunity against B. pertussis in the context of potential limited bacterial exposure in women of childbearing age. [11] . Lower limits of detection for IgG to PT, FHA and PRN were 0.2 IU/mL, 1 IU/mL and 0.6 IU/mL, respectively.

Statistics: Anti-B. pertussis IgG levels were log transformed and compared between the years 2020 vs. 2021 using a paired 2-sided student t-test, and the years 2018-2019 vs. 2020 using unpaired 2-sided student t-test. The proportions of subjects with anti-PT IgG levels ≥5 IU/mL, ≥15 IU/mL, ≥30 IU/mL or ≥40 IU/mL were also compared between 2021 and 2020, and between 2020 and 2018-2019 using chi-squared tests.

Although there is no clear antibody correlate of protection against pertussis, these arbitrary cut-offs were used to define the population with quantifiable anti-B.

pertussis antibodies (anti-PT IgG ≥5 IU/mL), and the seropositive or potentially protected population (with anti-PT IgG ≥15 IU/mL, ≥30 IU/mL or ≥ 40 IU/mL) as suggested previously [12] . P-value of 0.05 was assigned and statistical significance was set at P<0.016 after adjustment for multiple comparisons (n=3 for 3 B. pertussis antigen-specific IgG levels for each comparison) using Bonferroni correction. R IU/mL, ≥30 IU/mL or ≥40 IU/mL in 2021 compared with 2020 was 55.5% [10/18] pandemic [13] .

We showed that the incidence of reported B. pertussis declined in the years 2020 and 2021 compared to pre-pandemic years in all age groups. This is consistent with recent literature that showed a decrease in identification of B. pertussis infections in the population during the COVID-19 pandemic [6] [7] [8] [9] . Most recently, data from Public Health England showed that the incidence of pertussis decreased significantly in the years 2020 and 2021, compared to pre-pandemic years (2014-2019) in all age groups [14] . Of note, surveillance trends in BC related to pertussis incidence apply not only to the population as a whole but also to infants in whom severe outcomes are more likely and under-reporting is less likely on that basis.

The findings of low levels of anti-B. pertussis antibodies measured in 2020 are consistent with a previous study in Canada, which showed that 97% of pregnant women between 2008-2011 had anti-PT IgG levels <35 IU/ml, and 44% had levels <5 IU/ml [15] . Similar to our findings, the GMC of anti-PT IgG was 5.5 IU/mL in pregnant women in Canada [15] , and similar to findings from the Netherlands (10.1 IU/mL) [16] and the USA (6.0 IU/mL) [17] . However, these studies were conducted in settings of potential exposure to B. pertussis during the study period. [18] . Other studies showed that anti-B.

pertussis antibody levels either stabilize or increase during follow up observations, supporting that some level of immunity against B. pertussis may be maintained in the context of exposure to the bacterium. A study performed in Germany with samples collected in 1994 showed stable anti-B. pertussis antibodies over a 2-5-year observation period. This latter finding suggests that exposure to B. pertussis happened within the population prior to the pandemic, and were able to maintain stable antibody levels [19] . Based on a longitudinal study in the USA, 90% of adults showed serological evidence of exposure to B. pertussis in the era of the wP vaccine (1984) (1985) (1986) (1987) (1988) (1989) , with an increase in one or two antigen-specific anti-B. pertussis antibodies between 2 consecutive years (during 5-year period). These data suggest that B.

pertussis infections in adults may be more common than clinically recognized [20] .

Finally, a most recent study from Sweden showed a near disappearance of B. pertussis among young infants <1 year of age following non-strict mitigation strategies to limit the spread of COVID-19, where schools were still open and no lockdown or mandatory face masking mandates were issued [9] . Overall, these data support a more pertussis incidence is also evident in infants <1 year of age in 2020 (14/100,000) and 2021 (nil) compared to 2018 and 2019 (~50 per 100,000), comparable to or lower also than the trough years of 2010 (18/100,000) and 2011 (16/100,000) [21] . This temporal comparison among infants in particular is relevant because severe B. pertussis outcomes are more likely in that very young age group and less likely to be missed Although an absolute correlation cannot be claimed, higher anti-PT, anti-FHA, and anti-PRN IgG levels are generally associated with greater likelihood of clinical protection from pertussis [22, 23] . The potential significance of these low antibody levels may also vary as PT, FHA and PRN as virulence factors contribution to the development of pertussis disease in humans at different stages. PT is an important virulence factor that induces lymphocytosis, which can lead to pulmonary hypertension, respiratory failure and death [24] . FHA is implicated in the initiation of the disease by the attachment of the bacteria to the respiratory epithelium [25] . PRN is a surface-associated protein [26] , and also contributes to adherence of B. pertussis to ciliated respiratory epithelium [27] . It should be noted that due to pandemic related pressures across all health authorities in BC and prioritization of COVID-19 notifications, the standard surveillance data verification processes for non-COVID notifiable diseases were scaled back. We acknowledge, that surveillance data are subject to change as the usual audits and verifications of notifiable diseases, including retrospectively, resume post-pandemic. Our 2019-2021 surveillance summaries in particular need to be interpreted with caution. Our study is also limited by a small sample size of the 2020-2021 paired subjects and the small number of subjects in 2018-2019 cohort.

In conclusion, this study provides evidence for reduction in anti-B. pertussis IgG levels in women of childbearing age during a period of low pathogen exposure.

Although the clinical implications are uncertain, careful surveillance monitoring for potential increase in B. pertussis among infants at highest risk of severe outcomes seems prudent during the post-pandemic period. and one year after non-pharmaceutical measures (2021 in red dots; n=18 [for filamentous hemagglutinin n=17])).

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