Invasive pneumococcal disease before, during and after the SARS-CoV-2 pandemic

Abstract

Background

The aim of this study was to analyse the changes in the incidence of invasive pneumococcal disease (IPD) before, during, and after the SARS-CoV-2 pandemic.

Methods

Cases of IPD detected through active epidemiological surveillance in Navarre, Spain, from 2018 to 2024 were analysed. Incidence rates were compared across three periods: pre-pandemic (2018–2019), pandemic (2020–2022), and post-pandemic (2023–2024) overall and by age groups and serotypes

Results

From 2018 to 2024, a total of 437 IPD cases were diagnosed in Navarre. The incidence of IPD decreased from 11.6 to 5.6 cases per 100,000 persons during the pandemic period and return to 13.0 cases per 100,000 persons in the post-pandemic period. The incidence decreased across all age groups in both, serotypes included and not included in the 13-valent pneumococcal conjugate vaccine (PCV13). Serotype 3 was the most frequent in the three periods, representing 20.3% of all cases. In the post-pandemic period, 35.2% of cases were due to serotypes included in the PCV-13, 45.7% in the PCV-15 and 64.2% in the PCV-20.

Conclusions

During the SARS-CoV-2 pandemic, the incidence of IPD decreased across all age groups for both, PCV13-included and not included serotypes. In the post-pandemic period, incidence returned to pre-pandemic levels. Whole-genome sequencing techniques helped to serotyping of S. pneumoniae, and thus, complemented epidemiological surveillance.

Resumen

Introducción

El objetivo de este estudio fue analizar los cambios en la incidencia de la enfermedad neumocócica invasiva (ENI) antes, durante y después de la pandemia de SARS-CoV-2.

Métodos

Se analizaron los casos de ENI detectados en la vigilancia epidemiológica activa en Navarra desde 2018 hasta 2024. Se compararon las tasas de incidencia en tres periodos: prepandemia (2018−2019), pandemia (2020−2022) y pospandemia (2023−2024) para el total de los casos y según grupos de edad.

Resultados

Entre 2018 y 2024 se diagnosticaron 437 casos de ENI en Navarra. La incidencia se redujo en el periodo pandémico de 11,6 a 5,6 casos por 100.000 habitantes y retornó a 13,0 casos por 100.000 habitantes pasada la pandemia. El descenso en la incidencia durante la pandemia se observó en los serotipos incluidos en la vacuna conjugada 13-valente (VCN-13) y en los no incluidos, para todos los grupos de edad. El serotipo 3 fue el más frecuente durante los tres periodos, causando el 20,3% de todos los casos. En el periodo pospandémico, el 35,7% de los casos fueron debidos a serotipos incluidos en la VCN-13, el 45,7% en la VCN-15 y el 64,2% en la VCN-20.

Conclusiones

Durante la pandemia de SARS-CoV-2, la incidencia de ENI producida por serotipos incluidos y no incluidos en VCN-13 disminuyó en todos los grupos de edad. En la pospandemia, se recuperó el nivel de incidencia prepandémico. La secuenciación del genoma completo permite el serotipado de S. pneumoniae y complementa la vigilancia epidemiológica.

Introduction

Streptococcus pneumoniae causes infections with high morbidity and mortality rates.^1,2 Paediatric patients, older adults and those with chronic diseases are at increased risk of invasive pneumococcal disease (IPD).³S. pneumoniae is airborne and one of its main virulence factors is its capsule, which allows it to evade the host's immune response.¹ More than 100 different serotypes have been described on the basis of the polysaccharide capsule. Vaccines against S. pneumoniae target some of these capsular serotypes, but the serotype diversity limits the preventive potential of each vaccine against IPD overall.⁴ Two types of pneumococcal vaccines have been marketed, unconjugated pneumococcal polysaccharide vaccines and pneumococcal conjugate vaccines (PCV). The unconjugated 23-valent vaccine has shown moderate efficacy in preventing pneumococcal disease, but is not effective in children under two years of age, due to the immaturity of their immune system. The 7-valent conjugate vaccine became available in 2000, with the aim of preventing IPD in children under two years of age.³

In Spain, the 7-valent vaccine was replaced by the 13-valent vaccine (PCV13), which became available in pharmacies in June 2010, and was only funded for patients with risk factors, until it was included in the childhood immunisation schedule in 2016. PCV13 has been shown to be effective in preventing IPD due to the serotypes included in the vaccine, and has also demonstrated protection in unvaccinated individuals living in settings with medium or high vaccination coverage, through an indirect effect.⁵ The spread of conjugate vaccines tends to produce changes in circulating serotypes, with the serotypes present in these vaccines being replaced by others not included.⁵ To prevent disease caused by the pneumococcal serotypes which had become more common in Spain, in 2024 PCV13 was replaced by PCV15 in paediatric immunisation and PCV20 in adults.

SARS-CoV-2 is a new coronavirus virus and the cause of the COVID-19 pandemic in 2020. Although SARS-CoV-2 infection could increase the incidence of secondary bacterial infections, as with other respiratory viruses,^6,7 non-pharmacological preventive measures taken for the prevention of SARS-CoV-2 transmission significantly reduced the transmission of many respiratory infections,⁸ including S. pneumoniae, and even changed the epidemiology of IPD.^6,9

In May 2023 the World Health Organisation declared the SARS-CoV-2 health emergency to be at an end. The aim of this study was to assess changes in the incidence of IPD and the distribution of S. pneumoniae serotypes before, during and after the SARS-CoV-2 pandemic.

Material and methods

Design and sources of information

We designed a descriptive population-based study of cases registered in the active surveillance of IPD in Navarre, Spain, with an approximate population of 670,000 people. All clinical microbiology laboratories report confirmed cases of invasive S. pneumoniae disease, laboratory reports are reviewed and clinical and epidemiological information is collected from digitised medical records.

This study was approved by the Navarre Ethics Committee for Research with Medicines (PI2024/150). All analyses were done with anonymised data.

Inclusion criteria

We included all cases of IPD reported in Navarre from 2018 to 2024. IPD was defined as the isolation or detection of S. pneumoniae bacterial genome or antigen in usually sterile specimens, such as blood, cerebrospinal fluid (CSF) and pleural fluid.

Microbiological diagnosis

Identification of isolates obtained by conventional culture was performed by mass spectrometry [MALDI Biotyper®; Bruker Daltonics, USA] and optochin sensitivity. Bacterial DNA detection was performed by molecular biology techniques [RealCycler ® MENELI, Progenie Molecular, Spain] and antigen detection by immunochromatography [BinaxNOW®; Alere, USA]. The serotype was determined by PCR followed by reverse hybridisation [S.PneumoStrip, OPERON S.A., Zaragoza, Spain], and from 2023, by whole genome sequencing using the Illumina DNA Prep protocol and 2 × 150 cycle paired-end sequencing [Illumina, San Diego, CA, USA]. Genotype bioanalysis and serotype inference were carried out using the Pathogenwatch platform.

Serotypes were analysed individually and grouped into categories according to whether or not they were included in PCV13. Similar categorisation was done for each of the new vaccines (PCV15, PCV20 and PCV21) (Table 1). S. pneumoniae isolates which could not be serotyped were classified as a case of IPD produced by non-typed serotype.

Table 1.

Categories of S. pneumoniae serotypes according to their inclusion in different vaccines.

Category	Serotypes included
PCV13	1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F
Non-PCV13	Serotypes not included in PCV13
PCV15	1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F, 22F, 33F
PCV20	1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F, 22F, 33F, 8, 10A, 11A, 12F, 15B
PCV21	3, 6A, 7F, 8, 9N, 10A, 11A, 12F, 15A, 15B, 16F, 17F, 19A, 20A, 22F, 23A, 23B, 24F, 31, 33F, 35B
Non-typable	Unknown

PCV: pneumococcal conjugate vaccine.

Statistical analysis

We analysed anonymised computerised databases of epidemiological surveillance of IPD in Navarre, with the variables of date of diagnosis, age, gender, type of specimen and S. pneumoniae serotype.

The annual incidence of IPD was analysed and grouped into periods, according to serotype category and age group. The time periods considered were pre-pandemic (2018−2019), pandemic (2020−2022) and post-pandemic (2023−2024). Patients were grouped into three age groups: under 5 years of age, 5−64 and 65 and over.

As denominators for the calculation of the rates, we used the Instituto Nacional de Estadística [Spanish National Institute of Statistics] data for the resident population in Navarre. Mean annual incidence rates of IPD were estimated for each of the three periods. In the sub-analysis by serotype categories, we excluded cases where a specific serotype could not be determined.

For comparisons of incidence rates, we used the exact mid-p test with two-tailed p-value. P-values <0.05 were considered statistically significant.

Results

Characteristics of IPD cases

From 2018 to 2024, 437 cases of IPD were diagnosed in Navarre, 53 (12%) cases in children under 5 years of age, 189 (43%) in people aged 5−64 years, and 194 (44%) in people aged 65 and over. The mean age of the cases was 54 years (SD: 28 years). Among cases of IPD, the majority were male (59.7%).

S. pneumoniae was detected in blood in 83.1% of cases of IPD, in pleural fluid in 10.8%, CSF in 6.6% and in other fluids in 3.0%. In 15 patients, S. pneumoniae was detected in more than one sample: 13 in blood and CSF; one patient in blood and ascitic fluid; and one patient in blood and pleural fluid (Table 2).

Table 2.

Cases of invasive pneumococcal disease by period, gender, age and diagnostic sample in Navarre, 2018-2024.

	Number of cases (%)
	Pre-pandemic 2018−2019 (N = 151)	Pandemic 2020−2022 (N = 111)	Post-pandemic 2023−2024 (N = 175)	Total 2018−2024 (N = 437)
Gender
Male	95 (62.9)	57 (51.4)	109 (62.3)	261 (59.7)
Female	56 (37.1)	54 (48.7)	66 (37.7)	176 (40.3)
Age, years
<5	15 (9.9)	18 (16.2)	20 (11.4)	53 (12.1)
5−64	61 (40.4)	49 (44.1)	79 (45.1)	189 (43.3)
≥65	75 (49.7)	44 (39.6)	76 (43.4)	194 (44.4)
Diagnostic sample*
Blood	133 (88.1)	88 (79.3)	142 (81.4)	363 (83.1)
Pleural fluid	7 (4.6)	13 (11.7)	27 (15.4)	47 (10.8)
Cerebrospinal fluid	9 (6.0)	13 (11.7)	7 (4.0)	29 (6.6)
Other fluids	4 (2.7)	5 (4.5)	4 (2.3)	13 (3.0)

*

In 15 patients, the diagnosis of invasive pneumococcal disease was made in more than one specimen.

Trend in the incidence of IPD

The annual incidence of IPD, which started from rates of 11–12 per 100,000 population before the pandemic, fell by about half (5–6 per 100,000) in the pandemic period (2020−2022). In 2023 it showed a strong rebound, reaching 14 cases per 100,000 population and in 2024 it was at similar rates to the baseline (12 per 100,000). These changes in incidence followed a similar pattern across all age groups, although the post-pandemic spike happened earlier, in 2022, and was more pronounced in children under 5 years of age (Fig. 1). The same behaviour was observed for serotypes included and not included in PCV13, with declines in rates in the pandemic period and recovery of pre-pandemic levels in the years 2023 and 2024 (Fig. 2).

Figure 1.

Annual incidence of invasive pneumococcal disease by age group in Navarre, 2018–2024.

Figure 2.

Annual incidence of invasive pneumococcal disease by categories of serotypes included and not included in the 13-valent conjugate vaccine in Navarre, 2018–2024.

Table 3 shows the number of cases and the incidence rate of IPD by age group and study period, as well as the comparison of rates between the periods. For the total number of cases, for serotypes included and not included in PCV13 and for all three age groups, declines in rates were observed in the pandemic period and increases in the post-pandemic period to levels close to baseline.

Table 3.

Incidence of invasive pneumococcal disease in the three study periods according to serotype categories and age groups in Navarre, 2018–2024.

Serotype group and age	Pre-pandemic 2018−2019		Pandemic 2020−2022		Post-pandemic 2023−2024		Pandemic vs pre-pandemic		Post-pandemic vs pandemic		Post-pandemic vs pre-pandemic
	Cases	Rate/100,000	Cases	Rate/100,000	Cases	Rate/100,000	Rate difference/100,000	p-value	Rate difference/100,000	p-value	Rate difference/100,000	p-value
Total*
<5 years	15	24.4	18	20.9	20	37.9	−3.6	0.652	17.0	0.063	13.4	0.202
5−65 years	60	6.1	48	3.2	79	7.7	−2.9	<0.001	4.6	<0.001	1.6	0.164
≥65 years	76	29.9	45	11.3	76	27.3	−18.5	<0.001	16.0	<0.001	−2.5	0.586
Total	151	11.6	111	5.6	175	13.0	−6.0	<0.001	7.4	<0.001	1.3	0.328
PCV13
<5 years	6	9.8	5	5.8	9	17.0	−4.0	0.403	11.2	0.053	7.3	0.301
5−65 years	20	2.0	12	0.8	35	3.4	−1.2	0.010	2.6	<0.001	1.4	0.060
≥65 years	23	9.0	13	3.3	13	4.7	−5.8	0.003	1.4	0.370	−4.4	0.056
Total	49	3.8	30	1.5	57	4.2	−2.3	<0.001	2.7	<0.001	0.4	0.566
Non-PCV13
5 years	8	13.0	10	11.6	6	11.4	−1.4	0.803	−0.2	0.985	−1.7	0.812
5−65 years	38	3.9	32	2.1	39	3.8	−1.7	0.013	1.7	0.014	0.0	0.963
≥65 years	48	18.9	27	6.8	60	21.6	−12.1	<0.001	14.8	<0.001	2.7	0.490
Total	94	7.2	69	3.5	105	7.8	−3.8	<0.001	4.3	<0.001	0.5	0.614
Serotype 3
<5 years	5	8.1	3	3.5	9	17.0	−4.7	0.260	13.6	0.012	8.9	0.191
5−65 years	7	0.7	9	0.6	19	1.9	−0.1	0.729	1.3	0.004	1.2	0.024
≥65 years	15	5.9	6	1.5	9	3.2	−4.4	0.003	1.7	0.154	−2.7	0.157
Total	27	2.1	18	0.9	37	2.7	−1.2	0.006	1.8	<0.001	0.7	0.277
Serotype 8
<5 years	0	0.0	1	1.2	0	0.0	1.2	0.584	−1.2	0.620	0.0	NC
5−65 years	14	1.4	8	0.5	10	1.0	−0.9	0.025	0.4	0.205	−0.4	0.375
≥65 years	8	3.1	6	1.5	4	1.4	−1.6	0.184	−0.1	0.955	−1.7	0.208
Total	22	1.7	15	0.8	14	1.0	−0.9	0.020	0.3	0.399	−0.7	0.152

*

Includes non-serotyped cases. PCV: pneumococcal conjugate vaccine; NC: non-calculable.

In the pre-pandemic period (2018−2019), 151 cases of IPD were diagnosed, with an incidence of 11.6 cases per 100,000 population, which was highest in patients under 5 years of age and in adults aged 65 and over (24.4 and 29.9 per 100,000 respectively). Between the pre-pandemic and pandemic period, there was a decrease in the total incidence of IPD of six cases per 100,000 (p < 0.001). The decrease was statistically significant, both in cases caused by serotypes included in PCV13 (-2.3 per 100,000; p < 0.001) and in cases caused by serotypes not included in PCV13 (-3.8 per 100,000; p < 0.001). In all age groups, the incidence of IPD declined in the pandemic period, but this decline was not statistically significant in children under 5 years of age.

Compared to the pandemic period, the post-pandemic period (2023−2024) saw an increase in the incidence of IPD from 5.6 to 13.0 cases per 100,000 population (p < 0.001). Although the increase in cases was observed in all age groups, it was not statistically significant in children under 5 years of age (p = 0.063), probably due to the much smaller number of people in this age group. These trends were similar in the analyses of PCV13 and non-PCV13 serotypes, with the exception of the 65+ age group, in which the incidence of non-PCV13 serotypes increased markedly (+14.8 per 100,000: p < 0.001), but not that of PCV13 serotypes (+1.4 per 100,000; p = 0.370). The increase in the total incidence of IPD in children under 5 years of age was particularly marked in cases due to serotype 3, included in PCV13, which increased from 3.5 to 17.0 cases per 100,000 (p = 0.012).

Comparison of the total incidence of IPD in the post-pandemic period with the pre-pandemic period found no statistically significant change (+1.3 per 100,000 population; p = 0.328). The only statistically significant change in the comparison of the post-pandemic period with the pre-pandemic period was the increase in the incidence of serotype 3 cases in the population aged 5−65 years, from 0.7 to 1.9 cases per 100,000 population (p = 0.024).

Serotype distribution

S. penumoniae serotyping was obtained in 404 cases (92.4%). Thirty-four different serotypes were detected among the cases of IPD (Table 4).

Table 4.

Cases of invasive pneumococcal disease by period and S. pneumoniae, serotype and by whether or not they are included in conjugate vaccines.

Serotype	Pre-pandemic 2018−2019		Pandemic 2020−2022		Post-pandemic 2023−2024		Total 2018−2024
	Cases	%	Cases	%	Cases	%	Cases	%
PCV13	49	34.3	30	30.3	57	35.2	136	33.7
1	1	0.7	0	0.0	0	0.0	1	0.2
3	27	18.9	18	18.2	37	22.8	82	20.3
4	1	0.7	3	3.0	1	0.6	5	1.2
7 F	2	1.4	0	0.0	0	0.0	2	0.5
9 V	0	0.0	0	0.0	1	0.6	1	0.2
14	3	2.1	1	1.0	4	2.5	8	2.0
18C	2	1.4	1	1.0	2	1.2	5	1.2
19A	10	7.0	5	5.1	8	4.9	23	5.7
19 F	3	2.1	2	2.0	4	2.5	9	2.2
Non-PCV13 (PCV15)	6	6.3	4	4.0	17	10.5	30	7.4
22 F*	5	3.5	1	1.0	13	8.0	19	4.7
33 F*	4	2.8	3	3.0	4	2.5	11	2.7
Non-PCV15 (PCV20)	38	26.6	35	35.4	30	18.5	103	25.5
8	22	15.4	15	15.2	14	8.6	51	12.6
10A	3	2.1	7	7.1	5	3.1	15	3.7
11A*	4	2.8	7	7.1	7	4.3	18	4.5
12 F	5	3.5	1	1.0	2	1.2	8	2.0
15B*	4	2.8	5	5.14	2	1.2	11	2.7
Non-PCV20 (PCV21)	42	29.4	22	22.2	42	25.9	106	26.2
9 N*	11	7.7	1	1.0	8	4.9	20	5.0
15A*	7	4.9	3	3.0	5	3.1	15	3.7
15C	1	0.7	3	3.0	0	0.0	4	1.0
16 F	6	4.2	4	4.0	2	1.2	12	3.0
17 F	0	0.0	0	0.0	1	0.6	1	0.2
20A*	3	2.1	1	1.0	0	0.0	4	1.0
23A	1	0.7	2	2.0	5	3.1	8	2.0
23B	4	2.8	5	5.1	5	3.1	14	3.5
24 F*	6	4.2	2	2.0	9	5.6	17	4.2
31	3	2.1	0	0.0	7	4.3	10	2.5
35B	1	0.7	1	1.0	0	0.0	2	0.5
Other	5	3.5	8	8.1	16	9.9	29	7.2
6C*	3	2.1	3	3.0	7	4.3	13	3.2
Total typed	143	100	99	100	162	100	404	100
Untyped	8		12		13		33
Total	151		111		175		437

*

Includes some probable cases, where the technique used for serotyping did not allow discernment: 13 confirmed 22 F cases and six identified as 22 F/22A; seven 33 F cases and four identified as 33 F/33A; 12 11A cases and six identified as 11A/11D; 13 15A cases and two identified as 15A/15 F; four cases identified as 20 and six 20 F cases and 11 identified as 24.

Serotype 3 was the most common serotype with 82 cases (20.3%), being predominant in all three time periods: 27 cases (18.9%) in the pre-pandemic; 18 (18.2%) in the pandemic; and 37 (22.8%) in the post-pandemic. Among the serotypes included in PCV13, 19A also stood out with 23 cases (5.7%), being the second most common PCV13 serotype in frequency in the three periods. There were no cases of IPD caused by serotypes 5, 6A, 6B, and 23 F, all of which are included in PCV13.

Among the serotypes included in the new conjugate vaccines, serotype 8 stood out with 51 cases (12.6%), although the percentage decreased over the three periods: 22 (15.4%) cases in the pre-pandemic period; 15 (15.2%) in the pandemic period; and 14 (8.6%) in the post-pandemic period. The third most common serotype was 9 N (5.0%), which is not included in PCV15 or PCV20. The frequency of each of the other specific serotypes was less than 5%. Some 58.9% of all cases of IPD were due to serotypes not included in the PCV15 and 33.4%, serotypes not included in the PCV20.

Among the cases of IPD recorded in the post-pandemic period, 35.2% were due to serotypes included by PCV13, 45.7% in PCV15 and 64.2% in PCV20 (Table 4).

Discussion

Our study provides a detailed analysis of the incidence of invasive S. pneumoniae disease in Navarre in the period 2018−2024. We found a statistically significant reduction in the incidence of IPD during the SARS-CoV-2 pandemic, with 5.6 cases per 100,000 population compared to 11.6 per 100,000 in the previous period. However, in the post-pandemic period the incidence returned to levels similar to those pre-pandemic. The reduction in cases of IPD during the pandemic was found both for S. pneumoniae serotypes included in PCV13 and those not included.

Non-pharmacological preventive measures reduce the incidence of respiratory-transmitted infections, such as S. pneumoniae. Preventive measures taken during the SARS-CoV-2 pandemic may have reduced the circulation of other respiratory viruses which are often associated with pneumococcal co-infections, and this may have been the main cause of the decrease in cases of IPD.^6–12 A number of different respiratory viruses affect host immunity, facilitating secondary infections by bacteria colonising the respiratory tract.⁷ Pneumococcal infection secondary to SARS-CoV-2 infection is rare. However, this virus displaced other viruses which have a greater tendency to facilitate pneumococcal infection, and that may also have contributed to the decrease in cases of IPD during the SARS-CoV-2 pandemic.^7,11

In line with other studies, we found that, after the reduction in the incidence of IPD during the SARS-CoV-2 pandemic, a rebound effect occurred, reaching incidence levels similar to those pre-pandemic.^10,13,14 The decline in the incidence of IPD during the SARS-CoV-2 pandemic was found indistinctly with cases due to serotypes included in PCV13 and those not included, and the subsequent rise also affected both groups of serotypes equally, returning to a situation similar to the baseline.

The study period covered years in which PCV13 was recommended and funded for childhood vaccination and in adults who were over 65 years of age or immunocompromised. The possible replacement of cases due to PCV13 serotypes by other serotypes not included in this vaccine^15,16,17 may explain why the proportion of IPD cases due to serotypes included in PCV13 was relatively low (33.7%). In over-65 s, in the post-pandemic period the incidence increased for non-PCV13 serotypes, but not for those included in PCV13, possibly as a result of the progressive expansion of PCV13 vaccination in this age group.

S. pneumoniae serotype 3, despite being included in PCV13, was the most common serotype in Navarre and showed the greatest increase in incidence after the pandemic. Epidemiological studies have documented the reduction in the incidence of IPD by serotypes included in PCV13, with the exception of serotype 3.^4,15,18,19 Serotype 3 is of concern worldwide because it has characteristics that could contribute to vaccine escape and clonal expansion after the introduction of the PCV13 vaccine.²⁰ In Navarre, the increase in serotype 3 has been remarkable in the paediatric and young adult population, with an incidence in the post-pandemic period which exceeded that of the pre-pandemic period. The recent addition of PCV15 to the childhood immunisation schedule in 2024 could help reduce the incidence of IPD due to serotype 3 if a better immune response than with PCV13 is confirmed.^21,22

The post-pandemic stagnation in the incidence of IPD supports the recent decision to introduce vaccines such as PCV15 and PCV20, as they potentially prevent a higher rate of pneumococcal infections circulating in our environment.²³

As elsewhere, the increase in serotype 8 has been remarkable, with it being the second most common serotype in our series in the three study periods.^4,24 Circulation of a lineage of serotype 8 has been detected which could be particularly virulent.²⁵ Serotype 8 is included in PCV20, so the recent introduction of this vaccine could lead to a decrease in cases of IPD due to this serotype.^4,26

The development and possible approval of new 21-, 24-, or 26-valent conjugate vaccines with a different serotype profile, as well as the recent approval of PCV20 in paediatric patients, makes it necessary to continuously review the current recommendations, adapting them to the possible replacement of circulating serotypes at any given time.¹⁹

The strengths of our study are that it is based on consolidated IPD surveillance since 2001, covering the whole population and achieving serotyping in a high proportion of cases. The criteria for sensitivity, specificity and quality of information have been validated by participation in international studies.^15–17

The main limitation of our study is that it is limited to a single region, so the results may not be generalisable to other sites with different epidemiological situations. In addition, the time periods analysed may not exactly match those of implementation and relaxation during the SARS-CoV-2 pandemic. Another drawback is that at some points in the study the technique used in serotyping S. pneumoniae classified only 42 individually and in the remaining situations it was not possible to discern between two potential serotypes, as the genetic sequences varied by only a few mutations.^27,28 In 2023, the whole genome sequencing technique was introduced, which overcame this obstacle by enabling the complete serotyping of all isolates. Sequencing has proven to be a useful tool in serotype surveillance and also provides additional information on antibiotic resistance and virulence.²⁹ The misclassification of vaccine serotypes which may have occurred in some cases would include only cases of related serotypes, for which it has been suggested that there may be a certain degree of vaccine protection.³⁰

In conclusion, invasive pneumococcal disease continues to be a priority public health problem. Preventive measures to control the SARS-CoV-2 pandemic had the effect of reducing the incidence of IPD, but the relaxation of these measures led to the incidence of IPD returning to previous levels. Cases of IPD due to serotype 3 have increased despite its inclusion in the 13-valent conjugate vaccine. The recent introduction of new conjugate vaccines makes close epidemiological surveillance of circulating serotypes advisable in order to determine the potential impact of each of these vaccines, to design new vaccines more appropriate to the epidemiological situation in each location and to monitor emerging serotypes. Techniques based on whole genome sequencing are proving to be essential for understanding the serotypes circulating in the population.

Funding

None of the authors received funding for conducting this study.