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. 2024 Oct 4;121(20):673–679. doi: 10.3238/arztebl.m2024.0127

Invasive Group A Streptococcal Infections in Europe After the COVID-19 Pandemic

Eva Goldberg-Bockhorn 1,*, Benjamin Hagemann 2, Martina Furitsch 2, Thomas K Hoffmann 1
PMCID: PMC11966131  PMID: 38961826

Abstract

Background

The incidence of airborne respiratory infections fell as a result of the protective measures taken during the COVID-19 pandemic and rose again when these were stopped. In 2022, there was a notable rise in invasive group A streptococcal (iGAS) infections in many countries, including Germany. This rise was also reflected in the data of the university otorhinolaryngology department in Ulm, Germany.

Methods

This review is based on publications retrieved by a selective literature search on the rise of iGAS infections in Europe, with particular attention to the timing of disease onset, clinical presentation, pathogenic strains, and potential causes and risk factors.

Results

The rise in infections after the pandemic was especially marked among children up to age 10 and in older adults; in Germany, it affected all age groups equally, but predominantly persons older than 65. Rising prevalence figures were seen in Germany and elsewhere as early as the fall of 2022, outside the usual season, and peaked mainly in the first and second quarters of 2023. The increased incidence of iGAS-associated pneumonia was paralleled by that of viral airway infections and led to greater use of intensive-care measures for children. The main bacterial strain identified was emm1; a new variant (M1DK) played a role in Denmark, and an emm4 variant (M4NL22) became increasingly important in the Netherlands. In Germany, initial evidence suggested the predominance of M1UK. Increased antibiotic resistance was not found.

Conclusion

The reduced confrontation of the immune system with pathogens during the pandemic, along with the increased incidence of viral airway infections immediately after it, apparently accounted for the exceptionally high post-pandemic rise in iGAS infections and the increase in invasive pulmonary diseases in Europe. Consistent vaccination programs against coincident respiratory viruses could reduce the burden of iGAS infections. The further extension of multinational surveillance programs with obligatory participation could aid in the detection of factors affecting the course of disease and the spread of new bacterial strains.

CME plus+

This article has been recognized by the Medical Association North Rhine for the Medical Association‘s CME certificate. The CME questions on this article can be found at http://daebl.de/RY95.

The deadline for submission is 3 October 2025.

Participation is possible at cme.aerztebatt.de

In early December 2022, the UK reported a particularly high and early incidence of infections with invasive group A streptococci in children (iGAS) and older adults compared with the years before the COVID-19 pandemic (1). At almost exactly the same time, the European Centre for Disease Control and Prevention (ECDC) and the World Health Organization (WHO) warned of an increase in iGAS infections in several European countries (2, 3). In the university otorhinolaryngology department in Ulm, Germany, which looks after patients from a catchment area of around 100 km diameter (about 3.5 million population), a rapid increase in cases of mastoiditis was observed, primarily caused by Streptococcus pyogenes (group A streptococci, GAS) (Figure, eFigure). Such infections were especially marked in children. In Germany, an increase in iGAS cases was observed in all age groups but older people were predominantly affected (4). The national reference center for streptococci did not see any association with the emergence of a new bacterial strain (4).

Figure.

Figure

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Isolates of causative pathogens in acute mastoiditis, Department for Diseases of Ear, Nose and Throat medicine, head and neck surgery, of the University Hospital Ulm, 2017–2023

eFigure.

eFigure

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Proportion of pathogenic isolates in acute mastoiditis of the total number of cases per year, Department for Diseases of Ear, Nose and Throat medicine, head and neck surgery, of the University Hospital Ulm, 2017–2023

Case fatality rates of iGAS infections vary depending on the geographical location, income per head, and clinical symptoms: in industrialized countries they were between 5% and 23% and in countries in the global South between 3% and 50% (5). Socioeconomic factors and a genetic predisposition seem to have an influence on the development of invasive group A streptococcal disease (e1). The international increase in iGAS infections was the more important because beforehand, when pandemic measures were established in early 2020, a substantial fall was observed in viral and bacterial disorders transmitted by the respi ratory route, including iGAS infections (6–9). Different host related and pathogen related factors have been discussed as triggers. Box 1 and eBox 1 provide a brief overview of GAS and the virulence factors that are responsible for the development of invasive infections.

Box 1. Profile: group A streptococci (GAS)* (5, 26, 30, 36, e2, e3, e7–e17).

Gram positive coccal bacteria of Lancefield Group A

Main representative: Streptococcus pyogenes

  • Epidemiology of GAS infections:

    • High incidence and mortality in the 19th century, declining incidence in the beginning of the 20th century, continually rising incidence since the 1980s

    • Incidence of invasive infections in industrialized countries: 2–4/100 000 population

    • Case fatality rate of invasive infections in industrialized countries: 5–23%.

    • Periodic peaks with clusters of infection every 4–7 years

    • Increases in winter and spring months

  • Clinical symptoms:

    • Asymptomatic colonization of the nasopharynx and skin

    • Frequently: non-invasive disease: tonsillopharyngitis, impetigo

    • Rarely: invasive disease: phlegmons, necrotizing fasciitis, necrotizing pneumonias, meningitis, sepsis, scarlet fever (toxin mediated), streptococcal toxic shock syndrome (toxin mediated)

    • Secondary diseases: acute poststreptococcal glomerulonephritis, acute rheumatic fever

  • Risk factors developing invasive disease:

    • Older persons with underlying diseases, children < 10 years

    • Infection with Varicella zoster virus

    • Infections with respiratory viruses, particularly influenza viruses

  • Important virulence factors:

    • Surface protein, such as M protein (cell adhesion, reduced phagocytosis, inflammatory reaction)

    • Secreted toxins, among others superantigenes

    • Typing by surface M proteins (> 220 emm genotypes)

    • Dominant strains in Europe: emm1, emm3, emm12, emm28, emm89

* More detailed information about GAS is in eBox 1.

eBox 1. Group A streptococci (GAS) and virulence factors.

• Klinisches Erscheinungsbild

S. pyogenes is a gram positive coccus and—based on specific lipoteichoic acid and polysaccharide antigens in its cellular wall—is the main representative of Lancefield group A (e7). The bacterium can asymptomatically colonize mucosa and skin, but it can also cause several diseases of different degrees of severity. In addition to the most common non-invasive diseases, such as tonsillopharyngitis and contagious impetigo, GAS is also responsible for life threatening invasive infections, such as necrotizing fasciitis, necrotizing pneumonia, meningitis, sepsis, and the toxin mediated diseases scarlet fever and streptococcal toxic shock syndrome (STSS) (e8, e9). Cutaneous infections and sepsis are the most common manifestations (e8, e10). Furthermore, recurrent infections with GAS can trigger autoimmune reactions and cause secondary diseases such as acute post-streptococcal glomerulonephritis and acute rheumatic fever (e8). The association between GAS infections and the development of a pediatric autoimmune neuropsychiatric disorder (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection, PANDAS) is the subject of controversy in the literature (e8).

While in the 19th century, GAS infections were associated with very high morbidity and mortality (e11), the incidence fell drastically at the beginning of the 20th century, even before antibiotics were discovered; the likely reason being improved living conditions and diets (5, e11). Since the 1980s a continual increase in iGAS infections has been observed in Europe, with periodic peaks in the winter and spring months; this increase is being attributed—among others—to the emergence and selection of new, genetically modified GAS strains (25, 29, e2, e3, e10, e12, e13). But other phenomena, such as improved diagnostics and surveillance, probably also have a role in this context.

Older people with underlying diseases are markedly affected (5, e14), whereas in pediatric collectives it affects primarily children younger than 10 years (e10). The case fatality rate of GAS infection in Europe is between 2% and 80%, depending on the disease symptoms and collective (e8, e10). It is notably lower in children than in adults (10). Treatment in intensive care is on average more common in younger children (21–83 months, Ø 40 months) than in older ones (36–85 months, Ø 57 months) (e10). In addition to host related factors, complex virulence mechanisms, such as surface proteins and secreted toxin, are responsible for the wide range of clinical manifestations (e15). The release of extracellular toxins—so called superantigens—activates T-lymphocytes antigen-independently and thus effects the excess secretion of pro-inflammatory cytokines, with resultant tissue destruction and organ failure (e15).

• M-protein

M protein is a surface protein of relevance for cell adhesion, preventing phagocytosis, and inducing the inflammatory response (e9, e16). It is used to type clinical isolates for epidemiologic purposes. In the meantime more than 200 emm genotypes have been detected by molecular analysis (36, e15). In Europe, emm1, emm3, emm12, emm28, and emm89 dominate, but regional differences are relevant (35, e7). Some M types are more commonly presumed to be associated with certain clinical presentations and epidemiologic phenomena (e9). During the course of epidemics, in the past molecular changes were a regular occurrence within a strain, which enabled the development of highly virulent clones (e3). This also possibly explains the infection peaks that are being observed every 4–7 years (e33). One M strain that gained relevance over the past decade in Europe, is M1UK. It was detected for the first time in 2010 in nGAS infections and in 2012 in iGAS infections in the UK and is characterized by a particularly high production of the superantigen SpeA (e17).

• Antimicrobial treatment

In contrast to other streptococci, GAS are fully susceptible to penicillins; these are administered as the treatment of choice (e18). Individual cases of limited penicillin susceptibility have been described primarily outside Europe (e18). In treating iGAS the combination with clindamycin improves survival (e19). Macrolides constitute an alternative in the setting of penicillin allergy; their resistance rates vary drastically by country and they should therefore be administered for monotherapy in iGAS infections only after resistance testing (28).

Methods

We carried out a selective literature search in PubMed, regarding the increase in iGAS infections at the end of the COVID-19 pandemic from January 2022 compared with pre-pandemic years. We searched primarily for national surveillance data from European countries and for large prospective and retrospective studies that wherever pos sible included all age groups and an analysis of the causative bacterial strains. We did not include case reports and case series from individual hospitals. Since postpandemic data for Germany are largely lacking to date, we included prepandemic publications on the epidemiology of iGAS infections.

The epidemiologic situation in Europe 2022/2023

We analyzed 13 studies from six countries (Table) (10–22). The data were collected mainly through compulsory or voluntary surveillance programs (10, 11, 13–15, 17, 20, 21) and partly by different laboratories or hospitals/clinics joining forces (12, 16, 19, 22).

Table. Overview of evaluated publications on the increase in invasive Group A streptococcal-infections in Europe in 2022/2023.

Country Literature citations Data course/study format Time period of increase Comparison period Age of study collective Dominant clinical presentation M classification Virus association Case fatality
Netherlands de Gier B. et al., 2023 (11); Rapid Communication National surveillance data 01/2022– 12/2022 01/2016– 12/2019 All age groups Necrotising fasciitis, puerperal fever/-sepsis, STSS emm1, 4, 12, 22, 98 (> 80%) VZV 9/42 (21%)
children up to 5 years of age (2022)
van Kempen AB. et al., 2023 (18); Brief Report Multicenter study (7 hospitals) 07/2021– 06/2022 01/2018– 12/2019 0–18 years Pneumonia with empyema, necrotizing fasciitis emm12 (38%)
emm1 (25%)
emm4 (13%)		 VZV (33%),
IV (18%)		 9%
van der Putten BCL. et al., 2023 (19); Short Communication Nationwide data from different studies 01/2022– 05/2022 01/2009– 12/2019 All age groups N/A 100% emm4;
M4NL22 (85%)		 N/A N/A
van der Putten BCL. et al., 2023 (20); Original Article National surveillance data 01/2022– 03/2023 01/2013– 12/2021 All age groups Meningitis emm1 (86%)
5/2022–03/2023:
emm1UK (100%)		 N/A N/A
UK Guy R. et al., 2023 (21); Rapid Communication National surveillance data 09/2022– 11/2022 01/2017– 09/2022 All age groups N/A > 14 years:
emm 1 (31%)
emm 12 (16%)
emm 89 (6%)
emm 33 (5%)
< 15 years:
emm 1 (57%)
emm 12 (23%)
emm 4 (7%) 		RSV > hMPV
RV
(25.8%)		 14/202 (6.9%)
children < 15 years
Davies PJB. et al., 2023 (22); Dispatch Nationale public health and laboratory data from central Scotland 12/2022– 02/2023 12/2017– 11/2022 > 17 years Invasive pulmonary infections emm1/M1UK (96%) IV A (57.6%) 6/36 (16%)
Holdstock V. et al., 2023 (12); Correspondence Clinical data and lab data from three maximum care hospitals in Scotland 09/2022– 12/2022 01/2017– 12/2021 (excl 2020) 0–15 years Pleural empyema emm1 (75%)
emm12 (12,5%)
emm1.25 (12,5%) 		60% (hMPV > RSV >
IV A/RV/VZV)		 0%
Denmark Johannesen TB. et al., 2023 (10); Rapid Communication National surveillance data 01/2023– 02/2023 Seasons since 01/2018 All age groups N/A emm1 (57%)
emm1DK (30%)
emm12 (24%)		 N/A Total: 10–20%
84 years: 30%
< 5 years: 5%
Nielsen H. et al., 2023 (13); Research Letter National surveillance data 10/2022– 04/2023 01/2015– 10/2022 > 17 years Meningitis emm1 (36%)
emm12 (18%)
emm87 (9%)		 N/A 1/11 (9%)
Belgium Rodriguez-Ruiz JP. et al., 2023 (14); Rapid Communication National surveillance data 01/2022– 08/2023 01/2018– 12/2019 All age groups Sepsis 2022: emm1 (45%)
2023: emm1 (34%)
emm1UK (78%)		 N/A 13/149 (8%)
Portugal Gouveia C. et al., 2023 (15); Rapid Communication National surveillance data 09/2022– 05/2023 09/2014– 08/2019 0–17 years Pneumonia +/- empyema emm1 (54,5%)
emm1UK (47%)
emm12 (22%)		 VZV (24,6%), respirato ry viruses (24.6%) 4/79 (5.1%)
Spain Cobo-Vázquez E. et al., 2023 (16); Correspondence Multicenter network data (24 hospitals) 01/2022– 12/2022 01/2019– 12/2019 0–16 years Pneumonia, skin-/soft tissue- infections, STSS N/A RSV 3/105 (2.9%)
Bellés-Bellés A. et al., 2023 (17); Research Letter Regional surveillance data Lleida province 11/2022– 05/2023 01/2011– 12/2019 All age groups N/A emm1 (48%)
emm12 (16%)
emm49 (16%)
emm89 (13%)		 N/A 3/31 (9.7%)
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hMPV, human metapneumovirus; IV, influenza virus; N/A, not available; RSV, respiratory syncytial virus; RV, rhinovirus; STSS, streptococcal toxic shock syndrome; VZV, Varicella zoster virus

Progress and dynamic

In the UK, Denmark, and Spain, above average steep and high increases were observed from October/November 2022 (10, 16, 17, 21), whereas in the Netherlands, Belgium, and Portugal, case numbers were already higher from spring 2022 onwards and rose again notably at the end of 2022 to reach a maximum in the first half of 2023 (11, 14, 15, 18). Dutch surveillance data showed differences in the annual maximum values for the different clinical pictures (11). In Belgium, case numbers remained high until August 2023 (14).

Age distribution

In the 2022/2023 season, the UK, the Netherlands, and Denmark noted a particularly steep rise in iGAS infections in children compared with prepandemic years (10, 11, 21). Children up to 5 years of age were typically most affected (10, 11, 18). A study in a pediatric population in Spain found a fourfold increase in iGAS infections in December 2022 compared with 2019 (16). By contrast, another Spanish study reported the most infections in older adults (17). In Denmark, incidence rates were highest in persons older than 85 but the relative increase compared with children younger than 5 was notably lower (10). In Belgium during the rise in iGAS infections from 2022 onwards, no age group was more markedly affected than before the pandemic.

Clinical manifestations and association with viral infections

Of note was the increase in invasive pneumonias with or without empyema in children in the Netherlands, the UK, Spain, and Portugal (12, 15, 16, 18, 21). In the UK, and especially in central Scotland, the increase in pulmonary iGAS infections was evident (21, 22). Prior respiratory infections or those existing in parallel were associated in 18–60% of cases (12, 16, 18, 21, 22) (Table). In Belgium, much as in the preceding years, sepsis was the pathology most often triggered by iGAS in all age groups (74–82% of all iGAS infections from 2018 to 2023) (14). In the Netherlands, necrotizing fasciitis (NF) occurred frequently in the first six months of 2022 (11); six cases were in children, all of whom showed an association with prior infection with the Varicella zoster virus (VZV) (18). This pathology was not seen in children in the comparison period 2018/2019 (18). Prior VZV infections were observed in Portugal in 24.6% of pediatric cases without any association with a specific pathology (15). Nielsen et al did a time series analysis of national surveillance data in Denmark and showed a 23-fold increase in the incidence of iGAS meningitis in adults compared with the preceding seven years (13). A time series analysis of national specimens of cerebrospinal fluid from the Netherlands also showed a cluster of meningitis cases compared with earlier years (20).

Severity of illness and case fatality rates

In the 2022/2023 season, death rates in most countries remained unchanged (10, 17, 21, 22) (Table). An increase in the case fatality rate in children from 3% to 9% was observed only in the Netherlands, but this was primarily due to cases of necrotizing fasciitis, which did not occur in the comparison season (18). The iGAS outbreak did not increase the probability for intensive care in adults (13, 22). In pediatric collectives with mainly pulmonary infections, the need for intensive care rose compared with the pre-COVID season from 30.4% (24 of 79 cases, 2019) to 48.6% (51 of 105 cases, 2022) in Spain (16) and from 21% (8 of 39 cases, 2018/2019) to 32% (18 of 57 cases, 2021/2022) in the Netherlands (18).

Bacterial strains

Group A streptococci are typed at the molecular level by the emm genes coding for the M protein. The M protein, which is located on the cellular surface, is a crucial virulence factor of these bacteria (Box 1, eBox 1)

Independently of age, emm1 was detected most often, followed by emm12 (10–15, 17, 20–22) (Table). Variants of the emm1 gene were more frequently associated with intensive care (10, 15). Only in one pediatric study from the Netherlands (18) was emm12 confirmed more often than emm1. Furthermore, a relative increase in emm4 isolates was observed particularly in young children (11, 18). A selective analysis of these cases detected independently of age and clinical picture a new bacterial strain M4NL22 in 85% (19). Cases of meningitis were not associated with emm4. They were caused by M1 (especially M1UK) in 86% (20). Studies from England, Belgium, and Portugal also reported a dominance of M1UK (14, 15, 22). In Denmark, where M1UK was the most common bacterial strain responsible for iGAS infections before the pandemic, a new M1DK strain was confirmed in August 2022, which in 2023 caused 30% of all iGAS infections (10). M1DK differs from the original M1UK and M1global variants thanks to the exotoxin SpeC, which is also typical for M12 (10, 23). While for M1DK an association with iGAS infections was seen, M12 was much more commonly detected in non-invasive group A streptococcal (nGAS) infections (10). Possible relevance also applies to the emm49 variant, which to date has been confirmed only in the US and since 2021 for the first time in Spain (17).

Antibiotic resistance

Currently available surveillance data do not provide any indication of increased resistance development as a cause of the postpandemic rise in iGAS infections, especially not in the confirmed new variant M4NL22 (14, 15, 19). Only in the Netherlands have increasing rates of resistance to clindamycin (from 4% to 9%) and erythromycin (from 6% to 11%) been described between 2017 and 2021 (11).

The situation in Germany

For Germany, only limited national data exist regarding the postpandemic increase in iGAS infections. The surveillance of iGAS infections via the national reference center is carried out on a voluntary basis. To date, whole genome sequencing of specimens is not yet standard procedure. The analysis of routine data to identify pathogens causing invasive bacterial infections between 2017 and the first quarter of 2023 showed a strong and early rise in infections with S. pyogenes from the fourth quarter of 2022 in all age groups (24). The study did not provide any more detailed information about the clinical course or the case fatality rate of the infections, nor about the confirmed bacterial strains. A first single center study of iGAS isolates (10/2022–03/2023) confirmed M1UK for the first time in Germany as the dominant M1 strain (14 of 17 emm isolates, 30% of all isolates) (25). The isolates emm12 and emm89 were detected as the second most common variants (25). The single center study did not include any information on the kind of clinical presentation, its extent, or the therapeutic measures employed.

A national analysis of German iGAS specimens from 2009 to 2014 found that emm28 and emm29 were the most common strains (26). The comparison with earlier analyses showed apart from an increase in emm89 since 1996 no relevant change regarding the emm variants (26). Rates of resistance rates to macrolides and clindamycin were low in the international comparison (27, 28). The most common clinical diagnoses were sepsis (59.4%), erysipelas (7.6%), and pneumonia (7%) (26). Most iGAS infections affected children up to 5 years of age and adults older than 70 (24, 26). The most recent data regarding the lethality of iGAS infections in Germany were collected for the time period 1996–2002 in a collective of 165 cases. Case fatality rates were notably lower in children and young adults (11.1–20.8%) than in older people (42.1–65.2%) (e2).

Discussion

Analyzing studies of the increase in iGAS infections in Europe since 2022 provides only partial answers to the question about causes and future effects. Because of heterogeneous approaches to data collection and processing, international comparisons and general conclusions are possible only to a limited extent.

Crucial observations relate to the shift in the usual periods of infection (earlier and higher rise in absolute case numbers) (11, 14, 15, 18), changes in the age distribution of infected patients (10, 11, 16, 18, 21), and a shift in clinical presentations towards invasive pneumonias with empyema (12, 15, 16, 18, 22).

Reports about the increase in iGAS infections in children at the end of 2022 coincided in many countries with the end of pandemic measures, which makes an association seem obvious (2, 3). But in many countries a continuous increase in infections with scarlet fever and iGAS was observed years before the COVID-19 pandemic, whose causes have thus far not been sufficiently explained (17, 29, 30). As our own data for acute mastoiditis show (Figure, eFigure), repeated high case numbers every 4–7 years are typical for iGAS infections (e3). It is possible that the pandemic only interrupted this periodic event and, in principle, the high case numbers of nGAS and iGAS infections after the pandemic are not unusual. The markedly high increase in case numbers after the pandemic could have been triggered by factors we list in what follows.

The effectiveness of diverse hygiene measures and contact restrictions on the transmission of respiratory pathogens was shown as early as during the Spanish flu (e4) and was also evident during the COVID-19 pandemic (6, 9). The lifting of certain restrictions (such as the wearing of protective face masks) resulted in different countries as early as in 2021 in an increase in viral and bacterial infections outside the usual season (7, 9, 10, 14), long before the WHO declared the pandemic over in 2023 (e5). The different time points of the observed increase in iGAS infections in the individual European countries are bound to be associated with different management of restrictions and lifting of restrictions. More precise conclusions cannot be drawn because of the poor data. Bacterial respiratory infections can be reduced by means of protective measures (7, 8), but certain pathogens will still persist as colonization pathogens in the nasopharynx (31). Even though no concrete data are available for GAS it seems possible that after the pandemic restrictions were lifted, group A streptococci spread more easily as colonization pathogens in the context of viral infections of the upper respiratory tract. Because of low test rates, the current data relating to a coincidence between viral and iGAS infections probably do not reflect the actual postpandemic incidence rates. A relevant association was seen in the UK, the Netherlands, Portugal, and Spain (12, 15, 16, 18, 21, 22). Of interest, coinfection with SARS-CoV-2 was reported only in individual cases (21). The analyses imply that the coincidence with viral infection stimulates especially pulmonary infections and could be responsible for the observed shift towards more cases of pneumonia and empyema. Viral infections enable bacterial superinfection by directly injuring the mucosal barrier of the respiratory tract and the lung, thus enabling easier adhesion and invasion of the bacteria and, on the other hand, triggering changes to the host’s protective immune response (32). The complex interaction of viral, bacterial, and host related factors remains insufficiently understood (33).

During the 2022/2023 season, children in some countries were particularly affected by scarlet fever and iGAS infections (10, 11, 21). The suspected cause, among others, lies in immunologic factors. The increased susceptibility to airborne respiratory pathogens is partly explained with the reduced peripandemic exposure—among others, because of the closure of educational institutions (“immunity debt or gap”) (6, 10, 11, 15, 21, 34). The general fall in standard vaccinations during the pandemic and the lacking recommendation for vaccination against pathogens that enable iGAS infections (for example, influenza virus IV and VZV), should be discussed as a possible cause (6). Infection with VZV can increase the risk for developing iGAS infections by a factor of almost 60 (23, e6). The presumed cause is—in addition to the weakened immune system—the penetration of path ogenic bacteria through the damaged skin barrier, which could explain the clusters of NF (5, 18, 23). The Netherlands and the UK reported a particularly high incidence of VZV in 2022 (18, 21). An association between iGAS and VZV infections in younger children was observed in the Netherlands and also in Portugal (11, 15, 18). As in the UK, Belgium, Spain, and Denmark, no general recommendation for vaccination exists here: the risk for coinfection could, however, crucially depend on mandatory vaccination recommendations and vaccination rates (34, 35).

The postpandemic rise in iGAS infections in Europe cannot be explained with the expansion and selection of a specific new bacterial strain. For most infections, strains were responsible that were widespread before the pandemic, especially emm1 variants (26, 36, 37). The M1UK variant, which is currently dominant in Belgium (14), the UK (21, 22), the Netherlands (20), and Portugal, was already dominant before the COVID-19 pandemic in Denmark (10), the UK (30), and the Netherlands (38). Even though emm1 variants bore a higher risk for treatment in intensive care (10, 15), this was not the case for M1UK and M1DK specially (10, 14). For the first time, M1UK was also confirmed in German specimens (25). Further work-up of data from the prepandemic years may enable insights into the relevance during the observed rise in infections in Germany. In the increase of iGAS infections, colonization advantages of certain variants in association with certain special genes may play a role; for the new variants M1DK and M4NL22 this will have to be investigated in molecular genetic studies in larger (inter)national collectives (10, 15, 19).

An increase in antibiotic resistance in Europe has not been noticed to date, which means that standard treatment (Box 2) will work (11, 14, 15, 19). In the autumn/winter season 2022/2023, reported bottlenecks in the supply of oral antibiotics, especially penicillins (39), and additionally the rapidly increasing consumption of antibiotics in some countries after the pandemic (4) will in future have to be considered risk factors for the increasing development of resistance and need to be stringently monitored.

Box 2. Treating group A streptococcal infections (27, 28, e18–e20).

Narrow spectrum penicillins are the treatment of choice for infections caused by group A streptococci. Uncomplicated infections are treated orally, with dosage and duration of treatment depending on the patient’s age, type of disease, and clinical response. In contrast to other gram-positive pathogens, such as staphylococci, enterococci, but also pneumococci, GAS are fully susceptible to ß-lactam. The underlying mechanism is largely unexplained. Individual cases of impaired susceptibility to penicillin have been explained with mutations in the penicillin binding protein(pbp) gene.

Especially oral penicillin V has repeatedly been subject to supply bottlenecks. Alternatively, broad spectrum ß-lactams, such as aminopenicillins with ß-lactamase inhibitors or first generation cephalosporins, should be administered. In penicillin anaphylaxis and for the purpose of eradication of persistent pathogens, macrolides (clarithromycin or azithromycin) and lincosamides (clindamycin) are available. As GAS resistance rates to macrolides vary considerably (1.5% to 22.4% in Europe), these drugs should be used for monotherapy only after resistance testing.

In life threatening invasive GAS infections, penicillin G or, in case of penicillin anaphylaxis, third generation cephalosporins administered by the parenteral route are the treatment of choice. As clindamycin inhibits the synthesis of superantigens and other virulence factors, combination treatment is recommended to lower mortality. Recurring infections with GAS or a poor therapeutic response of invasive infections to penicillin are explained with different mechanisms. These include the secretion of ß-lactamases by resident mucosal pathogens, the development of biofilms, and the intracellular persistence of GAS in macrophages and epithelial cells. Macrolides or clindamycin are effective against intracellular persistent bacteria. Furthermore, in invasive tissue infections such as necrotizing fasciitis, extensive surgical debridement is required as the penetration of antimicrobial substances in tissue necroses is severely reduced.

Despite gaps in the data, which cannot completely explain the remarkably early and steep rise in iGAS infections, observations to date can be used to deduct general recommendations to prevent further relevant increases in iGAS infections in the future. These recommendations are summed up in Box 2.

eBox 2. Measures aiming to prevent increases in iGAS infections.

The work-up of historical data and comparisons between the observations regarding the latest increase in iGAS infections at the end of the COVID-19 pandemic allow drawing conclusions about potential risk factors for the development of such outbreaks. From these, fundamental recommendations can be drawn to prevent a further rise in iGAS infections.

Patients with risk factors should receive early antibiotic treatment because of their risk of developing invasive iGAS infections (11, 18). In treating sore throats and nGAS infections, a considered use of antibiotics is essential according to antibiotic stewardship and in adherence to valid guidelines, so as to prevent supply bottlenecks and the development of resistance. Testing for associated viruses does not only help identify coinfections but also better to understand associations with clinical courses of iGAS in the future (12). The development and introductions of new vaccines against high-risk virus infections—for example, respiratory syncytial virus (RSM) and human metapneumovirus (hMPV)—should be supported and promoted, as should the stringent recommendation of existing vaccinations (such as against Varicella zoster virus [VZV] and influenza virus [IV]) (12). To improve the comparability of European data, mandatory, standardized surveillance concepts should be developed and applied across countries; these should include not only whole genome sequencing but also data on clinical symptoms, course, and risk factors (10, e21). Recent suggestions for the standardized collection of data and case definitions can be found in Miller et al (e21). Until such time, sending microbiologic specimens to national reference centers on a voluntary basis (e22) supports the surveillance of further trends in iGAS infections.

Questions on the article.

Invasive Group A Streptococcal Infections in Europe After the COVID-19 Pandemic

The submission deadline is 3 October 2025. Only one answer is possible per question.

Please select the answer that is most appropriate.

Question 1

According to the article, which percentage range applies for the case fatality rate for iGAS infections in industrialized countries?

  1. Between 0.5% and 2,3%

  2. Between 2.5% and 4%

  3. Between 5% and 23%

  4. Between 25% and 33%

  5. Between 35% and 50%

Question 2

Which three countries mentioned in the article noted a particularly steep rise in iGAS infections in children in the 2022/2023 season compared with prepandemic years

  1. The UK, Netherlands, and Denmark

  2. Spain, France, and Switzerland

  3. France, Sweden, and Belgium

  4. Norway, Switzerland, and Portugal

  5. Switzerland, Finland und Luxemburg

Question 3

Typing of Group A streptococci is done on the basis of which molecular structure?

  1. E protein

  2. G protein

  3. L protein

  4. M protein

  5. A protein

Question 4

Which statement pertaining to the collection of data on iGAS infections in Germany is correct?

  1. The surveillance of iGAS infections is carried out on a voluntary basis via the national reference center.

  2. iGAS infections are notifiabl. Cases are notified to the Robert Koch-Institute by public health departments.

  3. At the moment, no notification option exists for iGAS infections because of the lack of a reference center.

  4. For the past four years, complete and extensive data sets exist for iGAS infections.

  5. For each iGAS infection, whole genome sequencing of the pathogen is standard.

Question 5

Which country reported a rise in fatalities in children as a result of iGAS (mainly necrotizing fasciitis) in the 2022/2023 season?

  1. Germany

  2. The UK

  3. France

  4. Denmark

  5. Netherlands

Question 6

Which of the following diseases caused by GAS is toxin mediated - according to the article?

  1. Meningitis

  2. Necrotizing fasciitis

  3. Scarlet fever

  4. Tonsillopharyngitis

  5. Phlegmons

Question 7

What is the drug treatment of choice to treat life threatening invasive infections caused by Group A streptococci?

  1. Doxycycline or minocycline

  2. Penicillin G, if required in combination with clindamycin

  3. Erythromycin in combination with imipenem

  4. Rifampicin or rifamixin

  5. Fosfomycin in combination with rifampicin

Question 8

Which substances are effective against intracellular persistent GAS?

  1. Fosfomycin or rifampicin

  2. Metronidazole or trimethoprim-sulfamethoxazole

  3. Macrolides or clindamycin

  4. Gentamicin and amikacin

  5. Ciprofloxacin and gentamicin

Question 9

Which GAS variants does the article refer to as “new variants” because of their more frequent occurrence after the pandemic?

  1. M2UK and M533DE

  2. E12DE and G4UK

  3. M4DE and L122SE

  4. M1DK and M4NL22’

  5. L522UK and A4DK

Question 10

According to the article, which statement regarding GAS infections is most applicable?

  1. GAS infections happen primarily in the autumn and summer months.

  2. Periodic peaks with clusters of infection occur every 2-3 years.

  3. GAS infections occur exclusively in association with viral respiratory infections (opportunistic infections).

  4. The postpandemic increase in GAS infections is explained primarily with a growing trend of antibiotic resistance.

  5. Periodic peaks with clusters of infection occur every 4–7 years.

Acknowledgments

Translated from the original German by Birte Twisselmann, PhD.

Footnotes

Conflict of interest statement

The authors declare that no conflict of interest exists.

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