Increase in Streptococcal Necrotizing Fasciitis During and After the Coronavirus Disease 2019 Pandemic

Abstract

Background:

Necrotizing fasciitis (NF) is a life-threatening and rare condition. However, we report and analyze a remarkably high number of NF cases during the coronavirus disease 2019 (COVID-19) pandemic and especially in the first months after the COVID-19 pandemic.

Patients and Methods:

We conducted a retrospective analysis of 17 cases of NF treated in our clinic between January and May 2023. Data were collected on demographics, comorbidities, risk factors, laboratory findings, and clinical outcomes. For each individual case two risk indicating scores, the Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) and Laboratory and Anamnestic Risk Indicator for Necrotizing Fasciitis (LARINF) were calculated.

Results:

In the pandemic years 2021 and 2022 there were 21 and 30 patients with NF, respectively, treated in our clinic. Of the 17 included NF cases in this study from January until May 2023, 16 cases required intensive care unit (ICU) admission, six cases required limb amputation, and four cases resulted in death. The microbiologic examination revealed seven cases of polymicrobial infections, eight cases of monomicrobial infections primarily caused by Streptococcus pyogenes, and two cases without microbial growth. The LRINEC score showed a sensitivity of 82%, whereas the LARINF score demonstrated a sensitivity of 100% for identifying cases of NF.

Conclusions:

This study highlights a notable increase in NF during and after the COVID-19 pandemic, predominantly associated with Streptococcus pyogenes-induced infections. These cases demonstrate a highly aggressive nature, leading to limb amputation or death in more than half of the cases.

Necrotizing fasciitis (NF) presents a rapidly progressive and life-threatening form of soft tissue infections. Although the fascia is the primary focus of infection in NF, distinction from other soft tissue infections such as cellulitis and erysipelas seem to be challenging especially in early stages.¹ In line with previous literature there are some accepted risk indicating scores^2–4 for the differentiation between NF and other soft tissue infections. However, it remains a primarily clinical diagnosis. Because of its rapid expansion, NF needs to be treated as an emergency, requiring immediate surgical debridement of non-viable and infected tissue to prevent further morbidity and mortality.¹

Referring to Morgan et al.,⁵ four different types of NF can be distinguished. They define type 1 as a polymicrobial infection representing the most common type of NF (70%–80%). Type 2 constitutes a monomicrobial infection mostly caused by group A streptococci followed by Staphylococcus aureus. Types 3 and 4 constitute gram-negative and fungal pathogens respectively.⁵

Nguyen et al.⁶ showed that the coronavirus disease 2019 (COVID-19) pandemic led to delayed presentations of NF by people avoiding seeking medical care even in life-threatening conditions. Contrary to what could be expected this observation did not result in any changes in operative time or mortality rate.⁶ Necrotizing fasciitis is generally considered to be rare with a reported incidence ranging from 0.3 to 15 per 100.000.¹ However, during the COVID-19 pandemic and especially after the pandemic, in the first quarter of 2023, we have observed an unusually high number of NF cases treated within our clinic with high morbidity and mortality. This prompted further analysis of this phenomenon and its cases.

The COVID-19 pandemic has been reported to have influenced the presentations and disease courses of many other medical conditions. An important component in this phenomenon is considered to be change in the immune system due to the imposed social distancing, either based on the hygiene hypothesis and changes in the human microbiome⁷ or through the effects of social isolation and stress.⁸ Another component is formed by the delayed presentations of even life-threatening conditions such as NF⁹ because of the general fear of contracting COVID-19 and worldwide encouragement to only seek medical care in emergencies to relieve the healthcare system.^10,11 These pandemic effects might be possible contributors to the observed increase in NF cases during and after the pandemic. In this study we report on the current situation with a high incidence of NF in our clinic and analyze the recently treated NF patients with their morbidity and mortality.

Patients and Methods

This study was approved by our Institutional Review Board and was conducted in accordance with the Declaration of Helsinki. An ethics vote was not deemed required.

We performed a retrospective analysis of patients presenting with NF in the Department of Plastic, Reconstructive, and Hand Surgery, Center for Severe Burn Injuries at Nuremberg Clinics (Nuremberg, Germany) between January and May 2023. This period was chosen because of the exceptionally high number of cases of NF admitted and treated at our hospital compared with previous years, reaching a new high. The cases were also associated with particularly fulminant outcomes. Patients treated in our clinic for defect reconstruction only after NF treatment elsewhere were excluded from the study. No additional case exclusion was performed beyond this. Data from one of our previous studies³ combined with a data query for the past few years were used to calculate the number of treated NF cases per year from 2005 until May 2023 in our clinic.

The indication for surgical debridement was based on high clinical suspicion of NF, with scoring systems used as a decision-aiding tools. These scoring systems included the Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) and the Laboratory and Anamnestic Risk Indicator for Necrotizing Fasciitis (LARINF).^2,4 The LRINEC score determines the risk for the presence of NF based on six laboratory parameters (C-reactive protein, leukocytes, hemoglobin, sodium, creatinine, and glucose) with varying degrees, with a score of five or less indicating low risk, of six or seven indicating moderate risk, eight or higher indicating high risk for the presence of NF in a patient. The LARINF score determines the risk for NF based on laboratory parameters (hemoglobin, procalcitonin, and C-reactive protein) as well as comorbidities (heart, liver, or renal insufficiency, immunosuppression, and obesity). The cutoff value for an increased risk of necrotizing fasciitis is a LARINF score of five or higher.

The diagnosis of NF was confirmed post-operatively after histopathologic evaluation reporting a “necrotizing soft tissue infection” and “fascial involvement,” as is standard procedure within our clinic. In two patients, histopathologic evaluation was not performed. In both cases there was a strong clinical and intra-operative suspicion for NF; however, one patient died on the day of admission before surgery could be performed.

Included patients were identified from a retrospective data query of our hospital's patient file system using the International Classification of Diseases, 10th revision (ICD-10) codes for NF (M72.6) and Fournier gangrene (N49.80 and N76.80). Other types of necrotizing soft tissue infections were not relevant to this study. Patient records were subsequently reviewed for the diagnosis of NF, as determined by the above criteria. Relevant data were collected from the hospital's patient file system. Each patient file was reviewed for demographics, comorbidities, risk factors, laboratory values upon admission, involved site of infection, causative micro-organisms, and for various clinical outcome parameters. These included hospitalization duration, intensive care unit (ICU) admission, occurrence of septic shock, limb loss and mortality. Some risk factors, such as smoking or laboratory parameters, such as D-dimer, were not included in the study because of limited retrospective data on these parameters. Microbiologic examination results referred to specimens obtained during the first surgical treatment whereby different numbers of specimens were sent for examination depending on the respective surgeon.

The data collection process was performed using Microsoft Excel (Microsoft, Redmond, WA), while the statistical analysis was conducted using both Microsoft Excel and SPSS Statistics (IBM Corp, Armonk, NY). Categorical variables were presented as total numbers, accompanied by percentages in parentheses when applicable. For quantitative variables, the mean value along with the corresponding standard deviation were reported.

Results

Figure 1 shows the yearly number of patients with NF treated within our clinic from 2005 until May 2023. As shown, the number of patients with NF has increased overall since 2005. Before the COVID-19 pandemic the maximum number of patients with NF treated within our clinic was 15 in 2019. Since the onset of the pandemic this number reached a peak of 30 patients in 2022. Up until May 2023 we have already treated 17 patients with NF.

FIG. 1.

Yearly number of patients with necrotizing fasciitis (NF) treated at Nuremberg Clinics from 2005 until May 2023.

All of these 17 cases (Table 1) of NF were included in this study. The mean age of the patients was 61.5 ± 15.1 years. The group consisted of 14 males (82%) and three females (18%). The lower extremity was affected 11 times (65%), the upper extremity three times (18%), and the trunk and genital/perineal area two times each (12%). The average length of hospital stay was 34.5.0 ± 23.7 days, with deceased patients omitted from the calculation. Major limb amputation was necessary in six patients. Intensive care was required in 16 patients (94%). Fourteen patients (82%) developed septic shock during the course of the disease and a total of four patients (24%) succumbed to the disease. One of these patients died on the day of admission before surgical debridement could be performed.

Table 1.

Patient Demographics, Site of Infection, Causative Micro-Organisms, and Clinical Outcome Parameters

Age	Gender	Site	Pathogen	Amputation	ICU^a	Septic shock	Mortality
68	M	Perineum/genital	Polymicrobial		X	X
49	M	Trunk and perineum/genital	Polymicrobial		X	X
69	M	Upper extremity	Streptococcus pyogenes	X	X	X
62	M	Lower extremity	Polymicrobial	X		X
38	M	Lower extremity	Streptococcus pyogenes		X
75	M	Lower extremity	No growth	X	X	X	X
66	M	Lower extremity	Polymicrobial		X	X
49	M	Lower extremity	Polymicrobial	X	X	X
80	F	Lower extremity	Escherichia coli	X	X	X
53	M	Lower extremity	Streptococcus pyogenes		X	X
64	M	Upper extremity	Streptococcus pyogenes		X	X	X
78	F	Lower extremity	No growth		X
83	M	Lower extremity	Polymicrobial		X
62	M	Lower extremity	Polymicrobial	X	X	X
72	M	Upper extremity	Streptococcus pyogenes		X	X
29	w	Trunk	Streptococcus pyogenes		X	X	X
49	m	Lower extremity	Streptococcus pyogenes		X	X	X

M = male; F = female;

Intensive care unit (ICU) admission.

The comorbidities, risk factors, laboratory results at admission, and the calculated LRINEC and LARINF scores are shown in Table 2. The most common comorbidities were heart, liver, or renal insufficiency and arterial hypertension, with nine affected patients (53%) each. Six patients had alcohol abuse as a risk factor (35%). Five patients had peripheral vascular disease (29%). Diabetes mellitus and obesity both were seen in four patients (24%), immunosuppression and drug abuse were seen in one patient only (6%). In our study, none of the patients had cancer (0%) as a comorbidity or underwent surgery (0%) within one month before the onset of NF.

Table 2.

Comorbidities, Risk Factors, Laboratory Results, LRINEC and LARINF Scores, and Scoring Results of the Cases of Necrotizing Fasciitis

Comorbidities and risk factors	Absolute frequency (relative frequency)
Diabetes mellitus	4 (24%)
Peripheral vascular disease	5 (29%)
Obesity	4 (24%)
Immunosuppression	1 (6%)
Cancer	0 (0%)
Heart, liver, or renal insufficiency	9 (53%)
Hypertension	9 (53%)
Alcohol abuse	6 (35%)
Drug abuse	1 (6%)
Prior surgery	0 (0%)

Laboratory results	Mean ± SD
Leukocyte count, per mm³	18.6 ± 12.5
Hemoglobin, g/dL	12.6 ± 2.0
Hematocrit, %	37.7 ± 5.3
Sodium, mmol/L	131.6 ± 7.3
Creatinine, mg/dL	2.6 ± 1.3
Glucose, mg/dL	144.9 ± 64.5
C-reactive protein, mg/dL	27.3 ± 12.6
Procalcitonin, ng/mL	25.9 ± 28.4

Scores	Mean ± SD
LRINEC	7.6 ± 3.0
LARINF	6.7 ± 1.3

LRINEC = Laboratory Risk Indicator for Necrotizing Fasciitis; LARINF = Laboratory and Anamnestic Risk Indicator for Necrotizing Fasciitis; SD = standard deviation.

The mean LRINEC score of 7.6 was in the moderate risk range for NF. The individual LRINEC scores classified three patients into the moderate risk group and 11 patients into the high-risk group. Three patients with NF were incorrectly classified by the LRINEC score as low-risk for NF. The LRINEC score of six or more accordingly had a sensitivity of 82%. Procalcitonin values were available in all but three cases. In all 14 cases in which procalcitonin values were available, we calculated the LARINF score, which averaged a value of 6.7. The LARINF score correctly classified all 14 patients as high-risk for NF, thereby demonstrating a sensitivity of 100%.

Of the 17 patients with NF, seven (41%) had polymicrobial infections and eight (47%) had monomicrobial infections. In two patients (12%), no microbial pathogens could be identified. According to the classification of Morgan et al.,⁵ seven cases of type 1, seven cases of type 2, and one case of type 3 NF were found. A total of 13 gram-positive micro-organisms were identified among the polymicrobial infections: Staphylococcus aureus (4), Streptococcus pyogenes (3), Streptococcus constellatus (2), Enterococcus faecium, Staphylococcus epidermidis, Staphylococcus hominis, and Streptococcus dysgalactiae. In addition, nine gram-negative pathogens were cultured among the polymicrobial infections: Klebsiella oxytoca (2), Prevotella intermedia (2), Bacteroides ovatus, Enterobacter cloacae, Escherichia coli, Pseudomonas aeruginosa, and Stenotrophomonas maltophilia. The monomicrobial infections were caused by the gram-positive pathogen Streptococcus pyogenes in seven of the eight cases. One case of monomicrobial infection was caused by the gram-negative pathogen Escherichia coli (Fig. 2).

FIG. 2.

Flowchart of causative micro-organisms in necrotizing fasciitis (NF).

Discussion

In this study we aimed to highlight and describe a trend of increasing incidence of NF in our clinic. To do this, we conducted a retrospective analysis of the 17 included cases of NF treated within our clinic between January and May 2023. We found a predominance of monomicrobial Streptoccocus pyogenes infections (in 7 cases) with fulminant disease progression, with 16 cases requiring ICU admission, six requiring limb amputation and four cases resulting in death.

Although it is too early and the analyzed number of patients with NF is too small to be making broad statistical analyses and comparisons with the pre-pandemic situation before 2020, the rising trend in the occurrence of NF (Fig. 1) over recent years in our department seems unmistakable. However, it should be noted that because of the type of study, namely being retrospective in nature, there is potential for bias in case identification. When analyzing Figure 1 we see striking numbers of 21 and 30 patients with NF treated in the pandemic years 2021 and 2022, respectively. The 17 patients with NF who have already been treated not even halfway through 2023 far exceeds the maximum yearly treated number of patients with NF before the pandemic, which was a total of 15 in 2019. If this trend were to be extrapolated for the rest of the year, we would expect to treat many more patients with NF in 2023. The observed decrease in the number of treated NF patients in 2020 could possibly be explained by the overall decrease in emergency department presentations of acute illness and injury worldwide due to the COVID-19 pandemic,^10,11 as mentioned before.

The subsequent increase in the number of patients with NF might possibly be explained by the aforementioned effects of the COVID-19 pandemic on the general immune status and on delayed presentations during the COVID-19 pandemic. A study by Mehanathan et al.¹² also found that this delayed presentation was associated with complicated courses and higher amputation rates. Since the COVID-19 pandemic has subsided and social restrictions have been lifted, some reports have been made on the increasing incidence or re-emergence of other infectious diseases. For instance, the increasing incidence of the respiratory syncytial virus (RSV) infections in young children, increasing influenza incidence as well as the increase in streptococcus group A infections.^13–15 The multiple lockdowns during the COVID-19 pandemic unintentionally might have also halted the spread of non-COVID-19 infectious diseases. Some hypothesize that as a result of reduced exposure our immunity against these non-COVID-19 infections has diminished. This is, however, in contrast to the slowly rising trend of NF in our clinic since the early beginnings of the COVID-19 pandemic, as opposed to a re-emergence post-pandemic as with RSV and influenza.

Literature on NF during the pandemic thus far is scarce. Feeney and colleagues⁹ report an increased incidence of NF in their clinic within one month of national lockdown. They describe three cases in which patients with most likely initial soft tissue infections progressed to NF because they delayed their presentation to the emergency department for one week to two months because of the national public health recommendations. This aligns with the so-called secondary victims of other COVID-19 unrelated pathologies such as cardiovascular and cancerous diseases. A study by McGee et al.¹⁶ reports a NF increase similar to our study with 17 patients between March 2020 and March 2021 with an increased mortality.

It seems possible that the aforementioned rise in streptococcus A infections plays an important part in the observed increasing occurrence of NF post-pandemic in this study group. However, it does not explain the earlier observed NF increase during the pandemic.

Streptococcus A has always been considered an important pathogen in NF. Contrary to what is reported by pre-pandemic literature, such as that by Morgan et al.,⁵ in this study group of 17 patients most (47%) were caused by a monomicrobial infection with Streptococcus pyogenes, as opposed to the reported 70% to 80% being caused by polymicrobial infections, being considered the most common type of NF. However, the frequency of type 1 and type 2 infections varies across literature, with some studies reporting type 2 to be the most common.^1,17 Compared with a study conducted by our department that examined the micro-organisms of NF cases from 2003 to 2021, we can also see an increase in NF cases caused by Streptococcus pyogenes.¹⁸ Whereas in the previous study 33% were caused by monomicrobial staphylococcal or streptococcal infections, now almost half of the cases are caused by the pathogen Streptococcus pyogenes alone.

Also noteworthy is the fact that in three of the polymicrobial infections in this study the Streptococcus pyogenes was one of the causing pathogens. Before the COVID-19 pandemic, there had already been reports of increases in Streptococcus pyogenes infections with severe disease progression.¹⁹ Considering the fact that Streptococcus pyogenes was not found to be multi-resistant within our study, its aggressive progression is concerning, leading to major amputation or death in half of the cases (n = 10), in spite of radical debridement and timely and adjusted antibiotic therapy. Although our study's sample size is limited, it is an interesting avenue for future research to explore the potential connection between COVID-19 patients and Streptococcus pyogenes infections, especially given the observed peak in NF cases during and after the COVID-19 pandemic.

The LARINF score was found to be a promising tool in this study. However, because the LARINF score has not yet been validated, there was no control group in this study to test the specificity of the score, and its application was not possible in all patients, external validation studies are still needed to verify the diagnostic value of this score. It should also be noted as a limitation that not all factors could be evaluated in this retrospective study and that, for instance, comorbidities and risk factors that were not documented could have acted as confounding factors. We acknowledge the need for continued vigilance and data collection to understand the dynamics of NF in the post-pandemic era. As the COVID-19 pandemic has had a significant impact on health-care–seeking behavior and immune status, we plan to monitor NF incidence further. This ongoing surveillance will help us assess whether the trends observed in the first half of 2023 persist, providing valuable insights into the lasting effects of the pandemic on NF incidence.

Conclusions

This study highlights a notable increase in the frequency of NF in our patient population during and after the COVID-19 pandemic with Streptococcus pyogenes as the predominant causative agent. These cases exhibit a highly aggressive nature, resulting in a substantial number of amputations and a high fatality rate. The LARINF score demonstrated its effectiveness as a sensitive tool in the decision-making process in all of the patients in this study as opposed to the LRINEC score. However, further validation is still required. Although statistically based conclusions are not yet possible so soon after the end of the COVID-19 pandemic, we aimed to report this trend and stress caution and vigilance in handling cases that are suspected to be NF, because this trend could also occur in other clinics and other countries.

Footnotes

Authors' Contributions

Conceptualization: Billner, Breidung. Methodology: Breidung, Marti Edo. Validation: Billner. Formal analysis: Breidung, Marti Edo. Resources: Reichert. Surgical procedures: Reichert, Billner, Marti Edo, Malsagova, Breidung. Writing—original draft: Breidung, Malsagova, Billner. Writing—review and editing: Malsagova, Breidung. Visualization: Breidung. Supervision: Reichert, Billner, Malsagova. Project administration: Breidung, Reichert. All authors have read and agreed to the published version of the manuscript.

Funding Information

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Author Disclosure Statement

The authors declare no conflict of interest.

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