Mpox outbreak 2022: an overview of all cases reported to the Cologne Health Department

Abstract

Purpose

The worldwide mpox outbreak starting in May 2022 marks the occurrence of another previously atypical infectious disease in Europe. This study’s objective was to present a comprehensive overview based on the gathered data and to illustrate the approach of the Cologne Health Department to contain the mpox outbreak.

Methods

In this retrospective observational study, 368 individuals reported to the Cologne Health Department as PCR-positive for mpox were included. Data were collected in structured telephone interviews and digitally processed.

Results

The first mpox case in Cologne was recorded on May 24, 2022. The local outbreak lasted approximately 4 months and reached its peak in July. The last reported case in Cologne occurred on September 17. Transmissions mostly occurred through sexual contacts (67.4%) or other close physical contacts (4.6%) between men, but also through fomites, in the context of events or occasionally in the work environment. In 21.5% of cases, no route of infection could be determined. The mean incubation period was 8.2 days. Clinically, mpox infections usually presented with skin and/or mucosal lesions accompanied by general symptoms. In 74.8% of cases, a prodromal stage was absent. Initially, the rash often had an unspecific appearance, but in the further clinical course, it usually passed through the typical stages. Most infections resolved spontaneously under home care. In 3.5% of cases, however, inpatient hospitalisation was required. Infected persons with a previous smallpox vaccination had 0.43 times the odds of unvaccinated persons to be affected by lesions in 3 or more body regions and 0.30 times the odds to develop lesions in all 5 body regions. Previous vaccination statistically reduced the total duration of symptoms by 2.0 days.

Conclusions

The mpox outbreak 2022 in Cologne primarily affected men who have sex with men and have reported recent sexual encounters. The observed average incubation period was shorter than initially assumed. Mucosal involvement and associated symptoms occur in a relevant number of cases and can lead to more severe clinical courses. Previous smallpox vaccination was statistically significantly associated with milder courses of mpox. In the case of an unclear rash or symptoms suggesting mucosal involvement, mpox should be considered as a differential diagnosis. An equally rapid and well-orchestrated public health response are crucial for infection control.

Introduction

In the wake of globalisation, the international mpox outbreak in May 2022 marked the emergence of a previously atypical infectious disease in Europe. This largest international mpox outbreak to date within Europe, North America and Asia [1] was declared a public health emergency of international concern by the WHO in July 2022.

Case-related data from a total of 25,183 confirmed cases from 42 European countries were reported to the ECDC and the WHO Regional Office for Europe via TESSy (the European Surveillance System) by 26 October 2022. Most cases occurred in Spain (7317), France (4084), Germany (3662) and the United Kingdom (3652). So far, 4 mpox-associated deaths were recorded in Europe [2].

Mpox (monkeypox) is a zoonotic viral disease caused by the mpox virus. It was first identified in monkeys under laboratory conditions in Copenhagen in 1958 [3]. Despite the name “monkeypox”, monkeys are dead-end hosts and wild rodents are the actual reservoir of the pathogen. In 1970, the virus was first detected in a human. Since then, mpox cases have been increasingly observed in Central and West Africa. There, transmission to humans occurred mainly through direct contact with infected animals or their meat. Human-to-human transmission has rarely been observed [4, 5].

Outside of the African continent, there have only been isolated outbreaks, such as in the USA in 2003 with 71 independent cases following contact with infected prairie dogs [6, 7]. In other cases, infected individuals reported a travel history to Africa [8]. While children had been predominantly affected in the 1970s, the average age of those infected rose to around 20 years by 2019 [9].

In late November 2022, the WHO initiated a change from the original term monkeypox to mpox.

Historically, mpox infection in humans typically presented with a non-specific prodromal stage (fever, muscle pain, night sweats, lymphadenopathy, general feeling of illness), followed by a rash. The efflorescences were described as simultaneously passing through the stages from spot to papule, blister and pustule until a scab forms [10]. An affected person is considered to be infectious from the onset of the first symptoms until all of the scabs fall off [11].

Smallpox vaccination is considered to be about 85% effective in the prevention of mpox infections [12]. In the Federal Republic of Germany, smallpox vaccination with the vaccine based on vaccinia virus or modified vaccinia Ankara virus (MVA) was administered until 1976 and in the GDR until 1982 [13]. Out of the smallpox vaccines used in response to the 2022 outbreak, MVA-BN (Imvanex^®) has been available in Germany. MVA-BN is a third-generation smallpox vaccine based on the replication-deficient strain of vaccinia Ankara virus. It is administered as a 2-dose subcutaneous injection [14]. In Cologne, Imvanex^® vaccination was offered as post-exposure prophylaxis for contact persons of exposure category 3 according to the criteria of the Robert Koch Institute (RKI; German federal government agency and research Institute, responsible for disease control and prevention) from June 20, 2022 onwards in accordance with the Standing Committee on Vaccination at the Robert Koch Institute (STIKO) recommendations, and as a pre-exposure vaccination for people at higher risk of infection in the further course of the outbreak.

The control of epidemic and pandemic infectious diseases is one of the core tasks of the public health service. The prompt identification of both suspected and confirmed cases of infection and subsequently, the ordering of domestic isolation and quarantine are of crucial importance to prevent further spread as well as offering comprehensive education about necessary hygiene measures to those affected including their close contacts. In Germany, infections with mpox virus are notifiable (according to §6 and §7 Infektionsschutzgesetz, IfSG, “Infection Protection Act”).

Since the first known occurrence of mpox in Cologne on May 24, 2022 until October 30, 2022, 368 PCR-confirmed cases were registered by the public health department and regularly contacted via telephone during the period of their officially mandated isolation of at least 21 days. Thus, the Cologne Health Department, as one of the largest in Germany, has a complete overview of the local outbreak. Therefore, the present analysis aims at evaluating routes of transmission, incubation periods and courses of disease on the basis of these data, in order to review current knowledge and official recommendations for dealing with mpox infections.

Additionally, we want to outline the approach and measures taken by the Cologne Health Department in reaction to the mpox outbreak as an example for an effective public health response in a large city.

Methods

Study design and population

This study takes the form of a retrospective observational study. 393 persons were reported to the Cologne health department with PCR-confirmed mpox infection according to §7 IfSG between 24 May, 2022 and 30 October, 2022.

7 of these persons were excluded because we were unable to contact them throughout their period of isolation. 18 individuals did not spend their isolation in Cologne and were therefore not under supervision by the Health Department of the City of Cologne. Thus, our evaluation includes complete data sets of 368 persons.

The information processing within the Cologne Health Department then took place via SurvNet and internally via DiKoMa, a digital contact management software developed in Cologne in the context of the COVID-19 pandemic [15]. In accordance with WHO recommendations, all individuals with a PCR-confirmed mpox infection were contacted regularly via telephone during their isolation period starting from the date the public health department was notified of the infection and lasting until all of the skin lesions were fully healed (more specifically, until the last scabs have fallen off) [16]. In the initial telephone call, a detailed structured interview was conducted by trained personnel.

Sociodemographic data, infection routes and incubation periods

Demographic data (age and sex), previous illnesses, smallpox vaccination status, social history including occupation, recent foreign travel and recreational activities, presumed source of infection, and contact persons were recorded during the initial structured telephone interview. The route of infection was assumed to be probable if an identifiable risk contact had taken place within 21 days prior to symptom onset, even if no reliable tracing to a PCR-confirmed mpox case was possible due to unknown identity. The incubation period was calculated on the basis of the symptom onset of infected individuals and the date of their probable or confirmed exposure.

Classification of symptoms

The symptoms were systematically recorded in a digital symptom diary during the initial interview and in the subsequent telephone conversations over the entire period of isolation. Infected persons were specifically asked about skin and mucosal lesions, as well as general symptoms such as fever, night sweats, muscle/limb pain, lymph node swelling, and fatigue. Furthermore, we asked all infected persons about their psychosocial situation. Several infected persons voluntarily sent us pictures of their skin lesions, these were also taken into account in the evaluation. In Germany, clinicians have to notify the local health authorities of suspected mpox cases (according to §6 IfSG). In many cases, these notifications included descriptions of the initial mpox symptomatology by the clinician who performed the swab test which were then included in the evaluation.

In order to evaluate the localisation of the rash, the body was divided into five regions: head, upper extremity, lower extremity, trunk, anogenital region.

Data processing

All personal data were compiled in a de-identified database and analysed descriptively by mean ± standard deviation (SD), 95% confidence interval (CI), frequency (%) and by median (MD) and interquartile range (IQR) specifically for the incubation period. We fitted a lognormal distribution to the observed incubation periods using maximum likelihood estimation. All data were compiled and processed using Microsoft Excel 2013.

Statistical analysis

In order to evaluate the relationship between previous vaccination and severity of disease, several logistic and linear regression models were fitted. Smallpox vaccination status was subdivided into the following categories: childhood vaccination, current vaccination (either pre- or post-exposure), vaccination in total (individuals who have received at least one vaccination, either past or current). These categories were treated as independent variables in the regression models. Individuals that received their post-exposure prophylaxis after their own symptom onset were not considered vaccinated in this analysis. Hospital admission, skin lesions in 3 or more body regions, skin lesions in all 5 body regions (all binary variables), as well as total duration of symptoms (in days) were respectively used as outcome variables serving as proxy variables for the severity of the disease. Each of the regression models was once run as a univariate analysis and once with the following covariates: age and HIV status. Statistical significance was defined using a two-sided significance level of α = 0.05. Results of the logistic regression models are presented as odds ratios (OR) for the univariate models or as adjusted odds ratios (aOR) for the multivariate models.

Results

Case numbers

Figure 1 shows the development of mpox case numbers in the period of observation. The first mpox cases reported to the Cologne public health department occurred in calendar week (CW) 21. From CW 25 onwards, there was a clear increase in the weekly incidence of mpox cases. This development reached its peak in CW 28 and 29 with 67 reported cases each. In the following weeks, the incidence decreased significantly. On September 17, the last mpox case to date was reported to the Cologne Health Department. From CW 38 onwards, no new cases were recorded in Cologne.

Fig. 1.

New reported cases in calendar weeks 21 to 38 in 2022, divided into origin of infection, either inside Germany or abroad (n = 368)

Age and gender

One infected person was female, the remaining 367 indicated male gender. The age distribution was between 12 and 80 years with a mean age of 41 years (SD = 10). In Cologne, there was one reported mpox infection in a person below the age of 18 (Fig. 2).

Fig. 2.

Age distribution among the Cologne mpox cases (n = 368)

Travel history

57 infected individuals (16%) had been outside of Germany within the last 21 days prior to the onset of their symptoms (potential incubation period according to RKI [17]) and suspected to have become infected during their travel abroad. We were able to observe that the first 5 infected persons in Cologne, which were recorded in CW 21 and 22, had all stayed in other European countries (Spain, France and Belgium) during the incubation period (see Fig. 1). In the further course of the outbreak, the proportion of persons with a history of recent foreign travel decreased significantly. In CW 28 and 29, only 13% of the infected stated that they had been abroad during the incubation period and that they presumably had become infected during that time. Since CW 34 the observed origins of infection lay exclusively in Germany. None of the infected persons throughout the entirety of the observational period had entered Germany from African countries prior to infection.

Pre-existing conditions

A total of 143 persons (39%) reported a known HIV infection. Some individuals reported other sexually transmitted diseases in their medical history; however, we did not systematically record these throughout. In a few cases each, the following pre-existing conditions were mentioned (listed in decreasing frequency): arterial hypertension, diabetes mellitus, coronary heart disease, thyroid diseases, bronchial asthma, chronic inflammatory bowel diseases, and rheumatic diseases. 16 persons (4%) had contracted COVID-19 at the same time as the mpox infection.

Previous or recent vaccination history

96 individuals (26%) reported having received smallpox vaccination in their childhood [13].

33 persons (9%) had already received a vaccination with the smallpox vaccine Imvanex^® at the time of diagnosis. Out of these, 19 persons (5.2%) received Imvanex^® as post-exposure vaccination and 14 persons (3.8%) as pre-exposure prophylaxis. 6 individuals (1.6%) received both childhood smallpox vaccination and current Imvanex^® vaccination. All persons vaccinated against smallpox showed symptomatic courses of mpox. The remaining 66% of the infected persons denied a previous smallpox vaccination or were unable to provide any reliable information on the matter.

Route of infection

In the evaluation, a distinction is made between sexual contacts, both within and outside of one’s own household, and other contacts. Household transmission without sexual contact was rare. 248 persons (67.4%) stated that they had presumably become infected through sexual contacts; 247 (67.1%) of these were reported as sexual contacts between men (MSM, men who have sex with men) and 1 (0.3%) as a non-MSM sexual contact. These contacts occurred in private settings, as well as sex on premises venues (e.g. sauna clubs, sex clubs) or in the context of pride events. Many of the sexual contacts were reported as anonymous.

17 persons (4.6%) suspected infection via non-sexual close physical contact. 3 persons (0.8%) suspected that they had been infected through fomites. In one case, transmission occurred via shared use of an insect bite heat pen. 18 persons (4.9%) suspected a route of infection in the context of an event (festival or club attendance) without sexual contact or other close physical contact. Furthermore, 3 persons (0.8%) indicated work contact as a probable source of infection. 79 persons (21.5%) did not provide any information about a possible source of infection (see Fig. 3).

Fig. 3.

Suspected or confirmed routes of infection reported by infected persons (n = 368)

45 persons (12.2%) attributed their infection to contacts while attending the Christopher Street Day (CSD) in Cologne (July 01–03, 2022). A confirmed source of infection, i.e. contact with a person who had tested positive, could be stated by 73 infected persons (19.8%).

Incubation period

209 persons (56%) were able to name the date of the exposure to the suspected or subsequently confirmed source of infection. For those cases, we were able to calculate the incubation period as difference between symptom onset and date of exposure. The results are presented in Fig. 4. In the observed group, the onset of symptoms occurred between 1 and 31 days after exposure. The mean incubation period was 8.2 days (SD = 4.7, MD = 7.0, IQR = 5–10). In 78% of cases, the incubation period was 10 days or fewer. When looking at only the incubation periods of cases with a confirmed source of infection, values between 2 and 20 days could be observed. For those cases, the mean incubation period was 7.6 days (SD = 4.1). We fitted a lognormal distribution to the observed incubation periods as it visually matched the empirical probability density function and has already been used for mpox incubation periods by Miura et al. [18]. Using this distribution, we estimated the mean incubation period to be 8.3 days (CI = 6.6–10.4) with an estimated standard deviation of 5.2.

Fig. 4.

Empirical probability density for incubation periods (incubation period calculated as the difference between symptom onset and exposure to suspected/confirmed source of infection) and estimated probability density function based on the lognormal distribution (n = 209)

Clinical course

Skin and/or mucosal lesions occurred in 361 cases (98.1%) during the period of observation. 3 persons (0.8%), in whom the mpox virus was detected via oral or rectal swab, did not show any symptoms during the period of isolation. 110 infected persons (29.9%) initially showed exclusively non-specific symptoms, such as fatigue, fever or lymphadenopathy in the sense of a prodromal stage with an average duration of 3.2 days (SD = 2.0) until the first appearance of skin changes. Accordingly, 255 persons (69.3%) showed skin and/or mucosal lesions as the first symptom. We observed that the lesions usually passed through different stages and were described as non-specific insect bite-like and itchy at the beginning and as painful pustules, vesicles or crusts in the further course of the disease. Figure 5 shows the different stages of a perioral skin lesion, from the first appearance until the crust falls off, which were photographically documented by an affected person.

Fig. 5.

Photographic documentation of a typical mpox skin lesion from first appearance until the crust falls off (day 1 to day 17 after symptom onset)

The average duration from onset until absence of symptoms was 16 days (SD = 5.2, CI = 15–16) (Fig. 6). In 45 subjects (12%), mandated isolation had to be extended beyond the required minimum of 21 days due to persistent skin lesions. The mean time between the first appearance of skin or mucosal lesions and the date the swab was taken was 5.4 days (SD = 3.8).

Fig. 6.

Duration of the symptoms reported by the infected persons (n = 345)

The occurrence of skin efflorescences was described in all body regions. They occurred either localized or disseminated. 249 persons (68%) reported efflorescences in the anogenital region, making this the most frequent localisation in the observed group. 162 persons (44%) reported skin lesions on at least 3 different body regions. We observed that the lesions generally appeared and healed asynchronously, especially between the individual localisations. The primary lesion was often located in the area of the presumed site of inoculation.

Mucosal lesions and/or characteristic symptoms (anorectal pain, haematochezia; alguria, haematuria; sore throat, difficulty swallowing) were described by 147 infected persons (40%). In 98 persons (27%), anorectal mucosal lesions were presumed due to the described symptoms. Oral mucosal lesions were present in 56 persons (15%), 12 persons (3.3%) reported signs of urethral mucosal involvement. 28 individuals (7.6%) initially presented exclusively with symptoms caused by mucosal lesions.

340 persons (92%) described general symptoms in addition to skin/mucosal lesions during the course of the disease. These are listed below in descending order of frequency: fatigue fever, night sweats, and muscle/limb pain (Fig. 7). Swollen and/or painful lymph nodes were seen in 192 persons (52%), most commonly in the inguinal and/or cervical region. It was observed that the general symptoms mostly manifested at the beginning of the infection, often either at the same time as or shortly after the first skin lesions [19]. Other symptoms not explicitly included as items in the structured telephone interviews but still reported by some infected persons were a maculopapular or urticaria-like rash (7 persons, 1.9%) and ocular manifestations (6 persons, 1.6%).

Fig. 7.

Symptom frequency in percentages during the entire isolation period of infected persons (n = 368). Multiple answers possible

Many infected persons reported increased psychological stress at the beginning or in the further course of the isolation.

In the observed group, hospitalisation was necessary for 13 persons (3.5%). 2 individuals (0.5%) received antiviral therapy with Tecovirimat. The reported reasons for hospitalisation were pain management, bacterial superinfections, abscesses and diagnostic clarification of haematochezia.

In no case was treatment in an intensive care unit required due to the mpox infection. There were no deaths associated with the mpox virus in Cologne during the observation period.

Vaccine performance

The association between previous vaccination and hospitalisation was not significant in the regression models. However, statistically significant associations could be shown between previous vaccination and skin lesions in 3 or more body regions, skin lesions in all 5 body regions and total duration of symptoms, respectively. Infected persons with a previous smallpox vaccination had 0.43 times the odds of unvaccinated persons to be affected by lesions in 3 or more body regions and 0.30 times the odds to develop lesions in all 5 body regions. Previous vaccination statistically reduced the total duration of symptoms by 2.0 days. The results remain significant when looking at the association between childhood smallpox vaccination and the defined outcome variables. No significant association could be found between current Imvanex^® vaccination and the outcome variables. The results of the regression analyses are compiled in Table 1; the analyses for recent Imvanex^® vaccination are not shown because they did not yield significant results.

Table 1.

Regression models for the relationship between either smallpox vaccination in total or specifically childhood smallpox vaccination and the different outcome variables

Outcome variable	OR	Coef	CI	p	aOR	Coef	CI	p
Vaccination in total
Hospitalisation	0.18	− 1.74	0.02–1.37	0.097	0.23	− 1.48	0.03–1.87	0.169
Lesions in ≥ 3 body regions	0.45	− 0.79	0.28–0.72	0.001	0.43	− 0.84	0.26–0.71	0.001
Lesions in 5 body regions	0.33	− 1.12	0.12–0.86	0.024	0.30	− 1.20	0.11–0.83	0.021
Total duration of symptoms	–	− 1.99	− 3.12 to − 0.86	0.001	–	− 2.01	− 3.22 to − 0.79	0.001
Childhood vaccination
Hospitalisation	0.23	− 1.48	0.03–1.78	0.158	0.32	− 1.14	0.04–2.70	0.294
Lesions in ≥ 3 body regions	0.32	− 1.14	0.19–0.54	< 0.001	0.28	− 1.28	0.16–0.49	< 0.001
Lesions in 5 body regions	0.07	− 2.64	0.01–0.53	0.010	0.06	− 2.86	0.01–0.44	0.006
Total duration of symptoms	–	− 2.13	− 3.32 to − 0.94	< 0.001	–	− 2.20	− 3.51 to − 0.90	0.001

Hospitalisation, lesions in ≥ 3 body regions, lesions in 5 body regions were treated as binary variables. For each of these outcome variables, two logistic regression models were fitted: one univariate model and one multivariate model with age and HIV-status as covariates. The results of the univariate regression models are depicted as odds ratio (OR) with corresponding regression coefficient (coef), 95% confidence interval of the odds ratio (CI) and p value (p) and are shown in the left side of the table. Conversely, the results of the multivariate models are given as adjusted odds ratio (aOR) with the same corresponding parameters and are depicted on the right side. Total duration of symptoms (in days) was treated as a continuous variable in a linear regression model. The linear regression models were also run both as univariate and multivariate analyses. The results are depicted as regression coefficient, 95% confidence interval of the regression coefficient and p-value. Statistical significance was defined using a two-sided significance level of α = 0.05

Public health approach in Cologne

In Cologne, all infected persons were attended to by trained personnel over the entire isolation period via regular telephone contacts. In the telephone calls, demographical, epidemiological and clinical data were collected and also infected persons were advised about typical courses of mpox and symptoms of complications that should prompt medical care as well as instructed for self-monitoring and hygiene measures. The telephone conversations ranged in frequency from twice a week to almost daily depending on the severity of symptoms and also on perceived psychological state of the infected. All cases were overseen by medical doctors working in the Cologne Health Department. Regular telephone calls enabled our staff to establish a relationship of trust with many individuals.

For each infected person, an extensive contact tracing was conducted. In accordance with RKI recommendations, contact persons were retrospectively recorded starting from the date of symptom onset of the respective infected person and categorised into three so called exposure categories. Contact persons at moderate or high risk of infection were also registered in our database and regularly contacted via telephone. Therefore, contact persons who developed symptoms after exposure could be quickly identified and receive our care and counselling right from the start. Furthermore, a hotline was set up as well as an email address for queries not only by infected and contact persons but also by the general public. This enabled contact persons or otherwise symptomatic persons to proactively come forward of whom we had no previous knowledge. In cooperation with GP practices and the Cologne clinics we were able to mediate access to PCR swabs for questionable lesions and also to vaccinations, either post- or pre-exposure. Regular meetings were held between the Cologne Health Department, clinicians from local infectious diseases specialist practices and hospitals and in some cases also with experts from regional or national health authorities in order to discuss and adjust the measures taken against the mpox outbreak, such distribution and prioritisation of vaccine doses.

Discussion

The mpox virus was introduced into the Cologne MSM community by singular index persons who had for the most part become infected at pride festivals abroad (e.g. “Gay Pride Maspalomas”, Gran Canary May 2022). After a few weeks of latency, community transmissions and case numbers increased significantly until reaching their peak in CW 28 and 29 (July 11–24). Unspecific symptom manifestation and initial lack of awareness for a then new disease among those infected, the MSM community, as well as clinicians may have contributed to the spread of the disease. CSD in Cologne, the largest pride event in the city and one of the largest in Germany (July 1–3, 2022; CW 26), and parties in the context of this event presumably played a role in the high number of new reported cases in the following weeks. 12% of all infected persons suspected an infection while attending the CSD events. After this peak, the incidence declined again until the last mpox case in Cologne to date was recorded on September 17. The decline and eventual disappearance of mpox cases in Cologne may be attributed to several factors. The swift public health response comprising mandated isolation of infected persons, extensive contact tracing, targeted information of the risk groups and access to vaccination may have played a role in the containment of the outbreak. Additionally, the increasing immunity in a limited risk group either via vaccination or infection over the course of the outbreak may have led to a decreasing (effective) reproduction number.

Mpox case numbers throughout Germany and Europe showed a comparable development with the first cases being recorded in April/May, a peak in the summer months and declining case numbers since August [20]. The origin of the infection of the first reported cases in Cologne lay in other European countries, whereas in the further course of the outbreak, most of the observed cases contracted mpox in Germany, oftentimes even within Cologne. This change from importation to autochthonous transmission is consistent with the published study results from Berlin [21].

Infections also occurred among persons who had received a smallpox vaccination either in childhood or as a current pre- or post-exposure vaccination. They also showed the typical symptoms of an mpox infection.

Data from the Cologne Public Health Department confirmed European findings that mpox predominantly affects MSM, often with multiple changing sexual partners [22–24]. The proportion of HIV-infected people among mpox cases was 39%, significantly higher than in the general population and correlated with the frequently reported sexual risk behaviour in the observed patient population. Since the likelihood of a concomitant STD is up to 30% in mpox patients [22, 25], patients presenting with mpox infection should be offered a screening for STDs including HIV. Conversely, mpox should be especially considered as a differential diagnosis in HIV-positive individuals presenting with skin/mucosal lesions or associated symptoms.

Sexual transmission was the main mode of transmission for mpox virus in the observed group and is consistent as such throughout many studies. Therefore, mpox is now considered as a sexually transmitted disease by some authors [26]. Many of the sexual contacts were reported as anonymous. Therefore, although they frequently represented the probable route of transmission, it was often not possible to confirm the source of infection and to identify further contact persons.

Nevertheless, there were also cases of non-sexual transmission via close physical contact or contact with fomites. In Cologne, not a single infection could be traced back to an exclusive close encounter without physical contact or shared objects. It must be taken into account that about a quarter of the persons could only provide insufficient or no information on the presumed route of infection. This can partially be attributed to the anonymity and the high number of risk contacts in some cases. Furthermore, privacy concerns, the intimate nature of the topic, and also fear of stigmatisation may have lead infected persons to withhold information from the interviewers. However, we are unable to rule out that the route of infection may have been truly unidentifiable to some persons. It remains unclear whether transmission via non-memorable contact situations or fomites/contaminated surfaces (e.g. in public bathrooms) played a role in these cases.

The mean incubation period was only 8.2 days and was thus shorter than assumed at the beginning of the international outbreak [6, 27]. Across several studies, a similarly shorter incubation period was determined [18, 28]. When only cases with a confirmed source of infection were taken into account, outliers of less than 2 or more than 20 days of incubation period disappeared completely in the observed group while the overall probability distribution remained roughly similar (both visually and concerning mean and standard deviation). These results should be taken into account in official recommendations for the management of close contact persons as the duration of monitoring or quarantine should reflect the incubation period.

Almost all infected persons developed typical symptoms at the beginning or in the later course of the disease. However, asymptomatic courses of the disease were observed in isolated cases in which screening swabs were taken due to risk contacts.

Although we explicitly asked for non-specific symptoms before the onset of the skin lesions in our telephone calls, only about 30% of the infected persons reported symptoms in the sense of a prodromal stage. This is consistent with other current study results [29]. Therefore, a prodromal stage seems to occur much less frequently than historically assumed or the initial symptoms are so unspecific that people do not relate them to the infection despite explicit questioning. Accordingly, skin or mucosal lesions were the initial symptomatology in 70% of the cases, with a very small proportion of asymptomatic infections. In our group, general symptoms largely occurred at the same time or shortly after the initial expression of the skin lesions. Characteristic skin or mucosal lesions were often observed in several body regions during the course of the disease. The anogenital region was named as the primarily affected region. This is probably due to transmission during sexual contact, which is the main route of infection in the observed group [19, 30].

The mean total duration of symptoms (16d) was 5 days shorter than the minimum required isolation time for infected persons according to the RKI recommendations [17]. Because of the unspecific clinical appearance and possible lack of general symptoms, mpox was often initially misjudged by those affected, as well as by some medical practitioners. This is evidenced by the rather long mean time span between the onset of the rash/mucosal lesions and the date the swab was taken. Mucosal involvement and corresponding symptoms were much more frequent than initially assumed. According to our findings, these are often responsible for increased suffering and an aggravated course of the disease, including hospitalisation. In case of a suitable medical history and the presence of such symptoms, an mpox infection should therefore always be considered. In this study, we were able to reproduce several clinical manifestations of mpox such as bacterial superinfections, abscesses or maculopapular rash which had been described as novel presentations of the disease during the 2022 outbreak [19], as well as ocular manifestations [31, 32].

Mpox infections may require inpatient treatment. The observed reasons for admission to the hospital are similar to those described by Thornhill et al. [23].

According to our analysis, a previous smallpox vaccination significantly decreases the odds of a widespread skin involvement and significantly decreases the total duration of symptoms. No significant association between hospitalisation and vaccination could be shown. This might be attributed to the low number of hospitalised individuals in the observation group. Out of the 13 hospitalised persons in this study, 2 had received a previous smallpox vaccination. But also, hospitalisation as an outcome variable is probably associated with a number of personal variables, such as comorbidities, which could not be included in the regression models. Looking specifically at childhood smallpox vaccination yields comparable results. No significant association could be found between current Imvanex® vaccination and the outcome variables. This might be due to the relatively small number of persons vaccinated with Imvanex® in this study. In summary, our data show that a previous smallpox vaccination and specifically childhood vaccination seem to favour a milder clinical course of mpox. This adds to a thus far limited body of evidence concerning vaccine efficiency against severe mpox disease. In a study by Hoffmann et al., a statistically significant association could be demonstrated between childhood smallpox vaccination and higher odds of limited cutaneous mpox disease (defined by lesion count ≤ 3) without systemic symptoms [33]. Vaccine efficiency for infection prevention cannot be assessed on the basis of the data gathered since only PCR-positive individuals were included in this study, but it is estimated to be between 80 and 85% depending on the type of smallpox vaccine [14].

The long isolation period and the pronounced symptoms in sensitive body regions such as the genital area or face were accompanied by increased psychological stress for many of the infected. Often, repeated counselling by our staff or, in individual cases, care by the social psychiatric service were necessary. Many infected persons expressed concern about social stigmatisation, especially in connection with their sexual orientation. Some explicitly feared that the mandated isolation would lead to involuntary disclosure of their sexual orientation to their families or employer.

Both in clinical management and in the care provided by the public health service, an especially sensitive approach to the interaction with those infected is advisable [29]. However, transparent communication remains equally important in order to protect the risk groups [21]. In our experience, close cooperation between clinics, laboratories, general practitioners, and local health departments is essential for adequate care.

The public health system consisting of local, regional and national health authorities plays a vital role in the management of a new or previously rare infectious disease such as mpox. In Cologne, we were able to draw on experiences gained during the COVID-19 pandemic as well as staff structures in the health department created in response to the pandemic. Thus, starting from the first mpox cases in Cologne and throughout the entire outbreak, a high standard of individual care and well as staff structures in the health department created in response to the pandemic. Thus, starting from the first mpox cases in Cologne and throughout the entire outbreak, a high standard of individual care as well as a rapid response time could be ensured. Officially ordered isolation or quarantine measures and infection prevention are core tasks of the public health service in response to outbreaks of infectious diseases. At the same time, the surveillance data collected in the health authorities provided important information for adapting the public health measures taken against the spread of mpox among the population.

Strengths and limitations

All mpox cases in the city area of Cologne were included, in contrast to studies that focus on a pre-selected group of patients. After Berlin, the city of Cologne recorded the second highest number of mpox cases in Germany (as of October 30, 2022). Thus, a relatively high number of infected persons could be included in this study all the while maintaining a high standard of data collection through the extensive structured telephone interviews conducted by trained personnel. All information provided by the infected persons was checked for plausibility. Through the regular telephone calls throughout the isolation period, a relationship of trust could be established with many of the infected. This potentially leads to more complete and plausible data.

While the number of cases in relation to the catchment area of a single health authority is large by comparison, it still represents only a fraction of the total number of cases both in Germany as well as worldwide.

As the number of cases increased, we also gained new insights and were able to understand, for instance, the significance of mucosal lesions and the corresponding symptoms.

Most data presented in this study are based on the statements of the infected persons in the telephone interviews. These statements are, by nature, subjective as well as dependent on compliance and memory, as in any medical history. Particularly with regard to personal and intimate questions, for example concerning the route of infection and contact persons, and even though the infected persons were asked repeatedly in case of missing information, the information provided remained incomplete in a relevant number of cases.

Conclusions

In the wake of globalisation, the worldwide mpox outbreak starting in May 2022 marked the emergence of another previously atypical infectious disease in Europe. Public health services play a crucial role in containing such outbreaks by isolating affected individuals and promptly identifying contact persons, by providing easily accessible information and low-threshold counselling services, as well as by gathering and analysing health surveillance data.

Key findings of this observational study are listed below:

1. Most infections were recorded in the MSM community. Persons outside the community were only affected in singular cases.

2. Most infections occurred via sexual contact, but transmissions via other physical contact or fomites was also reported.

3. The average incubation period was shorter than initially assumed, with the onset of symptoms occurring in the first 10 days after exposure in the majority of cases.

4. A prodromal stage was observed in only about 30% of cases.

5. Mucosal involvement and associated symptoms occurred in a relevant number of cases and could lead to increased suffering and more severe clinical courses.

6. Previous smallpox vaccination was significantly associated with milder courses of mpox.

As of October 2022, the local mpox outbreak in Cologne appears fully contained. The number of new cases has been similarly declining throughout Germany and Europe. Regardless, mpox infections can still cause considerable individual suffering. In the case of unclear skin lesions or symptoms suggesting mucosal involvement, especially combined with a suitable medical history, mpox should therefore be considered for differential diagnosis [34]. And even with declining case numbers in many parts of the world, a future mpox outbreak is certainly conceivable.

As evidenced by the mpox outbreak 2022 and also the COVID-19 pandemic, a reactive and well-organised public health system will be critical for managing future outbreaks of known or unknown infectious diseases.

Author contributions

STK and MCL are co-first authors/contributed equally and drafted the manuscript. STK, MCL, MT and BG contributed to conception and design of the project. STK and MCL performed data analysis. STK, MCL and AF performed statistical analysis. BG supervised the project. All authors were involved in the editing of the final manuscript.

Funding

The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

Availability of data and materials

The data used and analysed in the current study are not publicly available because they involve sensitive patient information and indirect identifiers. Anonymised data is available from the corresponding author, STK, on reasonable request.

Declarations

Conflict of interest

The authors have no competing interests to declare that are relevant to the content of this article.

Ethical approval

Due to the retrospective nature of the analyses and use of anonymized data listings, ethical committee approval and consent statements were not required.

Consent to publish

The authors affirm that the person depicted in Fig. 5 provided informed consent for publication of the images.