Toxic-Induced Encephalopathy Following Chemsex in a Young HIV-Positive Male: A Complex Case of Acute Cognitive Impairment with Anterograde Amnesia and Behavioral Alterations

Abstract

background

A broadened clinical spectrum of concomitant complications emerges among the escalating incidence of substance use, particularly within the ‘chemsex’ context. This case exemplifies the profound neurotoxic repercussions and neurological risk of chemsex in a young HIV-positive male and addresses the multifaceted challenges of such evolving paradigms in substance utilization.

Clinical finding

After consuming cannabis, poppers, methamphetamine, and cocaine, a 28-year-old HIV-positive male exhibited significant neurological and cognitive impairment. The initial presentation included dysarthria and profound anterograde amnesia. Laboratory findings showed leukocytosis with a PCR of 3 mg/dl — elevated cerebrospinal fluid protein levels with no cells. Urine toxicology returned positive for cannabis and amphetamines. A brain CT scan revealed bilateral and symmetrical hippocampi and pale globes hypodensity, indicative of toxic-metabolic encephalopathy. MRI further identified lesions in the globus pallidus, cerebellum, and hippocampi. Following the detection of toxic encephalopathy, Initial neuropsychological was performed screening using the Montreal Cognitive Assessment (MoCA), which highlighted immediate memory deficits. An in-depth neuropsychological assessment conducted 3 weeks later included the Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV), the Rey Auditory Verbal Learning Test (RAVLT), and tests for visuospatial skills, motor functions, and memory recall. The evaluations revealed pronounced anterograde amnesia, persistent long-term memory inconsistencies, and notable executive function challenges, detailed in Table 1.

Conclusions

The detailed analysis of this case underpins the severe neurological consequences that can manifest from heavy substance use. Comprehensive diagnostic evaluations, including neuroimaging and neuropsychological assessments, are crucial in elucidating the full spectrum of substance-induced cognitive impairments. There is an urgent need for enhanced public awareness and preventative measures, especially in the context of chemsex, to bring forth multifaceted health, social, and government implications that modern society must adeptly navigate.

Supplementary Information

The online version contains supplementary material available at 10.1007/s40121-024-00962-x.

Key Summary Points

Why carry out this study?

The study focuses on the rising trend of chemsex, particularly among individuals with HIV, and its potential neurochemical impacts, including acute amnestic syndromes and other severe neurological complications.

The hypothesis was to explore the neurological consequences of substance use in chemsex, particularly in patients with underlying conditions like HIV, and to understand the intricacies of clinical assessments and management of such cases.

What was learned from the study?

The study’s outcomes revealed significant neurological impairments, in a patient following heavy substance use in a chemsex setting. Neuroimaging showed lesions in critical brain regions correlating with the patient’s symptoms.

The findings highlight the severe and potentially lasting neurological impact of substance use in chemsex, emphasizing the need for careful and comprehensive clinical evaluations in such cases. The study also emphasizes the importance of considering the complex drug interactions, especially in HIV-positive individuals. It suggests the need for targeted interventions and public health strategies to address the risks associated with chemsex.

Introduction

Intoxications related to chemsex are becoming more prevalent among individuals with HIV, and their use as neurochemical substances as sexual boosters (chemsex is a term used to describe the intentional use of drugs to enhance or facilitate sexual activity) has become popular in this population [1, 2]. Neurological complications are the most prevalent in some European cohorts [3]. In this setting, emergencies occasionally bring forth rare clinical events known as acute amnestic syndromes [4]. Pinpointing the cause can be complex, given the array of potential origins. While some cases may be fully recoverable, others can come with additional neurological symptoms, leading to severe, permanent brain injury. The hippocampus plays a critical role in memory. Its alteration, either structural or functional, can alter memory. One common manifestation is transient global amnesia, distinguished by a swift onset of anterograde amnesia that lasts less than 24 h, devoid of other neurological indicators. Another brief memory disturbance is transient epileptic amnesia, attributed to localized seizure activity [4]. Memory impairments can also arise suddenly from strokes that affect crucial memory sites. Beyond neurological origins, amnesia can also signal psychiatric conditions like dissociative amnesia. It is essential to consider traumatic brain injuries, autoimmune encephalitis, and acute toxic metabolic disorders as potential causes of amnesia; for this discussion, we highlight the importance of toxic-induced disorders [5, 6].

This report presents a challenging case involving a 28-year-old male with a background of well-controlled HIV and documented substance use. Following an episode of heavy consumption of cannabis, poppers, methamphetamine, and cocaine within chemsex, the patient exhibited alarming neurological and cognitive symptoms, chiefly characterized by acute cognitive impairment and predominant anterograde amnesia. This case provides an opportunity to examine the potential neurological ramifications of substance use, especially in individuals with underlying conditions. It stresses the importance of prompt and comprehensive clinical assessments in understanding and managing such difficult presentations.

Clinical Case Overview: Comprehensive Profile of a 28-Year-Old Male Patient

Twenty-eight-year-old male patient with no known drug allergies. Educational background: He completed a degree in social communication in his home country (Colombia). Worked as a salesperson in stores and as a waiter. The patient is a heavy consumer of cannabis (weekly), poppers (weekly), smoked methamphetamine (monthly), and occasional alcohol in social settings and no slamming.

Past medical history: HIV infection diagnosed in November 2014. Started treatment in Colombia with switching from efavirenz/tenofovir/emtricitabine EFV/TDF/FTC after diagnosis (unknown CD4 nadir and viral load at diagnosis), apparently good adherence and tolerance. There was no history of virological failures or opportunistic infections. He arrived in Spain in 2021, EFV/TDF/FTC to dolutegravir/lamivudine (DTG/3TC). The patient showed reasonable immunovirological control with a CD4 count of 646 cells/mm³ and a viral load of less than 50 copies/ml, with no data before hospitalization.

On the night of July 14–15, he consumed cocaine, poppers, and cannabis in a recreational-sexual context, starting the same day with symptoms of sweating, holocranial headache (widespread headache), and general discomfort, which his partner initially interpreted as a result of partying, leading him to sleep most of the day. On July 16, around 11:00 am, he started experiencing language impairment (according to his partner, dysarthria "as if his tongue was tied"), and upon returning home, he began experiencing memory lapses, not remembering what had happened during the morning. Consequently, he was taken to the emergency room for assessment. A stroke code was activated due to possible neurological focal symptoms, but it was dismissed due to the temporal and progressive nature of the symptoms.

A blood test showed a slight elevation in acute-phase reactants with leukocytosis and a PCR of 3 mg/dl. Urine toxicology was positive for cannabis and amphetamines. A brain CT scan showed signs of toxic encephalopathy with bilateral and symmetrical hypodensity of both hippocampi and pale globes (Fig. 1) and reduced intensity in the bilateral occipital lobe, suggesting toxic-metabolic encephalopathy. A lumbar puncture revealed minimal hyperproteinorrachia, glucose within range, 200 red blood cells, and eight nucleated cells. Empirical coverage with acyclovir was initiated and discontinued as LCR multiplex PCR was negative.

Fig. 1.

CT scan findings indicative of bilateral toxic-ischemic encephalopathy. CT scans display coronal, axial, and sagittal views from left to right. The scans reveal no evidence of acute hemorrhagic events either within or surrounding the brain tissue. Symmetrical hypodensity is noted in the bilateral globus pallidus and hippocampi, with less pronounced hypodensity in the bilateral occipital lobes. No enhancement was observed post-intravenous contrast injection. These patterns are consistent with a primary diagnosis of toxic encephalopathy. The ventricular system is unremarkable in morphology and size, with the midline structures remaining centralized. Basal cisterns appear unobstructed. There is a partial opacification with mucosal characteristics in the right maxillary sinus. In summary, imaging findings are indicative of a toxic-ischemic encephalopathy characterized by bilateral and symmetrical hypodensities in both hippocampi and globus pallidus. Differential considerations may include carbon monoxide toxicity or central posterior reversible encephalopathy syndrome (PRES)

Nevertheless, the patient’s condition rapidly deteriorated in the hospital ward, with worsening dysarthria, neuropsychiatric alterations, and exacerbated anterograde amnesia. An EEG showed findings consistent with diffuse cerebral dysfunction. Doppler ultrasound and angio-MRI showed no abnormalities in the carotid territory. During the early hours of July 19, he developed significant psychomotor agitation about memory lapses, requiring mechanical and pharmacological restraint. Due to the progressive neurological deterioration and the likely need for sedation for a brain MRI, he was admitted to the ICU. After the MRI, he was transferred back to the conventional Infectious Diseases ward.

Neuroimaging (cranial CT Fig. 1 and cerebral MRI Fig. 2) showed lesions in the globus pallidus, cerebellum, and hippocampi. Upon reassessment, he presented primarily anterograde amnesia, increased response latency, childlike behavior, and a lack of awareness of his deficits. He occasionally confabulated. A MoCA test was performed, yielding a score of 19/30 (visuospatial/executive function 3/5; identification 3/3; attention 6/6; language 2/3; abstraction 2/2; delayed recall 0/5; orientation 3/6), primarily indicating a deficit in episodic memory with a score of 1/15 on the memory index scale (MIS). The patient’s neuropsychological assessment had indicated a pronounced presence of anterograde amnesia, accompanied by retrograde memory challenges and compromised executive functions, all consistent with the hallmarks of toxic encephalopathy.

Fig. 2.

Ten-day post-onset MRI: The imaging study, comprising coronal, axial, and sagittal views from left to right, encountered motion artifacts during acquisition, particularly affecting the FLAIR sequence. FLAIR sequences show signs of alterations in both globus pallidi, the cerebellum, and the hippocampi (B). An apparent alteration of the signal in both globus pallid can be observed. The cerebellum, hippocampi, and globus pallidum show uptake suggestive of toxic-metabolic-ischemic encephalopathy

Upon admission, in-depth neuropsychological screening, documented as Table 1, revealed significant anterograde amnesia, attention deficits, and executive function challenges. This was closely followed by further assessments, outlined in Table 2, at 38 days post-onset, where certain cognitive deficits persisted despite slight improvements in memory retention and retrieval. After 120 days, as detailed in Table 3, the patient still exhibited anterograde amnesia, impairment in complex visuospatial functions, yet showed some recovery in language function and cognitive flexibility with slight improvements in memory encoding and retention noted since the initial evaluation. Additionally, there has been a consolidation in the retrieval of retrograde information. The patient’s spontaneous language normalized, and attention remains average. Complementing these findings, MRI results 33 days post-onset (Fig. 3) revealed marked improvement in the globus pallidi’s signal alteration, with ongoing but diminished signal changes in the cerebellum and both hippocampi. These cognitive deficits, particularly anterograde amnesia, significantly impair the patient’s autonomy and ability to manage self-care, increasing vulnerability in personal decision-making.

Table 1.

Neuropsychological evaluation 1: Post-onset day 17

Test name/reference	Subject parameter	Score	Score interpretation
WAIS-IV (Wechsler, 2012)	Comprehension, digit span, symbol search, coding	CC 28 (5), DI (6 + 4), S 18 (8), CN 43 (4)	High comprehension, average digit span, good symbol search, low coding efficiency
TAP (Gomar et al., 2011)	Total score	22 (CI 100)	Average performance with a confidence interval at 100
RAVLT (Rey et al., 1964)	Trials interference Immediate memory Delayed memory Recognition Forgetting index	16, 5, 6, 4, 4 4 1/15 0/15 6/15 20	Initial learning difficulty with some retention; marked deficits in immediate and delayed memory recall; moderate ability to recognize learned words; significant information loss over time per high forgetting index
WMS-III (Wechsler, 1998)	Visual reproduction I Visual reproduction II, Logical memory I Logical memory II	79 (7) 0 (1) 15 (2) 0 (1)	Visual memory is high initially but poor delayed recall; Logical memory shows good immediate recall but poor delayed recall
TMT (Neuronorma) (Peña-Casanovas et al., 2003)	Part A, Part B	60 s (< 2), 123 s (5)	Slow processing speed and executive functioning
BNT (Neuronorma)	Total Score	54/60 (7)	Good naming ability
BLNB (Golden et al., 1979)	Poppelreuter, Clocks	5/5, 0/4	Perfect in complex figure recognition, poor in clock drawing
BADS Wilson et al. (1996)	ZooMap1	255 seg	Slow in planning and execution on task

Bolding formatting refers to percentile. Numerator/denominator

WAIS-IV Wechsler Adult Intelligence Scale—Fourth Edition, TAP Test of Attentional Performance, RAVLT Rey Auditory Verbal Learning Test, WMS-III Wechsler Memory Scale—Third Edition, TMT Trail Making Test, BNT Boston Naming Test, BLNB Batería Luria-Nebraska, BADS Behavioral Assessment of the Dysexecutive Syndrome

Table 2.

Neuropsychological evaluation 2: 38 days post-onset

Test name/reference	Subject parameter	Score	Score interpretation
WAIS-IV (Wechsler, 2012)	Digit span	DI (6 + 3)	Decrease in working memory and attention
RAVLT (Rey et al., 1964)	Trials, interference, immediate memory, delayed memory, recognition, Forgetting Index	5, 8, 7, 7, 8, B 6, 1/15, 0/15, 10/15, FI 4	Improvement in learning and memory, reduced forgetting
BNT (Peña-Casanovas et al., 2003)	Total score	54/60 (7)	Consistent good naming ability
BLNB (Golden et al., 1979)	Poppelreuter, clocks	Poppelreuter 5/5, Clocks 0/4	Good figure recognition, difficulty with spatial construction
LOBT (Peña-Casanovas et al., 2003)	Total score	14/30 (3)	Below-average problem-solving and planning

Bolding formatting refers to percentile. Numerator/denominator

WAIS-IV Wechsler Adult Intelligence Scale—Fourth Edition, RAVLT Rey Auditory Verbal Learning Test, BNT Boston Naming Test, BLNB Batería Luria-Nebraska, LOBT Luria-Nebraska Overlapping Figures Test

Table 3.

Neuropsychological evaluation 3: 120 days post-onset

Test name/reference	Subject parameter	Score	Score interpretation
WAIS-IV (Wechsler, 2012)	Digit span	DI (6 + 4)	Slight improvement in working memory
RAVLT (Rey et al., 1964)	Trials, interference, immediate memory, delayed memory, recognition, Forgetting Index	5, 6, 7, 6, 7, B 4, 3/15, 2/15, 4/15, FI 4	Consistent learning, slight memory recall improvement
WMS-III (Wechsler, 1998)	Visual reproduction I, visual reproduction II	75 (6), 15 (3)	Visual memory performance slightly improved
BLNB (Golden et al., 1979)	Poppelreuter, clocks	5/5, 1/4	Stable in figure recognition, some improvement in spatial construction

Bolding formatting refers to percentile. Numerator/denominator

WAIS-IV Wechsler Adult Intelligence Scale—Fourth Edition, RAVLT Rey Auditory Verbal Learning Test, WMS-III Wechsler Memory Scale—Third Edition, BLNB Batería Luria-Nebraska

Fig. 3.

Post-onset MRI at 33 days: The imaging study, comprising coronal, axial, and sagittal views from left to right, compared to a 10-day post-onset MRI. The latest scans show a notable reduction in signal abnormalities in the globus pallidum. However, persistent signal alterations remain in the cerebellum and both hippocampi, as seen on FLAIR sequences, although these have lessened since the previous imaging. Ventricular size is standard, and the basal cisterns are intact

Discussion

In recent years, like many other major cities worldwide, Barcelona has seen a significant rise in drug use, especially within chemsex [1, 11, 12]. This growing phenomenon raises not only concerns about the direct health consequences of drug misuse, such as addiction and overdose, but also the increased incidence of atypical presentations of diseases and a higher incidence of sexually transmitted infections or the recently described associated methicillin-resistant Staphylococcus aureus infection [2, 13].

In this case, the severe clinical presentation of the 28-year-old male offers a profound insight into the interplay between substance use and neurological implications. Neuroimaging shows lesions in the globus pallidus, cerebellum, and hippocampus, which merit a detailed neuroscientific exploration. These brain regions are integral to a range of cognitive functions: the globus pallidus plays a crucial role in regulating voluntary movement, the cerebellum contributes to motor control and mental functions such as attention and language, and the hippocampus is fundamentally involved in memory formation and retrieval. The pronounced anterograde amnesia observed in the patient is elucidating, given the hippocampal damage evidenced by neuroimaging. This aligns with the existing literature regarding the hippocampus’s role in consolidating new memories. The patient’s neurological state is characterized by significant memory deficits, neuropsychiatric alterations, and cognitive disturbances. The heavy consumption of these substances, especially within the setting of chemsex, can potentiate their neurotoxic effects. These side effects are not dose-dependent.

The precise mechanism behind these lesions is unclear, but potential causes include ischemia, direct toxicity, or their combination. Anoxia often leads to ischemic hippocampal injuries [14], resulting in marked anterograde amnesia. While anoxia-induced bilateral lesions in the basal ganglia are less common [15, 16], they can also arise from carbon monoxide exposure [17, 18]. Hippocampal lesions from anoxic events usually hint at a bleak prognosis [19, 20]. Research on rat models indicates that hypoxia can induce hyperpolarization and neuronal injury within the CA1 region of the hippocampus [21]. The unilateral counterpart usually shows less pronounced memory deficits than bilateral hippocampal damage [22]. Different conditions can induce ischemia and hypoxia in the hippocampus, and each carries its prognosis. For example, post-cardiac arrest ischemia often has a limited potential for memory recovery [19]. Though rare, cocaine-induced vasospasm and carbon monoxide intoxication are recognized instigators of bilateral ischemia in the hippocampus [23]. In this patient, we postulate that multiple drug exposures led to anoxia, culminating in bilateral hippocampal damage.

Stimulants, specifically cocaine, can produce ischemic lesions from vasospasm. There are prior cases of bilateral basal ganglia lesions in stimulant use. For example, there is a case of bilateral basal ganglia lesions following MDMA use [24] and an additional case involving methadone, cocaine, and amphetamines [25] producing basal ganglia lesions. A combination of cocaine and alcohol resulting in unconsciousness has also produced bilateral basal ganglia lesions [26]. Between 2012 and 2016 in Massachusetts, an unusual group of 14 cases emerged, each presenting with sudden amnesia due to acute and total bilateral ischemia in the hippocampus. While the exact cause remains uncertain, 13 of the 14 cases either tested positive for opioids or had a record of opioid use in their medical history at the time of their initial assessment [27]. In this particular situation, the patient tested negative for opioids, and there is no known current use of these substances within the chemsex context in Barcelona. In other studies, from a series studying bilateral globus pallidus necrosis, drug overdose was the cause in ten out of 27 cases, surpassing any other reason [28].

In a case echoing ours, a 55-year-old man presented with bilateral hippocampal and basal ganglia lesions following a myocardial infarction induced by cocaine and 3,4-methylenedioxy-methamphetamine consumption, resulting in explicit and procedural anterograde amnesia. Notably, both patients exhibited a similar memory impairment type – anterograde amnesia for explicit and implicit/procedural memory, which we attribute to bilateral lesions in the hippocampus and basal ganglia due to drug use [29].

Furthermore, bilateral hippocampal lesions have been observed concerning cocaine use, stemming from vasospasm without anoxia [30, 31]. It is also noteworthy to touch upon the patient’s childlike behavior and lack of awareness of his deficits. Such presentations may suggest frontal lobe involvement, a brain region responsible for executive functions, judgment, and self-awareness. Though not explicitly mentioned, the observed executive dysfunctions in the neuropsychological evaluation hint at possible frontal cortex implications.

Regarding neuroimaging findings in 50% of patients suffering from acute amnesic syndrome, MRI T2-fluid-attenuated inversion recovery (FLAIR) sequences reveal hyperintense lesions in locations such as the fornix, medial thalamus, mammillary bodies, and periventricular area around the third ventricle, and periaqueductal areas [4]. In our specific patient, the findings contrast with this, as we observed a definitive change in signal in both globus pallidus. The FLAIR sequences for this patient also detected signal variations in the cerebellum and hippocampus. Hence, the distinct findings centered around the cerebellum, hippocampi, and the globus pallidus. Postmortem examinations have detailed the neuropathological consequences of carbon monoxide (CO) toxicity. They reveal damage to the globus pallidus, diffuse white matter lesions, and encephalopathic changes [32]. We could not detect carboxyhemoglobin due to our patient’s delayed arrival time to the ER (the half-life of carboxyhemoglobin is about 74 min) [33].

Despite experiencing a severe outcome, our patient on dolutegravir and lamivudine was not exposed to the amplified risks of boosted ART. In a study of 172 HIV-positive chemsex participants, 30% used boosted ART. Of 2048 identified potential drug–drug interactions, 23% were deemed concerning, with 88% due to boosted ART [34]. Therefore, for the HIV chemsex community, it is crucial to consider non-boosted ART as a safer alternative to minimize potential drug interactions.

In our patient, while the underlying cause is likely drug toxicity, established ischemia is evident both on brain scanning and MRI, coupled with bilateral involvement. Medical literature extensively documents that anoxic damage causing hippocampal lesions predicts a less optimistic prognosis [19, 20]. Specifically, bilateral hippocampal damage tends to induce more profound memory deficits than unilateral lesions [22]. Numerous circumstances can precipitate ischemia and hypoxia in the hippocampus, each presenting its prognosis. As referenced from literature-based case reports and some case series, it is notable that patients who suffer from hypoxia but show no signs of ischemia, as well as those with histotoxic hypoxia stemming from incidents like carbon monoxide poisoning, might stand a better chance of recovery, irrespective of how severe the initial imaging might appear [35]. For example, post-cardiac arrest ischemia often culminates in a bleak outlook for memory recovery [19]. Even though rare, both cocaine-induced vasospasm and carbon monoxide poisoning are recognized precipitators for bilateral ischemia in the hippocampus [23, 36].

A notable limitation of this study is the inability to definitively identify the pathophysiological mechanisms underlying the neurological impairments observed in the patient, such as the exact cause of lesions in the brain regions like the globus pallidus, cerebellum, and hippocampus – this gap in understanding limits the ability to develop targeted interventions. Additionally, the lack of long-term follow-up is a significant limitation, as recovery from neurological impairments, particularly those involving memory and cognitive functions, can be prolonged. Insights into the patient’s recovery trajectory and the effectiveness of interventions over time are therefore unavailable. Another fundamental limitation is the absence of specific medical interventions or rehabilitation programs to enhance cognitive recovery in the patient’s care plan. Such interventions could aid in recovery, especially given the nature of the neurological deficits. The report also does not elaborate on rehabilitative or supportive care provided, which is crucial for recovery in cases involving drug misuse and neurological damage. Lastly, while the complexity of drug interactions in chemsex is acknowledged, the potential for underestimating the synergistic effects of multiple drugs used concurrently might limit a comprehensive understanding of the patient’s condition.

In this case, temporary legal safeguards have been considered essential to protect the patient’s health and welfare, with adjustments to be made according to clinical developments. Although the chances of complete recovery remain uncertain, it is advised to conduct a subsequent neuropsychological evaluation and begin specialized neuropsychological rehabilitation to optimize the potential for rehabilitation.

The adverse consequences of substances, particularly cocaine, cannabis, and poppers (alkyl nitrites), seem to be exacerbated when consumed in high doses, as observed in chemsex settings. While anoxia appears to be a plausible cause behind the observed injuries, considering the link between drug overdose and ischemia in specific brain regions, it is evident that multiple factors, such as direct toxicity or ischemia, contribute to the outcome. It is also vital to recognize the potential association of substance-induced ischemia without the involvement of anoxia. Noteworthy neuroimaging findings, particularly lesions in crucial brain regions such as the globus pallidus, cerebellum, and hippocampi, correspond with observed severe anterograde amnesia.

The complexity of drug interactions, especially in chemsex, brings forth multifaceted clinical implications that the modern healthcare system must adeptly navigate. Chemsex is a complex and dynamic phenomenon that, as demonstrated in this instance, can have potentially detrimental effects on a person’s life in a variety of ways. A proactive approach to public health, encompassing thorough research, targeted interventions, education, and public awareness, is tailored to the specific needs of this vulnerable population.

Supplementary Information

Below is the link to the electronic supplementary material.

Author Contributions

Alexy Inciarte (A.I.) was responsible for the conception, design, and writing of the case report. Berta Torres (B.T.), Alberto Foncillas (A.F.), Lorena de la Mora (L.DLM), and Silvia Cañizares (S.C.) provided clinical information and participated in the revision of the report. Alexy Inciarte (A.I.), Berta Torres (B.T.), Jose Luis Blanco (J.L.B.), Esteban Martínez (E.M.), Montserrat Laguno (M.L.), JM Miro (J.M.M.), Juan Ambrosioni (J.A.), Maria Martinez-Rebollar (M.M.R.), Elizabeth Zamora (E.Z.C.), Ivan Chivite (I.C.), Ana González-Cordón (A.G.C.), Alberto Foncillas (A.F.), Júlia Calvo (J.C.), and Josep Mallolas (J.M.) reviewed and made revisions to the manuscript.

Funding

This research received funding support from The Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), and publication dissemination charges were financed by the Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS). The Rapid Service Fee was funded by the authors.

Data Availability

Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.

Declarations

Conflict of Interest

The authors, Alexy Inciarte, Lorena de la Mora, Emilio Felipe Huaier Arriazu, Berta Torres, Silvia Cañizares, Elizabeth Zamora, Montserrat Laguno, Ana González-Cordón, Alberto Foncillas, Ivan Chivite, Júlia Calvo, Juan Ambrosioni, Esteban Martínez, Jose Luis Blanco, JM Miro, Maria Martinez-Rebollar, and Josep Mallolas, state that they have no competing interests to declare. Dr. Juan Ambrosini is an Editorial Board member of Infectious Diseases and Therapy. He was not involved in the selection of peer reviewers for this manuscript nor any of the subsequent editorial decision.

Ethical Approval

In compliance with ethical guidelines, we obtained publication consent from a patient’s family member, who actively gave written informed consent to publish the patient’s clinical details. Since the patient could not consent, the family member acted on his behalf. We used a standardized consent form for this process. This study was performed in accordance with the Helsinki Declaration of 1964 and its later amendments.