Risk factors for SEA include diabetes, immunosuppressed state, intravenous drug abuse, chronic renal or liver failure, spinal surgery, obesity, and bacteremia [2-9]. Despite the incidence of SEA progressively increased during the last decades [3-7,9], indeed SEA remains uncommon ranging from 1.2 to 3 per 10,000 hospitalized patients [3,7,9], with less than 1000 cases published over a 40 years period [5,10]. Cases of primary SEA that are cases without any evident infective source are even rarer accounting for 20% [1,2].
The bacteria may enter the epidural space spreading from adjacent local infections (such as discitis), contaminating invasive procedures (such as spinal surgery or spinal anesthesia), or through the hematogenous route [3-6,9]. SA, usually the MSSA, is responsible for 70% of cases [3,4,6,7,9].
The classic triad of SEA consists of back pain, fever, and neurologic deficits but it is just reported in 8% of cases [3-7,9]. Pain is constant, fever is present in less than 50% of cases, true neurological deficits affect a minority of patients [4-6,9,10]. Onset of symptoms may be sudden, or slowly progressive but back pain often evolves to paraplegia within few days . Accordingly, early diagnosis is crucial, but it is difficult, and half of cases are initially misdiagnosed [3-7,9].
White blood cell (WBC) count is normal in about half of patients, while erythrocyte sedimentation rate (ESR) and CRP are generally elevated [4,5,7,9-11]. Bacteremia causing or arising from SEA is detected in 60% of patients [5-7].
MRI with contrast is the diagnostic method of choice: SEA is generally seen as a T1 hypointense, T2 hyperintense mass with enhancing capsule in the epidural space [4-7]. Most of SEAs are lumbar and posterior because infections are more likely in larger fatty epidural spaces .
Decompressive laminectomy and drainage together with systemic antibiotics are mandatory in patients with neurological symptoms [5,9]. Spinal fusion is to be considered in secondary SEA when spondylodiscitis causes structural compromise to the spinal column [6,12]. Pending the identification of the causative organism, empiric therapy should start using broad spectrum antibiotics . Therapy usually include vancomycin, last generation cephalosporin, and sometimes aminoglycoside, and/or metronidazole [3,4,6,7]. There are no guidelines for the duration of therapy, but patients typically require 4-8 weeks of therapy [3-7,9]
Postoperative recovery depends on age, health status, comorbidities, and history duration [13-15] but above all on the patient’s neurologic status immediately before surgery [2,4,5,7]. Despite recent improvements, outcomes of SEA remain poor, with mortality ranging from 5% to 23% and neurological morbidity ranging from 4% to 55% [4-7,9,16].
COVID-19 primarily is a respiratory tract infection with significant systemic impaction on cardiovascular, neurologic, gastrointestinal, hematopoietic, hemostatic, and immune systems [17-19]. It is now widely accepted that a sort of disseminated intravascular coagulation (DIC) may develop with platelet consumption and hemorrhagic risk [19-21]. Recent studies show that the SARS-COV-2 provokes a diffuse damage to the vascular endothelium [20,21]. In a large autoptic series , all cases presented more or less degree of endothelial damage and arteriolar thrombosis was evident in 87% of cases. DIC and microembolisms are caused by this sort of endotheliitis and the IP can be de facto considered as a diffuse micro-infarction of the lung. The diffuse cellular damage would trigger autoimmune response with further cellular destruction. Lymphocytes and monocytes often decrease with possible impaired immune response to exogenous infective agents [17,22,23]. Bacterial infections have been reported in half of patients [18-20,22,23]. From a practical point of view, COVID-19 may consist of a complex clinical situation including disseminated microembolisms, bleeding diathesis, diffuse vasculitis, and autoimmune aggression with decreased antibacterial defence. However, asymptomatic or paucisymptomatic cases are common. Apart from direct antiviral therapy, treatment of COVID-19 mainly consists of anti-inflammatory drugs, anticoagulants, immunomodulators and antibiotics [18,19,23].
COVID-19 and primary SEA
During the last 10 years, we surgically treated a total of 7 patients with primary SEA that means without spondylodiscitis or evident infective source. Following the outbreak of COVID-19, we received 6 patients in a couple of months. Three of these patients complained of full-blown severe COVID-19. In another patient, the diagnosis was only based on clinical symptoms, but we think it was highly probable. In two patients, the viral infection was almost asymptomatic and just revealed by the serologic tests. Accordingly, the clinical severity of COVID-19 was not correlated to the SEA occurrence. Moreover, when SEA occurred, only two patients were still fighting against active COVID-19.
These six patients presented some differences from the classical SEA patients: they were relatively younger; none was drug-abuser; only two were obese and only one of these was diabetic; only one harboured lumbosacral SEA. All these patients had lymphopenia and three had previously received immunomodulators to face the viral infection. Mild immunodeficiency cannot be excluded even in those two patients who were asymptomatic for COVID-19. Nonetheless, we do not believe that immunodeficiency played a major role in the SEA development. As aforementioned, immunocompromised state represents a risk factor for developing SEA and lymphopenia is quite common in COVID-19 patients. Accordingly, an increased SEA incidence could be expected in COVID-19 patients. Conversely, to our knowledge, cases of SEA in COVID-19 patients have been not yet published. Theoretically, SEA could have been underdiagnosed in comatose or severely compromised COVID-19 patients. Otherwise, SEA simply could have been not reported because physicians focused on other aspects of the disease.
In two patients, the MSSA was also subsequently found in blood cultures. Perhaps, bacteremia could have caused the SEA, but it is also possible that the bacterium secondarily entered the blood from the SEA [5-7]. Both these patients were apyretic, never presented signs of sepsis, and WBC and neutrophils were just moderately increased.
All patients had never presented clinical evidence of pyogenic infection. Nosocomial infections may be perhaps suspected in the two hospitalized patients, but these presented no sign of sepsis or other infections. Three patients had history of recent asymptomatic SA presence in pharynx and expectoration, that had been interpreted as sample contamination. When SEA occurred, neither pharyngeal nor pulmonary infections were evident. Interestingly, within few weeks, the two patients with contaminated expectoration developed thoracic SEA, the one with contaminated swab suffered from cervical SEA. A retrograde spinal invasion is thus conceivable.
As aforementioned, the coronavirus is typically responsible of a diffuse endothelial damage [20,21]. In two of our patients with IP, the chest-CT-scan (Figure 1) also showed the “atoll-sign”, which is a well-known expression of inflammation and granulomatous reaction in organizing pneumonia and is classically associated to angioinvasive agents . All patients but one had history of arterial hypertension. We wonder if this could have had an effect on the vascular wall. Anyway, some degree of damage to the vascular endothelium is presumable in all our patients. This could have favoured the vascular penetration of SA even in absence of a clear SA infection. By this way, SA could have retrogradely reached the correspondent spinal epidural space causing progressive cellulitis of the epidural fat with the ultimate formation of SEA.
If this was the case, the higher than normal SEA incidence in this population might be explained. Of course, we are not stating that COVID-19 was responsible for SEA development but a role can be hypothesized. The viral infection might create the conditions for spinal invasion in subjects that are predisposed owing to the presence of a bacterium in a given location. This might also account for the cervical and thoracic SEAs that are relatively uncommon in classic SEA patients. Even the late onset of SEA following the recovery from the COVID-19 might be explained by the time to retrogradely invade the epidural space.
COVID-19 patients may present problems that can seriously hamper surgeries . However, we did not encounter particular surgical problems in these 6 patients whose platelets were normal and immunological, respiratory, and circulatory states were acceptable. Despite relatively prompt treatment, no patient completely recovered from the spinal cord damage. Since the preoperative status is the main determinant of favourable outcome [2,4,5,7] and SEA may be encountered at unexpected rates, careful neurological examination of COVID-19 patients is mandatory.