key: cord-0846524-8foha03n authors: Jena, Debasish; Sahoo, Jagannatha; Barman, Apurba; Dalai, Anchal; Patel, Suman title: Neuropathic pain in hospitalized COVID-19 patients: A prospective case-series date: 2022-02-27 journal: Arch Rehabil Res Clin Transl DOI: 10.1016/j.arrct.2022.100188 sha: b5b29ee6240e1cb0eeec43235e03eaa99e739bd9 doc_id: 846524 cord_uid: 8foha03n OBJECTIVE The objective of this study was to report the demographic and clinical characteristics of eight hospitalized cases of Coronavirus disease 2019 (COVID-19) presenting with neuropathic pain (NeuP). DESIGN A prospective case series with one month follow-up SETTINGS COVID-19 dedicated wards of a tertiary care center PARTICIPANTS We included eight consecutive cases of laboratory confirmed cases of COVID-19 (by reverse transcription polymerase chain reaction) who presented with NeuP during the course of their acute hospitalization. INTERVENTIONS Not Applicable MAIN OUTCOME MEASURES Verbal Rating Scale (VRS) was used to assess NeuP severity at presentation and at one month follow-up. Douleur Neuropathique (DN4) questionnaire was used to diagnose NeuP at presentation. RESULTS Most patients were diagnosed as moderate to severe COVID-19 (6/8) and presented with mild to moderate NeuP (6/8). A substantial proportion of the patients (4/8) displayed persistence of mild pain symptoms at one month follow-up. Furthermore, participants displayed a favourable response to gabapentinoids with or without antidepressants. CONCLUSION NeuP is a less commonly encountered symptom of COVID-19 but its early diagnosis and prompt management is of utmost importance. More studies including a larger cohort and longer follow-up are recommended for better understanding of COVID-19 associated NeuP. manifestations are not uncommon and may involve both central and peripheral nervous system involvement. Common neurological symptoms of COVID-19 are anosmia, ageusia, and headache. There are also reports of myelitis, stroke, and Guillain-Barr syndrome. 2 Furthermore, it is well established that pain symptoms are among the most common clinical manifestations of the disease. Myalgia and headache are among the most commonly reported pain symptoms. [3] [4] [5] But, COVID-19 associated neuropathic pain (NeuP) has been investigated in lesser detail so far with very scarce reports in the literature. A recent study reported possible neuropathic pain in up to 2.3% of hospitalized COVID-19 patients. 6 Therefore, we aim to report eight consecutive cases of COVID-19 associated NeuP and their detailed clinical and demographic characteristics. A confirmed case was defined as a person with laboratory confirmation of COVID-19 infection (by reverse transcription polymerase chain reaction), irrespective of clinical signs and symptoms. Severity classification was done according to the guidelines issued by the Ministry of Health and Family Welfare, Government of India. 7 Verbal rating scale (VRS; 0-10) was used for the severity assessment of NeuP and the Douleur Neuropathique (DN4) questionnaire was used for the diagnosis of NeuP. Pain severity classification was done as mild (VRS 1-3), moderate (VRS 4-7), and severe (VRS 7-10). A minimum score of 4 (out of 10) on the DN4 questionnaire was considered as NeuP. All patients were followed up at one month for the persistence of the symptoms. Written informed consent was signed by all participants before inclusion in the study. A 66-year-old male was diagnosed with moderate COVID-19 and was on corticosteroids and remdesivir injections along with other supportive treatments. He had a body mass index (BMI) of 24.9 kg/m 2 with no significant past medical history. On the 4 th day of his illness, he developed new-onset pain described as pins and needle-like sensations involving the lateral aspect of both his legs and feet. The pain symptoms were in the distribution of common peroneal nerve bilaterally. No objective signs could be elicited on clinical examination. Pain severity on VRS was 5 that got exaggerated with prolonged bed rest and relieved with standing or walking few steps. Also, the pain was persistent during the night and was interfering with his sleep with a DN4 score of 4. He was advised with tablet pregabalin 75 mg bedtime with amitriptyline 10 mg and to avoid prolonged bed rest. Pain improved significantly over the next three to four days and the VRS score was 2 at discharge. At onemonth follow-up, the pain had subsided completely with a score of 0 on VRS. At 1 month follow-up, there was a significant improvement in pain with a VRS score of 1. A 24-year male was diagnosed with mild COVID-19 who was on supportive treatment. He had no history of any significant medical illness but he was a chronic smoker. On 5 th day of his illness, he developed pin and needle sensations over both his upper and lower limbs. The pain severity was rated as 3 on VRS with a DN4 score of 5. There was no correlation of pain with postural change or activities. The symptom improved without any treatment over the next 2-3 days. At 1-month follow-up patient reported no pain with a score of zero on VRS. A 52-year male was diagnosed with severe COVID-19 and was on ceftriaxone, dexamethasone, and remdesivir along with supportive medications. He had a BMI of 27.1 kg/m 2 with a known history of type 2 diabetes mellitus. On the 8 th day of his illness, he developed new-onset pins and needles sensation in both of his hands along with the median nerve distribution, similar to that of carpal tunnel syndrome. There was an associated feeling of numbness & on examination hypoesthesia to touch was demonstrated. He rated his pain intensity as 6 on VRS and the DN4 score was rated 5. The patient also reported sleep impairment attributable to the pain symptoms. He was prescribed tab pregabalin 75 mg that was titrated up to 150 mg/day, along with amitriptyline 10 mg and methylcobalamin 1500 micrograms per day. At discharge, the VRS score was 4 with improvement in numbness. At the end of one month, the VRS score was 2/5 with reduced frequency of symptoms and improved sleep. A 62-year-old male with a history of hypertension and chronic kidney disease was diagnosed with severe COVID-19. His BMI was 21.3 kg/m2. On the 11 th day of his illness, he presented with burning sensations over his lower back and both the lower limbs with a severity rating of 8 walking few steps. The pain was associated with hypoesthesia to touch and the DN4 score was 4. He was started with tab pregabalin 75 mg along with methylcobalamin 1500 mcg per day. His pain improved over the next two weeks and at one month follow up there was significant relief in pain symptoms with a VRS score of 2 out of 10. In this study, NeuP was seen predominantly in the male population (7/8) and moderate to severe COVID-19 (6/8). The latter finding supports the fact that neurological symptoms are more common in severe COVID-19. The pain severity was predominantly mild to moderate (6/8) with a VRS score of 1-6. S v r N uP (VRS≄7) was pr s nt in only two patients. All patients responded to gabapentinoids with or without antidepressants supporting the neuropathic etiology of the pain symptoms. But it remains unclear if the improvement in NeuP was due to the anti-neuropathic pain medications, corticosteroids, or a synergistic effect of both. One important finding that needs special attention is the persistence of mild NeuP symptoms in 50 percent of patients at a one-month follow-up. In a study evaluating persistent neuropathic pain in COVID-19 patients, moderate to severe COVID-19, azithromycin intake and depression were identified as the associated factors. 8 The detailed demographic and pain characteristics of eight patients in this study are summarized in Tables 1 and 2. There are very few reports of incidence of NeuP among COVID-19 patients associated with or without other neurological complications. Aksan et al reported one case of a female in her forties who presented with intense burning pain during her COVID-19 illness. 9 The pain involved the neck and back from C1 to L4-L5 region, with an intensity rating of 7/10. Siepmann et al described a case of a 52-year-old man with neuralgic amyotrophy following SARS-CoV-2. 10 Another case of pure sensory neuralgic amyotrophy causing excruciating pain in the upper limb was reported by Cacciavillani et al. 11 In a more recent report, a 61year-old man developed intense burning pain involving whole body after a week of testing positive for SARS-CoV-2. 12 Much recently Berra et al reported a series of cases diagnosed with COVID-19 presenting with focal peripheral neuropathies. 13 Common peroneal neuropathy, sciatic neuropathy, ulnar neuropathy, brachial plexopathy and lumbosacral plexopathy are the commonly diagnosed conditions reported so far. [13] [14] Pain symptoms are the well-known clinical manifestation of SARS-CoV-2 but lesser is known about the incidence and characteristics of neuropathic pain caused by the virus. SARS-CoV-2 is known to cause neurological symptoms either by direct invasion of the nervous system or by virus-associated immune reactions. 15 Nevertheless, this study opens the door to further research focusing on NeuP characteristics on a wider population including their objective assessment. Furthermore, this study will guide health care workers in the early detection of such symptoms and their prompt management which may prevent the development of chronic pain. Neuropathic pain is a less frequent yet recognized manifestation of COVID-19. Considering the burden of COVID-19, we anticipate many patients infected with SARS-CoV-2 will develop NeuP during the acute stage of the disease. COVID-19 associated NeuP is mostly mild to moderate in severity and responds well to anti-neuropathic pain medications. Therefore, early diagnosis and proper management are of prior importance to prevent its persistence. If left untreated, the pain symptoms can persist in a substantial proportion of patients and prolong recovery thereby affecting the quality of life. Further prospective WHO. WHO Director-G n ral's op ning r marks at th m dia bri fing on Potential for increased prevalence of neuropathic pain after the COVID-19 pandemic Clinical characteristics of 30 medical workers infected with new coronavirus pneumonia Headache in patients with severe acute respiratory syndrome coronavirus 2 infection: a narrative review Strong associations and moderate predictive value of early symptoms for SARS-CoV-2 test positivity among healthcare workers Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China Ministry of Health and Family Welfare Characteristics and Risk Factors of Persistent Neuropathic Pain in Recovered COVID-19 Patients A COVID-19 patient with intense burning pain Neuralgic amyotrophy following infection with SARS-CoV-2 Pure sensory neuralgic amyotrophy in COVID-19 infection. Muscle Nerve Neuropathic pain post-COVID-19: a case report Unusual sensory-motor neuropathies in post Covid-19 patients admitted in rehabilitation hospitals: a case-series Focal Peripheral Neuropathies Observed in Patients Diagnosed With COVID-19 Neurologic features in severe SARS-CoV-2 infection Effects of COVID-19 on the nervous system evaluation is needed to delineate the prevalence, clinical characteristics, and persistence of NeuP among COVID-19 patients.