Decrease in Pain Perception During Acute SARS-CoV-2 Infection

A Case Series

Lisa Hentsch; Patrick Stancu; Gilles Allali; Karl-Olof Lövblad; Johannes A. Lobrinus; Sara Cocetta; Sophie Pautex; Marjolaine Uginet; Jacques Serratrice; Matteo Coen


Pain. 2022;163(6):1019-1022. 

In This Article


Patient 1

An 84-year-old man with a history of ischemic cardiopathy and a neuroendocrine carcinoma of unknown origin. Although the patient was suffering from chronic back pain, he lived alone and was independent in all activities of daily life. The pain started 2 months before hospitalization, was localized in his lumbar spine, and did not radiate to the lower limbs.

The patient was hospitalized on October 15, 2020, because of progressive asthenia, lower limb hypoesthesia, and new-onset urinary incontinence. On arrival, his back pain was evaluated at 8 of 10 on the Numerical Rating Scale (NRS). A CT scan showed lumbar spine stenosis at L3-L4 and medullary compression at D2 due to a perivertebral metastasis infiltrating the left root of D2 and associated with a pathological fracture of the vertebra. The patient was treated with oral paracetamol (1 g TID) and subcutaneous buprenorphine (0.2 mg TID), with suboptimal pain control. On day 4, he was tested positive for SARS-CoV-2 (reverse transcription polymerase chain reaction [RT-PCR] on a nasopharyngeal swab). On the same day, he reported pain disappearance (NRS score of 0/10). Surgery (C7-D4 fixation and D1-D2 laminectomy) was planned on day 5. In the postoperative phase, adequate pain control was obtained with paracetamol alone (1 gr TID PRN). Opioids (buprenorphine 0.2 mg TID PRN) were reintroduced 1 month later for the treatment of unspecific general discomfort. Pain scores however remained at 0 of 10 on the NRS. Unfortunately, the patient died of a probable inhalation pneumonia at the beginning of December 2020.

Patient 2

A 68-year-old man known for a multimetastatic (bone/lung/pleura/liver) thyroid carcinoma showing thymus-like differentiation (CASTLE) previously treated with surgery, radiotherapy, and chemotherapy; an adenocarcinoma of the prostate (Gleason 3 + 4 = 7); and a mixed type gastric adenocarcinoma, currently in remission. The patient suffered from painful bone metastases (fourth right rib and eighth left rib) treated with continuous and as-needed buprenorphine (87.5 μg/h by a transdermic patch and 0.2 mg PRN TID, respectively) with insufficient pain control (NRS score of 8/10 at rest).

He was hospitalized on November 18, 2020, because of fever and coughing. A first nasopharyngeal swab tested negative for SARS-CoV-2. On arrival his rib pain was noted at 7 of 10 on the NRS at rest. The buprenorphine patch was removed to introduce fast-acting, subcutaneous morphine. Opioid rotation was finally not necessary because the patient reported a spontaneous decrease of his pain score from 8 of 10 to 3 of 10. Neurological examination, including higher cortical functions, cranial nerves, sensory and motor testing, did not reveal any specific abnormalities. Furthermore, no signs of opioid withdrawal were observed.

Although the patient had progressively become pain free, respiratory deterioration (with desaturation and tachypnea) necessitated the introduction of morphine on day 2. He died on day 6. Autopsy revealed severe bacterial pneumonia as well as the presence of hyaline membranes and microscopic sites of organized pneumonia, compatible with a viral cause. SARS-CoV-2 RT-PCR in postmortem lung swabs was found positive. A detailed neuropathological examination was performed, with multiples samples for histology, including thalami and insular regions. Two small nonruptured saccular aneurisms were observed on the middle cerebral arteries, as well as focal loss of Purkinje cells in the cerebellum. No morphological lesions which could be related to SARS-CoV-2 infection were observed: no endotheliitis, no perivascular proteinaceous exudate, no microthrombi, no microbleeds, no ischemic lesions, no edema, and no lymphocytic infiltration.

Patient 3

A 67-year-old man known for chronic rectal pain due to an infiltration by a bladder carcinoma, and painful ophthalmoplegia (Tolosa–Hunt syndrome) of the left eye, treated with oxycodone–naloxone (25/12.5 mg BID), pregabalin (50 mg TID), and prednisone (50 mg SID). However, pain remained insufficiently controlled (NRS score of 8/10 at rest). Bladder cancer was treated with topotecan infusions.

On November 18, 2020, the patient developed symptoms compatible with a mild viral illness (cough and fatigue). Overall, he noticed that the intensity of his rectal pain improved significantly. Five days after the beginning of viral symptoms, the pain in his rectum had totally disappeared, including during defecation, which generally resulted in excruciating pain. Because of progressive worsening of respiratory symptoms and the onset of fever, he was finally hospitalized on December 1. Although the patient did not complain of dyspnea, room air saturation was 89%. A CT scan of the chest showed multiple infiltrates covering more than 25% of the lung surface. Reverse transcription polymerase chain reaction on a nasopharyngeal swab tested positive for SARS-CoV-2. At this point, he rated his pain at 0 of 10 on the NRS.

One week after admission, neurological examination revealed bradyphrenia, left visual neglect, left arm pyramidal weakness, and bilateral upper limb negative myoclonus. A brain MRI showed no vascular or neoplastic lesions; nevertheless, dedicated MRI wall imaging (T1 FS contrast-enhanced VISTA) highlighted bilateral vertebral artery gadolinium enhancement with a left predominance, a possible sign of SARS-CoV-2–mediated endotheliitis (Figure 1).[26]

Figure 1.

Cerebral MRI of Patient 3. Axial T1 FS contrast-enhanced MR wall imaging (VISTA) showed bilateral enhancement at the level of the vertebral arteries, with a left predominance. Left image: left vertebral artery enhancement predominance (arrow); right image: bilateral predominance (arrows).

The patient's evolution was characterized by the progressive onset of dyspnea (by December 12) accompanied by the reappearance of rectal pain that progressively returned to baseline (ie, before COVID-19) intensity, 19 days after having totally disappeared. Opioids had to be reintroduced. The patient succumbed to progressive respiratory failure at the beginning of January 2021.