Authors: Yu Dong, Huang Wenqi, Zhan Yongzhong, Xiao Guanhua, Li Jing, Tong Wancheng, Cai Shaoxi, Liu Laiyu
Affiliation: Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University
Cite this article: Yu Dong, Huang Wenqi, Zhan Yongzhong, et al. Diaphragmatic dysfunction after novel coronavirus infection: 2 cases [J] . Chinese Journal of Tuberculosis and Respiration, 2024, 47(3) : 244-248. DOI: 10.3760/cma.j.cn112147-20230825-00106.
summary
With the new coronavirus infection after the pandemic, the complications and long-term sequelae caused by the new coronavirus plague many patients, among which dyspnea is more common, and a few cases have been reported abroad are caused by diaphragm dysfunction after new coronavirus infection, but there are no relevant reports in China. In this paper, two patients with dyspnea after new coronavirus infection were reported to have diaphragmatic dysfunction through dynamic chest X-ray after admission, and the causes of diaphragmatic nerve and diaphragmatic lesions caused by new coronavirus infection were finally determined after further improvement of diaphragm ultrasound, neuroelectrophysiological examination, transdiaphragmatic pressure measurement, brain MRI, and antibody detection of autoimmune diseases. After treatment, the symptoms of both patients improved. This article summarizes and analyzes the diagnosis and treatment of this disease based on the review of relevant literature, aiming to improve clinicians' understanding of the diagnosis and treatment of this disease.
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Case 1 The patient, a 77-year-old male, was admitted to the hospital on February 21, 2023 with "chest tightness and shortness of breath for more than 1 month". The patient was infected with the new coronavirus (mild) in early January 2023, did not receive antiviral treatment, and still had chest tightness and shortness of breath after recovery, which worsened after activity and eating, and it was difficult to leave the room for activities, accompanied by awakening at night, abdominal distension after eating, and no discomfort such as low-grade fever, night sweats, and chest pain. The patient has been present to the local hospital several times, and there are few signs of chronic inflammation on chest CT. After anti-infection, tiotropium bromide inhalation, traditional Chinese medicine and other treatments (the details are unknown), the symptoms were not significantly relieved. The patient had a history of hypertension for 8 years and was treated with oral nifedipine antihypertensive therapy. Family history is unremarkable. Physical examination on admission: stable vital signs, clear breath sounds in both lungs, no dry and wet rales, no pleural friction rub, no abnormalities in the heart and abdomen, and no edema in both lower limbs. Modified Medical Research Council (mMRC): Grade 4. Arterial blood gas analysis showed that the pH value was 7.428, the PaO2 was 93.75 mmHg (1 mmHg=0.133 kPa), the PaCO2 was 32.93 mmHg, the HCO3- was 21.40 mmol/L, the OI was 446 mmHg, the MYO was 73.38 μg/L, the CK-MBm was 2.41 μg/L, the CK was 133 U/L, and the CRP was 2.12 mg/L. There were no obvious abnormalities in blood routine, liver function, renal function, blood electrolytes, thyroid function, coagulation function, D-dimer, tumor markers, fungal D-glucan, sputum culture, cardiac enzyme spectrum, Pro-BNP, and a full set of autoantibodies. Pulmonary ventilation and diffusion function were basically normal (VC 3.88 L, FVC 3.88 L, FEV1 3.09 L, FEV1 % predicted value: 130.4%, FEV1/FVC: 79.68%). FENO is 13 ppb. Chest x-ray showed no abnormalities. There was no pulmonary embolism in pulmonary artery CTA (CTPA), and a few manifestations of chronic inflammation in the posterior basal segment of the right lower lobe were seen. Dynamic Chest Radiation (DCR) showed lower than normal diaphragm mobility (calm breathing diaphragm mobility of 8.40 mm on the right and 11.60 mm on the left on 21 February 2023; diaphragmatic mobility on the right side was 19.60 mm on the right side and 34.40 mm on the left side) and poor ventilation (39% of the lungs were gray areas in both lungs), as shown in Figs. 1, 2, 3. Further ultrasonography of the diaphragm showed that bilateral diaphragm thickness was thin (mainly on the right side) and the bilateral diaphragm thickening rate was increased [diaphragm thickness (calm breathing): 0.16 cm on the right side, 0.19 cm on the left side; diaphragm thickening rate (end-inspiratory to end-expiratory thickness)/end-expiratory thickness: 125% on the right side, 109% on the left side]. The neurological examination showed that there was no ptosis of the upper eyelids, slight hoarseness, poor bilateral soft palate elevation, no atrophy of the tongue muscles, normal muscle strength and muscle tone of the limbs, and a positive fatigue test. Electromyography showed a low occurrence of F waves in the right median nerve and suspiciously positive bilateral accessory nerve repetition test. Myasthenia gravis antibodies were negative, and MRI of the cervical spine and head was unremarkable. Neuromuscular junction lesion is considered after consultation with neurology: myasthenia gravis (antibody negative). Diagnostic administration of bromopyristinemine (60 mg/dose, 4 times daily) showed improvement in symptoms. The fatigue test turned negative. Chest tightness, shortness of breath and awakening at night improve, activity endurance increases, and you can go out for a walk. mMRC: Level 2. Repeat ambulatory chest x-ray showed diaphragmatic mobility and pulmonary ventilation improved before and he was discharged from the hospital (diaphragmatic mobility for calm breathing on March 13, 2023, 13.20 mm on the right and 14.00 mm on the left; diaphragmatic mobility for maximum breathing, 16.00 mm on the right and 26.80 mm on the left; pulmonary ventilation scintigraphy: gray areas in both lungs accounted for 28% of both lungs, see Figs. 4, 5, 6). After 3 months of discharge, the patient's chest tightness and shortness of breath symptoms were completely relieved, neostigmine was discontinued, the condition did not recur, and the patient was able to work and live normally.
Fig.1 Patient 1's ambulatory chest X-ray (February 21, 2023) showed calm breathing, diaphragm mobility was 8.40 mm on the right and 11.60 mm on the leftFig.2 Patient 1's ambulatory chest X-ray (Feb. 21, 2023) showed exertion-effort diaphragm mobility, 19.60 mm on the right and 34.40 mm on the leftFig. 3 Ambulatory chest X-ray (Feb. 21, 2023) on ambulatory chest x-ray of patient 1 showed lung ventilation on the gray area of both lungs, accounting for 39% of both lungs, Fig. 4 Patient 1: Ambulatory chest X-ray (March 13, 2023) showed calm breathing, diaphragm mobility of 13.20 mm on the right and 14.00 mm on the leftFig. 5 Patient 1 showed ambulatory chest X-ray (March 13, 2023), diaphragm mobility of 16.00 mm on the right and 26.80 mm on the left
Fig.6 Patient 1: Ambulatory chest X-ray (March 13, 2023) showed that the gray area of both lungs accounted for 28% of both lungs on lung ventilation scintigraphy
Case 2 A 57-year-old female was admitted to the hospital on February 27, 2023 due to "chest tightness and shortness of breath for more than 3 months". The patient was infected with the new coronavirus (mild) in November 2022 without antiviral treatment, and continued to experience chest tightness and shortness of breath after recovery, without low-grade fever, night sweats, chest pain, hemoptysis and other discomforts. 1 month ago, the patient's shortness of breath worsened, manifested as chest tightness and shortness of breath when lying flat and when walking briskly, which improved after sitting and resting. There is nothing special about the past. Family history is unremarkable. Physical examination on admission: stable vital signs, oxygen saturation of 95% in sitting position, 80% oxygen saturation in supine position, weak breath sounds in both lungs, no dry and wet rales, no abnormalities in the heart and abdomen, and no edema in both lower limbs. mMRC: Level 3. The :p H value of the admitted arterial blood gas (lying position) was 7.44, PaO2 was 49 mmHg, PaCO2 was 44 mmHg, HCO3- was 29.9 mmol/L, OI was 233 mmHg(↓), CRP was 0.14 mg/L, ProCT was 0.031 μg/L, blood count, electrolytes, D-dimer, total IgE, respiratory tract infection pathogen IgM9 items, fungal D-glucan, sputum culture, cardiac enzyme profile, Pro-BNP, The test results of the full set of autoantibodies were not significantly abnormal. The patient's pulmonary function test showed severe mixed ventilatory dysfunction, VC was 1.24 L, FVC was 1.24 L, FEV1 was 0.86 L, FEV1 accounted for 39.1% of the predicted value, FEV1/FVC was 69.13%, and the diastolic test was negative (-), and the pulmonary diffusion function test could not be completed. FENO is 13 ppb. Chest x-ray shows left diaphragm elevation and partial consolidation with atelectasis, as shown in Figure 7. No pulmonary embolism was found in CTPA (prone position—changed to prone position due to inability to lie flat), and multiple inflammation of the lower lung base and partial consolidation with atelectasis were seen, as shown in Figure 8. Ambulatory chest x-ray showed lower than normal diaphragm mobility (13.2 mm on the right and 9.6 mm on the left on 28 February 2023; 36.8 mm on the right and 24.8 mm on the left) on 28 February 2023, see Figures 9, 10, 11. Diaphragm ultrasound showed that there was no obvious abnormality in the thickness of the diaphragm on both sides (0.25 cm on the right side and 0.24 cm on the left side of the calm breathing thickness), no obvious abnormality in the right diaphragm amplitude measurement, and low on the left diaphragm (1.8 cm on the right side and 0.8 cm on the left side of calm breathing). Neurophysiological examination showed that the sensory nerve action potential (SNAP) amplitude of the left median nerve sensory nerve was reduced, the sensory nerve conduction velocity (SCV) was slowed, the left median nerve was damaged, the latent period of the left phrenic nerve terminal was prolonged compared with the contralateral side, and the compound muscle action potential (compound muscle action). potential, CMAP) amplitude is reduced, the left phrenic nerve is damaged, and the right side is normal. Transdiaphragmatic pressure measurement showed that the maximal inspiratory diaphragm myoelectric electromyography decreased, and the bilateral phrenic nerve action potential and tremor transdiaphragmatic pressure could not be significantly elicited. Myasthenia gravis and idiopathic inflammatory myopathy are all negative for antibodies. After admission, the patient was given anti-infective therapy, pulmonary function rehabilitation training, bronchodilator nebulized inhalation therapy, and high-flow oxygen inhalation, but the patient's dyspnea did not improve significantly. Based on the above results, we considered that for phrenic nerve and diaphragm lesions caused by novel coronavirus infection, the patient's dyspnea when lying down was significantly improved after intravenous infusion of methylprednisolone sodium succinate (40 mg/d), gamma globulin (20 g/d), vegetative nerves, nocturnal non-invasive ventilation, and continuous positive airway pressure (CPAP) therapy, and the patient's dyspnea was significantly improved when lying down, and the oxygen saturation was 92%. mMRC: Level 1. Dynamic chest x-ray showed an increase in diaphragmatic mobility on the left side of calm breathing (12.8 mm on the right side and 10.4 mm on the left side of the diaphragm on 21 March 2023; diaphragmatic mobility on the right side and 20.8 mm on the left side of the diaphragm on exerted breathing; gray areas in both lungs accounted for 12% of both lungs on pulmonary ventilation scintigraph, Figs. 12, 13, 14). After 1 week of discharge, the patient was able to lie down and breathe normally, and the dynamic chest X-ray showed that the movement of the left diaphragm was increased compared with before, and the lung ventilation was improved (diaphragmatic mobility of calm breathing, 15.6 mm on the right side and 13.6 mm on the left side; breathing with all his might, 26.4 mm on the right side and 31.2 mm on the left side; the gray area of both lungs on lung ventilation imaging accounted for 10% of both lungs), as shown in Figs. 15, 16, 17).
Fig.7 Chest X-ray (February 28, 2023) showed left diaphragm elevation in patient 2
Fig. 8 Contrast-enhanced CT of the lungs of case 2 (March 1, 2023) showed no pulmonary embolism, multiple inflammation of the lower lung base, and partial consolidation with atelectasis
Fig. 9 Patient 2 showed ambulatory chest X-ray (February 28, 2023) showing calm breathing, diaphragm mobility of 13.2 mm on the right side and 9.6 mm on the left side
Fig. 10 Patient 2 on ambulatory chest X-ray (February 28, 2023) showed that the diaphragm mobility was 36.8 mm on the right side and 24.8 mm on the left side
Fig.11 Patient 2: Dynamic chest X-ray (February 28, 2023) showed that the gray area of both lungs accounted for 6.8% of both lungs on lung ventilation scintigraph.
Fig. 12 Patients with 2 patients on ambulatory chest X-ray (March 21, 2023) showed calm breathing, diaphragm mobility of 12.8 mm on the right side and 10.4 mm on the left side
Fig. 13 Patient 2 had a dynamic chest X-ray (March 21, 2023) showing that the diaphragm mobility was 24.8 mm on the right side and 20.8 mm on the left side
Fig. 14 Patient 2 on ambulatory chest X-ray (March 21, 2023) showed that the gray area of both lungs accounted for 12% of both lungs
Fig. 15 Patient 2 had ambulatory chest X-ray (March 30, 2023) showing calm breathing, diaphragm mobility of 15.6 mm on the right and 13.6 mm on the left
Fig. 16 Patients 2 showed ambulatory chest X-ray (March 30, 2023) showing that the diaphragm mobility was 26.4 mm on the right side and 31.2 mm on the left side
Fig. 17 Patient 2: Dynamic chest X-ray (March 30, 2023) showed that the gray area of both lungs accounted for 10% of both lungs on lung ventilation scintigraph.
discuss
The World Health Organization (WHO) defines post-COVID symptoms as new symptoms that persist or develop progressively within 3 months of infection with the novel coronavirus that persist for more than 2 months and cannot be explained by other causes [1]. It is estimated that 80 percent of patients with COVID-19 infection develop one or more long-term symptoms after recovery, and dyspnea is a common clinical complaint [2]. Any condition that affects phrenic nerve transmission or diaphragmatic function may result in diaphragmatic dysfunction [3]. Studies have shown that the novel coronavirus can damage the nervous and muscular systems, leading to loss of smell, dysgeusia, Guillain-Barré syndrome (GBS), myasthenia gravis, myositis, myalgia, rhabdomyolysis, muscle atrophy, and critical myopathy [4, 5, 6, 7]. As a result, diaphragm dysfunction is also common during hospitalization in critically ill patients. According to the results of the study [8, 9, 10, 11, 12, 13, 14, 15, 16], persistent respiratory symptoms after recovery in patients with COVID-19 are associated with diaphragm dysfunction. A prospective study [8] found that among 132 patients with persistent respiratory symptoms 3~4 months after COVID-19 infection, 13 patients developed diaphragm dysfunction. Another study [14] included 10 patients who had been admitted to the intensive care unit (ICU) for COVID-19 and ARDS, and found that six patients with persistent dyspnea had impaired diaphragm function one year after discharge. Regmi et al. [15] included 50 patients who had been discharged 15 months after they had been hospitalized for COVID-19 and found that about two-thirds had moderate or severe dyspnea and was significantly associated with significant impairment of transdiaphragmatic pressure. Published case reports include phrenic nerve damage, diaphragmatic paralysis, Guillain-Barré syndrome, myasthenia gravis, and low testosterone levels [17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29] that are distinct from previously common causes (eg, sepsis, mechanical ventilation, medications) [30, 31]. The two cases reported in this article were both mild cases of new coronavirus infection, and did not receive mechanical ventilation and corticosteroids, so common causes were ruled out, and one case was finally diagnosed as myasthenia gravis caused by new coronavirus infection, and the other case was phrenic nerve and diaphragm lesions caused by new coronavirus infection. Moreover, after targeted treatment, the symptoms of the two patients gradually improved. Current traditional tests to assess diaphragmatic function include transdiaphragmatic pressure measurement, diaphragmatic ultrasound, and pulmonary function tests [32, 33]. However, because transdiaphragmatic pressure measurement is an invasive procedure and neuroelectrophysiological examination is an unconventional examination, the above examination methods are not easy to carry out and popularize. Dynamic chest x-ray is a good candidate for diagnosing diaphragmatic dysfunction by taking continuous images of the chest during movement in real time and clearly identifying contradictory diaphragmatic movements [34], and the results are consistent with standard fluoroscopy or ultrasonography. Treatment of diaphragm dysfunction after novel coronavirus infection is mainly focused on the cause and symptoms, and the primary disease causing diaphragm dysfunction, such as myasthenia gravis and polyneuropathy caused by novel coronavirus infection, should be treated first, and targeted treatments such as neostigmine, corticosteroids, intravenous immunoglobulin, and plasma exchange should be used [17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29]. If the cause is unknown, corticosteroids, nutritional neuromuscular therapy, and early rehabilitation and respiratory muscle training may be used empirically to improve diaphragmatic function [35, 36, 37, 38, 39]. In addition, treatments such as non-invasive positive pressure ventilation, diaphragm plication, and diaphragm pacing are available. After the coronavirus infects the phrenic nerve or diaphragm, it takes time for neuromuscular damage to recover. Recovery of diaphragm function has been found to take up to three years, with an average recovery time of 14.9 months [40]. Of the 13 cases reported, only 74% of patients improved after treatment. When clinicians encounter dyspnea after unexplained new coronavirus infection, they can use dynamic chest X-ray, diaphragm ultrasound, etc. to screen for diaphragm dysfunction to avoid missed diagnosis and misdiagnosis.
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