Spinal cord injury (SCI) is often complicated by secondary injury as a result of the innate inflammatory response to tissue trauma and swelling. Previous studies have shown that excessive ATP release from peritraumatic regions contributes to the inflammatory response to SCI by activation of low-affinity P2X7 receptors. Because connexin hemichannels constitute an important route for astrocytic ATP release, we here evaluated the impact on post-traumatic ATP release of deletion of connexins (Cx30/Cx43) in astrocytes. In vivo bioluminescence imaging showed a significant reduction in ATP release after weight-drop injury in mice with deletion of Cx43 compared with Cx43-expressing littermates, both on a Cx30 knockout background. Moreover, astrogliosis and microglia activation were reduced in peritraumatic areas of those mice lacking Cx43; motor recovery was also significantly improved, and the traumatic lesion was smaller. Combined, these observations are consistent with a contribution by astrocytic hemichannels to post-traumatic ATP release that aggravates secondary injury and restrains functional recovery after experimental spinal cord injury. Connexins may thereby constitute a new therapeutic target in spinal cord injury.

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Pulmonary fibrosis (PF) is characterized by excessive deposition of extracellular matrix components and destruction of the pulmonary parenchyma. Studies have shown severe Coronavirus Disease 2019 can lead to PF with residual lung function abnormalities and fibrotic remodeling. As of today, there is no consensus on treatment for PF caused by COVID-19. We are reporting a case series of three post-COVID-19 PF patients treated with tapering prednisone. Case Series:Patient 1 is 52-year-old male presented to the clinic after a 3-month hospital course of COVID-19 requiring hyperbaric hood. He was discharged with 2L of home oxygen. The patient saturated at 95% at rest but desaturated to 70% on exertion. Chest X-ray (CXR) and CT thorax showed diffuse ground glass opacity with pulmonary fibrosis and scarring. Tapering prednisone from 40mg over 1 month was initiated. Follow-up visit after one month confirmed reduce home oxygen requirement. CXR also revealed mild improvement in interstitial infiltrates. Patient 2 is a 56-year-old male hospitalized 2 months ago for COVID-19 where he required non-rebreather mask for oxygen supply. In the office, he complained of shortness of breath on exertion. CXR showed diffuse bilateral airspace opacities and thickened interstitial lung markings. Pulmonary function test (PFT) revealed moderate restrictive pattern with reduced lung volumes. He was sent home with a course of tapering prednisone over 1 month and weekly office follow up. His symptoms improved. Repeat CXR showed improving bilateral diffuse reticular markings. Repeat PFT improved to mild restrictive lung pattern. Patient 3 is a 70-year-old male hospitalized for 1 moth for COVID-19 requiring face mask with recent discharge on 4L home oxygen. After 2 weeks of hospital discharge, the patient still required 2L of oxygen at home. CXR showed streaky lung opacities predominantly in the left lower lung field. The patient was started on tapering prednisone. At 2-month follow-up, he admitted clinical improvement of symptoms and was able to titrate off home oxygen at rest. Repeat CXR also showed improvement of streaky opacity in the left mid/lower lung. Discussion:No evidence-based treatment is available for post-COVID-19 PF. Corticosteroid is used for treatment of acute exacerbation of other forms of PF by decreasing inflammation in the lungs, and therefore may improve symptoms of post-COVID-19 PF. Our patients received 1-month course of tapering prednisone treatment showed mild clinical improvement with no major adverse effect. Further clinical trials should address the utility and risks of corticosteroid in post-COVID-19 PF.

Background Renal involvement in COVID-19 leads to severe disease and higher mortality. We study renal parameters in COVID-19 patients and their association with mortality and length of stay in hospital. Methods A retrospective study (n=340) of confirmed COVID-19 patients with renal involvement determined by the presence of acute kidney injury. Multivariate analyses of logistic regression for mortality and linear regression for length of stay (LOS) adjusted for relevant demographic, comorbidity, disease severity, and treatment covariates. Results Mortality was 54.4% and mean LOS was 12.9 days. For mortality, creatinine peak (OR:35.27, 95% CI:2.81, 442.06, p<0.01) and persistent renal involvement at discharge (OR:4.47, 95% CI:1.99,10.06, p<0.001) were each significantly associated with increased odds for mortality. Increased blood urea nitrogen peak (OR:0.98, 95%CI:0.97,0.996, p<0.05) was significantly associated with decreased odds for mortality. For LOS, increased blood urea nitrogen peak (B:0.001, SE:<0.001, p<0.01), renal replacement therapy (B:0.19, SE:0.06, p<0.01), and increased days to acute kidney injury (B:0.19, SE:0.05, p<0.001) were each significantly associated with increased length of stay. Conclusion Our study emphasizes the importance in identifying renal involvement parameters in COVID-19 patients. These parameters are associated with LOS and mortality, and may assist clinicians to prognosticate COVID-19 patients with renal involvement.

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