Self-Isolation and Its Impact on Chronic Pain (preprint)

In an effort to mitigate the spread of COVID-19, New York City enforced a "shelter-in-place" order from March 20 to June 13, 2020. This study aims to explore the impact of self-isolation resulting from this order on individuals with chronic pain. The primary outcomes, assessed through the Brief Pain Inventory questionnaire, included self-rated pain scores and functional scores. A total of 65 participants completed the questionnaire during the quarantine period and again during the reopening phase from July 1 to August 31, 2020. While most self-rated pain scores showed no significant difference between the two periods, 24-Hour Worst Pain demonstrated improvement in the post-quarantine period (median 0; IQR [-1, 0]; p = 0.034). Notably, various functional scores, such as General Activity, Mood, Normal Work, Relations, Sleep, and Enjoyment of Life, exhibited substantial improvement post-quarantine, resulting in an overall functional score difference of -1.30 on average (p < 0.001). Despite stable self-rated pain scores, the study reveals a significant increase in disability during quarantine, possibly attributed to factors like fear, social isolation, and resource scarcity. The findings underscore the importance of holistic pain management considering psychosocial factors.

Mouse models of lung-specific SARS-CoV-2 infection with moderate pathological traits

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19) has been a global health concern since 2019. The viral spike protein infects the host by binding to angiotensin-converting enzyme 2 (ACE2) expressed on the cell surface, which is then processed by type II transmembrane serine protease. However, ACE2 does not react to SARS-CoV-2 in inbred wild-type mice, which poses a challenge for preclinical research with animal models, necessitating a human ACE2 (hACE2)-expressing transgenic mouse model. Cytokeratin 18 (K18) promoter-derived hACE2 transgenic mice [B6.Cg-Tg(K18-ACE2)2Prlmn/J] are widely used for research on SARS-CoV-1, MERS-CoV, and SARS-CoV-2. However, SARS-CoV-2 infection is lethal at ≥105 PFU and SARS-CoV-2 target cells are limited to type-1 alveolar pneumocytes in K18-hACE2 mice, making this model incompatible with infections in the human lung. Hence, we developed lung-specific SARS-CoV-2 infection mouse models with surfactant protein B (SFTPB) and secretoglobin family 1a member 1 (Scgb1a1) promoters. After inoculation of 105 PFU of SARS-CoV-2 to the K18-hACE2, SFTPB-hACE2, and SCGB1A1-hACE2 models, the peak viral titer was detected at 2 days post-infection and then gradually decreased. In K18-hACE2 mice, the body temperature decreased by approximately 10°C, body weight decreased by over 20%, and the survival rate was reduced. However, SFTPB-hACE2 and SCGB1A1-hACE2 mice showed minimal clinical signs after infection. The virus targeted type I pneumocytes in K18-hACE2 mice;type II pneumocytes in SFTPB-hACE2 mice;and club, goblet, and ciliated cells in SCGB1A1-hACE2 mice. A time-dependent increase in severe lung lesions was detected in K18-hACE2 mice, whereas mild lesions developed in SFTPB-hACE2 and SCGB1A1-hACE2 mice. Spleen, small intestine, and brain lesions developed in K18-hACE2 mice but not in SFTPB-hACE2 and SCGB1A1-hACE2 mice. These newly developed SFTPB-hACE2 and SCGB1A1-hACE2 mice should prove useful to expand research on hACE2-mediated respiratory viruses.