SARS-CoV-2 mitochondriopathy in COVID-19 pneumonia exacerbates hypoxemia.

RATIONALE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19 pneumonia. We hypothesize that SARS-CoV-2 causes alveolar injury and hypoxemia by damaging mitochondria in airway epithelial cells (AEC) and pulmonary artery smooth muscle cells (PASMC), triggering apoptosis and bioenergetic impairment, and impairing hypoxic pulmonary vasoconstriction (HPV), respectively. OBJECTIVES: We examined the effects of: A) human betacoronaviruses, SARS-CoV-2 and HCoV-OC43, and individual SARS-CoV-2 proteins on apoptosis, mitochondrial fission, and bioenergetics in AEC; and B) SARS-CoV-2 proteins and mouse hepatitis virus (MHV-1) infection on HPV. METHODS: We used transcriptomic data to identify temporal changes in mitochondrial-relevant gene ontology (GO) pathways post-SARS-CoV-2 infection. We also transduced AECs with SARS-CoV-2 proteins (M, Nsp7 or Nsp9) and determined effects on mitochondrial permeability transition pore (mPTP) activity, relative membrane potential, apoptosis, mitochondrial fission, and oxygen consumption rates (OCR). In human PASMC, we assessed the effects of SARS-CoV-2 proteins on hypoxic increases in cytosolic calcium, an HPV proxy. In MHV-1 pneumonia, we assessed HPV via cardiac catheterization and apoptosis using the TUNEL assay. RESULTS: SARS-CoV-2 regulated mitochondrial apoptosis, mitochondrial membrane permeabilization and electron transport chain (ETC) GO pathways within 2 hours of infection. SARS-CoV-2 downregulated ETC Complex I and ATP synthase genes, and upregulated apoptosis-inducing genes. SARS-CoV-2 and HCoV-OC43 upregulated and activated dynamin-related protein 1 (Drp1) and increased mitochondrial fission. SARS-CoV-2 and transduced SARS-CoV-2 proteins increased apoptosis inducing factor (AIF) expression and activated caspase 7, resulting in apoptosis. Coronaviruses also reduced OCR, decreased ETC Complex I activity and lowered ATP levels in AEC. M protein transduction also increased mPTP opening. In human PASMC, M and Nsp9 proteins inhibited HPV. In MHV-1 pneumonia, infected AEC displayed apoptosis and HPV was suppressed. BAY K8644, a calcium channel agonist, increased HPV and improved SpO2. CONCLUSIONS: Coronaviruses, including SARS-CoV-2, cause AEC apoptosis, mitochondrial fission, and bioenergetic impairment. SARS-CoV-2 also suppresses HPV by targeting mitochondria. This mitochondriopathy is replicated by transduction with SARS-CoV-2 proteins, indicating a mechanistic role for viral-host mitochondrial protein interactions. Mitochondriopathy is a conserved feature of coronaviral pneumonia that may exacerbate hypoxemia and constitutes a therapeutic target.

A protocol for longitudinal monitoring of individual building occupants and their environments.

Buildings account for approximately 40% of the energy consumption across the European Union, so there is a requirement to strive for better energy performance to reduce the global impact of urbanised societies. However, energy performant buildings can negatively impact building occupants (e.g., comfort, health and/or wellbeing) due to a trade-off between airtightness and air circulation. Thus, there is a need to monitor Indoor Environmental Quality (IEQ) to inform how it impacts occupants and hence redefine value within building performance metrics. An individualised study design would enable researchers to gain new insights into the effects of environmental changes on individuals for more targeted e.g., health interventions or nuanced and improved building design(s). This paper presents a protocol to conduct longitudinal monitoring of an individual and their immediate environment. Additionally, a novel approach to environmental perception gathering is proposed that will monitor environmental factors at an individual level to investigate subjective survey data pertaining to the participant's perceptions of IEQ (e.g., perceived air quality, thermal conditions, light, and noise). This protocol has the potential to expose time-differential phenomena between environmental changes and an individual's behavioural and physiological responses. This could be used to support building performance monitoring by providing an interventional assessment of building performance renovations. In the future it could also provide building scientists with a scalable approach for environmental monitoring that focuses specifically on individual health and wellbeing.

The impact and restoration of colorectal services during the coronavirus disease 2019 pandemic: A view from Oxford.

Aim: The coronavirus pandemic has significantly disrupted the way we deliver healthcare worldwide. We have been flexible and creative in order to continue providing elective colorectal cancer operations and to restart services for benign cases during the recovery period of the pandemic. In this paper, we describe the impact of coronavirus on our elective services and how we have implemented new patient pathways to allow us to continue providing patient care. Patients and Methods: Data on major colorectal elective resections were prospectively collected in an Enhanced Recovery After Surgery (ERAS) database. Data on the number of proctology cases and telemed appointments were collected from the hospital theatre information management system and electronic patient record system, respectively. Results: During the pandemic, there was a complete shift towards cancer cases, with benign services and proctology cases being placed on hold. Hospital length of stay was reduced. We implemented earlier hospital discharge and more intense telephone follow-up after elective major surgery. This has not resulted in an increase in postoperative complications, nor any increase in readmission to hospital. During the recovery phase, we have introduced a higher proportion of telemed consultations, including one-stop telemed proctology clinics, resulting in straight to tests or investigations. Conclusion: We have created a streamlined multidisciplinary pathway to reinstate our elective colorectal services as soon as possible and to minimise potential harm caused to patients whose treatment have been delayed. We anticipate many of these changes will be permanently incorporated into our clinical practice once the pandemic is over.

Maintaining Standards in Colorectal Cancer Surgery During the Global Pandemic: A Cohort Study.

AIM: Cancer surgery in the COVID-19 pandemic presents many new challenges. For each patient, the risk of contracting COVID-19 during the perioperative period, with the potential for life-threatening sequelae (1), has to be weighed against the risk of delaying treatment. We assessed the response and short-term outcomes from elective colorectal cancer surgery during the pandemic at our institution. METHOD: We report a prospective cohort study of all elective colorectal surgery cases performed at our Trust during the 11 weeks following the national UK lockdown on 23rd March 2020, compared with the same time period in 2019. RESULTS: Eighty-five colorectal operations were performed during the 2020 (COVID) time period, and 179 performed in the 2019 (non-COVID) time period. A significantly higher proportion of cases during the COVID period were cancer-related (66% vs 26%, p < 0.00001). There was no difference in length of hospital stay, complications or readmissions. There were no mortalities in either cohort. Among the cancer patients, there were no differences in TMN staging, R1 resection rate or lymph node yields. No elective patient tested positive for COVID-19 during the perioperative period. CONCLUSION: At the height of the COVID pandemic, we maintained delivery the of high-quality elective colorectal cancer surgery, with no worsening of short-term outcomes and no compromise in the quality of cancer resections. Ongoing monitoring of this cohort is essential. The risks associated with COVID-19 will continue for some time, necessitating adaptive responses to maintain high-quality cancer services.