A Review of Persistent Post-COVID Syndrome (PPCS).

Persistent post-COVID syndrome, also referred to as long COVID, is a pathologic entity, which involves persistent physical, medical, and cognitive sequelae following COVID-19, including persistent immunosuppression as well as pulmonary, cardiac, and vascular fibrosis. Pathologic fibrosis of organs and vasculature leads to increased mortality and severely worsened quality of life. Inhibiting transforming growth factor beta (TGF-ß), an immuno- and a fibrosis modulator, may attenuate these post-COVID sequelae. Current preclinical and clinical efforts are centered on the mechanisms and manifestations of COVID-19 and its presymptomatic and prodromal periods; by comparison, the postdrome, which occurs in the aftermath of COVID-19, which we refer to as persistent post-COVID-syndrome, has received little attention. Potential long-term effects from post-COVID syndrome will assume increasing importance as a surge of treated patients are discharged from the hospital, placing a burden on healthcare systems, patients' families, and society in general to care for these medically devastated COVID-19 survivors. This review explores underlying mechanisms and possible manifestations of persistent post-COVID syndrome, and presents a framework of strategies for the diagnosis and management of patients with suspected or confirmed persistent post-COVID syndrome.

Remdesivir and Mortality in Patients With Coronavirus Disease 2019.

BACKGROUND: The impact of remdesivir (RDV) on mortality rates in coronavirus disease 2019 (COVID-19) is controversial, and the mortality effect in subgroups of baseline disease severity has been incompletely explored. The purpose of this study was to assess the association of RDV with mortality rates in patients with COVID-19. METHODS: In this retrospective cohort study we compared persons receiving RDV with those receiving best supportive care (BSC). Patients hospitalized between 28 February and 28 May 2020 with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection were included with the development of COVID-19 pneumonia on chest radiography and hypoxia requiring supplemental oxygen or oxygen saturation ≤94% with room air. The primary outcome was overall survival, assessed with time-dependent Cox proportional hazards regression and multivariable adjustment, including calendar time, baseline patient characteristics, corticosteroid use, and random effects for hospital. RESULTS: A total of 1138 patients were enrolled, including 286 who received RDV and 852 treated with BSC, 400 of whom received hydroxychloroquine. Corticosteroids were used in 20.4% of the cohort (12.6% in RDV and 23% in BSC). Comparing persons receiving RDV with those receiving BSC, the hazard ratio (95% confidence interval) for death was 0.46 (.31-.69) in the univariate model (P < .001) and 0.60 (.40-.90) in the risk-adjusted model (P = .01). In the subgroup of persons with baseline use of low-flow oxygen, the hazard ratio (95% confidence interval) for death in RDV compared with BSC was 0.63 (.39-1.00; P = .049). CONCLUSION: Treatment with RDV was associated with lower mortality rates than BSC. These findings remain the same in the subgroup with baseline use of low-flow oxygen.

Lung epithelial and endothelial damage, loss of tissue repair, inhibition of fibrinolysis, and cellular senescence in fatal COVID-19.

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is characterized by respiratory distress, multiorgan dysfunction, and, in some cases, death. The pathological mechanisms underlying COVID-19 respiratory distress and the interplay with aggravating risk factors have not been fully defined. Lung autopsy samples from 18 patients with fatal COVID-19, with symptom onset-to-death times ranging from 3 to 47 days, and antemortem plasma samples from 6 of these cases were evaluated using deep sequencing of SARS-CoV-2 RNA, multiplex plasma protein measurements, and pulmonary gene expression and imaging analyses. Prominent histopathological features in this case series included progressive diffuse alveolar damage with excessive thrombosis and late-onset pulmonary tissue and vascular remodeling. Acute damage at the alveolar-capillary barrier was characterized by the loss of surfactant protein expression with injury to alveolar epithelial cells, endothelial cells, respiratory epithelial basal cells, and defective tissue repair processes. Other key findings included impaired clot fibrinolysis with increased concentrations of plasma and lung plasminogen activator inhibitor-1 and modulation of cellular senescence markers, including p21 and sirtuin-1, in both lung epithelial and endothelial cells. Together, these findings further define the molecular pathological features underlying the pulmonary response to SARS-CoV-2 infection and provide important insights into signaling pathways that may be amenable to therapeutic intervention.

Correction to: Mesenchymal stem cells in the treatment of severe COVID-19.

[This corrects the article DOI: 10.1186/s41231-021-00095-0.].

Streamlining brain tumor surgery care during the COVID-19 pandemic: A case-control study.

BACKGROUND: The COVID-19 pandemic forced a reconsideration of surgical patient management in the setting of scarce resources and risk of viral transmission. Herein we assess the impact of implementing a protocol of more rigorous patient education, recovery room assessment for non-ICU admission, earlier mobilization and post-discharge communication for patients undergoing brain tumor surgery. METHODS: A case-control retrospective review was undertaken at a community hospital with a dedicated neurosurgery and otolaryngology team using minimally invasive surgical techniques, total intravenous anesthesia (TIVA) and early post-operative imaging protocols. All patients undergoing craniotomy or endoscopic endonasal removal of a brain, skull base or pituitary tumor were included during two non-overlapping periods: March 2019-January 2020 (pre-pandemic epoch) versus March 2020-January 2021 (pandemic epoch with streamlined care protocol implemented). Data collection included demographics, preoperative American Society of Anesthesiologists (ASA) status, tumor pathology, and tumor resection and remission rates. Primary outcomes were ICU utilization and hospital length of stay (LOS). Secondary outcomes were complications, readmissions and reoperations. FINDINGS: Of 295 patients, 163 patients were treated pre-pandemic (58% women, mean age 53.2±16 years) and 132 were treated during the pandemic (52% women, mean age 52.3±17 years). From pre-pandemic to pandemic, ICU utilization decreased from 92(54%) to 43(29%) of operations (p<0.001) and hospital LOS≤1 day increased from 21(12.2%) to 60(41.4%), p<0.001, respectively. For craniotomy cohort, median LOS was 2 days for both epochs; median ICU LOS decreased from 1 to 0 days (p<0.001), ICU use decreased from 73(80%) to 29(33%),(p<0.001). For endonasal cohort, median LOS decreased from 2 to 1 days; median ICU LOS was 0 days for both epochs; (p<0.001). There were no differences pre-pandemic versus pandemic in ASA scores, resection/remission rates, readmissions or reoperations. CONCLUSION: This experience suggests the COVID-19 pandemic provided an opportunity for implementing a brain tumor care protocol to facilitate safely decreasing ICU utilization and accelerating discharge home without an increase in complications, readmission or reoperations. More rigorous patient education, recovery room assessment for non-ICU admission, earlier mobilization and post-discharge communication, layered upon a foundation of minimally invasive surgery, TIVA anesthesia and early post-operative imaging are possible contributors to these favorable trends.

COVID-19 and cancer: A guide with suggested COVID-19 rule-out criteria to support clinical decision-making.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly contagious zoonotic pathogen that has exacted heavy public health, social and economic tolls. In February 2020, the World Health Organization acronymed the disease caused by SARS-CoV-2 as COVID-19, for coronavirus disease 2019. The number of confirmed COVID-19 infections, which has been detected in at least 103 countries, has reached 1,970,225 worldwide as of April 14, 2020 with 124,544 deaths, according to the U.S. Centers for Disease Control and Prevention (CDC). Many cases of COVID-19 resolve quickly. However, the disease, which, like other respiratory pathogens that cause common cold symptoms is believed to be transmitted through respiratory droplets. Infection with COVID-19 can also lead to significant morbidity and death; this is particularly the case for cancer patients. Moreover, because the signs and symptoms of COVID-19 are easily misattributed to the sequelae of cancer itself, such as pulmonary embolism, or its treatment, such as nausea and diarrhea, diagnosis may be delayed or missed. Potential COVID-19 rule out criteria, based on the Wells' criteria for pulmonary embolism, another protean disease entity, are provided as a decision-making aid. This review summarizes the current understanding of the transmission, clinical presentation, diagnosis and differential diagnosis, pathogenesis, rationale to treat the cancer or not, treatment and prevention of COVID-19 with an emphasis on implications in cancer.