The main characteristics of mechanically ventilated ARDS patients affected with COVID-19, and the adherence to lung-protective ventilation strategies are not well known. We describe characteristics and outcomes of confirmed ARDS in COVID-19 patients managed with invasive mechanical ventilation (MV). Methods: This is a multicenter, prospective, observational study in consecutive, mechanically ventilated patients with ARDS (as defined by the Berlin criteria) affected with with COVID-19 (confirmed SARS-CoV-2 infection in nasal or pharyngeal swab specimens), admitted to a network of 36 Spanish and Andorran intensive care units (ICUs) between March 12 and June 1, 2020. We examined the clinical features, ventilatory management, and clinical outcomes of COVID-19 ARDS patients, and compared some results with other relevant studies in non-COVID-19 ARDS patients. Results: A total of 742 patients were analysed with complete 28-day outcome data: 128 (17.1%) with mild, 331 (44.6%) with moderate, and 283 (38.1%) with severe ARDS. At baseline, defined as the first day on invasive MV, median (IQR) values were: tidal volume 6.9 (6.3-7.8) ml/kg predicted body weight, positive end-expiratory pressure 12 (11-14) cmH 2 O. Values of respiratory system compliance 35 (27-45) ml/cmH 2 O, plateau pressure 25 (22-29) cmH 2 O, and driving pressure 12 (10-16) cmH 2 O were similar to values from non-COVID-19 ARDS patients observed in other studies. Recruitment maneuvers, prone position and neuromuscular blocking agents were used in 79%, 76% and 72% of patients, respectively. The risk of 28-day mortality was lower in mild ARDS [hazard ratio (RR) 0.56 (95% CI 0.33-0.93), p = 0.026] and moderate ARDS [hazard ratio (RR) 0.69 (95% CI 0.47-0.97), p = 0.035] when compared to severe ARDS. The 28-day mortality was similar to other observational studies in non-COVID-19 ARDS patients. Conclusions: In this large series, COVID-19 ARDS patients have features similar to other causes of ARDS, compliance with lung-protective ventilation was high, and the risk of 28-day mortality increased with the degree of ARDS severity.

Background Awake prone positioning (awake-PP) in non-intubated coronavirus disease 2019 (COVID-19) patients could avoid endotracheal intubation, reduce the use of critical care resources, and improve survival. We aimed to examine whether the combination of high-flow nasal oxygen therapy (HFNO) with awake-PP prevents the need for intubation when compared to HFNO alone. Methods Prospective, multicenter, adjusted observational cohort study in consecutive COVID-19 patients with acute respiratory failure (ARF) receiving respiratory support with HFNO from 12 March to 9 June 2020. Patients were classified as HFNO with or without awake-PP. Logistic models were fitted to predict treatment at baseline using the following variables: age, sex, obesity, non-respiratory Sequential Organ Failure Assessment score, APACHE-II, C-reactive protein, days from symptoms onset to HFNO initiation, respiratory rate, and peripheral oxyhemoglobin saturation. We compared data on demographics, vital signs, laboratory markers, need for invasive mechanical ventilation, days to intubation, ICU length of stay, and ICU mortality between HFNO patients with and without awake-PP. Results A total of 1076 patients with COVID-19 ARF were admitted, of which 199 patients received HFNO and were analyzed. Fifty-five (27.6%) were pronated during HFNO; 60 (41%) and 22 (40%) patients from the HFNO and HFNO + awake-PP groups were intubated. The use of awake-PP as an adjunctive therapy to HFNO did not reduce the risk of intubation [RR 0.87 (95% CI 0.53–1.43), p = 0.60]. Patients treated with HFNO + awake-PP showed a trend for delay in intubation compared to HFNO alone [median 1 (interquartile range, IQR 1.0–2.5) vs 2 IQR 1.0–3.0] days (p = 0.055), but awake-PP did not affect 28-day mortality [RR 1.04 (95% CI 0.40–2.72), p = 0.92]. Conclusion In patients with COVID-19 ARF treated with HFNO, the use of awake-PP did not reduce the need for intubation or affect mortality.

Our work demonstrates for the first time a direct association between infection with herpes simplex virus 1, a ubiquitous human pathogen generally associated with facial cold sores, and multifocal brain demyelination in an otherwise normal host, the cotton rat Sigmodon hispidus. For a long time, demyelinating diseases were considered to be autoimmune in nature and were studied by indirect methods, such as immunizing animals with myelin components or feeding them toxic substances that induce demyelination. Treatment against demyelinating diseases has been elusive, partially because of their unknown etiology. This work provides the first experimental evidence for the role of HSV-1 as the etiologic agent of multifocal brain demyelination in a normal host and suggests that vaccination against HSV-1 can help to combat demyelinating disorders.

Heterogeneity of COVID-19 manifestations in human population is vast, for reasons unknown. Cotton rats are a clinically relevant small animal model of human respiratory viral infections. Here, we demonstrate for the first time that SARS-CoV-2 infection in cotton rats affects multiple organs and systems, targeting species- and age-specific biological processes. Infection of S. fulviventer, which developed a neutralizing antibody response and were more susceptible to SARS-CoV-2 replication in the upper respiratory tract, was accompanied by hyperplasia of lacrimal drainage-associated lymphoid tissue (LDALT), a first known report of mucosa-associated lymphoid tissue activation at the portal of SARS-CoV-2 entry. Although less permissive to viral replication, S. hispidus showed hyperplasia of bone marrow in the facial bones and increased pulmonary thrombosis in aged males. Augmentation of these features by SARS-CoV-2 infection suggests a virus-induced breach in regulatory mechanisms which could be devastating for people of all ages with underlying conditions and in particular for elderly with a multitude of ongoing disorders.

Although HSV-1 has been implicated in facial palsy for a long time, testing and treating for HSV is not routine. The lack of a meaningful demonstration of how HSV-1 would cause facial palsy has limited progress in this field. Herein we demonstrate that the depth of the lip HSV-1 infection defines the course of the disease, with deeper subcutaneous infection allowing virus access to the facial nerve and causing facial palsy. HSV-1 inoculated subcutaneously caused extensive facial paralysis in cotton rats Sigmodon hispidus, while virus inoculated in the same area of the lip by skin surface abrasion did not. Demyelination along the facial nerve (CN VII) accompanied subcutaneous HSV-1 infection and was identified as the possible underlying mechanism of the disease. This causality demonstration is particularly important in light of increased facial palsy outbreaks associated with SARS-CoV-2 infection and SARS-CoV-2 and influenza vaccinations.