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Background: Coronavirus Disease 2019 (COVID-19) caused by the enveloped RNA virus SARS-CoV-2 primarily affects the respiratory and gastrointestinal tracts. SARS-CoV-2 was isolated from faecal samples and active viral replication was reported in human intestinal cells. The human gut also harbors an enormous amount of resident viruses (collectively known as the virome) that play a role in regulating host immunity and disease pathophysiology. Understanding gut virome perturbation that underlies SARS-CoV-2 infection and severity is an unmet need.Methods: We enrolled 98 COVID-19 patients with varying disease severity (3 asymptomatic, 53 mild, 34 moderate, 5 severe, 3 critical) and 78 non-COVID-19 controls matched for gender and co-morbidities. All subjects had faecal specimens sampled at inclusion. Blood specimens were collected for COVID-19 patients at admission to test for inflammatory markers and white cell counts. Among COVID-19 cases, 37 (38%) patients had serial faecal samples collected 2 to 3 times per week from time of hospitalization until after discharge. Using shotgun metagenomics sequencing, we sequenced and profiled the faecal RNA and DNA virome. We investigated alterations and longitudinal dynamics of the gut virome in association with disease severity and blood parameters.Results: Patients with COVID-19 showed underrepresentation of Pepper mild mottle virus (RNA virus) and multiple bacteriophage lineages (DNA viruses) and enrichment of environment-derived eukaryotic DNA viruses in faecal samples, compared to non-COVID-19 subjects. Such gut virome alterations persisted up to 30 days after disease resolution. Faecal virome in SARS-CoV-2 infection harboured more stress-, inflammation- and virulence-associated gene encoding capacities including those pertaining to bacteriophage integration, DNA repair, and metabolism and virulence associated with their bacterial host. Baseline fecal abundance of 10 virus species (1 RNA virus, Pepper chlorotic spot virus, and 9 DNA virus species) inversely correlated with disease COVID-19 severity. These viruses inversely correlated with blood levels of pro-inflammatory proteins, white cells and neutrophils. Among the 10 COVID-19 severity-associated DNA virus species, 4 showed inverse correlation with age; 5 showed persistent lower abundance both during disease course and after disease resolution relative to non-COVID-19 subjects.Conclusions: Both enteric RNA and DNA virome in COVID-19 patients were different from non-COVID-19 subjects, which persisted after disease resolution of COVID-19. Gut virome may calibrate host immunity and regulate severity to SARS-CoV-2 infection. Our observation that gut viruses inversely correlated with both severity of COVID-19 and host age may partly explain that older subjects are prone to severe and worse COVID-19 outcomes. Altogether our data highlight the importance of human gut virome in severity and potentially therapeutics of COVID-19.

Purpose To provide recommendations and standard operating procedures (SOPs) for intensive care unit (ICU) and hospital preparations for an influenza pandemic or mass disaster with a specific focus on protection of patients and staff.

Purpose To provide recommendations and standard operating procedures for intensive care unit (ICU) and hospital preparations for a mass disaster or influenza epidemic with a specific focus on surge capacity and infrastructure considerations. Methods Based on a literature review and expert opinion, a Delphi process was used to define the essential topics including surge capacity and infrastructure considerations. Results Key recommendations include: (1) hospitals should increase their ICU beds to the maximal extent by expanding ICU capacity and expanding ICUs into other areas; (2) hospitals should have appropriate beds and monitors for these expansion areas; hospitals should develop contingency plans at the facility and government (local, state, provincial, national) levels to provide additional ventilators; (3) hospitals should develop a phased staffing plan (nursing and physician) for ICUs that provides sufficient patient care supervision during contingency and crisis situations; (4) hospitals should provide expert input to the emergency management personnel at the hospital both during planning for surge capacity as well as during response; (5) hospitals should assure that adequate infrastructure support is present to support critical care activities; (6) hospitals should prioritize locations for expansion by expanding existing ICUs, using postanesthesia care units and emergency departments to capacity, then step-down units, large procedure suites, telemetry units and finally hospital wards. Conclusions Judicious planning and adoption of protocols for surge capacity and infrastructure considerations are necessary to optimize outcomes during a pandemic.