Intrathecal inflammatory responses in the absence of SARS-CoV-2 nucleic acid in the CSF of COVID-19 hospitalized patients

Objective: Evaluate SARS-CoV-2 RNA and inflammatory cytokines and chemokines in the CSF of patients with acute COVID-19 and neurologic symptoms, and to compare these to controls and patients with known neurotropic pathogens. Background: Neurologic symptoms have been described in 30-60% of hospitalized patients with Coronavirus Disease 2019 (COVID-19). However, little is known about CSF profiles in these patients. Design/Methods: CSF from twenty-seven consecutive patients with COVID-19 and neurological symptoms was assayed for SARS-CoV-2 RNA using quantitative reverse transcription PCR (RT-qPCR) and unbiased metagenomic sequencing. Assays for blood brain barrier (BBB) breakdown (CSF:serum albumin ratio (Q-Alb)), and proinflammatory cytokines and chemokines (IL-6, IL-8, IL-15, IL-16, monocyte chemoattractant protein -1 (MCP-1) and monocyte inhibitory protein - 1β (MIP-1β)) were performed in 23 patients and compared to CSF from patients with HIV-1 (16 virally suppressed, 5 unsuppressed), West Nile virus (WNV) (n=4) and 16 healthy controls (HC). Results: Median CSF cell count for COVID-19 patients was 1 white blood cell/μL;two patients were infected with a second pathogen (Neisseria, Cryptococcus neoformans). No CSF samples had detectable SARS-CoV-2 RNA by either detection method. In patients with COVID-19 only, CSF IL-6, IL-8, IL-15, and MIP-1β levels were higher than HC and suppressed HIV (corrected-p < 0.05). MCP-1 and MIP-1β levels were higher, while IL-6, IL-8, IL-15 were similar in COVID-19 compared to WNV patients. Q-Alb correlated with all proinflammatory markers, with IL-6, IL-8, and MIP-1β (r≥0.6, p<0.01) demonstrating the strongest associations. Conclusions: Lack of SARS-CoV-2 RNA in CSF is consistent with pre-existing literature. Evidence of intrathecal proinflammatory markers in a subset of COVID-19 patients with BBB breakdown despite minimal CSF pleocytosis is atypical for neurotropic pathogens.

COVID-19: using chest CT of major trauma patients to monitor and evaluate the second wave in London and the development of routine monitoring in practice.

AIM: To follow-up previous work evaluating incidental findings of COVID-19 signs on computed tomography (CT) images of major trauma patients to include the second wave prior to any major effects from vaccines. MATERIALS AND METHODS: The study population included all patients admitted following major trauma between 1 January 2020 and 28 February 2021 with CT including the lungs (n=1776). Major trauma patients admitted pre-COVID-19 from alternate months from January 2019 to November 2019 comprised a control group (n=837). The assessing radiologists were blinded to the time period and used double reading in consensus to determine if the patient had signs of COVID-19. Lung appearances were classified as no evidence of COVID-19, minor signs, or major signs. RESULTS: The method successfully tracked the second wave of the COVID-19 pandemic in London. The estimated population affected by the disease based on those with major signs was similar to estimates of the proportion of the population in London with antibodies (around 30% by end February 2021) and the total of major and minor signs produced a much higher figure of 68%, which may include all those with both antibody and just T-cell responses. CONCLUSIONS: Incidental findings on CT from major trauma patients may provide a novel and sensitive way of tracking the virus. It is recommended that all major trauma units include a simple question on signs of COVID-19 to provide an early warning system for further waves.

Patient symptoms following discharge from hospital after COVID-19 pneumonia

Introduction The recovery of patients after COVID-19 has been poorly described. Related coronavirus infections (SARSCOV1 and MERS) have protracted recovery time-courses with significant respiratory morbidity,1 suggesting the same may be true for COVID-19. A service evaluation was therefore undertaken to evaluate the short-term effects of COVID-19. Methods Respiratory specialist doctors conducted structured telephone consultations of patients admitted between 17th March 2020 and 2nd May 2020 with a diagnosis of COVID- 19 pneumonia at a teaching hospital. Using time from discharge patients were allocated into 3 groups: 3-4 weeks, 4-5 weeks and 5+. Patients were asked to recall acute COVID-19 symptoms, current symptoms, activity levels, and exercise capacity after discharge. Exercise capacity was quantified by self-assessment of walking distance on flat (metres), stairs (flights). Patient reported outcome measures (MRC dyspnoea scale and WHO performance status) were also collated. Results A total of 102 patients were screened, 70 were included in the study, with the rest being unreachable (n=32) Cough, dyspnoea, fever and lethargy were the most common symptoms at time of admission. All these symptoms, except lethargy, improved following discharge (figure 1). Prevalence in the 5+ week cohort of other symptoms is as follows: dyspnoea 35.7%, cough 11.5%, fever 0%;however, 70% of patients had at least 1 symptom 5 weeks after discharge. Self-reported exercise capacity and MRC dyspnoea score also improved after discharge. Despite this 21.4% of patients had a persistent impairment in walking ability on the flat, 17.8% in stair-climbing with 28.5% persistent deficit in MRC dyspnoea score after 5 weeks. In contrast 40% of patients had a deficit in WHO performance status and this was not affected by time after discharge. In conclusion patients did improve following discharge from hospital for COVID-19 pneumonia, however many were left with residual symptoms and a functional deficit in short term (5 weeks). It remains to be seen whether this results in long term health problems.