Post COVID-19 Guillain Barre Syndrome in Immunocompromised Children - A report of two cases and review of literature (preprint)

IntroductionSevere acute respiratory syndrome Coronavirus 2 (SARS-CoV 2) is a novel coronavirus that caused an outbreak since 31 December 2019. Although the most commonly noted symptoms were fever and respiratory illness, a wide variety of other symptoms have also been seen. There has been increasing number of cases of neurological manifestations of Covid –19. Further, there has been growing association between Covid-19 and Guillain Barre Syndrome (GBS).Case presentationIn this report, we present two cases of acute lymphoblastic leukemia affected by Covid-19 who after recovery from Covid-19 developed symptoms of GBS. They presented with complaints of bilaterally symmetrical ascending motor paralysis and were diagnosed with Guillain Barre Syndrome by electrophysiological tests and were started on intravenous immunoglobins for five days @ 0.4mg/kg/day after which the condition of both children gradually improved.ConclusionThis case report adds to the emerging evidence that suggests the association of GBS post Covid infections. COVID-19 can result in several autoimmune neurological phenomena including GBS. In the setting of the pandemic, COVID-19 as an underlying trigger should be considered in all immunologic phenomena. This applies to all patients, including children.

Cardiovascular disease and severe hypoxemia associated with higher rates of non-invasive respiratory support failure in COVID-19 (preprint)

RationaleAcute hypoxemic respiratory failure (AHRF) is the major complication of coronavirus disease 2019 (COVID-19), yet optimal respiratory support strategies are uncertain. ObjectivesTo describe outcomes with high-flow oxygen delivered through nasal cannula (HFNC) and non-invasive positive pressure ventilation (NIPPV) in COVID-19 AHRF and identify individual factors associated with failure. MethodsWe performed a retrospective cohort study of hospitalized adults with COVID-19 treated with HFNC and/or NIPPV to describe rates of success (live discharge without endotracheal intubation (ETI)), and identify characteristics associated with failure (ETI and/or in-hospital mortality) using Fine-Gray sub-distribution hazard models. ResultsA total of 331 and 747 patients received HFNC and NIPPV as the highest level of non-invasive respiratory support, respectively; 154 (46.5%) in the HFNC cohort and 167 (22.4%) in the NIPPV cohort were successfully discharged without requiring ETI. In adjusted models, significantly increased risk of HFNC and NIPPV failure was seen among patients with cardiovascular disease (subdistribution hazard ratio (sHR) 1.82; 95% confidence interval (CI), 1.17-2.83 and sHR 1.40; 95% CI 1.06-1.84), respectively, and among those with lower oxygen saturation to fraction of inspired oxygen (SpO2/FiO2) ratio at HFNC and NIPPV initiation (sHR, 0.32; 95% CI 0.19-0.54, and sHR 0.34; 95% CI 0.21-0.55, respectively). ConclusionsA significant proportion of patients receiving non-invasive respiratory modalities for COVID-19 AHRF achieved successful discharge without requiring ETI, with lower success rates among those with cardiovascular disease or more severe hypoxemia. The role of non-invasive respiratory modalities in COVID-19 related AHRF requires further consideration.

Combined point of care nucleic acid and antibody testing for SARS-CoV-2: a prospective cohort study in suspected moderate to severe COVID-19 disease. (preprint)

BackgroundRapid COVID-19 diagnosis in hospital is essential for patient management and identification of infectious patients to limit the potential for nosocomial transmission. The diagnosis of infection is complicated by 30-50% of COVID-19 hospital admissions with nose/throat swabs testing negative for SARS-CoV-2 nucleic acid, frequently after the first week of illness when SARS-CoV-2 antibody responses become detectable. We assessed the diagnostic accuracy of combined rapid antibody point of care (POC) and nucleic acid assays for suspected COVID-19 disease in the emergency department. MethodsWe developed (i) an in vitro neutralization assay using a lentivirus expressing a genome encoding luciferase and pseudotyped with spike (S) protein and (ii) an ELISA test to detect IgG antibodies to nucleocapsid (N) and S proteins from SARS-CoV-2. We tested two lateral flow rapid fingerprick tests with bands for IgG and IgM. We then prospectively recruited participants with suspected moderate to severe COVID-19 and tested for SARS-CoV-2 nucleic acid in a combined nasal/throat swab using the standard laboratory RT-PCR and a validated rapid POC nucleic acid amplification (NAAT) test. Additionally, serum collected at admission was retrospectively tested by in vitro neutralisation, ELISA and the candidate POC antibody tests. We evaluated the performance of the individual and combined rapid POC diagnostic tests against a composite reference standard of neutralisation and standard laboratory based RT-PCR. Results45 participants had specimens tested for nucleic acid in nose/throat swabs as well as stored sera for antibodies. Using the composite reference standard, prevalence of COVID-19 disease was 53.3% (24/45). Median age was 73.5 (IQR 54.0-86.5) years in those with COVID-19 disease by our reference standard and 63.0 (IQR 41.0-72.0) years in those without disease. The overall detection rate by rapid NAAT was 79.2% (95CI 57.8-92.9%), decreasing from 100% (95% CI 65.3-98.6%) in days 1-4 to 50.0% (95% CI 11.8-88.2) for days 9-28 post symptom onset. Correct identification of COVID-19 with combined rapid POC diagnostic tests was 100% (95CI 85.8-100%) with a false positive rate of 5.3-14.3%, driven by POC LFA antibody tests. ConclusionsCombined POC tests have the potential to transform our management of COVID-19, including inflammatory manifestations later in disease where nucleic acid test results are negative. A rapid combined approach will also aid recruitment into clinical trials and in prescribing therapeutics, particularly where potentially harmful immune modulators (including steroids) are used.

Rapid point of care nucleic acid testing for SARS-CoV-2 in hospitalised patients: a clinical trial and implementation study (preprint)

BackgroundThere is urgent need for safe and efficient triage protocols for hospitalized COVID-19 suspects to appropriate isolation wards. A major barrier to timely discharge of patients from the emergency room and hospital is the turnaround time for many SARS-CoV-2 nucleic acid tests. We validated a point of care nucleic acid amplification based platform SAMBA II for diagnosis of COVID-19 and performed an implementation study to assess its impact on patient disposition at a major academic hospital. MethodsWe prospectively recruited COVID-19 suspects admitted to hospital (NCT04326387). In an initial pilot phase, individuals were tested using a nasal/throat swab with the SAMBA II SARS-CoV-2 rapid diagnostic platform in parallel with a combined nasal/throat swab for standard central laboratory RT-PCR testing. In the second implementation phase, we examined the utility of adding the SAMBA platform to routine care. In the pilot phase, we measured concordance and assay validity using the central laboratory as the reference standard and assessed assay turnaround time. In the implementation phase, we assessed 1) time to definitive bed placement from admission, 2) time spent on COVID-19 holding wards, 3) proportion of patients in isolation versus COVID negative areas following a test, comparing the implementation phase with the 10 days prior to implementation. ResultsIn phase I, 149 participants were included in the pilot. By central laboratory RT-PCR testing, 32 (21.5%) tested positive and 117 (78.5%). Sensitivity and specificity of the SAMBA assay compared to RT-PCR lab test were 96.9% (95% CI 0.838-0.999) and 99.1% (0.953-0.999), respectively. Median time to result was 2.6 hours (IQR 2.3 to 4.8) for SAMBA II SARS-CoV-2 test and 26.4 hours (IQR 21.4 to 31.4) for the standard lab RT-PCR test (p<0.001). In the first 10 days of the SAMBA implementation phase, we conducted 992 tests, with the majority (59.8%) used for hospital admission, and the remainder for pre-operative screening (11.3%), discharge planning (10%), in-hospital screening of new symptoms (9.7%). Comparing the pre-implementation (n=599) with the implementation phase, median time to definitive bed placement from admission was reduced from 23.4 hours (8.6-41.9) to 17.1 hours (9.0-28.8), P=0.02 in Cox analysis, adjusted for age, sex, comorbidities and clinical severity at presentation. Mean length of stay on a COVID-19 holding ward decreased from 58.5 hours to 29.9 hours (P<0.001). Use of single occupancy rooms amongst those tested fell from 30.8% before to 21.2% (P=0.03) and 11 hospital bay closures (on average 6 beds each) were avoided after implementation of the POC assay. ConclusionsThe SAMBA II SARS-CoV-2 rapid assay performed well compared to a centralized laboratory RT-PCR platform and demonstrated shorter time to result both in trial and real-world settings. It was also associated with faster time to definitive bed placement from the emergency room, greater availability of isolation rooms, avoidance of hospital bay closures, and greater movement of patients to COVID negative open "green" category wards. Rapid testing in hospitals has the potential to transform ability to deal with the COVID-19 epidemic.

Performance evaluation of the point-of-care SAMBA II SARS-CoV-2 Test for detection of SARS-CoV-2 (preprint)

Nucleic acid amplification for the detection of SARS-CoV-2 RNA in respiratory samples is the standard method for diagnosis. These tests are centralised and therefore turnaround times can be 2-5 days. Point-of-care testing with rapid turnaround times would allow more effective triage in settings where patient management and infection control decisions need to be made rapidly. Inclusivity and specificity of the SAMBA II SARS-CoV-2 assay was determined by in silico analyses of the primers and probes. Analytical and clinical sensitivity and specificity of the SAMBA II SARS-CoV-2 Test was evaluated for analytical sensitivity and specificity. Clinical performance was evaluated in residual clinical samples compared to the Public Health England reference tests. The limit of detection of the SAMBA II SARS-CoV-2 Test is 250 cp/mL and is specific for detection of 2 regions of the SARS-CoV-2 genome. The clinical sensitivity was evaluated in 172 clinical samples provided by the Clinical Microbiology and Public Health Laboratory, Addenbrookes Hospital, Cambridge (CMPHL), which showed a sensitivity of 98.9% (95% CI 94.03-99.97%), specificity of 100% (95% CI 95.55-100%), PPV of 100% and NPV of 98.78% (92.02-99.82%) compared to testing by CMPHLSAMBA detected 3 positive samples that were initially negative by PHE Test. The data shows that the SAMBA II SARS-CoV-2 Test performs equivalently to the centralised testing methods with a much quicker turnaround time. Point of care testing, such as SAMBA, should enable rapid patient management and effective implementation of infection control measures.