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1.
medrxiv; 2021.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2021.09.16.21263684

ABSTRACT

Summary Background The COVID-19 pandemic has overwhelmed the respiratory isolation capacity in hospitals; many wards lacking high-frequency air changes have been repurposed for managing patients infected with SARS-CoV-2 requiring either standard or intensive care. Hospital-acquired COVID-19 is a recognised problem amongst both patients and staff, with growing evidence for the relevance of airborne transmission. This study examined the effect of air filtration and ultra-violet (UV) light sterilisation on detectable airborne SARS-CoV-2 and other microbial bioaerosols. Methods We conducted a crossover study of portable air filtration and sterilisation devices in a repurposed ‘surge’ COVID ward and ‘surge’ ICU. National Institute for Occupational Safety and Health (NIOSH) cyclonic aerosol samplers and PCR assays were used to detect the presence of airborne SARS-CoV-2 and other microbial bioaerosol with and without air/UV filtration. Results Airborne SARS-CoV-2 was detected in the ward on all five days before activation of air/UV filtration, but on none of the five days when the air/UV filter was operational; SARS-CoV-2 was again detected on four out of five days when the filter was off. Airborne SARS-CoV-2 was infrequently detected in the ICU. Filtration significantly reduced the burden of other microbial bioaerosols in both the ward (48 pathogens detected before filtration, two after, p =0.05) and the ICU (45 pathogens detected before filtration, five after p =0.05). Conclusions These data demonstrate the feasibility of removing SARS-CoV-2 from the air of repurposed ‘surge’ wards and suggest that air filtration devices may help reduce the risk of hospital-acquired SARS-CoV-2. Funding Wellcome Trust, MRC, NIHR


Subject(s)
COVID-19
2.
medrxiv; 2020.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2020.12.05.20241927

ABSTRACT

SARS-CoV-2 Spike protein is critical for virus infection via engagement of ACE2, and amino acid variation in Spike is increasingly appreciated. Given both vaccines and therapeutics are designed around Wuhan-1 Spike, this raises the theoretical possibility of virus escape, particularly in immunocompromised individuals where prolonged viral replication occurs. Here we report chronic SARS-CoV-2 with reduced sensitivity to neutralising antibodies in an immune suppressed individual treated with convalescent plasma, generating whole genome ultradeep sequences by both short and long read technologies over 23 time points spanning 101 days. Although little change was observed in the overall viral population structure following two courses of remdesivir over the first 57 days, N501Y in Spike was transiently detected at day 55 and V157L in RdRp emerged. However, following convalescent plasma we observed large, dynamic virus population shifts, with the emergence of a dominant viral strain bearing D796H in S2 and{Delta} H69/{Delta}V70 in the S1 N-terminal domain NTD of the Spike protein. As passively transferred serum antibodies diminished, viruses with the escape genotype diminished in frequency, before returning during a final, unsuccessful course of convalescent plasma. In vitro, the Spike escape double mutant bearing{Delta} H69/{Delta}V70 and D796H conferred decreased sensitivity to convalescent plasma, whilst maintaining infectivity similar to wild type. D796H appeared to be the main contributor to decreased susceptibility, but incurred an infectivity defect. The{Delta} H69/{Delta}V70 single mutant had two-fold higher infectivity compared to wild type and appeared to compensate for the reduced infectivity of D796H. Consistent with the observed mutations being outside the RBD, monoclonal antibodies targeting the RBD were not impacted by either or both mutations, but a non RBD binding monoclonal antibody was less potent against{Delta} H69/{Delta}V70 and the double mutant. These data reveal strong selection on SARS-CoV-2 during convalescent plasma therapy associated with emergence of viral variants with reduced susceptibility to neutralising antibodies.

3.
ssrn; 2020.
Preprint in English | PREPRINT-SSRN | ID: ppzbmed-10.2139.ssrn.3724855

ABSTRACT

Background: The COVID-19 pandemic continues to grow at an unprecedented rate. Healthcare workers (HCWs) are at higher risk of SARS-CoV-2 infection than the general population but risk factors for HCW infection are not well described.Methods: We conducted a prospective sero-epidemiological study of HCWs at a UK teaching hospital using a SARS-CoV-2 immunoassay. Risk factors for seropositivity were analysed using multivariate logistic regression.Findings: 410/5,698 (7·2%) staff tested positive for SARS-CoV-2 antibodies. Seroprevalence was higher in those working in designated COVID-19 areas compared with other areas (9·47% versus 6·16%) Healthcare assistants (aOR 2·06 [95%CI 1·14-3·71]; p =0·016) and domestic and portering staff (aOR 3·45 [95% CI 1·07-11·42]; p =0·039) had significantly higher seroprevalence than other staff groups after adjusting for age, sex, ethnicity and COVID-19 working location. Staff working in acute medicine and medical sub-specialities were also at higher risk (aOR 2·07 [95% CI 1·31-3·25]; p <0·002). Staff from Black, Asian and minority ethnic (BAME) backgrounds had an aOR of 1·65 (95% CI 1·32 – 2·07; p <0·001) compared to white staff; this increased risk was independent of COVID-19 area working. The only symptoms significantly associated with seropositivity in a multivariable model were loss of sense of taste or smell, fever and myalgia; 31% of staff testing positive reported no prior symptoms.Interpretation: Risk of SARS-CoV-2 infection amongst HCWs is heterogeneous and influenced by COVID-19 working location, role, age and ethnicity. Increased risk amongst BAME staff cannot be accounted for solely by occupational factors.Funding: Wellcome Trust, Addenbrookes Charitable Trust, National Institute for Health Research, Academy of Medical Sciences, the Health Foundation and the NIHR Cambridge Biomedical Research Centre.Declaration of Interests: None to declare.Ethics Approval Statement: Ethical approval for this study was granted by the East of England – Cambridge Central Research Ethics Committee (IRAS ID: 220277).


Subject(s)
Musculoskeletal Pain , COVID-19 , Fever
4.
medrxiv; 2020.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2020.11.03.20220699

ABSTRACT

Background The COVID-19 pandemic continues to grow at an unprecedented rate. Healthcare workers (HCWs) are at higher risk of SARS-CoV-2 infection than the general population but risk factors for HCW infection are not well described. Methods We conducted a prospective sero-epidemiological study of HCWs at a UK teaching hospital using a SARS-CoV-2 immunoassay. Risk factors for seropositivity were analysed using multivariate logistic regression. Findings 410/5,698 (7.2%) staff tested positive for SARS-CoV-2 antibodies. Seroprevalence was higher in those working in designated COVID-19 areas compared with other areas (9.47% versus 6.16%) Healthcare assistants (aOR 2.06 [95%CI 1.14-3.71]; p=0.016) and domestic and portering staff (aOR 3.45 [95% CI 1.07-11.42]; p=0.039) had significantly higher seroprevalence than other staff groups after adjusting for age, sex, ethnicity and COVID-19 working location. Staff working in acute medicine and medical sub-specialities were also at higher risk (aOR 2.07 [95% CI 1.31-3.25]; p=0.002). Staff from Black, Asian and minority ethnic (BAME) backgrounds had an aOR of 1.65 (95% CI 1.32-2.07; p<0.0001) compared to white staff; this increased risk was independent of COVID-19 area working. The only symptoms significantly associated with seropositivity in a multivariable model were loss of sense of taste or smell, fever and myalgia; 31% of staff testing positive reported no prior symptoms. Interpretation Risk of SARS-CoV-2 infection amongst HCWs is heterogeneous and influenced by COVID-19 working location, role, age and ethnicity. Increased risk amongst BAME staff cannot be accounted for solely by occupational factors. Funding Wellcome Trust, Addenbrookes Charitable Trust, National Institute for Health Research, Academy of Medical Sciences, the Health Foundation and the NIHR Cambridge Biomedical Research Centre.


Subject(s)
Myalgia , COVID-19 , Infections , Fever
5.
medrxiv; 2020.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2020.05.31.20114520

ABSTRACT

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.


Subject(s)
COVID-19
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