High prevalence of SARS-CoV-2 antibodies in care homes affected by COVID-19: Prospective cohort study, England
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SciScore for 10.1101/2020.08.10.20171413: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources Microneutralisation assay and neutralising antibody titre: SARS-CoV-2 (isolate England/02/2020) specific neutralising antibody levels were measured using a modification of the WHO influenza microneutralisation methodology.9 Briefly, 200 TCID 50 of virus was incubated with serial dilutions of serum from participants, after which a suspension of Vero E6 cells were added. Vero E6suggested: RRID:CVCL_XD71)Software and Algorithms Sentences R… SciScore for 10.1101/2020.08.10.20171413: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources Microneutralisation assay and neutralising antibody titre: SARS-CoV-2 (isolate England/02/2020) specific neutralising antibody levels were measured using a modification of the WHO influenza microneutralisation methodology.9 Briefly, 200 TCID 50 of virus was incubated with serial dilutions of serum from participants, after which a suspension of Vero E6 cells were added. Vero E6suggested: RRID:CVCL_XD71)Software and Algorithms Sentences Resources Data were analysed using Stata version 15.0 (Statcorp, Tx) and GraphPad Prism. GraphPad Prismsuggested: (GraphPad Prism, RRID:SCR_002798)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:The very high seropositivity rates among symptomatic but RT-PCR negative residents and staff suggests that their original illness was also most likely due to COVID-19 and highlights the sensitivity limitations of single point nasal swabbing for diagnosis and the narrow window of SARS-CoV-2 detection in infected individuals, and significantly underestimated exposure to SARS-CoV-2 in these outbreak settings.15 The very high seropositivity of 75.0% among care home staff compared to 17-44% of patient-facing healthcare workers is staggering.10,11 A possible explanation may be more prolonged and intense exposure to the virus because of level of care required by the residents.2,15 In our initial investigations, we also found evidence of transmission between staff members in care homes, highlighting the importance of maintaining infection control practices for all contact, including those between staff, whilst on care home premises.8 Despite reinforcement of infection control measures at the outset, one further staff member and three residents became infected with SARS-CoV-2 at follow-up. Residents and staff who were SARS-CoV-2 RT-PCR positive at follow-up all had high Ct values, consistent with non-viable virus at the time of testing,4 and were also SARS-CoV-2 antibody positive. Further studies are needed to assess whether the presence of SARS-CoV-2 antibodies, including neutralising antibodies, are protective against re-infection and, if so, the duration of protection. Questions al...
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
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SciScore for 10.1101/2020.08.10.20171413: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources SARS-CoV-2 (isolate England/02/2020) specific neutralising antibody levels were measured using a modification of the WHO influenza microneutralisation methodology.9 Briefly, 200 TCID 50 of virus was incubated with serial dilutions of serum from participants, after which a suspension of Vero E6 cells were added. Vero E6suggested: RRID:CVCL_XD71)…SciScore for 10.1101/2020.08.10.20171413: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources SARS-CoV-2 (isolate England/02/2020) specific neutralising antibody levels were measured using a modification of the WHO influenza microneutralisation methodology.9 Briefly, 200 TCID 50 of virus was incubated with serial dilutions of serum from participants, after which a suspension of Vero E6 cells were added. Vero E6suggested: RRID:CVCL_XD71)Software and Algorithms Sentences Resources Data were analysed using Stata version 15.0 (Statcorp, Tx) and GraphPad Prism. GraphPad Prismsuggested: (GraphPad Prism, RRID:SCR_002798)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
The very high seropositivity rates among symptomatic but RT-PCR negative residents and staff suggests that their original illness was also most likely due to COVID-19 and highlights the sensitivity limitations of single point nasal swabbing for diagnosis and the narrow window of SARSCoV-2 detection in infected individuals, and significantly underestimated exposure to SARS-CoV-2 in these outbreak settings.15 The very high seropositivity of 75.0% among care home staff compared to 17-44% of patient-facing healthcare workers is staggering.10,11 A possible explanation may be more prolonged and intense exposure to the virus because of level of care required by the residents.2,15 In our initial investigations, we also found evidence of transmission between staff members in care homes, highlighting the importance of maintaining infection control practices for all contact, including those between staff, whilst on care home premises.8 Despite reinforcement of infection control measures at the outset, one further staff member and three residents became infected with SARS-CoV-2 at follow-up. Residents and staff who were SARS-CoV-2 RT-PCR positive at follow-up all had high Ct values, consistent with non-viable virus at the time of testing,4 and were also SARS-CoV2 antibody positive. Further studies are needed to assess whether the presence of SARS-CoV-2 antibodies, including neutralising antibodies, are protective against re-infection and, if so, the duration of protection. Questions also remain as to whether antibody concentrations provide a useful measure of protection in infected individuals.16 Notable, too in this study, was the observation that SARS-CoV-2 antibody levels were similar among symptomatic and asymptomatic residents and staff across the care homes, which contrasts with recent reports suggesting that higher antibody levels and persistence were achieved in patients with more severe disease compared to those with mild disease or asymptomatic infection.12 The high fatality rates among residents across the six care homes, particularly affecting those who had been symptomatic and SARS CoV-2 RT-PCR positive indicates that that the cohort described here is more representative of milder illness and depleted of individuals who suffered the most severe outcomes of infection.4 We also found that 90% of seropositive staff and residents had neutralising antibody responses, with no significant differences in neutralising antibody levels between by age, sex, symptom status or staff/resident status. There was a trend towards increasing neutralising antibody titres with increasing age (Figure 4c) but this was not statistically significant. These findings of such robust antibody responses in surviving care home residents, especially when compared to younger, healthier staff members with similar exposure risks to SARS-CoV-2, are novel and may play an important part in future recommendations for infection control practices and vaccination against SARS-CoV-2. Several key questions relating to this novel pandemic remain to be answered and are particularly relevant to this highly vulnerable population and setting. In particular, it is not known whether SARSCoV-2 antibodies are protective against re-infection.16 We identified a small number of residents who were still RT-PCR positive up to five weeks later; all had detectable antibodies, including some with neutralising antibodies at the time of the persistent virus detection.17 The RT-PCR Ct values were consistent with non-live virus in all residents and staff members who were RT-PCR positive on nasal swab at follow-up. The prolonged nasal swab RT-PCR positivity in a proportion of residents and staff is consistent with a recent large healthcare worker study where up to a quarter were still RTPCR positive up to six weeks later, highlighting yet another limitation of our understanding of the kinetics of viral replication and immune responses COVID-19.18,19 The strengths of our investigations include the extensive and robust epidemiological, virological and serological testing of residents and staff across six London care homes experiencing large outbreaks of COVID-19, the broad age ranges involved, the daily follow-up after initial testing and the high uptake for retesting five weeks later. The data collected have provided a wealth of information on SARS-CoV-2 infection, transmission and antibody responses in a high-risk care setting involving a very vulnerable cohort. A limitation is that the care homes were already in the middle of the outbreak. Consequently, some residents had already developed COVID-19 and some had died of their infection. Another limitation was that we did not obtain blood samples for antibody testing at the first visit, which could have provided additional useful information on antibody kinetics in a large cohort of elderly residents and younger staff members. The lower nasal swab positivity during the initial investigations compared to the antibody results five weeks later reflects the limited sensitivity of test, the quality of sampling, the stage of infection at the time of testing and the gene targets used by different RT-PCR assays.20 Some of these limitations could potentially have been mitigated by repeated swabbing at different time points. In conclusion, almost all residents and staff with confirmed SARS-CoV-2 infection had detectable antibodies five weeks later, irrespective of whether they were ever symptomatic or remained asymptomatic throughout the outbreak. Additionally, a high proportion of those who were symptomatic but SARS-CoV-2 RT-PCR negative were also seropositive. SARS-CoV-2 antibody levels were not associated with age, sex, PCR positivity, symptomatic/asymptomatic or resident/staff status. Our findings demonstrate the older and vulnerable residents are able to mount a robust antibody response to SARS-CoV-2 that is similar to younger and healthier staff members. Further studies are needed to determine whether SARS-CoV-2 antibodies protect against re-infection and, if so, the duration of protection. Ethics approval : The research protocol was approved by the PHE Research Ethics and Governance Group (REGG Ref: NR0204, 07 May 2020). Role of the funding source : This study was funded by Public Health England as part of the COVID-19 response. The authors had sole responsibility for the study design, data collection, data analysis, data interpretation, and writing of the report. The authors are all employed by Public Health England, the study funder, which is a public body — an executive agency of the Department of Health. The corresponding author had full access to all the data in the study and final responsibility for the decision to submit for publication. : The authors are very grateful to the care home managers, their staff and the
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
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