Background. Administration of convalescent plasma, serum, or hyperimmune immunoglobulin may be of clinical benefit for treatment of severe acute respiratory infections (SARIs) of viral etiology. We conducted a systematic review and exploratory meta-analysis to assess the overall evidence.Methods. Healthcare databases and sources of grey literature were searched in July 2013. All records were screened against the protocol eligibility criteria, using a 3-stage process. Data extraction and risk of bias assessments were undertaken.Results. We identified 32 studies of SARS coronavirus infection and severe influenza. Narrative analyses revealed consistent evidence for a reduction in mortality, especially when convalescent plasma is administered early after symptom onset. Exploratory post hoc meta-analysis showed a statistically significant reduction in the pooled odds of mortality following treatment, compared with placebo or no therapy (odds ratio, 0.25; 95% confidence interval, .14–.45; I2 = 0%). Studies were commonly of low or very low quality, lacked control groups, and at moderate or high risk of bias. Sources of clinical and methodological heterogeneity were identified.Conclusions. Convalescent plasma may reduce mortality and appears safe. This therapy should be studied within the context of a well-designed clinical trial or other formal evaluation, including for treatment of Middle East respiratory syndrome coronavirus CoV infection.

Background: Care homes are experiencing large outbreaks of COVID-19 associated with high case-fatality rates. We conducted detailed investigations in six London care homes reporting suspected COVID-19 outbreaks during April 2020. Methods: Residents and staff had nasal swabs for SARS CoV-2 testing using RT-PCR and were followed-up for 14 days. They were categorized as symptomatic, post-symptomatic or pre-symptomatic if they had symptoms at the time of testing, in the two weeks before or two weeks after testing, respectively, or asymptomatic throughout. Virus isolation and whole genome sequencing (WGS) was also performed. Findings: Across the six care homes, 105/264 (39.8%) residents were SARS CoV-2 positive, including 28 (26.7%) symptomatic, 10 (9.5%) post-symptomatic, 21 (20.0%) pre-symptomatic and 46 (43.8%) who remained asymptomatic. Case-fatality at 14-day follow-up was highest among symptomatic SARS-CoV-2 positive residents (10/28, 35.7%) compared to asymptomatic (2/46, 4.3%), post-symptomatic (2/10, 20.0%) or pre-symptomatic (3/21,14.3%) residents. Among staff, 53/254 (20.9%) were SARS-CoV-2 positive and 26/53 (49.1%) remained asymptomatic. RT-PCR cycle-thresholds and live-virus recovery were similar between symptomatic/asymptomatic residents/staff. Higher RT-PCR cycle threshold values (lower virus load) samples were associated with exponentially decreasing ability to recover infectious virus (P<0.001). WGS identified multiple (up to 9) separate introductions of different SARS-CoV-2 strains into individual care homes. Interpretation: A high prevalence of SARS-CoV-2 positivity was found in care homes residents and staff, half of whom were asymptomatic and potential reservoirs for ongoing transmission. A third of symptomatic SARS-CoV-2 residents died within 14 days. Symptom-based screening alone is not sufficient for outbreak control.

Background: Care homes have been disproportionately affected by the COVID-19 pandemic and continue to suffer lar ge outbreaks even when community infection rates are declining, thus representing important pockets of transmission. We assessed occupational risk factors for SARS-CoV-2 infection among staff in six care homes experiencing a COVID-19 outbreak during the peak of the pandemic in London, England. Methods: Care home staff were tested for SARS-COV-2 infection by RT-PCR and asked to report any symptoms, their contact with residents and if they worked in different care homes. Whole genome sequencing (WGS) was performed on RT-PCR positive samples. Results: In total, 53 (21%) of 254 staff were SARS-CoV-2 positive but only 12/53 (23%) were symptomatic. Among staff working in a single care home, SARS-CoV-2 positivity was 15% (2/13), 16% (7/45) and 18% (30/169) in those reporting no, occasional and regular contact with residents. In contrast, staff working across different care homes (14/27, 52%) had a 3.0-fold (95% CI, 1.9-4.8; P < 0.001) higher risk of SARS-CoV-2 positivity than staff working in single care homes (39/227, 17%). WGS identified SARS-CoV-2 clusters involving staff only, including some that included staff working across different care homes. Conclusions: SARS-CoV-2 positivity was significantly higher among staff working across different care homes than those who were working in the same care home. We found local clusters of SARS-CoV-2 infection between staff only, including those with minimal resident contact. Infection control should be extended for all contact, including those between staff, whilst on care home premises.

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Invasive group A streptococcal infection has a 15% case fatality rate and a risk of secondary transmission. This retrospective study used two national data sources from England; enhanced surveillance (2009) and a case management system (2011–2013) to identify clusters of severe group A streptococcal disease. Twenty-four household pairs were identified. The median onset interval between cases was 2 days (range 0–28) with simultaneous onset in eight pairs. The attack rate during the 30 days after first exposure to a primary case was 4,520 per 100,000 person-years at risk (95% confidence interval (CI): 2,900–6,730) a 1,940 (95% CI: 1,240–2,880) fold elevation over the background incidence. The theoretical number needed to treat to prevent one secondary case using antibiotic prophylaxis was 271 overall (95% CI: 194–454), 50 for mother-neonate pairs (95% CI: 27–393) and 82 for couples aged 75 years and over (95% CI: 46–417). While a dramatically increased risk of infection was noted in all household contacts, increased risk was greatest for mother-neonate pairs and couples aged 75 and over, suggesting targeted prophylaxis could be considered. Offering prophylaxis is challenging due to the short time interval between cases emphasising the importance of immediate notification and assessment of contacts.

Background: We investigated six London care homes experiencing a COVID-19 outbreak and found high rates of SARS-CoV-2 infection among residents and staff. Here we report follow-up investigations including antibody testing in the same care homes five weeks later. Methods: Residents and staff in the initial investigation had a repeat nasal swab for SARS-CoV-2 RT-PCR and a blood test for SARS CoV-2 antibodies using ELISA based on SARS-CoV-2 native viral antigens derived from infected cells and virus neutralisation. Findings: Of the 518 residents and staff in the initial investigation, 186/241 (77.2%) surviving residents and 208/ 254 (81.9%) staff underwent serological testing. Almost all SARS-CoV-2 RT-PCR positive residents and staff were seropositive five weeks later, whether symptomatic (residents 35/35, 100%; staff, 22/22, 100%) or asymptomatic (residents 32/33, 97.0%; staff 21/22, 95.5%). Symptomatic but SARS-CoV-2 RT-PCR negative residents and staff also had high seropositivity rates (residents 23/27, 85.2%; staff 18/21, 85.7%), as did asymptomatic RT-PCR negative individuals (residents 61/91, 67.0%; staff 95/143, 66.4%). Neutralising antibody was detected in 118/ 132 (89.4%) seropositive individuals and was not associated with age or symptoms. Ten residents (10/79 retested, 12.7%) remained RT-PCR positive but with higher RT-PCR cycle threshold values; 7/10 had serological testing and all were seropositive. New infections were detected in three residents and one staff. Interpretation: RT-PCR provides a point prevalence of SARS-CoV-2 infection but significantly underestimates total exposure in outbreak settings. In care homes experiencing large COVID-19 outbreaks, most residents and staff had neutralising SARS-CoV-2 antibodies, which was not associated with age or symptoms.

Background: We investigated six London care homes experiencing a COVID-19 outbreak and found high rates of SARS-CoV-2 infection among residents and staff. Here we report follow-up investigations including antibody testing in the same care homes five weeks later. Methods: Residents and staff in the initial investigation had a repeat nasal swab for SARS-CoV-2 RT-PCR and a blood test for SARS CoV-2 antibodies using ELISA based on SARS-CoV-2 native viral antigens derived from infected cells and virus neutralisation. Findings: Of the 518 residents and staff in the initial investigation, 186/241 (77.2%) surviving residents and 208/ 254 (81.9%) staff underwent serological testing. Almost all SARS-CoV-2 RT-PCR positive residents and staff were seropositive five weeks later, whether symptomatic (residents 35/35, 100%; staff, 22/22, 100%) or asymptomatic (residents 32/33, 97.0%; staff 21/22, 95.5%). Symptomatic but SARS-CoV-2 RT-PCR negative residents and staff also had high seropositivity rates (residents 23/27, 85.2%; staff 18/21, 85.7%), as did asymptomatic RT-PCR negative individuals (residents 61/91, 67.0%; staff 95/143, 66.4%). Neutralising antibody was detected in 118/ 132 (89.4%) seropositive individuals and was not associated with age or symptoms. Ten residents (10/79 retested, 12.7%) remained RT-PCR positive but with higher RT-PCR cycle threshold values; 7/10 had serological testing and all were seropositive. New infections were detected in three residents and one staff. Interpretation: RT-PCR provides a point prevalence of SARS-CoV-2 infection but significantly underestimates total exposure in outbreak settings. In care homes experiencing large COVID-19 outbreaks, most residents and staff had neutralising SARS-CoV-2 antibodies, which was not associated with age or symptoms.

Objective We describe cases of invasive group A Streptococcus (iGAS) in mothers or neonates and assess management according to national guidelines, which recommend administering antibiotics to both mother and neonate if either develops iGAS infection within 28 days of birth and investigation of clusters in maternity units.Design Cross-sectional retrospective study. Setting and population Notified confirmed iGAS cases in either mothers or neonates with onset within 28 days of birth in London and the South East of England between 2010 and 2016Method Review of public health records of notified cases.Main outcome measures Incidence and onset time of iGAS in postpartum mothers and babies, proportion given prophylaxis, maternity unit clusters within 6 months.Results We identified 134 maternal and 21 neonatal confirmed iGAS infections. The incidence (in 100 000 person years) of iGAS in women within 28 days postpartum was 109 (95% CI 90-127) compared with 1.3 in other females aged 15-44. For neonates the incidence was 1.5 (95% CI 9-23). The median onset time was 2 days postpartum [interquartile range (IQR) 0-5 days] for mothers and 12 days (IQR 7-15 days) for neonates. All eligible mothers and most (109, 89%) eligible neonates received chemoprophylaxis. Of 20 clusters (59 cases of GAS and iGAS) in maternity units, two clusters involved possible transmission. However, in 6 of 15 clusters, GAS isolates were not saved for comparison even after relevant guidance was issued.Conclusions iGAS infection remains a potential postpartum risk. Prophylaxis among neonates and storage of isolates from maternity cases can be improved.