Detailed analysis of in-hospital transmission of SARS-CoV-2 using whole genome sequencing.

BACKGROUND: Hospital transmission of SARS-CoV-2 has proved difficult to control, with healthcare-associated infections troublesome throughout. AIM: To understand factors contributing to hospital transmission of infections, which is necessary for containing spread. METHODS: An outbreak of 56 staff and patient cases of COVID-19 over a 31-day period in a tertiary referral unit is presented, with at least a further 29 cases identified outside of the unit and the hospital by whole genome sequencing (WGS). FINDINGS: Transmission is documented from staff to staff, staff to patients, and patients to staff, showing disruption of a tertiary referral service, despite implementation of nationally recommended control measures, superior ventilation, and use of personal protective equipment. There was extensive spread from the index case, despite this patient spending only 10 h bed bound on the ward in strict cubicle isolation and with an initial single target low level (CT = 32) polymerase chain reaction test. CONCLUSION: This investigation highlights how effectively and rapidly SARS-CoV-2 can spread in certain circumstances. It raises questions about infection control measures in place at the time and calls into question the premise that transmissibility can be reliably detected by using lower sensitivity rapid antigen lateral flow tests. We also highlight the value of early intervention in reducing impact as well as the value of WGS in understanding outbreaks.

Getting to the Heart of In-hospital Transmission of SARS-CoV-2 with the Help of Whole Genome Sequencing

We present an outbreak of 56 staff and patient cases of COVID-19 over a 31 day period in a tertiary referral unit, with at least a further 29 cases identified outside of the unit and the hospital by whole genome sequencing (WGS). We document transmission from staff-to-staff, staff-to-patients and patients-to-staff and show disruption of a tertiary referral service, despite implementation of nationally recommended control measures, superior ventilation and use of PPE. We demonstrate extensive spread from the index case, despite them spending only 10 hours bed bound on the ward in strict cubicle isolation and with an initial single target low level (CT=32) PCR test. This investigation highlights critical issues including how effectively and explosively SARS-CoV-2 can spread in certain circumstances. It raises questions about infection control measures in place at the time and calls into question the premise that transmissibility can be reliably detected using lower sensitivity rapid antigen lateral flow tests. We also highlight the value of early intervention in reducing impact as well as the value of WGS in understanding outbreaks.

A study protocol for a double-blind randomised placebo-controlled trial evaluating the efficacy of carrageenan nasal and throat spray for COVID-19 prophylaxis—ICE-COVID

Introduction At present, vaccines form the only mode of prophylaxis against COVID-19. The time needed to achieve mass global vaccination and the emergence of new variants warrants continued research into other COVID-19 prevention strategies. The severity of COVID-19 infection is thought to be associated with the initial viral load, and for infection to occur, viruses including SARS-CoV-2 must first penetrate the respiratory mucus and attach to the host cell surface receptors. Carrageenan, a sulphated polysaccharide extracted from red edible seaweed, has shown efficacy against a wide range of viruses in clinical trials through the prevention of viral entry into respiratory host cells. Carrageenan has also demonstrated in vitro activity against SARS-CoV-2. Methods and analysis A single-centre, randomised, double-blinded, placebo-controlled phase III trial was designed. Participants randomised in a 1:1 allocation to either the treatment arm, verum Coldamaris plus (1.2 mg iota-carrageenan (Carragelose®), 0.4 mg kappa-carrageenan, 0.5% sodium chloride and purified water), or placebo arm, Coldamaris sine (0.5% sodium chloride) spray applied daily to their nose and throat for 8 weeks, while completing a daily symptom tracker questionnaire for a total of 10 weeks. Primary outcome Acquisition of COVID-19 infection as confirmed by a positive PCR swab taken at symptom onset or seroconversion during the study. Secondary outcomes include symptom type, severity and duration, subsequent familial/household COVID-19 infection and infection with non-COVID-19 upper respiratory tract infections. A within-trial economic evaluation will be undertaken, with effects expressed as quality-adjusted life years. Discussion This is a single-centre, phase III, double-blind, randomised placebo-controlled clinical trial to assess whether carrageenan nasal and throat spray reduces the risk of development and severity of COVID-19. If proven effective, the self-administered prophylactic spray would have wider utility for key workers and the general population. Trial registration NCT04590365;ClinicalTrials.gov NCT04590365. Registered on 19 October 2020. Supplementary Information The online version contains supplementary material available at 10.1186/s13063-022-06685-z.

Lowered COVID-19 mRNA vaccine antibody response in MS patientstreated with B-cell depleting and S1P-receptor-targeting therapies compared to controls: interim analysis

Objective: Assess the SARS-CoV2 Spike antibody response in multiple sclerosis (MS) patients on high efficacy immunotherapies. Background: There is limited knowledge about SARS-CoV2 mRNA vaccine response in MS patients on immunotherapy. Design/Methods: Patients with MS, aged 18-65, on fingolimod, siponimod, ofatumumab, or ocrelizumab for at least 3 months prior to first mRNA SARS-CoV2 vaccine (Pfizer or Moderna) were offered enrollment. A cohort of healthy controls who received the mRNA vaccines were also enrolled. Blood samples for the SARS-CoV2 Spike antibody (Anti-SARS-CoV2 S, RocheElecsys) were collected 2-3 months after the second mRNA vaccine. The proportion who seroconverted (antibody>0.4 U/ml), and SARS-CoV2 Spike antibody levels were assessed. Results: A total of 39 MS patients (6 fingolimod, 33 ocrelizumab) and 31 controls were included in this interim analysis. 33%(13/39) of MS patients seroconverted, compared to 100%(31/31) in the control group, with an estimated risk difference of -0.67,(95% confidence interval: -0.81, -0.52;Fisher's exact test, p=9.0∗10-10 ). There was no difference in seroconversion rates between MS patients who received the Pfizer (34%, 10/29) versus the Moderna vaccine (30%, 3/10) (95% confidence interval -0.38, 0.29;Fisher's exact test=1). Seroconversion was found in 100% (31/31) of controls, 66.7% (4/6) of fingolimod-treated patients, and 27.3% (9/33) of ocrelizumab-treated patients (three group comparison, Fisher's exact test p-value =2.7∗10 -10). The median Spike antibody level was <0.4 U/ml in MS patients, and 1,663 U/ml in controls (Wilcoxon rank sum test, p-value= 1.0∗10-12 ). The median Spike antibody level in the ocrelizumab group was <0.4 U/ml, 3.45 U/ml in the fingolimod group, and 1,663 U/ml in the control group (Kruskal Wallis test, p-value=5.9∗10-12 ). Total IgG correlated with Spike antibody levels in the ocrelizumab-treated group only (Spearman correlation, p=0.025). Conclusions: MS patients on ocrelizumab and fingolimod have significantly lower rates of seroconversion, and lower median Spike antibody levels in response to the mRNA SARS-CoV2 vaccines compared to controls.

COVID-19 and neurologic outcomes in multiple sclerosis and related disorders

Introduction: SARs-CoV-19 infection (COVID-19) is associated with various neurologic symptoms. A full range of neurologic outcomes in patients with multiple sclerosis (MS) and related disorders (MSRD) following COVID-19 illness is not well understood. Objectives: To investigate neurologic outcomes in patients with MSRD post COVID-19. Methods: This was a retrospective medical records review study of adult patients with MSRD who had confirmed COVID-19 infection at the Brigham MS Center, between March 9, 2020 and April 1, 2021. We reviewed demographics, MS history, COVID-19 outcomes, neurologic symptoms, and MRI data. Neurologic worsening post-COVID-19 was defined as having a relapse, pseudo-relapse, new brain MRI activity, worsening of preexisting MS symptoms, or development of other long-term neurologic symptoms. Results: 111 patients, 85 (77%) females, with a mean [SD] age of 49 [12.2] years, and a mean [SD] EDSS of 3.4 [2.7] were identified. 72 (65%) had relapsing remitting MS, 21 (19%) had secondary and 8 (7%) had primary progressive MS, 2 (2%) had clinically isolated syndrome, and 8 (7%) had related disorders. 17 (15%) patients were asymptomatic, 63 (57%) had mild COVID-19 defined as symptoms not requiring hospitalization, 22 (20%) had moderate COVID-19 requiring hospitalization, 3 (3%) had severe COVID-19 requiring ICU admission, 2 (2%) died due to COVID-19 and 4 (4%) had unknown COVID-19 outcomes. 85 (77%) completely recovered from COVID-19. 41 patients (37%) had neurologic worsening post COVID-19. Of those with neurologic worsening, 19 (46%) had pseudo-relapses, 2 (4.8%) had relapses, and 27 (66%) patients reported worsening of preexisting MS symptoms, or other new longterm neurologic symptoms at the last follow up visit. 55 patients had brain MRI scans post COVID-19 with a mean [SD] between MRI and infection of 144.6 [107.8] days. 5 patients had new lesions on T2 or T1Gd+ scans. Neurologic worsening was associated with moderate or severe COVID-19 (p=0.0006), treatment for COVID-19 (p=0.0061), and incomplete COVID-19 recovery (p=0.0267) but not with age, sex, MS type, ethnicity, disease duration, EDSS, vitamin D use, or type or presence of disease modifying therapy. Conclusions: COVID-19 severity and lack of complete systemic recovery was associated with new or worsening neurologic symptoms in 37% of MSRD patients.

Health Care Workers and Patients as Trojan Horses: a COVID19 ward outbreak.

BACKGROUND: Transmission in healthcare settings can result in significant infections in healthcare workers and patients. Understanding infection dynamics has important implications for methods employed in hospitals to prevent nosocomial transmission events. METHODS: In this case series report we describe a cluster of COVID-19 (Coronavirus disease 2019) in a tertiary care university hospital, in the early phases of the epidemic, after hospital visiting had been stopped and when the UK lockdown was in place. FINDINGS: A 48 year old patient developed COVID-19 31 days post-admission and four days after admission to a medical ward from ITU. Infection was likely acquired from an asymptomatic or minimally symptomatic healthcare worker (HCW). Subsequent investigation over a 14 day period revealed symptoms in 23 staff members and five linked cases in patients on the same ward.Nine of the 23 affected staff members provided care for and had direct exposure with the index case. Four staff reported caring for the index case without use of personal protective equipment. One was coughed on directly by the patient 24 hours prior to the onset of symptoms. CONCLUSION: SARS CoV2 infection can be introduced to a ward area by asymptomatic and minimally symptomatic healthcare workers. Staff members and patients can act as Trojan horses carrying infection into and around the hospital, setting up unexpected transmission events.Transmission of infection from pre-symptomatic, asymptomatic and minimally symptomatic individuals means that universal use of measures to prevent transmission is required for successful reduction of transmission events in the hospital setting.