ABSTRACT
Clinically, COVID-19 is often a mild or asymptomatic illness. However, in a subset of patients, a more severe illness with one or more organ dysfunction requiring intensive care (ICU) admission occurs (stated as critical COVID-19). Most studies assessing the immune responses in COVID-19 focus on patients with non-critical COVID-19, often assessing single biological domain (such as cytokines, leukocytes, proteomics, or transcriptomics) at single time point in patient’s illness. In this context, our cohort study of patients with critical COVID-19 with demographically similar pre-pandemic controls, characterised the longitudinal changes in multiple biological domains (28 plasma cytokines, 30 immune cell subsets identified using mass cytometry and pan-leukocyte transcriptome) at four clinically relevant timepoints between ICU admission and discharge. When compared with controls, on ICU admission day, patients with critical COVID-19, had altered cytokine/chemokine profile (high interleukin-6 (IL-6), IL-10, IL-13, CXCL10, with low CCL17, and CXCL5)), raised histones (H3.1, H3R8), robust plasmablast response despite lymphopenia, with enrichment of immunoglobulin production and interferon pathways in the transcriptome. Analyses of longitudinal transcriptome data highlights three immunologically distinct clusters that were discordant to clinical time points, indicating that the clinical time points do capture immune response trajectory. Complete integration of this multi-domain longitudinal data indicated that ~ 70% of immunological heterogeneity is explained by the transcriptome.
Subject(s)
COVID-19 , LymphopeniaABSTRACT
Background: The global COVID-19 pandemic has caused worldwide disruption with its exponential spread mandating national and international lockdown measures. Hospital-associated transmission has been identified as a major factor in the perpetuation of COVID-19, with healthcare workers at high-risk of becoming infected with SARS-CoV-2 and representing important vectors for spread, but not routinely having their clinical observations monitored or being tested for COVID-19. Methods: A single-center, prospective observational study of 60 healthcare workers will explore how many healthcare workers in high-risk areas develop COVID-19 infection over a thirty day period. High-risk areas are defined as COVID positive wards, the intensive care unit or the accident and emergency department. Healthcare workers (HCWs) will be recruited and have daily self-administered nasopharyngeal SARS-CoV-2 PCR tests. They will also be provided with a wearable medical device to measure their clinical observations during non-working hours, and be asked to complete a daily self-reported symptom questionnaire over the study period. Statistical analysis will assess the proportion of healthcare workers who develop COVID-19 infection as a primary objective, with secondary objectives exploring what symptoms are developed, time-to-event, and deviations in clinical observations. Discussion: At present clinical observations, symptoms and COVID-19 PCR swabs are not routinely undertaken for healthcare workers. If the CEDiD (COVID-19 Early Detection in Doctors and Healthcare Workers) study is successful, it will provide useful information for workforce decisions in reducing hospital-associated transmission of COVID-19. The data will help in determining whether there are early warning signs for development of COVID-19 infections amongst healthcare workers and may contribute to the evidence base advocating for more regular testing of healthcare workers observations, symptoms and COVID-19 status. Trial registration ClinicalTrials.gov, NCT04363489. Registered on 27th July 2020
Subject(s)
COVID-19ABSTRACT
Antibody (Ab) responses to SARS-CoV-2 can be detected in most infected individuals 10-15 days following the onset of COVID-19 symptoms. However, due to the recent emergence of this virus in the human population it is not yet known how long these Ab responses will be maintained or whether they will provide protection from re-infection. Using sequential serum samples collected up to 94 days post onset of symptoms (POS) from 65 RT-qPCR confirmed SARS-CoV-2-infected individuals, we show seroconversion in >95% of cases and neutralizing antibody (nAb) responses when sampled beyond 8 days POS. We demonstrate that the magnitude of the nAb response is dependent upon the disease severity, but this does not affect the kinetics of the nAb response. Declining nAb titres were observed during the follow up period. Whilst some individuals with high peak ID50 (>10,000) maintained titres >1,000 at >60 days POS, some with lower peak ID50 had titres approaching baseline within the follow up period. A similar decline in nAb titres was also observed in a cohort of seropositive healthcare workers from Guys and St Thomas Hospitals. We suggest that this transient nAb response is a feature shared by both a SARS-CoV-2 infection that causes low disease severity and the circulating seasonal coronaviruses that are associated with common colds. This study has important implications when considering widespread serological testing, Ab protection against re-infection with SARS-CoV-2 and the durability of vaccine protection.