Cheryl Cohen

Bio: Cheryl Cohen is an academic researcher from University of the Witwatersrand. The author has contributed to research in topics: Medicine & Population. The author has an hindex of 46, co-authored 221 publications receiving 9512 citations. Previous affiliations of Cheryl Cohen include National Institute of Communicable Diseases & University of London.

SARS-CoV-2 501Y.V2 escapes neutralization by South African COVID-19 donor plasma.

Abstract: SARS-CoV-2 501Y.V2 (B.1.351), a novel lineage of coronavirus causing COVID-19, contains substitutions in two immunodominant domains of the spike protein. Here, we show that pseudovirus expressing 501Y.V2 spike protein completely escapes three classes of therapeutically relevant antibodies. This pseudovirus also exhibits substantial to complete escape from neutralization, but not binding, by convalescent plasma. These data highlight the prospect of reinfection with antigenically distinct variants and foreshadows reduced efficacy of spike-based vaccines. Substitutions in SARS-CoV-2 spike protein present in the B.1.351 variant first detected in South Africa, when expressed in pseudoviruses, mediate escape from neutralization by monoclonal antibodies under clinical development and by plasma from individuals previously infected with SARS-CoV-2, but do not prevent binding of convalescent plasma to recombinant spike protein containing B.1.351 lineage substitutions.

Increased risk of SARS-CoV-2 reinfection associated with emergence of Omicron in South Africa

Abstract: We provide two methods for monitoring reinfection trends in routine surveillance data to identify signatures of changes in reinfection risk and apply these approaches to data from South Africa’s severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic to date. Although we found no evidence of increased reinfection risk associated with circulation of the Beta (B.1.351) or Delta (B.1.617.2) variants, we did find clear, population-level evidence to suggest immune evasion by the Omicron (B.1.1.529) variant in previously infected individuals in South Africa. Reinfections occurring between 1 November 2021 and 31 January 2022 were detected in individuals infected in all three previous waves, and there has been an increase in the risk of having a third infection since mid-November 2021. Description Omicron and reinfection risk So far, our experience with pandemic coronavirus has been that the emergence of new variants is not detected until there has been substantial community transmission. Early in November 2021, South African scientists spotted reinfections consistent with the timing of the emergence of the Omicron variant (B.1.1.529). In a population largely untouched by vaccines but widely infected, Pulliam et al. found that Beta or Delta variants rarely caused reinfection. However, after 31 October 2021, individuals were found who had had three experiences of infection (see the Perspective by Zelner and Eisenberg). The culprit was the rapidly emerging Omicron variant, with multiple mutations in the Spike protein. This variant’s chief advantage is its ability to evade naturally acquired immunity. Fortunately, the Omicron variant does not fully evade vaccine-derived immunity, but only those privileged to have been vaccinated can benefit. —CA Analysis of routine surveillance data from South Africa indicates that the Omicron variant of SARS-CoV-2 evades immunity from prior infection. INTRODUCTION Globally, there have been more than 404 million cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with 5.8 million confirmed deaths as of February 2022. South Africa has experienced four waves of SARS-CoV-2 transmission, with the second, third, and fourth waves being driven by the Beta, Delta, and Omicron variants, respectively. A key question with the emergence of new variants is the extent to which they are able to reinfect those who have had a prior natural infection. RATIONALE We developed two approaches to monitor routine epidemiological surveillance data to determine whether SARS-CoV-2 reinfection risk has changed through time in South Africa in the context of the emergence of the Beta (B.1.351), Delta (B.1.617.2), and Omicron (B.1.1.529) variants. We analyzed line-list data on positive tests for SARS-CoV-2 with specimen receipt dates between 4 March 2020 and 31 January 2022 collected through South Africa’s National Notifiable Medical Conditions Surveillance System. Individuals having sequential positive tests at least 90 days apart were considered to have suspected reinfections. Our routine monitoring of reinfection risk included comparison of reinfection rates with the expectation under a null model (approach 1) and estimation of the time-varying hazards of infection and reinfection throughout the epidemic (approach 2) based on model-based reconstruction of the susceptible populations eligible for primary and second infections. RESULTS A total of 105,323 suspected reinfections were identified among 2,942,248 individuals with laboratory-confirmed SARS-CoV-2 who had a positive test result at least 90 days before 31 January 2022. The number of reinfections observed through the end of the third wave in September 2021 was consistent with the null model of no change in reinfection risk (approach 1). Although increases in the hazard of primary infection were observed after the introduction of both the Beta and Delta variants, no corresponding increase was observed in the reinfection hazard (approach 2). Contrary to expectation, the estimated hazard ratio for reinfection versus primary infection was lower during waves driven by the Beta and Delta variants than for the first wave: the relative hazard ratio for wave 2 versus wave 1 was 0.71 [95% confidence interval (95% CI): 0.60 to 0.85]; the relative hazard ratio for wave 3 versus wave 1 was 0.54 (95% CI: 0.45 to 0.64). By contrast, the recent spread of the Omicron variant has been associated with an increase in reinfection hazard coefficient. The estimated relative hazard ratio for reinfection versus primary infection versus wave 1 was 1.75 (95% CI: 1.48 to 2.10) for the period of Omicron emergence (1 November 2021 to 30 November 2021) and 1.70 (95% CI: 1.44 to 2.04) for wave 4 versus wave 1. Individuals with identified reinfections since 1 November 2021 had experienced primary infections in all three prior waves, and an increase in third infections has been detected since mid-November 2021. Many individuals experiencing third infections had second infections during the third (Delta) wave that ended in September 2021, strongly suggesting that these infections resulted from immune evasion rather than waning immunity. CONCLUSION Population-level evidence suggests that the Omicron variant is associated with a marked ability to evade immunity from prior infection. In contrast, there is no population-wide epidemiological evidence of immune escape associated with the Beta or Delta variants. This finding has important implications for public health planning, particularly in countries such as South Africa with high rates of immunity from prior infection. The further development of methods to track reinfection risk during pathogen emergence, including refinements to assess the impact of waning immunity, account for vaccine-derived protection, and monitor the risk of multiple reinfections, will be important for future pandemic preparedness. SARS-CoV-2 reinfection patterns in South Africa. South Africa has experienced four waves of SARS-CoV-2 transmission, each driven by the emergence of a new variant. Reinfection of previously infected individuals was relatively rare through the end of the third wave. Methods developed in South Africa to monitor reinfection trends led to the early detection of increased reinfection risk associated with the Omicron variant.

Harrison's Principles of Internal Medicine

Abstract: The 11th edition of Harrison's Principles of Internal Medicine welcomes Anthony Fauci to its editorial staff, in addition to more than 85 new contributors. While the organization of the book is similar to previous editions, major emphasis has been placed on disorders that affect multiple organ systems. Important advances in genetics, immunology, and oncology are emphasized. Many chapters of the book have been rewritten and describe major advances in internal medicine. Subjects that received only a paragraph or two of attention in previous editions are now covered in entire chapters. Among the chapters that have been extensively revised are the chapters on infections in the compromised host, on skin rashes in infections, on many of the viral infections, including cytomegalovirus and Epstein-Barr virus, on sexually transmitted diseases, on diabetes mellitus, on disorders of bone and mineral metabolism, and on lymphadenopathy and splenomegaly. The major revisions in these chapters and many

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

Abstract: Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

Nextstrain: real-time tracking of pathogen evolution.

Abstract: Summary Understanding the spread and evolution of pathogens is important for effective public health measures and surveillance. Nextstrain consists of a database of viral genomes, a bioinformatics pipeline for phylodynamics analysis, and an interactive visualization platform. Together these present a real-time view into the evolution and spread of a range of viral pathogens of high public health importance. The visualization integrates sequence data with other data types such as geographic information, serology, or host species. Nextstrain compiles our current understanding into a single accessible location, open to health professionals, epidemiologists, virologists and the public alike. Availability and implementation All code (predominantly JavaScript and Python) is freely available from github.com/nextstrain and the web-application is available at nextstrain.org.

Features, Evaluation and Treatment Coronavirus (COVID-19)

Abstract: According to the World Health Organization (WHO), viral diseases continue to emerge and represent a serious issue to public health In the last twenty years, several viral epidemics such as the severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002 to 2003, and H1N1 influenza in 2009, have been recorded Most recently, the Middle East respiratory syndrome coronavirus (MERS-CoV) was first identified in Saudi Arabia in 2012 In a timeline that reaches the present day, an epidemic of cases with unexplained low respiratory infections detected in Wuhan, the largest metropolitan area in China's Hubei province, was first reported to the WHO Country Office in China, on December 31, 2019 Published literature can trace the beginning of symptomatic individuals back to the beginning of December 2019 As they were unable to identify the causative agent, these first cases were classified as "pneumonia of unknown etiology " The Chinese Center for Disease Control and Prevention (CDC) and local CDCs organized an intensive outbreak investigation program The etiology of this illness is now attributed to a novel virus belonging to the coronavirus (CoV) family, COVID-19 On February 11, 2020, the WHO Director-General, Dr Tedros Adhanom Ghebreyesus, announced that the disease caused by this new CoV was a "COVID-19," which is the acronym of "coronavirus disease 2019" In the past twenty years, two additional coronavirus epidemics have occurred SARS-CoV provoked a large-scale epidemic beginning in China and involving two dozen countries with approximately 8000 cases and 800 deaths, and the MERS-CoV that began in Saudi Arabia and has approximately 2,500 cases and 800 deaths and still causes as sporadic cases This new virus seems to be very contagious and has quickly spread globally In a meeting on January 30, 2020, per the International Health Regulations (IHR, 2005), the outbreak was declared by the WHO a Public Health Emergency of International Concern (PHEIC) as it had spread to 18 countries with four countries reporting human-to-human transmission An additional landmark occurred on February 26, 2020, as the first case of the disease, not imported from China, was recorded in the United States Initially, the new virus was called 2019-nCoV Subsequently, the task of experts of the International Committee on Taxonomy of Viruses (ICTV) termed it the SARS-CoV-2 virus as it is very similar to the one that caused the SARS outbreak (SARS-CoVs) The CoVs have become the major pathogens of emerging respiratory disease outbreaks They are a large family of single-stranded RNA viruses (+ssRNA) that can be isolated in different animal species For reasons yet to be explained, these viruses can cross species barriers and can cause, in humans, illness ranging from the common cold to more severe diseases such as MERS and SARS Interestingly, these latter viruses have probably originated from bats and then moving into other mammalian hosts — the Himalayan palm civet for SARS-CoV, and the dromedary camel for MERS-CoV — before jumping to humans The dynamics of SARS-Cov-2 are currently unknown, but there is speculation that it also has an animal origin The potential for these viruses to grow to become a pandemic worldwide seems to be a serious public health risk Concerning COVID-19, the WHO raised the threat to the CoV epidemic to the "very high" level, on February 28, 2020 Probably, the effects of the epidemic caused by the new CoV has yet to emerge as the situation is quickly evolving World governments are at work to establish countermeasures to stem possible devastating effects Health organizations coordinate information flows and issues directives and guidelines to best mitigate the impact of the threat At the same time, scientists around the world work tirelessly, and information about the transmission mechanisms, the clinical spectrum of disease, new diagnostics, and prevention and therapeutic strategies are rapidly developing Many uncertainties remain with regard to both the virus-host interac ion and the evolution of the epidemic, with specific reference to the times when the epidemic will reach its peak At the moment, the therapeutic strategies to deal with the infection are only supportive, and prevention aimed at reducing transmission in the community is our best weapon Aggressive isolation measures in China have led to a progressive reduction of cases in the last few days In Italy, in geographic regions of the north of the peninsula, political and health authorities are making incredible efforts to contain a shock wave that is severely testing the health system In the midst of the crisis, the authors have chosen to use the "Statpearls" platform because, within the PubMed scenario, it represents a unique tool that may allow them to make updates in real-time The aim, therefore, is to collect information and scientific evidence and to provide an overview of the topic that will be continuously updated