Predictive symptoms for COVID-19 in the community: REACT-1 study of over 1 million people.

BACKGROUND: Rapid detection, isolation, and contact tracing of community COVID-19 cases are essential measures to limit the community spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We aimed to identify a parsimonious set of symptoms that jointly predict COVID-19 and investigated whether predictive symptoms differ between the B.1.1.7 (Alpha) lineage (predominating as of April 2021 in the US, UK, and elsewhere) and wild type. METHODS AND FINDINGS: We obtained throat and nose swabs with valid SARS-CoV-2 PCR test results from 1,147,370 volunteers aged 5 years and above (6,450 positive cases) in the REal-time Assessment of Community Transmission-1 (REACT-1) study. This study involved repeated community-based random surveys of prevalence in England (study rounds 2 to 8, June 2020 to January 2021, response rates 22%-27%). Participants were asked about symptoms occurring in the week prior to testing. Viral genome sequencing was carried out for PCR-positive samples with N-gene cycle threshold value < 34 (N = 1,079) in round 8 (January 2021). In univariate analysis, all 26 surveyed symptoms were associated with PCR positivity compared with non-symptomatic people. Stability selection (1,000 penalized logistic regression models with 50% subsampling) among people reporting at least 1 symptom identified 7 symptoms as jointly and positively predictive of PCR positivity in rounds 2-7 (June to December 2020): loss or change of sense of smell, loss or change of sense of taste, fever, new persistent cough, chills, appetite loss, and muscle aches. The resulting model (rounds 2-7) predicted PCR positivity in round 8 with area under the curve (AUC) of 0.77. The same 7 symptoms were selected as jointly predictive of B.1.1.7 infection in round 8, although when comparing B.1.1.7 with wild type, new persistent cough and sore throat were more predictive of B.1.1.7 infection while loss or change of sense of smell was more predictive of the wild type. The main limitations of our study are (i) potential participation bias despite random sampling of named individuals from the National Health Service register and weighting designed to achieve a representative sample of the population of England and (ii) the necessary reliance on self-reported symptoms, which may be prone to recall bias and may therefore lead to biased estimates of symptom prevalence in England. CONCLUSIONS: Where testing capacity is limited, it is important to use tests in the most efficient way possible. We identified a set of 7 symptoms that, when considered together, maximize detection of COVID-19 in the community, including infection with the B.1.1.7 lineage.

COVID-19 symptoms and SARS-CoV-2 infection among people living with HIV in the US: the MACS/WIHS combined cohort study.

BACKGROUND: SARS-CoV-2 infection among People Living With HIV (PLWH) is not well-described. OBJECTIVE: To study COVID-19 symptoms and SARS-CoV-2 PCR-based swab testing among participants of the Multicenter AIDS Cohort Study (MACS) and Women's Interagency HIV Study (WIHS). METHODS: A telephone survey was collected April-June 30, 2020. Symptom and testing prevalence were explored. Multivariable logistic regression was used to examine the factors associated with SARS-CoV-2 positivity. RESULTS: The survey was completed by 3411 participants, including 2078 (61%) PLWH and 1333 HIV-seronegative (SN) participants from across the US. Thirteen percent (n = 441) were tested for SARS-CoV-2 infection (13.4% of PLWH vs 12.2% of SN). Among those tested, positivity was higher in PLWH than SN (11.2% vs 6.1%, p = 0.08). Reasons for not being tested included testing not being available (30% of participants) and not knowing where to get tested (16% of participants). Most symptoms reported since January 2020 were similar in PLWH and SN, including headache (23% vs. 24%), myalgias (19% vs 18%), shortness of breath (14% vs 13%), chills (12% vs 10%), fever (6% vs 6%) and loss of taste or smell (6% vs 7%). Among PLWH who tested positive for SARS-CoV-2 DNA, the most common symptoms were headache (71%), myalgia (68%), cough (68%) and chills (65%). In multivariable analysis among those tested, the odds of SARS-CoV-2 positivity were higher among PLWH than SN (aOR = 2.22 95%CI = 01.01-4.85, p = 0.046) and among those living with others versus living alone (aOR = 2.95 95%CI = 1.18-7.40). CONCLUSION: Prevalence and type of COVID-19 symptoms were similar in PLWH and SN. SARS-CoV-2 infection may be elevated among PLWH.

Correlations of Clinical and Laboratory Characteristics of COVID-19: A Systematic Review and Meta-Analysis.

(1) Background: The global threat of Coronavirus disease 2019 (COVID-19) continues. The diversity of clinical characteristics and progress are reported in many countries as the duration of the pandemic is prolonged. We aimed to perform a novel systematic review and meta-analysis focusing on findings about correlations between clinical characteristics and laboratory features of patients with COVID-19. (2) Methods: We analyzed cases of COVID-19 in different countries by searching PubMed, Embase, Web of Science databases and Google Scholar, from the early stage of the outbreak to late March. Clinical characteristics, laboratory findings, and treatment strategies were retrospectively reviewed for the analysis. (3) Results: Thirty-seven (n = 5196 participants) COVID-19-related studies were eligible for this systematic review and meta-analysis. Fever, cough and fatigue/myalgia were the most common symptoms of COVID-19, followed by some gastrointestinal symptoms which are also reported frequently. Laboratory markers of inflammation and infection including C-reactive protein (CRP) (65% (95% confidence interval (CI) 56-81%)) were elevated, while lymphocyte counts were decreased (63% (95% CI 47-78%)). Meta-analysis of treatment approaches indicated that three modalities of treatment were predominantly used in the majority of patients with a similar prevalence, including antiviral agents (79%), antibiotics (78%), and oxygen therapy (77%). Age was negatively correlated with number of lymphocytes, but positively correlated with dyspnea, number of white blood cells, neutrophils, and D-dimer. Chills had been proved to be positively correlated with chest tightness, lung abnormalities on computed tomography (CT) scans, neutrophil/lymphocyte/platelets count, D-dimer and CRP, cough was positively correlated with sputum production, and pulmonary abnormalities were positively correlated with CRP. White blood cell (WBC) count was also positively correlated with platelet counts, dyspnea, and neutrophil counts with the respective correlations of 0.668, 0.728, and 0.696. (4) Conclusions: This paper is the first systematic review and meta-analysis to reveal the relationship between various variables of clinical characteristics, symptoms and laboratory results with the largest number of papers and patients until now. In elderly patients, laboratory and clinical characteristics indicate a more severe disease course. Moreover, treatments such as antiviral agents, antibiotics, and oxygen therapy which are used in over three quarters of patients are also analyzed. The results will provide "evidence-based hope" on how to manage this unanticipated and overwhelming pandemic.

A phase I clinical trial of Ad5/3-Δ24, a novel serotype-chimeric, infectivity-enhanced, conditionally-replicative adenovirus (CRAd), in patients with recurrent ovarian cancer.

OBJECTIVE: The conditionally replicative adenovirus Ad5/3-Δ24 has a type-3 knob incorporated into the type-5 fiber that facilitates enhanced ovarian cancer infectivity. Preclinical studies have shown that Ad5/3-Δ24 achieves significant oncolysis and anti-tumor activity in ovarian cancer models. The purpose of this study was to evaluate in a phase I trial the feasibility and safety of intraperitoneal (IP) Ad5/3-Δ24 in recurrent ovarian cancer patients. METHODS: Eligible patients were treated with IP Ad5/3-Δ24 for 3 consecutive days in one of three dose cohorts ranging 1 × 10(10)-1 × 10(12)vp. Toxicity was assessed utilizing CTC grading and efficacy with RECIST. Ascites, serum, and other samples were obtained to evaluate gene transfer, generation of wildtype virus, viral shedding, and antibody response. RESULTS: Nine of 10 patients completed treatment per protocol. A total of 15 vector-related adverse events were experienced in 5 patients. These events included fever or chills, nausea, fatigue, and myalgia. All were grades 1-2 in nature, transient, and medically managed. Of the 8 treated patients evaluable for response, six patients had stable disease and 2 patients had progressive disease. Three patients had decreased CA-125 from pretreatment levels one month after treatment. Ancillary biologic studies indicated Ad5/3-Δ24 replication in patients in the higher dose cohorts. All patients experienced an anti-adenoviral neutralizing antibody effect. CONCLUSIONS: This study suggests the feasibility and safety of a serotype chimeric infectivity-enhanced CRAd, Ad5/3-Δ24, as a potential therapeutic option for recurrent ovarian cancer patients.

Viral load and clinical features in children infected with seasonal influenza B in 2006/2007.

BACKGROUND/PURPOSE: In influenza B infection, viral load is believed to be related to the severity of clinical illness. The correlation between viral load and symptoms is not known. We conducted a study to assess the relationship between virus load and clinical features in children infected with influenza B, in the hope that clinical features could be used as surrogate markers of viral load to guide treatment. METHODS: Between December 2006 and February 2007, 228 patients with fever and respiratory symptoms were prospectively enrolled in our tertiary hospital-based study. Real-time reverse transcription polymerase chain reaction (RT-PCR) was performed to determine viral load. RESULTS: Real-time RT-PCR was positive for influenza B in 76 patients. Using virus culture as the gold standard, the sensitivity and specificity were 95% and 87%, respectively. Influenza culture positive rate significantly correlated with viral load (p = 0.03). The median copy number of influenza B virus in the 76 RT-PCR positive patients was 9735 copies/ml (range 4.8×10¹-2.0×106 copies/ml). Samples obtained later in the clinical course tended to have lower viral load (p = 0.7), while patient age (p = 0.72) and fever duration (p = 0.96) positively related to viral load. In patients >3 years of age, myalgia was related to statistically lower viral loads (14300 vs. 1180; p = 0.025). Patients with chills tended to have higher viral loads (72450 vs. 7640; p = 0.1). Patients with abdominal pain tended to have lower viral loads (1998 vs. 12550; p = 0.06). CONCLUSION: Culture rate positively correlated with viral load. Patients with myalgia had a lower viral load.

West Nile virus encephalitis.

West Nile virus (WNV) is a mosquito-borne virus that has caused a large number of deaths in the United States since the first outbreak in New York City in 1998. The outbreak initially was limited to the northeast but has since spread across the entire continental United States. WNV causes a variety of clinical symptoms, but the most severe consequences result from central nervous system infection, resulting in meningitis, encephalitis, or meningoencephalitis. We present a case of a 62-year-old male with metastatic cancer, who died as a result of WNV encephalitis. This is followed by a discussion on the epidemiology of WNV and a detailed summary of the methods and resources available to make a diagnosis of WNV infection postmortem. The material presented in the discussion should provide the forensic pathologist with all the information necessary to make a diagnosis of WNV infection postmortem. If nothing else, the routine collection and storage of serum, cerebrospinal fluid, and tissue for every case can enable the forensic pathologist to make this diagnosis even in cases in which WNV is not suspected until after autopsy.