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.

Neurological symptoms and axonal damage in COVID-19 survivors: are there sequelae?

The persistence of neurological symptoms after SARS-CoV-2 infection, as well as the presence of late axonal damage, is still unknown. We performed extensive systemic and neurological follow-up evaluations in 107 out of 193 consecutive patients admitted to the COVID-19 medical unit, University Hospital of Verona, Italy between March and June 2020. We analysed serum neurofilament light chain (NfL) levels in all cases including a subgroup (n = 29) of patients with available onset samples. Comparisons between clinical and biomarker data were then performed. Neurological symptoms were still present in a significant number (n = 49) of patients over the follow-up. The most common reported symptoms were hyposmia (n = 11), fatigue (n = 28), myalgia (n = 14), and impaired memory (n = 11) and were more common in cases with severe acute COVID-19. Follow-up serum NfL values (15.2 pg/mL, range 2.4-62.4) were within normal range in all except 5 patients and did not differentiate patients with vs without persistent neurological symptoms. In patients with available onset and follow-up samples, a significant (p < 0.001) decrease of NfL levels was observed and was more evident in patients with a severe acute disease. Despite the common persistence of neurological symptoms, COVID-19 survivors do not show active axonal damage, which seems a peculiar feature of acute SARS-CoV-2 infection.

'Long COVID' syndrome.

SARS-CoV-2 has resulted in a global pandemic and an unprecedented public health crisis. Recent literature suggests the emergence of a novel syndrome known as 'long COVID', a term used to describe a diverse set of symptoms that persist after a minimum of 4 weeks from the onset of a diagnosed COVID-19 infection. Common symptoms include persistent breathlessness, fatigue and cough. Other symptoms reported include chest pain, palpitations, neurological and cognitive deficits, rashes, and gastrointestinal dysfunction. We present a complex case of a previously well 28-year-old woman who was diagnosed with COVID-19. After resolution of her acute symptoms, she continued to experience retrosternal discomfort, shortness of breath, poor memory and severe myalgia. Investigations yielded no significant findings. Given no alternative diagnosis, she was diagnosed with 'long COVID'.

Symptom Profiles and Progression in Hospitalized and Nonhospitalized Patients with Coronavirus Disease, Colorado, USA, 2020.

To improve recognition of coronavirus disease (COVID-19) and inform clinical and public health guidance, we randomly selected 600 COVID-19 case-patients in Colorado. A telephone questionnaire captured symptoms experienced, when symptoms occurred, and how long each lasted. Among 128 hospitalized patients, commonly reported symptoms included fever (84%), fatigue (83%), cough (73%), and dyspnea (72%). Among 236 nonhospitalized patients, commonly reported symptoms included fatigue (90%), fever (83%), cough (83%), and myalgia (74%). The most commonly reported initial symptoms were cough (21%-25%) and fever (20%-25%). In multivariable analysis, vomiting, dyspnea, altered mental status, dehydration, and wheezing were significantly associated with hospitalization, whereas rhinorrhea, headache, sore throat, and anosmia or ageusia were significantly associated with nonhospitalization. General symptoms and upper respiratory symptoms occurred earlier in disease, and anosmia, ageusia, lower respiratory symptoms, and gastrointestinal symptoms occurred later. Symptoms should be considered alongside other epidemiologic factors in clinical and public health decisions regarding potential COVID-19 cases.

[Features of 164 SARS-CoV-2 (+) patients consulting at an emergency room]. / Características clínicas y epidemiológicas del COVID-19 en la Unidad de Emergencia del Hospital Barros Luco: los primeros 164 pacientes.

BACKGROUND: The clinical manifestations, mortality rates, laboratory and imaging findings of SARS-CoV-2 infection are not yet fully elucidated. AIM: To describe the clinical manifestations, imaging and laboratory findings of 164 SARS-CoV-2 (+) patients consulting at an emergency room of a public general hospital in Santiago, Chile. MATERIAL AND METHODS: Review of medical records, imaging and laboratory results of 164 patients aged between 16 and 92 years (57.9% males) consulting at the emergency room between March 12 and April 27, 2020. RESULTS: The most common presenting symptom was dry cough in 47% of patients, followed by headache in 42% and myalgias in 42%. Forty five percent referred contact with an infected patient or having travelled out of town. Thirty-three (20%) required hospital admission and 5% required admission to an intensive care unit. CONCLUSIONS: These patients were predominantly young, and their most common symptoms were dry cough, headache and myalgias.

Prevalence of anosmia among COVID-19 patients in Taif City, Kingdom of Saudi Arabia.

OBJECTIVES: To assess the prevalence of anosmia in coronavirus-19 (COVID-19) patients. Coronavirus-19-related anosmia and hyposmia is a new emerging concept in the medical literature. METHODS: A retrospective study on COVID-19 patients with anosmia and hyposmia was performed during the period between May-July, 2020. The inclusion criteria were all clinically stable COVID-19 patients less than 15 years old with positive reverse transcription-polymerase chain reaction (RT-PCR). Patients who refused to participate or leave incomplete questions were excluded. In this study, we investigated 1022 patients who met our criteria. RESULTS: Olfactory dysfunction (OD) was reported by 53% of our COVID-19 patients, of which 32.7% were anosmic and 20.3% were hyposmic. Other neurological symptoms included ageusia (51.4%), fatigue (63%), myalgia (59.2%), and headache (50.9%), all of which showed significant association with OD. In addition, anosmia had a significant association with young age and female gender. However, there was no association between OD and pre-existing neurological disease. CONCLUSION: Half of our COVID-19 patients presented OD (anosmia/hyposmia), which often associated with ageusia and many neurological symptoms.

Updated experience of a tertiary pandemic center on 533 pregnant women with COVID-19 infection: A prospective cohort study from Turkey.

OBJECTIVE: To investigate the clinical course and impact of coronavirus disease 2019 (COVID-19) infection on pregnant women. METHODS: A prospective cohort study was conducted on pregnant women with confirmed COVID-19 infection. Demographic features, clinical characteristics, and perinatal outcomes were prospectively evaluated. RESULTS: Of the 533 cases, 161 (30.2%) had co-morbidities and 165 (30.9%) were asymptomatic. Cough (n = 178, 33.4%) and myalgia (n = 168, 31.5%) were the leading symptoms. In total, 261 patients (48.9%) received COVID-19 therapy, 509 (95.5%) had mild disease, 7 (1.3%) were admitted to the intensive care unit (ICU), and invasive mechanical ventilation was necessary in 2 (0.4%) patients. Maternal mortality was observed in 2 (0.4%) cases. Of the patients, 297 (55.7%) were hospitalized, 39 (7.3%) had suspicious radiologic imaging findings, 66 (12.4) had pregnancy complications (preterm delivery [n =22, 4.1%] and miscarriage [n =12, 2.2%] were the most common pregnancy complications), 131 births occurred, and the cesarean section rate was 66.4%. All neonates were negative for COVID-19. The rate of admission to the neonatal ICU was 9.9%. One specimen of breast milk was positive for the infection. CONCLUSION: The course of COVID-19 was mild in the majority of cases. However, increased rates of pregnancy complications and cesarean delivery were observed.

Case Report: A COVID-19 Patient Presenting with Mild Rhabdomyolysis.

The news was reported from the Wuhan region of China about a novel corona virus in the end of 2019. After spreading around the world, a pandemic was declared by the WHO. Depending on the different involvement of the disease, the most common symptoms are fever, cough, and dyspnea. However, some indeterminate symptoms that make diagnosis difficult, such as myalgia and fatigue, can also be seen alone, without the typical clinical picture. We describe a patient with COVID-19 pneumonia, the only complaint of which is myalgia, and the first diagnosis is mild rhabdomyolysis. The patient had no evidence or history other than viral infection that could explain muscle pain and also increased level of muscle enzymes. When mild rhabdomyolysis lack of myoglobinuria and complications was diagnosed, treatment-related rhabdomyolysis was also avoided as no treatment related to COVID-19 was initiated yet. Apart from the typical symptoms leading to the typical diagnosis of COVID-19 at the first admission, SARS-CoV-2 related with rhabdomyolysis should also be kept in mind.

Main symptoms in patients presenting in the COVID-19 period.

BACKGROUND: The first case of a novel coronavirus (COVID-19) infection was detected in Wuhan, fever and respiratory symptoms have been frequently reported in patients infected with this virus. AIM: It was aimed to compare the symptoms of patients with COVID-19 positivity and patients without COVID-19 positivity hospitalized with suspicion of COVID-19. METHODS: Patients presenting to the Sakarya University Training and Research Hospital with suspicion of COVID-19 were included in the study. Samples were obtained from the patients and PCR tests were performed; the patients were grouped as COVID-19 positive and COVID-19 negative; these two groups were questioned for 15 symptoms and the results were compared. RESULTS: A total of 297 patients with suspicion of COVID-19 were included in the study. COVID-19 was positive in 143 patients and negative in 154 patients. The most common symptoms in the COVID-19 positive group were: cough (56.6%), weakness (56.6%), taste disorder (35.7%), myalgia (34.3%), and fever (33.6%); and in the COVID-19 negative group: cough (63%), weakness (45.5%), dyspnea (29.9%), headache (27.3%) and fever (24.7%). When these two groups were compared, taste disorder, smell disorder and diarrhea were significantly higher in the COVID-19 positive group (p = <0,00001, p = 0,00001 and p = 0,02). CONCLUSION: Our study showed that taste and smell disorders and diarrhea were important markers in COVID-19 infection.

Serum Protein Profiling Reveals a Landscape of Inflammation and Immune Signaling in Early-stage COVID-19 Infection.

Coronavirus disease 2019 (COVID-19) is a highly contagious infection and threating the human lives in the world. The elevation of cytokines in blood is crucial to induce cytokine storm and immunosuppression in the transition of severity in COVID-19 patients. However, the comprehensive changes of serum proteins in COVID-19 patients throughout the SARS-CoV-2 infection is unknown. In this work, we developed a high-density antibody microarray and performed an in-depth proteomics analysis of serum samples collected from early COVID-19 (n = 15) and influenza (n = 13) patients. We identified a large set of differentially expressed proteins (n = 132) that participate in a landscape of inflammation and immune signaling related to the SARS-CoV-2 infection. Furthermore, the significant correlations of neutrophil and lymphocyte with the CCL2 and CXCL10 mediated cytokine signaling pathways was identified. These information are valuable for the understanding of COVID-19 pathogenesis, identification of biomarkers and development of the optimal anti-inflammation therapy.

Augmented curation of clinical notes from a massive EHR system reveals symptoms of impending COVID-19 diagnosis.

Understanding temporal dynamics of COVID-19 symptoms could provide fine-grained resolution to guide clinical decision-making. Here, we use deep neural networks over an institution-wide platform for the augmented curation of clinical notes from 77,167 patients subjected to COVID-19 PCR testing. By contrasting Electronic Health Record (EHR)-derived symptoms of COVID-19-positive (COVIDpos; n = 2,317) versus COVID-19-negative (COVIDneg; n = 74,850) patients for the week preceding the PCR testing date, we identify anosmia/dysgeusia (27.1-fold), fever/chills (2.6-fold), respiratory difficulty (2.2-fold), cough (2.2-fold), myalgia/arthralgia (2-fold), and diarrhea (1.4-fold) as significantly amplified in COVIDpos over COVIDneg patients. The combination of cough and fever/chills has 4.2-fold amplification in COVIDpos patients during the week prior to PCR testing, in addition to anosmia/dysgeusia, constitutes the earliest EHR-derived signature of COVID-19. This study introduces an Augmented Intelligence platform for the real-time synthesis of institutional biomedical knowledge. The platform holds tremendous potential for scaling up curation throughput, thus enabling EHR-powered early disease diagnosis.

Early neurological manifestations of hospitalized COVID-19 patients.

INTRODUCTION: Neurological manifestations can occur during coronavirus disease 19 (COVID-19). Several pathogenic mechanisms have been hypothesized, without conclusive results. In this study, we evaluated the most frequent neurological symptoms in a cohort of hospitalized COVID-19 patients, and also investigated the possible relationship between plasmatic inflammatory indices and olfactory disorders (ODs) and between muscle pain and creatine kinase (CK). METHODS: We consecutively enrolled hospitalized COVID-19 patients. A structured questionnaire concerning typical and neurological symptoms, focusing on headache, dizziness, ODs, taste disorders (TDs), and muscle pain, was administrated by telephone interviews. RESULTS: Common neurological symptoms were reported in the early phase of the disease, with a median onset ranging from 1 to 3 days. Headache showed tension-type features and was more frequently associated with a history of headache. Patients with ODs less frequently needed oxygen therapy. Inflammatory indices did not significantly differ between patients with and without ODs. Muscle pain did not show any association with CK level but was more frequently associated with arthralgia and headache. CONCLUSION: In our cohort, ODs were an early symptom of COVID-19, more frequently reported by patients with milder forms of disease. Headache in association with arthralgia and muscle pain seems to reflect the common symptoms of the flu-like syndrome, and not COVID-19 infection-specific.

COVID-19 symptoms predictive of healthcare workers' SARS-CoV-2 PCR results.

BACKGROUND: Coronavirus 2019 disease (COVID-19) is caused by the virus SARS-CoV-2, transmissible both person-to-person and from contaminated surfaces. Early COVID-19 detection among healthcare workers (HCWs) is crucial for protecting patients and the healthcare workforce. Because of limited testing capacity, symptom-based screening may prioritize testing and increase diagnostic accuracy. METHODS AND FINDINGS: We performed a retrospective study of HCWs undergoing both COVID-19 telephonic symptom screening and nasopharyngeal SARS-CoV-2 assays during the period, March 9-April 15, 2020. HCWs with negative assays but progressive symptoms were re-tested for SARS-CoV-2. Among 592 HCWs tested, 83 (14%) had an initial positive SARS-CoV-2 assay. Fifty-nine of 61 HCWs (97%) who were asymptomatic or reported only sore throat/nasal congestion had negative SARS-CoV-2 assays (P = 0.006). HCWs reporting three or more symptoms had an increased multivariate-adjusted odds of having positive assays, 1.95 (95% CI: 1.10-3.64), which increased to 2.61 (95% CI: 1.50-4.45) for six or more symptoms. The multivariate-adjusted odds of a positive assay were also increased for HCWs reporting fever and a measured temperature ≥ 37.5°C (3.49 (95% CI: 1.95-6.21)), and those with myalgias (1.83 (95% CI: 1.04-3.23)). Anosmia/ageusia (i.e. loss of smell/loss of taste) was reported less frequently (16%) than other symptoms by HCWs with positive assays, but was associated with more than a seven-fold multivariate-adjusted odds of a positive test: OR = 7.21 (95% CI: 2.95-17.67). Of 509 HCWs with initial negative SARS-CoV-2 assays, nine had symptom progression and positive re-tests, yielding an estimated negative predictive value of 98.2% (95% CI: 96.8-99.0%) for the exclusion of clinically relevant COVID-19. CONCLUSIONS: Symptom and temperature reports are useful screening tools for predicting SARS-CoV-2 assay results in HCWs. Anosmia/ageusia, fever, and myalgia were the strongest independent predictors of positive assays. The absence of symptoms or symptoms limited to nasal congestion/sore throat were associated with negative assays.

Ear nose throat-related symptoms with a focus on loss of smell and/or taste in COVID-19 patients.

PURPOSE: To determine the frequency and severity of general and ear nose throat (ENT)- related symptoms, especially smell and/or loss of sense of taste (STL) in COVID-19 disease, as well as to investigate the recovery process of STL. MATERIALS AND METHODS: Patients with a positive COVID-19 diagnosis were given a questionnaire consisting of general questions (age, sex, date of symptoms, smoking history, concomitant diseases), questions about the most obvious symptom at presentation (one option only), the severity and frequency of symptoms (general and ENT), and STL (recovery time and degree of recovery). RESULTS: The study population consisted of 172 patients, 18-65 years old (mean age, 37.8 ± 12.5 years; 51.2% female; 76.2% nonsmokers). Cough (n = 30, 17.4%) and loss of sense of smell (n = 18, 10.4%) were the most obvious general and ENT symptoms, respectively. Eighty-eight patients (51.2%) reported loss of sense of smell, and 81 patients (47.1%) reported loss of sense of taste. The mean recovery times for loss of sense of smell and loss of sense of taste were 8.02 ± 6.41 and 8.20 ± 7.07 days, respectively. The loss of sense of smell and loss of sense of taste were the unique symptoms in four (4.54%) and one (1.23%) patients, respectively. CONCLUSION: STL is a common symptom in COVID-19 and may be the first and/or only symptom of this disease. In patients presenting with STL complaints, surveillance for possible COVID-19 disease and screening tests will facilitate the struggle against the disease.

Neurological manifestations of COVID-19.

Coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) has turned out to be a formidable pandemic. Upcoming evidence from confirmed cases of COVID-19 suggests an anticipated incursion of patients with neurological manifestations in the weeks to come. An expression of the angiotensin-converting enzyme 2 (ACE 2), the cellular receptor for SARS-CoV-2 over the glial cells and neurons have made the brain a potential target. Neurotoxicity may occur as a result of direct, indirect and post-infectious complications. Attention to neurological deficits in COVID-19 is fundamental to ensure appropriate, timely, beneficial management of the affected patients. Most common neurological manifestations seen include dizziness, headache, impaired consciousness, acute cerebrovascular disease, ataxia, and seizures. Anosmia and ageusia have recently been hinted as significant early symptoms in COVID-19. As cases with neurological deficits in COVID-19 emerge, the overall prognosis is yet unknown.

Musculoskeletal Consequences of COVID-19.

Coronavirus disease 2019 (COVID-19) is an emerging pandemic disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although the majority of patients who become infected with SARS-CoV-2 are asymptomatic or have mild symptoms, some patients develop severe symptoms that can permanently detract from their quality of life. SARS-CoV-2 is closely related to SARS-CoV-1, which causes severe acute respiratory syndrome (SARS). Both viruses infect the respiratory system, and there are direct and indirect effects of this infection on multiple organ systems, including the musculoskeletal system. Epidemiological data from the SARS pandemic of 2002 to 2004 identified myalgias, muscle dysfunction, osteoporosis, and osteonecrosis as common sequelae in patients with moderate and severe forms of this disease. Early studies have indicated that there is also considerable musculoskeletal dysfunction in some patients with COVID-19, although long-term follow-up studies have not yet been conducted. The purpose of this article was to summarize the known musculoskeletal pathologies in patients with SARS or COVID-19 and to combine this with computational modeling and biochemical signaling studies to predict musculoskeletal cellular targets and long-term consequences of the SARS-CoV-2 infection.

COVID-19 and the nervous system.

A pandemic due to novel coronavirus arose in mid-December 2019 in Wuhan, China, and in 3 months' time swept the world. The disease has been referred to as COVID-19, and the causative agent has been labelled SARS-CoV-2 due to its genetic similarities to the virus (SARS-CoV-1) responsible for the severe acute respiratory syndrome (SARS) epidemic nearly 20 years earlier. The spike proteins of both viruses dictate tissue tropism using the angiotensin-converting enzyme type 2 (ACE-2) receptor to bind to cells. The ACE-2 receptor can be found in nervous system tissue and endothelial cells among the tissues of many other organs.Neurological complications have been observed with COVID-19. Myalgia and headache are relatively common, but serious neurological disease appears to be rare. No part of the neuraxis is spared. The neurological disorders occurring with COVID-19 may have many pathophysiological underpinnings. Some appear to be the consequence of direct viral invasion of the nervous system tissue, others arise as a postviral autoimmune process, and still others are the result of metabolic and systemic complications due to the associated critical illness. This review addresses the preliminary observations regarding the neurological disorders reported with COVID-19 to date and describes some of the disorders that are anticipated from prior experience with similar coronaviruses.

CT Manifestations and Clinical Characteristics of 1115 Patients with Coronavirus Disease 2019 (COVID-19): A Systematic Review and Meta-analysis.

RATIONALE AND OBJECTIVES: We aimed to assess the prevalence of significant computed tomographic(CT) manifestations and describe some notable features based on chest CT images, as well as the main clinical features of patients with coronavirus disease 2019(COVID-19). MATERIALS AND METHODS: A systematic literature search of PubMed, EMBASE, the Cochrane Library, and Web of Science was performed to identify studies assessing CT features, clinical, and laboratory results of COVID-19 patients. A single-arm meta-analysis was conducted to obtain the pooled prevalence and 95% confidence interval (95% CI). RESULTS: A total of 14 articles (including 1115 patients) based on chest CT images were retrieved. In the lesion patterns on chest CTs, we found that pure ground-glass opacities (GGO) (69%, 95% CI 58-80%), consolidation (47%, 35-60%) and "air bronchogram sign" (46%, 25-66%) were more common than the atypical lesion of "crazy-paving pattern" (15%, 8-22%). With regard to disease extent and involvement, 70% (95% CI 46-95%) of cases showed a location preference for the right lower lobe, 65% (58-73%) of patients presented with ≥3 lobes involvement, and meanwhile, 42% (32-53%) of patients had involvement of all five lobes, while 67% (55-78%) of patients showed a predominant peripheral distribution. An understanding of some important CT features might be helpful for medical surveillance and management. In terms of clinical features, muscle soreness (21%, 95% CI 15-26%) and diarrhea (7%, 4-10%) were minor symptoms compared to fever (80%, 74-87%) and cough (53%, 33-72%). CONCLUSION: Chest CT manifestations in patients with COVID-19, as well as its main clinical characteristics, might be helpful in disease evolution and management.