Functional and transcriptional heterogeneity within the massively expanding HLADR+CD38+ CD8 T cell population in acute febrile dengue patients.

IMPORTANCE: CD8 T cells play a crucial role in protecting against intracellular pathogens such as viruses by eliminating infected cells and releasing anti-viral cytokines such as interferon gamma (IFNγ). Consequently, there is significant interest in comprehensively characterizing CD8 T cell responses in acute dengue febrile patients. Previous studies, including our own, have demonstrated that a discrete population of CD8 T cells with HLADR+ CD38+ phenotype undergoes massive expansion during the acute febrile phase of natural dengue virus infection. Although about a third of these massively expanding HLADR+ CD38+ CD8 T cells were also CD69high when examined ex vivo, only a small fraction of them produced IFNγ upon in vitro peptide stimulation. Therefore, to better understand such functional diversity of CD8 T cells responding to dengue virus infection, it is important to know the cytokines/chemokines expressed by these peptide-stimulated HLADR+CD38+ CD8 T cells and the transcriptional profiles that distinguish the CD69+IFNγ+, CD69+IFNγ-, and CD69-IFNγ- subsets.

Rio Negro Virus Infection, Bolivia, 2021.

In May 2021, an agricultural worker originally from Trementinal, Argentina, sought treatment for febrile illness in Tarija, Bolivia, where he resided at the time of illness onset. The patient tested negative for hantavirus RNA, but next-generation sequencing of a serum sample yielded a complete genome for Rio Negro virus.

Clinical Profile and Lab Findings of Dengue Fever in Children Admitted in a Tertiary Care Hospital.

Dengue is an arboviral infection dengue virus (DENV 1-4) transmitted by Aedes mosquito. It shows a wide range of clinical presentation from asymptomatic cases to undifferentiated fever, dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS) or non-severe and severe dengue. Most cases of dengue are self-limiting; however, severe dengue has high mortality if not diagnosed and managed early during the disease. Dengue virus (DENV) infection is a serious global public health challenge resulting approximately 200 million cases of morbidity and 50,000 cases of mortality annually. Management is based on clinical and lab parameters with certain lab tests aiding in the early forecast of severe dengue. While serological tests (detection of nonstructural protein 1 [NS1] antigen, immunoglobulin IgM and IgG antibodies aid in diagnosis of dengue, simple, cost-effective, easy tests such as hematocrit and platelet counts have great utility in resource-poor healthcare systems for predicting onset of severe dengue. To determine the clinical profile and lab findings of different varieties of Dengue fever in children admitted in a tertiary care hospital. This retrospective observational study was designed to collect data from the medical records of children of both sexes, aged up to 12 years old. The study was conducted from April 2019 to September 2019 in pediatrics department of BSMMU, Dhaka. A total of 50 children who were admitted with the complaints of fever and were found positive for either NS1 antigen or dengue IgM or IgG antibodies were included in the study. Patients with chronic diseases or any concurrent infections were excluded. Samples were collected from hospital record and kept in a separate management system only for dengue patients. The demographics, clinical and laboratory findings were recorded via structured data collection sheet. Among 50 cases, 22 were dengue fever, 17 were dengue hemorrhagic fever and 11 were dengue shock syndrome. The mean age of study participant was 6.95. Out of 50 patients, Male 62.0% were predominant over the female 38.0% and majority 74.0% came from urban area. Fever (95.5%) was mostly the presenting feature in dengue fever. Bleeding (29.4%) and tourniquet test positive (47.0%) were most in DHF. Hypotension (90.0%), tachycardia (90.9%), edema (18.2%), shock (90.9%) and hepatomegaly (72.7%) were mostly present in DSS. Neutropenia (72.7%) was significant in DSS. Platelet count (32,588.24±22,335.67) was significantly low in DHF. Albumin count (27.82±5.25) and TCO2 (18.27±1.8) were significantly low in DSS. Statistical analysis was done by Kuskalwallis test for categorical data analysis and one way ANOVA test for comparison of continuous data. P value <0.05 is considered as significant. This time it was seen that bleeding, tourniquet test positivity with low platelet count is seen in DHF. But DSS was marked by hepatomegaly and hypoalbuminaemia.

Acompanhamento do comportamento do HIV através de exames laboratoriais em portadora do vírus: relato de caso / Monitoring of HIV behavior through laboratory tests in a virus carrier: case report

O vírus da imunodeficiência humana é o agente etiológico da AIDS, doença crônica que destrói o sistema imunológico e é caracterizada pela baixa contagem de células TCD4, alta contagem de partículas virais no sangue e manifestações clínicas da doença. O diagnóstico se dá com o aparecimento de infecções oportunistas, que levam a contagem de TCD4 a níveis menores que 200 céls/mm³. Os exames laboratoriais para o diagnóstico do HIV foram os principais avanços para o início do tratamento, reduzindo a transmissão. Detecção de anticorpos, detecção de antígenos e amplificação do genoma do vírus são alguns dos exames laboratoriais utilizados para diagnóstico. Os dois principais biomarcadores são os exames de contagem de células TCD4, que verifica o sistema imune, e a quantificação de carga viral, que informa a quantidade de partículas virais, mostrando a progressão da infecção. Quanto maior a carga viral, maior o dano ao sistema imune. Uma carga viral indetectável é inferior a 50 cópias/mL, mas valores menores ou iguais a 200 cópias/mL também impedem a transmissão. Uma declaração de consenso afirma que Indetectável é igual a Intransmissível. Portanto, quando indetectável, a transmissão inexiste. O presente estudo relata e discute o caso clínico de uma paciente diagnosticada com HIV/AIDS aos 28 anos, que sobreviveu, apesar do diagnóstico tardio, e sob presença de doença oportunista com um grave grau de diminuição de células TCD4 (22 cél/mm³). Por meio do diagnóstico, introdução e adesão correta da terapia antirretroviral e monitorização de exames laboratoriais, conseguiu evitar a morte e ter uma vida semelhante à de um HIV negativo. Ultrapassou a expectativa de vida que na descoberta era de 10 anos, com uma qualidade de vida considerável, não sendo transmissora do vírus, diminuindo assim o estigma e preconceito. O biomédico é peça fundamental nesse contexto, considerando que deve fornecer informações precisas e fidedignas, tão necessárias ao acompanhamento de pessoas vivendo com HIV, para que autoridades e profissionais de saúde adotem medidas adequadas, tanto na prevenção, quanto no diagnóstico e monitoramento da doença.

The human immunodeficiency virus is the etiological agent of AIDS, a chronic disease that destroys the immune system and is characterized by low TCD4 cell count, high viral particle count in blood and clinical manifestations of the disease. The diagnosis is due to the appearance of opportunistic infections, which lead to TCD4 counts below 200 cells / mm³. Laboratory tests for the diagnosis of HIV were the main advances in starting treatment, reducing transmission. Antibody detection, antigen detection and virus genome amplification are some of the laboratory tests used for diagnosis. The two main biomarkers are the TCD4 cell count tests, which checks the immune system, and viral load quantification, which reports the number of viral particles, showing the progression of infection. The higher the viral load, the greater the damage to the immune system. An undetectable viral load is less than 50 copies / mL, but values less than or equal to 200 copies / mL also prevent transmission. A consensus statement states that Undetectable equals Non-Transmissible. Therefore, when undetectable, transmission does not exist. The present study reports and discusses the clinical case of a patient diagnosed with HIV / AIDS at age 28, who survived despite late diagnosis and under the presence of opportunistic disease with a severe degree of TCD4 cell reduction (22 cells / mm³). Through the diagnosis, introduction and correct adherence of antiretroviral therapy and monitoring of laboratory tests, she was able to avoid death and have a life similar to that of an HIV negative. Exceeded the life expectancy that in the discovery was 10 years, with a considerable quality of life, not transmitting the virus, thus reducing the stigma and prejudice. The biomedical is a key player in this context, considering that he must provide accurate and reliable information, which is so necessary for the monitoring of people living with HIV, so that authorities and health professionals adopt appropriate measures, both in prevention, diagnosis and monitoring of the disease.

MIS-C among return visits for fever in a pediatric emergency department during the COVID-19 pandemic.

Return visits (RV) to a pediatric emergency department (PED) can be secondary to illness progression, parental concerns, call backs or rarely due to a diagnostic error during the first visit. Fever accounts for nearly half of these RVs and is also one of the most common presenting complaints of Corona Virus Disease 2019 (COVID- 19) due to severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) infection in children. Although majority of children with COVID 19 have a mild illness, severe complications such as Multisystem inflammatory syndrome in children (MIS-C) can occur. These children are often critically ill with a mortality rate of 2-4%. Initial symptoms of MIS- C are non- specific and mimic other viral illness making early diagnosis challenging. We report five patients who were evaluated for fever and discharged from our PED and were subsequently diagnosed with MIS-C (n = 3) or Kawasaki Disease (n = 2) during their RV within 7 days. All patients presented with fever during the initial visit and three of the five children had gastrointestinal symptoms. They were all noted have persistent tachycardia during the index visit. Three patients presented in cardiogenic shock and echocardiographic abnormalities were noted in four patients during the RV. Significant interventions were required in majority of these children (PICU admission: 4, inotropes: 3, mechanical ventilation:2). Clinicians need to maintain a high index of suspicion for diagnosis of MIS-C especially in those who present with persistent fever and have abnormal vital signs during the COVID-19 pandemic.

[A clear cerebrospinal fluid - but an unclear diagnosis]. / Liquor klar ­ Diagnose (un)klar.

HISTORY: A 35-year-old, previously healthy woman presented with short history of headache and fever. Several other family members reported active hand, foot, and mouth disease. FINDINGS: Clinical findings showed subfebrile temperatures and a prominent meningism. Cerebrospinal fluid and computed tomography of the head were unrevealing. Subsequent PCR-analysis of the cerebrospinal fluid was positive for Enteroviral-RNA. DIAGNOSIS AND THERAPY: Enteroviral-meningitis was diagnosed. The empirically administered antimicrobial therapy was stopped and further diagnostic tests could be withheld. COURSE: Symptom-oriented therapy resulted in complete resolution within the next few days. CONCLUSIONS: Our case emphasizes that, in patients with typical signs of meningeal irritation, normal cellular analysis of the cerebrospinal fluid does not exclude the presence of infectious meningitis. The astute clinician should be reminded that this constellation is highly suggestive of enteroviral meningitis.

Evaluation of early antibiotic use in patients with non-severe COVID-19 without bacterial infection.

OBJECTIVES: The use of antibiotics was common in some countries during the early phase of the coronavirus disease 2019 (COVID-19) pandemic, but adequate evaluation remains lacking. This study aimed to evaluate the effect of early antibiotic use in patients with non-severe COVID-19 admitted without bacterial infection. METHODS: This multi-centre retrospective cohort study included 1,373 inpatients with non-severe COVID-19 admitted without bacterial infection. Patients were divided into two groups according to their exposure to antibiotics within 48 h of admission. The outcomes were progression to severe COVID-19, length of stay >15 days and mortality rate. A mixed-effect Cox model and random effect logistic regression were used to explore the association between early antibiotic use and outcomes. RESULTS: During the 30-day follow-up period, the proportion of patients who progressed to severe COVID-19 in the early antibiotic use group was almost 1.4 times that of the comparison group. In the mixed-effect model, the early use of antibiotics was associated with higher probability of developing severe COVID-19 and staying in hospital for >15 days. However, there was no significant association between early use of antibiotics and mortality. Analysis with propensity-score-matched cohorts displayed similar results. In subgroup analysis, patients receiving any class of antibiotic were at increased risk of adverse health outcomes. Azithromycin did not improve disease progression and length of stay in patients with COVID-19. CONCLUSIONS: It is suggested that antibiotic use should be avoided unless absolutely necessary in patients with non-severe COVID-19, particularly in the early stages.

Clinical Features and Laboratory Examination to Identify Severe Patients with COVID-19: A Systematic Review and Meta-Analysis.

BACKGROUND: With the COVID-19 epidemic breakout in China, up to 25% of diagnosed cases are considered to be severe. To effectively predict the progression of COVID-19 via patients' clinical features at an early stage, the prevalence of these clinical factors and their relationships with severe illness were assessed. METHODS: In this study, electronic databases (PubMed, Embase, Web of Science, and Chinese database) were searched to obtain relevant studies, including information on severe patients. Publication bias analysis, sensitivity analysis, prevalence, sensitivity, specificity, likelihood ratio, diagnosis odds ratio calculation, and visualization graphics were achieved through software Review Manager 5.3, Stata 15, Meta-DiSc 1.4, and R. RESULTS: Data of 3.547 patients from 24 studies were included in this study. The results revealed that patients with chronic respiratory system diseases (pooled positive likelihood 6.07, 95% CI: 3.12-11.82), chronic renal disease (4.79, 2.04-11.25), cardiovascular disease (3.45, 2.19-5.44), and symptoms of the onset of chest tightness (3.8, 1.44-10.05), shortness of breath (3.18, 2.24-4.51), and diarrhea (2.04, 1.38-3.04) exhibited increased probability of progressing to severe illness. C-reactive protein, ratio of neutrophils to lymphocytes, and erythrocyte sedimentation rate increased a lot in severe patients compared to nonsevere. Yet, it was found that clinical features including fever, cough, and headache, as well as some comorbidities, have little warning value. CONCLUSIONS: The clinical features and laboratory examination could be used to estimate the process of infection in COVID-19 patients. The findings contribute to the more efficient prediction of serious illness for patients with COVID-19 to reduce mortality.

Serological Evidence of Zika Virus Infection in Febrile Patients and Healthy Blood Donors in Sabah, Malaysian Borneo, 2017-2018.

Several Zika virus (ZIKV) seroprevalence studies have been conducted in Africa, Asia, Oceania, the Americas, and the Caribbean. However, studies on ZIKV seroprevalence are limited in Malaysia though several studies have shown that the disease is endemic in the Malaysian state of Sabah. To evaluate the seroprevalence of ZIKV infection, 818 serum samples were collected from febrile patients and healthy blood donors from the Kudat and Kota Kinabalu districts in Sabah from 2017 to 2018. They were screened for ZIKV infection by IgM and IgG ELISA, and positive ZIKV IgM samples were subjected to a 90% neutralization test for confirmation. Twenty-four (6% [95% CI 4 to 8]) confirmed and two (0.5% [95% CI 0.13 to 1.8]) probable ZIKV infections were detected among 400 febrile illness patients. Of 418 healthy blood donor samples, six (1.4% [95% CI 0.65 to 3]) were determined as confirmed ZIKV infections and six (1.4% [95% CI 0.65 to 3]) indicated probable ZIKV infection. This is the first study on the seroprevalence of ZIKV infections among patients and healthy blood donors in Sabah. Compared with previous studies in Malaysia, this study shows that the incidence of ZIKV infection has increased. It also suggests that a sero-surveillance system is essential to determine the circulation of ZIKV in Sabah, Malaysia.

Discovery and Full Genome Characterization of SARS-CoV-2 in Stool Specimen from a Recovered Patient, China.

SARS-CoV-2 was found in a recovered patient's stool specimen by combining quantitative reverse transcription PCR (qRT-PCR) and genome sequencing. The patient was virus positive in stool specimens for at least an additional 15 days after he was recovered, whereas respiratory tract specimens were negative. The discovery of the complete genome of SARS-CoV-2 in the stool sample of the recovered patient demonstrates a cautionary warning that the potential mode of the virus transmission cannot be excluded through the fecal-oral route after viral clearance in the respiratory tract.

Clinical Characteristics of Patients with Coronavirus Disease 2019 (COVID-19) in a Teaching Hospital in Malaysia.

INTRODUCTION: Information on the clinical characteristics of local patients with confirmed COVID-19 is limited. This study aims to report the clinical characteristics of 147 patients admitted and receiving treatment at a teaching hospital. METHODOLOGY: Patients' socio-demographic and epidemiological data, clinical features, laboratory findings and clinical outcomes were extracted using a data sheet. RESULTS: The median patient age was 25 [interquartile range (IQR)] 20-44) years, and most of patients were male (68.7%) and of Malaysian nationality (88.4%). Almost half of the patients were from a case cluster related to a religious event (48.3%) and 12.9% had a history of overseas travel. A total of 33.3% of patients were not related to any case cluster, i.e. sporadic cases. Radiological investigation showed that 13.6% of the patients had chest X-ray changes and all laboratory parameters were within the normal ranges. Sixty-six patients (44.9%) experienced symptoms. The most common symptoms were rhinitis (66.7%), followed by fever (19.7%) and cough (15.2%). Age, gender, case cluster, comorbidity status, haemoglobin, albumin, total protein, bilirubin total and alkaline phosphatase level were associated with symptomatic status. CONCLUSIONS: In this single-centre study, COVID-19 infection led not only to case clusters, but also to sporadic infections, with patients being either symptomatic or asymptomatic. These sporadic cases and asymptomatic patients may hamper effective contact tracing, leading to rapid human-to-human transmission in our population. Future studies on the prevalence and clinical significance of asymptomatic and presymptomatic COVID-19 patients would pre-emptively address issues on further containment of the pandemic.

Clinical and laboratory factors associated with coronavirus disease 2019 (Covid-19): A systematic review and meta-analysis.

SARS Coronavirus-2 is one of the most widespread viruses globally during the 21st century, whose severity and ability to cause severe pneumonia and death vary. We performed a comprehensive systematic review of all studies that met our standardised criteria and then extracted data on the age, symptoms, and different treatments of Covid-19 patients and the prognosis of this disease during follow-up. Cases in this study were divided according to severity and death status and meta-analysed separately using raw mean and single proportion methods. We included 171 complete studies including 62,909 confirmed cases of Covid-19, of which 148 studies were meta-analysed. Symptoms clearly emerged in an escalating manner from mild-moderate symptoms, pneumonia, severe-critical to the group of non-survivors. Hypertension (Pooled proportion (PP): 0.48 [95% Confident interval (CI): 0.35-0.61]), diabetes (PP: 0.23 [95% CI: 0.16-0.33]) and smoking (PP: 0.12 [95% CI: 0.03-0.38]) were highest regarding pre-infection comorbidities in the non-survivor group. While acute respiratory distress syndrome (PP: 0.49 [95% CI: 0.29-0.78]), (PP: 0.63 [95% CI: 0.34-0.97]) remained one of the most common complications in the severe and death group respectively. Bilateral ground-glass opacification (PP: 0.68 [95% CI: 0.59-0.75]) was the most visible radiological image. The mortality rates estimated (PP: 0.11 [95% CI: 0.06-0.19]), (PP: 0.03 [95% CI: 0.01-0.05]), and (PP: 0.01 [95% CI: 0-0.3]) in severe-critical, pneumonia and mild-moderate groups respectively. This study can serve as a high evidence guideline for different clinical presentations of Covid-19, graded from mild to severe, and for special forms like pneumonia and death groups.

A novel nairovirus associated with acute febrile illness in Hokkaido, Japan.

The increasing burden of tick-borne orthonairovirus infections, such as Crimean-Congo hemorrhagic fever, is becoming a global concern for public health. In the present study, we identify a novel orthonairovirus, designated Yezo virus (YEZV), from two patients showing acute febrile illness with thrombocytopenia and leukopenia after tick bite in Hokkaido, Japan, in 2019 and 2020, respectively. YEZV is phylogenetically grouped with Sulina virus detected in Ixodes ricinus ticks in Romania. YEZV infection has been confirmed in seven patients from 2014-2020, four of whom were co-infected with Borrelia spp. Antibodies to YEZV are found in wild deer and raccoons, and YEZV RNAs have been detected in ticks from Hokkaido. In this work, we demonstrate that YEZV is highly likely to be the causative pathogen of febrile illness, representing the first report of an endemic infection associated with an orthonairovirus potentially transmitted by ticks in Japan.

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.

Evidence of chikungunya virus infections among febrile patients at three secondary health facilities in the Ashanti and the Bono Regions of Ghana.

BACKGROUND: Chikungunya is now of public health concern globally due to its re-emergence in endemic areas and introduction into new areas of the world. Worldwide, the vectors for transmission of the chikungunya virus are Aedes mosquitoes and these are prevalent in Ghana. Despite its global significance, the true burden of chikungunya virus infection in Ghana is largely unknown and the threat of outbreak remains high owing to international travel. This study sought to determine chikungunya virus infection among febrile patients suspected of having malaria infections at some selected health facilities in the Ashanti, Bono East, and Bono Regions of Ghana. METHODOLOGY: This cross-sectional study recruited six hundred (600) febrile patients suspected of having malaria who submitted their clinical samples to the laboratories of the selected health facilities for the diagnosis of their infections. Five to ten millilitres (5-10ml) of venous blood were collected from each study participant. Sera were separated and tested for anti-chikungunya (IgM and IgG) antibodies using InBios ELISA kit following the manufacturer's instruction. Samples positive for chikungunya IgM and IgG were selected and tested for chikungunya virus RNA using Reverse Transcription-quantitative Polymerase Chain Reaction. Malaria Rapid Diagnostic Test kits were used to screen the participants for malaria. Structured questionnaires were administered to obtain demographic and clinical information of the study participants. RESULT: Of the 600 samples tested, the overall seroprevalence of chikungunya was 6%. The seroprevalence of chikungunya IgM and IgG antibodies were 1.8% and 4.2% respectively. None of the chikungunya IgM and IgG positive samples tested positive for chikungunya RNA by RT-qPCR. Of the 600 samples, tested 32.3% (194/600) were positive for malaria parasites. Malaria and chikungunya co-infection was detected in 1.8% (11/600) of the participants. CONCLUSION: Findings from the current study indicate low-level exposure to the chikungunya virus suggesting the virus is circulating and potentially causing morbidity in Ghana.

Seroconversion and fever are dose-dependent in a nonhuman primate model of inhalational COVID-19.

While evidence exists supporting the potential for aerosol transmission of SARS-CoV-2, the infectious dose by inhalation remains unknown. In the present study, the probability of infection following inhalation of SARS-CoV-2 was dose-dependent in a nonhuman primate model of inhalational COVID-19. The median infectious dose, assessed by seroconversion, was 52 TCID50 (95% CI: 23-363 TCID50), and was significantly lower than the median dose for fever (256 TCID50, 95% CI: 102-603 TCID50), resulting in a group of animals that developed an immune response post-exposure but did not develop fever or other clinical signs of infection. In a subset of these animals, virus was detected in nasopharyngeal and/or oropharyngeal swabs, suggesting that infected animals without signs of disease are able to shed virus and may be infectious, which is consistent with reports of asymptomatic spread in human cases of COVID-19. These results suggest that differences in exposure dose may be a factor influencing disease presentation in humans, and reinforce the importance of public health measures that limit exposure dose, such as social distancing, masking, and increased ventilation. The dose-response data provided by this study are important to inform disease transmission and hazard modeling, and, ultimately, mitigation strategies. Additionally, these data will be useful to inform dose selection in future studies examining the efficacy of therapeutics and vaccines against inhalational COVID-19, and as a baseline in healthy, young adult animals for assessment of the importance of other factors, such as age, comorbidities, and viral variant, on the infectious dose and disease presentation.

Add-on effect of Chinese herbal medicine in the treatment of mild to moderate COVID-19: A systematic review and meta-analysis.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) has emerged as a global pandemic since its outbreak in Wuhan, China. It is an urgent task to prevent and treat COVID-19 effectively early. In China's experience combating the COVID-19 pandemic, Chinese herbal medicine (CHM) has played an indispensable role. A large number of epidemiological investigations have shown that mild to moderate COVID-19 accounts for the largest proportion of cases. It is of great importance to treat such COVID-19 cases, which can help control epidemic progression. Many trials have shown that CHM combined with conventional therapy in the treatment of mild to moderate COVID-19 was superior to conventional therapy alone. This review was designed to evaluate the add-on effect of CHM in the treatment of mild to moderate COVID-19. METHODS: Eight electronic databases including PubMed, EMBASE, Cochrane Central Register of Controlled Trials, the Clinical Trials.gov website, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), Wanfang Database and China Biology Medicine (CBM) were searched from December 2019 to March 2021 without language restrictions. Two reviewers searched and selected studies, and extracted data according to inclusion and exclusion criteria independently. Cochrane Risk of Bias (ROB) tool was used to assess the methodological quality of the included RCTs. Review Manager 5.3.0 software was used for statistical analysis. RESULTS: Twelve eligible RCTs including 1393 participants were included in this meta-analysis. Our meta-analyses found that lung CT parameters [RR = 1.26, 95% CI (1.15, 1.38), P<0.00001] and the clinical cure rate [RR = 1.26, 95%CI (1.16, 1.38), P<0.00001] of CHM combined with conventional therapy in the treatment of mild to moderate COVID-19 were better than those of conventional therapy. The rate of conversion to severe cases [RR = 0.48, 95%CI (0.32, 0.73), P = 0.0005], TCM symptom score of fever [MD = -0.62, 95%CI (-0.79, -0.45), P<0.00001], cough cases [RR = 1.43, 95%CI (1.16, 1.75), P = 0.0006], TCM symptom score of cough[MD = -1.07, 95%CI (-1.29, -0.85), P<0.00001], TCM symptom score of fatigue[MD = -0.66, 95%CI (-1.05, -0.28), P = 0.0007], and CRP[MD = -5.46, 95%CI (-8.19, -2.72), P<0.0001] of combination therapy was significantly lower than that of conventional therapy. The WBC count was significantly higher than that of conventional therapy[MD = 0.38, 95%CI (0.31, 0.44), P<0.00001]. Our meta-analysis results were robust through sensitivity analysis. CONCLUSION: Chinese herbal medicine combined with conventional therapy may be effective and safe in the treatment of mild to moderate COVID-19. More high-quality RCTs are needed in the future.

Prevalence of COVID-19 in 10,000 samples from 7853 patients in Eastern Turkey by positive real-time PCR.

Aim: COVID-19, caused by SARS-CoV-2, started in December 2019 and has spread across the world. Materials & methods: We analyzed real-time PCR results of 10,000 samples from 2 April to 30 May 2020 in three neighbor cities located in the East of Turkey. The final study population was 7853 cases, after excluding screening tests. Results: Real-time PCR was performed to detect the SARS-CoV-2-specific RNA-dependent-RNA-polymerase gene fragment. The number of total positive samples out of 7853 were 487; however, the number of nonrepeating positive patient was 373 (4.8%). Cough and fever were the most common symptoms in positive cases. Conclusion: Epidemiologic studies should be performed about the prevalence of SARS-CoV-2 infection to better understand the effect of the virus across the world.

Ear, Nose, and Throat Manifestations of COVID-19 in Children.

The article reviews and analyzes the different ear, nose, and throat (ENT)-related manifestations reported in coronavirus disease 2019 (COVID-19)-positive pediatric patients (age <18 years) in peer-reviewed and published literature. We searched the PubMed database using medical subject headings and associated key words, focusing on ENT symptoms in children with COVID-19. We included relevant published and peer-reviewed articles in English and excluded case reports and articles in press. There were 1,140 children positive for COVID-19 (56% boys) in the 23 studies included in this review. Although 11% of patients were asymptomatic, the most common symptoms reported were fever (48%) and cough (37%). Nasal symptoms (stuffy nose, nasal congestion, rhinorrhea) and sore throat occurred in about 22% of all patients. Otitis, dizziness, anosmia, and ageusia are hardly reported in children with COVID-19. Although fever and cough are the most common symptoms, ENT manifestations are frequently observed in pediatric patients with COVID-19. [Pediatr Ann. 2021;50(7):e277-e281.].