Positive Real-time Reverse Transcriptase-polymerase Chain Reaction Research Articles

Machine learning enabled detection of COVID-19 pneumonia using exhaled breath analysis: a proof-of-concept study

Detection of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) relies on real-time-reverse-transcriptase polymerase chain reaction (RT-PCR) on nasopharyngeal swabs. The false-negative rate of RT-PCR can be high when viral burden and infection is localized distally in the lower airways and lung parenchyma. An alternate safe, simple and accessible method for sampling the lower airways is needed to aid in the early and rapid diagnosis of COVID-19 pneumonia. In a prospective unblinded observational study, patients admitted with a positive RT-PCR and symptoms of SARS-CoV-2 infection were enrolled from three hospitals in Ontario, Canada. Healthy individuals or hospitalized patients with negative RT-PCR and without respiratory symptoms were enrolled into the control group. Breath samples were collected and analyzed by laser absorption spectroscopy (LAS) for volatile organic compounds (VOCs) and classified by machine learning (ML) approaches to identify unique LAS-spectra patterns (breathprints) for SARS-CoV-2. Of the 135 patients enrolled, 115 patients provided analyzable breath samples. Using LAS-breathprints to train ML classifier models resulted in an accuracy of 72.2%–81.7% in differentiating between SARS-CoV2 positive and negative groups. The performance was consistent across subgroups of different age, sex, body mass index, SARS-CoV-2 variants, time of disease onset and oxygen requirement. The overall performance was higher than compared to VOC-trained classifier model, which had an accuracy of 63%–74.7%. This study demonstrates that a ML-based breathprint model using LAS analysis of exhaled breath may be a valuable non-invasive method for studying the lower airways and detecting SARS-CoV-2 and other respiratory pathogens. The technology and the ML approach can be easily deployed in any setting with minimal training. This will greatly improve access and scalability to meet surge capacity; allow early and rapid detection to inform therapy; and offers great versatility in developing new classifier models quickly for future outbreaks.

Diagnostic Efficacy of Chest Computed Tomography for Coronavirus Disease 2019.

A significant discrepancy between the results of previous studies is identified regarding the diagnostic efficacy of chest computed tomography (CT) for coronavirus disease 2019 (COVID-19). We aimed to evaluate the diagnostic efficacy of chest CT for COVID-19. Suspected cases of COVID-19 with fever, cough, dyspnea, and evidence of pneumonia on chest CT scan were enrolled in the study. The accuracy, sensitivity, and specificity of chest CT were determined according to real-time reverse transcriptase-polymerase chain reaction (RT-PCR) results as the gold standard method. The study population comprised 356 suspected cases of COVID-19 (174 men and 182 women; age range 3-96 years; mean age ± standard deviation, 55.21 ± 18.38 years). COVID-19 patients were diagnosed using chest CT with 89.8% sensitivity, 78.1% accuracy, 21.3% specificity, 84.7% positive predictive value, and 30.23% negative predictive value. The odds ratio was 2.39 (95% confidence interval, 1.16-4.91). Typical CT manifestations of COVID-19 were observed in 48 (13.5%) patients with negative RT-PCR results and 30 (8.4%) patients with confirmed positive RT-PCR results had no radiological manifestations. Kappa coefficient of chest CT for diagnosis of COVID-19 was 0.78. The results show that when RT-PCR results are negative, chest CT could be considered as a complementary diagnostic method for the diagnosis of COVID-19 patients. A more comprehensive diagnostic method could be established by combining the chest CT examination, clinical symptoms, and RT-PCR assay.

Comparison of clinician diagnosis of COVID-19 with real time polymerase chain reaction in an adult-representative population in Sweden

BackgroundDue to the high transmissibility of SARS-CoV-2, accurate diagnosis is essential for effective infection control, but the gold standard, real-time reverse transcriptase-polymerase chain reaction (RT-PCR), is costly, slow, and test capacity has at times been insufficient. We compared the accuracy of clinician diagnosis of COVID-19 against RT-PCR in a general adult population.MethodsCOVID-19 diagnosis data by 30th September 2021 for participants in an ongoing population-based cohort study of adults in Western Sweden were retrieved from registers, based on positive RT-PCR and clinician diagnosis using recommended ICD-10 codes. We calculated accuracy measures of clinician diagnosis using RT-PCR as reference for all subjects and stratified by age, gender, BMI, and comorbidity collected pre-COVID-19.ResultsOf 42,621 subjects, 3,936 (9.2%) and 5705 (13.4%) had had COVID-19 identified by RT-PCR and clinician diagnosis, respectively. Sensitivity and specificity of clinician diagnosis against RT-PCR were 78% (95%CI 77–80%) and 93% (95%CI 93–93%), respectively. Positive predictive value (PPV) was 54% (95%CI 53–55%), while negative predictive value (NPV) was 98% (95%CI 98–98%) and Youden’s index 71% (95%CI 70–72%). These estimates were similar between men and women, across age groups, BMI categories, and between patients with and without asthma. However, while specificity, NPV, and Youden’s index were similar between patients with and without chronic obstructive pulmonary disease (COPD), sensitivity was slightly higher in patients with (84% [95%CI 74–90%]) than those without (78% [95%CI 77–79%]) COPD.ConclusionsThe accuracy of clinician diagnosis for COVID-19 is adequate, regardless of gender, age, BMI, and asthma, and thus can be used for screening purposes to supplement RT-PCR.

One-year cardiovascular outcomes after coronavirus disease 2019: The cardiovascular COVID-19 registry.

The long-term cardiovascular (CV) outcomes of COVID-19 have not been fully explored. This was an international, multicenter, retrospective cohort study conducted between February and December 2020. Consecutive patients ≥18 years who underwent a real-time reverse transcriptase-polymerase chain reaction (RT-PCR) for SARS-CoV2 were included. Patients were classified into two cohorts depending on the nasopharyngeal swab result and clinical status: confirmed COVID-19 (positive RT-PCR) and control (without suggestive symptoms and negative RT-PCR). Data were obtained from electronic records, and clinical follow-up was performed at 1-year. The primary outcome was CV death at 1-year. Secondary outcomes included arterial thrombotic events (ATE), venous thromboembolism (VTE), and serious cardiac arrhythmias. An independent clinical event committee adjudicated events. A Cox proportional hazards model adjusted for all baseline characteristics was used for comparing outcomes between groups. A prespecified landmark analysis was performed to assess events during the post-acute phase (31-365 days). A total of 4,427 patients were included: 3,578 (80.8%) in the COVID-19 and 849 (19.2%) control cohorts. At one year, there were no significant differences in the primary endpoint of CV death between the COVID-19 and control cohorts (1.4% vs. 0.8%; HRadj 1.28 [0.56-2.91]; p = 0.555), but there was a higher risk of all-cause death (17.8% vs. 4.0%; HRadj 2.82 [1.99-4.0]; p = 0.001). COVID-19 cohort had higher rates of ATE (2.5% vs. 0.8%, HRadj 2.26 [1.02-4.99]; p = 0.044), VTE (3.7% vs. 0.4%, HRadj 9.33 [2.93-29.70]; p = 0.001), and serious cardiac arrhythmias (2.5% vs. 0.6%, HRadj 3.37 [1.35-8.46]; p = 0.010). During the post-acute phase, there were no significant differences in CV death (0.6% vs. 0.7%; HRadj 0.67 [0.25-1.80]; p = 0.425), but there was a higher risk of deep vein thrombosis (0.6% vs. 0.0%; p = 0.028). Re-hospitalization rate was lower in the COVID-19 cohort compared to the control cohort (13.9% vs. 20.6%; p = 0.001). At 1-year, patients with COVID-19 experienced an increased risk of all-cause death and adverse CV events, including ATE, VTE, and serious cardiac arrhythmias, but not CV death. URL: https://www.clinicaltrials.gov. Unique identifier: NCT04359927.

Vaccination, symptomatic infection and negative conversion of viral RNA by body mass index, diabetes, and age: An observational study

BackgroundThe associations of doses of vaccine received with symptomatic infection with SARS-CoV-2 and negative conversion rate of viral RNA by BMI, diabetes, and age are unclear. MethodsIncluded were adult cases of SARS-CoV-2 infection hospitalized at a makeshift hospital in Shanghai (N = 38,592). Each case received a real-time reverse transcriptase–polymerase chain reaction (RT-PCR) test every day until discharge. Symptomatic cases had ≥1 pre-specified symptoms. Negative conversion time (NCT) was the duration between the specimen collection date associated with the first positive RT-PCR test and the first test date of the two consecutive negative tests at least 24 h apart. BMI-, diabetes- and age-stratified multivariable logistic and Poisson regressions were applied. FindingsCoexistence of overweight/obesity and diabetes was associated with a higher risk of symptomatic infection and a longer NCT compared with coexistence of normal weight and without diabetes, but this association was primarily attributed to underlying comorbidities. Compared with absence of vaccination, booster vaccination, but not full vaccination, was consistently associated with a 42 %–56 % lower odds of symptomatic infection and ∼1.6–1.8 days of shorter NCT across different strata separately for weight and diabetes. Age-stratified analyses found that the effectiveness of booster vaccination did not attenuate with age, except for preventing symptomatic infection among adults with diabetes. InterpretationBMI and diabetes co-determined their associations with symptomatic infection and NCT. Booster vaccination but not full vaccination was associated a lower risk of symptomatic infection, a shorter NCT or both regardless of BMI, diabetes status and age.

Could self-reported symptoms be predictors of RT-PCR positivity in suspected COVID-19 cases? The Libya experience.

COVID-19 has symptoms similar to several other respiratory and non-respiratory diseases, which makes differentiating them a challenging task and could lead to unnecessary use of realtime reverse transcriptase polymerase chain reaction (RT-PCR) resources. The study aimed to assess self-reported symptoms as predictors for RT-PCR positivity in suspected COVID-19 cases. This was a cross-sectional study. We retrospectively reviewed the database of COVID-19 care centres in the eastern district of Tripoli, Libya, from May to December 2020. Presenting symptoms and RT-PCR test data were extracted. Of the 4593 subjects, 923 (20.1%) had positive RT-PCR result. Sensitivity for COVID-19 disease diagnosis was very low (≤ 18.2%) for all symptoms, except for myalgia (82.1%). Specificity was high for all symptoms (90.7-99.8%), except for myalgia (11.0%). Loss of taste and smell had the highest positive likelihood ratio (LR) for RT-PCR positivity (LR+ = 3.59, 95% CI: 2.95-4.37). In the multiple logistic regression, three symptoms maintained significant contribution to RT-PCR positivity; these were loss of taste and smell (odds ratio (OR) = 3.90, 95% CI: 3.04-4.99), sore throat (OR = 1.50, 95% CI: 1.02-2.19), and myalgia (OR = 0.65, 95% CI: 0.49-0.85). Other significant predictors were history of contact with a COVID-19 case (OR = 0.50, 95% CI: 0.39-0.62), and being female (OR = 1.33, 95% CI: 1.15-1.55). The findings of this study do not support the use of self-reported symptoms for the confirmation of COVID-19 disease in suspected cases because of their poor diagnostic properties.

Did the SARS-CoV-2 effect pregnancy complications?

This study aimed to evaluate the effect of SARS-CoV-2 on pregnancy complications, which increased compared to the same period before the pandemic. This prospective study was conducted at Etlik Zübeyde Hanım Women›s Health Practices & Research Center between June 2020 and July 2020. The asymptomatic term PROM and miscarriage pregnant women were screened for SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2) positivity by using IgM and IgG antibody tests. All the positive cases were confirmed by real-time reverse transcriptase-polymerase chain reaction (RT-PCR). All the patients answered 12 questions to determine their approach to COVID-19. Four of the 205 (2%) term PROM patients had positive anti-SARS-CoV-2 IgM antibody tests, one of the 205 (0.5%) term PROM patients had a positive anti-SARS-CoV-2 IgG antibody test, and one of the 205 (% 0.5) term PROM patients had positive anti-SARS-CoV-2 IgM and IgG antibody tests. All 230 miscarriage patients had negative IgM/IgG antibody tests. Four of the positive antibody cases had positive RT-PCR tests (2%) and were referred to a pandemic hospital. The patients thought that 93.2% and 95.6% of pregnant women with term PROM and miscarriage, respectively, SARS-CoV-2 would infect themselves, and 89.8% and 92.6%, respectively, would infect their children. The number of patients who would not consider pregnancy if they were not pregnant during this period was significantly higher in the term PROM (48.3%) compared to the miscarriage (27.8%) patients (p < 0.005). No COVID-19 cases were determined in the asymptomatic miscarriage patients. In the asymptomatic term PROM patients, the effects of COVID were not observed.

Current challenges in COVID-19 diagnosis: a narrative review and implications for clinical practice

Early diagnosis of coronavirus disease 2019 (COVID-19) is crucial to early treatment and quarantine measures. In this narrative review, diagnostic tools for COVID-19 diagnosis and their main critical issues were reviewed. The COVID-19 real-time reverse transcriptase-polymerase chain reaction (RT-PCR) test is considered the gold standard test for the qualitative and quantitative detection of viral nucleic acid. In contrast, tests can be used for epidemiological surveys on specific communities, including occupational cohorts, but not for clinical diagnosis as a substitute for swab tests. Computed tomography (CT) scans can be useful for the clinical diagnosis of COVID-19, especially in symptomatic cases. The imaging features of COVID-19 are diverse and depend on the stage of infection after the onset of symptoms. CT sensitivity seems to be higher in patients with positive RT-PCR. Conventional chest sensitivity shows a lower sensitivity. An important diagnostic screening tool is ultrasounds, whose specificity and sensitivity depend on disease severity, patient weight, and operator skills. Nevertheless, ultrasounds could be useful as a screening tool in combination with clinical features and molecular testing to monitor disease progression. Clinical symptoms and non-specific laboratory findings may be useful if used in combination with RT-PCR test and CT-scanning.

Detection of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) RNA in the Human Eye

ABSTRACT Purpose To determine the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in postmortem ocular specimens of patients with severe COVID-19 disease. Patients and methods Postmortem conjunctival (28 samples), aqueous humor (30 samples) and vitreous humor (30 samples) specimens were obtained bilaterally from the eyes of 15 deceased COVID-19 patients within one hour of death. The presence of viral RNA was evaluated in samples using Real-time reverse transcriptase-polymerase chain reaction (RT-PCR). Results Positive RT-PCR SARS-COV-2 results were found in one conjunctival and 2 vitreous humor samples. All aqueous humor samples tested negative for the presence of SARS-COV-2 RNA. Of note, three positive samples were obtained from three different patients. The overall prevalence of positive RT-PCR ocular samples was 3.4% among all samples and 20% at the patient level. Conclusion SARS-CoV-2 RNA is detectable in postmortem conjunctival and vitreous humor samples of patients with severe COVID-19.

Correlations between chest-CT and laboratory parameters in SARS-CoV-2 pneumonia: A single-center study from Italy.

To investigate the relationship between damaged lung assessed by chest computed tomography (CT) scan and laboratory biochemical parameters with the aim of finding other diagnostic tools.Patients who underwent chest CT for suspected Corona Virus Disease-2019 (COVID-19) pneumonia at the emergency department admission in the first phase of COVID-19 epidemic in Italy were retrospectively analyzed. Patients with both negative chest CT and absence of the novel coronavirus in nasopharyngeal or oropharyngeal real-time reverse transcriptase polymerase chain reaction (RT-PCR) swabs were excluded from the study. A total of 462 patients with positive CT scans for interstitial pneumonia were included in the study (250 males and 212 females, mean age 57 ± 17 years, range 18–89). Of these, 344 were positive to RT-PCR test, 118 were negative to double RT-PCR tests.CTs were analyzed for quantification of affected lung volume visually and by dedicated software. Statistical analysis to evaluate the relationship between laboratory analyses and CT patterns and amount of damaged lung related with COVID-19 pneumonia was performed in 2 groups of patients: positive RT-PCR COVID-19 group and negative RT-PCR COVID-19 group, but both with positive CT scans for interstitial pneumonia.Lymphocytopenia, C-reactive protein (CRP), lactate dehydrogenase (LDH), d-dimer, and fibrinogen increased levels occurred in most patients without statistically significant differences between the 2 groups with CT scans suggestive for COVID-19. In fact, in both groups the volume of lung damage was strongly associated with altered laboratory test results, even for patients with negative RT-PCR test.The decreased number of lymphocytes, and the increased levels of CRP, LDH, d-dimer, and fibrinogen levels are associated with SARS-CoV 2 related pneumonia. This may be useful as an additional diagnostic tool in patients with double negative RT-PCR assay and with highly suspected clinic and chest CT features for COVID-19 to isolate patients in a pandemic period.

Use of the COVID-19 Reporting and Data System (CO-RADS) classification and chest computed tomography involvement score (CT-IS) in COVID-19 pneumonia.

PurposeThe increasing tendency of chest CT usage throughout the COVID-19 epidemic requires new tools and a systematic scheme for diagnosing and assessing the lung involvement in Coronavirus Disease 2019 (COVID-19). To investigate the use of the COVID-19 Reporting and Data System (CO-RADS) classification and chest CT Involvement Score (CT-IS) in COVID-19 pneumonia.Material and methodsThis retrospective study enrolled 280 hospitalized patients diagnosed with COVID-19 pneumonia in a tertiary hospital in Turkey. All patients underwent non-contrast CT chest imaging. Two radiologists interpreted all CT images according to CO-RADS classification without knowing the clinical features, laboratory findings. We used CT involvement score (CT-IS) for assessing chest CT images of COVID-19 patients. Also, we examined the relationship between CT-IS and clinical outcomes in COVID-19 patients.ResultsOf the patients, 111(39.6%) had positive real-time reverse transcriptase-polymerase chain reaction (RT-PCR) results. CO-RADS 5 group patients had statistically significant positive RT-PCR results than the other groups (P < 0.001). All of the CO-RADS 2 group patients (30) had negative RT-PCR results. The mean total CT-IS in CO-RADS 2 group was 3.4 ± 2.8. The mean total CT-IS in CO-RADS 5 group was 8.2 ± 4.7. Total CT-IS was statistically significantly different among CO-RADS groups (P < 0.001). The mean total CT-IS was statistically significantly different between survivors and patients died of COVID-19 pneumonia (P < 0.001).ConclusionsCO-RADS is useful in detecting COVID-19 disease, even if RT-PCR testing is negative. CT-IS is also helpful as an imaging tool for evaluation of the severity and extent of COVID-19 pneumonia.

Real Time PCR and Culture-Based Virus Isolation Test in Clinically Recovered Patients: Is the Subject Still Infectious for SARS-CoV2?

Background. The highly variable manifestation of the COVID-19 disease, from completely asymptomatic to fatal, is both a clinical and a public health issue. The criteria for discharge of hospitalized patients have been based so far on the negative result of Real-Time Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) tests, but the persistence of viral fragments may exceed that of the integral virus by weeks. The aim of our study was to verify the clearance of the virus at viral culture in patients hospitalized for COVID-19 that have clinically recovered but are still positive on nasopharyngeal swab. Methods. The study was conducted in hospitalized patients with positive RT-PCR on nasopharyngeal swab. Patients included were from asymptomatic to severe cases and performed nasopharyngeal control swabbing on day 14 for asymptomatic patient or at least three days after remission of symptoms. RT-PCR positive specimens were sent to a biosafety level 3 laboratory for viral culture. Results. We performed a combined analysis of RT-PCR and a highly sensitive in vitro culture from 84 samples of hospitalized patients. The average age was 46 ± 20.29, and 40.5% of the subjects had radiologically confirmed pneumonia, with average PaO2 of 72.35 ± 12.12and P/F ratio of 315 ± 83.15. Ct values for the N gene were lower in the first swab than in the control one (p < 0.001). The samples from 83 patients were negative at viral culture, and RT-PCR on the respective supernatants always confirmed the absence of viral growth. Conclusions. Our preliminary results demonstrate that patients clinically recovered for at least three days show the viral clearance at viral culture, and presumably they continued to not be contagious.

Are asymptomatic gastrointestinal findings on imaging more common in COVID-19 infection? Study to determine frequency of abdominal findings of COVID-19 infection in patients with and without abdominal symptoms and in patients with chest-only CT scans.

PurposeTo identify incidence of abdominal findings in COVID-19 patients with and without abdominal symptoms on various imaging modalities including chest-only CT scans and to correlate them with clinical, laboratory and chest CT findings.Materials and methodsIn this retrospective study, we searched our clinical database between March 1st, 2020 and May 22nd, 2020 to identify patients who had positive real-time reverse transcriptase polymerase chain reaction (RT-PCR) on throat swabs for COVID-19, had availability of clinical, laboratory information and had availability of CT scan of chest or abdominal radiograph, abdominal ultrasound or CT scan within 2 weeks of the diagnosis. Abdominal imaging findings on all imaging modalities were documented. Chest CT severity score (CT-SS) was assessed in all patients. Clinical and laboratory findings were recorded from the electronic medical record. Statistical analysis was performed to determine correlation of abdominal findings with CT-SS, clinical and laboratory findings.ResultsOut of 264 patients with positive RT-PCR, 73 patients (38 males and 35 females; 35 African American) with mean age of 62.2 (range 21–94) years were included. The median CTSS was 13.5 (IQR 75–25 18–8). Most common finding in the abdomen on CT scans (n = 72) were in the gastrointestinal system in 13/72 patients (18.1%) with fluid-filled colon without wall thickening or pericolonic stranding (n = 12) being the most common finding. Chest-only CT (n = 49) found bowel findings in 3 patients. CTSS did not differ in terms of age, sex, race or number of comorbidities but was associated with longer duration of hospitalization (p = 0.0.0256), longer intensive care unit stay (p = 0.0263), more frequent serum lactate dehydrogenase elevation (p = 0.0120) and serum C-reactive protein elevation (p = 0.0402). No statistically significant correlation of occurrence of bowel abnormalities with CTSS, clinical or laboratory features. Deep venous thrombosis was seen in 7/72 patients (9.8%) with three patients developing pulmonary embolismConclusionAbnormal bowel is the most common finding in the abdomen in patients with COVID-19 infection, is often without abdominal symptoms and occurs independent of severity of pulmonary involvement, other clinical and laboratory features.

Outcome of COVID-19 infection in cancer patients during active systemic anticancer treatment. Single-institution experience. A retrospective analysis.

IntroductionPatients with cancer undergoing active systemic anticancer treatment (chemotherapy, immunotherapy, targeted, or combination therapy) are at greater risk of COVID-19 infection than persons without cancer. In this paper, the authors analyse the spread of the coronavirus among cancer patients undergoing systemic therapy, and the impact of COVID-19 infection on the continuation of cancer treatment and its outcome at one community hospital in a mid-sized city in the south of Poland.Material and methodsNasopharyngeal swab was the only collection method used to obtain specimens for testing via real-time reverse-transcriptase polymerase chain reaction (RT-PCR). Only those with positive RT-PCR results were considered as confirmed SARS-CoV-2 cases. We analysed the medical records of patients quarantined in a hospital clinical oncology ward due to confirmed COVID-19 infection in one member of the group. Qualitative measures are presented as the percentage of their occurrence, and these were evaluated with Fisher’s test. Differences were considered significant at p < 0.05.ResultsCancer patients had more frequent confirmed COVID-19 infection than other patients (3.7% vs. 1.2%). Among cancer patients COVID-19 infection was significantly more frequent in women than in men, p = 0.005. The fatality rate was 27.3% in cancer patients undergoing active anticancer therapy, compared to 3% in the general Polish population. Neither heparin nor G-CSF use had any influence on COVID-19 infection.ConclusionsIn this analysis, the only significant negative factor for COVID-19 infection was female sex, RR (95% CI) = 4.5 (1.3–15.8), (p = 0.005), and this was attributable to individual behaviour.

Middle-aged and elderly patients with COVID-19 pneumonia arising from asymptomatic carriers: A report of six cases.

Middle-aged and elderly patients with COVID-19 pneumonia arising from asymptomatic carriers: A report of six cases.

Prolonged SARS-CoV-2 detection and reversed RT-PCR results in mild or asymptomatic patients

Background The clinical course and viral detection period in mild or asymptomatic coronavirus disease 2019 (COVID-19) patients are not yet known. The presumed low diagnostic sensitivity of upper respiratory specimens for Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) makes it difficult to confirm infection and recommend de-isolation. Methods We retrospectively reviewed real-time reverse transcriptase-polymerase chain reaction (RT-PCR) test results of mild or asymptomatic COVID-19 patients who were admitted at the Daegu-Gyeongbuk 7th community treatment centre in Korea between 9 March 2020 and 10 April 2020. Patients underwent an upper respiratory RT-PCR test every week until discharge. From the RT-PCR results, we evaluated the rate of prolonged (>3 weeks) SARS-CoV-2 RNA positivity. We analysed the proportion of reversed results, defined as a positive or indeterminate result one day after a negative RT-PCR result, according to time (<14, 15–21, 22–28, >28 days) from the initial positive RT-PCR result. Results In 23% (69/300) of patients, SARS-CoV-2 was detected more than 3 weeks after the initial positive RT-PCR. In 14% (42/300) of patients, the RT-PCR results were positive for more than 4 weeks. For 37.5% (152/405) of negative RT-PCR results, the results were reversed in the next day’s test. And 43.5% (123/283) of negative RT-PCR results were reversed within 3 weeks of diagnosis. Conclusions The detection of SARS-CoV-2 lasting more than 3 weeks was common in mild or asymptomatic patients. Upper respiratory RT-PCR results were frequently reversed from negative to positive.

RECURRENT COVID-19 INFECTION IN RECOVERED PATIENTS (A CRITICAL REVIEW)

The pandemic of Coronavirus Disease 2019 (COVID-19) is still grooming throughout the world. However, the number of recovered patients with COVID-19 is also increasing day by day. Some discharged patients from hospitals had shown fever and radiological abnormalities again along with positive real-time reverse transcriptase-polymerase chain reaction (RT-PCR). This might be due to relapse of COVID-19 in recovered patients, secondary bacterial infection, the false-positive result after discharging, or a false negative at discharging yet to determine. In this review, a total of seven studies retrieved, in which 1052 COVID-19 infected patients were studied and followed them for one to six weeks. Among 1,052 patients, 12.1% (n=127) patients were found re-infected having positive RT-PCR with different clinical samples including nasopharyngeal swab, an anal swab, throat swab, and sputum samples. All re-infected patients were found with mild to moderate clinical symptoms. These findings suggest that recurrence of COVID-19 is exist. It is important to develop diagnostic tools further to avoid the false negative or positive results. Moreover, followup studies are required to determine the reason behind the recurrence of COVID-19 in recovered. Besides, we suggest because of the current review, further management of discharged patients is crucial especially for immunocompromised patients, old age patients, or patients with comorbidities. The discharge criteria should be ensured for a recovered patient to prevent the relapse of COVID-19. Keywords: COVID-19, Discharge, Recurrence, Recovered Patients, RT-PCR

Pre-emptive Therapy for the Cytomegalovirus Infection After Liver Transplantation in Endemic Areas and Its Optimal Diagnostic Method

BackgroundThe incidence of positive cytomegalovirus (CMV) IgG tests among Asian populations is high. Both universal prophylaxis and pre-emptive therapy (PT) have been recommended for the moderate-risk group (D+/R+), whose incidence of CMV infection has been reported variously, and for whom the optimal diagnostic method has not been firmly established. Herein, we sought to analyze our experience with CMV infections using PT and to discuss the optimal diagnostic method. MethodsWe retrospectively, analyzed 32 consecutive liver transplant recipients between December 2009 and April 2012 for clinicopathologic data including mortality and rejection rates, comparing 2 diagnostic tools for CMV: pp65 antigen assay and real-time reverse-transcriptase polymerase chain reaction (RT-PCR). ResultsTwenty-one patients (65.6%) were positive for the CMV antigen assay, and 13 (40.6%) had positive RT-PCR results. There were no cases of CMV disease during the follow-up and no difference in rejection (P = .529) or mortality (P = .471) rates with regard to PCR positivity. The mean diagnosis time was 26.5 days postoperative. Among the patients who exhibited negative RT-PCR results, 7 (41.18%) were positive on the pp65 antigen assay. ConclusionCMV infection rates were higher when compared to same-risk population from Western countries. As a diagnostic tool for CMV infection, screening with the pp65 antigen assay and confirmation with real-time RT-PCR seemed to provide an optimal diagnostic tool.

Detection of Airborne Influenza A Virus in Experimentally Infected Pigs With Maternally Derived Antibodies

This study assessed whether recently weaned piglets with maternally derived antibodies were able to generate infectious influenza aerosols. Three groups of piglets were assembled based on the vaccination status of the dam. Sows were either non-vaccinated (CTRL) or vaccinated with the same (VAC-HOM) strain or a different (VAC-HET) strain to the one used for challenge. Piglets acquired the maternally derived antibodies by directly suckling colostrum from their respective dams. At weaning, pigs were challenged with influenza virus by direct contact with an infected pig (seeder pig) and clinical signs evaluated. Air samples, collected using a liquid cyclonic air collector, and individual nasal swabs were collected daily for 10 days from each group and tested by matrix real-time reverse transcriptase polymerase chain reaction (RRT-PCR) assay. Virus isolation and titration were attempted for air samples on Madin-Darby canine kidney cells. All individual pigs from both VAC-HET and CTRL groups tested positive during the study but only one pig in the VAC-HOM group was positive by nasal swab RRT-PCR. Influenza virus could not be detected or isolated from air samples from the VAC-HOM group. Influenza A virus was isolated from 3.2% and 6.4% air samples from both the VAC-HET and CTRL groups, respectively. Positive RRT-PCR air samples were only detected in VAC-HET and CTRL groups on day 7 post-exposure. Overall, this study provides evidence that recently weaned pigs with maternally derived immunity without obvious clinical signs of influenza infection can generate influenza infectious aerosols which is relevant to the transmission and the ecology of influenza virus in pigs.

Clinical Features of 2009 Pandemic Infuenza A (H1N1) Virus Infection in Chronic Hemodialysis Patients

Background/Aims: Infection is one of the most common complications and is considered the second leading cause of death in dialysis patients with end-stage renal disease. After the first cases of 2009 pandemic influenza A (H1N1) virus in China became public, persons with suspected infection and those who were in contact with persons with suspected infection were tested. Whether the presentation and clinical course of H1N1 influenza is similar in the dialysis population to the general population is currently unknown. Hemodialysis patients in whom an infection was confirmed were hospitalized and quarantined, and patients on chronic hemodialysis were closely observed for the purpose of investigating the nature and duration of the disease. Methods: From May 2009 to February 2010, we observed 15 hemodialysis patients infected with the 2009 pandemic influenza A (H1N1) virus who were quarantined in Beijing Chao-Yang Hospital, Capital Medical University. Real-time reverse transcriptase polymerase chain reaction (RT-PCR) testing was used to confirm infection, the clinical features of the disease were closely monitored. Results: The mean age of the 15 patients was 47.6 years, and 9 of the 15 patients were male. The diagnoses were all made in the hospital. All of the 15 patients had fluid overload. The median incubation period of the virus in hemodialysis patients was 4 days (range: 1–7 days). The most common symptoms were dyspnea (in all of the 15 patients) and productive cough (in all of the 15 patients). One of the 15 patients had low-grade fever, and the other 14 patients were afebrile. Lymphopenia, which was common in 12 of the patients, typically occurred on day 2 (range: days 1–3) and resolved by day 9 (range: days 7–11). Hypoxemia was observed in all of the patients. Six of the 15 patients developed respiratory failure requiring mechanical ventilation on days 7–9 because they were complicated by Escherichia coli nosocomial pneumonia. All the patients were placed in respiratory isolation and were treated with oseltamivir. The median length of time during which patients had positive real-time RT-PCR test results was 12 days (range: 7–19 days), which was longer than that in general population. Conclusions: The presentation and clinical course of H1N1 influenza A in the hemodialysis patients was atypical and relatively serious, which differed from the general population in China. Furthermore, these patients may have an extended period of viral shedding.