Scalp eschar and neck lymphadenopathy after tick bite (SENLAT) caused by Bartonella henselae in Korea: a case report.

BACKGROUND: Tick-borne lymphadenopathy (TIBOLA) is an infectious disease, mainly caused by species from the spotted fever group rickettsiae and is characterized by enlarged lymph nodes following a tick bite. Among cases of TIBOLA, a case of scalp eschar and neck lymphadenopathy after tick bite (SENLAT) is diagnosed when an eschar is present on the scalp, accompanied by peripheral lymphadenopathy (LAP). Only a few cases of SENLAT caused by Bartonella henselae have been reported. CASE PRESENTATION: A 58-year-old male sought medical advice while suffering from high fever and diarrhea. Three weeks before the visit, he had been hunting a water deer, and upon bringing the deer home discovered a tick on his scalp area. Symptoms occurred one week after hunting, and a lump was palpated on the right neck area 6 days after the onset of symptoms. Physical examination upon presentation confirmed an eschar-like lesion on the right scalp area, and cervical palpation revealed that the lymph nodes on the right side were non-painful and enlarged at 2.5 × 1.5 cm. Fine needle aspiration of the enlarged lymph nodes was performed, and results of nested PCR for the Bartonella internal transcribed spacer (ITS) confirmed B. henselae as the causative agent. CONCLUSION: With an isolated case of SENLAT and a confirmation of B. henselae in Korea, it is pertinent to raise awareness to physicians in other Asian countries that B. henselae could be a causative agent for SENLAT.

Clinical Score System to Differentiate Severe Fever with Thrombocytopenia Syndrome Patients from Patients with Scrub Typhus or Hemorrhagic Fever with Renal Syndrome in Korea.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with high mortality in East Asia. This study aimed to develop, for primary care providers, a prediction score using initial symptoms and basic laboratory blood tests to differentiate between SFTS and other endemic zoonoses in Korea. METHODS: Patients aged ≥ 18 years diagnosed with endemic zoonoses during a 3-year period (between January 2015 and December 2017) were retrospectively enrolled from 4 tertiary university hospitals. A prediction score was built based on multivariate logistic regression analyses. RESULTS: Of 84 patients, 35 with SFTS and 49 with other endemic zoonoses were enrolled. In multivariate logistic regression analysis, independent predictors of SFTS included neurologic symptoms (odds ratio [OR], 12.915; 95% confidence interval [CI], 2.173-76.747), diarrhea (OR, 10.306; 95% CI, 1.588-66.895), leukopenia (< 4,000/mm³) (OR, 19.400; 95% CI, 3.290-114.408), and normal C-reactive protein (< 0.5 mg/dL) (OR, 24.739; 95% CI, 1.812-337.742). We set up a prediction score by assigning one point to each of these four predictors. A score of ≥ 2 had 82.9% sensitivity (95% CI, 71.7%-87.5%) and 95.9% specificity (95% CI, 88.0%-99.2%). The area under the curve of the clinical prediction score was 0.950 (95% CI, 0.903-0.997). CONCLUSION: This study finding suggests a simple and useful scoring system to predict SFTS in patients with endemic zoonoses. We expect this strategic approach to facilitate early differentiation of SFTS from other endemic zoonoses, especially by primary care providers, and to improve the clinical outcomes.

Delays in Isolating Patients Admitted to Hospital with Pulmonary Tuberculosis in Korea.

BACKGROUND: Delays in isolating patients admitted to hospital with active pulmonary tuberculosis (PTB) can contribute to nosocomial transmission; however, in Korea, patients with clinically diagnosed PTB are not routinely isolated while awaiting microbiological confirmation of the diagnosis. We aimed to assess the extent of delays in isolating patients admitted with PTB and to identify the factors associated with delayed isolation. METHODS: We retrospectively reviewed the electronic medical records of patients aged ≥ 18 years with active PTB, between January 2008 and December 2017, from two Korean hospitals. RESULTS: Among 1,062 patients, 612 (57.6%) were not isolated on admission day. The median time from admission to isolation was 1 day (interquartile range: 0-2 days). The independent risk factor most strongly associated with delayed isolation was admission to departments other than pulmonology or infectious diseases departments (adjusted odds ratio [aOR], 5.302; 95% confidence interval [CI], 3.177-8.847; P < 0.001). Factors associated with isolation on admission day were a past history of tuberculosis (TB) (aOR, 0.669; 95% CI, 0.494-0.906; P = 0.009), night sweats (aOR, 0.530; 95% CI, 0.330-0.851; P = 0.009), and apical infiltrates on chest radiographs (aOR, 0.452; 95% CI, 0.276-0.740; P = 0.002). CONCLUSION: Concerning patients subsequently diagnosed with active PTB, > 50% were not isolated on admission day. We suggest that the patients with clinically suspected PTB including the elderly who have a past history of TB, night sweats, or apical infiltration on chest radiographs, be presumptively isolated on admission, without waiting for microbiological confirmation of the diagnosis.

SARS-CoV-2 antigenemia and RNAemia in association with disease severity in patients with COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19, causes a spectrum of symptoms ranging from mild upper to severe lower respiratory tract infections. However, the dynamics of nucleocapsid (N) protein antigenemia and RNAemia are not fully understood. We conducted a cohort study involving 117 patients with clinically confirmed COVID-19, focusing on the kinetics of antigenemia and RNAemia and their association with various clinical characteristics. The patients had a median age of 66.0 years (52.0-79.0 years), with a gender distribution of 46.2% male and 53.8% female. Antigenemia reached 100% in fatal cases during the first week after admission. The sensitivity/specificity of antigenemia for diagnosis were 64.7%/73.0% at admission, 69.1%/100% in Week 1, and 66.3%/100% in Week 2. Additionally, the rates of antigenemia in asymptomatic patients were 27.3% upon admission and 22.0% in Week 1, respectively; however, no antigenemia was in samples collected in Week 2. Viral RNAemia was not detected in asymptomatic patients, but RNAemia viral loads were elevated in fatal cases. Kaplan-Meier survival curves demonstrated a higher mortality rate when antigenemia concentrations were elevated in the follow-up samples (P = 0.005). Our study provides a comprehensive analysis of the kinetics of viral N-protein antigenemia and RNAemia according to disease severity and clinical classification. Our findings suggest that highest concentrations of antigenemia in fatal cases occur in the first week after admission, indicating that early elevated antigenemia may serve as a marker of mortality risk.

Updated Clinical Practice Guidelines for the Diagnosis and Management of Long COVID.

"Long COVID" is a term used to describe a condition when the symptoms and signs associated with coronavirus disease 2019 (COVID-19) persist for more than three months among patients infected with COVID-19; this condition has been reported globally and poses a serious public health issue. Long COVID can manifest in various forms, highlighting the need for appropriate evaluation and management by experts from various fields. However, due to the lack of clear clinical definitions, knowledge of pathophysiology, diagnostic methods, and treatment protocols, it is necessary to develop the best standard clinical guidelines based on the scientific evidence reported to date. We developed this clinical guideline for diagnosing and treating long COVID by analyzing the latest research data collected from the start of the COVID-19 pandemic until June 2023, along with the consensus of expert opinions. This guideline provides recommendations for diagnosis and treatment that can be applied in clinical practice, based on a total of 32 key questions related to patients with long COVID. The evaluation of patients with long COVID should be comprehensive, including medical history, physical examination, blood tests, imaging studies, and functional tests. To reduce the risk of developing long COVID, vaccination and antiviral treatment during the acute phase are recommended. This guideline will be revised when there is a reasonable need for updates based on the availability of new knowledge on the diagnosis and treatment of long COVID.

Clinical utility of universal 16S rRNA PCR using sterile body fluids: lung abscess caused by Nocardia farcinica.

Nocardiosis is an infectious disease caused by Gram-positive rod-shaped bacteria and presents as a suppurative granulomatous disease in patients with compromised immune systems. Few studies have investigated the clinical utility of the universal 16S rRNA polymerase chain reaction (PCR) method using sterile body fluids for diagnosing nocardiosis. A 64-year-old female patient was admitted to Chosun University Hospital with the complaint of fever. Computed tomography scans of her chest revealed the presence of empyema and an abscess in the right lung. Pus samples were collected using closed chest thoracostomy and were cultured. The results revealed the presence of Gram-positive bacilli, but the culture tests were unable to identify the causative microorganism. Despite antibiotic treatment, the patient died of the suspected empyema and abscess. Universal 16S PCR of her sterile body fluids in combination with sequencing was performed, which led to the diagnosis of Nocardia farcinica infection. Postmortem, the remainder of the pus samples cultured for 8 days confirmed the presence of N. farcinica. This study illustrates the importance of using routine universal 16S rRNA PCR with sterile body fluids to help diagnose atypical bacterial infections such as nocardiosis.

Evaluation of humoral immune response in relation to COVID-19 severity over 1 year post-infection: critical cases higher humoral immune response than mild cases.

Introduction: Coronavirus disease 2019 (COVID-19) is caused by SARS-CoV-2. We investigated the antibody response against SARS-CoV-2 until 1 year after symptom onset. Methods: We collected 314 serum samples from 97 patients with COVID-19. Antibody responses were tested using an indirect immunofluorescence assay (IFA), enzyme-linked immunosorbent assay (ELISA), and plaque reduction neutralization test (PRNT) to detect specific neutralizing antibodies. Results: The positivity rates for neutralizing antibodies at a 1:10 titer cutoff were 58.1% at 1 week, 97.8% at 4 weeks, and 78% at 1 year after symptom onset (53.8% in asymptomatic patients and 89.3% in symptomatic patients). The IFA and anti-S1 ELISA IgG results significantly correlated with neutralizing antibody titers. Critical/fatal cases showed significantly higher antibody titers than the asymptomatic or mild-to-moderate illness groups. Nonetheless, the median number of days to the seroconversion of neutralizing antibodies was 10 and 15 in asymptomatic and symptomatic patients, respectively. The asymptomatic group had a significantly higher neutralizing potency index than the mild-to-severe illness groups. Conclusions: Neutralizing antibodies corresponded to earlier seroconversion but had a shorter presence in the asymptomatic group than in the symptomatic group and were still present 1 year after symptom onset in critical/fatal cases.

Diagnostic Sensitivity of Saliva and Other Respiratory Tract Samples of SARS-CoV-2 Variants in Patients with COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants continue to emerge during the ongoing coronavirus disease 2019 (COVID-19) pandemic. Contrasting studies on the omicron variant have demonstrated higher viral loads in different clinical specimens, which is consistent with its high transmissibility. We investigated the viral load in clinical specimens that were infected with the SARS-CoV-2 wild-type, delta, and omicron variants, and we analyzed the diagnostic accuracy of upper and lower respiratory specimens for these variants. We performed nested reverse transcription (RT)-polymerase chain reaction (PCR), targeting the spike gene and sequencing for variant classification. RT-PCR was performed using upper and lower respiratory specimens, including saliva from 78 COVID-19 patients (wild-type, delta, and omicron variants). A comparison of the sensitivity and specificity, using the area under the receiver operating characteristic curve (AUC) values from the N gene, showed that the omicron variant saliva samples had a higher sensitivity (AUC = 1.000) than did the delta (AUC = 0.875) and the wild-type (AUC = 0.878) variant samples. The sensitivity of the omicron saliva samples was greater than that of the wild-type nasopharynx and sputum samples (P < 0.001). The viral loads of the saliva samples containing the wild-type, delta, and omicron variants were 8.18 × 105, 2.77 × 106, and 5.69 × 105, respectively, which did not differ significantly (P = 0.610). Statistically significant differences were not observed in the saliva viral loads between vaccinated and nonvaccinated patients who were infected with the omicron variant (P = 0.120). In conclusion, omicron saliva samples had higher sensitivity than did wild-type and delta samples, and the viral load did not significantly differ between vaccinated and nonvaccinated patients. Further research is necessary to elucidate the mechanisms underlying the sensitivity differences. IMPORTANCE Owing to the vast heterogeneity of the studies focused on the correlation between the SARS-CoV-2 omicron variant and COVID-19, accurate comparisons of the specificity and sensitivity of samples and associated outcomes are still inconclusive. Moreover, limited information is available on the leading causes of infection and the factors that are associated with the conditions that underlie the spread of infection. Although several studies have contributed important knowledge regarding infectious specimens, the impact of saliva samples remains unknown. This study showed that the sensitivity of the omicron variant saliva samples was higher than that of the wild-type nasopharyngeal and sputum samples. Moreover, neither vaccinated nor nonvaccinated patients who were infected with the omicron variant showed any significant differences in SARS-CoV-2 viral loads. Hence, this study is an important step toward understanding how saliva sample results are correlated with other specimen results, regardless of the vaccination status of patients who are infected with the SARS-CoV-2 omicron variant.

Transverse myelitis caused by herpes zoster following COVID-19 vaccination: A case report.

BACKGROUND: Transverse myelitis (TM) is characterized by sudden lower extremity progressive weakness and sensory impairment, and most patients have a history of advanced viral infection symptoms. A variety of disorders can cause TM in association with viral or nonviral infection, vascular, neoplasia, collagen vascular, and iatrogenic, such as vaccination. Vaccination has become common through the global implementation against coronavirus disease 2019 (COVID-19) and reported complications like herpes zoster (HZ) activation has increased. CASE SUMMARY: This is a 68-year-old woman who developed multiple pustules and scabs at the T6-T9 dermatome site 1 wk after vaccination with the COVID-19 vaccine (Oxford/AstraZeneca ([ChAdOx1S{recombinant}]). The patient had a paraplegia aggravation 3 wk after HZ symptoms started. Spinal magnetic resonance imaging (MRI) showed transverse myelitis at the T6-T9 Level. Treatment was acyclovir with steroids combined with physical therapy. Her neurological function was slowly restored by Day 17. CONCLUSION: HZ developed after COVID-19 vaccination, which may lead to more severe complications. Therefore, HZ treatment itself should not be delayed. If neurological complications worsen after appropriate management, an immediate diagnostic procedure, such as magnetic resonance imaging and laboratory tests, will start and should treat the neurological complications.

SARS-CoV-2 RNAemia and Disease Severity in COVID-19 Patients.

OBJECTIVE: The clinical implications of SARS-CoV-2 RNA viremia in blood (RNAemia) remain uncertain despite gaining more prognostic implications for coronavirus disease 2019 (COVID-19). However, the clinical relevance of SARS-CoV-2 RNAemia has not been well documented. METHODS: We conducted a cohort study on 95 confirmed COVID-19 patients and explored the prospects with evidence of SARS-CoV-2 RNAemia in association with various clinical characteristics. We performed reverse transcription-polymerase chain reaction and studied the risk factors of SARS-CoV-2 RNAemia using logistic regression analysis. RESULTS: The presence of SARS-CoV-2 RNAemia in critical or fatal cases was the highest (66.7%), followed by severe (12.5%) and mild to moderate (1.7%) in admission samples. SARS-CoV-2 viral RNAemia was detected on admission and 1st week samples; however, RNAemia was not detected on the samples collected on the second week post-symptom onset. Multiple regression analysis showed that the severity of the disease was an independent predictor of RNAemia (p < 0.021), and the Kaplan-Meier survival curve estimated an increased mortality rate in SARS-CoV-2 RNAemia cases (p < 0.001). CONCLUSIONS: Our study demonstrated that SARS-CoV-2 RNAemia is a predictive risk factor for clinical severity in COVID-19 patients. Hence, we showed that blood RNAemia might be a critical marker for disease severity and mortality.

Risk factors for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA environmental contamination in rooms of patients with coronavirus disease 2019 (COVID-19).

The risk factors of environmental contamination by SARS-CoV-2 are largely unknown. We analyzed 1,320 environmental samples obtained from COVID-19 patients over 1 year. The risk factors for contamination of COVID-19 patients' surrounding environment were higher viral load in the respiratory tract and shorter duration from symptom onset to sample collection.

Efficacy of Plant-Made Human Recombinant ACE2 against COVID-19 in a Golden Syrian Hamster Model.

Coronavirus disease 2019 (COVID-19) is a novel infectious respiratory disease caused by SARS-CoV-2. We evaluated the efficacy of a plant-based human recombinant angiotensin-converting enzyme 2 (hrACE2) and hrACE2-foldon (hrACE2-Fd) protein against COVID-19. In addition, we analyzed the antiviral activity of hrACE2 and hrACE2-Fd against SARS-CoV-2 using real-time reverse-transcription PCR and plaque assays. The therapeutic efficacy was detected using the Golden Syrian hamster model infected with SARS-CoV-2. Both hrACE2 and hrACE2-Fd inhibited SARS-CoV-2 by 50% at concentrations below the maximum plasma concentration, with EC50 of 5.8 µg/mL and 6.2 µg/mL, respectively. The hrACE2 and hrACE2-Fd injection groups showed a tendency for decreased viral titers in nasal turbinate tissues on day 3 after virus inoculation; however, this decrease was not detectable in lung tissues. Histopathological examination on day 9 after virus inoculation showed continued inflammation in the SARS-CoV-2 infection group, whereas decreased inflammation was observed in both the hrACE2 and hrACE2-Fd injection groups. No significant changes were observed at other time points. In conclusion, the potential therapeutic efficacy of plant-based proteins, hrACE2 and hrACE2-Fd, against COVID-19 was confirmed in a SARS-CoV-2-inoculated Golden Syrian hamster model. Further preclinical studies on primates and humans are necessary to obtain additional evidence and determine the effectiveness of these therapies.

The Seroprevalence of Severe Fever with Thrombocytopenia Syndrome: An Epidemiological Study of Korean Veterinary Hospital Workers.

Severe fever with thrombocytopenia syndrome (SFTS) is a zoonotic tick-borne infectious disease caused by the SFTS virus (SFTSV). Few studies have assessed SFTS seroprevalence among veterinary hospital staff and their awareness of SFTS. From January to May 2021, serum samples from 103 veterinary hospital staff were tested for SFTS using an enzyme-linked immunosorbent assay (ELISA), an immunofluorescence assay, and a 50% plaque reduction neutralization antibody test, which yielded positive results in four (3.9%), three (2.9%), and two (1.9%) participants, respectively. A questionnaire was used for an epidemiological investigation. ELISA positivity was higher among those who lacked awareness of possible animal-to-human SFTS transmission (p = 0.029). SFTS awareness was significantly lower among veterinary hospital staff than among the veterinarians (p < 0.001). Providing staff with training concerning standard precautions and the use of appropriate personal protective equipment is important.

Effectiveness of Antiviral Therapy on Long COVID: A Systematic Review and Meta-Analysis.

Antiviral treatment reduces the severity and mortality of SARS-CoV-2 infection; however, its effectiveness against long COVID-19 is unclear. This study aimed to evaluate the effectiveness of antiviral drugs in preventing long COVID and related hospitalizations/deaths. Scientific and medical databases were searched from 1 January 2020 to 30 June 2023. We included observational cohort studies comparing individuals receiving early antiviral therapy for COVID-19 and those receiving supportive treatment. A fixed-effects model was used to merge the effects reported in two or more studies. The risk of post-acute sequelae of COVID-19 (PASC) was combined as an odds ratio (OR). Six studies were selected, including a total of 3,352,235 participants. The occurrence of PASC was 27.5% lower in patients who received antiviral drugs during the early stages of SARS-CoV-2 infection (OR = 0.725; 95% confidence interval [CI] = 0.409-0.747) than in the supportive treatment group. Moreover, the risk of PASC-associated hospitalization and mortality was 29.7% lower in patients receiving early antiviral therapy than in the supportive treatment group (OR = 0.721; 95% CI = 0.697-0.794). Early antiviral therapy was associated with a reduced risk of PASC and related hospitalization or death. Thus, early antiviral therapy is recommended for at-risk individuals.

Clinically differential diagnosis of human granulocytic anaplasmosis and severe fever with thrombocytopenia syndrome.

This study analyzed HGA and SFTS in patients with suspected tick-borne infection by focusing on key differences that clinicians can easily recognize. A retrospective analysis was performed on confirmed patients with HGA or SFTS in 21 Korean hospitals from 2013 to 2020. A scoring system was developed by multivariate regression analysis and accuracy assessment of clinically easily discriminable parameters was performed. The multivariate logistic regression analysis revealed that sex (especially male sex) (odds ratio [OR] 11.45, P = 0.012), neutropenia (< 1500) (OR 41.64, P < 0.001), prolonged activated partial thromboplastin time (OR 80.133, P < 0.001), and normal C-reactive protein concentration (≤ 1.0 mg/dL; OR 166.855, P = 0.001) were significantly associated with SFTS but not with HGA. Each factor, such as meaningful variables, was given 1 point, and a receiver-operating characteristic curve with a cutoff value (> 1) in a 5-point scoring system (0-4 points) was analyzed to evaluate the accuracy of differentiation between HGA and SFTS. The system showed 94.5% sensitivity, 92.6% specificity, and an area under the receiver-operating characteristic curve of 0.971 (0.949-0.9). Where HGA and SFTS are endemic, the scoring system based on these four parameters such as sex, neutrophil count, activated partial thromboplastin time, and C-reactive protein concentration will facilitate the differential diagnosis of HGA and SFTS in the emergency room in patients with suspected tick-borne infectious diseases.

Coinfection With Severe Fever With Thrombocytopenia Syndrome and Scrub Typhus in Korea.

Background: Scrub typhus and severe fever with thrombocytopenia syndrome (SFTS) are the 2 most common tick-borne infectious diseases in Korea. Every year, an increasing number of cases are reported, which is a public health concern. Therefore, we aimed to investigate the prevalence of SFTS-scrub typhus coinfection in patients with SFTS. Methods: Clinical samples were collected from 129 patients with SFTS. One-step reverse-transcription polymerase chain reaction (PCR) was performed to identify the SFTS virus (SFTSV), and real-time PCR followed by nested PCR was performed to detect the Orientia tsutsugamushi gene for scrub typhus. Phylogenetic analysis was conducted to confirm the evolutionary relationships among different species. Results: Among 129 SFTS cases, 2 patients with SFTSV were positive for O. tsutsugamushi with a prevalence of coinfection of 1.6% (95% confidence interval, .001-.06). Phylogenetic analysis confirmed these as O. tsutsugamushi strain Boryong. Conclusions: Our study found that 1.6% of patients were coinfected with SFTS and scrub typhus infection. We believe that this information will add a new dimension to clinical diagnosis, which should be considered for better public health management. Further research is needed to better understand the ecological transmission dynamics and geographical distribution of SFTSV and O. tsutsugamushi in endemic countries.

Coronavirus Disease 2019-Associated Coagulopathy.

Coronavirus disease 2019 (COVID-19)-associated coagulopathy is an acute illness characterized by thrombosis with or without hemorrhage after COVID-19 infection. Clinical symptoms of COVID-19-associated coagulopathy can occur at any anatomical site. Various forms of venous thromboembolism, including deep vein thrombosis and pulmonary embolism, are common in acutely ill patients with COVID-19. Laboratory findings, such as D-dimer and platelet counts, can help diagnose COVID-19-associated coagulopathy. Anticoagulation using direct oral anticoagulants and low-molecular-weight heparin is essential for the treatment of COVID-19-associated coagulopathy. Prophylactic anticoagulants are important in preventing COVID-19-associated coagulopathy in patients with severe COVID-19. In particular, the early initiation of prophylactic anticoagulation in patients with COVID-19 can improve survival rates without the risk of serious bleeding events.

Whole-genome analysis and mutation pattern of SARS-CoV-2 during first and second wave outbreak in Gwangju, Republic of Korea.

To investigate the specific genomic features and mutation pattern, whole and near-complete SARS-CoV-2 genome sequences were analyzed. Clinical samples were collected from 18 COVID-19-positive patients and subjected to nucleic acid purification. Cell culture was performed to extract various SARS-CoV-2 isolates. Whole-genome analysis was performed using next-generation sequencing, and phylogenetic analyses were conducted to determine genetic diversity of the various SARS-CoV-2 isolates. The next-generation sequencing data identified 8 protein-coding regions with 17 mutated proteins. We identified 51 missense point mutations and deletions in 5' and 3' untranslated regions. The phylogenetic analysis revealed that V and GH are the dominant clades of SARS-CoV-2 circulating in the Gwangju region of South Korea. Moreover, statistical analysis confirmed a significant difference between viral load (P < 0.001) and number of mutations (P < 0.0001) in 2 mutually exclusive SARS-CoV-2 clades which indicates frequent genomic alterations in SARS-CoV-2 in patients with high viral load. Our results provide an in-depth analysis of SARS-COV-2 whole genome which we believe, can shed light in the understanding of SARS-COV-2 pathogenesis and mutation pattern which can aid in the development of prevention methods as well as future research into the pathogenesis of SARS-CoV-2 and therapeutic development.

Accuracy of Real-Time Polymerase Chain Reaction in COVID-19 Patients.

Coronavirus disease 2019 (COVID-19) is a mild to severe respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The diagnostic accuracy of the Centers for Disease Control and Prevention (CDC)- or World Health Organization (WHO)-recommended real-time PCR (RT-qPCR) primers in clinical practice remains unproven. We conducted a prospective study on the accuracy of RT-qPCR using an in-house-designed primer set (iNP) targeting the nucleocapsid protein as well as various recommended and commercial primers. The accuracy was assessed by culturing or seroconversion. We enrolled 12 confirmed COVID-19 patients with a total of 590 clinical samples. When a cutoff value of the cycle threshold (Ct) was set to 35, RT-qPCRs with WHO RdRp primers and CDC N1, N2, and N3 primers showed sensitivity of 42.1% to 63.2% and specificity of 90.5% to 100% in sputum, and sensitivity of 65.2% to 69.6% and specificity of 65.2% to 69.6% in nasopharyngeal samples. The sensitivity and specificity of iNP RT-qPCR in sputum and nasopharyngeal samples were 94.8%/100% and 69.6%/100%, respectively. Sputum testing had the highest sensitivity, followed by nasopharyngeal testing (P = 0.0193); self-collected saliva samples yielded better characteristics than oropharyngeal samples (P = 0.0032). Our results suggest that iNP RT-qPCR has better sensitivity and specificity than RT-PCR with WHO (P < 0.0001) or CDC (N1: P = 0.0012, N2: P = 0.0013, N3: P = 0.0012) primers. Sputum RT-qPCR analysis has the highest sensitivity, followed by nasopharyngeal, saliva, and oropharyngeal assays. Our study suggests that considerable improvement is needed for the RT-qPCR WHO and CDC primer sets for detecting SARS-CoV-2. IMPORTANCE Numerous research campaigns have addressed the vast majority of clinical and diagnostic specificity and sensitivity of various primer sets of SARS-CoV2 viral detection. Despite the impressive progress made to resolve the pandemic, there is still a need for continuous and active improvement of primers used for diagnosis in clinical practice. Our study significantly exceeds the scale of previously published research on the specificity and sensitivity of different primers comparing with different specimens and is the most comprehensive to date in terms of constant monitoring of primer sets of current usage. Henceforth, our results suggest that sputum samples sensitivity is the highest, followed by nasopharyngeal, saliva, and oropharyngeal samples. The CDC recommends the use of oropharyngeal specimens, leading to certain discrepancy between the guidelines set forth by the CDC and IDSA. We proved that the oropharyngeal samples demonstrated the lowest sensitivity for the detection of SARS-CoV-2.

Preliminary Guidelines for the Clinical Evaluation and Management of Long COVID.

Long-lasting coronavirus disease 2019 (COVID-19) symptoms beyond 12 weeks, the so-called 'long COVID' have been increasingly reported worldwide. Long COVID can be manifested in various forms, and there is an increasing demand for proper assessment and management. However, it is challenging when trying to determine the best-practice standards of care based on the current evidence because there is no internationally agreed clinical definition or clear treatment pathway. Therefore, the present guidelines have been drafted to provide advice on diagnosis and management based on the latest updated available evidence and the consensus of expert opinion. So far, no standard test and drug treatment can be strongly recommended for patients with long COVID because of a lack of evidence. The present guidelines provide advice based on 12 key questions, including appropriate interventions for long COVID that can be used in clinical practice. Continuous careful observation and studies related to long COVID are needed for the long-term impact of COVID-19 and proper management for long COVID to be determined.