Prolonged viral shedding of SARS-CoV-2 in an immunocompromised patient

The duration of viral shedding of SARS-CoV-2 is usually less than 10 days. We experienced a COVID-19 case with prolonged viral shedding for 2 months. His cell mediated immunity has been depressed (CD4⁺T cell <100/μl) due to advanced malignant lymphoma and chemotherapy which had been completed 4 months prior to the onset of symptoms of COVID-19. We administered several treatments against COVID-19, however the results of Polymerase Chain Reaction (PCR) from nasopharyngeal specimens remained positive to SARS-CoV-2 for 2 months. Moreover, virus isolation assays performed on Day 59 also remained positive. He was finally discharged on Day 69 with two consecutive negative PCR results for SARS-CoV-2. Immunocompromised status may prolong viral shedding and it is therefore important for the clinician to take into account this when assessing such patients.     

Discrepancy of SARS-CoV-2 PCR results due to the sample collection sites and possible improper sampling

Polymerase chain reaction (PCR) testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is necessary for confirming a diagnosis of Coronavirus disease 2019 (COVID-19). Here we present a COVID-19 case of an elderly woman whose SARS-CoV-2 PCR tests showed false negative repeatedly by evaluating with different sampling sites and procedures. Nasopharyngeal swabs, suctioned sputum, and tongue swabs were collected for SARS-CoV-2-PCR. As for tongue swabs, we compared between two different sample conditions; one obtained with dry condition and the other obtained with moistened condition inside the oral cavity. SARS-CoV-2-PCR showed positive for an extended period with suctioned sputum samples compared with nasopharyngeal swabs and tongue swabs. No SARS-CoV-2 from a nasopharyngeal swab sample obtained on day 46 after symptoms onset was isolated despite high viral load (183740.5 copies/5μL). An adequate production of neutralizing antibody in a serum sample on day 46 was also confirmed. The number of RNA copies of the tongue swab samples was higher with moistened condition than with dry condition.The present case suggests that the difference of sampling site or sample condition can affect PCR results. High loads viral RNA detection does not always correlate with infectivity.     

Efficacy of convalescent plasma therapy for COVID-19 in Japan: An open-label,randomized, controlled trial

BackgroundConvalescent plasma is a potential therapeutic option for patients with coronavirus disease 2019 (COVID-19). Despite its use for treating several viral infections, we lack comprehensive data on its efficacy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).MethodsWe conducted a multicenter, open-label, randomized controlled trial of convalescent plasma therapy with high neutralizing activity against SARS-CoV-2 in high-risk patients within five days after the onset of COVID-19 symptoms. The primary endpoint was the time-weighted average change in the SARS-CoV-2 viral load in nasopharyngeal swabs from days 0–5.ResultsBetween February 24, 2021, and November 30, 2021, 25 patients were randomly assigned to either convalescent plasma (n = 14) or standard of care (n = 11) groups. Four patients discontinued their allocated convalescent plasma, and 21 were included in the modified intention-to-treat analysis. The median interval between the symptom onset and plasma administration was 4.5 days (interquartile range, 3–5 days). The primary outcome of the time-weighted average change in the SARS-CoV-2 viral load in nasopharyngeal swabs did not significantly differ between days 0–5 (1.2 log₁₀ copies/mL in the convalescent plasma vs. 1.2 log₁₀ copies/mL in the standard of care (effect estimate, 0.0 [95% confidence interval, −0.8–0.7]; P = 0.94)). No deaths were observed in either group.ConclusionsThe early administration of convalescent plasma with high neutralizing activity did not contribute to a decrease in the viral load within five days compared with the standard of care alone.     

Early nasal type I IFN immunity against SARS-CoV-2 is compromised in patients with autoantibodies against type I IFNs

IFN-I and IFN-III immunity in the nasal mucosa is poorly characterized during SARS-CoV-2 infection. We analyze the nasal IFN-I/III signature, namely the expression of ISGF-3–dependent IFN-stimulated genes, in mildly symptomatic COVID-19 patients and show its correlation with serum IFN-α₂ levels, which peak at symptom onset and return to baseline from day 10 onward. Moreover, the nasal IFN-I/III signature correlates with the nasopharyngeal viral load and is associated with the presence of infectious viruses. By contrast, we observe low nasal IFN-I/III scores despite high nasal viral loads in a subset of critically ill COVID-19 patients, which correlates with the presence of autoantibodies (auto-Abs) against IFN-I in both blood and nasopharyngeal mucosa. In addition, functional assays in a reconstituted human airway epithelium model of SARS-CoV-2 infection confirm the role of such auto-Abs in abrogating the antiviral effects of IFN-I, but not those of IFN-III. Thus, IFN-I auto-Abs may compromise not only systemic but also local antiviral IFN-I immunity at the early stages of SARS-CoV-2 infection.     

The hotspots and trends of coronavirus disease 2019 (COVID-19) and physical therapy: a bibliometric and visual analysis

[Purpose] With the COVID-19 pandemic, more and more articles have been published to explore the role of physical therapy on COVID-19. In order to analyze the research hotspots and the trends of physical therapy and COVID-19, we conducted bibliometric and visual analysis. [Methods] Data were collected from the Science Citation Index Expanded (SCI-EXPANDED) and Social Sciences Citation Index (SSCI) of the Web of Science Core Collect (WoSCC) from 2019 to 2021. CiteSpace and VOSviewer were used to perform the visual analysis of keywords and references to help quickly get key information. [Results] A total of 466 publications were retrieved. Exercise, sedentary behavior, and mental health were research hotspots. The relationship between exercise and immunity, as well as the management of COVID-19 patients after discharge were the research trends. [Conclusion] This study provided relevant information for future research. Findings suggested that physical therapy is beneficial for suspected or confirmed COVID-19 patients during isolation. It is hoped that academic exchanges can be quickly established in the face of infectious diseases. And in the future, we should focus on the rehabilitation of discharged patients.     

Quantitative analysis of different respiratory specimens on two automated test systems for detection of SARS-CoV-2 RNA

Molecular testing of SARS-CoV-2 RNA is essential during the pandemic. Here, we compared the results of different respiratory specimens including anterior nasal swabs, pharyngeal swabs, saliva swabs, and gargle lavage samples to nasopharyngeal swabs on two automated SARS-CoV-2 test systems. Samples were collected and tested simultaneously from a total of 36 hospitalized symptomatic COVID-19 patients. Detection and quantification of SARS-CoV-2 was performed on cobas®6800 (Roche) and NeuMoDx? (Qiagen) systems. Both assays showed reliable detection and quantification of SARS-CoV-2 RNA, with nasopharyngeal swabs showing the highest sensitivity. SARS-CoV-2 RNA concentrations in other respiratory specimens were lower (mean 2.5 log10 copies/ml) or even undetectable in up to 20%. These data clearly indicate that not all respiratory materials are equally suitable for the management of hospitalized patients, especially, in the late phase of COVID-19, when the viral phase subsides and inflammation becomes the predominant factor, making detection of even lower viral loads increasingly important.     

Selection and viral load kinetics of an oseltamivir-resistant pandemic influenza A (H1N1) virus in an immunocompromised patient during treatment with neuraminidase inhibitors

Prolonged viral excretion in immunocompromised hosts leads to long oseltamivir treatment and to the subsequent development of oseltamivir-resistant pandemic influenza virus selection. We report the selection and nasopharyngeal shedding kinetics of an oseltamivir-resistant strain in a hospitalized immunocompromised patient with prolonged influenza illness. Viral load quantification and genotyping methods were performed from 7 serial nasopharyngeal samples. Before initial oseltamivir treatment, the viral load was 5.78 log(10) copies/mL of sample and only wild-type virus population was detected. The nasopharyngeal viral load remained above the detection limit although there was a second course of oseltamivir treatment. Twelve days after the onset of symptoms, an oseltamivir-resistant strain was selected. After 12 days of inhaled zanamivir treatment, the patient was discharged asymptomatic. The study emphasizes the importance of viral load quantification and surveillance of emergence of resistant strains prospectively because the information provided has important implications in the clinical management of the patient.     

Validation of Roche LightCycler Epstein-Barr virus quantification reagents in a clinical laboratory setting

Epstein-Barr virus (EBV) is associated with a wide range of benign and malignant diseases, including infectious mononucleosis, lymphoma, posttransplant lymphoproliferative disorder, and nasopharyngeal carcinoma. Measurement of EBV viral load in plasma is increasingly used for rapid assessment of disease status. We evaluated the performance characteristics of an EBV polymerase chain reaction assay that uses commercial reagents and instruments from Roche Diagnostics (Indianapolis, IN). DNA was extracted from plasma using a MagNaPure instrument, and viral load was measured by real-time polymerase chain reaction on a LightCycler. Analyte-specific reagents included primers and hybridization probes targeting the EBV LMP2 gene and a spiked control sequence. Accuracy and reproducibility were established using DNA from three cell lines. The assay was sensitive to approximately 750 copies of EBV DNA per milliliter of plasma and was linear across at least four orders of magnitude. The assay detected EBV DNA in three of five samples from nasopharyngeal carcinoma patients, seven of nine infectious mononucleosis samples, and 34/34 samples from immunosuppressed patients with clinically significant EBV-related disease, whereas EBV DNA was undetectable in plasma from 21 individuals without EBV-related disease. In conclusion, this LightCycler EBV assay is rapid, sensitive, and linear for quantifying EBV viral load. The assay appears to be useful for measuring clinically significant EBV levels in immunodeficient patients.     

Epidemiological and clinical characteristics of 65 hospitalized patients with COVID-19 in Liaoning,China

BACKGROUNDCoronavirus disease 2019 (COVID-19) has spread rapidly to multiple countries through its infectious agent severe acute respiratory syndrome coronavirus 2. The severity, atypical clinical presentation, and lack of specific anti-viral treatments have posed a challenge for the diagnosis and treatment of COVID-19. Understanding the epidemiological and clinical characteristics of COVID-19 cases in different geographical areas is essential to improve the prognosis of COVID-19 patients and slow the spread of the disease.AIMTo investigate the epidemiological and clinical characteristics and main therapeutic strategy for confirmed COVID-19 patients hospitalized in Liaoning Province, China.METHODSAdult patients (n = 65) with confirmed COVID-19 were enrolled in this retrospective study from January 20 to February 29, 2020 in Liaoning Province, China. Pharyngeal swabs and sputum specimens were collected from the patients for the detection of severe acute respiratory syndrome coronavirus 2 nucleic acid. Patient demographic information and clinical data were collected from the medical records. Based on the severity of COVID-19, the patients were divided into nonsevere and severe groups. All patients were followed until March 20, 2020.RESULTSThe mean age of 65 COVID-19 patients was 45.5 ± 14.4 years, 56.9% were men, and 24.6% were severe cases. During the 14 d before symptom onset, 25 (38.5%) patients lived or stayed in Wuhan, whereas 8 (12.3%) had no clear history of exposure. Twenty-nine (44.6%) patients had at least one comorbidity; hypertension and diabetes were the most common comorbidities. Compared with nonsevere patients, severe patients had significantly lower lymphocyte counts [median value 1.3 × 10⁹/L (interquartile range 0.9-1.95) vs 0.82 × 10⁹/L (0.44-1.08), P < 0.001], elevated levels of lactate dehydrogenase [450 U/L (386-476) vs 707 U/L (592-980), P < 0.001] and C-reactive protein [6.1 mg/L (1.5-7.2) vs 52 mg/L (12.7-100.8), P < 0.001], and a prolonged median duration of viral shedding [19.5 d (16-21) vs 23.5 d (19.6-30.3), P = 0.001]. The overall median viral shedding time was 19.5 d, and the longest was 53 d. Severe patients were more frequently treated with lopinavir/ritonavir, antibiotics, glucocorticoid therapy, immunoglobulin, thymosin, and oxygen support. All patients were discharged following treatment in quarantine.CONCLUSIONOur findings may facilitate the identification of severe cases and inform clinical treatment and quarantine decisions regarding COVID-19.     

Successful treatment of a centenarian with coronavirus disease 2019 (COVID-19) using convalescent plasma

BackgroundBecause treatment options for coronavirus disease 2019 (COVID-19) are very limited, the use of convalescent plasma has bee explored.Case presentation and treatmentA male centenarian with cough and dyspnea for 2 months was diagnosed with COVID-19. Without effective treatments and with the increased risks of antiviral therapy for the elderly, this patient was given convalescent plasma. The viral load, complete blood count, inflammatory indicators, vital signs, and clinical symptoms were observed before and after COVID-19 convalescent plasma transfusion.ResultsAfter convalescent plasma transfusion, significant improvement was observed on laboratory indicators and clinical symptoms of the patient. Concurrently, SARS-CoV-2 viral load decreased sharply after the first transfusion (from 2.55 × 104 to 1.39 × 103 copies/mL) and became undetectable after the second transfusion.ConclusionsWith the substantial increase of COVID-19 in recent months,treatment for elderly patients has become restricted in some countries. The successful treatment of this 100-year-old patient using convalescent plasma suggests that we should consider adding convalescent plasma in th management of the elderly.     

Fecal Microbiota Transplantation for Recurrent C difficile Infection During the COVID-19 Pandemic: Experience and Recommendations

ObjectiveTo report experience with fecal microbiota transplantation (FMT) for recurrent Clostridioides difficile infection (rCDI) and provide recommendations for management of rCDI and donor testing during the COVID-19 pandemic.MethodsA retrospective study of patients with rCDI who underwent FMT from May 26, 2020, to September 30, 2020, with stool from well-screened donors with health and infectious screening and a newly implemented strategy for COVID-19 screening with every 2-week bookend testing with stool quarantine. Patients were followed up for development of rCDI and COVID-19.ResultsOf the 57 patients who underwent FMT for rCDI, 29 were tested for COVID-19 via nasopharyngeal polymerase chain reaction (PCR) and 22 via serology. All results were negative, except for 1 positive serology. Donor testing every 2 weeks for COVID-19 via serology and nasopharyngeal swab PCR was negative, except for 2 donors at 1 center who were excluded. Three patients had rCDI after FMT, and 1 underwent repeat FMT. One patient developed respiratory symptoms suggestive of COVID-19 and tested negative via nasopharyngeal PCR. Eleven patients who underwent COVID-19 testing for elective procedures or hospitalizations tested negative. No SARS-CoV-2 transmission was noted.ConclusionsWith appropriate donor screening, FMT can be performed safely for rCDI during the COVID-19 pandemic. Development of a validated stool assay for SARS-CoV-2 will simplify this process further.