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Sci Rep ; 11(1): 16535, 2021 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-34400739


Adaptive immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) dynamics remain largely unknown. The neutralizing antibody (NAb) levels in patients with coronavirus disease 2019 (COVID-19) are helpful for understanding the pathology. Using SARS-CoV-2 pseudotyped virus, serum sample neutralization values in symptomatic COVID-19 patients were measured using the chemiluminescence reduction neutralization test (CRNT). At least two sequential serum samples collected during hospitalization were analyzed to assess NAbs neutralizing activity dynamics at different time points. Of the 11 patients, four (36.4%), six (54.5%), and one (9.1%) had moderate, severe, and critical disease, respectively. Fifty percent neutralization (N50%-CRNT) was observed upon admission in 90.9% (10/11); all patients acquired neutralizing activity 2-12 days after onset. In patients with moderate disease, neutralization was observed at earliest within two days after symptom onset. In patients with severe-to-critical disease, neutralization activity increased, plateauing 9-16 days after onset. Neutralization activity on admission was significantly higher in patients with moderate disease than in patients with severe-to-critical disease (relative % of infectivity, 6.4% vs. 41.1%; P = .011). Neutralization activity on admission inversely correlated with disease severity. The rapid NAb response may play a crucial role in preventing the progression of COVID-19.

Imunidade Adaptativa , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , COVID-19/diagnóstico , SARS-CoV-2/imunologia , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antivirais/imunologia , COVID-19/sangue , COVID-19/imunologia , COVID-19/virologia , Teste de Ácido Nucleico para COVID-19 , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes de Neutralização/estatística & dados numéricos , Estudos Retrospectivos , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de Doença , Fatores de Tempo
J Med Virol ; 2021 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-34411312


This study aimed to determine the frequency of SARS-CoV-2 RNA in serum and its association with the clinical severity of COVID-19. This retrospective cohort study performed at Toyama University Hospital included consecutive patients with confirmed COVID-19. The prevalence of SARS-CoV-2 RNAemia and the strength of its association with clinical severity variables were examined. Fifty-six patients were included in this study. RNAemia was detected in 19.6% (11/56) patients on admission, and subsequently in 1.0% (1/25), 50.0% (6/12), and 100.0% (4/4) moderate, severe, and critically ill patients, respectively. Patients with RNAemia required more frequent oxygen supplementation (90.0% vs. 13.3%), ICU admission (81.8% vs. 6.7%), and invasive mechanical ventilation (27.3% vs. 0.0%). Among patients with RNAemia, the median viral loads of nasopharyngeal (NP) swabs that were collected around the same time as the serum sample were significantly higher in critically ill (5.4 log10 copies/µl; interquartile range [IQR]: 4.2-6.3) than in moderate-severe cases (2.6 log10 copies/µl; [IQR: 1.1-4.5]; p = 0.030) and were significantly higher in nonsurvivors (6.2 log10 copies/µl [IQR: 6.0-6.5]) than in survivors (3.9 log10 copies/µl [IQR: 1.6-4.6]; p = 0.045). This study demonstrated a relatively high proportion of SARS-CoV-2 RNAemia and an association between RNAemia and clinical severity. Moreover, among the patients with RNAemia, the viral loads of NP swabs were correlated with disease severity and mortality, suggesting the potential utility of combining serum testing with NP tests as a prognostic indicator for COVID-19, with higher quality than each separate test.

J Infect Chemother ; 27(7): 1122-1125, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33853730


This study aimed to assess the nasopharyngeal viral load at discharge or time of discontinued isolation in coronavirus 2019 (COVID-19) patients admitted to our hospital and discharged under the current symptom-based criteria in Japan. Patients diagnosed with COVID-19 by reverse transcription polymerase chain reaction and hospitalized at Toyama University Hospital were included in the analysis. Nasopharyngeal viral load was measured when symptom-based criteria for discharge or end of isolation in the accommodations were met, and examined the relationship between viral load and days after onset or age. From the perspective of virus isolation limit, the amount of infectious viral load was defined at 50 copies/µL by nasopharyngeal sample. Thirty-three patients with laboratory-confirmed COVID-19 were included in the analysis, after excluding critical and fatal cases. Mean nasopharyngeal viral load at discharge or end of isolation was 1.90 log-copies/µL, and 64% of patients were discharged with over 50 copies/µL. No correlation was apparent between age and viral load at discharge, and viral load remained relatively high at discharge or end of isolation in all age groups. Although attempts at infectious virus isolation are necessary, infection control precautions even after discharge or discontinued isolation in accommodations may be needed, as the date of onset mostly depended on self-reporting by patients.

COVID-19 , Alta do Paciente , Humanos , Japão , SARS-CoV-2 , Carga Viral
Int J Infect Dis ; 106: 33-35, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33746092


As of October 2020, there is still no specific drug to treat COVID-19 as it rages worldwide. Favipiravir, indicated for the treatment of new and re-emerging influenza infections, has been suggested to be effective against SARS-CoV-2, although this is not yet fully validated. We administered favipiravir to a 64-year-old female patient with COVID-19. Her symptoms resolved quickly after the start of treatment, with reduction of SARS-CoV-2 viral load, but she developed a fever again on day 12. Since the fever was relieved by discontinuation of favipiravir, and based on positive results with a drug-induced lymphocyte stimulation test, we diagnosed her with favipiravir-induced drug fever. A decrease in the serum concentration of favipiravir was observed along with resolution of the fever. The present case suggests that drug fever should be considered in the differential diagnosis of relapsing fever episodes in COVID-19 patients receiving favipiravir.

Amidas/efeitos adversos , COVID-19/tratamento farmacológico , COVID-19/imunologia , Febre/induzido quimicamente , Ativação Linfocitária/efeitos dos fármacos , Pirazinas/efeitos adversos , Amidas/farmacologia , Amidas/uso terapêutico , COVID-19/diagnóstico , Feminino , Humanos , Pessoa de Meia-Idade , Pirazinas/farmacologia , Pirazinas/uso terapêutico , Carga Viral/efeitos dos fármacos
BMC Pharmacol Toxicol ; 22(1): 13, 2021 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-33663616


BACKGROUND: Linezolid is administered as a fixed dose to all patients despite evidence of overexposure and thrombocytopenia in renal impairment. The aims of this study were to evaluate the risk of thrombocytopenia and the utility of therapeutic drug monitoring (TDM), and to propose alternate dosing regimens in patients with renal impairment. METHODS: We retrospectively reviewed patients ≥13 years old for whom serum linezolid trough concentration (Cmin) was measured during linezolid treatment. Patients with episodes of infection were divided into groups by presence of renal impairment (RI group) or absence of renal impairment (non-RI group), and by use of Cmin-based TDM (TDM group) or not (non-TDM group) during linezolid treatment. RESULTS: In the 108 patients examined by multivariable analyses, renal impairment was independently associated with increased risk of thrombocytopenia (OR 3.17, 95%CI 1.10-9.12) and higher Cmin. Analysis of the utility of TDM in the RI group showed that clinical failure rate was significantly lower in the TDM subgroup than in the non-TDM subgroup. Furthermore, in the RI group, dosage adjustments were needed in 90.5% of the TDM subgroup. All episodes administered a reduced dose of 300 mg every 12 h in the RI group showed Cmin ≥ 2.0 mg/L. Additional analysis of 53 episodes in which Cmin was measured within 48 h after starting administration showed that the initial standard dose for 2 days was sufficient to rapidly reach an effective therapeutic concentration in the RI group. CONCLUSIONS: Empirical dose reduction to 300 mg every 12 h after administration of the initial fixed dose for 2 days and Cmin-based TDM may improve safety outcomes while maintaining appropriate efficacy among patients with renal impairment.