•The level of SARS-CoV-2 in wastewater varied over time during the outbreak in Gothenburg.•A peak of SARS-CoV-2 in wastewater preceded an increase in newly hospitalized patients with COVID-19 by ...19-21 days.•The level of SARS-CoV-2 in wastewater varied when comparing different parts of Gothenburg.•SARS-CoV-2 was released to the recipient water from the wastewater treatment plant with a 4-log10 reduction.
SARS-CoV-2 was discovered among humans in Wuhan, China in late 2019, and then spread rapidly, causing a global pandemic. The virus was found to be transmitted mainly by respiratory droplets from infected persons or by direct contact. It was also shown to be excreted in feces, why we investigated whether the virus could be detected in wastewater and if so, to which extent its levels reflects its spread in society. Samples of wastewater from the city of Gothenburg, and surrounding municipalities in Sweden were collected daily from mid-February until June 2020 at the Rya wastewater treatment plant. Flow proportional samples of wastewater were collected to ensure that comparable amounts were obtained for analysis. Daily samples were pooled into weekly samples. Virus was concentrated on a filter and analyzed by RT-qPCR. The amount of SARS-CoV-2 varied with peaks approximately every four week, preceding variations in number of newly hospitalized patients by 19-21 days. At that time virus testing for COVID-19 was limited to patients with severe symptoms. Local differences in viral spread was shown by analyzing weekly composite samples of wastewater from five sampling sites for four weeks. The highest amount of virus was found from the central, eastern, and northern parts of the city. SARS-CoV-2 was also found in the treated effluent wastewater from the WWTP discharged into the recipient, the Göta River, although with a reduction of 4-log10. The viral peaks with regular temporal intervals indicated that SARS-CoV-2 may have a cluster spread, probably reflecting that the majority of infected persons only spread the disease during a few days. Our results are important for both the planning of hospital care and to rapidly identify and intervene against local spread of the virus.
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Hepatic steatosis in HCV patients has been postulated as a risk factor associated with a higher frequency of fibrosis and cirrhosis. A single genetic variant, PNPLA3 I148M, has been widely associated ...with increased hepatic steatosis. Previous studies of the PNPLA3 I148M sequence variant in HCV infected individuals have reported an association between this variant and prevalence of steatosis, fibrosis, and cirrhosis. To evaluate the impact of PNPLA3 I148M variant on metabolic traits and treatment response in HCV genotype 2 and 3 infected patients.
Three hundred and eighty-two treatment naïve HCV genotype 2 or 3 infected patients were included in a phase III, open label, randomized, multicenter, investigator-initiated trial (the NORDynamIC study), in which pretreatment liver biopsies were mandatory. PNPLA3I148M genotyping was performed in a total of 359 Caucasian patients.
In HCV genotype 2 infected patients carrying the PNPLA3 148M allele, there was significantly increased insulin resistance (P = 0.023) and lower viral load (P = 0.005) at baseline as well as the first seven days of antiviral treatment. These results were not observed in HCV genotype 3 infected patients.
Our results suggest a possible association between the PNPLA3 148M allele and insulin resistance as well as baseline viral load in HCV genotype 2, but not in genotype 3.
Infection with hepatitis C virus (HCV) generally progresses to chronic disease, although a minority of patients appear to clear viremia spontaneously. In this investigation, serum samples were ...analyzed for virological parameters, serum alanine aminotransferase (ALT) levels, and neutralizing antibody response against pseudotyped vesicular stomatitis virus (VSV) generated using chimeric envelope glycoprotein 1 (El) or 2 (E2) of HCV. Testing of sequential serum samples that were collected beginning at the onset of acute-phase disease demonstrated intermittent viremia, elevated ALT levels, and detectable neutralization activity against VSV in 9 of 10 patients. Serum neutralization activity did not exhibit a correlation with the genotype of the infecting HCV or with virus load. On the other hand, patients with chronic HCV infection consistently had detectable amounts of virus present but no significant variation in ALT levels, and serum samples from a majority (> 90%) of patients failed to show detectable neutralization activity.
The quantification of viral genomes in wastewater reflects the prevalence of viral infections within the community. Knowledge of how the spread of common enteric viruses in the community was affected ...by the Swedish COVID-19 interventions is limited. To investigate this, the weekly wastewater samples collected for monitoring SARS-CoV-2 throughout the COVID-19 pandemic at the Rya sewage treatment plant in Gothenburg were also analyzed for adenovirus, norovirus GII, astrovirus, and rotavirus. The amount of each viral genome was quantified by real-time-qPCR and compared with the quantity of these viral genomes in wastewater from 2017. The results showed that the winter seasonality of norovirus GII and rotavirus in wastewater observed in 2017 was interrupted shortly after the introduction of the COVID-19 interventions, and they remained at low level throughout the pandemic. The circulation pattern of astrovirus and adenovirus was less affected. When the COVID-19 restrictions were lifted in 2022, a dramatic increase was observed in the amount of norovirus GII, rotavirus, and adenovirus genomes in wastewater. The changes in abundance and seasonality of some viruses identified through wastewater monitoring were consistent with changes in the number of patients diagnosed with these viruses. These findings suggest that moderate intervention to prevent COVID-19 significantly reduced the spread of some enteric viruses in the community. The results show that wastewater monitoring is a valuable tool for detecting the spread and outbreaks of viral infections that may cause gastroenteritis also when people do not seek medical help, such as during the COVID-19 pandemic.
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•Changes in the amount of viruses in wastewater correspond to changes in the diagnosed patients.•COVID-19 interventions reduced norovirus and rotavirus spread in the Swedish community.•Astrovirus and adenovirus circulation pattern were less affected by COVID-19 interventions.•Increase in the amount of adenovirus, norovirus GII, and rotavirus in wastewater after restrictions were removed.
This study analyzed whole blood samples (
n
= 56) retrieved from 30 patients at 1 to 21 (median 9) mo after verified COVID-19 to determine the polarity and duration of antigen-specific T cell ...reactivity against severe acute respiratory syndrome coronavirus 2–derived antigens. Multimeric peptides spanning the entire nucleocapsid protein triggered strikingly synchronous formation of interleukin (IL)-4, IL-12, IL-13, and IL-17 ex vivo until ∼70 d after confirmed infection, whereafter this reactivity was no longer inducible. In contrast, levels of nucleocapsid-induced IL-2 and interferon-γ remained stable and highly correlated at 3 to 21 mo after infection. Similar cytokine dynamics were observed in unvaccinated, convalescent patients using whole-blood samples stimulated with peptides spanning the N-terminal portion of the spike 1 protein. These results unravel two phases of T cell reactivity following natural COVID-19: an early, synchronous response indicating transient presence of multipolar, antigen-specific T helper (T
H
) cells followed by an equally synchronous and durable T
H
1-like reactivity reflecting long-lasting T cell memory.
The genomic region encoding the hepatitis C virus (HCV) core protein was cloned into a mammalian expression vector to study its role on the transcriptional regulation of cellular proto-oncogene and ...viral promoters. Using a transient transfection assay in human hepato-cellular carcinoma (HepG2) cells, we demonstrate that the HCV core protein activates the human c-
myc, Rous sarcoma virus long terminal repeat (LTR), and simian virus 40 (SV40) early promoters; and suppresses the c-
fos promoter and human immunodeficiency virus type 1 (HIV-1) LTR activity. The transcriptional regulation of cellular proto-oncogenes by the HCV core protein suggests possible involvement of the core protein in the deregulation of normal hepatocyte growth and hepatocarcinogenesis.
We monitored early viral response during the treatment of hepatitis C virus (HCV) infection with the aim of identifying predictors of treatment outcome. We studied 53 patients with genotype 1 ...infection who received 180 μg/week pegylated interferon alfa-2a and 1,000 or 1,200 mg/day ribavirin depending on body weight and serially assessed HCV RNA in serum, using the Cobas TaqMan assay. Thirty-one patients (58%) achieved sustained viral response (SVR). SVR was obtained in 100% (10/10) of patients with pretreatment viremia concentrations below 400,000 IU/ml, in 100% (14/14) of patients with more than 1.5 log reduction of HCV RNA after 4 days of treatment, and in 95% (22/23) of patients with a rate of decline in viremia higher than 0.70 log units/week during the second phase. Non-SVR was seen in all patients with a second-phase decline rate lower than 0.35 log units/week. Patients with slopes between 0.50 and 0.80 log units/week achieved SVR (4/4) unless the treatment dose was modified (3/3). We conclude that the second-phase slope appears to be an accurate and useful predictor of treatment response. On the basis of these findings, we propose a model of tailored treatment which takes into account the second-phase slope and the amount of HCV RNA after 21 days of treatment.
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