To test the hypothesis that coronavirus disease 2019 (COVID-19) has an impact on the CNS by measuring plasma biomarkers of CNS injury.
We recruited 47 patients with mild (n = 20), moderate (n = 9), ...or severe (n = 18) COVID-19 and measured 2 plasma biomarkers of CNS injury by single molecule array, neurofilament light chain protein (NfL; a marker of intra-axonal neuronal injury) and glial fibrillary acidic protein (GFAp; a marker of astrocytic activation/injury), in samples collected at presentation and again in a subset after a mean of 11.4 days. Cross-sectional results were compared with results from 33 age-matched controls derived from an independent cohort.
The patients with severe COVID-19 had higher plasma concentrations of GFAp (
= 0.001) and NfL (
< 0.001) than controls, while GFAp was also increased in patients with moderate disease (
= 0.03). In patients with severe disease, an early peak in plasma GFAp decreased on follow-up (
< 0.01), while NfL showed a sustained increase from first to last follow-up (
< 0.01), perhaps reflecting a sequence of early astrocytic response and more delayed axonal injury.
We show neurochemical evidence of neuronal injury and glial activation in patients with moderate and severe COVID-19. Further studies are needed to clarify the frequency and nature of COVID-19-related CNS damage and its relation to both clinically defined CNS events such as hypoxic and ischemic events and mechanisms more closely linked to systemic severe acute respiratory syndrome coronavirus 2 infection and consequent immune activation, as well as to evaluate the clinical utility of monitoring plasma NfL and GFAp in the management of this group of patients.
To accurately interpret COVID-19 seroprevalence surveys, knowledge of serum-IgG responses to SARS-CoV-2 with a better understanding of patients who do not seroconvert, is imperative. This study aimed ...to describe serum-IgG responses to SARS-CoV-2 in a cohort of patients with both severe and mild COVID-19, including extended studies of patients who remained seronegative more than 90 days post symptom onset.
SARS-CoV-2-specific IgG antibody levels were quantified using two clinically validated and widely used commercial serological assays (Architect, Abbott Laboratories and iFlash 1800, YHLO), detecting antibodies against the spike and nucleocapsid proteins.
Forty-seven patients (mean age 49 years, 38% female) were included. All (15/15) patients with severe symptoms and 29/32 (90.6%) patients with mild symptoms of COVID-19 developed SARS-CoV-2-specific IgG antibodies in serum. Time to seroconversion was significantly shorter (median 11 vs. 22 days, P = 0.04) in patients with severe compared to mild symptoms. Of the three patients without detectable IgG-responses after >90 days, all had detectable virus-neutralizing antibodies and in two, spike-protein receptor binding domain-specific IgG was detected with an in-house assay. Antibody titers were preserved during follow-up and all patients who seroconverted, irrespective of the severity of symptoms, still had detectable IgG levels >75 days post symptom onset.
Patients with severe COVID-19 both seroconvert earlier and develop higher concentrations of SARS-CoV-2-specific IgG than patients with mild symptoms. Of those patients who not develop detectable IgG antibodies, all have detectable virus-neutralizing antibodies, suggesting immunity. Our results showing that not all COVID-19 patients develop detectable IgG using two validated commercial clinical methods, even over time, are vital for the interpretation of COVID-19 seroprevalence surveys.
Viruses cause 10-15% of all human cancers. Massively parallel sequencing has recently proved effective for uncovering novel viruses and virus-tumour associations, but this approach has not yet been ...applied to comprehensive patient cohorts. Here we screen a diverse landscape of human cancer, encompassing 4,433 tumours and 19 cancer types, for known and novel expressed viruses based on >700 billion transcriptome sequencing reads from The Cancer Genome Atlas Research Network. The resulting map confirms and extends current knowledge. We observe recurrent fusion events, including human papillomavirus insertions in RAD51B and ERBB2. Patterns of coadaptation between host and viral gene expression give clues to papillomavirus oncogene function. Importantly, our analysis argues strongly against viral aetiology in several cancers where this has frequently been proposed. We provide a virus-tumour map of unprecedented scale that constitutes a reference for future studies of tumour-associated viruses using transcriptome sequencing data.
In this study, next generation sequencing was used to explore the virome in 20L up to 10,000L water from different purification steps at two Swedish drinking water treatment plants (DWTPs), and in ...tap water. One DWTP used ultrafiltration (UF) with 20 nm pores, the other UV light treatment after conventional treatment of the water. Viruses belonging to 26 different families were detected in raw water, in which 6–9 times more sequence reads were found for phages than for known environmental, plant or vertebrate viruses. The total number of viral reads was reduced more than 4-log10 after UF and 3-log10 over UV treatment. However, for some viruses the reduction was 3.5-log10 after UF, as for hepatitis E virus (HEV), which was also detected in tap water, with sequences similar to those in raw water and after treatment. This indicates that HEV had passed through the treatment and entered into the supply network. However, the viability of the viruses is unknown. In tap water 10–130 International Units of HEV RNA/mL were identified, which is a comparable low amount of virus. The risk of getting infected through consumption of tap water is probably negligible, but needs to be investigated. The HEV strains in the waters belonged to subtypes HEV3a and HEV3c/i, which is associated with unknown source of infection in humans infected in Sweden. None of these subtypes are common among pigs or wild boar, the major reservoirs for HEV, indicating that water may play a role in transmitting this virus. The results indicate that monitoring small fecal/oral transmitted viruses in DWTPs may be considered, especially during community outbreaks, to prevent potential transmission by tap water.
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•Viruses from 26 viral families were detected in raw water i.e. before purification.•Number of viral families were reduced to 16 after ultrafiltration.•By ultrafiltration with 20 nm pores most viruses were reduced with 4-log.•In tap water viruses from 12 to 18 families were still detected.•Hepatitis E virus 3 strains were present in tap water in low level.
The frequency of viral respiratory pathogens in asymptomatic subjects is poorly defined. The aim of this study was to explore the prevalence of respiratory pathogens in the upper airways of ...asymptomatic adults, compared with a reference population of symptomatic patients sampled in the same centers during the same period. Nasopharyngeal (NP) swab samples were prospectively collected from adults with and without ongoing symptoms of respiratory tract infection (RTI) during 12 consecutive months, in primary care centers and hospital emergency departments, and analyzed for respiratory pathogens by a PCR panel detecting 16 viruses and four bacteria. Altogether, 444 asymptomatic and 75 symptomatic subjects completed sampling and follow-up (FU) at day 7. In the asymptomatic subjects, the detection rate of viruses was low (4.3%), and the most common virus detected was rhinovirus (3.2%).
was found in 5.6% of the asymptomatic subjects and
in 1.4%. The only factor independently associated with low viral detection rate in asymptomatic subjects was age ≥65 years (
= 0.04). An increased detection rate of bacteria was seen in asymptomatic subjects who were currently smoking (
< 0.01) and who had any chronic condition (
< 0.01). We conclude that detection of respiratory viruses in asymptomatic adults is uncommon, suggesting that a positive PCR result from a symptomatic patient likely is relevant for ongoing respiratory symptoms. Age influences the likelihood of virus detection among asymptomatic adults, and smoking and comorbidities may increase the prevalence of bacterial pathogens in the upper airways.
Sewage contains a mixed ecosystem of diverse sets of microorganisms, including human pathogenic viruses. Little is known about how conventional as well as advanced treatments of sewage, such as ...ozonation, reduce the environmental spread of viruses. Analyses for viruses were therefore conducted for three weeks in influent, after conventional treatment, after additional ozonation, and after passing an open dam system at a full-scale treatment plant in Knivsta, Sweden. Viruses were concentrated by adsorption to a positively charged filter, from which they were eluted and pelleted by ultracentrifugation, with a recovery of about 10%. Ion Torrent sequencing was used to analyze influent, leading to the identification of at least 327 viral species, most of which belonged to 25 families with some having unclear classification. Real-time PCR was used to test for 21 human-related viruses in inlet, conventionally treated, and ozone-treated sewage and outlet waters. The viruses identified in influent and further analyzed were adenovirus, norovirus, sapovirus, parechovirus, hepatitis E virus, astrovirus, pecovirus, picobirnavirus, parvovirus, and gokushovirus. Conventional treatment reduced viral concentrations by one to four log10, with the exception of adenovirus and parvovirus, for which the removal was less efficient. Ozone treatment led to a further reduction by one to two log10, but less for adenovirus. This study showed that the amount of all viruses was reduced by conventional sewage treatment. Further ozonation reduced the amounts of several viruses to undetectable levels, indicating that this is a promising technique for reducing the transmission of many pathogenic human viruses.
In an outbreak of measles in Gothenburg, Sweden, breakthrough infections (i.e. infections in individuals with a history of vaccination) were common. The objective of this study was to compare measles ...RNA levels between naïve (i.e. primary) and breakthrough infections. We also propose a fast provisional classification of breakthrough infections. Medical records were reviewed and real-time PCR-positive samples genotyped. Cases were classified as naïve, breakthrough or vaccine infections. We compared clinical symptoms and measles RNA cycle threshold (Ct) values between breakthrough and naïve infections. Sixteen of 28 confirmed cases of measles in this outbreak were breakthrough infections. A fast provisional classification, based on previous history of measles vaccination and detectable levels of measles IgG in acute serum, correctly identified 14 of the 16 breakthrough infections, confirmed by IgG avidity testing. Measles viral load was significantly lower in nasopharyngeal samples from individuals with breakthrough compared with naïve infections (median Ct-values: 32 and 19, respectively, p < 0.0001). No onward transmission from breakthrough infections was identified. Our results indicate that a high risk of onward transmission is limited to naïve infections. We propose a fast provisional classification of breakthrough measles that can guide contact tracing in outbreak settings.
This study aimed to examine current symptom severity and general health in a sample of primarily non-hospitalized persons with polymerase chain reaction (PCR) confirmed COVID-19 in comparison to PCR ...negative controls. During the first quarter of 2021, we conducted an online survey among public employees in West Sweden, with a valid COVID-19 test result. The survey assessed past-month severity of 28 symptoms and signs, self-rated health, the WHO Disability Assessment Schedule (WHODAS) 2.0 and illness severity at the time of test. We linked participants' responses to their SARS-CoV-2 PCR tests results. We compared COVID-19 positive and negative participants using univariable and multivariable regression analyses. Out of 56,221 invited, 14,222 (25.3%) responded, with a response rate of 50% among SARS-CoV-2 positive individuals. Analysis included 10,194 participants (86.4% women, mean age 45 years) who tested positive 4-12 weeks (N = 1425; subacute) and > 12 weeks (N = 1584; postcovid) prior to the survey, and 7185 PCR negative participants who did not believe that they had had COVID-19. Symptoms were highly prevalent in all groups, with worst symptoms in subacute phase participants, followed by postcovid phase and PCR negative participants. The most specific symptom for COVID-19 was loss of smell or taste. Both WHODAS 2.0 score and self-rated health were worst in subacute participants, and modestly worse in postcovid participants than in negative controls. Female gender, older age and acute illness severity had larger effects on self-rated health and WHODAS 2.0 score in PCR positive participants than in PCR negative. Studies with longer follow-up are needed to determine the long-term improvement after COVID-19.
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