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1.
Preprint in English | medRxiv | ID: ppmedrxiv-21260925

ABSTRACT

BackgroundHousehold transmission studies offer the opportunity to assess both secondary attack rate and persistence of SARS-CoV-2 antibodies over time. MethodsWe invited confirmed COVID-19 cases and their household members to attend up to four household visits with collection of nasopharyngeal and serum samples over 28 days after index case onset. We calculated secondary attack rates (SAR) based on the presence of SARS-CoV-2 nucleoprotein IgG antibodies (IgG Ab) and/or neutralizing antibodies (NAb) overall and per households. Three and six months later, we assessed the persistence of SARS-CoV-2 antibodies. FindingsWe recruited 39 index cases and 90 household members. Among 87 household members evaluated, SAR was 48% (n=42), including 37 symptomatic secondary cases. In total, 80/129 (62%) participants developed both IgG Ab and NAb, while three participants only developed IgG Ab. Among participants who had both IgG Ab and NAb during the initial follow-up, 68/69 (99%) and 63/70 (90%) had IgG Ab and NAb at 3 months, while at 6 months, 59/75 (79%) and 63/75 (84%) had IgG Ab and NAb, respectively. Participants who required hospital care had initially 5-fold IgG Ab concentrations compared to cases with mild symptoms and 8-fold compared to asymptomatic cases. InterpretationFollowing detection of a COVID-19 case in a household, other members had a high risk of becoming infected. Follow-up of participants showed strong persistence of antibodies in most cases. FundingThis study was supported by THL coordinated funding for COVID-19 research (Finnish Governments supplementary budget) and by the Academy of Finland (Decision number 336431). Research in contextO_ST_ABSEvidence before this studyC_ST_ABSHousehold transmission studies are pivotal to the characterization of transmission dynamics of emerging infectious diseases in a closed setting with homogenous exposure, including proportion of asymptomatic cases using serologic assessment of infection. Additionally, data on long-term persistence of immune response, including neutralizing antibodies following COVID-19 remains scarce. Our search on PubMed for articles published between January 1st 2020, and June 1st, 2021 using the search terms "household" AND "transmission" AND ("COVID-19" OR "SARS-CoV-2") retrieved 381 results including 35 relevant articles: 21 original household transmission studies, 5 reviews and 9 statistical transmission, modelling or register linkage studies. Depending on the diagnosis method and the duration of follow-up, secondary attack rates (SAR) ranged from 4.6% when household contacts were followed for 14 days and tested only in case of symptoms to close to 90%. None of the household transmission studies involved long-term convalescent follow-up. Added value of this studyThis extensive (one month) active follow-up, using RT-PCR diagnosis and serological testing for SARS-CoV-2 nucleoprotein IgG antibodies (IgG Ab) and neutralizing antibodies (NAb) showed that household transmission was high, with a 48% (42/87) SAR overall and 50% [IQR: 0-100%] at the level of the household. All but one out of 64 RT-PCR confirmed participants had developed both IgG Ab and NAb after immediate convalescence. Six months after inclusion, majority of previously seropositive (IgG and/or NAb) participants still had IgG Ab (59/75) or NAb (63/75) showing long-term persistence of humoral immunity to SARS-CoV-2. Implications of all the available evidenceThe risk of transmission of SARS-CoV-2 infections within households is considerable. Isolation of the primary case, especially from household contacts with a high risk of severe disease, e.g. due to age or comorbidities, should be considered even though viral shedding might occur before confirmed diagnosis in household contacts. Long-term persistence of antibodies following infection, even in asymptomatic and mild cases, suggests enduring natural immunity and possibly protection from severe COVID-19.

2.
Preprint in English | medRxiv | ID: ppmedrxiv-21255857

ABSTRACT

The gold standard for SARS-CoV-2 infection diagnosis is RT-PCR from nasopharyngeal specimen (NPS). Its collection involves a close contact between patients and healthcare workers requiring a significant amount of workforce and putting them at risk of infection. We evaluated self-collection of alternative specimens and compared their sensitivity and Ct values to NPS. We visited acute COVID-19 outpatients to collect concomitant nasopharyngeal and gargle specimens and had patients self-collect a gargle and either sputum or spit specimens on the next morning. We included 40 patients and collected 40 concomitant nasopharyngeal and gargle specimens, as well as 40 gargle, 22 spit and 16 sputum specimens on the next day, as 2 patients could not produce sputum. All specimens were as sensitive as NPS. Gargle specimens had a sensitivity of 0.97 (CI 95% 0.92-1,00), whether collected concomitantly to NPS or on the next morning. Next morning spit and sputum specimens showed a sensitivity of 1.00 CI (95% 1.00-1.00) and 0.94 (CI 95% 0.87-1.00), respectively. The gargle specimens had a significantly higher mean cycle threshold (Ct) values, 29.89 (SD 4.63) (p-value <0.001) and 29.25 (SD 3.99) (p-value <0.001) when collected concomitantly and on the next morning compared to NPS (22.07, SD 4.63). Ct value obtained with spit (23.51, SD 4.57, p-value 0.11) and sputum (25.82, SD 9.21, p-value 0.28) specimens were close to NPS. All alternative specimen collection methods were as sensitive as NPS, but spit collection appeared more promising, with a low Ct value and ease of collection. Our findings warrant further investigation.

3.
Preprint in English | medRxiv | ID: ppmedrxiv-21250086

ABSTRACT

Novel SARS coronavirus causing COVID-19 was recognized in late 2019. Diagnostics was quickly ramped up worldwide based on the detection of viral RNA. Based on the scientific knowledge for pre-existing coronaviruses, it was expected that the RNA of this novel coronavirus will be detected from symptomatic and at significant rates also from asymptomatic individuals due to persistence of non-infectious RNA. To increase the efficacy of diagnostics, surveillance, screening and pandemic control, rapid methods, such as antigen tests, are needed for decentralized testing and to assess infectiousness. The objective was to validate the analytical and clinical performance, and usability of a novel automated mariPOC SARS-CoV-2 test, which is based on the detection of structural viral proteins using sophisticated optical laser technology. Clinical performance of the test was evaluated against qRT-PCR with nasopharyngeal swab specimens collected from patients suspected of acute SARS-CoV-2 infection. Sensitivity of the mariPOC test was 100.0% (13/13) directly from swab specimens and 84.4% (38/45) from swab specimens in undefined transport mediums. Specificity of the test was 100.0% (201/201). The tests limit of detection was 2.7 TCID50/test and had no cross-reactions with the tested respiratory microbes. Our study shows that the mariPOC can detect infectious individuals already in 20 minutes with clinical sensitivity close to qRT-PCR. The test targets conserved epitopes of SARS-CoV-2 nucleoprotein, making it robust against strain variations. The new test is a promising and versatile tool for syndromic testing of symptomatic cases and for high capacity infection control screening.

4.
Preprint in English | medRxiv | ID: ppmedrxiv-20156018

ABSTRACT

BackgroundThe role of children in SARS-CoV-2 transmission is unclear. We investigated two COVID-19 school exposure incidents in the Helsinki area. MethodsWe conducted two retrospective cohort studies after schools exposures, with a household transmission extension. We defined a case as an exposed person with either a positive RT-PCR, or positive microneutralisation testing (MNT) as confirmation of SARS-CoV-2 nucleoprotein IgG antibodies detection via fluorescent microsphere immunoassay (FMIA). We recruited close school contacts and families of school cases, calculated attack rates (AR) on school level and families, and identified transmission chains. FindingsIn incident A, the index was a pupil. Participation rate was 74% (89/121), and no cases were identified. In incident B, the index was a member of school personnel. Participation rate was 81% (51/63). AR was 16% (8/51): 6 pupils and 1 member of school personnel were MNT and FMIA positive; 1 pupil had a positive RT-PCR, but negative serology samples. We visited all school cases families (n=8). The AR among close household contacts was 42% (9/20 in 3/8 families) but other plausible sources were always reported. At three months post-exposure, 6/8 school cases were re-sampled and still MNT positive. InterpretationWhen the index was a child, no school transmission was identified, while the occurrence of an adult case led to a 16% AR. Further cases were evidenced in 3 families, but other transmission chains were plausible. It is likely that transmission from children to adults is limited. FundingThe Finnish Institute for Health and Welfare funded this study. Research in contextO_ST_ABSEvidence before the studyC_ST_ABSThe first autochthonous case of COVID-19 in Finland was identified on February 29th. Transmission of the virus has led to more than 7250 cases and over 300 deaths (As of July 12th 2020). On March 16th, assuming that children might have a role in transmission, the Finnish government ordered school closures, to the exclusion of pre-school and grades 1-3. Schools were closed from March 18 and reopened on May 14th. At the stage of closure, a very limited number of reports of school related COVID-19 clusters or exposure incidents had been published, and the potential extent of transmission in a school setting was unknown. Added value of this studyWe investigated two exposure incidents in two different schools from the Helsinki area to assess transmission among pupils, school personnel and household contacts of identified cases. In school A, contact with a COVID-19 pupil did not lead to further transmission, while in school B, out of 51 recruited contacts, eight (16%) were proved to have had COVID-19 infection, including one member of staff. Among the close household contacts of pupils who were tested positive, COVID-19 attack rate was 31% (5/16). However, in all investigated households, other sources of infections were plausible; hence household transmission following a pediatric COVID-19 case appears to be limited. Implications of all of the available evidenceIncidence of COVID-19 infections in children following school related exposure was limited, as well as secondary transmission within their household. We hope our findings will help prioritize mitigation measures as well as reduce worry among parents of school aged children as most EU countries are preparing for the start of a new school year in autumn.

5.
Preprint in English | medRxiv | ID: ppmedrxiv-20140632

ABSTRACT

ObjectiveWe compared the clinical characteristics, findings and outcomes of hospitalized patients with coronavirus disease 2019 (COVID-19) or influenza to detect relevant differences. MethodsFrom December 2019 to April 2020, we recruited all eligible hospitalized adults with respiratory infection to a prospective observational study at the HUS Jorvi Hospital, Finland. Influenza and SARS-CoV-2 infections were confirmed by RT-PCR. Follow-up lasted for at least 30 days from admission. ResultsWe included 61 patients, of whom 28 were COVID-19 and 33 influenza patients with median ages of 53 and 56 years. Majority of both COVID-19 and influenza patients were men (61% vs 67%) and had at least one comorbidity (68% vs 85%). Pulmonary diseases and current smoking were less common among COVID-19 than influenza patients (5 [18%] vs 15 [45%], P=0.03 and 1 [4%] vs 10 [30%], P=0.008). In chest x-ray at admission, ground-glass opacities and consolidations were more frequent among COVID-19 than influenza patients (19 [68%] and 7 [21%], P < 0.001). Severe disease and intensive care unit (ICU) admission occurred more often among COVID-19 than influenza patients (26 [93%] vs 19 [58%], P=0.003 and 8 [29%] vs 2 [6%], P=0.034). COVID-19 patients were hospitalized longer than influenza patients (6 days [IQR 4-21] vs 3 [2-4], P<0.001). ConclusionBilateral ground-glass opacities and consolidations in chest X-ray may help to differentiate COVID-19 from influenza. Hospitalized COVID-19 patients had more severe disease, required longer hospitalization and were admitted to ICU more often than influenza patients, which has important implications for public health policies.

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