Long-term complications after coronavirus disease 2019 (COVID-19) are common in hospitalized patients, but the spectrum of symptoms in milder cases needs further investigation. We conducted a long-term follow-up in a prospective cohort study of 312 patients—247 home-isolated and 65 hospitalized—comprising 82% of total cases in Bergen during the first pandemic wave in Norway. At 6 months, 61% (189/312) of all patients had persistent symptoms, which were independently associated with severity of initial illness, increased convalescent antibody titers and pre-existing chronic lung disease. We found that 52% (32/61) of home-isolated young adults, aged 16–30 years, had symptoms at 6 months, including loss of taste and/or smell (28%, 17/61), fatigue (21%, 13/61), dyspnea (13%, 8/61), impaired concentration (13%, 8/61) and memory problems (11%, 7/61). Our findings that young, home-isolated adults with mild COVID-19 are at risk of long-lasting dyspnea and cognitive symptoms highlight the importance of infection control measures, such as vaccination.

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Background Households studies reflect the natural spread of SARS-CoV-2 in immunologically naive populations with limited preventive measures to control transmission. We hypothesise that seropositivity provides more accurate household attack rates than RT-PCR. Here, we investigated the importance of age in household transmission dynamics. Methods We enroled 112 households (291 participants) in a case-ascertained study in Bergen, Norway from 28th February to 4th April 2020, collecting demographic and clinical data from index patients and household members. SARS-CoV-2-specific antibodies were measured in sera collected 6–8 weeks after index patient nasopharyngeal testing to define household attack rates. Findings The overall attack rate was 45% (95% CI 38–53) assessed by serology, and 47% when also including seronegative RT-PCR positives. Serology identified a higher number of infected household members than RT-PCR. Attack rates were equally high in children (48%) and young adults (42%). The attack rate was 16% in asymptomatic household members and 42% in RT-PCR negative contacts. Older adults had higher antibody titres than younger adults. The risk of household transmission was higher when the index patient had fever (aOR 3.31 [95% CI 1.52–7.24]; p = 0.003) or dyspnoea (aOR 2.25 [95% CI 1.80–4.62]; p = 0.027) during acute illness. Interpretation Serological assays provide more sensitive and robust estimates of household attack rates than RT-PCR. Children are equally susceptible to infection as young adults. Negative RT-PCR or lack of symptoms are not sufficient to rule out infection in household members. Funding Helse Vest (F-11628), Trond Mohn Foundation (TMS2020TMT05).

Background During the coronavirus disease 2019 (COVID-19) pandemic, many countries experienced infection in healthcare workers (HCW) due to overburdened healthcare systems. However, whether infected HCW acquire protective immunity against SARS-CoV-2 is unclear. Here, we characterized SARS-CoV-2-specific antibody responses in Norwegian HCW in a prospective cohort study. Methods We enrolled 607 HCW pre- and post-the first COVID-19-pandemic wave. Exposure history, COVID-19-like symptoms and serum samples were collected. SARS-CoV-2-specific antibodies were characterized by spike-protein IgG/IgM/IgA enzyme-linked immunosorbent and live-virus neutralization assays. Results Spike-specific IgG, IgM, and IgA antibodies increased after the first pandemic wave in HCW with COVID-19-patient exposure, but not in HCW without patient exposure. Thirty-two HCW (5.3%) had spike-specific antibodies (11 seroconverted with ≥4-fold increase, 21 were seropositive at baseline). Neutralizing antibodies were found in 11 HCW that seroconverted, of whom 4 (36.4%) were asymptomatic. Ninety-seven HCW were tested by reverse-transcriptase-polymerase chain reaction (RT-PCR) during follow-up, 8 were positive (7 seroconverted and 1 had undetectable antibodies). Conclusions We found increases in SARS-CoV-2-neutralizing antibodies in infected HCW, especially after COVID-19-patient exposure. Our data show a low number of SARS-CoV-2-seropositive HCW in a low prevalence setting, however, the proportion of seropositivity was higher than RT-PCR positivity, highlighting the importance of antibody testing.

Enterotoxigenic Escherichia coli (ETEC) are a common cause of diarrheal illness in young children and travelers. There is yet no licensed broadly protective vaccine against ETEC. One promising vaccine development strategy is to target strains expressing the heat-stable toxin (ST), particularly the human ST (STh), since infections with these strains are among the leading causes of diarrhea in children in low-and-middle income countries. A human challenge model based on an STh-only ETEC strain will be useful to evaluate the protective efficacy of new ST-based vaccine candidates. To develop this model, we experimentally infected 21 healthy adult volunteers with the epidemiologically relevant STh-only ETEC strain TW10722, identified a suitable dose, assessed safety, and characterized clinical outcomes and immune responses caused by the infection. Doses of 1×1010 colony-forming units (CFU) of TW10722 gave a suitable attack risk of 67% for moderate or severe diarrhea and an overall diarrhea attack risk of 78%. Non-diarrheal symptoms were mostly mild or moderate, and there were no serious adverse events. During the first month after ingesting the challenge strain, we measured significant increases in both activated CD4+ T cells and levels of serum IgG and IgA antibodies targeting coli surface antigen 5 (CS5) and 6 (CS6), as well as the E. coli mucinase YghJ. The CS5-specific CD4+ T cell and antibody responses were still significantly elevated one year after experimental infection. In conclusion, we have developed a safe STh-only ETEC-based human challenge model which can be efficiently used in Phase 2B trials to evaluate the protective efficacy of new ST-based vaccine candidates.Trial registrationClinicalTrials.gov ClinicalTrials.gov, Project ID: NCT02870751

Long-term complications following COVID-19 are common in hospitalised patients, but the spectrum of symptoms in milder cases remains unclear. In a Norwegian prospective cohort study of 312 patients, 61% of COVID-19 patients (247 home-isolated and 65 hospitalised) had persistent symptoms at six months, most commonly fatigue (37%), impaired concentration (26%), disturbed smell and/or taste (25%), memory loss (24%) and dyspnoea (21%). In young home-isolated adults, aged 16–30, 52% had symptoms at six months, with fatigue (21%), dyspnoea (13%), impaired concentration (13%) and memory loss (11%) posing particular challenges. Pre-existing chronic lung disease and high convalescent antibody titres predicted persistent symptoms, particularly fatigue. Our finding that young, home-isolated adults with mild COVID-19 are at risk of long-lasting dyspnoea and cognitive symptoms highlights the importance of infection control measures, such as vaccination.

Pandemic vaccination elicited durable antibodies, supporting the incorporation of adjuvant. Our findings support the current recommendation of annual influenza vaccination in HCWs.

BackgroundEnterotoxigenic Escherichia coli (ETEC) is an important cause of childhood diarrhea in resource-limited regions. It is also an important cause of diarrhea in travellers to these areas.To evaluate the protective efficacy of new ETEC vaccines that are under development, there is a need to increase the capacity to undertake Phase IIB (human challenge) clinical trials and to develop suitable challenge models.MethodsAn in-hospital study was performed where fasting adult volunteers were experimentally infected with 1 × 106 to 1 × 109 colony forming units (CFUs) of the wild-type ETEC strain TW10598, which had been isolated from a child with diarrhea in West Africa in 1997. We recorded symptoms and physical signs and measured serum immune response to the TW10598 bacterium.ResultsWe included 30 volunteers with mean age 22.8 (range 19.8, 27.4) years. The most common symptoms were diarrhea (77%), abdominal pain (67%), nausea (63%), and abdominal cramping (53%). Seven subjects (23%) experienced fever, none were hypotensive. Most of the volunteers responded with a substantial rise in the level of serum IgA antibodies against the challenge strain.ConclusionsWe established the capacity and methods for safely undertaking challenge studies to measure the efficacy of ETEC vaccine candidates in a hospital ward. Strain TW10598 elicited both clinical symptoms and an immune response across the doses given.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2334-14-482) contains supplementary material, which is available to authorized users.