COVID-19

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Objectives: Many vaccines require higher/additional doses or adjuvants to provide adequate protection for people living with HIV (PLWH). Our objective was to compare COVID-19 vaccine immunogenicity in PLWH to HIV-negative individuals.Design: In a Canadian multi-centre prospective, observational cohort of PLWH receiving ≥2 COVID-19 vaccinations, we measured vaccine-induced immunity at three and six months post 2nd and one month post 3rd doses.Methods: The primary outcome was the percentage of PLWH mounting vaccine-induced immunity (co-positivity for anti-IgG against SARS-CoV2 Spike(S) and receptor binding domain (RBD) proteins) six months post 2nd dose. Univariable and multivariable logistic regression were used to compare COVID-19-specific immune responses between groups and within sub-groups.Results: Data from 294 PLWH and 267 controls were analyzed. Immunogenicity was achieved in over 90% at each time point in both groups. The proportions of participants achieving comparable anti-RBD levels were similar between the group at each time point. Anti-S IgG levels were similar by group at month 3 post 2nd dose and one month post 3rd dose. A lower proportion of PLWH vs controls maintained vaccine-induced anti-S IgG immunity 6 months post 2nd dose (92% vs 99%; OR 0.14[95% CI 0.03, 0.80; p = 0.027)]. In multivariable analyses, neither age, immune non-response, multimorbidity, sex, vaccine type or timing between doses were associated with reduced IgG response.Conclusion: Vaccine-induced IgG was elicited in the vast majority of PLWH and overall similar between groups. A slightly lower proportion of PLWH vs controls maintained vaccine-induced anti-S IgG immunity 6 months post 2nd dose demonstrating the importance of timely boosting in this population.Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.

First cases of the ongoing COVID-19 pandemic were identified in France in January 2020 and on February 28, 2020, in Corsica, an island situated in the Mediterranean Sea. A major outbreak hit early the ultra-peripheral region in the following of three imported cases returning from religious gathering in mainland France. Corsica has one of the oldest population in the world and a limited beds capacity in its 2 hospitals. Therefore, the healthcare systems were rapidly overwhelmed by influx of difficult-to-transfer patients in particular elderly cases.

Abstract Background Bacterial infections are a common complication in patients with seasonal viral respiratory tract infections and are associated with poor prognosis, increased risk of intensive care unit admission and 29–55% mortality. Yet, there is limited data on the burden of bacterial infections among COVID-19 patients in Africa, where underdeveloped healthcare systems are likely to play a pertinent role in the epidemiology of the COVID-19 pandemic. Here, we evaluated the etiologies, antimicrobial resistance profiles, risk factors, and outcomes of bacterial infections in severely ill COVID-19 patients. Methods A descriptive cross-sectional study design was adopted in severely ill COVID-19 patients at Kenyatta National Hospital, Kenya, from October to December 2021. We used a structured questionnaire and case report forms to collect sociodemographics, clinical presentation, and hospitalization outcome data. Blood, nasal/oropharyngeal swabs and tracheal aspirate samples were collected based on the patient's clinical presentation and transported to the Kenyatta National Hospital microbiology laboratory for immediate processing following the standard bacteriological procedures. Results We found at least one bacterial infection in 44.2% (53/120) of the patients sampled, with a 31.7% mortality rate. Pathogens were mainly from the upper respiratory tract (62.7%, 42/67), with gram-negative bacteria dominating (73.1%, 49/67). Males were about three times more likely to acquire bacterial infection (p = 0.015). Those aged 25 to 44 years (p = 0.009), immunized against SARS-CoV-2 (p = 0.027), and admitted to the infectious disease unit ward (p = 0.031) for a short length of stay (0–5 days, p < 0.001) were more likely to have a positive outcome. Multidrug-resistant isolates were the majority (64.3%, 46/67), mainly gram-negative bacteria (69.6%, 32/46). The predominant multidrug-resistant phenotypes were in Enterococcus cloacae (42.9%, 3/7), Klebsiella pneumonia (25%, 4/16), and Escherichia coli (40%, 2/5). Conclusion Our findings highlight a high prevalence of multidrug-resistant bacterial infections in severely ill COVID-19 patients, with male gender as a risk factor for bacterial infection. Elderly Patients, non-SARS-CoV-2 vaccination, intensive care unit admission, and long length of hospital stay were associated with poor outcomes. There is a need to emphasize strict adherence to infection and prevention at KNH-IDU and antimicrobial stewardship in line with local and global AMR control action plans. …

Abstract Background The efficacy of early treatment with convalescent plasma in patients with COVID-19 is debated. Nothing is known about the potential effect of other plasma components other than anti-SARS-CoV-2 antibodies. Methods To determine whether convalescent or standard plasma would improve outcomes for adults in early phase of Covid19 respiratory impairment we designed this randomized, three-arms, clinical trial (PLACO COVID) blinded on interventional arms that was conducted from June 2020 to August 2021. It was a multicentric trial at 19 Italian hospitals. We enrolled 180 hospitalized adult patients with COVID-19 pneumonia within 5 days from the onset of respiratory distress. Patients were randomly assigned in a 1:1:1 ratio to standard of care (n = 60) or standard of care + three units of standard plasma (n = 60) or standard of care + three units of high-titre convalescent plasma (n = 60) administered on days 1, 3, 5 after randomization. Primary outcome was 30-days mortality. Secondary outcomes were: incidence of mechanical ventilation or death at day 30, 6-month mortality, proportion of days with mechanical ventilation on total length of hospital stay, IgG anti-SARS-CoV-2 seroconversion, viral clearance from plasma and respiratory tract samples, and variations in Sequential Organ Failure Assessment score. The trial was analysed according to the intention-to-treat principle. Results 180 patients (133/180 [73.9%] males, mean age 66.6 years [IQR 57–73]) were enrolled a median of 8 days from onset of symptoms. At enrollment, 88.9% of patients showed moderate/severe respiratory failure. 30-days mortality was 20% in Control arm, 23% in Convalescent (risk ratio [RR] 1.13; 95% confidence interval [CI], 0.61–2.13, P = 0.694) and 25% in Standard plasma (RR 1.23; 95%CI, 0.63–2.37, P = 0.544). Time to viral clearance from respiratory tract was 21 days for Convalescent, 28 for Standard plasma and 23 in Control arm but differences were not statistically significant. No differences for other secondary endpoints were seen in the three arms. Serious adverse events were reported in 1.7%, 3.3% and 5% of patients in Control, Standard and Convalescent plasma arms respectively. Conclusions Neither high-titer Convalescent nor Standard plasma improve outcomes of COVID-19 patients with acute respiratory failure. Trial Registration Clinicaltrials.gov Identifier: NCT04428021. First posted: 11/06/2020 …

AbstractBackgroundWe assessed COVID-19 vaccination impact on illness severity among adults hospitalized with COVID-19 August 2021–March 2022.MethodsWe evaluated differences in intensive care unit (ICU) admission, in-hospital death, and length of stay among vaccinated (2 or 3 mRNA vaccine doses) versus unvaccinated patients aged ≥18 years hospitalized for ≥24 hours with COVID-19-like illness (CLI) and positive SARS-CoV-2 molecular testing. We calculated odds ratios for ICU admission and death and subdistribution hazard ratios (SHR) for time to hospital discharge adjusted for age, geographic region, calendar time, and local virus circulation.ResultsWe included 27,149 SARS-CoV-2 positive hospitalizations. During both Delta and Omicron-predominant periods, protection against ICU admission was strongest among 3-dose vaccinees compared with unvaccinated patients (Delta OR [CI]: 0.52 [0.28–0.96]); Omicron OR [CI]: 0.69 [0.54–0.87]). During both periods, risk of in-hospital of death was lower among vaccinated compared with unvaccinated but ORs were overlapping; during Omicron, lowest among 3-dose vaccinees (OR [CI] 0.39 [0.28–0.54]). We observed SHR >1 across all vaccination strata in both periods indicating faster discharge for vaccinated patients.ConclusionsCOVID-19 vaccination was associated with lower rates of ICU admission and in-hospital death in both Delta and Omicron periods compared with being unvaccinated.

New England Journal of Medicine, Volume 387, Issue 21, November 2022.

Proceedings of the National Academy of Sciences, Volume 119, Issue 48, November 2022.

The first-in-human study of intranasal COVID-19 vaccination with an adenovirus-vector vaccine did not induce a consistent mucosal antibody response or a strong systemic response.

AbstractBackgroundWe report primary results of a phase 3 trial of AZD7442 (tixagevimab/cilgavimab) for post-exposure prophylaxis to prevent symptomatic coronavirus disease 2019 (COVID-19)MethodsAdults without prior SARS-CoV-2 infection or COVID-19 vaccination were enrolled within 8 days of exposure to a SARS-CoV-2–infected individual and randomized 2:1 to a single 300-mg AZD7442 dose (one 1.5-mL intramuscular injection each of tixagevimab and cilgavimab consecutively) or placebo. Primary endpoints were safety and first post-dose SARS-CoV-2 reverse-transcription–polymerase-chain-reaction (RT-PCR)–positive symptomatic COVID-19 event before day 183.Results1121 participants were randomized and dosed (mean age 46 years; 49% females; AZD7442, n=749; placebo, n=372). Median (range) follow-up was 49 (5–115) and 48 (20–113) days for AZD7442 and placebo, respectively. Adverse events occurred in 162/749 (21.6%) and 111/372 (29.8%) participants with AZD7442 and placebo, respectively, mostly mild/moderate. RT-PCR–positive symptomatic COVID-19 occurred in 23/749 (3.1%) and 17/372 (4.6%) AZD7442- and placebo-treated participants, respectively (relative risk reduction 33.3%; 95% confidence interval [CI] –25.9 to 64.7; P=.21). In predefined subgroup analyses of 1073 (96%) participants who were SARS-CoV-2 RT-PCR–negative (n=974 [87%]) or missing an RT-PCR result (n=99 [9%]) at baseline, AZD7442 reduced RT-PCR–positive symptomatic COVID-19 by 73.2% (95% CI 27.1 to 90.1) versus placebo.ConclusionsThis study did not meet the primary efficacy endpoint of post-exposure prevention of symptomatic COVID-19 with AZD7442 versus placebo. However, predefined analysis of participants who were SARS-CoV-2 RT-PCR–negative or missing an RT-PCR result at baseline support a role for AZD7442 in preventing symptomatic COVID-19.

AbstractWe assessed changes in sexual behaviour among people with HIV (PWH) over 20 years. Condom use with stable partners steadily declined from over 90% to 29% since the Swiss U = U statement with similar trajectories between men who have sex with men (MSM) and heterosexuals. Occasional partnership remained higher among MSM compared to heterosexuals even during COVID-19 social distancing.

AbstractBackgroundThe impact variant-specific immune evasion and waning protection have on declining COVID-19 vaccine effectiveness remains unclear. Using whole-genome-sequencing (WGS), we examined the contribution of these factors on the decline observed following the introduction of the Delta variant. Further, we evaluated the utility of calendar-period-based classification as an alternative to WGS.MethodsWe conducted a test-negative-case-control study among people who received SARS-CoV-2 RT-PCR testing in the Yale New Haven Health System between April 1 and August 24, 2021. Variant classification was performed using WGS and calendar-period.ResultsOverall, 2,029 cases (RT-PCR positive, sequenced samples [infections]) and 343,985 controls (negative RT-PCRs) were included. VE 14-89 days after 2nd dose was significantly higher against WGS-classified Alpha-infection (84.4%, CI: 75.6-90.0%) than Delta-infection (68.9%, CI: 58.0-77.1%, p-value = 0.013). The odds of WGS-classified Delta-infection were significantly higher 90-149 than 14-89 days after 2nd dose (p-value = 0.003). VE estimates against calendar-period-classified infections approximated estimates against WGS-classified infections, however, calendar-period-based classification was subject to outcome misclassification (35%: Alpha-period, 4%: Delta-period).ConclusionsBoth waning protection and variant-specific immune evasion contributed to the lower effectiveness. While VE estimates against calendar-period-classified infections mirrored those against WGS-classified infections, our analysis highlights the need for WGS when variants are co-circulating and misclassification is likely.

Proceedings of the National Academy of Sciences, Volume 119, Issue 48, November 2022.

The omicron variant (B.1.1.529) of severe acute respiratory virus 2 (SARS-CoV-2) was first identified in November 2021 (Viana et al., 2022) and has dramatically increased the transmission of Coronavirus disease 2019 (COVID-19) globally. The COVID-19 vaccine protects against serious disease, hospitalization, and death. However, vaccination does not entirely prevent infection and transmission to others. Massive two-dose vaccination campaigns cannot prevent breakthrough infections caused by the variants (Cele et al., 2022, Kuhlmann et al., 2022).

Abstract Background Our understanding of the influence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on bacterial colonization in the children’s upper nasopharyngeal tract during the coronavirus infectious disease (COVID-19) pandemic is limited. This study aimed to determine whether there were any differences in bacterial colonization between asymptomatic children with or without a positive SARS-CoV-2 quantitative reverse transcriptase-polymerase chain reaction (RT-qPCR) results in the community setting. Methods A cross-sectional community-based exploratory study was conducted from March to May 2021 in Semarang, Central Java Province, Indonesia. Using stored nasopharyngeal swabs collected from children under 18 years as a contact tracing program, we performed a real-time quantitative (qPCR) for the most important bacterial colonizing pathogens: Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus, and Klebsiella pneumoniae. Results Swabs from a total of 440 children were included in this study, of which 228 (51.8%) were RT-qPCR-confirmed SARS-CoV-2 positive. In the 440 children, colonization rates were highest for H. influenzae (61.4%), followed by S. pneumoniae (17.5%), S. aureus (12.0%), and K. pneumoniae (1.8%). The co-occurrence of both S. pneumoniae and H. influenzae in the upper respiratory tract was significantly associated with a SARS-CoV-2 negative RT-qPCR. In contrast, colonization with only S. aureus was more common in SARS-CoV-2-positive children. Conclusion Overall, this exploratory study concludes that there is a significant difference in the bacterial nasopharyngeal colonization pattern between SARS-CoV-2 positive and negative in asymptomatic children in the community in Indonesia. …

Publication date: Available online 17 November 2022Source: ImmunityAuthor(s): Iker Valle Aramburu, Dennis Hoving, Spyros I. Vernardis, Martha Tin, Marianna Ioannou, Mia I. Temkin, Nathalia M. De Vasconcelos, Vadim Demichev, Elisa Theresa Helbig, Lena Lippert, Klaus Stahl, Matthew White, Helena Radbruch, Jana Ihlow, David Horst, Scott T. Chiesa, John E. Deanfield, Sascha David, Christian Bode, Florian Kurth…

BackgroundGlobally, there is a scarcity of effective treatments for SARS-CoV-2 infections (causing COVID-19). Repurposing existing medications may offer the best hope for treating patients with COVID-19 to curb the pandemic. IMU-838 is a dihydroorotate dehydrogenase inhibitor, which is an effective mechanism for antiviral effects against respiratory viruses. When used synergistically with oseltamivir, therapeutic effects have been observed against influenza and SARS-CoV-2 in rodents. The IMU-838 and Oseltamivir in the Treatment of COVID-19 (IONIC) trial is a randomised controlled trial that will investigate whether time to clinical improvement in patients with COVID-19 is improved following a 14-day course of IMU-838+oseltamivir versus oseltamivir alone.MethodsIONIC trial is an open-label study in which participants will be randomised 1:1 in two parallel arms: the intervention arm (IMU-838+oseltamivir) and the control arm (oseltamivir only). The primary outcome is time to clinical improvement; defined as the time from randomisation to a two-point improvement on WHO ordinal scale; discharge from hospital, or death (whichever occurs first). The study is sponsored by the University Hospitals Coventry and Warwickshire NHS Trust and funded by LifeArc.DiscussionThe IONIC protocol describes an overarching trial design to provide reliable evidence on the effectiveness of IMU-838 (vidofludimus calcium) when delivered in combination with an antiviral therapy (oseltamivir) (IONIC intervention) for confirmed or suspected COVID-19 infection in adult patients receiving usual standard of care.Ethics and disseminationThis study has been independently reviewed and approved by Wales Research Ethics Committee. In addition, required regulatory approvals were received from Medicines and Healthcare products Regulatory Agency.Trial registration numberEudraCT 2020-001805-21, ISRCTN53038326, NCT04516915.…

ObjectivesCOVID-19 has differentially affected countries, with health infrastructure and other related vulnerability indicators playing a role in determining the extent of its spread. Vulnerability of a geographical region to COVID-19 has been a topic of interest, particularly in low-income and middle-income countries like India to assess its multifactorial impact on incidence, prevalence or mortality. This study aims to construct a statistical analysis pipeline to compute such vulnerability indices and investigate their association with metrics of the pandemic growth.DesignUsing publicly reported observational socioeconomic, demographic, health-based and epidemiological data from Indian national surveys, we compute contextual COVID-19 Vulnerability Indices (cVIs) across multiple thematic resolutions for different geographical and spatial administrative regions. These cVIs are then used in Bayesian regression models to assess their impact on indicators of the spread of COVID-19.SettingThis study uses district-level indicators and case counts data for the state of Odisha, India.Primary outcome measureWe use instantaneous R (temporal average of estimated time-varying reproduction number for COVID-19) as the primary outcome variable in our models.ResultsOur observational study, focussing on 30 districts of Odisha, identified housing and hygiene conditions, COVID-19 preparedness and epidemiological factors as important indicators associated with COVID-19 vulnerability.ConclusionHaving succeeded in containing COVID-19 to a reasonable level during the first wave, the second wave of COVID-19 made greater inroads into the hinterlands and peripheral districts of Odisha, burdening the already deficient public health system in these areas, as identified by the cVIs. Improved understanding of the factors driving COVID-19 vulnerability will help policy makers prioritise resources and regions, leading to more effective mitigation strategies for the present and future.…

ObjectiveWe undertook a systematic review of strategies adopted to scale up COVID-19 testing in countries across income levels to identify successful approaches and facilitate learning.MethodsScholarly articles in English from PubMed, Google scholar and Google search engine describing strategies used to increase COVID-19 testing in countries were reviewed. Deductive analysis to allocate relevant text from the reviewed publications/reports to the a priori themes was done.Main resultsThe review covered 32 countries, including 11 high-income, 2 upper-middle-income, 13 lower-middle-income and 6 low-income countries. Most low- and middle-income countries (LMICs) increased the number of laboratories available for testing and deployed sample collection and shipment to the available laboratories. The high-income countries (HICs) that is, South Korea, Germany, Singapore and USA developed molecular diagnostics with accompanying regulatory and legislative framework adjustments to ensure the rapid development and use of the tests. HICs like South Korea leveraged existing manufacturing systems to develop tests, while the LMICs leveraged existing national disease control programmes (HIV, tuberculosis, malaria) to increase testing. Continent-wide, African Centres for Disease Control and Prevention-led collaborations increased testing across most African countries through building capacity by providing testing kits and training.ConclusionStrategies taken appear to reflect the existing systems or economies of scale that a particular country could leverage. LMICs, for example, drew on the infectious disease control programmes already in place to harness expertise and laboratory capacity for COVID-19 testing. There however might have been strategies adopted by other countries but were never published and thus did not appear anywhere in the searched databases.…

ObjectiveMigrants and ethnic minority groups have been disproportionately impacted by COVID-19 and have lower levels of vaccine uptake in some contexts. We aimed to determine the extent and nature of social media use in migrant and ethnic minority communities for COVID-19 information, and implications for preventative health measures including vaccination intent and uptake.DesignA systematic review of published and grey literature following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched databases including Embase, Web of Science, PubMed NIH, CINAHL, facilitated through the WHO Global Research on COVID-19 database from 31 December 2019 to 9 June 2021.Eligibility criteria for study selectionResearch reporting the use of social media by migrants and/or ethnic minority groups in relation to COVID-19.Data extractionWe extracted data on key outcomes, study design, country, population under study and sample size.Results1849 unique records were screened, and 21 data sources were included, including populations in the UK, USA, China, Jordan, Qatar and Turkey. We found evidence of consistent use of a range of social media platforms for COVID-19 information in some migrant and ethnic minority populations (including WeChat, Facebook, WhatsApp, Instagram, Twitter, YouTube), which may stem from difficulty in accessing COVID-19 information in their native languages or from trusted sources. Some evidence suggested circulating misinformation and social media use may be associated with lower participation in preventative health measures, including vaccine intent and uptake, findings which are likely relevant to multiple population groups.ConclusionsSocial media platforms are an important source of information about COVID-19 for some migrant and ethnic minority populations. Urgent actions and further research are now needed to better understand effective approaches to tackling circulating misinformation, and to seize on opportunities to better use social media platforms to support public health communication and improve vaccine uptake.RegistrationThis study has been registered with PROSPERO (CRD42021259190).…

AbstractTixagevimab and cilgavimab treatment was associated with higher rates of cardiovascular events in a post-hoc analysis of a phase 3 trial. In this large population-based propensity-matched study, we found no increased risk of cardiovascular events up to 90 days after tixagevimab and cilgavimab administration, including in patients with pre-existing cardiovascular disease.

Little is known about the real-world effectiveness of oral antivirals against the SARS-CoV-2 omicron (B.1.1.529) variant. We aimed to assess the clinical effectiveness of two oral antiviral drugs among community-dwelling COVID-19 outpatients in Hong Kong.

Data on the effectiveness of oral antivirals in patients with mild-to-moderate COVID-19 are urgently needed. This retrospective cohort study aimed to evaluate the clinical and virological outcomes associated with molnupiravir or nirmatrelvir-ritonavir use in hospitalised patients with mild-to-moderate COVID-19 during a pandemic wave dominated by the omicron BA.2 subvariant.

The oral protease inhibitor nirmatrelvir has shown substantial efficacy in high-risk, unvaccinated patients infected with the B.1.617.2 (delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Data regarding the effectiveness of nirmatrelvir in preventing severe coronavirus disease 2019 (Covid-19) outcomes from the B.1.1.529 (omicron) variant are limited.

Treatment of coronavirus disease-2019 (Covid-19) with nirmatrelvir plus ritonavir (NMV-r) in high-risk non-hospitalized unvaccinated patients reduced the risk of progression to severe disease. However, the potential benefits of NMV-r among vaccinated patients are unclear.

Nirmatrelvir is an orally administered severe acute respiratory syndrome coronavirus 2 main protease (M) inhibitor with potent pan-human-coronavirus activity in vitro.

Coronavirus disease 2019 (Covid-19) disproportionately results in hospitalization or death in older patients and those with underlying conditions. Sotrovimab is a pan-sarbecovirus monoclonal antibody that was designed to prevent progression of Covid-19 in high-risk patients early in the course of disease.

A daily dose with 6 mg of dexamethasone is recommended for up to 10 days in patients with severe and critical COVID-19, but a higher dose may benefit those with more severe disease.

Monoclonal antibodies (mAbs) are laboratory-produced molecules derived from the B cells of an infected host. They are being investigated as a potential therapy for coronavirus disease 2019 (COVID-19).

REGEN-COV (previously known as REGN-COV2), a combination of the monoclonal antibodies casirivimab and imdevimab, has been shown to markedly reduce the risk of hospitalization or death among high-risk persons with coronavirus disease 2019 (Covid-19). Whether subcutaneous REGEN-COV prevents severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and subsequent Covid-19 in persons at high risk for infection because of household exposure to a person with SARS-CoV-2 infection is unknown.

The acute clinical manifestations of COVID-19 have been well characterized, but the post-acute sequelae of this disease have not been comprehensively described. Here we use the national healthcare databases of the US Department of Veterans Affairs to systematically and comprehensively identify 6-month incident sequelae-including diagnoses, medication use and laboratory abnormalities-in patients with COVID-19 who survived for at least 30 days after diagnosis. We show that beyond the first 30 days of illness, people with COVID-19 exhibit a higher risk of death and use of health resources. Our high-dimensional approach identifies incident sequelae in the respiratory system, as well as several other sequelae that include nervous system and neurocognitive disorders, mental health disorders, metabolic disorders, cardiovascular disorders, gastrointestinal disorders, malaise, fatigue, musculoskeletal pain and anaemia. We show increased incident use of several therapeutic agents-including pain medications (opioids and non-opioids) as well as antidepressant, anxiolytic, antihypertensive and oral hypoglycaemic agents-as well as evidence of laboratory abnormalities in several organ systems. Our analysis of an array of prespecified outcomes reveals a risk gradient that increases according to the severity of the acute COVID-19 infection (that is, whether patients were not hospitalized, hospitalized or admitted to intensive care). Our findings show that a substantial burden of health loss that spans pulmonary and several extrapulmonary organ systems is experienced by patients who survive after the acute phase of COVID-19. These results will help to inform health system planning and the development of multidisciplinary care strategies to reduce chronic health loss among individuals with COVID-19.

The degree to which infection with SARS-CoV-2 confers protection towards subsequent reinfection is not well described. In 2020, as part of Denmark's extensive, free-of-charge PCR-testing strategy, approximately 4 million individuals (69% of the population) underwent 10·6 million tests. Using these national PCR-test data from 2020, we estimated protection towards repeat infection with SARS-CoV-2.

The efficacy of interleukin-6 receptor antagonists in critically ill patients with coronavirus disease 2019 (Covid-19) is unclear.

Coronavirus disease 2019 (Covid-19) pneumonia is often associated with hyperinflammation. Despite the disproportionate incidence of Covid-19 among underserved and racial and ethnic minority populations, the safety and efficacy of the anti-interleukin-6 receptor antibody tocilizumab in patients from these populations who are hospitalized with Covid-19 pneumonia are unclear.

Recent data suggest that complications and death from coronavirus disease 2019 (Covid-19) may be related to high viral loads.

The COVID-19 pandemic has created a public health crisis. Because SARS-CoV-2 can spread from individuals with presymptomatic, symptomatic, and asymptomatic infections, the reopening of societies and the control of virus spread will be facilitated by robust population screening, for which virus testing will often be central. After infection, individuals undergo a period of incubation during which viral titers are too low to detect, followed by exponential viral growth, leading to peak viral load and infectiousness and ending with declining titers and clearance. Given the pattern of viral load kinetics, we model the effectiveness of repeated population screening considering test sensitivities, frequency, and sample-to-answer reporting time. These results demonstrate that effective screening depends largely on frequency of testing and speed of reporting and is only marginally improved by high test sensitivity. We therefore conclude that screening should prioritize accessibility, frequency, and sample-to-answer time; analytical limits of detection should be secondary.

Viral epidemics or pandemics of acute respiratory infections (ARIs) pose a global threat. Examples are influenza (H1N1) caused by the H1N1pdm09 virus in 2009, severe acute respiratory syndrome (SARS) in 2003, and coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 in 2019. Antiviral drugs and vaccines may be insufficient to prevent their spread. This is an update of a Cochrane Review published in 2007, 2009, 2010, and 2011. The evidence summarised in this review does not include results from studies from the current COVID-19 pandemic.

The efficacy of interleukin-6 receptor blockade in hospitalized patients with coronavirus disease 2019 (Covid-19) who are not receiving mechanical ventilation is unclear.

Severe pneumonia with hyperinflammation and elevated interleukin-6 is a common presentation of coronavirus disease 2019 (COVID-19).

The coronavirus disease 2019 (COVID-19) pandemic is threatening billions of people worldwide. Tocilizumab has shown promising results in retrospective studies in patients with COVID-19 pneumonia with a good safety profile.

Population-level knowledge on individuals at high risk of severe and fatal coronavirus disease 2019 (COVID-19) is urgently needed to inform targeted protection strategies in the general population.

This is the twelfth version (eleventh update) of the living guideline, replacing earlier versions (available as data supplements). New recommendations will be published as updates to this guideline.

Remdesivir demonstrated clinical benefit in a placebo-controlled trial in patients with severe coronavirus disease 2019 (COVID-19), but its effect in patients with moderate disease is unknown.

Coronavirus disease 2019 (Covid-19) is associated with diffuse lung damage. Glucocorticoids may modulate inflammation-mediated lung injury and thereby reduce progression to respiratory failure and death.

Remdesivir is an RNA polymerase inhibitor with potent antiviral activity in vitro and efficacy in animal models of coronavirus disease 2019 (Covid-19).

Although several therapeutic agents have been evaluated for the treatment of coronavirus disease 2019 (Covid-19), no antiviral agents have yet been shown to be efficacious.

The clinical presentation of European patients with mild-to-moderate COVID-19 infection is still unknown.

There is no specific antiviral therapy recommended for coronavirus disease 2019 (COVID-19). In vitro studies indicate that the antiviral effect of chloroquine diphosphate (CQ) requires a high concentration of the drug.

Since the outbreak of coronavirus disease (COVID-19) in Wuhan in December 2019, by March 10, 2020, a total of 80,932 confirmed cases have been reported in China. Two consecutively negative RT-PCR test results in respiratory tract specimens is required for the evaluation of discharge from hospital, and oropharyngeal swabs were the most common sample. However, false negative results occurred in the late stage of hospitalization, and avoiding false negative result is critical essential.

Coronavirus disease 2019 (COVID-19) or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus strain disease, has recently emerged in China and rapidly spread worldwide. This novel strain is highly transmittable and severe disease has been reported in up to 16% of hospitalized cases. More than 600,000 cases have been confirmed and the number of deaths is constantly increasing. COVID-19 hospitalized patients, especially those suffering from severe respiratory or systemic manifestations, fall under the spectrum of the acutely ill medical population, which is at increased venous thromboembolism risk. Thrombotic complications seem to emerge as an important issue in patients infected with COVID-19. Preliminary reports on COVID-19 patients' clinical and laboratory findings include thrombocytopenia, elevated D-dimer, prolonged prothrombin time, and disseminated intravascular coagulation. As the pandemic is spreading and the whole picture is yet unknown, we highlight the importance of coagulation disorders in COVID-19 infected patients and review relevant data of previous coronavirus epidemics caused by the severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) and the Middle East Respiratory Syndrome coronavirus (MERS-CoV).

The pandemic of coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents an unprecedented challenge to identify effective drugs for prevention and treatment. Given the rapid pace of scientific discovery and clinical data generated by the large number of people rapidly infected by SARS-CoV-2, clinicians need accurate evidence regarding effective medical treatments for this infection.

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, Coronavirus Disease 2019 (COVID-19), affecting thousands of people around the world. Urgent guidance for clinicians caring for the sickest of these patients is needed.

No therapeutics have yet been proven effective for the treatment of severe illness caused by SARS-CoV-2.

The 2019 novel coronavirus (2019-nCoV) causing an outbreak of pneumonia in Wuhan, Hubei province of China was isolated in January 2020. This study aims to investigate its epidemiologic history, and analyze the clinical characteristics, treatment regimens, and prognosis of patients infected with 2019-nCoV during this outbreak.