Covid19-Sources

SARS-CoV-2 variants of concern (VOCs) emerged during the COVID-19 pandemic. Here, we used unbiased systems approaches to study the host-selective forc…

This randomized clinical trial evaluates a plain language recommendation format vs a standard language version for understanding COVID-19 health recommendations among youths.

Systemic corticosteroids are helpful for patients with severe COVID-19 who require hospitalization with supplemental oxygen. The role of inhaled

available. Here we show that, beyond the acute phase of illness, 30-day survivors of COVID-19 exhibited higher risks of AKI, eGFR decline, ESKD, major adverse kidney events (MAKE), and steeper longitudinal decline in eGFR. The risks of kidney outcomes increased according to the severity of the acute infection (categorized by care setting into non-hospitalized, hospitalized, and admitted to intensive care). The findings provide insight into the long-term consequences of COVID-19 on kidney outcomes and suggest that post-acute COVID-19 care should include attention to kidney function and disease. Background COVID-19 is associated with increased risk of post-acute sequelae involving pulmonary and extrapulmonary organ systems—referred to as long COVID. However, a detailed assessment of kidney outcomes in long COVID is not yet available. Methods We built a cohort of 1,726,683 US Veterans identified from March 1, 2020 to March 15, 2021, including 89,216 patients who were 30-day survivors of COVID-19 and 1,637,467 non-infected controls. We examined risks of AKI, eGFR decline, ESKD, and major adverse kidney events (MAKE). MAKE was defined as eGFR decline ≥50%, ESKD, or all-cause mortality. We used inverse probability–weighted survival regression, adjusting for predefined demographic and health characteristics, and algorithmically selected high-dimensional covariates, including diagnoses, medications, and laboratory tests. Linear mixed models characterized intra-individual eGFR trajectory. Results Beyond the acute illness, 30-day survivors of COVID-19 exhibited a higher risk of AKI (aHR, 1.94; 95% CI, 1.86 to 2.04), eGFR decline ≥30% (aHR, 1.25; 95% CI, 1.14 to 1.37), eGFR decline ≥40% (aHR, 1.44; 95% CI, 1.37 to 1.51), eGFR decline ≥50% (aHR, 1.62; 95% CI, 1.51 to 1.74), ESKD (aHR, 2.96; 95% CI, 2.49 to 3.51), and MAKE (aHR, 1.66; 95% CI, 1.58 to 1.74). Increase in risks of post-acute kidney outcomes was graded according to the severity of the acute infection (whether patients were non-hospitalized, hospitalized, or admitted to intensive care). Compared with non-infected controls, 30-day survivors of COVID-19 exhibited excess eGFR decline (95% CI) of −3.26 (−3.58 to −2.94), −5.20 (−6.24 to −4.16), and −7.69 (−8.27 to −7.12) ml/min per 1.73 m2 per year, respectively, in non-hospitalized, hospitalized, and those admitted to intensive care during the acute phase of COVID-19 infection. Conclusions Patients who survived COVID-19 exhibited increased risk of kidney outcomes in the post-acute phase of the disease. Post-acute COVID-19 care should include attention to kidney disease....

The COVID-19 pandemic has exposed a number of key challenges that need to be urgently addressed. In particular, rapid identification and validation of prognostic markers is required. Mass spectrometric studies of blood plasma proteomics provide a deep understanding of the relationship between the severe course of infection and activation of specific pathophysiological pathways. Analysis of plasma proteins in whole blood may also be relevant for the pandemic as it requires minimal sample preparation. Here, for the first time, frozen whole blood samples were used to analyze 189 plasma proteins using multiple reaction monitoring (MRM) mass spectrometry and stable isotope-labeled peptide standards (SIS). A total of 128 samples (FRCC, Russia) from patients with mild (n=40), moderate (n=36) and severe (n=19) COVID-19 infection and healthy controls (n=33) were analyzed. Levels of 114 proteins were quantified and compared. Significant differences between all of the groups were revealed for 61 proteins. Changes in the levels of 30 reproducible COVID-19 markers (SERPING1, CRP, C9, ORM1, APOA1, SAA1/SAA2, LBP, AFM, IGFALS, etc.) were consistent with studies performed with serum/plasma samples. Levels of 70 proteins correlated between whole blood and plasma samples. The best-performing classifier built with 13 significantly different proteins achieved the best combination of ROC-AUC (0.93-0.95) and accuracy (0.87-0.93) metrics and distinguished patients from controls, as well as patients by severity and risk of mortality. Overall, the results support the use of frozen whole blood for MRM analysis of plasma proteins and assessment of the status of patients with COVID-19. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement In part of targeted proteomic analysis E.N.N., A.S.K., P.A.S and A.G.B. acknowledge the support by a MegaGrant of the Ministry of Science and Higher Education of the Russian Federation [Agreement with Skolkovo Institute of Science and Technology, #075-10-2022-090 (075-10-2019-083)]. In part of sample preparation and data analysis I.N.K., A.E.B, N.V.Z., M.I.I. gratefully appreciate funding from the Ministry of Science and Higher Education of the Russian Federation (# 44.1, 44.2 and 44.4). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was approved by the ethical committee of the Federal Research Clinical Center (FRCC) under Federal Medical and Biological Agency (Russia) (clinical protocol No. 5, 11 May 2021). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All experimental results were uploaded to the PeptideAtlas SRM Experiment Library (PASSEL) and are available via link: (accessed on 4 September 2023).

DMZ – WISSENSCHAFT¦ Anton Aeberhard ¦ Seit dem Ausbruch der SARS-CoV-2-Pandemie haben Epidemiologen Schätzungen zufolge in der WHO-Region Europa allein in den letzten drei Jahren etwa 36 Millionen Menschen identifiziert, die unter den Symptomen von Long Covid leiden. Neben den bekannten physischen Beschwerden treten bei Long Covid-Patienten häufig auch kognitive Beeinträchtigungen auf, die oft als "Brain Fog" bezeichnet werden. Britische Wissenschaftler haben kürzlich in einer bahnbrechenden Studie herausgefunden, dass es eine bedeutsame Verbindung zwischen Long Covid, verstärkter Thromboseanfälligkeit und diesen kognitiven Problemen gibt. Die Forschungsarbeit, angeführt von Maxime Taquet von der Abteilung für Psychiatrie an der Universität Oxford, hat wichtige Erkenntnisse über die Ursache von kognitiven Beeinträchtigungen nach einer akuten SARS-CoV-2-Infektion geliefert. Die Ergebnisse der Studie sind alarmierend: Einer von acht Covid-19-Patienten erhält innerhalb von sechs Monaten nach der akuten Infektion eine Diagnose von neurologischen oder psychiatrischen Problemen. Besonders besorgniserregend ist dabei das häufig auftretende Symptom des "Brain Fog", das die Patienten lange begleiten kann. Die Forscher entdeckten während ihrer Analyse und den Nachuntersuchungen bemerkenswerte Zusammenhänge. Während der akuten Phase einer Covid-19-Erkrankung führten erhöhte Werte des Blutgerinnungsfaktors I, auch bekannt als Fibrinogen, im Vergleich zum Entzündungsmarker CRP (c-reaktives Protein) häufiger zu objektiv messbaren kognitiven Störungen. Fibrinogen wird in der Leber produziert, und erhöhte Werte im Blut weisen auf Entzündungsvorgänge hin, die auch die Blutgerinnung aktivieren können. Darüber hinaus zeigten die Studienteilnehmer mit erhöhten Fibrinogenwerten signifikant schlechtere Ergebnisse in Tests zur subjektiven Wahrnehmung kognitiver Probleme. Dies legt nahe, dass die Bildung von Mikrothromben im Gehirn mit diesen Beeinträchtigungen in Verbindung stehen könnte. Zusätzlich besteht die Möglichkeit, dass Fibrinogen direkt Nervenzellen im Gehirn schädigt. Ein weiterer bedeutender Marker in der Studie war D-Dimer, ein bekannter Indikator für Thrombosen. Die britischen Wissenschaftler fanden auch hier einen klaren Zusammenhang zwischen erhöhten D-Dimer-Werten und kognitiven Störungen. Diese Erkenntnisse wurden durch die Analyse von über 90 Millionen britischen elektronischen Krankenakten bestätigt. Die mögliche Erklärung für diese Zusammenhänge liegt in der Vermutung, dass erhöhte D-Dimer-Konzentrationen im Blut auf die Bildung von Thromben in den kleinen Blutgefäßen der Lunge hinweisen könnten. Dies könnte wiederum zu einer langfristigen Verringerung der Sauerstoffaufnahme führen und somit Erschöpfungszustände verursachen. Die Forschungsergebnisse legen nahe, dass in schweren Covid-19-Verläufen die Verwendung von Medikamenten zur Hemmung der Blutgerinnung erwogen werden sollte. Dies könnte möglicherweise dazu beitragen, Long Covid-Probleme zu verhindern oder zumindest erheblich zu lindern. Die Studie hat nicht nur das Verständnis von Long Covid vertieft, sondern könnte auch neue Wege zur Behandlung und Prävention dieser Langzeitfolgen der Krankheit eröffnen.

Severe acute respiratory distress syndrome-coronavirus-2 (SARS-CoV-2) provokes symptoms ranging from mild viral illness to a systemic inflammatory syndrome with multi-organ failure and has been associated with cases of arthritis. We report a clinical case of SARS-CoV-2 associated arthritis in which …

We systematically reviewed and appraised the epidemiological evidence on allergic diseases as risk factors for Long-COVID. Meta-analysis revealed that pre-existing asthma measured in hospital-based p...

Correspondence from The New England Journal of Medicine — Receipt of mRNA Covid-19 Vaccines and Risk of Spontaneous Abortion

While the BA.2.86 variant demonstrated significant antigenic drift and enhanced ACE2 binding affinity, its ability to evade humoral immunity was relatively moderate compared to dominant strains like EG.5 and HK.3. However, the emergence of a new subvariant, JN.1 (BA.2.86.1.1), which possesses an additional spike mutation, L455S, compared to BA.2.86, showed a markedly increased prevalence in Europe and North America, especially in France. Here, we found that L455S of JN.1 significantly enhances immune evasion capabilities at the expense of reduced ACE2 binding affinity. This mutation enables JN.1 to effectively evade Class 1 neutralizing antibodies, offsetting BA.2.86’s susceptibility and thus allowing it to outcompete both its precursor BA.2.86 and the prevailing variants HV.1 (XBB.1.5+L452R+F456L) and JD.1.1 (XBB.1.5+L455F+F456L+A475V) in terms of humoral immune evasion. The rapid evolution from BA.2.86 to JN.1, similar to the earlier transition from BA.2.75 to CH.1.1, highlights the importance of closely monitoring strains with high ACE2 binding affinity and distinct antigenicity, despite their temporarily unremarkable immune evasion capabilities. Such strains could survive and transmit at low levels, since their large antigenic distance to dominant strains allow them to target distinct populations and accumulate immune-evasive mutations rapidly, often at the cost of receptor binding affinity. ### Competing Interest Statement Y.C. is the inventor of the provisional patent applications for BD series antibodies, which includes BD55-5514 (SA55). Y.C. is the founder of Singlomics Biopharmaceuticals. Other authors declare no competing interests.

We still have much to learn about many aspects of COVID-19 — including its lingering health effects and the mechanics of its mutations — but we do know we can’t let our guard down, write Dawn Bowdish and Andrew Costa.

Journal of Medical Virology is a clinical virology journal focused on the diagnosis, epidemiology, immunology and pathogenesis of human viral infections & diseases.

There's still so much we don't know about COVID-19.

Persistent symptoms following the acute phase of COVID-19 present a major burden to both the affected and the wider community. We conducted a cohort study including over 856,840 first COVID-19 cases, 72,422 re-infections and more than 3.1 million first negative-test controls from primary care electronic health records from Spain and the UK (Sept 2020 to Jan 2022 (UK)/March 2022 (Spain)). We characterised post-acute COVID-19 symptoms and identified key symptoms associated with persistent disease. We estimated incidence rates of persisting symptoms in the general population and among COVID-19 patients over time. Subsequently, we investigated which WHO-listed symptoms were particularly differential by comparing their frequency in COVID-19 cases vs. matched test-negative controls. Lastly, we compared persistent symptoms after first infections vs. reinfections.Our study shows that the proportion of COVID-19 cases affected by persistent post-acute COVID-19 symptoms declined over the study period. Risk for altered smell/taste was consistently higher in patients with COVID-19 vs test-negative controls. Persistent symp- toms were more common after reinfection than following a first infection. More research is needed into the definition of long COVID, and the effect of interventions to minimise the risk and impact of persistent symptoms.

Nature - Single-nucleus transcriptomes of frontal cortex and choroid plexus samples from patients with COVID-19 reveal pathological cell states that are similar to those associated with human...

The survey identified 34 cases of acute encephalopathy associated with COVID-19 infection among those under 18 between January 2020 and May 2022.

Deutschland steuert auf den vierten Winter seit der weltweiten Ausbreitung des Coronavirus zu. Die Fallzahlen steigen, doch welche Varianten gehen um?

The post–COVID-19 condition (PCC) is a disabling syndrome affecting at least 5%–10% of subjects who survive COVID-19. SARS-CoV-2 mediated vagus nerve dysfunction could explain some PCC symptoms, such as dysphonia, dysphagia, dyspnea, dizziness, tachycardia, orthostatic hypotension, gastrointestinal disturbances, or neurocognitive complaints. Participants were mostly women (24 of 30, 80%), and the median age was 44 years (interquartile range [IQR] 35–51 years). Their most prevalent symptoms were cognitive dysfunction 25 of 30 (83%), dyspnea 24 of 30 (80%), and tachycardia 24 of 30 (80%). Compared with COVID-19-recovered and uninfected controls, respectively, subjects with PCC were more likely to show thickening and hyperechogenic vagus nerve in neck ultrasounds (cross-sectional area [CSA] [mean ± standard deviation]: 2.4 ± 0.97mm2 vs. 2 ± 0.52mm2 vs. 1.9 ± 0.73 mm2; p 0.08), reduced esophageal-gastric-intestinal peristalsis (34% vs. 0% vs. 21%; p 0.02), gastroesophageal reflux (34% vs. 19% vs. 7%; p 0.13), and hiatal hernia (25% vs. 0% vs. 7%; p 0.05). Subjects with PCC showed flattening hemidiaphragms (47% vs. 6% vs. 14%; p 0.007), and reductions in maximum inspiratory pressure (62% vs. 6% vs. 17%; p ≤ 0.001), indicating respiratory muscle weakness. The latter findings suggest additional involvement of the phrenic nerve.

SARS-CoV-2 omicron XBB sublineages efficiently evade immunity from infection or vaccination, requiring vaccine adaptation. Updated monovalent omicron XBB.1.5-containing vaccines were approved in September, 2023. Although preliminary manufacturer data suggest neutralisation of currently emerging sublineages, real-world evidence is scarce,1 and persisting immune imprinting2,3 might compromise elicitation of antibodies against new SARS-CoV-2 sublineages. We monitored immune responses in 65 health-care workers from our ongoing CoCo Study4 who were vaccinated with 30 μg of the updated BNT162b2 omicron XBB.1.5 vaccine (Raxtozinameran, BioNTech, Mainz, Germany) in September, 2023, and analysed 53 individuals 8–10 days after vaccination (appendix p 12).

What are the rates of ongoing COVID-19 symptoms in 2023 and beyond?

As part of an ongoing partnership with the Census Bureau, the National Center for Health Statistics (NCHS) recently added questions to assess the prevalence of post-COVID-19 conditions (long COVID), on the experimental Household Pulse Survey. This 20-minute online survey was designed to complement the ability of the federal statistical system to rapidly respond and provide relevant information about the impact of the coronavirus pandemic in the U.S. Data collection began on April 23, 2020.

Evolution of SARSCoV2 Omicron spike:⬆️infectivity &⬆️immune evasion &⬆️no of mutations compared to previous (VOCs) characterize Omicron variant-evolution has lengthened fallout;diff from previous VOCs-outcompete other variants, https://t.co/NmV7zTmS7f— Prof. Dr. Sanjeev Bagai (@BagaiDr) November 22, 2023

There is no evidence that an individual is worse off for having avoided earlier infection

The reduced pathogenicity of the omicron BA.1 sub-lineage compared to earlier variants is well described, although whether such attenuation is retained for later variants like BA.5 and XBB remains controversial. We show that BA.5 and XBB isolates were significantly more pathogenic in K18-hACE2 mice than a BA.1 isolate, showing increased neurotropic potential, resulting in fulminant brain infection and mortality, similar to that seen for original ancestral isolates. BA.5 also infected human cortical brain organoids to a greater extent than the BA.1 and original ancestral isolates. In the brains of mice, neurons were the main target of infection, and in human organoids neuronal progenitor cells and immature neurons were infected. The results herein suggest that evolving omicron variants may have increasing neurotropic potential.

Information on the protein-based severe acute respiratory syndrome (SARS-CoV-2) vaccine-NVX-CoV2373 (Novavax), as a heterologous booster remains limit…

Background Rapid antigen tests (RATs) for SARS-CoV-2 have been used to combat the still ongoing Covid-19 pandemic. This study is the extension of the COVAG study originally performed from February 1 to March 31, 2021. We compared two RATs, the Panbio COVID-19 Ag Rapid Test (Abbott) and the SD Biosensor Q SARS-CoV-2 Rapid Antigen Test (Roche), against RT-PCR on the foil of new variants. Methods We included 888 all-comers at a diagnostic center between October 20, 2021, and March 18, 2022. RT-PCR-positive samples with a Ct value ≤ 32 were examined for SARS-CoV-2 variants. Findings The sensitivity of the Abbott-RAT and Roche-RAT were 65% and 67%, respectively. For both RATs, lower Ct values were significantly correlated with higher sensitivity. For samples with Ct values ≤ 25, the sensitivities of the Roche-RAT and of the Abbott-RAT were 96% and 95%, for Ct values 25-30 both were 19%, and for Ct values ≥ 30 they were 6% and 2%, respectively. The RATs had substantially higher sensitivities in symptomatic than asymptomatic participants (76, 77%, vs. 29, 31%, for Abbott-RAT, Roche-RAT, respectively) and in participants referred to testing by their primary care physician (84%, 85%) compared to participants who sought testing due to referral by the health department (55%, 58%) or a warning by the Corona-Warn-App (49%, 49%). In persons with self-reported previous Covid-19 sensitivities were markedly lower than in patients without previous Covid-19: 27% vs. 75% for Roche-RAT and 27% vs. 73% for Abbott-RAT. Depending on the vaccination status, the sensitivity of the RATs is 67.6%, 61.5% and 70.6% for non-vaccinated, vaccinated and boostered participants, respectively. For the considered subpopulation of 888 participants, we find no significant correlation between vaccination status and sensitivity. The Omicron variant was detected with a sensitivity of 94% and 92%, the delta variant with a sensitivity of 80% and 80% for Abbott-RAT and Roche-RAT, respectively. This difference is attributable to the lower Ct values of the Omicron samples compared to the Delta samples. When adjusted for the Ct value, a multivariate logistic regression did not show a significant difference between Omicron and Delta. In terms of sensitivity, we found no significant difference between the wild-type and the Omicron and Delta variants, but a significantly lower sensitivity to the alpha variant compared to the other variants. For a Ct value ≤ 25 the sensitivities were 95.2% and 96.0% for the Abbott-RAT and the Roche-RAT, respectively (Table 4). For a Ct value of 25-30 both RATs had a sensitivity of 18.8%. For a Ct value of 30-32, the sensitivities were 0.0% and 7.1% respectively, for Ct values ≥32 the sensitivities were 3.0% and 6.0% for Abbott-RAT and Roche-RAT, respectively. The specificities were 99% overall. Interpretation: The sensitivity of the RATs for asymptomatic carriers is unsatisfactory questioning their use for screening. When used in symptomatic patients or when requested by a primary care physician the sensitivities were higher. Our study does not suggest that the vaccination status influences the sensitivity of RATs. ### Competing Interest Statement CW, HB, AS, NL, EW, MR, and WM were employed by SYNLAB Holding Germany GmbH or its regional subsidiaries. AD is the owner of Company Dr. Dressel Consulting. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. ### Funding Statement The costs of the study were defrayed by SYNLAB Holding Deutschland GmbH. The management had no role in writing of the report or the decision to submit for publication. There was no financial support to SYNLAB Holding Deutschland GmbH from the manufacturers of the assays used in this evaluation and there has been no other financial support for this work that could have influenced its outcome. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was approved by Ethics Committee II (Mannheim) of the University of Heidelberg (reference number 2020-417MF) and the German Institute for Drugs and Medical Devices I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data will be made available to researchers upon justified request and formal agreement to make sure that rules of good scientific practice are obeyed, and that credit is given to the people who have been in charge of the design and the organization of the study. Interested researchers are invited to address their request or proposal to WM (winfried.maerz{at}synlab.com). The authors confirm that they accessed and validated these data and that all other researchers can access the data in the same manner the authors did.

The rise of the JN.1 variant

Nature - A study shows that US children who received mRNA COVID-19 vaccines have some protection against developing long-lasting symptoms of the coronavirus SARS-CoV-2.

Companies have been ignoring the enormous long Covid risk for too long. Now they're paying for it – literally. Implementing the Swiss cheese system could make them largely Covid-proof in no time. So what needs to be done?