Covid19-Sources

Jeremy Nicholson is a world-leader in understanding how disease interacts with people’s genetic make-up. But when he got long COVID, he had a whole new level of insight.

Published evidence indicates that Severe Acute Respiratory Syndrome-Corona Virus (SARS-CoV-2) infection causes endothelial cell (EC) injury in the Coronavirus Disease 2019 (COVID-19). Endothelial junctions (EJ) are crucial to maintain EC integrity and normal microvascular functions due to the adhesive properties of Vascular endothelial (VE)-cadherin to glue EC together. Here we report studies in vitro and in vivo that indicate VE-cadherin to be a target for cleavage by ACE2. We have identified that the extracellular domain of VE-cadherin contains these two amino acid sequences at the positions 256P-F257 and 321PMKP-325L for ACE2 substrate recognition. Incubation of purified sVE with ACE2 revealed a dose-dependent loss of immunoreactivity detected with an antibody directed against the Extracellular domain 1 (EC1) domain of sVE. We confirmed the presence of ACE2 on ECs using immunofluorescence studies, and by western blotting on ECs extracts. We also present evidence from patients with severe COVID-19 disease for a circulating form of ACE2. Its apparent molecular weight of 70 kDa is in agreement with a previously described extracellular form of ACE2 bearing the catalytic site of the ectopeptidase. Consistent with the experimental evidence for our hypothesis, the level of circulating soluble VE-cadherin fragments was increased in the blood of patients with severe COVID-19 disease. Further studies are needed to determine if increased circulating fragments of ACE2 and VE-cadherin may contribute to the future development of post-acute COVID-19 syndrome characterized by vascular endothelial injury, hypoxia, and inflammatory state. Impact Statement SARS-CoV-2 infection promotes vascular dysfunction but the processes are not completely understood. The vascular endothelium is composed of a monolayer of endothelial cells (ECs) that exclusively express VE-cadherin at adherens junctions (AJs). The published structure of VE-cadherin has revealed crucial residues in the domains EC1-2 for ECs adhesiveness. In this report, we demonstrate for the first time that VE-cadherin is a target for ACE2 ectoenzyme in the domains EC2-3. In addition, in COVID-19 patients’ blood, we identify truncated forms of ACE2 and VE-cadherin that are correlated with severe SARS-CoV-2 infection. Because the turnover rate of ECs is very low, this could provide part of the explanation for Long CoVID-19 disease. These exciting results highlight the role of proteases and AJs, and the need for continuing efforts to elucidate whether these circulating proteins might be of prime significance for clinicians to facilitate personalized medicine. ### Competing Interest Statement The authors have declared no competing interest.

Scientific Reports - Cognitive impairment in young adults with post COVID-19 syndrome

Stillbirth is a recognized complication of COVID-19 in pregnant women that has recently been demonstrated to be caused by SARS-CoV-2 infection of the placenta. Multiple global studies have found that the placental pathology present in cases of stillbirth consists of a combination of concurrent destructive findings that include increased fibrin deposition that typically reaches the level of massive perivillous fibrin deposition, chronic histiocytic intervillositis, and trophoblast necrosis. These 3 pathologic lesions, collectively termed SARS-CoV-2 placentitis, can cause severe and diffuse placental parenchymal destruction that can affect 75% of the placenta, effectively rendering it incapable of performing its function of oxygenating the fetus and leading to stillbirth and neonatal death via malperfusion and placental insufficiency. Placental infection and destruction can occur in the absence of demonstrable fetal infection. Development of SARS-CoV-2 placentitis is a complex process that may have both an infectious and immunologic basis. An important observation is that in all reported cases of SARS-CoV-2 placentitis causing stillbirth and neonatal death, the mothers were unvaccinated. SARS-CoV-2 placentitis is likely the result of an episode of SARS-CoV-2 viremia at some time during the pregnancy. This article discusses clinical and pathologic aspects of the relationship between maternal COVID-19 vaccination, SARS-CoV-2 placentitis, and perinatal death.

This cohort study describes trends in severe outcomes among patients hospitalized with COVID-19 from March 2020 to May 2022 in the Canadian Nosocomial Infection Surveillance Program.

Background and Objectives: Post-COVID condition (PCC) is common and often involves neuropsychiatric symptoms. This study aimed to use blood-oxygenation-level-dependent functional MRI (BOLD-fMRI) to assess whether participants with PCC had abnormal brain activation during working memory (WM), and whether the abnormal brain activation could predict cognitive performance, motor function or psychiatric symptoms. Methods: The PCC participants had documented COVID-19 at least 6 weeks prior to enrollment. Healthy control participants had no prior history of COVID-19 and negative tests for SARS-CoV-2. Participants were assessed using three NIH-Toolbox (NIHTB) batteries for Cognition (NIHTB-CB), Emotion (NIHTB-EB) and Motor function (NIHTB-MB), as well as selected tests from the Patient-Reported Outcomes Measurement Information System (PROMIS). Each had BOLD-fMRI at 3 Tesla, during WM (N-back) tasks with increasing attentional/WM load. Results: 169 participants were screened; 50 fulfilled the study criteria and had complete and usable datasets for this cross-sectional cohort study. 29 PCC participants were diagnosed with COVID-19 242±156 days earlier, had similar ages (42±12 vs. 41±12 years), gender proportion (65% vs. 57%), racial/ethnic distribution, handedness, education, and socioeconomic status, as the 21 uninfected healthy controls. Despite the high prevalence of memory (79%) and concentration (93%) complaints, the PCC group had similar and normal performance on the NIHTB-CB as the controls. However, PCC participants had greater brain activation than the controls across the network (p-FDR-corrected=0.003, T-max=4.17), with greater activation in the right superior frontal gyrus (p=0.009, Cohen’s- d =0.81, 95%CI [0.15-1.46]) but lesser deactivation in the default mode regions (p=0.001, d =1.03, 95%CI [0.61-1.99]). Compared to controls, PCC participants also had poorer dexterity and endurance on the NIHTB-MB, higher T-scores for negative affect and perceived stress, but lower T-scores for psychological well-being on the NIHTB-EB, as well as more pain symptoms and poorer mental and physical health on measures from PROMIS. Greater brain activation also predicted poorer scores on measures that were abnormal on the NIHTB-EB. Discussion: PCC participants with neuropsychiatric symptoms demonstrated compensatory neural processes with greater usage of alternate brain regions, and reorganized networks, to maintain normal performance during WM tasks. BOLD-fMRI was sensitive for detecting brain abnormalities that correlated with various quantitative neuropsychiatric symptoms.

SARS-CoV-2 Omicron variants emerged in 2022 with 30 novel amino acid mutations in the spike protein alone. While most studies focus on the impact of receptor binding domain changes, mutations in the C-terminal of S1 (CTS1), adjacent to the furin cleavage site, have largely been ignored. In this study, we examined three Omicron mutations in CTS1: H655Y, N679K, and P681H. Generating a SARS-CoV-2 triple mutant (YKH), we found that the mutant increased spike processing, consistent with prior reports for H655Y and P681H individually. Next, we generated a single N679K mutant, finding reduced viral replication in vitro and less disease in vivo . Mechanistically, the N679K mutant had reduced spike protein in purified virions compared to wild-type; spike protein decreases were further exacerbated in infected cell lysates. Importantly, exogenous spike expression also revealed that N679K reduced overall spike protein yield independent of infection. Together, the data show that N679K is a loss-of-function mutation reducing overall spike levels during omicron infection, which may have important implications for disease severity, immunity, and vaccine efficacy. One Sentence Summary Spike substitution N679K attenuates SARS-CoV-2 Omicron variants by decreasing spike protein and has potential implications for immunity and vaccine efficacy. ### Competing Interest Statement VDM has filed a patent on the reverse genetic system and reporter SARS-CoV-2. MNV and VDM have filed a provisional patent on a stabilized SARS-CoV-2 spike protein. Other authors declare no competing interests.

Nature Immunology - Phetsouphanh and colleagues show that individuals with long COVID have persistent activation of the innate and adaptive immune system at 8 months after infection and define a...

@JadeKhalife: Damage to the immune system has been an ongoing debate throughout this pandemic. Very few warned of this early on (& some abused!). But it was logical to avoid finding out (preventing infection). There...…

1/7 SARS-CoV-2 upregulates endogenous opioids& influences behaviorIt upregulates OPRPN, which encodes opiorphinOpiorphin?https://t.co/8fxVdYGobX* painkilling effect greater than morphine* anti-depressant* shown to be antipanic agent (panicolytic)https://t.co/4StXu0lBMT— 🔴 tohmes (@tohmes1) March 31, 2023

Human-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) interaction can have an array of various outcomes-it could be mortal, morbid or merely carrying minor health consequences. The very rapid global spread has raised the issue whether there are further multi-dimensional consequences of …

Alterations in brain functioning, especially in regions associated with cognition, can result from infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and are predicted to result in various psychiatric diseases. Recent studies have shown that SARS-CoV-2 infection and coronavi …

Acute COVID-19 infection is followed by prolonged symptoms in approximately one in ten cases: known as Long COVID. The disease affects ~65 million ind…

COV-BOOST is a multicentre, randomised, controlled, phase 2 trial of seven COVID-19 vaccines used as a third booster dose in June 2021. Monovalent mes…

Background: Post-acute sequelae of COVID, termed “Long COVID”, is an emerging chronic illness potentially affecting ~10% of those with COVID-19. We so

We assessed effectiveness of the BNT162b2 vaccine against infection with the B.1.1.529 (Omicron) variant (mostly BA.1 subvariant), among children 5-11 years of age in Israel. Using a matched case-control design, we matched SARS-CoV-2-positive children (cases) and SARS-CoV-2-negative children (contro …

Bay-VOC - SARS-CoV-2 (Corona) Abwassermonitoring in Bayern

Purpose The recent coronavirus disease (COVID-19) pandemic mainly affects the respiratory system; however, several oral and maxillofacial post-COVID-19 complications have also been observed. This series reports the growing number of osteonecrosis cases associated with post-COVID-19 patients. Materials and methods This is a retrospective, multi-center case series that reports cases with maxillary osteonecrosis after various periods of SARS-CoV-2 infection in the period between January and August 2021 based on the PROCESS guidelines. Results Twelve cases were reported with post-COVID-19 manifestation of spontaneous osteonecrosis of the maxillary jaw. Five patients were hospitalized during COVID-19 management and all of the twelve cases had at least one systematic Co-morbidity, and undertake corticosteroids prescription based on the COVID-19 disease treatment protocol. The mean onset of osteonecrosis symptoms appearance was 5.5 ± 2.43 weeks calculated from the day of the negative PCR test. The management was successfully done through surgical debridement and pre and post-operative antibiotics. No anti-fungal medications were prescribed as the fungal culture and the histopathological report were negative. Conclusion Post-COVID-related osteonecrosis of the jaw (PC-RONJ) could be now considered as one of the potential post-COVID-19 oral and maxillofacial complications that occurs unprovokedly and mainly in the maxilla.

To investigate the relationship between avascular osteonecrosis (AVN) and corticosteroid treatment given to patients with severe acute respiratory syndrome (SARS). Methods Longitudinal study of 71 former SARS patients (mainly health care workers) who had been treated with corticosteroids, with an observation time of 36 months. Magnetic resonance images (MRI) and X-rays of hips, knees, shoulders, ankles and wrists were taken as part of the post-SARS follow-up assessments. Results Thirty-nine per cent developed AVN of the hips within 3–4 months after starting treatment. Two more cases of hip necrosis were seen after 1 year and another 11 cases of AVN were diagnosed after 3 years, one with hip necrosis and 10 with necrosis in other joints. In total, 58% of the cohort had developed AVN after 3 years of observation. The sole factor explaining AVN in the hip was the total dose of corticosteroids received. Conclusion The use of corticosteroids in SARS has been debated; opinions conflict about whether the immediate benefits in terms of saving lives compensate for the adverse effects, including AVN.

Persistence of symptoms beyond the initial acute phase of coronavirus disease-2019 (COVID-19) is termed post-acute SARS-CoV-2 (PASC) and includes neurological, autonomic, pulmonary, cardiac, psychiatric, gastrointestinal, and functional impairment. PASC autonomic dysfunction can present with dizziness, tachycardia, sweating, headache, syncope, labile blood pressure, exercise intolerance and “brain fog.” A multidisciplinary team can help manage this complex syndrome with non-pharmacologic and pharmacologic interventions.

The clinical and laboratory findings in four cases of acute renal failure following the onset of influenza A viral infection (Port Chalmers/1/73) are presented. Although the pathophysiologic mechanisms affecting the kidney in these cases varied, the ensuing renal failure in each patient was severe. …

BackgroundAs face masks became mandatory in most countries during the COVID-19 pandemic, adverse effects require substantiated investigation.MethodsA systematic review of 2,168 studies on adverse medical mask effects yielded 54 publications for synthesis and 37 studies for meta-analysis (on n = 8,641, m = 2,482, f = 6,159, age = 34.8 ± 12.5). The median trial duration was only 18 min (IQR = 50) for our comprehensive evaluation of mask induced physio-metabolic and clinical outcomes.ResultsWe found significant effects in both medical surgical and N95 masks, with a greater impact of the second. These effects included decreased SpO2 (overall Standard Mean Difference, SMD = −0.24, 95% CI = −0.38 to −0.11, p 0.001) and minute ventilation (SMD = −0.72, 95% CI = −0.99 to −0.46, p 0.001), simultaneous increased in blood-CO2 (SMD = +0.64, 95% CI = 0.31–0.96, p 0.001), heart rate (N95: SMD = +0.22, 95% CI = 0.03–0.41, p = 0.02), systolic blood pressure (surgical: SMD = +0.21, 95% CI = 0.03–0.39, p = 0.02), skin temperature (overall SMD = +0.80 95% CI = 0.23–1.38, p = 0.006) and humidity (SMD +2.24, 95% CI = 1.32–3.17, p 0.001). Effects on exertion (overall SMD = +0.9, surgical = +0.63, N95 = +1.19), discomfort (SMD = +1.16), dyspnoea (SMD = +1.46), heat (SMD = +0.70), and humidity (SMD = +0.9) were significant in n = 373 with a robust relationship to mask wearing (p 0.006 to p 0.001). Pooled symptom prevalence (n = 8,128) was significant for: headache (62%, p 0.001), ac...

On September 1, 2022, the Moderna and Pfizer–BioNTech bivalent vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) containing equal amounts of spike messenger RNA from the ancestral and omicron BA.4–BA.5 subvariants replaced their monovalent counterparts as booster doses for persons who are 12 years of age or older in the United States. We previously reported surveillance data from North Carolina on the effectiveness of these two bivalent boosters against coronavirus disease 2019 (Covid-19) during the first 3 months after deployment (September 1 to December 8, 2022); the BA.4–BA.5 subvariants were predominant during the first 2.5 months of this period.1 Here, we present two additional months of data that were obtained during a period when the omicron BQ.1–BQ.1.1 and XBB–XBB.1.5 subvariants had become predominant to show the durability of protection conferred by these two bivalent boosters against a wider range of clinical outcomes than were included in our previous report.

Long COVID patients who experienced severe acute SARS-CoV-2 infection can present with humoral autoimmunity. However, whether mild SARS-CoV-2 infection provokes autoantibody responses and whether vaccination can decrease these responses in long COVID patients is unknown. Here, we demonstrate that mild SARS-CoV-2 infection increases autoantibodies associated with systemic lupus erythematosus (SLE) and inflammatory myopathies in long COVID patients with persistent neurologic symptoms to a greater extent than convalescent controls at more than 8 months post-infection. Furthermore, high titers of SLE-associated autoantibodies in long COVID patients are associated with impaired cognitive performance and greater symptom severity, and subsequent vaccination does not decrease autoantibody titers. In summary, we found that mild SARS-CoV-2 infection can induce long-term humoral autoimmunity in both long COVID patients and healthy COVID convalescents, suggesting that a reappraisal of vaccination and mitigation strategies is warranted. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement L.V. is supported by grant B48 from the philanthropic COVID research fund through Balvi Ops. P.P.M is supported by grants from the National Institute on Drug Abuse (NIDA, DP2DA051912) and from the National Institute of Biomedical Imaging and Bioengineering (NIBIB, U54EB027049). I.K. is supported by a grant from the National Institute of Aging (NIA, R01AG059291). ### 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: This study was approved by the Northwestern University Institutional Review Board, protocol number STU00212583. 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 The full datasets generated in the current study are available from the corresponding author upon requests.

Nature - A self-taught Indiana man is among a cadre of community scientists who scour the SARS-CoV-2 genome for problematic mutations.

Prior to vaccine availability, indoor mask mandates were associated with lower SARS-CoV-2 cases during the 12 weeks following policy adoption in high-, critical

Introduction: Post-COVID-19 syndrome (PCS) is characterized by a wide range of symptoms, predominantly fatigue and exertional intolerance. While disease courses during the first year post infection have been repeatedly described, little is known about long-term health consequences. Methods: We assessed symptom severity and various biomarkers at three time points post infection (3-8 months (mo), 9-16mo, 17-20mo) in 106 PCS patients with moderate to severe fatigue and exertional intolerance. A subset of patients fulfilled diagnostic criteria of myalgic encephalomyelitis/chronic fatigue syndrome (PCS-ME/CFS) based on the Canadian Consensus Criteria. Results: While PCS-ME/CFS patients showed persisting symptom severity and disability up to 20mo post infection, PCS patients reported an overall health improvement. Inflammatory biomarkers equally decreased in both groups. Lower hand grip force at onset correlated with symptom persistence especially in PCS-ME/CFS. Discussion: Debilitating PCS may persist beyond 20mo post infection, particularly in patients fulfilling diagnostic criteria for ME/CFS. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work is supported by a grant from the Weidenhammer-Zoebele Foundation. The work of F. K. was supported by the Volkswagen Foundation. ### 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: Ethics committee of Charite in accordance with the 1964 Declaration of Helsinki and its later amendments (EA2/006/20) gave ethical approval for this work 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 data produced in the present study are available upon reasonable request to the authors

Here are our diagrams as can be seen in the paper. pic.twitter.com/9vnu4LGgPS— Resia Pretorius (@resiapretorius) April 19, 2023

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Long covid follows 10-20% of first-time SARS-CoV-2 infections, but the societal burden of long covid and risk factors for the condition are not well-understood. Here, we report findings about self-reported sick leave and risk factors thereof from a hybrid survey and register study, which included 37,482 RT- PCR confirmed SARS-CoV-2 cases and 51,336 test-negative controls who were tested during the index and alpha waves. An additional 33 individuals per 1000 took substantial sick leave following acute infection compared to persons with no known history of infection, where substantial sick leave was defined as 1 month of sick leave within the period 1-9 months after the RT-PCR test date. Being female, ≥50 years, and having certain pre-existing conditions such as fibromyalgia increased risks for taking substantial sick leave. Further research exploring this heterogeneity is urgently needed and may provide important evidence for more targeted preventative strategies. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement No specific funding was received for this work. The study was conducted as part of the advisory tasks of the governmental institution Statens Serum Institut for the Danish Ministry of Health. ### 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: Ethics approval This study was performed as a surveillance study as part of the advisory tasks conducted by the governmental institution Statens Serum Institut (SSI) for the Danish Ministry of Health. The purpose of Statens Serum institut is to monitor and fight the spread of disease in accordance with section 222 of the Danish Health Act. According to Danish law, national surveillance activities carried out by SSI do not require approval from an ethics committee. Participation in the study was voluntary. The invitation letter to participants contained information about their rights under the Danish General Data Protection Regulation (rights to access data, rectification, deletion, restriction of processing and objection). After reading this information, it was considered informed consent if participants agreed and clicked on the link to fill in the questionnaires. 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 The datasets used in this study comprise sensitive, individual-level information from completed questionnaires and national register data. According to the Danish data protection legislation, the authors are not permitted to share these sensitive data directly upon request. However, the data are available for research purposes upon request to the Danish Health Authority (register data, email: kontakt@sundhedsdata.dk) and Statens Serum Institut (questionnaire data, email: aii@ssi.dk), as well as within the framework of the Danish data protection legislation and any required permission from authorities. Data request processing can take an expected three to six months.