Distinct COVID-19 vaccine combinations result in divergent immune responses (preprint)

Waning antibody responses after COVID-19 vaccination combined with the emergence of the SARS-CoV-2 Omicron lineage led to reduced vaccine effectiveness. As a countermeasure, bivalent mRNA-based booster vaccines encoding the ancestral spike protein in combination with that of Omicron BA.1 or BA.5 were introduced. Since then, BA.2-descendent lineages have become dominant, such as XBB.1.5 or BA.2.86. Here, we assessed how different COVID-19 priming regimens affect the immunogenicity of the recently used bivalent booster vaccinations and breakthrough infections. BA.1 and BA.5 bivalent vaccines boosted neutralizing antibodies and T-cells up to 3 months after boost; however, cross-neutralization of XBB.1.5 was poor. Interestingly, different combinations of prime-boost regimens induced divergent responses: participants primed with Ad26.COV2.S developed lower binding antibody levels after bivalent boost while neutralization and T-cell responses were similar to mRNA-based primed participants. In contrast, the breadth of neutralization was higher in mRNA-primed and bivalent BA.5 boosted participants. Combined, we highlight important "lessons learned" from the employed COVID-19 vaccination strategies. Our data further support the use of monovalent vaccines based on circulating strains when vaccinating risk groups, as recently recommended by the WHO. We emphasize the importance of the continuous assessment of immune responses targeting circulating variants to guide future COVID-19 vaccination policies.

Current understanding of the airborne transmission of important viral animal pathogens in spreading disease

Current research on airborne transmission of African swine fever virus (ASFV), porcine epidemic diarrhoea virus (PEDV), avian influenza (AIV), porcine reproductive and respiratory syndrome virus (PRRSV), and foot and mouth disease virus (FMDV) was reviewed to evaluate commonalities, knowledge gaps, and methodologies of studying airborne transmission of animal diseases. The reviewed studies were categorised as short-range transmission (within a single facility) and long-range transmission (beyond a single site). Short-range airborne transmission was demonstrated for at least one strain of the above-mentioned pathogens in experimental settings. Most studies reported in the literature concern FMDV, with limited information for ASFV and PEDV, particularly for short-range airborne transmission. Air sampling upwind, downwind, and within infected facilities has been commonly used to demonstrate long-range airborne transmission. The amount of evidence from air sampling for each of the reviewed viruses varies from no evidence on ASFV to evidence from multiple settings for AIV. Computer modelling has been used to study past outbreaks of infectious diseases to assess the contribution of airborne transmission with a multitude of computer models reported in the literature for simulating long-range airborne transmission of FMDV based on past outbreaks. This has resulted in predictive tools for assessing future risk of airborne transmission. Some important computer models are based on epidemiology analysis, weather analysis, and air dispersion. Few models are reported for ASFV, PEDV, and PRRSV. Studies in the literature indicate that airborne transmission is generally affected by virus strain, aerosol type, shedding duration and concentration, environmental conditions, and infectious dose.

Food festival research review in contemporary tourism

Purpose: Food festivals are prevalent for those passionate about food experience globally. More importantly, feedback from food reviewers on mass media platforms has been becoming a critical factor in facilitating the decision-making process of tourists in particular cities. Moreover, stimulating local tourism activities, thanks to food festivals, prove advantageous to the well-being of local habitants. The purpose of this paper is to provide readers with a general overview of food festival research trends in tourist cities, as tourism has the potential to contribute to targets in Goals 8, 12 and 14 on sustainable consumption and production and the sustainable use of resources, respectively, (UNWTO: World Tourism Organization). Design/methodology/approach: This study searched and filtered documents from the Scopus and Web of Science databases, as well as used bibliometric analysis and other mathematical and statistical methods, to better understand the food festival research context between 1970 and 2021. The carriers with mathematical and statistical methods. VOSviewer algorithm was used to identify critical input for visualizing bibliometric networks and to create a framework for this academic food festival research. Findings: The findings are primarily related to pre and post-COVID-19 research on food festivals worldwide. Furthermore, using an inductive approach, this paper reveals the impact of food festivals in cities and tourist behaviors. According to the findings, the food festival research trends are about “food festivals,” “slow food festivals” and “local food festivals.” Factor analysis is one of the most common analyses in this type of research. Other studies could use the findings and limitations to select appropriate themes and analysis approaches for their research topics. Research limitations/implications: Research data sets are mainly from articles that may not account for all actual trends during this pandemic. Originality/value: This review expects to provide insights into food festivals and help future researchers to recognize several research gaps such as the lack of research on food festival manufacturers and producers or the consistency in visitors' aspect research of quality service, visitors' loyal intentions, satisfaction and culinary experience. The tourism industry can find research trends of food festivals and issues following COVID-19 to find their management styles to fit the context of the post-COVID-19 pandemic, facilitating organizing a safe and effective food festival. © 2022, International Tourism Studies Association.

Main changes in the “covid-19 in paediatrics” clinical practice guideline Principales modificaciones en la guía de práctica clínica “covid-19 en pediatría”

We present a summary of the main modifications to the “COVID-19 in Paediatrics” clinical practice guideline made from its initial version, published in 2021, and the version published in 2022. The document was developed following the structured steps of evidence-based medicine and applying the GRADE system to synthesize the evidence, assess its quality and, when appropriate, issue graded recommendations (based on the quality of the evidence, values and preferences, the balance between benefits, risks and costs, equity and feasibility). This update also includes the modifications proposed by external reviewers. We summarised the main modifications in the following sections: epidemiology, clinical features, diagnosis, prevention, treatment and vaccines. In relation to the body of knowledge achieved in the first year of the pandemic, the literature published in the second year contributed additional data, but without substantial modifications in many the areas. The main changes took place in the field of vaccine research. This update was completed in December 2021, coinciding with the emergence of infections by the omicron variant, so the document will need to be updated in the future.

PRINCIPALES MODIFICACIONES EN LA GUÍA DE PRÁCTICA CLÍNICA “COVID-19 EN PEDIATRÍA” MAIN CHANGES IN THE “COVID-19 IN PAEDIATRICS” CLINICAL PRACTICE GUIDELINE

Presentamos el resumen de las principales modificaciones surgidas en la guía de práctica clínica “COVID-19 en Pediatría” entre su versión inicial publicada en el año 2021 y la publicada en el año 2022. El documento se ha elaborado siguiendo los pasos estructurados de la Medicina basada en la evidencia e incorporando el sistema GRADE para realizar síntesis de la evidencia, con valoración de su calidad y, cuando se consideró apropiado, emitir recomendaciones jerarquizadas (en función de la calidad de la evidencia, los valores y preferencias, el balance entre beneficios, riesgos y costes, la equidad y la factibilidad). En esta actualización se incluyen también los cambios recomendados por los revisores externos. Se sintetizan las principales modificaciones en los siguientes apartados: epidemiología, clínica, diagnóstico, prevención, tratamiento y vacunas. En el conjunto del conocimiento alcanzado a lo largo del primer año de pandemia, las publicaciones durante el segundo año añaden nuevos datos, sin que en muchas de las áreas se produzcan modificaciones sustanciales. Los principales cambios acaecen en el campo de investigación de las vacunas. Esta actualización finaliza en diciembre de 2021, coincidiendo con el aumento de la infección por ómicron, por lo que será necesario una futura actualización del documento.

Divergent SARS CoV-2 Omicron-specific T- and B-cell responses in COVID-19 vaccine recipients (preprint)

The severe acute respiratory distress syndrome coronavirus-2 (SARS-CoV-2) Omicron variant (B.1.1.529) is spreading rapidly, even in vaccinated individuals, raising concerns about immune escape. Here, we studied neutralizing antibodies and T-cell responses to SARS-CoV-2 D614G (wildtype, WT), and the B.1.351 (Beta), B.1.617.2 (Delta), and B.1.1.529 (Omicron) variants of concern (VOC) in a cohort of 60 health care workers (HCW) after immunization with ChAdOx-1 S, Ad26.COV2.S, mRNA-1273 or BNT162b2. High binding antibody levels against WT SARS-CoV-2 spike (S) were detected 28 days after vaccination with both mRNA vaccines (mRNA-1273 or BNT162b2), which significantly decreased after 6 months. In contrast, antibody levels were lower after Ad26.COV2.S vaccination but did not wane. Neutralization assays with authentic virus showed consistent cross-neutralization of the Beta and Delta variants in study participants, but Omicron-specific responses were significantly lower or absent (up to a 34-fold decrease compared to D614G). Notably, BNT162b2 booster vaccination after either two mRNA-1273 immunizations or Ad26.COV.2 priming partially restored neutralization of the Omicron variant, but responses were still up to-17-fold decreased compared to D614G. CD4+ T-cell responses were detected up to 6 months after all vaccination regimens; S-specific T-cell responses were highest after mRNA-1273 vaccination. No significant differences were detected between D614G- and variant-specific T-cell responses, including Omicron, indicating minimal escape at the T-cell level. This study shows that vaccinated individuals retain T-cell immunity to the SARS-CoV-2 Omicron variant, potentially balancing the lack of neutralizing antibodies in preventing or limiting severe COVID-19. Booster vaccinations may be needed to further restore Omicron cross-neutralization by antibodies.

Thyroid as a target of adjuvant autoimmunity/inflammatory syndrome due to mRNA-based SARS-CoV2 vaccination: from Graves' disease to silent thyroiditis.

BACKGROUND: As COVID-19 became a pandemic, the urgent need to find an effective treatment vaccine has been a major objective. Vaccines contain adjuvants which are not exempt from adverse effects and can trigger the autoimmune/inflammatory syndrome induced by adjuvants (ASIA). There is very little information about autoimmune endocrine disease and the ASIA after the use of mRNA-based SARS-CoV2 vaccination. CASE SERIES: We report three cases and also review the literature showing that the thyroid gland can be involved in the ASIA induced by the mRNA-based SARS-CoV2 vaccination. We present the first case to date of silent thyroiditis described in the context of SARS-CoV2 vaccination with Pfizer/BioNTech. Also, we discuss the first subacute thyroiditis in the context of SARS-CoV2 vaccination with the Moderna's vaccine. Finally, we provide another case to be added to existing evidence on Graves' disease occurring post-vaccination with the Pfizer/BioNTech vaccine. DISCUSSION: Adjuvants play an important role in vaccines. Their ability to increase the immunogenicity of the active ingredient is necessary to achieve the desired immune response. Both the Moderna and the Pfizer/BioNTech vaccines use mRNA coding for the SARS-CoV2 S protein enhanced by adjuvants. In addition, the cross-reactivity between SARS-CoV2 and thyroid antigens has been reported. This would explain, at least, some of the autoimmune/inflammatory reactions produced during and after SARS-CoV2 infection and vaccination. CONCLUSION: The autoimmune/inflammatory syndrome induced by adjuvants involving the thyroid could be an adverse effect of SARS-CoV2 vaccination and could be underdiagnosed.

Volume balance and AKI in critically ill patients with SARS-CoV-2

Background: Evidence from the management of critically ill patients suggests restrictive volume management strategies and avoidance of volume overload improve ICU outcomes. Restrictive practices have been applied to the management of patients with SARS-CoV-2 (COVID-19), but data describing volume management and its associated outcomes in those with and without acute kidney injury (AKI) in this setting are lacking. Methods: We conducted a single-center retrospective cohort study of ICU patients with COVID-19. 7-day cumulative volume balance from ICU admission in excess of -5% (negative balance) or +5% (positive balance) of ICU admission weight as well as AKI based on KDIGO guidelines were identified. Associations between volume balance, AKI and clinical outcomes (dialysis, mechanical ventilation, and inpatient mortality) were explored. Results: 194 of 374 ICU admissions (51.9%) had AKI with 60 of 374 (194) (16.0%, 30.9% of those with AKI) requiring dialysis. 110 of 374 (29.4%) developed negative balance and 40 of 374 (10.7%) developed positive balance. Inpatient mortality was higher in those with AKI and negative balance (28%) and positive balance (35%) compared to those with neutral balance (16%) (p=0.039). Of the subjects with negative balance (Table), despite no difference in their net volume balance, inpatient mortality was significantly higher in those with AKI compared to those without AKI (p=0.048). Using the Kaplan-Meier estimator, patients with no AKI had no difference in inpatient survival when compared on the basis of volume balance (p=0.69). However, in those with AKI, inpatient survival was significantly lower for positive and negative volume balance compared to neutral balance (p=0.01). Conclusions: Negative and positive volume balance are associated with higher inpatient mortality particularly in patients with AKI. Future research must investigate the impact of negative balance on morbidity and mortality in patients with and without AKI.

Neutrophils and secondary infections in COVID-19 induced acute respiratory distress syndrome.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus is the cause of the current global pandemic and has affected more than 188 countries worldwide. Infection by the virus can have diverse clinical manifestations, with one of the most severe clinical manifestation being respiratory failure and the development of acute respiratory distress syndrome. Clinical manifestations of acute respiratory distress syndrome secondary to SARS-CoV-2 are also diverse with a lack of diagnostic tools to distinguish between primary viral infection and secondary bacterial infections. This was a single-centre, retrospective case-control study of bronchoalveolar lavage fluid cell counts, flow cytometry and culture results from mechanically ventilated patients with SARS-CoV-2 (COVID-19) pneumonia and acute respiratory distress syndrome. Neutrophils were the predominant cell type in bronchoalveolar fluid samples up to 2 weeks into mechanical ventilation. There also was a strong correlation between positive respiratory cultures and significant elevation in bronchoalveolar fluid neutrophil counts/percentages and serum C-reactive protein levels. Absolute levels of T cell subtypes correlated with reduced lung compliance measurements. Patients with SARS-CoV-2 and severe respiratory disease are at risk for secondary infections. In some COVID-19 patients, serum C-reactive protein and bronchoalveolar fluid neutrophils may be correlated with a secondary infection.

Percutaneous tracheostomy in COVID patients. Experience in our hospital center after one year of pandemic and review of the literature.

BACKGROUND: The pandemic caused by SARS-COV-2 has caused an increase in the need of tracheostomies in patients affected with respiratory distress syndrome. In this article we report our experience during a year of pandemic, we develop our surgical technique to perform percutaneous tracheostomy with the patient in apnea and we compare our results with those of other centers through a bibliographic review. MATERIAL AND METHODS: A one-year retrospective clinical study was carried out on tracheotomies performed on patients admitted to the intensive care unit with severe SARS-CoV-2, with difficulty for ventilation or weaning. The technique performed was percutaneous, with fibroscopic control through the endotracheal tube, keeping the patient under apnea during the opening of the airway, reducing by this method the risk of exposure to the virus. RESULTS: From 35 percutaneous tracheotomies performed, 31% of the patients died from respiratory complications due to SARS-COV-2, but none due to the surgical procedure. The most frequent complication (8.5% of patients) was bleeding around the tracheostoma, resolved with local measures. No healthcare provider involved in the performance of the technique had symptoms or was diagnosed with COVID-19. CONCLUSIONS: Our technique of performing percutaneous tracheostomy maintaining apnea during the procedure, under fibroscopic control, has proven to be safe for all those involved in the procedure, and for the patient.

[COVID-19: critical appraisal of the evidence]

We present the summary of a critical appraisal document of the available evidence on COVID-19, developed with a clinical practice guide format following GRADE methodology. The document tries to provide answers to a series of structured clinical questions, with an explicit definition of the population, intervention / exposure, comparison and outcome, and a rating of the clinical relevance of the outcome measures. We conducted a systematic review of the literature to answer the questions, grouped into six chapters: epidemiology, clinical practice, diagnosis, treatment, prevention, and vaccination. We assessed the risk of bias of the selected studies with standard instruments (RoB-2, ROBINS-I, QUADAS and Newcastle-Ottawa). We constructed evidence tables and, when necessary and possible, meta-analysis of the of the most relevant outcome measures. We followed the GRADE system to synthesize the evidence, assessing its quality, and, when appropriate, giving recommendations, rated according to the quality of the evidence, the values and preferences, the balance between benefits, risks and costs, equity and feasibility.

Prone positioning in acute respiratory distress syndrome at late pregnancy

INTRODUCTION: The high incidence of acute respiratory distress syndrome (ARDS) in coronavirus-19 (COVID-19) has highlighted the use of prone positioning and brought this maneuver to national attention. Clinical trials have demonstrated mortality benefits of early prone positioning for patients with ARDS. However, pregnant women have been excluded in these trials. We report a case of a young woman in her third trimester of gestation admitted for ARDS due to COVID-19 pneumonia and highlight the physiologic and logistical considerations involved in prone positioning in late pregnancy. METHODS: A 31-year-old Hispanic G3P2002 27 weeks, 5 day presented for 1 week duration of flu-like symptoms secondary to COVID 19. She was admitted to intensive care unit with tachypnea, tachycardia, and Spo2 84% on 4L NC oxygen. Upon admission, she was started on remdesivir, dexamethasone, and venous thromboembolism prophylaxis. Within 24 hours of admission, she experienced rapidly worsening hypoxia requiring hi-flo nasal cannula (HFNC) 70% FiO2, 60 LPM. A multidisciplinary team of ICU, OB/ GYN, and respiratory therapists devised a plan to prone the patient to prevent intubation. She was assisted with proning by 3 nurses, one of which was a L&D nurse and supported by padding, pillows and blankets to support her gravid uterus. Patient was proned for at least 8 hours a day. There was significant improvement in clinical signs and symptoms within 72 hours of initiation of proning. After 10 days, she had improvement in oxygenation down to 3L nasal cannula. RESULTS: We successfully avoided intubation in a third trimester pregnant woman with severe hypoxemia with ARDS from COVID-19 by initiating early proning. This case demonstrates pregnancy is not a contraindication in prone positioning in an awake patient however great consideration must be given to prevent skin breakdown, pressure ulcers, dislodgment of fetal monitoring, and compression of the gravid uterus. Prone positioning is technically difficult particularly in late pregnancy (beyond 24-28 weeks) due to the risk of aortocaval compression but has shown to be safe with a multidisciplinary effort including maternal-fetal medicine, anesthesia, and critical care teams.

Peginterferon-Lambda for the Treatment of COVID-19 in Outpatients (preprint)

Background: There are currently no effective treatments for outpatients with coronavirus disease. 2019 (COVID-19). Interferon-lambda-1 is a Type III interferon involved in the innate antiviral response with activity against respiratory pathogens.Methods: In this double-blind, placebo-controlled trial, outpatients with laboratory-confirmed COVID-19 were randomized to a single subcutaneous injection of peginterferon-lambda 180μg or placebo within 7 days of symptom onset or first positive swab if asymptomatic. The primary endpoint was proportion negative for SARS-CoV-2 RNA on Day 7 post-injection.Results: There were 30 patients per arm, with median baseline SARS-CoV-2 viral load of 6.71 (IQR 1.3-8.0) log copies/mL. The decline in SARS-CoV-2 RNA was greater in those treated with peginterferon-lambda than placebo (p=0.04). On Day 7, 24 participants (80%) in the peginterferon-lambda group had an undetectable viral load compared to 19 (63%) in the placebo arm (p=0.15). After controlling for baseline viral load, peginterferon-lambda treatment resulted in a 4.12-fold (95CI 1.15-16.7, p=0.029) higher likelihood of viral clearance by Day 7. Of those with baseline viral load above 10E6 copies/mL, 15/19 (79%) in the peginterferon-lambda group were undetectable on Day 7 compared to 6/16 (38%) in the placebo group (p=0.012). Adverse events were similar between groups with only mild reversible transaminase elevations more frequently observed in the peginterferon-lambda group.Conclusion: Peginterferon-lambda accelerated viral decline in outpatients with COVID-19 resulting in a greater proportion with viral clearance by Day 7, particularly in those with high baseline viral load. Peginterferon-lambda may have potential to prevent clinical deterioration and shorten duration of viral shedding.Trial Registration: NCT04354259Funding Statement: This study was supported by the Toronto COVID-19 Action Initiative, University of Toronto and the Ontario First COVID-19 Rapid Research Fund. Medication was supplied by Eiger BioPharma. Declaration of Interests: JJF reports research support unrelated to this work from Eiger BioPharmaceuticals. BC has received research support unrelated to this work from Nubiyota LLC and Sanofi. IC and CH are employees of Eiger BioPharmaceuticals. JSG is a board member and founder of Eiger BioPharmaceuticals, Inc., in which he has an equity interest, and is an inventor on a patent application for the use of interferon lambda to treat coronavirus infections. All other authors have nothing to declare. Ethics Approval Statement: The Research Ethics Boards of all participating institutions approved the study, which was conducted under a Clinical Trial Application approved by Health Canada.

Making the case for strong health information systems during a pandemic and beyond (preprint)

Background: The Sars-CoV-2 pandemic exacerbates existing inequalities across health care systems globally, both within countries and between countries. It also highlights, like no other crisis before, existing weaknesses in health information systems (HIS). This article summarizes these key challenges for HIS in times of a pandemic and beyond, with a focus on European countries. It builds on the experiences of a large consortium representing HIS experts in key positions in national public health or similar institutes across Europe.Methods: Data were collected in bi-weekly conference calls organized by the InfAct project between February and June 2020. Emerging themes were clustered and analysed around a WHO framework for health information systems (HIS). We analyse strengths of HIS at two levels: (i) dealing with health information directly, and (ii) dealing with other parts of information systems that allow for a holistic assessment of the pandemic (including health-related aspects). Results: The analysis highlights the need for capacity-building in HIS before a pandemic hits, the relevance of going beyond health information only related to health care but taking a broader perspective (e.g. on vulnerable groups), the need for strong reporting systems on staffing numbers and in primary care. Further, data linkage emerges as a crucial precondition to identify unmet needs for essential health care services in a timely manner. Finally, room for innovation and digitalisation is key to be able to react flexibly in times of crisis. Trust for health information stakeholders is another important factor to create strong HIS.Conclusions: The strengths and shortcomings of European HIS that have been observed during the COVID-19 crisis highlight the need for strong HIS beyond the crisis. The experiences reported leave as a central message that successful reactions to the pandemic are (also) grounded in strong HIS that ultimately not only benefit the health of the population but also create a number of economic and psycho-social benefits. Strong data reporting schemes may also support fine-tuning of containment measures during a pandemic as well as transition phases.

Novel SARS-CoV-2 Whole-genome sequencing technique using Reverse Complement PCR enables fast and accurate outbreak analysis (preprint)

Current transmission rates of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are still increasing and many countries are facing second waves of infections. Rapid SARS-CoV-2 whole genome sequencing (WGS) is often unavailable but could support public health organizations and hospitals in monitoring and determining transmission links. Here we report a novel reverse complement polymerase chain reaction (RC-PCR) technology for WGS of SARS-CoV-2. This technique is unique as it enables library preparation in a single PCR saving time, resources and enables high throughput screening. A total of 173 samples tested positive for SARS-CoV-2 between March and September 2020 were included. RC-PCR WGS applicability for outbreak analysis in public health service and hospital settings was tested on six predefined clusters containing samples of healthcare workers and patients. RC-PCR resulted in WGS data for 146 samples. It showed a genome coverage of up to 98,2% for samples with a maximum Ct value of 32. Three out of six suspected clusters were fully confirmed, while in other clusters four healthcare workers were not associated. Importantly, a previously unknown chain of transmission was confirmed in the public health service samples. These findings confirm the reliability and applicability of the RC-PCR technology for SARS-CoV-2 sequencing in outbreak analysis and surveillance.

Shedding of infectious virus in hospitalized patients with coronavirus disease-2019 (COVID-19): duration and key determinants (preprint)

BackgroundLong-term shedding of viral RNA in COVID-19 prevents timely discharge from the hospital or de-escalation of infection prevention and control practices. Key questions are the duration and determinants of infectious virus shedding. We assessed these questions using virus cultures of respiratory tract samples from hospitalized COVID-19 patients as a proxy for infectious virus shedding. MethodsClinical and virological data were obtained from 129 hospitalized COVID-19 patients (89 intensive care, 40 medium care). Generalized estimating equations were used to identify if viral RNA load, detection of viral subgenomic RNA, serum neutralizing antibody response, duration of symptoms, or immunocompromised status were predictive for a positive virus culture. FindingsInfectious virus shedding was detected in 23 of the 129 patients (17,8%). The median duration of shedding was 8 days post onset of symptoms (IQR 5 - 11) and the probability of detecting infectious virus dropped below 5% after 15,2 days post onset of symptoms (95% confidence interval (CI) 13,4 - 17,2). Multivariate analyses identified viral loads above 7 log10 RNA copies/mL (odds ratio [OR]; CI 14,7 (3,57-58,1; p<0,001) as independently associated with isolation of infectious SARS-CoV-2 from the respiratory tract. A serum neutralizing antibody titre of at least 1:20 (OR of 0,01 (CI 0,003-0,08; p<0,001) was independently associated with non-infectious SARS-CoV-2. InterpretationInfection prevention and control guidelines should take into account that patients with severe or critical COVID-19 may shed infectious virus for longer periods of time compared to what has been reported for in patients with mild COVID-19. Infectious virus shedding drops to undetectable levels below a viral RNA load threshold and once serum neutralizing antibodies are present, which warrants the use of quantitative viral RNA load assays and serological assays in test-based strategies to discontinue or de-escalate infection prevention and control precautions. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSWe searched PubMed, bioRxiv, and medRxiv for articles that reported on shedding of infectious virus in COVID-19 patients using the search terms ("coronavirus" OR "SARS" OR "SARS-CoV-2" OR "COVID-19") AND ("shedding" OR "infectivity" OR "infectious" OR "virus culture") with no language or time restrictions. A detailed study on nine patients with mild COVID-19 reported that infectious virus could not be isolated after more than eight days of symptoms. The probability of isolating infectious virus was less than 5% when viral loads dropped below 6,51 Log10 RNA copies/mL. Similar results were obtained with a larger diagnostic sample set, but that study did not report on clinical parameters such as disease severity. Finally there is a report of a single patient shedding infectious virus up to 18 days after onset of symptoms. No published works were found on the shedding of infectious virus in patients with severe or critical COVID-19, and no published works were found on factors independently associated with shedding of infectious virus. Added value of this studyWe assessed the duration and determinants of infectious virus shedding in 129 patients with severe or critical COVID-19. The duration of infectious virus shedding ranged from 0 to 20 days post onset of symptoms (median 8 days, IQR 5 - 11). The probability of detecting infectious virus dropped below 5% after 15,2 days post onset of symptoms (95% confidence interval (CI) 13,4 - 17,2). Viral loads above 7 log10 RNA copies/mL were independently associated with detection of infectious SARS-CoV-2 from the respiratory tract (odds ratio [OR]; CI 14,7 (3,57-58,1; p<0,001). A serum neutralizing antibody titre of at least 1:20 (OR of 0,01 (CI 0,003-0,08; p<0,001) was independently associated with non-infectious SARS-CoV-2. Implications of all the available evidenceInfection prevention and control guidelines should take into account that patients with severe or critical COVID-19 may shed infectious virus for longer periods of time compared to what has been reported for in patients with mild COVID-19. Quantitative viral RNA load assays and serological assays should be used for test-based strategies to discontinue or de-escalate infection prevention and control precautions.

Lung ultrasound findings in patients with novel SARS-CoV2 (preprint)

Background: Over 2 million people worldwide have been infected with Severe Acute Respiratory Distress Syndrome Corona Virus 2 (SARS CoV2). Lung ultrasound has been proposed to diagnose and it. However, little is known about ultrasound findings in these patients. Our aim is to present an overview of lung ultrasound characteristics in critically ill patients with SARS CoV2 pneumonia overall and in relation to the duration of symptoms and clinical parameters. Methods: On the Intensive Care Unit of two academic hospitals, adult patients who tested positive for SARS-CoV2 were included. Images were analyzed for pleural line characteristics, number and appearance of B-lines, BLUE-profiles (Bedside Lung Ultrasound in Emergency), pathology in the PLAPS (Postero Lateral Alveolar and Pleural Syndrome) point and a LUS-score (lung ultrasound). The primary outcomes were frequencies, percentages and differences in lung ultrasound findings overall and between short ([≤]14 days) and long (>14 days) duration of symptoms and their correlation with clinical parameters. Results: In this pilot observational study, 61 patients were included with 75 examinations for analysis. The most prevalent ultrasound findings were decreased lung sliding (36%), thickening of the pleural line (42%) and a C-profile per view (37%). Patients with ''long'' duration of symptoms presented more frequently with a thickened and irregular pleural line (21% (32) vs 9% (11), p=.01), C-profile per patient (47% (18) vs. 25% (8),p=.01) and pleural effusion (19% (14) vs 5% (3),p=.02) compared to patients with short duration of symptoms. Lung ultrasound findings did not correlate with P/F ratio, fluid balance or dynamic compliance, with the exception of the LUS-score and dynamic compliance (R2=0.27, p=.02). Conclusion: SARS CoV2 results in significant ultrasound changes, with decreased lung sliding, thickening of the pleural line and a C-profile being the most observed. With time, a thickened and irregular pleural line, C-profile and pleural effusion become more common findings.