Genomic epidemiology of SARS-CoV-2 in Russia reveals recurring cross-border transmission throughout 2020.

In 2020, SARS-CoV-2 has spread rapidly across the globe, with most nations failing to prevent or substantially delay its introduction. While many countries have imposed some limitations on trans-border passenger traffic, the effect of these measures on the global spread of COVID-19 strains remains unclear. Here, we report an analysis of 3206 whole-genome sequences of SARS-CoV-2 samples from 78 regions of Russia covering the period before the spread of variants of concern (between March and November 2020). We describe recurring imports of multiple COVID-19 strains into Russia throughout this period, giving rise to 457 uniquely Russian transmission lineages, as well as repeated cross-border transmissions of local circulating variants out of Russia. While the phylogenetically inferred rate of cross-border transmissions was somewhat reduced during the period of the most stringent border closure, it still remained high, with multiple inferred imports that each led to detectable spread within the country. These results indicate that partial border closure has had little effect on trans-border transmission of variants, which helps explain the rapid global spread of newly arising SARS-CoV-2 variants throughout the pandemic.

Estimates of Quality-Adjusted Life-Year Loss for Injuries in the United States.

PURPOSE: The goal of this study is to develop an approach for estimating nationally representative quality-adjusted life-year (QALY) loss from injury and poisoning conditions using data collected in the Medical Expenditure Panel Survey (MEPS) and the National Health Interview Survey (NHIS). METHODS: This study uses data from the 2002-2015 NHIS and MEPS surveys. Injuries were identified in the MEPS medical events file and through self-reporting of medical conditions. We restricted our model to 163,731 adults, for which we predict a total of 294,977 EQ-5D scores using responses to the self-administered questionnaire. EQ-5D scores were modeled using age, sex, comorbidities, and binary indicators of the presence and duration of injury at the time of the health status questionnaire. These models consider nonlinearity over time during the first 3 y following the injury event. RESULTS: Injuries are identified in MEPS using medical events that provide a reasonable proxy for the date of injury occurrence. Health-related quality of life (HRQL) decrements can be estimated using binary indicators of injury during different time periods. When grouped into 29 injury categories, most categories were statistically significant predictors of HRQL scores in the first year after injury. For these groups of injuries, mean first-year QALY loss estimates range from 0.005 (sprains and strains of joints and adjacent muscles, n = 7067) to 0.109 (injury to nerves and spinal cord, n = 71). Fewer estimates are significant in the second and third years after injury, which may reflect a return to baseline HRQL. CONCLUSION: This research presents both a framework for estimating QALY loss for short-lived medical conditions and nationally representative, community-based HRQL scores associated with a wide variety of injury and poisoning conditions. HIGHLIGHTS: This research provides a catalog of nationally representative, preference-based EQ-5D score decrements associated with surviving a large set of injuries, based on patient-reported health status.Mean first-year QALY loss estimates range from 0.005 (sprains and strains of joints and adjacent muscles, n = 7067) to 0.109 (injury to nerves and spinal cord, n = 71).This article presents a novel methodology for assessing quality-of-life impacts for acute conditions by calculating the time elapsed between injury and health status elicitation. Researchers may explore adapting these methods to study other short-lived conditions and health states, such as COVID-19 or chemotherapy.

Left ventricular global longitudinal strain as a parameter of mild myocardial dysfunction in athletes after COVID-19 (preprint)

Background Whether impaired left ventricular (LV) function contributes to persistent cardiopulmonary symptoms or decreased exercise capacity after COVID-19 remains unclear. The aim of this prospective study was to determine differences in LV global longitudinal strain (GLS) between athletes who did not have a history of LV dysfunction but had a positive COVID-19 test (PCAt) and healthy control (CON) athletes and relate them to symptoms during COVID-19. Methods We performed 151 transthoracic echocardiographies in our high-performance laboratory. GLS was determined in four-, two-, and three-chamber views and assessed offline by a blinded investigator in 88 PCAt (35% women) at a median of two months after COVID-19 who trained at least three times per week with more than 20 MET per week and 52 CONs from the German national squad (38% women). Results GLS was significantly lower (GLS -18.53 {+/-}1.94% vs. -19.94{+/-}1.42%, p<0.001) and diastolic function significantly reduced (E/A 1.54{+/-}0.52 vs. 1.66{+/-}0.43, p=0.020; E`l 0.15{+/-}0.04 vs. 0.17{+/-}0.04, p=0.009; E/E'l 5.74{+/-}1.74 vs. 5.22{+/-}1.36, p=0.024) in PCAt. There was no association between GLS and acute symptoms like resting dyspnea, exertional dyspnea during or after COVID-19, palpitations, chest pain or increased resting heart rate. However, there was a trend toward lower GLS in PCAt with subjectively perceived performance limitation (p=0.054). Conclusions In a cohort of athletes at a median two months after COVID-19, significantly lower GLS and diastolic function were observed, suggesting mild myocardial dysfunction. GLS could be used as a screening element during return-to-sport examinations.

Trampoline centre injuries in children and adolescents: a systematic review and meta-analysis.

CONTEXT: No evidence-based review has compared injury risks sustained on trampolines at home and in trampoline centres. OBJECTIVE: To present pooled results for injury type, site and treatment from studies reporting injuries that occurred on trampolines at home and in trampoline centres. DATA SOURCES: MEDLINE, Scopus, Google Scholar and Embase databases were searched to 31 December 2021. STUDY SELECTION: Inclusion criteria: (1) assessment of trampoline injuries (home and trampoline centres); (2) children and adolescents; (3) the point estimate was reported as an odds ratio (OR); and (4) an internal comparison was used. DATA EXTRACTION: Data were reported according to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. A random-effects model was used to estimate effect. RESULTS: There were 1 386 843 injuries (n=11 studies). There was an increased likelihood of musculoskeletal and/or orthopaedic injuries (OR 2.45, 95% CI 1.66 to 3.61, p<0.001), lower extremity injury (OR 2.81, 95% CI 1.99 to 3.97, p<0.001), sprains (OR 1.64, 95% CI 1.36 to 1.97, p<0.001) and a need for surgery (OR 1.89, 95% CI 1.37 to 2.60, p<0.001) at trampoline centres compared with home trampolines. Conversely, upper extremity injury (OR 0.49, 95% CI 0.25 to 0.95, p=0.03), concussion (OR 0.48, 95% CI 0.35 to 0.65, p<0.001) and lacerations (OR 0.46, 95% CI 0.35 to 0.59, p<0.001) were less likely to occur at trampoline centres than at home. CONCLUSIONS: Children using trampoline centres are more likely to suffer severe trauma and require surgical intervention than children using home trampolines. Development and implementation of preventative strategies, public awareness, and mandatory safety standards are urgently required for trampoline centres.

Identification of differences in the magnitude and specificity of SARS-CoV-2 nucleocapsid antibody responses in naturally infected and vaccinated individuals (preprint)

Background: As there are limited data on B cell epitopes for the nucleocapsid protein in SARS-CoV-2, we sought to identify the immunodominant regions within the N protein, recognized by patients with varying severity of natural infection with the Wuhan strain (WT), delta, omicron and in those who received the Sinopharm vaccines, which is an inactivated, whole virus vaccine. Methods: Using overlapping peptides representing the N protein, with an in-house ELISA, we mapped the immunodominant regions within the N protein, in seronegative (n=30), WT infected (n=30), delta infected (n=30), omicron infected+vaccinated (n=20) and Sinopharm (BBIBP-CorV) vaccinees (n=30). We then investigated the sensitivity and specificity of these immunodominant regions and analysed their conservation with other SARS-CoV-2 variants of concern, seasonal human coronaviruses and bat Sarbecoviruses. We then investigated the kinetics of responses to these regions in those with varying severity of acute COVID-19. Results: We identified four immunodominant regions aa 29-52, aa 155-178, aa 274 to 297 and aa 365 to 388, were highly conserved within SARS-CoV-2 and the bat coronaviruses. The magnitude of responses to these regions varied based on the infecting SARS-CoV-2 variants, with WT infected individuals predominantly recognizing aa155 to 178 regions, delta infected individuals and vaccinated+omicron infected individuals predominantly recognizing regions aa 29 to 52 and aa 274 to 294 regions. Sinopharm vaccinees recognized all four regions, with the magnitude of responses significantly lower than other groups. >80% of individuals gave responses above the positive cut-off threshold to many of the four regions, with some differences with individuals who were infected with different VoCs. These regions were found to be 100% specific, as none of the seronegative individuals gave any responses. Conclusions: N-protein specific responses appear to be detectable in over 90% of those who were naturally infected or vaccinated with a whole virus inactivated vaccine, with responses mainly directed against four regions of the protein, which were highly conserved. As these regions were highly specific with high sensitivity, they have a potential to be used to develop diagnostic assays and to be used in development of vaccines.

A broad-spectrum macrocyclic peptide inhibitor of the SARS-CoV-2 spike protein (preprint)

The ongoing COVID-19 pandemic has had great societal and health consequences. Despite the availability of vaccines, infection rates remain high due to immune evasive Omicron sublineages. Broad-spectrum antivirals are needed to safeguard against emerging variants and future pandemics. We used mRNA display under a reprogrammed genetic code to find a spike-targeting macrocyclic peptide that inhibits SARS-CoV-2 Wuhan strain infection and also pseudoviruses containing spike proteins of SARS-CoV-2 variants or related sarbecoviruses. Structural and bioinformatic analyses reveal a conserved binding pocket between the receptor binding domain and other domains, distal to the ACE2 receptor-interaction site. Collectively, our data reveal a hitherto unexplored site of vulnerability in sarbecoviruses that can be targeted by peptides and potentially other drug-like molecules.

Persistent Myocardial Dysfunction Assessed by Global Myocardial Strain in Covid-19 Recovered Patients with Cardiovascular Comorbidities at 3 Months after Acute Infection (preprint)

Background Previous studies reported the Coronavirus disease (COVID-19) has long implications, which involve multiple organs, including the cardiovascular system. This study aims to assess myocardial dysfunction by echocardiograph myocardial longitudinal strain Left ventricular-Global Longitudinal Strain (LV-GLS) and Right Ventricular-Free Wall Strain (RV-FWS) measurements as a marker for myocardial dysfunction and heart fibrosis. Additionally, we aim to identify admission factors that may serve as a predictor of long COVID syndrome.Methods This cross-sectional study assessed echocardiograph global longitudinal strain (GLS) values measurement done three months after initial hospitalization. Multivariate analysis was done to investigate admission factors associated with differences in GLS values.Results 100 subjects with cardiovascular comorbidities and prior COVID-19 infection were enrolled. Echocardiography examination showed lower GLS values in this group compared to the normal population. Demographic and risk factors-matched subjects without a history of COVID-19 (n = 31, Control 1) and healthy subjects (n-31, Control 2) were included as comparisons to validate GLS results. The case group had significantly lower LV-GLS values compared to other groups (p < 0.05, mean ± SD -16.17 ± 3.379, -19.48 ± 1.141, -21.48 ± 1.777 respectively for case, control one, and control two groups). Upon admission, a history of coronary artery disease was found to be associated with decreased LV GLS values in recovered COVID-19 patients with cardiovascular comorbidity.Conclusion LV GLS values significantly decreased in recovered COVID-19 patients with cardiovascular comorbidities. Upon admission, a history of CAD may predict cardiac long COVID-19 syndrome.

A case of COVID-19 masquerading as presumed Trastuzamab induced subclinical cardiotoxicity (preprint)

A 48-year-old woman was diagnosed with right-sided Grade 2 invasive breast carcinoma. Prior to initiation of chemotherapy, transthoracic echocardiogram (TTE) demonstrated normal systolic function with left ventricular ejection fraction (LVEF) 64% and global longitudinal strain (GLS) 21%. Following adjuvant chemotherapy with four cycles of anthracycline, twelve cycles of Paclitaxel, and two cycles of Trastuzamab chemotherapies, TTE demonstrated reduction in LVEF to 56% and GLS of -18% (14% relative reduction compared to baseline). Further investigation revealed recent symptomatic COVID-19 infection coinciding with functional impairment and decision was made to continue Trastuzumab therapy without cardioprotective agents. Subsequent TTE demonstrated improved systolic function, indicating the importance of taking history of significant viral infections during chemotherapy standard of care.

Mid-term subclinical myocardial injury detection in patients recovered from COVID-19 according pulmonary lesion severity (preprint)

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV 2) may cause damage of the cardiovascular system during the acute phase of infection. However, Recent studies described a mid and long-term subtle cardiac injuries after recovery from acute Coronavirus disease 19 (COVID-19).The aim of this study was to determine the relationship between the severity of chest computed tomography (CT) lesions and the persistence of subtle myocardial injuries at mid-term follow-up of patients recovered from COVID-19 infection. Methods All COVID-19 patients were enrolled prospectively in this study. Sensitive troponin T (hsTnT) and chest CT scan was performed in all patients at the acute phase of Covid-19 infection. At the mid-term follow up, conventional transthoracic echocardiograph and global longitudinal strain (GLS) of left and right ventricles (LV and RV) were determined and compared between patients with chest CT scan lesions less than 50% (Group 1) and those with severe chest CT scan greater or equal to 50% (Group 2). Results The mean age was 55 more or less than 14 years. Both LV GLS and RV GLS were significantly decreased in the group 2 (p=0.013 and p=0.011, respectively). LV GLS value more than -18% was noted in 43% of all the patients and RV GLS value more than -20% was observed in 48% of them. The group with severe chest CT scan lesions included more patients with reduced LV GLS and reduced RV GLS than the group with mild chest CT scan lesions (G1:29% vs. G2:57%, p=0.002) and (G1:36% vs. G2:60 %, p=0.009) respectively). Conclusion Patients with severe chest CT scan lesions are more likely to develop subclinical myocardial damage. TTE could be recommended in patients recovering from COVID-19 to detect subtle LV and RV lesions. Trial registration The cohort of patients is a part of the research protocol (IORG 00093738 N°102/OMB 0990-0279) approved by the Hospital Ethics Committee.

Comprehensive humoral and cellular immune responses to SARS-CoV-2 variants in diverse Chinese populations: A benefit perspective of national vaccination (preprint)

The emerging SARS-CoV-2 variants have made great challenges to current vaccine and pandemic control strategies. B.1.1.529 (Omicron), which was classified as a variant of concern (VOC) by the World Health Organization on November 26th, 2021, has quickly become the dominant circulating variant and causing waves of infections. It is urgent to understand the current immune status of the general population given that pre-existing immunity has been established by national vaccination or exposure to past variants. Using sera from 85 individuals (including 21 convalescents of natural infection, 15 cases suffered a breakthrough infection after vaccination, and 49 vaccinated participants without infection history), we showed that the cross-neutralizing activity against VOCs such as Omicron can be detected in 53 (62.4%) cases, although less potent than against the Wuhan-1 strain (WT), with a 3.9-fold reduction in geometric mean neutralizing titer (GMT) (130.7, 95% CI 88.4-193.3 vs 506, 355.8-719.7, respectively). Subgroup analysis revealed significantly enhanced neutralizing activity against WT and VOCs in Delta convalescent sera. The neutralizing antibodies against Omicron were detectable in 75% of convalescents and 44.9% of healthy donors (p = 0.006), with a GMT of 289.5, 180.9-463.3 and 42.6, 31.3-59, respectively. However, the protective effect against VOCs was weaker in young convalescents (aged < 18y), with a detectable rate of 50% and a GMT of 46.4 against Omicron, similar to vaccinees. The pan-sarbecovirus neutralizing activities were not observed in vaccinated SARS-CoV-1 survivors. A booster dose significantly increased the breadth and magnitude of neutralization against WT and VOCs to different degrees than full vaccination. In addition, we showed that COVID-19 inactivated vaccines can elicit Omicron-specific T cell responses. The positive rates of ELISpot reactions were 26.7% (4/15) and 43.8% (7/16) in the full vaccination group and the booster vaccination group, respectively. The neutralizing antibody titers declined while T-cell responses remain robust over 6 months. These findings will inform the optimization of public health vaccination and intervention strategies to protect diverse populations against SARS-CoV-2 variants.

Validity of a Rehab and Reconditioning Program Following an Adductor Longus Injury in Professional Soccer.

CONTEXT: The high rates of adductor injuries and reinjuries in soccer have suggested that the current rehabilitation programs may be insufficient; therefore, there is a need to create prevention and reconditioning programs to prepare athletes for the specific demands of the sport. OBJECTIVE: The aim of this study is to validate a rehab and reconditioning program (RRP) for adductor injuries through a panel of experts and determine the effectiveness of this program through its application in professional soccer. DESIGN: A 20-item RRP was developed, which was validated by a panel of experts anonymously and then applied to 12 injured male professional soccer players. SETTING: Soccer pitch and indoor gym. PARTICIPANTS: Eight rehabilitation fitness coaches (age = 33.25 [2.49] y) and 8 academic researchers (age = 38.50 [3.74] y) with PhDs in sports science and/or physiotherapy. The RRP was applied to 12 male professional players (age = 23.75 [4.97] y; height = 180.56 [8.41] cm; mass = 76.89 [3.43] kg) of the Spanish First and Second Division (La Liga). INTERVENTIONS: The experts validated an indoor and on-field reconditioning program, which was based on strengthening the injured muscle and retraining conditional capacities with the aim of reducing the risk of reinjury. MAIN OUTCOME MEASURES: Aiken V for each item of the program and number of days taken by the players to return to full team training. RESULTS: The experts evaluated all items of the program very highly as seen from Aiken V values between 0.77 and 0.94 (range: 0.61-0.98) for all drills, and the return to training was in 13.08 (±1.42) days. CONCLUSION: This RRP following an injury to the adductor longus was validated by injury experts, and initial results suggested that it could permit a faster return to team training.

Evaluation of Post-COVID-19 Chest Pain and Dyspnea in Outpatients Using Speckle Tracking Echocardiography (preprint)

Clinicians are frequently facing patients complaining of post-COVID-19 chest pain and dyspnea. However, it remains to be seen if these symptoms indicate pathology of the cardiovascular system. We aimed to evaluate heart functions in outpatients with post-COVID-19 chest pain and dyspnea, using 2D-speckle tracking echocardiography (2D-STE). This cross-sectional study recruited consecutive patients who presented to cardiology outpatient clinics between June 15 and July 15, 2021. Subjects had recovered from COVID-19 1-2 months prior to admission. ECG, echocardiography including 2D-STE images, were obtained for all patients. Findings were compared with sex and an age-matched control group consisting of 67 healthy adults. A total of 78 patients were included. The median age was 38 (IQR, 34-45) years, and 64.1% were female. There were no significant differences between the patients and control group regarding laboratory, ECG, and echocardiography findings. Moreover, left ventricle global longitudinal strain (LVGLS) measurements in both patient and control groups were within the normal ranges and did not show a significant difference [-20.5 (-21.8- -17.9) vs. -19.8 (-21.4- -18.9), p=0.894]. Post-COVID-19 chest pain and dyspnea are unlikely signs of cardiovascular involvement in outpatient young adults who had not been hospitalized with COVID-19.

Inhibiting ACSL1 related ferroptosis restrains MHV-A59 infection (preprint)

Murine hepatitis virus strain A59 (MHV-A59) belongs to the β -coronavirus and is considered as a representative model for studying coronavirus infection. MHV-A59 was shown to induce pyroptosis, apoptosis and necroptosis of infected cells, especially the murine macrophages. However, whether ferroptosis, a recently identified form of lytic cell death, was involved in the pathogenicity of MHV-A59, is unknown. Here, we demonstrate inhibiting ferroptosis suppresses MHV-A59 infection. MHV-A59 infection upregulates the expression of Acsl1 , a novel ferroptosis inducer. MHV-A59 upregulates Acsl1 expression depending on the NF-kB activation, which is TLR4-independent. Ferroptosis inhibitor inhibits viral propagation, inflammatory cytokines release and MHV-A59 infection induced cell syncytia formation. ACSL1 inhibitor Triacsin C suppresses MHV-A59 infection induced syncytia formation and viral propagation. In vivo administration of liproxstatin-1 ameliorates lung inflammation and tissue injuries caused by MHV-A59 infection. Collectively, these results indicate that ferroptosis inhibition protects hosts from MHV-A59 infection. Targeting ferroptosis may serves as a potential treatment approach for dealing with hyper-inflammation induced by coronavirus infection.

Infective endocarditis (MRSA)with COVID-19 concomitant：a case report (preprint)

Introduction: Since 2019,the COVID-19（a1） epidemic has rapidly spread across China,and the global spread trendappeared,which not only endangered people’s health, but also had a huge impact on the social economy.Infective endocarditis (IE(a2)) is aninflammation of the inner wall of the cardiac valves or ventricle caused by direct infection of bacteria,fungi and other pathogenic microorganisms. It is related to several and the main etiological agents are the Gram-positive cocci. At present,there is limited evidence in the literature for both conditions. Case presentation Here，we report a case of Infective endocarditis concomitant with COVID-19. A blood culture results and toe secretions culture indicated MRSA（a3） strain infection.Because it has no special past history,we consider that is communityassociated (CA-MRSA )strain. TTE（a4） did not identify endocardial vegetations. TEE（a5） was then performed and outlined IE of anterior mitral valve leaflet. CT scan of the patient revealed multiple diffuse abscesses. We tried high-flow nasal cannula(HFNC（a6）) for COVID-19,and we used a combined anti-infection approach(daptomycin, Fosfomycin, linezolid). Conclusion With aggressive anti-infective therapy,our case has achieved a good treatment outcome.

Subclinical left ventricular dysfunction in COVID-19 recovered patients using speckle tracking echocardiography (preprint)

Objectives: Myocardial injury during active coronavirus disease-2019 (COVID-19) infection is well described however, its persistence during recovery is unclear. We assessed left ventricle (LV) global longitudinal strain (GLS) using speckle tracking echocardiography (STE) in COVID-19 recovered patients and studied its correlation with various parameters. Methods: A total of 134 subjects within 30-45 days post recovery from COVID-19 infection and normal LV ejection fraction were enrolled. Routine blood investigations, inflammatory markers (on admission) and comprehensive echocardiography including STE were done for all. Results: Of the 134 subjects, 121 (90.3%) were symptomatic during COVID-19 illness and were categorized as mild: 61 (45.5%), moderate: 50 (37.3%) and severe: 10 (7.5%) COVID-19 illness. Asymptomatic COVID-19 infection was reported in 13 (9.7%) patients. Subclinical LV and right ventricle (RV) dysfunction were seen in 40 (29.9%) and 14 (10.5%) patients respectively. Impaired LVGLS was reported in 1 (7.7%), 8 (13.1%), 22 (44%) and 9 (90%) subjects with asymptomatic, mild, moderate and severe disease respectively. LVGLS was significantly lower in patients recovered from severe illness (mild: -21 ± 3.4%; moderate: -18.1 ± 6.9%; severe: -15.5 ± 3.1%; P < 0.0001). Subjects with reduced LVGLS had significantly higher interleukin-6 (P < 0.0001), C-reactive protein (P = 0.001), lactate dehydrogenase (P = 0.009) and serum ferritin (P = 0.03) levels during index admission. Conclusions: Subclinical LV dysfunction was seen in nearly a third of recovered COVID-19 patients while 10.5% had RV dysfunction. Our study suggests a need for closer follow-up among COVID-19 recovered subjects to elucidate long-term cardiovascular outcomes.

The Effect of Lockdown Due to the COVID-19 Pandemic on Digital Eye Strain Symptoms Among the General Population: A Cross-Sectional Study (preprint)

Purpose: the study examined the effect of prolonged lockdown on the development and increased severity of digital eye strain (DES) symptoms among the general population. Methods: : An online survey was conducted in March 2020 on social media platforms in Jordan. The questionnaire consisted of questions related to demographic characteristics, past medical and ocular history, frequency of using digital devices before and during lockdown, and the emergence and severity of DES symptoms. Results: : Data from 1,460 responders were analyzed. About half of the respondents were between 30- 49 years, 28.4 % were retired, 21% had chronic systemic illness, and 23% reported chronic eye problems. A rise in the use of digital devices during lockdown was reported by 957 participants, with 33% of them used digital devices more than 4 hours a day. The most common symptoms before and during lockdown were neck and shoulder pain, which revealed the most significant association (X 2 201.61, p 0.000). Female gender, existence of chronic eye problems and systemic diseases, and duration of using digital devices were found to be statistically significant factors associated with increasing severity of eye symptoms during lockdown. Regarding developing new eye complaints during the lockdown, only taking regular breaks was not significant ( p 0.336) . People with chronic eye problems and increased time using devices during lockdown developed new eye complaints three times more than before the lockdown and males were two times more likely than females to have more severe eye symptoms. Conclusion: The majority of the population developed new DES symptoms due to the lockdown. Public awareness of healthy practices and ergonomic use of digital devices is recommended.

Cardiovascular findings in Echocardiography in post Covid-19 mild infection population in Argentina (preprint)

Objectives: The aim of this study was to assess differences in echocardiographic findings between a normal adult and a post Covid-19 population. Background: Coronavirus disease (Covid-19) is known to produce a systemic inflammatory syndrome, with pulmonary and cardiac involvement. However, the cardiovascular impact in patients with mild clinical forms of the disease is uncertain. There is small evidence supporting the finding of global ventricular longitudinal strain (GLS) alterations in these patients. Methods: One hundred and five consecutive patients admitted to an ambulatory care center, underwent a conventional transthoracic echocardiographic (TTE) study with acquisition of GLS. Patients were included if they underwent a positive diagnostic reverse transcriptase polymerase chain reaction (PCR) test, having no relevant preexisting conditions, with exception of obesity. Demographic and clinical data were prospectively obtained. For this purpose, we considered a normal cut off point of -17,09%, based on previous studies. Echocardiographic findings were compared with those of 67 healthy individuals. Results: Out of 172 patients, 105 correspond to Covid-19 group, and 67 to healthy individuals. There were no significant differences in GLS regarding age, left ventricular mass index (LVMI) and E/e’ ratio. The multivariate analysis showed that the percentage of patients with pathological GLS values was significantly higher within the Covid-19 and male groups (OR 6.02 IC 1.88-22.57; p 0.004 and OR 3.17 IC 1.03-10.50; p 0.05, respectively). Conclusion: These data support that Covid-19 infection could affect ventricular GLS and encourage the use of conventional TTE with GLS measurements in patients with non-significant forms of the disease.

Orthopaedic assessment unit: a service model for the delivery of orthopaedic trauma care in a major trauma centre during the global pandemic (COVID-19).

INTRODUCTION: We describe a new service model, the Orthopaedic Assessment Unit (OAU), designed to provide care for trauma patients during the COVID-19 pandemic. Patients without COVID-19 symptoms and isolated musculoskeletal injuries were redirected to the OAU. METHODS: We prospectively reviewed patients throughput during the peak of the global pandemic (7 May 2020 to 7 June 2020) and compared with our historic service provision (7 May 2019 to 7 June 2019). The Mann-Whitney and Fisher Exact tests were used to test the statistical significance of data. RESULTS: A total of 1,147 patients were seen, with peak attendances between 11am and 2pm; 96% of all referrals were seen within 4h. The majority of patients were seen by orthopaedic registrars (52%) and nurse practitioners (44%). The majority of patients suffered from sprains and strains (39%), followed by fractures (22%) and wounds (20%); 73% of patients were discharged on the same day, 15% given follow up, 8% underwent surgery and 3% were admitted but did not undergo surgery. Our volume of trauma admissions and theatre cases decreased by 22% and 17%, respectively (p=0.058; 0.139). There was a significant reduction of virtual fracture clinic referrals after reconfiguration of services (p<0.001). CONCLUSIONS: Rapid implementation of a specialist OAU during a pandemic can provide early definitive trauma care while exceeding national waiting time standards. The fall in trauma attendances was lower than anticipated. The retention of orthopaedic staff in the department to staff the unit and maintain a high standard of care is imperative.

A preceding low-virulence strain pandemic inducing immunity against COVID-19 (preprint)

Countries highly exposed to incoming traffic from China were expected to be at the highest risk of COVID-19 spread. However, COVID-19 case numbers (infection levels) are negatively correlated with incoming traffic-level. Moreover, infection levels are positively correlated with population-size, while the latter should only affect infection-level once herd immunity is reached. These could be explained if a low-virulence strain (LVS) began spreading a few months earlier from China, providing immunity from the later emerging known SARS-CoV-2 high-virulence strain (HVS). We find that the dynamics of the COVID-19 pandemic depend on the LVS and HVS spread doubling-times and the delay between their initial onsets. We find that LVS doubling-time to be $T_L\sim1.59\pm0.17$ times slower than the HVS ($T_H$), but its earlier onset allowed its global wide-spread to the levels required for herd-immunity. In countries exposed earlier to the LVS and/or having smaller population-size, the LVS achieved herd-immunity earlier, allowing less time for the spread of the HVS, and giving rise to lower HVS-infection levels. Such model accurately predicts a country's infection-level ({\rm R^{2}=0.74}; p-value of {\rm 5.2\times10^{-13}}), given only its population-size and incoming-traffic from China. It explains the negative correlation with incoming-traffic ($c_{exp}$), the positive correlation with the population size (n_{pop}) and their specific relations (${\rm N}_{{\rm cases}}\propto n_{pop}^{{\rm T_{L}/{\rm T_{H}}}}\times c_{exp}^{{\rm T_{L}/{\rm T_{H}-1}}}$). We find that most countries should have already achieved herd-immunity. Further COVID-19-spread in these countries is limited and is not expected to rise by more than a factor of 2-3. We suggest tests/predictions to further verify the model and biologically identify the LVS, and discuss the implications.

A preceding low-virulence strain pandemic inducing immunity against COVID-19 (preprint)

The COVID-19 pandemic is thought to began in Wuhan, China in December 2019. Mobility analysis identified East-Asia and Oceania countries to be highly-exposed to COVID-19 spread, consistent with the earliest spread occurring in these regions. However, here we show that while a strong positive correlation between case-numbers and exposure level could be seen early-on as expected, at later times the infection-level is found to be negatively correlated with exposure-level. Moreover, the infection level is positively correlated with the population size, which is puzzling since it has not reached the level necessary for population-size to affect infection-level through herd immunity. These issues are resolved if a low-virulence Corona-strain (LVS) began spreading earlier in China outside of Wuhan, and later globally, providing immunity from the later appearing high-virulence strain (HVS). Following its spread into Wuhan, cumulative mutations gave rise to the emergence of an HVS, known as SARS-CoV-2, starting the COVID-19 pandemic. We model the co-infection by an LVS and an HVS and show that it can explain the evolution of the COVID-19 pandemic and the non-trivial dependence on the exposure level to China and the population-size in each country. We find that the LVS began its spread a few months before the onset of the HVS and that its spread doubling-time is \sim1.59\pm0.17 times slower than the HVS. Although more slowly spreading, its earlier onset allowed the LVS to spread globally before the emergence of the HVS. In particular, in countries exposed earlier to the LVS and/or having smaller population-size, the LVS could achieve herd-immunity earlier, and quench the later-spread HVS at earlier stages. We find our two-parameter (the spread-rate and the initial onset time of the LVS) can accurately explain the current infection levels (R^2=0.74); p-value (p) of 5.2x10^-13). Furthermore, countries exposed early should have already achieved herd-immunity. We predict that in those countries cumulative infection levels could rise by no more than 2-3 times the current level through local-outbreaks, even in the absence of any containment measures. We suggest several tests and predictions to further verify the double-strain co-infection model and discuss the implications of identifying the LVS.