Preventing Cardiotoxicity in Personalized Breast Irradiation (preprint)

Background: to assess the benefit of a deep inspiration breath hold (DIBH) over standard irradiation technique, and eventually to identify anatomical and/or treatment preplanning characteristics correlated with LAD dose. Methods: We retrospectively identified patients with left-sided breast cancer who underwent whole breast radiotherapy in DIBH. All patients had both plans in DIBH and free-breathing (FB). Receiving operating characteristics (ROC analysis) were performed to define the cut-off point of parameters to predict LAD maximum dose >10 Gy and LAD mean dose > 4 Gy. Areas under the curve (AUCs) were calculated for all variables. Post-test probability has been calculated to evaluate advantage for parameters combination. Results: One hundred ninety-seven patients were identified. LAD dose was significantly reduced in DIBH plans with maximum and mean dose reduced by 31.7% (mean value 3.5 Gy vs 4.8 Gy, p=<0.001) and 28.1% (mean value 8.2 Gy vs 12.8 Gy, p=<0.001) in DIBH plans compared to FB plans. The strongest predictor of LAD maximum dose > 10 Gy and a LAD mean dose > 4 Gy was the minimum distance of LAD from tangent open fields. Other parameters were lung volume and heart volume for LAD Dmax > 10 Gy and lung volume, heart volume and breast separation for LAD Dmean > 4 Gy. Conclusion: The dosimetric benefit of DIBH is valid for all patients and DIBH should be preferred for all left sided patients.

Prevalence of Long COVID-associated symptoms in adults with and without SARS-CoV-2 infection in Germany: Results of the population-based study: Corona Monitoring Nationwide 2021/22 (RKI-SOEP-2) (preprint)

Background Controlled population-based studies on long-term health sequelae of SARS-CoV-2 can help to identify clinical signs specific to Long COVID and to evaluate this emerging public health challenge. Aim To examine prevalence differences of Long COVID-associated symptoms among adults with and without SARS-CoV-2 infection in Germany. Methods This population-based, retrospective study (11/2021-2/2022) included 7,683 working aged adults (18-65 years), a subset of the Corona Monitoring Nationwide study in Germany. Prior SARS-CoV-2 infection was defined based on self-reported PCR-confirmed infections and IgG-antibody dried blood spot testing. Participants answered a questionnaire including 19 common symptoms of Long COVID experienced in the six months preceding the survey. We estimated population-weighted prevalence of (1) individual symptoms, and (2) [≥]1 symptom, with and without impact on work ability, by infection status within strata of sex, age group, income and comorbidity. We calculated model-adjusted prevalence differences and the probability that symptoms among infected are attributable to infection. Results 12 of 19 symptoms showed a significantly higher prevalence in infected than non-infected participants, including fatigue (27.5% versus 18.3%; p<0.001), concentration problems (22.2% vs. 13.1%; p<0.001), shortness of breath (15.6% vs. 7.5%; p<0.001), and smell and taste disorder (10% vs. 1.2%; p<0.001). [≥]1 symptom with impact on work ability was more prevalent following infection (16.0% vs. 12.2%; p=0.06) with a model-adjusted prevalence difference of 3.8% (95%-CI -0.5-8.0). Conclusion We observed a rather small excess prevalence attributable to SARS-CoV-2 infection. However, the absolute number of persons places great demands on the health care system and may affect economic productivity.

Quantity of SARS-CoV-2 RNA copies exhaled per minute during natural breathing over the course of COVID-19 infection (preprint)

SARS-CoV-2 is spread through exhaled breath of infected individuals. A fundamental question in understanding transmission of SARS-CoV-2 is how much virus an individual is exhaling into the environment while they breathe, over the course of their infection. Research on viral load dynamics during COVID-19 infection has focused on internal swab specimens, which provide a measure of viral loads inside the respiratory tract, but not on breath. Therefore, the dynamics of viral shedding on exhaled breath over the course of infection are poorly understood. Here, we collected exhaled breath specimens from COVID-19 patients and used RTq-PCR to show that numbers of exhaled SARS-CoV-2 RNA copies during COVID-19 infection do not decrease significantly until day 8 from symptom-onset. COVID-19-positive participants exhaled an average of 80 SARS-CoV-2 viral RNA copies per minute during the first 8 days of infection, with significant variability both between and within individuals, including spikes over 800 copies a minute in some patients. After day 8, there was a steep drop to levels nearing the limit of detection, persisting for up to 20 days. We further found that levels of exhaled viral RNA increased with self-rated symptom-severity, though individual variation was high. Levels of exhaled viral RNA did not differ across age, sex, time of day, vaccination status or viral variant. Our data provide a fine-grained, direct measure of the number of SARS-CoV-2 viral copies exhaled per minute during natural breathing, including 312 breath specimens collected multiple times daily over the course of infection, in order to fill an important gap in our understanding of the time course of exhaled viral loads in COVID-19.

The Effects of Diabetes and Being Overweight on Patients with Post-COVID-19 Syndrome (preprint)

In the aftermath of the COVID pandemic, post-COVID-19 syndrome (PCS) remains a challenge and may continue to represent a major health problem in the future. Moreover, the influence of type 2 diabetes and being overweight on PCS remains unclear. This study aimed to assess this influence. We performed an observational study from October 2020 to July 2022, which included 466 patients (269 males and 197 females) with a median age of 65. They were hospitalized due to COVID-19 pneumonia and had persistent symptoms after 1 month of COVID-19 infection. The patients were divided into four groups according to the study objectives: patients with type 2 diabetes, overweight patients, overweight patients with type 2 diabetes, and normal-weight patients without type 2 diabetes. The clinical and demographic data collected during hospitalization and regular visits at the Community Healthcare Center dr. Adolf Drolc Maribor were analyzed. Our results showed that type 2 diabetes patients had a more difficult course of treatment and longer hospitalization. Moreover, more type 2 diabetes patients underwent rehabilitation than the other study groups. The prevailing symptoms in our patients with PCS were dyspnea and fatigue, mostly in female patients with type 2 diabetes. Our study also showed that more women with type 2 diabetes and more overweight women with type 2 diabetes suffered from secondary infections. Further, more overweight patients were treated in the intensive care unit compared to the other groups. However, our study showed an interesting result that patients with type 2 diabetes had the shortest PCS durations. Type 2 diabetes and being overweight are risk factors for PCS onset and prolonged duration. Therefore, our data that revealed a shorter duration of PCS in type 2 diabetes patients compared to the other investigated groups was unexpected. We believe that answering this question regarding the results will enable us to improve PCS treatment in general.

Prevalence and pattern of Post Covid-19 symptoms in recovered patients of Delhi: A Population-Based study (preprint)

Background: Post-coronavirus disease (COVID) is widely reported but the data of Post COVID-19 after infection with the Omicron variant is limited. This prospective study was conducted to determine the prevalence, pattern, and duration of symptoms related to Covid-19 recovered patients. Methods: Adults (>18 years old) in 11 districts of Delhi who had recovered from Covid-19 were followed up at 3 months and 6 months post-recovery. Results: The study found that the participants had a mean age of 42.07 years, with a standard deviation of 14.89. Additionally, a significant proportion of the participants (79.7%) experienced post-Covid symptoms. The participants elicited a history of Joint Pain (36%), Persistent dry cough (35.7%), anxiousness (28.4%) and shortness of breath (27.1%). The other symptoms reported were persistent fatigue (21.6%), persistent headache (20%), forgetfulness (19.7%) and weakness in limbs (18.6%). The longest duration of symptom was observed in participants reporting anxiousness (138.75 +54.14) followed by fatigue (137.57+48.33), shortness of breath (131.89+60.21) and joint pain/swelling (131.59+58.76). During the first follow-up, 2.2% of participants had an abnormal ECG reading, while no abnormalities were reported during the second follow-up. Additionally, 4.06% of participants had abnormal chest X-ray findings during the first follow-up, with this number decreasing to 2.16% during the second follow-up. Conclusion: Our study concluded that the clinical symptoms persist in participants until 6 months and a multi-system involvement is seen in the post-COVID period. Thus, the findings necessitate long-term, regular follow-ups.

Assessing Chest Pain Management and Outcomes in Percutaneous Coronary Intervention Patients: A Retrospective Analysis in Saudi Arabian Emergency Departments (preprint)

This study aimed to investigate the characteristics and outcomes of patients who underwent per-cutaneous coronary intervention (PCI) and visited an emergency department (ED) with chest pain in Saudi Arabia. A retrospective analysis of patient data was conducted, focusing on demographics, risk factors, pain assessment, triage, diagnostic testing, and management. The results revealed a young adult population (40-59 years old) at risk for coronary heart disease (CHD), highlighting the need for increased awareness and education. Gender differences in cardiovascular disease (CVD) presentation and underdiagnoses in women also require attention for effective prevention and treatment. Accurate pain assessment during triage was found to be essential to prevent mistriage and negative patient outcomes. Chest pain and shortness of breath were common symptoms, emphasizing the importance of recognizing acute myocardial infarction (AMI) symptoms for proper triage, diagnostic testing, and prompt treatment. The study identified modifiable CVD risk factors, including diabetes (51.1%), hypertension (43.8%), and smoking (25.9%), stressing the importance of lifestyle modifications to reduce CVD risk. Saudi Arabia faces significant challenges in addressing cardiovascular disorders, but efforts to improve healthcare access and establish specialized centers are promising. In conclusion, this study underscores the need for increased awareness of CHD among young adults, accurate pain assessment during triage, and lifestyle modifications to address modifiable CVD risk factors. Furthermore, healthcare teams must stay updated on new chest pain guidelines in the ED and prioritize early detection of implicated arteries and prompt reperfusion. Further research investigating chest pain patient triage and assessments across Saudi Arabia is recommended to identify areas of improvement and implement necessary changes in clinical practice.

Risk of long COVID and associated symptoms after acute SARS-COV-2 infection in ethnic minorities: a Danish nationwide cohort study (preprint)

BackgroundEthnic minorities living in high-income countries have been disproportionately affected by COVID-19 in terms of infection rates and hospitalisations; however, less is known about long COVID in this population. Our aim was to examine the risk of long COVID and associated symptoms among ethnic minorities. Methods and FindingsA Danish nationwide register-based cohort study of individuals diagnosed with COVID-19 aged [≥]18 years (n=2 334 271) between January 2020 and August 2022. We calculated the risk of long COVID diagnosis and long COVID symptoms among ethnic minorities compared with native Danes using multivariable Cox proportional hazard regression and logistic regression, respectively. Ethnic minorities from North Africa (adjusted hazard ratio [aHR] 1.41; 95% CI 1.12-1.79), Middle East (aHR 1.38; 95% CI 1.24-1.55), Eastern Europe (aHR 1.35; 95% CI 1.22-1.49), and Asia (aHR 1.23; 95% CI 1.09-1.40) had significantly greater risk of long COVID diagnosis than native Danes in both unadjusted and adjusted models. In the analysis by largest countries of origin, the greater risks of long COVID diagnosis were found in Iraqis (aHR 1.56; 95% CI 1.30- 1.88), Turks (aHR 1.42; 95% CI 1.24-1.63), and Somalis (aHR 1.42; 95% CI 1.07-1.91) after adjustment for confounders. Significant factor associated with an increased risk of long COVID diagnosis was COVID-19 hospitalisation. Furthermore, the odds of reporting cardiopulmonary symptoms (including dyspnoea, cough, and chest pain) and any long COVID symptoms were higher among North African, Middle Eastern, Eastern European, and Asian than among native Danes in both unadjusted and adjusted models. ConclusionsBelonging to an ethnic minority group was significantly associated with an increased risk of long COVID indicating the need to better understand long COVID drivers and address care and treatment strategies in this population.

Post-recovery health domain scores among outpatients by SARS-CoV-2 testing status during the pre-Delta period (preprint)

Background: Symptoms of COVID-19 including fatigue and dyspnea, may persist for weeks to months after SARS-CoV-2 infection. This study compared self-reported disability among SARS-CoV-2-positive and negative persons with mild to moderate COVID-19-like illness who presented for outpatient care before widespread COVID-19 vaccination. Methods: Unvaccinated adults with COVID-19-like illness enrolled within 10 days of illness onset at three US Flu Vaccine Effectiveness Network sites were tested for SARS-CoV-2 by molecular assay. Enrollees completed an enrollment questionnaire and two follow-up surveys (7-24 days and 2-7 months after illness onset) online or by phone to assess illness characteristics and health status. The second follow-up survey included questions measuring global health, physical function, fatigue, and dyspnea. Scores in the four domains were compared by participants SARS-CoV-2 test results in univariate analysis and multivariable Gamma regression. Results: During September 22, 2020 - February 13, 2021, 2,712 eligible adults were enrolled, 1,541 completed the first follow-up survey, and 650 completed the second follow-up survey. SARS-CoV-2-positive participants were more likely to report fever at acute illness but were otherwise comparable to SARS-CoV-2-negative participants. At first follow-up, SARS-CoV-2-positive participants were less likely to have reported fully or mostly recovered from their illness compared to SARS-CoV-2-negative participants. At second follow-up, no differences by SARS-CoV-2 test results were detected in the four domains in the multivariable model. Conclusion: Self-reported disability was similar among outpatient SARS-CoV-2-positive and -negative adults 2-7 months after illness onset.

Subphenotypes of Self-Reported Symptoms and Outcomes in Long COVID: a prospective cohort study with latent class analysis. (preprint)

Objective: To characterize subphenotypes of self-reported symptoms and outcomes(SRSOs) in Post-acute sequelae of COVID-19(PASC). Design: Prospective, observational cohort study of PASC subjects. Setting: Academic tertiary center from five clinical referral sources. Participants: Adults with COVID-19 [≥] 20 days before enrollment and presence of any new self-reported symptoms following COVID-19. Exposures: We collected data on clinical variables and SRSOs via structured telephone interviews and performed standardized assessments with validated clinical numerical scales to capture psychological symptoms, neurocognitive functioning, and cardiopulmonary function. We collected saliva and stool samples for quantification of SARS-CoV-2 RNA via qPCR. Primary and Secondary outcomes of measure: Description of PASC SRSOs burden and duration, derivation of distinct PASC subphenotypes via latent class analysis (LCA), and relationship between viral load with SRSOs and PASC subphenotypes. Results: Baseline data for 214 individuals were analyzed. The study visit took place at a median of 197.5 days after COVID-19 diagnosis, and participants reported ever having a median of 9/16 symptoms (interquartile range 6-11) after acute COVID, with muscle-aches, dyspnea, and headache being the most common. Fatigue, cognitive impairment, and dyspnea were experienced for a longer time. Participants had a lower burden of active symptoms (median 3, interquartile range 1-6) than those ever experienced (p<0.001). Unsupervised LCA of symptoms revealed three clinically-active PASC subphenotypes: a high burden constitutional symptoms (21.9%) , a persistent loss/change of smell and taste (20.6%) , and a minimal residual symptoms subphenotype (57.5%). Subphenotype assignments were strongly associated with self-assessments of global health, recovery and PASC impact on employment (p<0.001). Viral persistence (5.6% saliva and 1% stool samples positive) did not explain SRSOs or subphenotypes. Conclusions: We identified distinct PASC subphenotypes and highlight that although most symptoms progressively resolve, specific PASC subpopulations are impacted by either high burden of constitutional symptoms or persistent olfactory/gustatory dysfunction, requiring prospective identification and targeted preventive or therapeutic interventions.

OUTCOME OF COVID-19 PATIENTS ON STEROID THERAPY: A LONGITUDINAL STUDY (preprint)

ABSTRACT: Introduction: SARS-CoV-2 is responsible for global pandemic that originates from Wuhan, China (1). Patients presentation van be varied from asymptomatic to severe ARDS and multiorgan dysfunction likely due the dysregulated systemic inflammation (2). Glucocorticoids inhibits the inflammation by down streaming of cytokine receptor and promote resolution (3). The role of corticosteroid in COVID-19 still remains controversial. Corticosteroids associated with many long terms side effects. Previous MARS outbreak had experienced avascular necrosis with corticosteroid use (4). Objectives: The aim of the study was to evaluate the outcome of covid-19 patients on the corticosteroid therapy and estimate mortality rate with corticosteroid therapy and investigate potential long-term adverse events associated with its use. Methods: We did a longitudinal follow up study at the AIIMS Rishikesh to assess the side effects of corticosteroids in COVID-19 patients. Patients with moderate to severe COVID-19 pneumonia requiring the oxygen support were included in the study. According to the institutional protocol patients received conventional dose steroids versus pulse dose steroids. (Based on CT/ X-ray findings). Patients were followed up in the hospital till discharge/death for assessment of adverse events due to corticosteroids and all other biochemical parameters (Inflammatory markers) and SOFA score were obtained during hospitalisation till discharge. And at the 6 month follow up patient was assessed for infection and avascular necrosis of the femur. Results: A total of 600 patients were screened out of which 541 patients who received corticosteroids were included in this study. 71.3% were male and 26.6 % were females. Most prevalent comorbidity was systemic hypertension (38.8%) followed by diabetes mellitus (38%). Most common presenting symptoms was dyspnoea followed by fever and cough. Majority patients received dexamethasone (95%). 65.8 % patients received conventional dose while 34.2% of patients received pulse dose. Mortality was more associated with pulse dose (44%) then a conventional dose (30%) (p-value 0.0015). the median duration of the corticosteroids was 10 days with an IQR of 7-13 days. During the hospitalisation 142 patients (26.2%) develops hyperglycaemia. Hyperglycaemia was more prevalent in the pulse dose steroid group (16.8% versus 9.4%). One patient develops pancreatitis. There was a significant reduction in the levels of inflammatory markers (p<0.005) after steroid initiation. At the 6th month of follow patients were assessed for AVN and suspected infection. 25 patients (8.25%) had infection out of which 19 received pulse dose. Out of 25 patients cultures was available for 7 patients and 2 patients grows pathogenic organism in the urine (pseudomonas and E. coli). 02 patients develop non-specific joint pain at 6 months. No patient had AVN during the follow up.

Radiological and Functional Pulmonary Evolution in Post-COVID-19 Patients: An Observational Study (preprint)

COVID-19 generated a scenario for global health with multiple systemic impairments. This retrospective study evaluated the clinical, radiological, and pulmonary functional evolution in 302 post-COVID-19 patients. Regarding post-COVID-19 pulmonary symptoms, dry cough, dyspnea, and chest pain were the most frequent. Of the associated comorbidities, asthma was more frequent (23.5%). Chest Tomography (CT) initially showed a mean pulmonary involvement of 69.7%, and the evaluation in the subsequent months showed an improvement in the evolutionary image, and with less than six months post-pathology, there was a commitment of 37 .7%, from six to twelve months, 20% and after 12 months, 9.9%. And as for most of the sample, 50.3% of the patients presented CT normalization in less than six months after infection, 23% normalized between six and twelve months, and 5.2% normalized the images after twelve months, with one remaining. Percentage of 17.3% who maintained post-COVID-19 pulmonary residual sequelae. Regarding spirometry, in less than six months after the pathology, 59.3% of the patients already showed a regular exam; 12.3% normalized their function within six to twelve months, and 6.3% concluded a normal exam after twelve months of post-pathology evaluation. Only 3.6% of the patients still showed some alteration in this period.

Clinical manifestations and mortality among hospitalized COVID-19 patients in Tanzania, 2021-2022. (preprint)

Abstract Background There have been differential mortality rates from Corona Virus Disease of 2019 (COVID-19) in different parts of the world. It is not clear whether the clinical presentation does also differ, thus the need for this study in a Sub-Saharan African country. The aim of this study was to describe clinical manifestations and outcome of patients diagnosed with COVID-19 in selected tertiary hospitals in Tanzania. Methods and Findings A retrospective analysis of archived data from 26th March, 2021 to 30th September, 2022 was done for adults aged ≥18 years who were admitted in five tertiary-level   hospitals in Tanzania.  Information collected included socio-demographic, radiological and clinical characteristics of the patients as well as outcome of the admission (discharge vs death). Categorical variables were presented as frequencies and proportions and compared using Chi square test. Logistic regression was used to assess the relationship between COVID-19 mortality and the collected variables. Out of 1387 COVID-19 patients, approximately 52% were males.  The median age was 60 years [ (IQR)= (19-102)). The most common symptoms were dyspnea (943,68%), cough (889, 64%), fever (597,43%) and fatigue (570, 41%). In-hospital mortality was (476, 34%). Mortality significantly increased with increasing age, being the most in age >90 years [aOR (95% CI) =6.72 (1.94-20.81), P<0.001. Other predictors of death were not possessing a health insurance, [aOR (95% CI) = 2.78 (2.09-3.70), P<0. 001],  dyspnea [aOR (95% CI) = 1.40(1.02-2.06), P=0.03]; chest pain, [aOR (95% CI) = 1.78 (1.12-3.21), P=0.03]; HIV positivity, [aOR (95% CI) = 4.62 (2.51-8.73), P<0.001]; neutrophilia, [aOR (95% CI) = 1.02 (1.01 – 1.03), P=0.02]; none use of ivermectin, [aOR (95% CI) = 1.46 (1.09 – 2.22), P=0.02] and non-use of steroid, [aOR (95% CI) = 1.40 (1.2 – 2.5), P=0.04]. Retrospective nature of this study which based on documented patients records, with a large number of patients left out of the analysis due to missed data, this might in a way affect the results of the present study. Conclusions The most common presenting symptoms were dyspnea, cough and fever, just as what was common elsewhere in the world.  Mortality increased significantly with age, in HIV-infected patients, in those without a health insurance, those presenting with dyspnea, chest pain, or neutrophilia and those who did not use steroid or ivermectin. Clinicians should actively look for the predictors of mortality and take appropriate management to reduce mortality.

The smarty4covid dataset and knowledge base: a framework enabling interpretable analysis of audio signals (preprint)

Harnessing the power of Artificial Intelligence (AI) and m-health towards detecting new bio-markers indicative of the onset and progress of respiratory abnormalities/conditions has greatly attracted the scientific and research interest especially during COVID-19 pandemic. The smarty4covid dataset contains audio signals of cough (4,676), regular breathing (4,665), deep breathing (4,695) and voice (4,291) as recorded by means of mobile devices following a crowd-sourcing approach. Other self reported information is also included (e.g. COVID-19 virus tests), thus providing a comprehensive dataset for the development of COVID-19 risk detection models. The smarty4covid dataset is released in the form of a web-ontology language (OWL) knowledge base enabling data consolidation from other relevant datasets, complex queries and reasoning. It has been utilized towards the development of models able to: (i) extract clinically informative respiratory indicators from regular breathing records, and (ii) identify cough, breath and voice segments in crowd-sourced audio recordings. A new framework utilizing the smarty4covid OWL knowledge base towards generating counterfactual explanations in opaque AI-based COVID-19 risk detection models is proposed and validated.

Predicting Outcomes in Long COVID Patients with Spatiotemporal Attention (preprint)

Long COVID is a general term of post-acute sequelae of COVID-19. Patients with long COVID can endure long-lasting symptoms including fatigue, headache, dyspnea and anosmia, etc. Identifying the cohorts with severe long-term complications in COVID-19 could benefit the treatment planning and resource arrangement. However, due to the heterogeneous phenotype presented in long COVID patients, it is difficult to predict their outcomes from their longitudinal data. In this study, we proposed a spatiotemporal attention mechanism to weigh feature importance jointly from the temporal dimension and feature space. Considering that medical examinations can have interchangeable orders in adjacent time points, we restricted the learning of short-term dependency with a Local-LSTM and the learning of long-term dependency with the joint spatiotemporal attention. We also compared the proposed method with several state-of-the-art methods and a method in clinical practice. The methods are evaluated on a hard-to-acquire clinical dataset of patients with long COVID. Experimental results show the Local-LSTM with joint spatiotemporal attention outperformed related methods in outcome prediction. The proposed method provides a clinical tool for the severity assessment of long COVID.

Polymerized type I collagen down-regulates STAT-1 phosphorylation through engagement to LAIR-1 in M1-macrophages avoiding long COVID (preprint)

Background: The polymerized type I collagen (PTIC) is a g-irradiated mixture of pepsinized porcine type I collagen and polyvinylpyrrolidone (PVP). It has immunomodulatory properties. However, the receptor and signaling pathway through which it exerts its therapeutic effects has not yet been identified. Aim: To evaluate LAIR-1 as a potential receptor for PTIC and the signaling pathway evoked by ligand-receptor binding. Methods: LAIR-1 binding assay was performed by incubating various concentrations of recombinant human LAIR-1 with native type I collagen or PTIC. Macrophages M1-derived from THP-1 cells were cultured with 2-10% PTIC for 24 h. Cell lysates from THP-1, monocytes-like cells (MLCs), M1, M1+IFN-{gamma}, M1+LPS, and 2 or 10% PTIC treated M1 were analyzed by western blot for the transcription factors NF-{kappa}B (p65), p38, STAT-1, and pSTAT-1. Cytokines, Th1 cells, and M1/M2 macrophages were analyzed by luminometry and flow cytometry from blood samples of symptomatic COVID-19 outpatients on treatment with intramuscular administration of PTIC. Results: PTIC binds LAIR-1 with a similar affinity to native collagen. This binding decreases STAT-1 signaling IFN-{gamma}-induced and IL-1{beta} expression in M1 macrophages by down-regulating STAT-1 phosphorylation. Moreover, intramuscular PTIC treatment of symptomatic COVID-19 outpatients decreased at statistically significant levels the percentage of M1 macrophages and cytokines (IP-10, MIF, eotaxin, IL-8, IL-1RA, and M-CSF) associated with STAT-1 transcription factor and increased M2 macrophages and Th1 cells. The downregulation of inflammatory mediators was related to better oxygen saturation and decreased dyspnea, chest pain, cough, and chronic fatigue syndrome in the acute phase of infection and the long term. Conclusion: PTIC is an agonist of LAIR-1 and down-regulates STAT-1 phosphorylation. PTIC could be relevant for treating STAT-1-mediated inflammatory diseases, including COVID-19 and long COVID.

Severe pneumonia with co-infection of H5N1 and SARS-CoV-2: a case report (preprint)

Background H5N1 influenza is a cause of severe pneumonia. Co-infection with influenza and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may lead to poor prognosis in the epidemic of COVID-19. However, few studies have reported regarding patients co-infected with avian influenza and SARS-CoV-2. Case presentation A 52-year-old woman presented with fever for eight days and worsening shortness of breath and decreased blood pressure. Computed tomography (CT) revealed air bronchogram, lung consolidation and bilateral pleural effusion. Furthermore, polymerase chain reaction (PCR) of the bronchoalveolar lavage fluid (BALF) showed positivity for H5N1 and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Conclusion H5N1 influenza is a cause of severe pneumonia. The clinical presentation of the patient had a predomination of H5N1 influenza rather than COVID-19. A viral PCR analysis is necessary to demonstrate the pathogen of severe pneumonia. The patient exhibited an excellent prognosis upon the appropriate use of antiviral medicine.