Cardiovascular symptoms of PASC are associated with trace-level cytokines that affect the function of human pluripotent stem cell derived cardiomyocytes (preprint)

Globally, over 65 million individuals are estimated to suffer from post-acute sequelae of COVID-19 (PASC). A large number of individuals living with PASC experience cardiovascular symptoms (i.e. chest pain and heart palpitations) (PASC-CVS). The role of chronic inflammation in these symptoms, in particular in individuals with symptoms persisting for >1 year after SARS-CoV-2 infection, remains to be clearly defined. In this cross-sectional study, blood samples were obtained from three different sites in Australia from individuals with i) a resolved SARS-CoV-2 infection (and no persistent symptoms i.e. Recovered), ii) individuals with prolonged PASC-CVS and iii) SARS-CoV-2 negative individuals. Individuals with PASC-CVS, relative to Recovered individuals, had a blood transcriptomic signature associated with inflammation. This was accompanied by elevated levels of pro-inflammatory cytokines (IL-12, IL-1beta;, MCP-1 and IL-6) at approximately 18 months post-infection. These cytokines were present in trace amounts, such that they could only be detected with the use of novel nanotechnology. Importantly, these trace-level cytokines had a direct effect on the functionality of pluripotent stem cell derived cardiomyocytes in vitro. This effect was not observed in the presence of dexamethasone. Plasma proteomics demonstrated further differences between PASC-CVS and Recovered patients at approximately 18 months post-infection including enrichment of complement and coagulation associated proteins in those with prolonged cardiovascular symptoms. Together, these data provide a new insight into the role of chronic inflammation in PASC-CVS and present nanotechnology as a possible novel diagnostic approach for the condition.

The Aftermath of COVID-19: Exploring Long-Term Effects on the Organ Systems (preprint)

Background: Post-acute sequelae of SARS-CoV-2 infection (PASC) is a complicated disease that affects millions of people all over the world. Previous studies have shown that PASC impacts 10% of SARS-CoV-2 infected patients of which 50-70% are hospitalized. It has also been shown that 10-12% of those vaccinated against COVID-19 were affected with PASC and its complications. The severity and the later development of PASC symptoms is positively associated with the early intensity of the infection. Results: The generated health complications caused by PASC involve a vast variety of organ systems. Patients affected by PASC have been diagnosed with neuropsychiatric and neurological symptoms. Cardiovascular system also has been involved and several diseases such as myocarditis, pericarditis, and coronary artery diseases were reported. Chronic hematological problems such as thrombotic endothelialitis and hypercoagulability were described as a condition that could increase the risk of clotting disorders and coagulopathy in PASC patients. Chest pain, breathlessness, and cough in PASC patients were associated with respiratory system in long COVID-19 causing respiratory distress syndrome. The observed immune complications were notable, involving several diseases. Renal system also was impacted and result in raising the risk of diseases such as thrombotic issues, fibrosis, and sepsis. Endocrine gland malfunction can lead to diabetes, thyroiditis, and male infertility. Symptoms such as diarrhea, nausea, loss of appetite and taste were also among reported observations due to several gastrointestinal disorders. Skin abnormalities might be an indication of infection and long-term implications such as persistent cutaneous complaints were linked to PASC. Conclusions: Long COVID is a multidimensional syndrome with considerable public health implications, affecting several physiological systems and demanding thorough medical therapy as well as more study to address its underlying causes and long-term effects.

Real-world Nuvaxovid COVID-19 vaccine safety profile after first 100,000 doses in Australia, 2022-2023 (preprint)

Introduction Nuvaxovid became available in Australia from February 2022, a year later than the first COVID-19 vaccines were released. It was a much-anticipated alternative vaccine for people that had either suffered an adverse event to and/or were hesitant to receive one of the mRNA or adenovirus based COVID-19 vaccines. Although safety from clinical trials was reassuring, small trial population size, relatively low administration rates worldwide and limited post-licensure intelligence meant potential rare adverse events were underinformed. Methods We conducted a retrospective observational analysis of adverse events following immunisation (AEFI) spontaneously reported to SAFEVAC, the integrated vaccine safety surveillance system used by Victoria and Western Australia, Australia. Reports received from 14 Feb 2022 to 30 June 2023 were analysed by vaccinee demographics, reported reactions and COVID-19 vaccine dose received and compared as reporting rates (RR) per 100,000 doses administered. Results 356 AEFI reports were received, following 102,946 Nuvaxovid doses administered. Rates were higher post dose 1 than dose 2 (rate ratio 1.5, p=0.0008); primary series than booster (rate ratio 2.4, p<0.0001); in females than males (rate ratio 1.4, p<0.01), especially those aged 30-49 years (RR=1.6, p=0.002). Serious AEFI included 76 chest pain (RR=73.8), two myocarditis (RR=1.9) and 20 pericarditis (RR=19.4). No cases of Guillain Barre or thrombosis with thrombocytopaenia syndromes were reported and no deaths attributable to vaccination. Conclusion The shared SAFEVAC platform enables pooling of clinically reviewed data across jurisdictions, increasing the safety profile evidence base of novel vaccines like Nuvaxovid and improving the odds for identification and description of rare events across all vaccines.

Predictors of mortality among COVID-19 patients at Kilimanjaro Christian Medical Centre in Northern Tanzania: A hospital-based retrospective cohort study (preprint)

Background: COVID-19 disease is a global public health disaster causing a range of social, economic, and healthcare difficulties, border restrictions, high human loss, lockdown, and transportation challenges. Despite it being a global pandemic, there are few studies conducted in Tanzania to examine the predictors of mortality. This disease has caused a significant number of mortalities worldwide but literature shows low mortality and better survival in Africa than in other WHO regions. Therefore, this study aimed to determine the predictors of mortality among COVID-19 patients at KCMC Hospital in Northern Tanzania. Methodology This was the hospital-based retrospective cohort study, conducted at KCMC Hospital in Northern Tanzania among all admitted patients with confirmed COVID-19, from 10th March 2020 to 26th January 2022. The main study event was COVID-19 mortality. The predictors of mortality were determined by using the Weibull survival regression model and the statistically significant results were declared at a p-value of <0.05. Results A total of 547 confirmed COVID-19 patient records were included in the study. Their median age was 63 (IQR; 53-83), about 60% were aged 60 years and above, and 56.7% were males. The most common clinical features were; fever (60.8%), a severe form of the disease (44.4%), difficulty in breathing (73.3%), chest pain (46.1%), and generalized body weakness (71.3%). Of all participants, over one-third (34.6%) died (95%CI; 0.31-0.39). The median survival time was 7 days (IQR; 3-12). The overall mortality rate was 32.33 per 1000 person-days while the independent predictors of higher mortality risk were age ≥60 years (AHR=2.01; 95%CI 1.41-2.87; P<0.001), disease severity (AHR=4.44; 95%CI 2.56-7.73; P<0.001) and male sex (AHR=1.28; 95%CI; 0.93-1.73; P=0.128). Conclusion Mortality was higher in elderly male patients, with a severe form of the disease and those with any comorbidities. Therefore, more attention should be provided to older patients including uptake of the current vaccine and ensuring standard and supportive care at primary health facilities is available.

Myocarditis and Pericarditis Following the COVID-19 Vaccination: A Single-Centre Case Seriese (preprint)

The Surveillance of rare adverse events following vaccination, particularly related to COVID-19 vaccines, requires thorough examination. This paper investigates vaccine-associated myocarditis and/or pericarditis (VAMPS), presenting insights into clinical manifestations, management, and outcomes. Conducted at the Prince Sultan Cardiac Center in Saudi Arabia from March 2021 to May 2022, this retrospective case series comprises 20 patients with an average age of 27.9 ± 14.0 years, predominantly males (70%). Pfizer-BioNTech, AstraZeneca, and Moderna vaccines were administered in 74%, 21%, and 5% of cases, respectively, with 53% receiving the second dose, 26% the booster, and 21% the initial dose. Common symptoms included shortness of breath (60%), chest pain (50%), palpitations (40%), premature ventricular contractions (35%), and fever (25%). Cardiac magnetic resonance imaging revealed preserved left ventricular function (80%), subepicardial and/or mid-wall late gadolinium enhancement (65%), and lateral (39%), anterolateral (15%), inferolateral (15%), and anteroseptal (15%) segments affected. Myocarditis, pericarditis, and myopericarditis were diagnosed in 40%, 20%, and 40% of cases, respectively. C-reactive protein was elevated in two-thirds of patients. Recovery was achieved with anti-inflammatory medications, primarily colchicine (72%), aspirin(39%), and ibuprofen (33%). While no fatalities occurred, 30% experienced severe complications, and 15% had minor complications. In conclusion, VAMPS exhibits distinct characteristics and may lead to serious complications. Cardiologists should consider VAMPS in the differential diagnosis for symptomatic patients recently vaccinated against COVID-19, emphasizing the importance of ongoing surveillance and understanding of rare adverse events.

Causal relationship between COVID-19 and the risk of asthma: A Mendelian Randomisation study (preprint)

Background Existing research has focused on new-onset asthma and viral infections, particularly respiratory syncytial virus (RSV). However, studies on whether COVID-19 can induce asthma are limited.Methods We performed bidirectional two-sample Mendelian Randomization (MR) to assess the potential causal relationship between COVID-19 and asthma using genome-wide association study (GWAS) summary data obtained from the COVID-19 Host Genetic Initiative GWAS Meta-analysis Round 5 (release date: 18 January 2021). Several methods (random-effects inverse variance weighted, weighted median, MR-Egger regression, and MR-PRESSO) were used to ensure the robustness of the causal effects. Heterogeneity was measured using Cochran's Q value. Horizontal pleiotropy was evaluated using MR-Egger regression and leave-one-out analyses.Results We observed a significant causal association between COVID-19 hospitalisation and asthma (odds ratio (OR) = 1.042, 95% Confidence Interval (CI) = 1.004–1.081, p = 0.031), indicating a significantly increased risk of COVID-19 hospitalisation associated with asthma. However, no statistically significant causal relationships were observed for COVID-19 susceptibility (OR = 1.023, 95% CI = 0.931–1.124, p = 0.637), COVID-19 severity (OR = 1.006, 95% CI = 0.978–1.035, p = 0.669), and asthma.Conclusions COVID-19 can trigger the onset of asthma. Individuals experiencing prolonged coughing, chest tightness, or difficulty in breathing long after recovery from COVID-19 should remain vigilant about the possibility of developing asthma.

The Effect of Host Risk Factors in Determining the Mortality in Covid 19 Pneumonia and a Novel Covid-19 Mortality Index: Co-AMSCA (preprint)

Aim: The purpose of this study was to determine the host risk factors associated with mortality in COVID-19 patients who are hospitalized for pneumonia, and also, to find a COVID-19 mortality score based on these. Methods: All patients diagnosed as confirmed or probable COVID-19 pneumonia whom hospitalised in our Chest Diseases Education and Research Hospital between March 11, 2020 and October 1,2020 were enrolled. The optimal cut-off values, sensitivity and specificity values and odds ratios to be used in mortality prediction of the novel scoring system created from these parameters were calculated by ROC analysis according to the area under the curve and Youden index. Results: Over 422 patients (n: 51 mortal, n: 371 survivors) univariate regression analysis showed that age, male gender, smoking, comorbidity, and using ACE inhibitor were prognostic host risk factors for COVID-19-related mortality. Using this analysis, a novel scoring model Co-AMSCA (Age, Male, Smoking history, Comorbidity, ACE inh)was established. The cut-off value of this scoring system (including only host risk factors), which determines the mortality risk in patients, was 3.5 points with 88.4% sensitivity and 65.5 % specificity (AUC = 0.761, 95% CI 0.697-0.826, P < .001) (Figure 1). The mortality risk in patients with a Co-AMSCA mortality score above 3.5 points was 7.8 times higher than patients with lower than 3.5 (OR= 7.8; P < .001).In multivariate logistic regression analysis, older age and smoking (smoker/ex-smoker) were found to be important risk factors for mortality (OR = 12.09; 95% CI 2,564-57,054 P =0.004 and OR = 3.1; 95% CI 1,381-7,295; P = 0.007,respectively). Counclusion:We created a simple mortality score, which is easily calculated and does not require laboratory and time.This study showed that by using Co-AMSCA mortality score that has only host risk factors achieved a prediction of mortality in COVID-19 patients who are hospitalized for pneumonia.

Analysis of long-term antibody response in COVID-19 patients by symptoms grade, gender, age, BMI, and treatments regimens (preprint)

Objective: The severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) and the resulting COVID-19 pandemic pose significant challenges in terms of diagnosis and recurrent infections. Literature data suggest that age, gender and BMI factors are associated with immune response. The first aim of the study was to analyze the change in antibody titer at 15-day intervals until 60 days post symptom onset (PSO) The second aim was to analyze relationship between antibody titer and symptom grade, gender, age, BMI, therapeutic drugs, vitamin supplements, and herbal therapies. Materials and methods: Blood samples were collected from 43 patients (5 mild, 21 moderate, 17 severe diseases), 18 women (41.9 %), and 25 men (58.1 %), on 15, 30, 45, and 60 days PSO after COVID-19 infection. The serum antibody titers were determined by measuring the COVID-19 IgG antibodies by ELISA. Associations between the duration of symptoms, demographic and clinical parameters, medications and vitamins used, and herbal therapies were evaluated by interviewing the participants. Results: Within the first 15 days of illness, 81.4% of the patients were positive. From day 45 PSO, seropositivity was 89.5%. The anti-SARS-CoV-2 antibody titers were statistically higher in men than women at all-time (p<0.01). Antibody titer was higher in older participants compared to younger participants (p<0.02). Plaquenil or Favipiravir use did not effect antibody response (p>0.05). Men had higher fever (p=0.006), shortness of breath (p=0.004), and chest pain (p=0.03) than women. Conclusion: We found powerful antibody response by sixty days PSO, as well as higher antibody response and severity of symptoms in men gender. Data also showed that SARS-CoV-2 antibodies are higher in individuals with older age, whereas BMI, coexisting chronic disease, and drug used had no effect on antibody titers.

Strain Echocardiography and Cardiac MRI Evaluation of a Symptomatic Myopericarditis after the Pfizer-BioNTech mRNA COVID-19 Vaccine (preprint)

Background: The COVID-19 pandemic and the accompanying new generation vaccines have entered our lives with many unknown effects. Method and result: This is a case report of myopericarditis diagnosed with fever and chest pain 3 days after the 2nd dose of Pfizer-BioNTech COVID-19 mRNA Vaccine in an 18-year-old man. The diagnosis was confirmed by cardiac MRI(CMR), but we presented that this diagnosis and follow-up could be made accurately with strain echocardiography(SE). Conclusion: It would be beneficial for the cardiologists who perform the primary follow-up of these patients to know that it is possible with SE to support the diagnosis and follow-up of these patients, even if CMR is not accesible.

Improving Fairness of Automated Chest X-ray Diagnosis by Contrastive Learning (preprint)

Purpose: Limited studies exploring concrete methods or approaches to tackle and enhance model fairness in the radiology domain. Our proposed AI model utilizes supervised contrastive learning to minimize bias in CXR diagnosis. Materials and Methods: In this retrospective study, we evaluated our proposed method on two datasets: the Medical Imaging and Data Resource Center (MIDRC) dataset with 77,887 CXR images from 27,796 patients collected as of April 20, 2023 for COVID-19 diagnosis, and the NIH Chest X-ray (NIH-CXR) dataset with 112,120 CXR images from 30,805 patients collected between 1992 and 2015. In the NIH-CXR dataset, thoracic abnormalities include atelectasis, cardiomegaly, effusion, infiltration, mass, nodule, pneumonia, pneumothorax, consolidation, edema, emphysema, fibrosis, pleural thickening, or hernia. Our proposed method utilizes supervised contrastive learning with carefully selected positive and negative samples to generate fair image embeddings, which are fine-tuned for subsequent tasks to reduce bias in chest X-ray (CXR) diagnosis. We evaluated the methods using the marginal AUC difference ($\delta$ mAUC). Results: The proposed model showed a significant decrease in bias across all subgroups when compared to the baseline models, as evidenced by a paired T-test (p<0.0001). The $\delta$ mAUC obtained by our method were 0.0116 (95\% CI, 0.0110-0.0123), 0.2102 (95% CI, 0.2087-0.2118), and 0.1000 (95\% CI, 0.0988-0.1011) for sex, race, and age on MIDRC, and 0.0090 (95\% CI, 0.0082-0.0097) for sex and 0.0512 (95% CI, 0.0512-0.0532) for age on NIH-CXR, respectively. Conclusion: Employing supervised contrastive learning can mitigate bias in CXR diagnosis, addressing concerns of fairness and reliability in deep learning-based diagnostic methods.

Prevalence of post-COVID symptoms in a cohort of hospitalized patients in the North Coast of Colombia (preprint)

Understanding the prevalence and severity of post-COVID-19 conditions among hospitalized patients is crucial for developing effective strategies for managing the long-term consequences of the disease. This study aimed to estimate the prevalence and severity of post-COVID-19 conditions in previously hospitalized COVID-19 patients. The study involved two phases: first, participants were contacted via phone call by trained personnel from the healthcare company and surveyed. In the second phase, two months after the telephone survey, a medical visit was conducted in the group of individuals who reported persistent symptoms in the previous call. Summary statistics such as mean, standard deviation (SD), interquartile range (IQR), 95%CI as well as absolute and relative frequencies of patients' baseline characteristics were reported. Changes were assessed through statistical tests for differences in means and proportions. Multivariate analyses were also conducted. The prevalence of at least one post-hospitalization condition after three months of COVID-19 hospitalization was 78.7 per 100 people. The most common symptoms included fatigue (55.4%), joint pain (46.0%), dyspnea (44.6%), sleep disorders (36.1%), anorexia (33.7%), and chest pain (31.7%). These conditions were frequent and disabling, experiencing at least one condition after three months. Within this group, more than 70% showed a deterioration in their health status (EQ5D-5L Scale) or experienced new or worsened disability in at least one domain of the Washington Group. Our study demonstrates that post-COVID-19 conditions in previously hospitalized patients are highly prevalent, which can adversely affect patients' quality of life and lead to increased demand for healthcare services.

Quantitative susceptibility mapping at 7 Tesla in COVID-19: mechanistic and outcome associations (preprint)

Post mortem studies have shown that patients dying from severe SARS-CoV-2 infection frequently have pathological changes in their central nervous system, particularly in the brainstem. Many of these changes are proposed to result from para-infectious and/or post-infection immune responses. Clinical symptoms such as fatigue, breathlessness, and chest pain are frequently reported in post-hospitalized COVID-19 patients. We propose that these symptoms are in part due to damage to key neuromodulatory brainstem nuclei. While brainstem involvement has been demonstrated in the acute phase of the illness, the evidence of long-term brainstem change on magnetic resonance imaging (MRI) is inconclusive. We therefore used ultra-high field (7T) quantitative susceptibility mapping (QSM) to test the hypothesis that brainstem abnormalities persist in post-COVID patients and that these are associated with persistence of key symptoms. We used 7T QSM data from 30 patients, scanned 93 - 548 days after hospital admission for COVID-19 and compared them to 51 age-matched controls without prior history of COVID-19 infection. We correlated the patients QSM signals with disease severity (duration of hospital admission and COVID-19 severity scale), inflammatory response during the acute illness (C-reactive protein, D-Dimer and platelet levels), functional recovery (modified Rankin scale; mRS), depression (PHQ-9) and anxiety (GAD-7). In COVID-19 survivors the MR susceptibility increased in the medulla, pons and midbrain regions of the brainstem. Specifically, there was increased susceptibility in the inferior medullary reticular formation and the raphe pallidus and obscurus. In these regions, patients with higher tissue susceptibility had worse acute disease severity, higher acute inflammatory markers, and significantly worse functional recovery. Using non-invasive ultra-high field 7T MRI, we show evidence of brainstem pathophysiological changes associated with inflammatory processes in post-hospitalized COVID-19 survivors. This study contributes to understanding the mechanisms of long-term effects of COVID-19 and recovery.

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.

Prevalence of Long COVID19 among paediatric age group in Duhok Kurdistan region, Iraq (preprint)

Background A range of persistent symptoms that can develop in some people after they have recovered from acute COVID-19, is known as Long COVI-19. It can affect people of all ages and severity of initial illness, including those who had mild or asymptomatic infections. . Dealing with Long COVID-19 can be challenging, and the best course of action will depend on the specific symptoms and individual needs of the patient. This study aims to detect the prevalence of long covid-19 among the children who tested positive for IgG test. If IgG antibodies are detected in a person's blood sample, it suggests that they have been infected with SARS-CoV-2 at some point in the past and their immune system has responded by producing antibodies against the virus. Material and Methodology From (October 22nd till December 4th 2022) the data of this study had been collected through a face-to-face interview with withdrawing blood samples for serum Immunoglobin-G test in laboratory of (General zakho Teaching Hospital in Zakho) and (Hevi Pediatric Teaching Hospital in Duhok) . A total number of 330 children aged between 5-12 ages participated in this study. Moreover, If IgG antibodies are detected in a person's blood sample, it suggests that they have been infected with SARS-CoV-2 at some point in the past and their immune system has responded by producing antibodies against the virus. Results ( Fatigue 12/ 85.7% ) , ( cough 10/ 71.4% ) , ( post exertional malaise 5/ 35.7%) were the most detected symptoms among the 14 positive patients. Followed by ( headache, dizziness , hair loss , loss of appetite, loss/change in smell and taste , difficulty in sleep , mood change, abdominal pain, change in bowel habits, chest pain) to lesser extent. Conclusion long-term sequelae of Covid-19 now is becoming a challenge that needs more continued research and collaboration among healthcare providers, researchers, and patients are essential. Long COVID-19 is a public health concern that requires ongoing attention and resources, as well as support for those who are experiencing its debilitating effects. Out of 330 children only 4.6% ( 14 children) were experiencing long covid-19 symptoms for more than 4 weeks after acute infections in Duhok city.

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.

Nationally representative prevalence and determinants of post-acute sequelae of SARS-CoV-2 infection (Long COVID) amongst Mexican adults in 2022 (preprint)

OBJECTIVETo characterize the epidemiology of post-acute sequelae after SARS-CoV-2 infection (PASC) in Mexico during 2022 and identify potential predictors of PASC prevalence using nationally representative data. METHODSWe analyzed data from the 2022 Mexican National Health and Nutrition Survey (ENSANUT) totaling 24,434 participants, representing 85,521,661 adults [≥]20 years. PASC was defined using both the World Health Organization definition and a PASC score [≥]12. Estimates of PASC prevalence were stratified by age, sex, rural vs. urban setting, social lag quartiles, number of reinfections, vaccination status and by periods of predominance of SARS-CoV-2 circulating variants. Predictors of PASC were assessed using logistic regression models adjusted by survey weights. RESULTSPersistent symptoms after SARS-CoV-2 infection were reported by 12.44% (95%CI 11.89-12.99) of adults [≥]20 years in Mexico during 2022. The most common persistent symptoms were musculoskeletal pain, headache, cough, loss of smell or taste, fever, post-exertional malaise, brain fog, anxiety, chest pain, and sleep disorders. PASC was present in 21.21% (95%CI 7.71-9.65) subjects with previously diagnosed COVID-19. Over 28.6% patients with PASC reported symptoms persistence [≥]6 months and 14.05% reported incapacitating symptoms. Higher PASC prevalence was associated with SARS-CoV-2 reinfections, depressive symptoms and living in states with high social lag. PASC prevalence, particularly its more severe forms, decreased with COVID-19 vaccination and for infections during periods of Omicron variant predominance. CONCLUSIONSPASC implies a significant public health burden in Mexico as the COVID-19 pandemic transitions into endemicity. Promoting reinfection prevention and booster vaccination may be useful to reduce PASC burden.

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.

Clinical and Epidemiological Risk Factors Associated with Hospitalization and Mortality Rate of COVID-19 Patients in Banja Luka County: Retrospective Observational Cohort Study on 40,000 patients (preprint)

Background and Objectives: Since the beginning of COVID-19 pandemic, the infection primarily affected patients with following chronic conditions: cardiovascular disease, hypertension, chronic obstructive pulmonary disease, diabetes mellitus, obesity and cancer. The aim of this study was to explore clinical and epidemiological characteristics associated with COVID-19 outcomes in patients at the primary health care centre from March 2020 to September 2022. Materials and Methods: The study included 40,692 citizens of Banja Luka County, Bosnia and Herzegovina, who were confirmed and registered as RT-PCR positive on COVID-19. Differences regarding the distributions of patients between groups were analysed using Pearson chi square test and Mantel-Haenszel chi square test for trends, while differences in mean values were compared using independent samples t test. Relationship between mortality and independent variables were examined using logistic regression. Results: Out of 40,692 COVID-19 positive patients, 7.76% were hospitalized. The average age of hospitalized patients was significantly higher than the age of non-hospitalized patients (64.2±16.1 vs. 45.4±18.7; p<0.001). The average age of patients with lethal outcome was nearly twice higher compared to patients with non-lethal outcome (74.6±11.5 vs. 45.7±18.6; p<0.001). Male patients had higher hospitalization and mortality rate, compared to females (9.8% vs. 5.9%, p<0.001; 4.8% vs. 3%, p<0.001, respectively). The highest hospitalization rate was in patients with chronic renal failure, diabetes and cardiovascular diseases, while the death rate was the highest among patients with CRF and hearth comorbidities. Fever, cough, fatigue, nausea and vomiting, chest pain, shortness of breath and appetite loss favoured hospitalization. Patients with fatigue and appetite loss had higher percentage of lethal outcome. Vaccinated patients had significantly lower rate of lethal outcome. Conclusions: Clinical symptoms, signs and outcomes, are posing as predictive parameters for further management of COVID-19. Vaccination has an important role in clinical outcomes of COVID-19.

Post-COVID-19 Complications and their Laboratory Findings: A Cohort Study.

Type 2 severe acute respiratory syndrome caused by coronavirus infection has become the most well-known pandemic infectious viral disease in the present century. This study aims to find out the post-COVID-19 infection complications via a well-designed observational study. A total of 986 recovered cases (only the period ranged between 2 to 3 months after recovery) were obtained from public and private hospitals in Kirkuk and Erbil governorates\Iraq. The admitted patients were asked to answer a questionnaire through interviews; the laboratory findings were obtained from the patients. The results suggested that approximately half of post-COVID-19 patients (%45.606) were suffering from chest pain, while (%32.357) of the cases suffered headache and chest pain. Liver enzymes (ALT, AST, and ALP) showed abnormal percent values of 38.6,24.07, and 26.09, respectively. Renal function enzymes, mainly urea, were found to be abnormal in 45.37% of recovered individuals. Furthermore, abnormal LDH levels were found in (77.9%) of post-COVID-19 patients. This finding revealed that chest pain was an inflammatory condition and liver and renal enzyme disturbances, while elevation in LDH was the predominant long-term complication in post-COVID-19 patients.