Dynamics of SARS-CoV-2 Seroprevalence in a Large US population Over a Period of 12 Months (preprint)

Due to a combination of asymptomatic or undiagnosed infections, the proportion of the United States population infected with SARS-CoV-2 was unclear from the beginning of the pandemic. We previously established a platform to screen for SARS-CoV-2 positivity across a representative proportion of the US population, from which we reported that almost 17 million Americans were estimated to have had undocumented infections in the Spring of 2020. Since then, vaccine rollout and prevalence of different SARS-CoV-2 variants have further altered seropositivity trends within the United States population. To explore the longitudinal impacts of the pandemic and vaccine responses on seropositivity, we re-enrolled participants from our baseline study in a 6- and 12- month follow-up study to develop a longitudinal antibody profile capable of representing seropositivity within the United States during a critical period just prior to and during the initiation of vaccine rollout. Initial measurements showed that, since July 2020, seropositivity elevated within this population from 4.8% at baseline to 36.2% and 89.3% at 6 and 12 months, respectively. We also evaluated nucleocapsid seropositivity and compared to spike seropositivity to identify trends in infection versus vaccination relative to baseline. These data serve as a window into a critical timeframe within the COVID-19 pandemic response and serve as a resource that could be used in subsequent respiratory illness outbreaks.

The macroeconomic and epidemiological impacts of Covid-19 in Pakistan. (preprint)

'Coronavirus Disease 2019' (C19) is a respiratory illness caused by 'new Coronavirus' SARS-CoV-2. The C19 pandemic, which engulfed the world in 2021, also caused a national C19 epidemic in Pakistan, who responded with initial forced lockdowns (15-30 March 2020) and a subsequent switch to a smart lockdown strategy, and, by 31 December 2020, Pakistan had managed to limit confirmed cases and case fatalities to 482,506 (456 per 100,000) and 10,176 (4.8 per 100,000). The early switch to a smart lockdown strategy, and successful follow-up move to central coordination and effective communication and enforcement of Standard Operating Procedures, was motivated by a concern over how broad-based forced lockdowns would affect poor households and day-labour. The current study aims to investigate how the national Pakistan C19 epidemic would have unfolded under an uncontrolled baseline scenario and an alternative set of controlled non-pharmaceutical intervention (NPI) policy lockdown scenarios, including health and macroeconomic outcomes. We employ a dynamically-recursive version of the IFPRI Standard Computable General Equilibrium model framework (Lofgren, Lee Harris and Robinson 2002), and a, by now, well-established epidemiological transmission-dynamic model framework (Davies, Klepac et al 2020) using Pakistan-specific 5-year age-group contact matrices on four types of contact rates, including at home, at work, at school, and at other locations (Prem, Cook & Jit 2017), to characterize an uncontrolled spread of disease. Our simulation results indicate that an uncontrolled C19 epidemic, by itself, would have led to a 0.12% reduction in Pakistani GDP (-721mn USD), and a total of 0.65mn critically ill and 1.52mn severely ill C19 patients during 2020-21, while 405,000 Pakistani citizens would have lost their lives. Since the majority of case fatalities and symptomatic cases, respectively 345,000 and 35.9mn, would have occurred in 2020, the case fatality and confirmed case numbers, observed by 31. December 2020 represents an outcome which is far better than the alternative. Case fatalities by 31. December 2020 could possibly have been somewhat improved either via a more prolonged one-off 10 week forced lockdown (66% reduction) or a 1-month forced lockdown/2-months opening intermittent lockdown strategy (33% reduction), but both sets of strategies would have carried significant GDP costs in the order of 2.2%-6.2% of real GDP.

survInTime - Exploring surveillance methods and data analysis on Brazilian respiratory syndrome dataset and community mobility changes (preprint)

Background: The covid-19 pandemic brought negative impacts in almost every country in the world. These impacts were observed mainly in the public health sphere, with a rapid raise and spread of the disease and failed attempts to restrain it while there was no treatment. However, in developing countries, the impacts were severe in other aspects such as the intensification of social inequality, poverty and food insecurity. Specifically in Brazil, the miscommunication among the government layers conducted the control measures to a complete chaos in a country of continental dimensions. Brazil made an effort to register granular informative data about the case reports and their outcomes, while this data is available and can be consumed freely, there are issues concerning the integrity and inconsistencies between the real number of cases and the number of notifications in this dataset. Results: We projected and implemented four types of analysis to explore the Brazilian public dataset of Severe Acute Respiratory Syndrome (srag dataset) notifications and the google dataset of community mobility change (mobility dataset). These analysis provides some diagnosis of data integration issues and strategies to integrate data and experimentation of surveillance analysis. The first type of analysis aims at describing and exploring the data contained in both datasets, starting by assessing the data quality concerning missing data, then summarizing the patterns found in this datasets. The Second type concerns an statistical experiment to estimate the cases from mobility patterns organized in periods of time. We also developed, as the third analysis type, an algorithm to help the understanding of the disease waves by detecting them and compare the time periods across the cities. Lastly, we build time series datasets considering deaths, overall cases and residential mobility change in regular time periods and used as features to group cities with similar behavior. Conclusion: The exploratory data analysis showed the under representation of covid-19 cases in many small cities in Brazil that were absent in the srag dataset or with a number of cases very low than real projections. We also assessed the availability of data for the Brazilian cities in the mobility dataset in each state, finding out that not all the states were represented and the best coverage occurred in Rio de Janeiro state. We compared the capacity of place categories mobility change combination on estimating the number of cases measuring the errors and identifying the best components in mobility that could affect the cases. In order to target specific strategies for groups of cities, we compared strategies to cluster cities that obtained similar outcomes behavior along the time, highlighting the divergence on handling the disease. Availability: https://github.com/YasCoMa/dashboard-srag-mobility

Emerging Links Between COVID-19 and Cardiovascular & Cerebrovascular Thromboembolic Events: A Systematic Review (preprint)

COVID-19, caused by the SARS-CoV-2 virus, initially identified as a respiratory illness, has increasingly been linked to a broader range of organ complications. This systematic review explores the impact of COVID-19 on cardiovascular and cerebrovascular health, focusing on thromboembolic events in post-COVID patients. A comprehensive literature search was conducted in PubMed and Google Scholar databases up to July 2023, utilizing the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies meeting eligibility criteria were analyzed for outcomes and associations between COVID-19 and cardiovascular and cerebrovascular events. The review includes 6 studies involving over 12 million patients, demonstrating a strong connection between COVID-19 and elevated risks of cardiovascular and cerebrovascular thromboembolic events. The risk of these events is evident in conditions such as ischemic heart disease, stroke, and cardiac arrhythmias. The burden of these events beyond the acute phase of the disease is concerning, warranting further exploration of long-term implications. Variability in event rates among different cohorts and healthcare settings underscores the need for understanding underlying factors influencing these differences. Potential mechanisms behind these events include endothelial dysfunction, systemic inflammation, and viral invasion. Implications for public health policies, clinical guidelines, and future research directions are discussed. This review serves as a valuable resource for healthcare providers, policymakers, and researchers to enhance patient care, outcomes, and preparedness for future waves of COVID-19 infections. However, there remain unexplored aspects of the COVID-19 and thromboembolic events relationship, urging further investigations into mechanistic insights and potential therapeutic interventions.

A Causal Inference of the Effect of Vaccination on COVID-19 Disease Severity and Need for Intensive Care Unit Admission Among Hospitalized Patients in an African Setting (preprint)

BackgroundThe COVID-19 pandemic is a respiratory illness that has spread to over 210 countries and killed over 6 million people. There is no specific treatment for COVID-19, but vaccines have been developed that can help prevent severe illness and death. A number of studies have investigated the effect of vaccination on disease severity and outcome, and the findings indicate that vaccination is linked to a significant reduction in the risk of hospitalization, intensive care unit admission, and death from the disease. However, there is a scarcity of evidence in Africa in general, and no similar study has been conducted in Ethiopia yet. Therefore, the study aimed to assess the effect of vaccination on COVID-19 disease severity and need for Intensive Care Unit (ICU) admission among hospitalized patients at a private specialty clinic in Ethiopia. MethodsA retrospective cohort study was conducted among 126 patients with COVID-19, 41 vaccinated and 85 unvaccinated, who were hospitalized between September 2021 and May 2022. Data was summarized using frequency (percentage) and median (interquartile range). To compare the characteristics of the two groups, Chi-square/ Fishers Exact and Mann Whitney U tests at p-value of [≤] 0.05 were used. To identify the effect of vaccination on COVID-19 disease severity, Marginal Structural Model (MSM) with inverse probability weighting (IPW) approach using robust poisson regression model was fitted and adjusted relative risk (ARR) and 95% CI for ARR were used for interpreting the result. ResultsThe cohort included groups that were fairly comparable in terms of their sociodemographic and clinical characteristics. More than half of the participants were older than 60 years (52.4%), were males (56.3%) and had one or more comorbid illness (52.4%). At admission 85 (67.5%) had severe disease and 11 (8.7%) progressed after hospitalization and required ICU admission, of which three unvaccinated cases died. From the final model, vaccination was found to be associated with a 62% decreased risk of developing severe COVID-19 disease if infected, compared to not getting vaccinated (ARR=0.38, 95% CI=0.23-0.65, p<0.0001). ConclusionsThe studys findings support previous reports that vaccinated people are less likely to develop severe COVID-19 disease if infected with the virus, emphasizing the importance of continuing efforts to promote COVID-19 vaccination not only to safeguard individuals but also to confer community-level immunity.

Neutralizing antibody responses and cellular responses against severe acute respiratory syndrome coronavirus 2 omicron subvariant BA.5 after an mRNA severe acute respiratory syndrome coronavirus 2 vaccine dose in kidney transplant recipients (preprint)

We examined the anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein IgG antibody and neutralizing antibody titers and cellular immunity in 73 uninfected recipients and 17 uninfected healthy controls who received three doses of a coronavirus 2019 mRNA vaccine. Neutralizing antibody titers were evaluated using GFP-carrying recombinant SARS-CoV-2 with spike protein of B.1.1, omicron BA.1, or BA.5. For cellular immunity, peripheral blood mononuclear cells were stimulated with peptides corresponding to spike protein antigens of B.1.1, BA.1, and BA.5; spike-specific CD4/CD8 memory T cells were evaluated using intracellular cytokine staining. The median IgG antibody titers were 7.8 AU/mL in recipients and 143.0 AU/mL in healthy controls (p < 0.0001). Neutralizing antibody titers against all three viral variants were significantly lower in recipients (p < 0.0001). The number of spike-specific CD8 + memory T cells significantly decreased in recipients (p < 0.0001). Twenty recipients and seven healthy controls additionally received a bivalent omicron-containing booster vaccine, and IgG antibody and neutralizing antibody titers increased in both groups; however, the increase was significantly lower in recipients. Recipients did not gain sufficient immunity with a third dose of vaccine, suggesting a need to explore methods other than vaccines.

Prolonged exposure to lung-derived cytokines is associated with inflammatory activation of microglia in patients with COVID-19 (preprint)

Neurological impairment is the most common finding in patients with post-acute sequelae of COVID-19. Furthermore, survivors of pneumonia from any cause have an elevated risk of dementia. Dysfunction in microglia, the primary immune cell in the brain, has been linked to cognitive impairment in murine models of dementia and in humans. Here, we report a transcriptional response in human microglia collected from patients who died following COVID-19 suggestive of their activation by TNF- and other circulating pro-inflammatory cytokines. Consistent with these findings, the levels of 55 alveolar and plasma cytokines were elevated in a cohort of 341 patients with respiratory failure, including 93 unvaccinated patients with COVID-19 and 203 patients with other causes of pneumonia. While peak levels of pro-inflammatory cytokines were similar in patients with pneumonia irrespective of etiology, cumulative cytokine exposure was higher in patients with COVID-19. Corticosteroid treatment, which has been shown to be beneficial in patients with COVID-19, was associated with lower levels of CXCL10, CCL8, and CCL2 - molecules that sustain inflammatory circuits between alveolar macrophages harboring SARS-CoV-2 and activated T cells. These findings suggest that corticosteroids may break this cycle and decrease systemic exposure to lung-derived cytokines and inflammatory activation of microglia in patients with COVID-19.

Comparative effectiveness of sotrovimab versus no treatment in non-hospitalised high-risk patients with COVID-19 in North West London: aretrospective cohort study using the Discover dataset (preprint)

IntroductionThere is uncertainty regarding how in vitro antibody neutralisation activity translates to the clinical efficacy of sotrovimab against severe acute respiratory syndrome coronavirus 2, although real-world evidence has demonstrated continued effectiveness during both BA.2 and BA.5 predominance. We previously reported descriptive results from the Discover dataset for patients treated with sotrovimab, nirmatrelvir/ritonavir or molnupiravir, or patients at highest risk per National Health Service (NHS) criteria but who were untreated. This study sought to assess the effectiveness of sotrovimab compared with no early coronavirus disease 2019 (COVID-19) treatment in highest-risk patients with COVID-19. MethodsRetrospective cohort study using the Discover dataset in North West London. Patients had to be non-hospitalised at index, aged [≥]12 years old and meet [≥]1 of the NHS highest-risk criteria for receiving early COVID-19 treatment with sotrovimab. The primary objective was to assess the risk of COVID-19-related hospitalisation and/or COVID-19-related death within 28 days of the observed/imputed treatment date between patients treated with sotrovimab and highest-risk patients who received no early COVID-19 treatment. We also performed subgroup analyses for patients aged <65 and [≥]65 years, patients with renal dysfunction, and by Omicron subvariant prevalence period (BA.1/2 emergence: 1 December 2021-12 February 2022 [period 1]; BA.2 reaching and at its peak: 13 February-31 May 2022 [period 2]; BA.2 falling and BA.4/5 emergence: 1 June-31 July 2022 [period 3]). Inverse probability of treatment weighting based on propensity scores was used to adjust for measured known and likely confounders between the cohorts. Cox proportional hazards models with stabilised weights were performed to assess hazard ratios (HRs). ResultsA total of 599 highest-risk patients treated with sotrovimab and 5,191 untreated highest-risk patients were included. Compared with untreated patients, sotrovimab treatment reduced the risk of COVID-19 hospitalisation or death by 50% (HR=0.50; 95% confidence interval [CI] 0.24, 1.06); however, statistical significance was not reached (p=0.07). In addition, sotrovimab reduced the risk of COVID-19 hospitalisation by 57% (HR=0.43; 95% CI 0.18, 1.00) compared with the untreated group, although also not statistically significant (p=0.051). Among patients aged [≥]65 years and patients with renal disease, sotrovimab treatment was associated with a significantly reduced risk of COVID-19 hospitalisation, by 89% (HR=0.11; 95% CI 0.02, 0.82; p=0.03) and 82% (HR=0.18; 95% CI 0.05, 0.62; p=0.007), respectively. In period 1, sotrovimab treatment was associated with a 75% lower risk of COVID-19 hospitalisation or death compared with the untreated group (HR=0.25; 95% CI 0.07, 0.89; p=0.032). In periods 2 and 3, HRs of COVID-19 hospitalisation or death were 0.53 (95% CI 0.14, 2.00; p=0.35) and 0.78 (95% CI 0.23, 2.69; p=0.69), respectively, for the sotrovimab versus untreated groups, but differences were not statistically significant. ConclusionsSotrovimab treatment was associated with a significant reduction in risk of COVID-19 hospitalisation in patients aged [≥]65 years and those with renal disease compared with the untreated cohort. For the overall cohort, the risk of hospitalisation following sotrovimab treatment was also lower compared with the untreated group; however, this did not achieve statistical significance (p=0.051). The risk of hospitalisation and/or death was lower for the sotrovimab-treated cohort across all time periods but did not reach significance for periods 2 and 3.

New approach to estimate effectiveness of vaccination against COVID - 19: a proportional case vaccinated-based model (preprint)

Background Over the past decades, Outbreaks of numerous infectious diseases have become international emergencies; one of the epidemics of the 21st century was the Covid-19 pandemic. Since the beginning of the corona virus, mass vaccination has been proposed as one of the most effective ways to end this epidemic. Yet, even after vaccination, re-infection with severe acute respiratory syndrome coronavirus2 (SARS-CoV-2) may occur which is called breakthrough infections, because the Covid-19 vaccines do not offer 100% protection. For this reason, our goal is to investigate the effectiveness of the covid-19 vaccination in reducing cases of infection and mortalityMethods In this study, Proportional Vaccinated Case (P.V.C) was used to calculate the effectiveness of vaccination in the city of Shiraz and the cities covered by Shiraz University of Medical Sciences between August 23 and December 21, 2022. Our data is gathered from electronic collection systems, including the Sib system, the CORONA LAB system, and the MCMC system.Result the Effectiveness of all vaccines were studied in reducing morbidity and mortality in people who had injected their second dose of vaccine and 14 days or more had passed since their injection was 48.17% and 97.47%, respectively. In contrast, for BIBP-CorV vaccine these numbers are estimated to be 49.58% and 92.88% respectively.Conclusion Finally, the aim of this study was to use a new approach to calculate the effectiveness of the vaccine in reducing mortality and infection. Our study showed that vaccination has been effective in reducing deaths caused by covid-19، although the effective results of vaccination in our study in reducing cases of infection wasn't very high .Yet, more and more extensive studies on different strains of the Covid-19 virus are required to prove this issue.

Six-Month Post-Intensive Care Outcomes During High and Low Bed Occupancy due to the COVID-19 Pandemic: a Multicenter Prospective Cohort Study (preprint)

Purpose: The COVID-19 pandemic can be seen as a natural experiment to test how bed occupancy affects post-intensive care unit (ICU) patient's functional outcomes. Therefore, we compared by bed occupancy the frequency of mental, physical, and cognitive impairments in patients admitted to ICU during the COVID-19 pandemic. Methods: Prospective cohort of adults mechanically ventilated >48 hours in one of 19 ICUs in seven Chilean public and private hospitals. Ninety per cent of nationwide beds occupied was the cut-off for low versus high bed occupancy. At ICU discharge, 3- and 6-month follow-up, we assessed disability using the World Health Organization Disability Assessment Schedule 2.0, quality of life, mental, physical, and cognitive outcomes following the core outcome set for acute respiratory failure. Results: 252 eligible participants were enrolled, 103(41%) during low and 149(59%) during high occupancy. Patients treated during high occupancy were younger (P50[P25-P75]: 55[44-63] vs 61[51-71]; p<0.001), more likely to be admitted due to COVID-19 (126[85%] vs 65[63%]; p<0.001), and have higher education qualification (94[63%] vs 48[47%]; p=0.03). No differences were found in the frequency of at least one mental, physical or cognitive impairment by bed occupancy at ICU discharge (low vs high: 93% vs 91%; p=0.6), 3-month (74% vs 63%; p=0.2) and 6-month (57% vs 57%; p=0.9) follow-up. Conclusions: There were no differences in post-ICU outcomes between high and low bed occupancy. Most patients had at least one mental, physical or cognitive impairment at ICU discharge, which remained high at 6-month follow-up.

Inclusion Criteria for Extracorporeal Membrane Oxygenation (ECMO) in Patients with Acute Respiratory Distress Syndrome (ARDS) Due to COVID-19: A Systematic Review (preprint)

IntroductionAt the end of 2019, in the city of Wuhan, China, a virus of the family of coronaviruses first appeared, mainly affecting the respiratory system, which was called SARS-COV-2 and causes COVID-19. Although in most patients, it occurs with mild symptomatology, however, a significant percentage (15-30%) will develop acute respiratory distress syndrome (ARDS) with increased chances of intubation and mechanical ventilation. In special cases of severe disease, where the oxygenation of the patient is not improved by the use of the ventilator, extracorporeal membrane oxygenation (ECMO) can be applied, a technique that has been used in previous pandemics that affected the respiratory system. AimTo investigate the evidence of the appliance of the ECMO, based on international literature, of the extracorporeal membrane oxygenator in patients with severe respiratory failure due to Covid-19 disease. MethodArticles were searched on the international bases of scientific studies PubMed, Cochrane Library, and Google Scholar. This review was carried out using meta-analysis and international guidelines. ResultsFour articles were included where there was an agreement on the basic characteristics of patients, which can be considered as selection criteria. The primary criteria indicate the age, where the patient must be under 65 years old, and the body mass index (BMI) should be below 40. In addition, it is very important that there is no serious underlying pathology such as multi-organ failure syndrome. Also, the mechanical ventilation should not exceed seven (7) days until the placement of the ECMO, while all the other therapeutic methods, such as the prone position, neuromuscular blockers, and the appropriate positive end-expiratory pressure of the airways (Positive end-expiratory pressure - PEEP) should be already applied. ConclusionsThe application of ECMO is widely used as a treatment for patients with severe COVID-19 disease. However, in order to have the best therapeutic results while reducing hospitalization costs, it is necessary to follow the guidelines regarding the selection of patients who will benefit substantially.

Clinical Profile, Comorbidities, and Outcome of the Unvaccinated and Hospitalized for COVID-19 in Northern Brazil: Retrospective Cohort (preprint)

Over the course of the pandemic, COVID-19 affected health, the economy and quality of life in Brazil. The worst years for the country were the first and second. There were delays in vaccine purchases for political reasons at the time. The northern region of the country had a higher mortality rate compared to other regions, associated with local vulnerabilities and fragility of surveillance due to geographic and population characteristics. This study aims to investigate the clinical profile, comorbidities, and outcome of unvaccinated people hospitalized for COVID-19 in the state of Para in 2022. Retrospective cohort epidemiological study, with data from the national epidemiological surveillance of acute and severe respiratory syndromes. Cases reported in 2022 with vaccinated yes or no field and completed doses were included. Only closed cases cure or death were included. We performed a chi-square test on categorical variables and a Mann-Whitney test on numerical variables. We compared vaccinated VS non-vaccinated; we performed the Odds Ratio in the significant variables. We used the SPSS 20.0 software. The study worked with 2,634 cases of COVID-19 hospitalized in the study period, confirmed by RT-PCR (851/32.30%) and (1,784/67.70%) rapid antigen test. The lethality was (778/29.53%), and those vaccinated with two doses were (1,473/55.90%) and those unvaccinated with no dose (1,162/44.10%). Death represents p- <0.001 (HR 1.306 - CI 1.124/1.517) higher risk of the event occurring in the unvaccinated cases, followed by male sex p-0.004 (HR 1.188 - CI 1.058/1.334).. The first cohort in Brazil and in the north of the country to evaluate the clinical profile, comorbidities, and outcome of COVID-19 in hospitalized patients in this Amazon region, which is a region characterized by local vulnerability factors unique to the other regions of Brazil, showed that the unvaccinated were males, younger, with fewer comor-bidities, and that they were associated the deaths.

Follow-Up In Patients With Respiratory Disability After ARDS Related To COVID-19: A Systematic Review (preprint)

Introduction: Acute Respiratory Distress Syndrome (ARDS) is an acute inflammatory pulmonary process that leads to protein-rich, non-hydrostatic pulmonary edema, undesirable hypoxemia, and lung stiffness. Due to COVID-19, a significant proportion of people who will require hospitalization to treat COVID-19, between 15%-30%, will develop severe respiratory failure, ARDS, and an increased likelihood of intubation for mechanical respiratory support. Aim: To investigate the pulmonary function in COVID-19-related ARDS survivors after hospitalization. Methods: A search was performed on the Greek and international literature, as well as at the online Databases PubMed, Cochrane, Embase, and Google Scholar. Exclusion and integration criteria were set for the studies found, and a flow chart was created for the studies included. Results: Through the search, 352 articles were found matching the subject under study, and after further evaluation, four articles were included. The majority of the articles highlight that after ARDS occurs due to COVID-19, patients face impaired pulmonary function in combination with other physical and psychological symptoms like weakness, anxiety, depression, and generalized functional disability. Conclusions: It is a fact that COVID-19 disease, in severe form and following the need for hospitalization due to the development of ARDS, results in an increased likelihood of prolonged occurrence of some symptoms of impaired respiratory function. Impaired CO2 diffusion is observed in the majority of studies as well as impaired respiratory function regarding prolonged imaging findings and impaired physical function. Keywords: ARDS, SARS-CoV-2, ICU, COVID-19, follow up, respiratory function

Hemodynamic Effects of Awake Prone Positioning With COVID-19 Acute Respiratory Failure.

INTRODUCTION: Awake prone positioning (PP) reduces need for intubation for patients with COVID-19 with acute respiratory failure. We investigated the hemodynamic effects of awake PP in non-ventilated subjects with COVID-19 acute respiratory failure. METHODS: We conducted a single-center prospective cohort study. Adult hypoxemic subjects with COVID-19 not requiring invasive mechanical ventilation receiving at least one PP session were included. Hemodynamic assessment was done with transthoracic echocardiography before, during, and after a PP session. RESULTS: Twenty-six subjects were included. We observed a significant and reversible increase in cardiac index (CI) during PP compared to supine position (SP): 3.0 ± 0.8 L/min/m2 in PP, 2.5 ± 0.6 L/min/m2 before PP (SP1), and 2.6 ± 0.5 L/min/m2 after PP (SP2, P < .001). A significant improvement in right ventricular (RV) systolic function was also evidenced during PP: The RV fractional area change was 36 ± 10% in SP1, 46 ± 10% during PP, and 35 ± 8% in SP2 (P < .001). There was no significant difference in PaO2 /FIO2 and breathing frequency. CONCLUSION: CI and RV systolic function are improved by awake PP in non-ventilated subjects with COVID-19 with acute respiratory failure.

What else in times of COVID-19? The role of minimally invasive autopsy for the differential diagnosis of acute respiratory failure in a case of kala-azar.

Visceral leishmaniasis (VL) is a chronic vector-borne zoonotic disease caused by trypanosomatids, considered endemic in 98 countries, mainly associated with poverty. About 50,000-90,000 cases of VL occur annually worldwide, and Brazil has the second largest number of cases in the world. The clinical picture of VL is fever, hepatosplenomegaly, and pancytopenia, progressing to death in 90% of cases due to secondary infections and multi-organ failure, if left untreated. We describe the case of a 25-year-old female who lived in the metropolitan area of Sao Paulo, who had recently taken touristic trips to several rural areas in Southeastern Brazil and was diagnosed post-mortem. During the hospitalization in a hospital reference for the treatment of COVID-19, the patient developed acute respiratory failure, with chest radiographic changes, and died due to refractory shock. The ultrasound-guided minimally invasive autopsy diagnosed VL (macrophages containing amastigote forms of Leishmania in the spleen, liver and bone marrow), as well as pneumonia and bloodstream infection by gram-negative bacilli.

Unchanged Characteristics and Survival among Critically Ill COVID-19 Patients during First, Second, and Third Waves: A Prospective Observational Cohort.

BACKGROUND: This study was carried out to compare characteristics and outcomes in patients with acute respiratory failure related to COVID-19 during first, second, and third waves. METHODS: We included consecutive adults admitted to the intensive care unit between March 2020 and July 2021. We compared three groups defined by the epidemic intake phase: waves 1 (W1), 2 (W2), and 3 (W3). RESULTS: We included 289 patients. Two hundred and eight (72%) patients were men with a median age of 63 years (IQR: 54-72), of whom 68 (23.6%) died in hospital. High-flow nasal oxygen (HFNO) was inversely associated with the need for invasive mechanical ventilation (MV) in multivariate analysis (p = 0.003) but not dexamethasone (p = 0.25). The day-90 mortality rate did not vary from W1 (27.4%) to W2 (23.9%) and W3 (22%), p = 0.67. By multivariate analysis, older age (odds ratio [OR]: 0.94/year, p < 0.001), immunodeficiency (OR: 0.33, p = 0.04), acute kidney injury (OR: 0.26, p < 0.001), and invasive MV (OR: 0.13, p < 0.001) were inversely associated with higher day-90 survival as opposed to the use of intermediate heparin thromboprophylaxis dose (OR: 3.21, p = 0.006). HFNO use and dexamethasone were not associated with higher day-90 survival (p = 0.24 and p = 0.56, respectively). CONCLUSIONS: In patients with acute respiratory failure due to COVID-19, survival did not change between first, second, and third waves while the use of invasive MV decreased. HFNO or intravenous steroids were not associated with better outcomes, whereas the use of intermediate dose of heparin for thromboprophylaxis was associated with higher day-90 survival. Larger multicentric studies are needed to confirm our findings.

Impact of impaired pulmonary function on clinical outcomes in survivors of severe COVID-19 without pre-existing respiratory disease.

OBJECTIVE: To investigate the impact of impaired pulmonary function on patient-centered outcomes after hospital discharge due to severe COVID-19 in patients without preexisting respiratory disease. METHODS: This is an ongoing prospective cohort study evaluating patients (> 18 years of age) 2-6 months after hospital discharge due to severe COVID-19. Respiratory symptoms, health-related quality of life, lung function, and the six-minute walk test were assessed. A restrictive ventilatory defect was defined as TLC below the lower limit of normal, as assessed by plethysmography. Chest CT scans performed during hospitalization were scored for the presence and extent of parenchymal abnormalities. RESULTS: At a mean follow-up of 17.2 ± 5.9 weeks after the diagnosis of COVID-19, 120 patients were assessed. Of those, 23 (19.2%) reported preexisting chronic respiratory diseases and presented with worse lung function and exertional dyspnea at the follow-up visit in comparison with their counterparts. When we excluded the 23 patients with preexisting respiratory disease plus another 2 patients without lung volume measurements, a restrictive ventilatory defect was observed in 42/95 patients (44%). This subgroup of patients (52.4% of whom were male; mean age, 53.9 ± 11.3 years) showed reduced resting gas exchange efficiency (DLCO), increased daily-life dyspnea, increased exertional dyspnea and oxygen desaturation, and reduced health-related quality of life in comparison with those without reduced TLC (50.9% of whom were male; mean age, 58.4 ± 11.3 years). Intensive care need and higher chest CT scores were associated with a subsequent restrictive ventilatory defect. CONCLUSIONS: The presence of a restrictive ventilatory defect approximately 4 months after severe COVID-19 in patients without prior respiratory comorbidities implies worse clinical outcomes.

Transcutaneous Spinal Cord Stimulation Facilitates Respiratory Functional Performance in Patients with Post-acute COVID-19 (preprint)

Background: A growing number of studies have reported Coronavirus disease (COVID-19)-related to both respiratory and central nervous system dysfunctions. This study evaluates the neuromodulatory effects of spinal cord transcutaneous stimulation (scTS) on the respiratory functional state in healthy controls and patients with post-COVID-19 respiratory deficits as a step toward the development of a rehabilitation strategy for these patients.; Methods: In this before-after, interventional, case-controlled clinical study, ten individuals with post-acute COVID-19 respiratory deficits and eight healthy controls received a single twenty-minute-long session of modulated monophasic scTS delivered over the T5 and T10 spinal cord segments. Forced Vital Capacity (FVC), Peak Forced Inspiratory Flow (PIF), Peak Expiratory Flow (PEF), Time-To-Peak of Inspiratory Flow (tPIF), and Time-To-Peak of Expiratory Flow (tPEF) were assessed before and after the intervention; Results: In COVID-19 group, the scTS intervention led to significantly increased PIF (p= .040) and PEF (p= .049) in association with significantly decreased tPIF (p= .035) and tPEF (p= .013). In the Control Group, the exposure to scTS also resulted in significantly increased PIF (p= .010) and significantly decreased tPIF (p= .031). Unlike the results in COVID-19 group, there was significantly decreased PEF (p= .028) in association with significantly increased tPEF (p= .036). There were no changes for FVC after scTS in both groups (p= .67 and p= .503); Conclusions: In post-COVID-19 patients scTS facilitates excitation of both inspiratory and expiratory spinal neural networks leading to an immediate improvement of respiratory functional performance. This neuromodulation approach could be utilized in rehabilitation programs for patients with COVID-19 respiratory deficits.