The Heavy Burden of Sars-Cov-2 Related Pneumonia Requiring High-Oxygen Flow

Aim: there is evidence of significant clinical sequelae of COVID-19 that may impair both life length and its quality. Aim of this study was to assess the long-term consequences of moderate to severe SARS-CoV-2-related pneumonia in patients requiring high-flow oxygen treatment. Method(s): This prospective follow-up study included 45 patients with confirmed COVID-19 admitted to a medical ward at the Montichiari Hospital, Brescia, Italy from November 2020 to April 2021 Patients had COVID-19 related pneumonia with respiratory failure and needed at least treatment with an inspired fraction of oxygen of 40% (of them, 59% were treated with Venturi mask and 41% needed noninvasive ventilation). Patients underwent a clinical assessment with standard laboratory testing, chest CT scan, lung function tests with DLCO, and evaluation of vital parameters after a mean of 382 days after hospital discharge. A quality-of-life questionnaire was administered to each willing patient. Result(s): See table for details. While standard laboratory testing showed a substantial normalization, we found persistence of radiological alterations (i.e. groundglass opacities, irregular linear/reticular opacities) in 61% of patients;mean Tiffenau index (FEV1/FVC) was reduced, although not clearly pathologic (79%) and 38% of patients showed a mild to moderate reduction in CO lung diffusion (DLCO). Interestingly, 54% of subjects showed concomitant presence of radiologic alterations AND persistence of dyspnea OR reduction in CO lung diffusion, while 21% had all three concomitant conditions, compatible with the diagnosis of lung fibrosis. Overall, a total of 75% patients had some degree of functional or structural alteration of respiratory apparatus. We also evaluated quality of life thorough a structured questionnaire: after more than one year 62% of the patients still lamented fatigue, 62% effort dyspnea, 12% anorexia, 29% dysgeusia or anosmia, 31% insomnia and 43% anxiety. Conclusion(s): these data seem to demonstrate that SARS-CoV-2-related pneumonia requiring high flow oxygen has a heavy long-term burden, both in terms of persistence of functional and structural pulmonary damage (which may be progressive and evolve to a more severe degree) and of burden on overall quality daily life. (Figure Presented).

Absence of Major Cardiovascular Event in a Group of Patients Followed for More Than One Year after Severe Covid-19 Pneumoniae

Introduction: The Coronavirus disease 2019 (COVID-19), doesn't affect only respiratory system, but it also involves other organs including cardiovascular system, possibly causing acute or chronic cardiovascular events. Preexisting cardiovascular diseases enhance COVID-19 morbidity, as well. Aim(s): In this retrospective analysis we investigated the onset of cardiovascular events during a time-span of more than one year since hospitalization (384 days). Method(s): The analysis included 43 patients, who were hospitalized in Internal Medicine Department of Montichiari Hospital (ASST Spedali Civili of Brescia) for moderate to severe SARS-CoV2 related pneumonia treated with high-flow oxygen support (ranging from 40% fraction of inspired oxygen to non-invasive ventilation) Mean age was 63 years, 28% (12/43) were female and 72% (31/43) were male. Thirty-five percent of the patients suffered from heart diseases, 56% of them were hypertensives and 23% had type 2 diabetes;12% had chronic kidney disease (CKD) and 5% an active neoplasm. 49% of the sample was obese. Nineteen percent took ACE inhibitors and 19% was on ARBs. Statins were taken by 37% of the patients;an antiaggregant by 21%, and an anticoagulant by 2% (see table) Results: The follow-up visit included the evaluation of post-covid infection quality-of-life, standard laboratory tests, chest computed tomography, spirometry with evaluation of DLCO. The onset of cardiovascular events during the average period of 384 days was evaluated. None of the 43 patients had major cardiovascular events: coronary heart disease, cerebrovascular disease, peripheral arterial disease, deep vein thrombosis and pulmonary embolism. Conclusion(s): Even if this study failed to demonstrate new-onset CV events, longer follow-up studies performed to evaluate cardiovascular risk following SARS-CoV1 infection showed persistent hyperlipidemia, cardiovascular system abnormalities, and glucose metabolism disorders in a very high number of patients. Further analyses are needed to further investigate longer term cardiovascular consequences of SARS-CoV2 infection. (Figure Presented).

Moderate to Severe Sars-Cov2 and Cardiovascular Events at One Year: A Descriptive Retrospective Analysis

Introduction: The Coronavirus disease 2019 (COVID-19), doesn't affect only respiratory system, but it also involves other organs including cardiovascular system, possibly causing acute or chronic cardiovascular events. Preexisting cardiovascular diseases enhance COVID-19 morbidity, as well. Aim(s): In this retrospective analysis we investigated the onset of cardiovascular events during a time-span of more than one year since hospitalization (384 days). Method(s): The analysis included 43 patients, who were hospitalized in Internal Medicine Department of Montichiari Hospital (ASST Spedali Civili of Brescia) for moderate to severe SARS-CoV2 related pneumonia treated with high-flow oxygen support (ranging from 40% fraction of inspired oxygen to non-invasive ventilation) Results: Mean age was 63 years, 28% (12/43) were female and 72% (31/43) were male. Thirty-five percent of the patients suffered from heart diseases, 56% of them were hypertensives and 23% had type 2 diabetes;12% had chronic kidney disease (CKD) and 5% an active neoplasm. 49% of the sample was obese. Nineteen percent took ACE inhibitors and 19% was on ARBs. Statins were taken by 37% of the patients;an antiaggregant by 21%, and an anticoagulant by 2% (see table) Table 1: Main demographic data, comorbidities and ongoing therapies The follow-up visit included the evaluation of post-covid infection quality-of-life, standard laboratory tests, chest computed tomography, spirometry with evaluation of DLCO. The onset of cardiovascular events during the average period of 384 days was evaluated. None of the 43 patients had major cardiovascular events: coronary heart disease, cerebrovascular disease, peripheral arterial disease, deep vein thrombosis and pulmonary embolism. Conclusion(s): Even if this study failed to demonstrate new-onset CV events, longer follow-up studies performed to evaluate cardiovascular risk following SARS-CoV1 infection showed persistent hyperlipidemia, cardiovascular system abnormalities, and glucose metabolism disorders in a very high number of patients. Future analyses are needed to further investigate longer term cardiovascular consequences of SARS-CoV2 infection.

Ongoing Ace-Inhibitor or Atii-Antagonist Treatment Doesn't Impact on Outcome nor on Sequelae of Patients with Moderate to Severe Covid-19 Pneumonia

Introduction: COVID-19 pandemic still represents a major clinical problem worldwide. Many studies are actively being carried out to better understand prognostic factors of outcome as well as optimal treatment. Aim(s): ACE-2 receptor is highly expressed on the surface of cardiac and pulmonary cells, and it is used by coronaviruses to enter host cells;this makes the role of ACE-inhibitors and Angiotensin Receptor Blockers (ARBs) drugs controversial. Moreover, it is still unclear whether these drugs may have any impact on sequelae. Method(s): In this retrospective study, we analysed a group of 244 hypertensive unvaccinated patients (134 on ACE-inhibitors, 110 on ARBs) admitted for moderate to severe COVID-19 pneumonia. As shown in Table 1, the two groups were homogeneous. Of these patients, 46 (20 treated with ACE-I and 26 treated with ARBs) came to a follow-up visit after a mean of 260 days;they underwent a quality-of-life assessment, laboratory and radiologic tests and spirometry (with DLCO). Result(s): A total of 20 of 110 (18%) patients under treatment with ARBs and 23 of 134 (17%) died during hospitalization (p = 0.8, NS). At discharge, biochemical, radiological and respiratory data were not significantly different. We did not find any significant difference in terms of radiological alterations, lung fibrosis, spirometry data, DLCO, persisting effort dyspnea. Biochemical data were substantially super-imposable in the two groups. Conclusion(s): In conclusion, we could not detect any difference in outcome nor in complications type or number in the two groups of hypertensive patients undergoing treatment with ACE-inhibitor or ARBs. This result seems to support and to strengthen the idea that ACE-inhibitors and ARBs do not play a significant role in onset, evolution and outcome of moderate to severe COVID-19 pneumoniae. Although the number of follow-up patients is small, we did not find any difference in follow-up sequelae in both groups.

MICROCIRCULATION AND SARS-COV-2 INFECTION: A FOLLOW UP STUDY

Objective: SARS-CoV2 infection can lead to several clinical scenarios, named COVID-19, ranging from mild manifestations to acute respiratory distress syndrome (ARDS), coagulation alterations and endothelial dysfunction. The functional impairment of the microcirculation seems play a key role in the pathophysiology and clinical consequences of COVID-19. However, to date there is no evidence of structural microvascular damage related to COVID-19. Design and method: The aim of this study is to investigate microvascular alterations by adaptive optics and vide-ocapillaroscopy in patients recently admitted for COVID-19 and re-evaluated one year later. Methods: We enrolled 153 patients admitted between February and April 2020 at the Hospital of Montichiari (Brescia) and at the Internal Medicine Department of ASST Spedali Civili - University of Brescia for respiratory failure due to SARSCoV2- related interstitial pneumonia. Patients were evaluated two months after nalysed sation and after one year. All patients underwent a venous blood sampling for hematochemical tests, evaluation of retinal arteriolar morphology by adaptive optics, assessment of basal and total capillary density (BCD and TCD respectively) at the dorsum of the fourth finger of the non-dominant hand by videocapillaroscopy. Results: Fifty patients with completed follow-up were nalysed. An increase of internal lumen (93.8 ± 13.3 vs. 97.3 ± 14.2 micron, p < 0.001) and a reduction of wall to lumen ratio (WLR 0.30 ± 0.03 vs. 0.27 ± 0.03, p < 0.001) were observed at the follow up visit after one year (Figure). No significant differences were observed in BCD in the dorsum of the finger after one year, whereas a significant reduction in TCD was observed (p < 0.001). Microvascular changes were independent of body mass index and the presence of hypertension or diabetes mellitus. Conclusions: Preliminary data from this study show that patients with SARSCov2 infection present an improvement of microvascular structure after one year from the disease, such as a reduction in WLR of retinal arterioles. This suggests that COVID19 might induce structural alterations in the microcirculation which contribute to vascular damage. These changes do not seem to be influenced by the weight, presence of hypertension or diabetes.

Positive, Mildly Positive, and Uncertain Nasopharyngeal Swab and Outcome in COVID-19 Patients

Introduction and Aim Diagnosis of SARS-CoV-2 infection is mainly based on gene detection through polymerase chain reaction analysis on nasopharyngeal swab. The Allplex TM 2019-nCoV assay targets 3 different viral genes: RNA-dependent RNA polymerase, envelope, and nucleocapside. A coding system was developed based on different number of genes expressed: a nasopharyngeal swab was considered "positive" if all 3 genes tested underwent amplification, "mildly positive" if only 2 out of 3 genes were detected, "uncertain" if only 1 gene and "negative" if none resulted amplified from the test. Our aim was to assess whether this classification correlates with clinical outcome in a cohort of COVID-19 patients. Methods This is a retrospective study including patients admitted with diagnosis of SARS-CoV-2 infection to a medical ward at the Montichiari Hospital, Brescia, Italy, from February 28 to April 30, 2020. All patients underwent the nasopharyngeal swab upon admission. Results A total of 204 patients were included in this study. Patients with full positive nasopharyngeal swab showed higher values of C-reactive protein and neutrophiles/lymphocytes ratio compared with patients with mildly positive or uncertain nasopharyngeal swab. Mortality did not differ between the 2 groups. A Cox multivariate analysis showed that age, male sex, and CRP values are independent predictors of in-hospital mortality. Conclusions Our study demonstrated that patients with a complete SARS-CoV-2 gene detection nasopharyngeal swab show a higher inflammatory profile, and this can be an indirect measurement of viral load in COVID-19 patients.

Effect of ongoing treatment and different therapies on prognosis in COVID-19 patients in An hospital setting

Objective: Patients affected by novel pandemic SARS-CoV-2 may develop COVID-19 related pneumonia, which is potentially fatal. To date, the role of ongoing treatments for different conditions (such as hypertension) has been clarified in terms of their impact on survival and there is no established specific therapy for the disease, although many molecules are under investigation. Aim of the present study was testing those two issues in a population of 258 consecutive patients admitted from 29 February to 30 April 2020 to General Medicine ward of the Hospital of Montichiari (Brixia). Design and method: A group of 258 patients (173 males and 85 females, aged 71 ± 14) was enrolled. Their medical record and ongoing treatment were assessed. Patients were treated according to emerging information with oxygen, anti-malarian agents, anti-viral drugs, different antibiotics (azithromycin and others), tocilizumab and low molecular weight heparin (LMWH) at different doses. As of June 10th, 65 deaths had been observed. Survival curves were calculated according to Kaplan-Meier method. Comparison between groups was performed with Breslow and Mantel-Cox test Results: Ongoing therapy with ACE-inhibitors at the time of admission was associated with a worse prognosis (p=0.004), while no difference in survival was observed in patients under treatment with ARBs (p=0.68). Ongoing treatment with statins (p<0.001), low-dose aspirin (p<0.001) and steroids (p<0.001) was associated with a poorer outcome as well Administration during hospitalization of LMWH (p<0.001), steroids (p<0.001), anti-viral drugs (p=0.002), anti-malarian drugs (p<0.001) and tocilizumab (p<0.001), improved prognosis, while antibiotics (azithromycin and other) didn't have any impact. Conclusions: our experience confirms most findings in ongoing trials. Surprisingly, treatment with ACE-inhibitors seems to impact negatively on survival in patients affected by SARS-CoV-2 pneumonia. A possible explanation may be that patients treated with certain drugs are more comorbid and due to this, more fragile.

Low molecular weight heparin at high dose impacts on outcome of COVID-19 hospitalized patients, while standard dose doesn't

Objective: COVID-19 is a new disease caused by pandemic SARS-CoV-2, that involves multiple organs and can cause a potentially fatal respiratory distress syndrome. Accumulating evidence point out that an “endothelitis” due to a cytokines storm causes intravascular thrombosis, especially in the lungs, and is related to the poor outcome. We tested possible relationships between anticoagulant treatment and/or administration of low molecular weight heparin (LMWH) at different doses and outcome in a population of 258 COVID-19 patients admitted from February 28th to April 30th, 2020 to General Medicine ward of the Hospital of Montichiari (Brixia, Italy). Design and method: A group of 258 consecutive patients (174 males and 84 females, mean age 71 years +/-14) was included in the present study. In 168 patients, high-flow oxygen was required (Venturi mask), 6 patients needed orotracheal intubation and 20 were given continuous positive pressure oxygen therapy (CPAP). Patient were treated (unless a pulmonary embolism was detected) with different doses of prophylactic LMWH, according to emerging evidence during pandemic period. As of June 10th, 65 deaths had been observed. Survival curves were calculated according to Kaplan-Meier method. Comparison between groups was performed with Breslow and Mantel-Cox test. Results: LMWH at standard dose (4000 IU once daily) didn't reduce mortality compared to no treatment (p=ns), while LMWH at a higher dose than usual prophylactic dose (enoxaparin 6000 IU once daily or 4000 IU bid) was associated with better outcome (p<0.001 vs untreated and treated with standard dose). Significance was confirmed adding patients treated with oral anti-coagulant (OAC)for any reason. None of the patients treated with LMWH at higher doses or OAC died. Conclusions: The administration of subcutaneous LMWH at a higher dose than indicated for deep vein thrombosis prophylaxis is associated with a better outcome in patients with SARS-CoV-2 pneumonia, confirming some emerging evidence.

Role of hypertension, cardiovascular disease and cardiovascular risk factors on outcome in hospitalized COVID-19 patients

Objective: Emerging data show that hypertension as well as other cardiovascular risk factors may have a major role on outcome in terms of death on patients with COVID-19. We analysed a population of 258 consecutive patients admitted to General Medicine ward of the Hospital of Montichiari (Brixia, Italy) from 29 February to 30 April 2020. Design and method: A group of 258 consecutive patients (173 males and 85 females, aged 71 ± 14) was enrolled. In 168 patients, high-flow oxygen was required (Venturi mask), 20 patients needed orotracheal intubation and 11 were given continuous positive pressure oxygen therapy (CPAP). Patients were treated with the best approach according to available evidence during pandemic period: anti-malaria agents, anti-viral drugs, antibiotics (azithromycin and others), tocilizumab and low molecular weight heparin (LMWH). As of June 10th, 65 deaths had been observed. Survival curves were calculated according to Kaplan-Meier method. Comparison between groups was performed with Breslow and Mantel-Cox test. Results: As shown in the table, a significant raise in mortality was observed in patients older than 65 years (p<0.001), of male sex (p<0.001), hypertensives (p<0.001) as well as in patients with heart disease (picture 1;p<0.001), COPD (picture 2;p=0.004), diabetes (p<0.001) and neoplasms (p=0.03) compared with patients with no comorbidities or different diseases, both at discharge and at standard follow-up. The number of comorbidities impacted on survival as well. Conclusions: Hypertension, heart disease and cardiovascular risk factors play a significant role as a negative prognostic factor in patients affected by SARSCoV-2 pneumonia. This confirms previous observations (Pol Arch Intern Med 2020;130(4):304-309) and outlines the importance of prevention of contagion in population with cardiovascular risk factors or established cardiovascular disease.