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).

Ace-Inhibitors and Angiotensin Receptor Blockers Do Not Impacton Outcome nor in Long Term Consequences of Covid-19

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 formoderate to severe COVID-19 pneumonia. As shown in the table, the two groups where 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 radiologic alterations, lung fibrosis, spirometry data, DLCO, persisting effort dyspnea. Biochemical data were substantially super-imposable in the two groups. Conclusion(s): we could not detect any difference in outcome nor in complications type or number in the two groups 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. (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.

DETERMINANTS OF OUTCOME OF MODERATE TO SEVERE COVID-19 IN A HOSPITAL SETTING: A COMPARISON BETWEEN FIRST AND SECOND/THIRD WAVE IN LOMBARDY

Objective: Coronavirus disease 2019 (COVID-19) represents a major clinical problem in terms of death and long-term sequelae. We conducted a retrospective cohort study at Montichiari Hospital (Brescia, Italy) to better understand different determinants of outcome in different COVID-19 outbreaks. Design and method: A total of 635 patients admitted from local emergency room with a confirmed diagnosis of SARS-CoV-2 infection and a moderate to severe COVID-19 were included in the present study. A group of 260 consecutive patients during SARS-CoV-2 first wave (from February to May 2020) and 375 consecutive patients during SARS-CoV-2 second/third wave (from October 2020 to May 2021) were considered. Demographic data, comorbidities, ongoing treatment and bio-humoral, respiratory and haemodynamic data were recorded and compared. Results: Main demographic data (Table 1) were not significantly different in the two considered time-lapses, except a lower prevalence of female sex during first wave. Mortality rate was significantly lower during the latter period (25% vs 11%;p < 0.001). Time from symptoms onset to hospital admission was longer during first wave (7.8 ± 5.6 vs 5.6 ± 4.3 days;p < 0.001) while hospital staying was significantly shorter (11 ± 10 vs 15 ± 12 days;p < 0.001). Other significant differences were a wider use of corticosteroids and low-molecular weight heparin (LMWH) as well less antibiotic prescription during the second wave (Table 2). Respiratory, bio-humoral and x-Ray score were significantly poorer at the time of admission in first-wave patients (Table 3). After a multivariate regression analysis, C-reactive protein and procalcitonin values, % fraction of inspired oxygen at admission, days after symptoms onset and duration of hospital staying were the strongest predictors of outcome in both periods. Concomitant anti-hypertensive treatment (including ACE-inhibitors and ARBs) did not affect outcome. Conclusions: Our preliminary data suggest that an earlier diagnosis, a timely hospital admission and a rational use of the therapeutic options allowed to reduce the rate of systemic inflammation response (of which CRP is a hallmark) and granted a better outcome during the second of the two time-lapses considered.

COMPARISON BETWEEN FIRST AND SECOND/THIRD WAVE OF SARS-COV-2 MODERATE TO SEVERE INFECTION IN ELDERLY PATIENTS IN AN NORTH ITALIAN HOSPITAL SETTING

Objective: Worldwide spread of SARS-CoV-2 caused a pandemic as never were seen in the last fifty years and represented a major clinical problem in Lombardy, one of the most affected Italian Regions, in terms of death toll and long-term sequelae. This is particularly true when elder people are considered;therefore, we conducted a retrospective cohort study in the General Medicine of our Hospital. Design and method: In the present study we recorded data of patients older than 65 years, admitted to a COVID-19 unit during 2020 and 2021;we compared the characteristics of in-patients admitted in the first (March-May 2020) and the second/ third pandemic waves (October 2020-May 2021) Results: A total of 407 patients 65 year-old and older were included, 185 during the first wave and 222 during second/third waves;63 (34%) of them died during the first and 36 (16%) during the second/third wave. No significant differences were found according to main comorbidities and chronic prescriptions between the two groups of patients, whereas those admitted during the second/third wave were slightly older. Number of in-hospital adverse events were similar in the two samples. Main differences between the two groups were: a lower mean number of days with symptoms before hospitalization, and a less severe laboratory, respiratory ed radiologic profile. Further, steroid treatment was highly implemented during the second/third wave. Conclusions: Older patients admitted to hospital since the beginning of the pandemic showed diverse clinical severity profile according to different waves;patient admitted during the first wave had worse respiratory, radiological and laboratory parameters than those admitted in the second/third wave;further difference was found in COVID-19 treatment during hospital stay as steroids were largely administered during the latter waves.

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.

Skin capillary alterations in patients with acute SARS-COV-2 infection

Objective: Acute SarsCoV2 infection is associated with endothelial dysfunction and endothelitis which might explain systemic microvascular impairment. The presence of endothelial damage can promote vasoconstriction with consequent organ ischemia, inflammation, tissue edema and a procoagulant state resulting in an increase in the incidence of cardio-and cerebrovascular events. Microvascular thrombosis has been demonstrated in post-mortem autopsy of COVID19 patients;however no data are available about skin capillary alterations in these patients. Design and method: We evaluated skin microvascular alterations in 14 patients admitted to our hospital with SarsCov2 infection. Basal capillary density was performed by capillaroscopy bedside in the nailfold and in the dorsum of the 4th finger. Results: Fourteen patients (9 males, 5 females) were evaluated: average age was 66±1 years, BMI 26±3. Nine patients were hypertensive (64%), 4 diabetic (29%), 3 were dyslipidemic (21%), 3 with cerebrovascular or cardiovascular disease history (21%). Seven patients were treated with ev steroid (50%), 3 with tocilizumab (21%) and 7 were treated with non-invasive ventilation (50%). During the hospitalisation all patients presented interstitial pneumonia SarsCov2 associated whereas vascular complication (ischaemic stroke or pulmonary embolism) were observed in 3 patients (21%) with SarsCov2 infection. Nine patients showed skin capillary alterations (5 thrombosis, 5 haemorrhage/ microbleeding, 4 neoangiogenesis). Interestingly, capillary alterations were present only in patients treated with non-invasive ventilation and/or with cardio-or cerebrovascular complications. These alterations were not detected after 2 month from the discharge. Conclusions: This is the first in vivo evidence of skin capillary thrombosis, microhaemorragia and angiogenesis in patients with acute SARS-CoV2 infection which support the presence of endothelial dysfunction and inflammation. Capillary alterations might reflect systemic vascular effects of viral infection.