Surviving COVID-19 in Bergamo province: a post-acute outpatient re-evaluation

Abstract

Bergamo province was badly hit by the coronavirus disease 2019 (COVID-19) epidemic. We organised a public-funded, multidisciplinary follow-up programme for COVID-19 patients discharged from the emergency department or from the inpatient wards of ‘Papa Giovanni XXIII’ Hospital, the largest public hospital in the area. As of 31 July, the first 767 patients had completed the first post-discharge multidisciplinary assessment. Patients entered our programme at a median time of 81 days after discharge. Among them, 51.4% still complained of symptoms, most commonly fatigue and exertional dyspnoea, and 30.5% were still experiencing post-traumatic psychological consequences. Impaired lung diffusion was found in 19%. Seventeen per cent had D-dimer values two times above the threshold for diagnosis of pulmonary embolism (two unexpected and clinically silent pulmonary thrombosis were discovered by investigating striking D-dimer elevation). Survivors of COVID-19 exhibit a complex array of symptoms, whose common underlying pathology, if any, has still to be elucidated: a multidisciplinary approach is fundamental, to address the different problems and to look for effective solutions.

Prevalence of post-COVID-19 symptoms in hospitalized and non-hospitalized COVID-19 survivors: A systematic review and meta-analysis

“…A total of 29 published studies [15] , [16] , [17] , [18] , [19] , [20] , [21] , [22] , [23] , [24] , [25] , [26] , [27] , [28] , [29] , [30] , [31] , [32] , [33] , [34] , [35] , [36] , [37] , [38] , [39] , [40] , [41] , [42] , [43] and five medRxiv preprints [44] , [45] , [46] , [47] , [48] were initially included in the review/meta-analysis ( Figure 1 ) . One preprint [44] was excluded because the same study has been posteriorly published in a peer-reviewed journal [30] .…”

“…Of the twenty-one studies [ 15 , 16 , 18 , [22] , [23] , [24] , [25] , 27 , 29 , [32] , [33] , [34] , [35] , [36] , [37] , [40] , [41] , [42] , [43] , 46 , 47 ] investigating the presence of post-COVID-19 symptoms in hospitalized patients, four analyzed symptoms 30 days after hospital discharge [ 15 , 33 , 41 , 43 ], nine showed a follow-up period of 60 days [ 15 , 18 , 24 , 27 , 29 , 36 , 37 , 42 , 47 ], whereas ten reported symptoms ≥90 days after discharge [ 16 , 22 , 23 , 25 , 26 , [33] , [34] , [35] , 40 , 46 ]. Overall, hospitalized COVID-19 patients were assessed a mean of 83.6±48.4 after hospital discharge.…”

Characteristics and predictors of acute and chronic post-COVID syndrome: A systematic review and meta-analysis

“…The lack of standardisation between enrolment and assessments into the trial precluded one study for the chronic post-COVID syndrome sub-group analysis [27]. Studies reported 8 predominant symptoms allowing for pooled analysis (Fig.…”

Immunothrombotic dysregulation in chagas disease and COVID-19: a comparative study of anticoagulation

“…In addition, there is prothrombotic activation with an increase of endogenous thrombin potential (ETP) and F1 + 2 levels, plasmin-antiplasmin complexes (PAP) [ 9 , 34 ], PAI-1, and fibrinogen [ 121 ] In structural studies, it has been reported that platelets are not only related to microthrombi but also erythrocytes and amyloid microclots. [ 122 ] A study of Post-acute COVID-19 syndrome in Bergamo, Italy, found hypercoagulation in 17% of patients with D-dimer values that increased more than two times above 500 ng/mL [ 123 ]. In addition, ischemic cardiovascular events are increasing in COVID-19 [ 124 ], myocardial injury and elevated troponin levels are also reported [ 125 ] Inflammation and vascular leakage Trypomastigotes boost their infectivity through activation of the mast cell/kallikrein-kinin system pathway, resulting in inflammatory oedema [ 126 ] At the site of infection by T cruzi , C5a, and bradykinin are released and modulate innate and adaptive immunity, inflammation, and plasma leakage [ 127 ] The severity of COVID-19 is related to increased inflammation markers such as C-reactive protein (CRP), interleukin-6, nuclear factor kappa B (NFκB), and tumour necrosis factor-alpha (TNFα) as well as multiorgan failure [ 128 ] Mid-Regional proAdrenomedullin (MR-proADM), a marker of endothelial integrity and vascular leakage, is also related to severity and mortality in COVID-19 [ 129 ] During COVID-19, inflammation, vasodilation, hypotension, and plasma leakage may be due to the bradykinin system, in particular des-Arg9-BK, which acts on Bradykinin 1 (B1) receptor [ 130 ] …”

“…A study of Post-acute COVID-19 syndrome in Bergamo, Italy, found hypercoagulation in 17% of patients with D-dimer values that increased more than two times above 500 ng/mL [ 123 ]. In addition, ischemic cardiovascular events are increasing in COVID-19 [ 124 ], myocardial injury and elevated troponin levels are also reported [ 125 ]…”