Prognostic factors and predictors of outcome in patients with COVID-19 and related pneumonia: a retrospective cohort study

Abstract

The aim of the present study was to simultaneously assess several potential predictors of outcome (co-morbidity, previous and in-hospital treatment, radiologic Brixia score) in patients with COVID-19. This retrospective cohort study included 258 consecutive patients with confirmed COVID-19 admitted to a medical ward at Montichiari Hospital, Brescia, Italy from February 28th to April 30rd, 2020. Patients had SARS-CoV-2 related pneumonia with respiratory failure, and were treated with hydroxychloroquine and lopinavir plus ritonavir. In some patients, additional treatment with tocilizumab, dexamethasone and enoxaparin was adopted. Outcomes (death or recovery) were assessed at the end of the discharge period or at the end of the follow-up (August 2020). During hospitalization, 59 patients died, while 6 died after discharge. The following variables were demonstrated to be associated with a worse prognosis: Radiologic Brixia score higher than 8, presence at baseline of hypertension, diabetes, chronic obstructive pulmonary disease, heart disease, cancer, previous treatment with ACE-inhibitors or anti-platelet drugs. Anticoagulant treatment during hospital admission with enoxaparin at a dose higher than 4000 U once daily was associated with a better prognosis. In conclusion, our study demonstrates that some co-morbidities and cardiovascular risk factors may affect prognosis. The radiologic Brixia score may be a useful tool to stratify the risk of death at baseline. Anticoagulant treatment with enoxaparin might be associated to a clinical benefit in terms of survival in patients with COVID-19.

Keywords: ACE-inhibitors; COVID-19; SARS-CoV2; cardiovascular risk factors; enoxaparin; hypertension.

Figure 1. Kaplan–Meier survival curve for the Brixia radiologic score

Analysis run using group as factor; death as event and time to death/discharge or time to death/re-evaluation at follow up as time variable. (A) Brixia score ≥ 8 (red line) or < 8 (blue line), time to death/re-evaluation at follow up as time variable, (B) Brixia score ≥ 8 (red line) or < 8 (blue line), time to death/discharge as time variable, (C) Brixia score ≥ 10 (red line) or < 8 (blue line), time to death/re-evaluation at follow up as time variable, (D) Brixia score ≥ 10 (red line) or < 8 (blue line), time to death/discharge as time variable.

Figure 2. Kaplan–Meier survival curve for the presence or absence of cardiovascular risk factors or comorbidities

Analysis run using group as factor; death as event and time to death/discharge or time to death/re-evaluation at follow up as time variable. (A) age ≥ 65 (red line) or < 65 (blue line), time to death/re-evaluation at follow up as time variable, (B) age ≥ 65 (red line) or < 65 (blue line), time to death/discharge as time variable, (C) presence (red line) or absence (blue line) of hypertension at entry, time to death/re-evaluation at follow up as time variable, (D) presence (red line) or absence (blue line) of hypertension at entry, time to death/discharge as time variable, (E) presence (red line) or absence (blue line) of diabetes mellitus at entry, time to death/re-evaluation at follow up as time variable, (F) presence (red line) or absence (blue line) of diabetes mellitus at entry, time to death/discharge as time variable, (G) presence (red line) or absence (blue line) of chronic obstructive pulmonary disease at entry, time to death/re-evaluation at follow up as time variable, (H) presence (red line) or absence (blue line) of chronic obstructive pulmonary disease at entry, time to death/discharge as time variable, (I) presence (red line) or absence (blue line) of any cardiac disease at entry, time to death/re-evaluation at follow up as time variable, (J) presence (red line) or absence (blue line) of any cardiac disease at entry, time to death/discharge as time variable, (K) presence (red line) or absence (blue line) of any active tumor entry at entry, time to death/re-evaluation at follow up as time variable, (L) presence (red line) or absence (blue line) of any active tumor entry, time to death/discharge as time variable

Figure 3. Kaplan–Meier survival curve for pre-admission chronic treatments

Analysis run using group as factor; death as event and time to death/discharge or time to death/re-evaluation at follow up as time variable. (A) previous treatment with ACE-inhibitors (red line) or no treatment with ACE-inhibitors (blue line), time to death/re-evaluation at follow up as time variable, (B) previous treatment with ACE-inhibitors (red line) or no treatment with ACE-inhibitors (blue line), time to death/discharge as time variable, (C) previous treatment with angiotensin-receptor blockers (red line) or no treatment with angiotensin-receptor blockers (blue line), time to death/re-evaluation at follow up as time variable, (D) previous treatment with angiotensin-receptor blockers (red line) or no treatment with angiotensin-receptor blockers (blue line), time to death/discharge as time variable, (E) previous treatment with statins (red line) or no treatment with statins (blue line), time to death/re-evaluation at follow up as time variable, (F) previous treatment with statins (red line) or no treatment with statins (blue line), time to death/discharge as time variable, (G) previous treatment with anti-platelet drugs (red line) or no treatment with anti-platelet drugs (blue line), time to death/re-evaluation at follow up as time variable, (H) previous treatment with anti-platelet drugs (red line) or no treatment with anti-platelet drugs (blue line), time to death/discharge as time variable, (I) previous treatment with steroids (red line) or no treatment with steroids (blue line), time to death/re-evaluation at follow up as time variable, (J) previous treatment with steroids (red line) or no treatment with steroids (blue line), time to death/discharge as time variable.

Figure 4. Kaplan–Meier survival curve for the anticoagulant drug treatments during admission

Analysis run using group as factor; death as event and time to death/discharge or time to death/re-evaluation at follow up as time variable. (A) treatment with enoxaparin 4000 Units subcutaneously once daily (red line) or no anticoagulant treatment (blue line), time to death/re-evaluation at follow up as time variable, (B) treatment with enoxaparin 4000 Units subcutaneously once daily (red line) or no anticoagulant treatment (blue line), time to death/discharge as time variable, (C) treatment with treatment with enoxaparin 100 Units/kg twice daily (anticoagulation dose) (red line) or no anticoagulant treatment (blue line), time to death/re-evaluation at follow up as time variable, (D) treatment with enoxaparin 100 Units/kg twice daily (anticoagulation dose) (red line) or no anticoagulant treatment (blue line), time to death/discharge as time variable, (E) treatment with treatment with any dose of enoxaparin greater than 4000 Units subcutaneously once daily (red line) or no anticoagulant treatment (blue line), time to death/re-evaluation at follow up as time variable, (F) treatment with any dose of enoxaparin greater than 4000 Units subcutaneously once daily (red line) or no anticoagulant treatment (blue line), time to death/discharge as time variable, (G) treatment with treatment with any dose of enoxaparin or no anticoagulant treatment (blue line), time to death/re-evaluation at follow up as time variable, (H) treatment with any dose of enoxaparin once daily (red line) or no anticoagulant treatment (blue line), time to death/discharge as time variable, (I) treatment with treatment with any dose of enoxaparin ±any new oral direct anticoagulant or no anticoagulant treatment (blue line), time to death/re-evaluation at follow up as time variable, (J) treatment with any dose of enoxaparin once daily (red line) ± any new oral direct anticoagulant or no anticoagulant treatment (blue line), time to death/discharge as time variable.