Can we predict the severe course of COVID-19 - a systematic review and meta-analysis of indicators of clinical outcome?

Abstract

Background COVID-19 has been reported in over 40million people globally with variable clinical outcomes. In this systematic review and meta-analysis, we assessed demographic, laboratory and clinical indicators as predictors for severe courses of COVID-19. Methods This systematic review was registered at PROSPERO under CRD42020177154. We systematically searched multiple databases (PubMed, Web of Science Core Collection, MedRvix and bioRvix) for publications from December 2019 to May 31st 2020. Random-effects meta-analyses were used to calculate pooled odds ratios and differences of medians between (1) patients admitted to ICU versus non-ICU patients and (2) patients who died versus those who survived. We adapted an existing Cochrane risk-of-bias assessment tool for outcome studies. Results Of 6,702 unique citations, we included 88 articles with 69,762 patients. There was concern for bias across all articles included. Age was strongly associated with mortality with a difference of medians (DoM) of 13.15 years (95% confidence interval (CI) 11.37 to 14.94) between those who died and those who survived. We found a clinically relevant difference between non-survivors and survivors for C-reactive protein (CRP; DoM 69.10 mg/L, CI 50.43 to 87.77), lactate dehydrogenase (LDH; DoM 189.49 U/L, CI 155.00 to 223.98), cardiac troponin I (cTnI; DoM 21.88 pg/mL, CI 9.78 to 33.99) and D-Dimer (DoM 1.29mg/L, CI 0.9 to 1.69). Furthermore, cerebrovascular disease was the co-morbidity most strongly associated with mortality (Odds Ratio 3.45, CI 2.42 to 4.91) and ICU admission (Odds Ratio 5.88, CI 2.35 to 14.73). Discussion This comprehensive meta-analysis found age, cerebrovascular disease, CRP, LDH and cTnI to be the most important risk-factors that predict severe COVID-19 outcomes and will inform clinical scores to support early decision-making.

Prediction of the need for intensive oxygen supplementation during hospitalisation among subjects with COVID-19 admitted to an academic health system in Texas: a retrospective cohort study and multivariable regression model

“…A recent meta-analysis by Katzenschlager et al evaluated the association between LDH levels and admission to the intensive care unit (ICU) (12 studies) or death (23 studies) in patients with COVID-19. Although LDH levels were statistically higher in those critically ill (pooled difference of medians: 140 U/L (95% CI 81 to 199)) and those who died (pooled difference of medians: 189 U/L (95% CI 155 to 223)), the modest absolute increase in LDH levels was deemed clinically irrelevant by the authors 19. The differences between these studies and ours may be explained by the different outcome definitions used.…”

A Model Predicting Mortality of Hospitalized Covid-19 Patients Four Days After Admission: Development, Internal and Temporal-External Validation

“…Undoubtedly the most important predictor of severe Covid-19 is age. A meta-analysis of 88 articles (69,762 patients) shows that age along with CRP were strong risk-factors for ICU admission and/or mortality ( Katzenschlager et al., 2020 ). Concerning fever, a recent meta-analysis reported that fever is a predictor of adverse outcome in Covid-19 ( Li et al., 2020 ).…”

Safety and revisit related to discharge the sixty-one spanish emergency department medical centers without hospitalization in patients with COVID-19 pneumonia. A prospective cohort study UMC-Pneumonia COVID-19

“…In a situation in which the health-care system has bordered on the collapse, and health-care personnel have been exposed to a high risk of contagion and an unprecedented workload, emergency medicine physicians have been up against an unforeseeable situation. All of these circumstances have occurred within the context of a new, previously unknown infectious disease linked with an elevated need for hospital admission due to the presentation of severe, heterogeneous complications such as multiorgan dysfunction, ARDS, septic shock, disseminated intravascular coagulation, and thromboembolic events requiring ICU admission and with a high mortality [8][9][10][11][12]16 . For all these reasons, it is logical that our results reflect the high number of hospital admissions in patients with COVID-19 with pneumonia, even in patients who did not present criteria of severe pneumonia.…”

“…It is likely that the clinical presentation in men is more severe and more often leads to the decision for hospital admission. The presence of lymphopenia is a common characteristic of this infection and has been related to more severe clinical forms with worse outcomes [8][9][10][11][12]25 . The reduction of total lymphocytes is also reflected by a reduction in its subsets, and therefore, CD4+ T cells, CD8+ T cells, B cells, and natural killer cells are reduced in patients with COVID-19.…”

“…These decisions must be supported by scientific evidence to safeguard against inadequate discharges that result in bad clinical results. The data of large series collected in studies of patients with COVID-19 have reported some variables related to bad prognoses such as age, the presence of chronic comorbidities, an elevation of inflammatory parameters and D-dimer, and the presence of acute respiratory failure or lymphopenia, among others [9][10][11] . There are currently models for predicting severe manifestations and mortality from COV-ID-19 12 .…”