The COVID-19 pandemic, caused by SARS-CoV-2, has resulted in millions of cases and deaths globally. While many experience asymptomatic or mild illness, a significant proportion develop severe bilateral interstitial pneumonia, necessitating hospitalization. Severe COVID-19 is often characterized by multiple organ dysfunction syndrome (MODS), triggered by systemic inflammation. This inflammatory response is reflected in altered laboratory parameters, including blood counts and inflammatory biomarkers. Key biomarkers associated with severe COVID-19 include C-reactive protein (CRP), procalcitonin (PCT), ferritin, D-dimers, fibrinogen, interleukin-6 (IL-6), interleukin-10 (IL-10), and reduced lymphocyte counts. The wide spectrum of COVID-19 severity necessitates rapid identification of patients at high risk of death to guide treatment strategies. Elderly patients and those with pre-existing conditions are at increased risk. This retrospective study aimed to identify clinical and laboratory features differentiating survivors and non-survivors among hospitalized COVID-19 patients in Southern Italy, to define threshold values predictive of patient outcome. The researchers sought to pinpoint independent risk factors for death and potentially establish valuable prognostic indicators.

The existing literature on COVID-19 biomarkers presents conflicting findings. While studies have shown an association between elevated inflammatory markers (CRP, PCT, IL-6) and severe disease, other studies have reported contradictory results. Similarly, lymphopenia, a decrease in lymphocyte count, has been observed in COVID-19 patients, and its association with mortality is not universally agreed upon. The literature highlights the role of age and comorbidities as independent risk factors, with patients over 65 and those with conditions such as hypertension, diabetes, obesity, and heart disease exhibiting higher mortality rates. Several studies highlight the prognostic potential of PCT, CRP, LDH, and IL-6, though their predictive power varies among studies. Lymphocytopenia is consistently observed in severe cases, potentially due to immune system exhaustion or lymphocyte migration to the lungs. These inconsistencies highlight the need for further investigation to clarify the prognostic value of different biomarkers in predicting COVID-19 mortality.

This retrospective cohort study enrolled 150 patients hospitalized with COVID-19 from March to June 2021 at the F. Perinei Murgia Hospital in Altamura, Italy. Patients were divided into survivors (n=100) and non-survivors (n=50). COVID-19 was confirmed using RT-PCR on nasal and pharyngeal swab specimens. Blood samples collected within 24 hours of admission were analyzed for various parameters. These included complete blood counts (including lymphocyte subsets using flow cytometry), inflammatory markers (IL-6, LDH, CRP, PCT, D-dimers, ferritin, fibrinogen), and clinical data (age, sex, comorbidities). Statistical analysis involved comparing means using Student's t-test (normally distributed data) or Mann-Whitney U test (non-normally distributed data). Proportions were compared using the χ² test, and ROC curve analysis was used to assess the diagnostic accuracy of biomarkers. Multivariable logistic regression was used to identify independent risk factors for in-hospital mortality. The study was approved by the Ethics Committee of "Azienda Ospedaliero Universitaria Consorziale Policlinico", Bari, Italy, and conducted according to the Declaration of Helsinki.

The median age of non-survivors (79 years) was significantly higher than that of survivors (65 years) (p<0.001). A significantly higher proportion of males were in the non-survivor group (p<0.0001). The median lymphocyte count was significantly lower in non-survivors (0.70 × 10³/µL) compared to survivors (1.0 × 10³/µL) (p<0.0001). Similarly, CD3+, CD4+, and CD8+ T lymphocyte subsets were significantly lower in non-survivors. Non-survivors exhibited significantly higher serum levels of IL-6, LDH, CRP, and PCT (p<0.0001 for all). D-dimers and ferritin levels also showed a trend towards higher values in non-survivors, reaching statistical significance (p=0.0114 and p=0.0018 respectively). Multivariable logistic regression analysis identified age > 65 years (OR = 1.14; 95% CI, 1.07–1.22, p = 0.0001) and the number of comorbidities (OR = 1.84; 95% CI, 1.11–3.05; p = 0.0178) as independent risk factors for in-hospital mortality. IL-6 levels > 20 pg/mL and LDH levels > 489 U/L showed borderline significance as independent risk factors. The ROC curve analysis demonstrated good predictive ability for CD3+, CD4+, and CD8+ T cells, IL-6, and LDH in predicting in-hospital mortality. Common comorbidities included hypertension, obesity, diabetes mellitus, chronic cardiac disease, and chronic neurological disorders.

This study confirms the association between inflammation and poor prognosis in hospitalized COVID-19 patients. Elevated levels of IL-6, LDH, CRP, and PCT, markers of inflammation and tissue damage, were strongly associated with in-hospital mortality. Lymphocytopenia, reflecting immune dysfunction, also emerged as a predictor of death. The findings align with previous research on the role of inflammation in COVID-19 severity. Age and comorbidities independently predicted mortality, consistent with prior reports. The borderline significance of IL-6 and LDH suggests they may warrant further investigation as potential prognostic factors. The study's limitations, including its retrospective design and limited sample size, emphasize the need for larger prospective studies to validate these findings. While the study points towards the importance of these markers in predicting mortality, it's crucial to note that these biomarkers are not specific to COVID-19, and their interpretation should be done in the context of the overall clinical picture.

This study highlights the significant role of inflammation and lymphocytopenia in predicting in-hospital mortality among COVID-19 patients. Elevated levels of IL-6, LDH, CRP, and PCT, along with reduced lymphocyte counts, were strongly associated with increased risk of death. Age and the presence of comorbidities were independent risk factors. While IL-6 and LDH showed borderline significance as independent risk factors, their potential predictive value warrants further investigation. Future research should focus on larger, prospective studies to validate these findings and develop more comprehensive prognostic scores incorporating these and other clinical parameters.

This study is limited by its retrospective design and the relatively small sample size, potentially affecting the generalizability of the findings. The study was conducted in a single center, which could limit the diversity of the patient population and the generalizability of the results to other settings. The study period was limited to a few months during the pandemic, potentially limiting the applicability of the findings to different phases of the pandemic or to variations in viral strains. Despite the use of statistical methods to analyze the data, the potential for confounding factors remains. More research is needed to confirm these findings in different contexts and to develop more robust predictive models.