Clinical Features in Predicting COVID-19

The coronavirus COVID-19 disease is being a hard task for emergency care units worldwide due to the uncharacteristic...


Introduction
The first cases of COVID-19 in Italy were confirmed on February %). The abnormal ABG profile was characteristics of an acute respiratory hypoxemic, hypocapnic state with a compesatory alkalosis, suggestive of a progressive pulmonary micro-embolism revealing an internal, persistent hypercoagulable process with endothelial activation as consequence of an uncotrolled increase of proinflammatory cytokines [1].
The body's response to the hypoxaemic state, is described by an increase in minute ventilation that drives to an unrestrainable hypocapnia, as the CO 2 diffuses through tissues about 20 times faster than O 2 . Though the pathoanatomical and pathophysiological basis for respiratory failure in COVID-19 remains unclear, the presence of progressive and diffuse tissue and alveolar damages with interstitial thickening and thromboembolisms and gas exchange impairments seem to be the reasonable mechanism. A scenario that is often accompanied with atelectasis and lung consolidations clearly seen in CT-scan images with typical ground glass opacities [2,3]. Nevertheless, the combination of ABG analysis, (the oxygen saturation level (PaO 2 ) and the CT-scan revealed to be a better tool in diagnosting COVID-19 than swab RT-PCR alone (total patients   Table 2: Covid-19 admitted patients (n=310) into 118 Emergency Department were screened for arterial blood gas (ABG) analysis, Swab Buffer (oral-nasal-pharinx) analyzed by RT-PCR and thoracic CT scan were then performed and results were compared. Notably, based on the oxygen saturation level (pO 2 ) the CT scan revealed, in line with different published data, a better degree of accuracy compared to swab-RT-PCR outcomes, the PaO 2 up to 60 mmHg on total of 59 patients the CT+ was 27 vs 11 swab+ (column 1); the PaO 2 from 61 to 70 mmHg, total 64 cases, 20 CT+ vs 12 swab+ (column 2); the PaO 2 from 71 to 90 mmHg, total 132 cases, 22 CT+ vs 17 swab+ (column 3); the PaO 2 90 mmHg, total 55 cases, 5 CT+ vs 2 swab+ (column 4).

Prognostic Factors of Severe Illness
The pathogenic mechanism that produces pneumonia seems to be particularly complex, especially with regard to the infection progression which eventually evolves into compromised multi-organ disease. At the moment, the data available seem to indicate a Sars-CoV-2 as the main pathogen capable of triggering the entire immune chain reaction that takes place with an increasing intensity within not only within the broncho-alveolar interstices but to surrounding tissues and organs as well. The induced endothelitis has been seen as major causative factors that affected microcirculatory activity with the insurgence of the "happy hypoxia", a phenomena described by J. Couzin-Frankel [7]. According to the author, the tissue necrosis should be linked to a generalized augmentation of inflammatory processes co-existing with a progressive state of infection driving to microvascular thrombosis that is often carachterized by a non-specific suggestive lymphopenia that may substantially refer to a dangerassociated molecular pattern predictive of an auto-generating necroinflammatory loop arrangement [7][8][9][10]. The unexpected worsening of the entire condition that eventually resolved into a massive and disseminated intravascular coagulation (DIC), deep intravascular thrombotic processess and sepsis syndrome has been generally accepted as typical clinical trait of COVID-19 affected patients ( Figures 1& 2) [11][12][13][14][15].  : An algorithm to clearly understand the disseminated intravascular coagulation (DIC), the intravascular thrombotic process (ITP) and sepsis syndrome (SS) in COVID-19 patients admitted in our Hospital. Thrombocytic evoltutive mechanism associated with high level of pro-inflammatory cytokines and interleukins, macrophage, T cells, DCs, NK and neutrophils hyper responses with scattering presence of both bacteria and virus lead to a progressive organ dysfunction and sepsis. Abnormal coagulation process, fibrinogen concentration and D-dimers are evident part of this mechanism and revealed to be a key factor for the differentiation of DIC from thrombotic microangiopathies (TMAs). Once DIC has been proved, the underlying superinflammatory process with multiple tissue and organ disseminated infection must be identified. This would be diagnosed by the identification of low eGFR, high level of troponin and fibrinogen together with high levels of ESR and D-Dimer associated with an increased level of neutrophils and a low level of lymphocytes. Positive netrophilia and lymphopenia, with high level of IL-6 strongly suggests a deteriorating DIC with an associated complement-activating condition like infection and progressive multi-organ failure [16][17][18][19][20][21][22][23] (Ciro Gargiulo, Rita Lazzaro, Mario Balzanelli).
Descriptive statistics were used to summarize the data; results are reported as medians ranges as appropriate. Categorical variables were summarized as counts and percentages. Statistical analysis was supported by Student-t test. The null hypotheswas H0 was calculated by using t-statistics. Preliminary results from this study suggested that the ABG test performed and CBC analysis upon admission of patients with suspected COVID-19 in the 118 Emergency Department may be suggestive of the extent of lung inflammatory/infectious process providing warnings for the patient's prognosis. The obtained results from ABG analysis measured at this time, performed before CT scan image and swab RT-PCR, indicated that 33 patients on a total of 46 confirmed COVID-19 (72%) revealed alkalosis, hypocapnia and hypoxia (pH > 7.45; low PaO 2 <75; low PaCO 2 < 35) ( Table 1) and 46 on 46 showed CT-scan with ground glass opacities (significance level 0.05). These results were in line with findings observed in precedent studies, in which a higher percentage of the lung being involved in the inflammatory process, as then presented on the CT scan images that appeared to correlate with decreased oxygenation capacity [16].
This clinical picture appeared to emphasize the severity of the patient's disease progression. Reduced ABG values and abnormal CBC and microbiology parameters into 118 Emergency Department arrival may be suggestive of greater essential severity of the disease process and allowing to recognize who eventually present with a subtle unfavorable condition even if not clinically compromised [16]. A quantitative assessment allowed us to assess in a predictable manner and with a certain precision the progression of the Sars-CoV-2 infection. The current study and data were obtained on a group of confirmed COVID-19 patients divided according to ABG, CT scan and RT-PCR results We were able to assess significative markers that could characterize the COVID-19 infection allowing better future prognosis and prediction. These specific features were reported as follow (Table 7): a) The sex, male patients resulted higher in number with higher affected rate than females.
b) The compromised ABG profile, characterized by a marked hypoxia, hypocapnia and alkalosis at the time of the admission, revealing either low PaO 2 saturation or low PaCO 2 strongly suggestive of COVID-19 even before the RT-PCR and CT-scan procedure.
c) The lymphopenia was seen also a higher specific COVID-19 marker. In general, though the CT scan and RT-PCR are considered to be categorical markers of COVID-19 diagnosis, in our opinion this would be an error due to their non-specificity towards the diseases itself. Said that, an extensive lung infection confirmed by an ABG analysis indicating an alkalotic, hypocapnic and hypoxic state accompanied by a "ground glass opacity" CT images could be more suggestive for an immediate hospitalization in specific departments.

Conclusion
The results of this study suggest that in COVID-19 patients, the ABG test showed to be an important tool in evaluating and assessing the Sars-CoV-2 risk progression due to its rapidity and applicability. Due to the high risk of having a sudden worsening of the disease, we would suggest the physicians to act as soon as the first symptoms appear and move the patients to the nearest COVID Hospital. Worrisome signs would be a persistent low fever in a range between 37,0° to 37,5° C, severe and persistent dry cough, increasing dyspnoea, with an ABG result showing alkalosysis, low PaO 2 and PaCO 2 . We are well aware that further studies are needed mainly related to the poor information regarding COVID-19. In addition, we also know that the relatively small number of the involved patients could eventually weaken the solidity of statistical analysis. Nevertheless, this model has been shown to be functional to the diverse application in different clinical scenarios of COVID-19, especially in supporting treatment decisions.

Conflicts of Interest
The authors whose names are listed above report the details of affiliation in an organization and entity with non-financial interest in the subject matter and materials discussed in this manuscript.