Current study is a descriptive report on the clinical/para-clinical characteristics of 233 patients with laboratory proven evidence of COVID-19 attending Buali Hospital, Zahedan, Iran. It represents the recent status of the COVID-19 in east of Iran where biggest state of Iran is located. Collectively, 1,911 patients who were suspected to carry the disease were referred to our center over a three month period, of which approximately 629 patients had mild/moderate to serious, sometimes fatal, pneumonia and were hospitalized. Given RT-PCR is regarded as reference standard method for diagnosis of SARS-CoV-2 infection [14], the para-clinical data of only 37% (233/629) of patients with positive RT-PCR results were investigated in the present study.
Human coronavirus is one of the main viral pathogens involving respiratory system. SARS-CoV and MERS-CoV besides four other human coronaviruses (HCoV-OC43, HCoV-229E, HCoV-NL63 and HCoV-HKU1) are the main pathogenic viruses belong to coronavirus family causing either severe respiratory syndrome or mild upper respiratory disease [15]. The major SARS-CoV outbreak affected 8,422 patients of 29 countries during 2002-2003 [16, 17]. Also, in 2012, MERS-CoV was emerged in Middle East countries [18]. Although, the genomic sequence of SARS-CoV-2 has been shown to be relatively different from the six other coronavirus subtypes but it can be classified as betacoronavirus [15]. In case of SARS-CoV and MERS-CoV, the viruses can be transmitted directly from civets and dromedary camels to humans, respectively, and bats were considered as the origin of both viruses, but the origin of SARS-CoV-2 is still not clear and needs further investigation [15, 19]. Rate of transmission is not exactly documented for SARS-CoV-2; however, human to human transmission has been evidenced [7, 15]. In concert with previous reports, it has been revealed that the clinical manifestations of COVID-19 mimic those presented in SARS-CoV [4, 7, 15, 20]. Fever and cough were the most predominant symptoms manifested in 70% and 63% of our patients, respectively. However, gastrointestinal upsets were infrequently presented (10%), which suggests a different viral tropism and pathogenesis in comparison with SARS-CoV, MERS-CoV, and seasonal influenza [7, 21-23]. The frequency of afebrile patients suffering from COVID-19 (20%) is more frequent than in SARS-CoV (1%) and MERS-CoV infection (2%) [7, 18] implying that presence of fever is not a trustworthy finding to be focused in case definition because afebrile patients will be missed. Similar to previous reports [4, 7, 15], reduced absolute lymphocytes count, and elevated level of CRP and ESR were the main laboratory findings. Damage to T lymphocytes might be a contributing factor leading to substantial decrease in total lymphocytes count and exacerbation of patient's status [24] as we observed statistically significant abnormalities in laboratory findings (including lymphopenia, elevated NLR, PLR and SII) of patients who expired (deceased group) when compared with survival group. In consistent with our result, a previous study conducted by Liu, et al [3], documented NLR as the independent risk factor for prediction of severe illness in patients with SARS-CoV-2 infection and should thus have rapid access to an ICU if necessary. So that, in 50% of patients with age ≥ 50 who had NLR ≥ 3.13, severe form of the disease were observed [3, 10]. Furthermore, in another study, a correlation between elevated PLR and the length of hospitalization day was evidenced and it has been concluded that if PLR increased more during treatment, the patient needs longer hospitalization day and had greater possibility of severe pneumonia[25]. Furthermore, Chan et al. in a meta-analysis concluded that NLR and PLR can be served as independent prognostic markers of disease severity in COVID-19 [26]. Recently, NLR and PLR have been validated as prognostic factors in various disorders such as cardiac conditions, solid tumors, sepsis, pneumonia, and ARDS [26]. The SII has been proposed as a prognostic indicator in the follow-up of sepsis patients (Systemic immune inflammatory index in sepsis). In addition, SII has been found to be useful in predicting the prognosis of small cell lung cancer and hepatocellular carcinoma [27, 28]. In consistent with previous study [29], rate of SII was found to be significantly higher in deceased patients when compared with survival group, meaning that it can also be used as predictor of COVID-19 severity and outcome. Therefore, indicators of systemic inflammation such as NLR, PLR and SII may be utilized to predict disease severity, outcome, and mortality of COVID-19. Acute phase proteins such as CRP, LDH, ferritin, procalcitonin, D-Dimer, ESR and IL-6 have also been well correlated with the disease severity, progression and poor outcome in COVID-19 [30]. In our study, CRP protein did not show any significant difference between survival and deceased groups. By the way, pathophysiology of COVID-19 is majorly associated with exaggerated inflammatory responses during the lung involvement. Lymphocytes, especially T lymphocytes, are the main cell to be targeted and consumed by SARS-CoV-2, as does SARS-CoV [24]. Virus particles pass across the respiratory mucosa and attack other cells, resulting in rise of proinflammatory cytokines and stimulate a cytokine storm and a cascade of immune responses in the body, leading to lymphocytic apoptosis, changes in peripheral white blood cells and immune cells such as lymphocytes [15, 31]. In current study, patients who suffered from severe form of COVID-19 (31.3%) required ICU hospitalization and oxygen therapy. Consequently, ARDS and septic shock progressed rapidly in some of our patients, which were eventually followed by multiple organ failure and death. As a result, level of creatinine, BUN and total/direct bilirubin were significantly increased in deceased patients when compared to alive patients which suggesting acute kidney and liver injury in our deceased patients similar to whatever evidenced in former report [32]. Therefore, early diagnosis and promptly treatment initiation of critically ill individuals is issue of crucial importance [15]. Only one patient in our investigation was medical worker. The mortality rate of SARS-CoV and MERS-CoV has been reported as more than 10% and 35%, respectively[33, 34]. The rate of mortality in our SARS-CoV-2 infected population was 12%, resembling to previous study [15]. It necessary to be noted that since patients who had uncomplicated illness and who did not need medical attention were not included in our study, the rate of case fatality in a real world scenario might be even lower. COVID-19 was more commonly observed in men than women (64% vs 36%) in our study. This gender preponderance was in agreement with previous studies [4, 7, 15]. Also, higher rate of MERS-CoV and SARS-CoV infection were documented in males than females [35, 36]. The lower frequency rate of COVID-19, MERS-CoV and SARS-CoV infection in females are thought to be attributed to the protection originating from sex hormones and X chromosome, which play contributing role in innate and adaptive immunity [37]. Additionally, it has been documented that COVID-19 is more probably to occur in older adult males due to weaker immune functions particularly those with chronic underlying diseases [15]. Our patient’s age ranged from 16 to 90 years with a mean age of 49.8 years. The data was in consistent with the previous studies which more and less reported similar mean age [7, 15]. The highest positive rate of COVID-19 RT-PCR was observed in age group 40-60 years. Since, our aim was to investigate the COVID-19 patients with positive RT-PCR as reference method, of 629 hospitalized patients who were clinically suspected cases of COVID-19 and also had initial positive CT scan suggesting COVID-19, only small quantity of our subjects had positive RT-PCR assay suggesting two scenarios: first, it may be indeed be true to say that the sensitivity rate of RT-PCR is as low as 37% which somehow has been also demonstrated in previous studies and may be justified by a list of confounding factors which is regarded to influence the result of RT-PCR and lead to false-negative including: improperly collected, transported or handled specimens, presence of amplification inhibitors in the specimen or inadequate numbers of organisms [14, 38, 39]. Second, due to the overlap of CT imaging patterns between COVID-19 and other viral pneumonia, false-positive cases of COVID-19 may be identified on chest CT scan[14]. Nevertheless, given the rapidly spreading of COVID-19, the priority should be to identify and isolate any suspicious CT scan case in order to administer appropriate treatment. By the way, in the context of disease control, some false-positive cases may be acceptable [14]. Therefore, one negative result of RT-PCR does not rule out SARS-CoV-2 infection and should not be used as the sole basis for patient management decisions and treatment.