The present study is one of the primary reports with a large number of COVID-19 patients in Iran. We have observed that Hb, neutrophil, BUN, SpO2, and patchy consolidation in the CT assessment at admission time are statistically related to mortality. Although other factors may effect on outcome(Table5).
Interestingly, just one quarter of our study patients revealed a history of contact with suspected patients, which is comparable with the another finding (11). The virus transmission rout remains an important issue, which may play a major role in development of disease. Besides the common routs, nosocomial, fecal-oral, and aerosol transmission should be considered (12–14). Nosocomial transmission of the disease may occur mainly during the incubation period as well as close contact with patients with minimal symptoms (5, 15–17). Although the outbreak in China has been started via zoonotic transmission, in the city of Qom, the main rout of transmission seems to be person-to-person. None of our patients had a history of travel to China in the last two months before the outbreak and had a history of wild animal contact. All of our patients have inhabited in Qom too. Indeed, familial cluster was common in the city that close contact have happened. We should emphasize that transmission can be occurred by asymptomatic cases during incubation period even by potential routs such as saliva and urine (11, 18). The important point is the need to use well protective techniques, isolation and laboratory assessment, particularly for the healthcare staff. Moreover, in present study we did not estimate the virus reproductive value but according to the contamination speed, it may be higher than the previous reported data. Earlier studies indicated that the reproductive value (R0) of COVID‐19 was estimated to be between 2 and 3.5. It means that one infected patient could infect 2 to 3.5 individuals (17, 19, 20).
The gender distribution in our study shows that the male gender is prominent. Although there was no significant association between gender and the outcome. This is similar to the previous reports (21, 22). Furthermore, we have observed the association of mortality with increasing age, although it was not an independent risk factor for the mortality and lower than former study of China. In this context, previous studies verified that aging has a positive relation with mortality rate in MERS, SARS as well as COVID-19. It may be secondary to either sever pneumonia or its own associated morbidities during elderly (23) (2, 11). Recent report of CDC team for COVID-19, revealed that 80% of deaths are secondary to COVID-19 and it was among adults aged ≥ 65 years (24). In a pathophysiology view, studies on immune system in elderly patients disclosed the impaired T and B cell function. In fact, at older age the alteration of cytokines has a key role in the immune system function, as excess production of type 2 cytokines has been reported. Altogether, cytokines dysregulation could lead to defect control of viral infection and inflammatory responses (25, 26).
In present study, the main presentations were dyspnea and shortness of breath, cough, and fatigue/weakness. Bilateral opacities in CT scan assessments were particularly frequent in patients. Among them, bilateral consolidation associated significantly with risk of mortality. The relation between drop of SpO2 level with poor outcome may work in this context. The CT scan imaging is one of the principal and rapid diagnosis in COVID-19 for initiation of treatment and follow-up in order to find the healing changes in lungs. It was stated that consolidation with ground glass feature in both lungs were more prominent, particularly in dead patients, which was similar to our findings (27–29). The mechanism of lung damage needs more studies. It may be due to direct invasion of virus or inflammatory cascade, altogether, there is a need for more studies in order to identify the exact imaging feature of the disease for prognosis estimation and improvement assessment.
Clinical presentations of our study patients have some differences with other studies (29, 30). We have found fever more than 38oc was not a common symptom. In this regard the 87 (43.5%) subjects were fibril patients. This fact may reduce the predictive value of fever during surveillance. Moreover, number of patients with gastrointestinal manifestations at the time of admission was low and not significant differences between survivor and non-survivor patients regarding liver biochemistries has been observed. However, recent studies indicated the close relationship of abnormal liver function tests with severity of COVID-19 (1, 2, 11) that is not compatible with our findings.
Since this disease is a new disaster, we don’t have a lot of documents regarding its epidemiologic features and clinical course. Rodrigez et al, based on a meta-analysis, have reported that fever (88.7%), cough (57.6%) and dyspnea (45.6%) were the most prevalent clinical manifestations (31). These findings have some differences with SARS or MERS observations but almost comparable with the previous reports of COVID-19 (32, 33). Furthermore, Borges do Nascimento et al. reported that lymphopenia (0.93 × 103/µL, 95% CI 0.83–1.03 × 103/µL, n = 464), and abnormal CRP (33.72 mg/dL, 95% CI 21.54–45.91 mg/dL; n = 1637) are the most common laboratories findings in the patients with COVID-19 (34).
Neutrophilia (> 7.7count103/µL ) was common among our patients that significantly associated with mortality. This is also consistent with the previous studies as it was observed that patients increased blood neutrophil counts had severe symptoms (35–37). In severe cases lymphopenia has a great potential prognostic value and neutrophilia involved in inflammatory process. Wu et al in Wuhan revealed that the risk of ARDS significantly associated with neutrophilia, as well as aging and coagulation dysfunction (38). Furthermore, almost all of non-survivor patients suffered from ARDS. In addition, we have revealed a strong significance association between low Hb level and poor prognosis. In previous studies Hb value was found to be significantly lower in COVID-19 patients with severe disease than in those with milder forms. Hb level may reflect the severity of disease and probably involved in pathophysiology of organ failure on these patients and worse clinical outcome. Decline of Hb level could be secondary of inflammation process (1, 39). Therefore; regular assessment of CBC with differentiate at beginning and during patients' follow up, clinically would strongly recommended.
It is documented that patients with acute viral and bacterial pneumonia are at the risk of acute cardiac events during and after elimination of infection. Unfortunately, due to the outbreak emergency, patients were not regularly evaluated for cardiac enzymes or echocardiography. Hence, we did not have enough data regarding cardiac events. Among patients with COVID-19, many of them had underlying cardiovascular diseases and developed acute cardiac injury during the course of the illness (40). The mechanism has not been fully cleared but it can be due to neutrophils activity and inflammation process or direct invasion of pathogen (41, 42). Moreover, it is documented that preexisting coronary heart disease can be associated with acute cardiac events and eventually poor outcome in respiratory viral infection such as influenza (43, 44).
In conclusion, this is a large study among patients with definite outcome. In fact, COVID19 is a clinically complex virus that affects all the vital organs either via direct attack or inflammatory processes. Shortness of breath or dyspnea and cough were the common and valuable clinical manifestations. Low value of Hb, neutrophilia, and high BUN along with consolidation in CT scan images were risk factors of mortality that need to pay more attention during surveillance of patients.