This is a large cohort study of hospitalized patients with SARS-CoV-2 in Saudi Arabia. There was no significant disparity in the ratio of female and male patients, and infection in children was exceptionally low, which was consistent with the findings of other studies [1, 8, 9].
The median age of our cohort was 36 years, which is identical to the discoveries of a national study, indicating that COVID-19 affects a younger age group in Saudi Arabia compared to the rest of the world . This might be attributed mainly to the differences in the inclusion criteria and the population age groups in our study. However, all the age groups might have been infected, including those younger than 2 and older than 80. Our findings concur with previous studies, showing that patients infected with SARS-CoV-2 may present primarily with cough, fever ≥ 38 °C, lethargy, sore throat, shortness of breath, headache, and muscle pain with accompanying symptoms of sputum production, rhinorrhea, diarrhea, dysgeusia and anosmia like common cold [8, 9].
Mild severity patients may present without a fever and without signs of pneumonia; moderate patients usually have a fever ≥ 38 °C or respiratory symptoms, mainly shortness of breath, cough, and sore throat. There are many similarities between COVID-19, SARS-CoV, and new microorganisms such as avian influenza virus H7N9. However, there are also key differences. COVID-19 cases can vary from mild to moderate or even severe, while SARS cases or avian influenza virus H7N9, in general, were more severe . Unlike SARS-CoV infections which usually result in a high-grade fever at the early onset of infection , some COVID-19 patients included in our report presented with atypical symptoms and only low-grade fever and a long incubation period leading to a higher potential for COVID-19 viral transmission and greater infectiousness.
In our study, abnormal chest X-ray findings were more than twice as common as chest CT abnormalities in all patients (34.9% vs 16.7%). Since some of the mild severity patients were asymptomatic, it has been proposed that a CT examination should be the earliest choice in the screening and diagnosis of COVID-19. This is because the sensitivity of CT scan for SARS-CoV-2 was found to be 98%, compared to the RT-PCR sensitivity of 71% . Swift detection of COVID-19 is vital for disease therapy and control, and hence, a chest CT may be a more dependable, useful, and quick method to diagnose and evaluate COVID-19 .
As Al-Omari, et al. had recently pointed out, we deemed it necessary to investigate the laboratory and radiological features of COVID-19 patients in the Saudi population . Our mild and moderate COVID-19 patients had elevated inflammatory markers (e.g., CRP, D-dimer, and ferritin), similar to cytokine release syndrome, with persistent fevers [16, 17]. A recent study from Saudi Arabia also had similar findings with higher CRP, D-dimer, ferritin, and glucose levels in moderate severity patients . At the initial stage of COVID-19, the level of inflammation and lung lesions were positively linked with CRP levels, and thus, CRP levels could signify disease severity and were suggested to be utilized as a major marker for disease monitoring . Recently, Wang, et al. also demonstrated that a CRP finding of > 26.9 mg/L could be used as a predictive marker for aggravating severity of COVID-19 . An elevated level of D-dimer in patients with COVID-19 disease may provoke an emergent thrombotic complication and may due to the hyperactivation of the coagulation cascade. There is a systemic inflammatory response triggered by viral infections that can cause an imbalance between anticoagulant and procoagulant homeostatic processes . Ferritin is a fundamental mediator of immune dysregulation and contributes to the cytokine storm via direct immune-suppressive and pro-inflammatory effects .
Higher neutrophil absolute count has been related to a greater severity in COVID-19 as well as lymphopenia [21, 22]; higher levels of lymphocytes has not. Moreover, higher levels of liver enzymes were more manifested in the moderate patients compared to the mild cases, indicating that liver inflammation and liver damage in moderate patients are more evident . However, additional studies in Saudi Arabia are required to precisely identify which laboratory markers can potentially predict outcomes of COVID-19 patients in the Saudi population.
The ideal approach to the treatment of SARS-CoV-2 is uncertain and is based on limited data and evolves rapidly as clinical data emerge. Lack of a defined optimal management plan for COVID-19 disease results in the use of various treatment options and adjuvant therapies during hospital stay. For patients with non-severe disease, care is primarily supportive, with close monitoring for disease progression. Supportive measures offered to all patients in this study included the prevention of secondary infections, respiratory support, circulatory support, and preservation of renal, hepatic, and neurological function. In addition to the implementation of the basic principles of critical care medicine, patients received pharmacologic prophylaxis for venous thromboembolism. The frequencies of the supportive measures used for mild and moderate severity patient groups were not similar, but no conclusions can be made about efficacy. Hydroxychloroquine was used partly to treat the patients in both groups even though its routine use is not suggested outside the circumstances of a clinical trial given the lack of clear benefit from limited data and potential for cardiotoxicity [23, 24]. Given the lack of clear benefit and potential for toxicity, use of hydroxychloroquine in hospitalized patients is not suggested . However, hydroxychloroquine was used when the data about its benefit were scarce, considering that we have accumulated enough information now to ensure that hydroxychloroquine is not effective as a COVID-19 treatment or prophylaxis.
Our analysis demonstrates that therapy of COVID-19 patients with hydroxychloroquine resulted in a non-statistically significant effect on QTc interval. Hydroxychloroquine inhibits voltage-gated sodium and potassium channels, prolonging the QT interval, and is also structurally analogous to the class IA antiarrhythmic quinidine . Changes in QTc and prolongation findings due to hydroxychloroquine use aligned with previous studies of substantial QTc prolongation in 11–23% of patients [26, 27]. While the addition of azithromycin to hydroxychloroquine might have been implicated in QTc prolongation , it is still conceivable that the genuine degree of QTc prolongation associated with hydroxychloroquine was estimated imprecisely, given patient severity and characteristics variation and a limited follow-up period.
It is pertinent to recognize some limitations of this study. First, the retrospective study design could have introduced potential reporting bias due to reliance on clinical case records. Second, without a control group, we were unable to determine that hydroxychloroquine and azithromycin increases cardiotoxic risk; but, compared with solely hydroxychloroquine, changes in QTc differences were likely related to the addition of azithromycin. Furthermore, we were not able to provide details on the radiological characters of our SARS-CoV-2-infected patients. Moreover, many of the study patients are still hospitalized at the time of the writing of this manuscript. Consequently, there may have been some partiality regarding the prognosis of the patients. Finally, some follow-up data were unavailable. Clinical follow-up data for patients after recovery from SARS-CoV-2 infection could be used to examine longer-term functional and psychological abnormalities.