COVID-19 is currently experiencing an outbreak period, and the number of patients has continued to rise. The total number of patients has far exceeded those of SARS or MERS. Genome-wide sequencing and phylogenetic tree analysis suggest that COVID-19 is a distinct branch of β coronavirus associated with SARS (SARS-CoV) and MERS (MERS-CoV). COVID-19 is characteristic of the coronavirus family and is classified as a β coronavirus 2β spectrum. Research findings demonstrate that COVID-19 has a similar gene sequence to that of SARS, and that they have a common origin (bats) and common intracellular receptors (ACE2)27. Thus, its symptoms are also similar to those of SARS, often manifesting as a fever, shortness of breath, cough, or breathing difficulty, and, in severe cases, pneumonia or even death may occur28. A study by Zhong et al. found that only 43.1 percent of patients with COVID-19 presented with a fever when they were admitted to the hospital, and more developed a fever in the hospital29. In contrast, SARS and MERS patients almost all present fevers when they are diagnosed, and only 1-2% do not present a fever30. This means that if the examination of suspected COVID-19 cases for the prevention and control of the epidemic is carried out only by measuring body temperature, huge amounts of infected patients without fevers may be omitted. Therefore, COVID-19 is more concealed and more contagious than SARS, and this outbreak will be more difficult to deal with than SARS or MERS. Many mild patients who have rapidly progressed to severe illness have not yet undergone effective targeted therapy for COVID-19. Therefore, understanding the development of the disease is particularly important for reducing the critical rate.
The present study revealed that chest tightness with a positive likelihood ratio 3.8(1.44,10.05) and shortness of breath with a positive likelihood ratio 3.18(2.24,4.51) have strong correlations with severe patients. Chest tightness and shortness of breath is a sign that the disease has seriously affected the respiratory system. Diarrhea also has a relatively high positive likelihood ratio 2.04(1.38,3.04), which may be related to severe illness. The main reason for this may be that the throat is connected to the esophagus, and the virus may enter the digestive tract through the throat in severe patients by infecting intestinal epithelial cells and activating the intestinal immune response, thereby stimulating the gastrointestinal tract and causing diarrhea. It has also been recently reported that the disease may be transmitted via the fecal-oral pathway, and intestinal syndrome may be a marker of high viral load. Meta-analysis of the selected data also revealed that the prevalence of hypertension is 19%, 95% CI: 15-23%, followed by diabetes (9%, 95% CI: 7-11%) and cardiovascular disease (8%, 95% CI: 5-10%). And compared to patients with no comorbidities, severe cases are significantly correlated with chronic respiratory system diseases (pooled positive likelihood 6.07, 95% CI: 3.12,11.82), chronic renal disease (4.79, 2.04-11.25), and cardiovascular disease (3.45, 2.19-5.44). The chronic conditions that influence the severity of COVID-19, such as chronic respiratory system diseases and chronic renal disease, were also reported to affected other coronavirus–infected pneumonia, such as MERS and SARS31. Therefore, the roles of comorbidities in severe COVID-19 cases were further investigated. Most healthy young people are mild patients because their lung epithelial cells are in good condition, and their natural response to virus invasion is rapid and effective. Their immune cells are intact and well-functioning, and even after COVID-19 infection and relatively few lower respiratory tract infections, they may not have clinical symptoms, or only symptoms that are very mild. In the condition of chronic respiratory disease, especially COPD, lower respiratory tract infections, both acute and chronic, occur with increased frequency32. AS chronic respiratory disease has a great influence on the clinical course of COVID-19, it can be regarded as a major comorbidity of COVID-19. A large number of immune cells are stimulated by the COVID-19 virus to be recruited to the alveolar site, thus releasing a large number of inflammatory cytokines (known medically as cytokine storms)33. These inflammatory factors act on the alveolar-vascular membrane, destroy its integrity, greatly increase its permeability, and result in a large amount of blood in the alveoli, thus leading to human hypoxia and exacerbating respiratory disease like COPD31. In addition, since the use of inhaled corticosteroids in COPD patients is positively correlated with the occurrence of pneumonia, it has received considerable attention in recent years 34. Several studies have determined the role of COPD in the pathogenesis of viral infectious pneumonia35, 36. It can also reasonably explain why chronic respiratory diseases (mainly COPD) are more likely to cause disease deterioration. Studies have found that, compared with non-HIV-infected patients, patients with chronic respiratory disease are more likely to become ill with HIV infection 37. Therefore, the over use of hormone drugs makes patients with chronic respiratory diseases more susceptible to viruses such as COVID-19.
Chronic metabolic diseases such as diabetes, chronic cardiovascular diseases, chronic renal diseases and related conditions can be etiologically linked to the pathogenesis of COVID-19. Existing research has found that COVID-19 may be a self-limiting disease, and the body can clear the virus on its own if it has sufficient immunity. These comorbidities are known as “down regulators” of the innate immune system of the host during the progress of the body’s response to pathogenesis. Chronic diseases have shown similar potential in causing infectious disorders of the immune system38, 39. For example, diabetes decreases the synthesis of pro-inflammatory cytokines, interleukins, and their downstream acute phase reactant40. Metabolic disorders also influence macrophage and lymphocyte functions result in a decline of immunity system, and may finally cause patients to be more susceptible to COVID-19. In elderly patients with cardiovascular disease, diabetes, or other basic diseases, the immune system function is weaker, their ability to resist the virus is worse, and they are more vulnerable to infection by COVID-19. Therefore, improving the basic conditions of the body, such as lowering blood sugar, is likely to control the deterioration of COVID-19 and reduce mortality.
In addition, the patient's laboratory examination is also expected to be used as an important indicator to predict the severity of the patient's disease. When the patient's C-reactive protein, ratio of neutrophils to lymphocytes and erythrocyte sedimentation rate increased, the patient is more likely to progress to severe disease and require critical care. C-reactive protein is an indicator of the degree of infection. When it increases violently, it indicates that the patient is in serious condition and has a high probability of worsening into severe. The same is true of other relevant indicators, reflecting the progress of the disease infection. Therefore, laboratory examination must not be ignored, so that clinicians can detect patients' deteriorating progress earlier and take effective treatment in time.
In conclusion, this study has found that those who have been diagnosed with chronic conditions especially chronic respiratory disease are more susceptible to COVID-19, and we should be more alert to the serious development of COVID-19 in patients with chest tightness and shortness of breath, diarrhea, also the neglected laboratory examination like increased C-reactive protein, ratio of neutrophils to lymphocytes, and erythrocyte sedimentation rate. Our research could be used to properly monitor and predict the serious progression in patients with COVID-19 to reduce mortality.
The present study has several limitations. First, the largest sample in this study occupies 1099/3547 (31.0%) of the total sample, which is a large proportion and may have a greater impact on the overall conclusion. Second, different articles have different definitions of severe patients, which may cause deviations in result. Third, some of the articles have overlapping definitions of certain test indicators, affecting the data and results. Fourth, it is not clear whether the indicators in some studies were determined at the time of admission, and the time order of the occurrence of symptoms and the severity of the disease may affect the results. Fifth, the end points of the patients in the including studies were unclear, and the cut-off point was the publication time of the article. It was difficult to determine whether the future mutual conversion between mild and severe cases would affect the results. Nevertheless, the conclusions drawn so far are still of great significance to the treatment of COVID-19 today.