Increased levels of serum CRP, PCT, IL-6 were also found.
Extreme rise in inflammatory cytokines including IL2, IL7, IL10, GCSF, IP10, MCP1, MIP1A, and TNFα
Lymphopenia (lymphocyte count, 0.67 109/L [SD, 0.33]) occurred in 24 patients (70.59%), decreased albumin (30.18, [SD, 4.76]) in 25 patients (80.65%), elevated D-dimer (8.64 [IQR, 2.39-20]) in 27 patients (100%), and elevated lactate dehydrogenase (502.5 U/L [IQR, 410-629]) in 26 patients (100%). Nearly all of the patients have elevated CRP (106.3 mg/L [IQR, 60.83 225.3]), PCT (0.61 ng/ml [IQR, 0.16-2.10]) and IL-6 (100.6 pg/ml [IQR, 51.51-919.5]). [6]
The most common laboratory abnormalities were hypoalbuminemia, lymphopenia, decreased percentage of lymphocytes (LYM) and neutrophils (NEU), elevated C-reactive protein (CRP) and lactate dehydrogenase (LDH), and decreased CD8 count. The viral load of 2019-nCoV detected from patient respiratory tracts was positively linked to lung disease severity. ALB, LYM, LYM (%), LDH, NEU (%), and CRP were highly correlated to the acute lung injury. Age, viral load, lung injury score, and blood biochemistry indexes, albumin (ALB), CRP, LDH, LYM (%), LYM, and NEU (%), may be predictors of disease severity. [8]
Introduction:
Beginning in December, 2019, a cluster of cases of pneumonia with unknown cause was reported in Wuhan, in the Hubei province of China.1 On Jan 7, 2020, a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARSCoV2; previously known as 2019nCoV), was identified as the causative organism by Chinese facilities via deep sequencing analysis of patients’ respiratory tract samples.2,3 SARSCoV2 has been shown to infect human respiratory epithelial cells through an interaction between the viral S protein and the angiotensin converting enzyme 2 receptor on human cells; thus, SARSCoV2 possesses a strong capability to infect humans. Most of the initial cases of coronavirus disease 2019 (COVID19), the disease caused by SARSCoV2, were epidemiologically linked to exposure to Wuhan’s Huanan seafood market, where wild animals are traded. Although the market has been closed since Jan 1, 2020, as part of efforts to contain the outbreak, patients without exposure to the market but with a history of travel to Wuhan or close physical contact with a patient confirmed to have COVID19, including healthcare workers, have also been identified, suggesting strong human to human transmission. The number of cases has been increasing rapidly. [1]
Detection:
Chest CT vs. RT-PCR viral nucleic acid testing. The real-time reverse transcriptase polymerase chain reaction (RT-PCR) test for COVID-19 is believed to have high specificity but sensitivity has been reported to be as low as 60%–70%. Thus, excluding a diagnosis of COVID-19 requires multiple negative tests, with test kits in short supply or unavailable. In response to reports of lung abnormalities on CT predating conversion to positive RT-PCR, Chinese authorities initially broadened the official definition of infection to include patients with typical findings at CT, even with a first negative RT-PCR result. This broader definition has resulted in a higher number of presumptive cases of COVID-19 and an increasing role for CT in diagnosis. However, the presence of mild or no CT findings in many early cases of infection highlights the difficulties of early detection. [4]
The importance of CT for detecting COVID-19 infection continues to increase as public health authorities grapple with the clinical complexities of early diagnosis. Future challenges include distinguishing COVID-19 infection from other conditions that present with similar findings at radiography and CT. Serial CT imaging shows the progression of lung abnormalities with the development of crazy-paving and increase in consolidation, more extensive lung involvement, and slow resolution—the typical evolution of acute lung injury. The character and extent of abnormalities beyond 4 weeks remains unknown, but one can expect similarities to other acute lung injuries with resolution or residual scar. Furthermore, detailed pathologic analysis of patients infected with or who died from COVID-19 infection remains unreported. In the appropriate setting of patient exposure or in areas of endemic disease, chest CT findings have played a key role in evaluation of COVID-19 infection. [4]
The chest X-ray (CXR) usually shows bilateral infiltrates but may be normal in early disease. The CT is more sensitive and specific. CT imaging generally shows infiltrates, ground glass opacities and sub segmental consolidation. It is also abnormal in asymptomatic patients/ patients with no clinical evidence of lower respiratory tract involvement. In fact, abnormal CT scans have been used to diagnose COVID-19 in suspect cases with negative molecular diagnosis; many of these patients had positive molecular tests on repeat testing. [5]
Symptoms:
COVID-19 infection causes a severe lower respiratory tract infection with bilateral, basal and peripheral predominant ground-glass opacity, consolidation or both as the most common reported CT findings—features typical of an organizing pneumonia pattern of lung injury. These findings peak around 9–13 days and slowly begin to resolve thereafter.[4]
Most patients with lower respiratory tract infection caused by COVID-19 present with fever, cough, dyspnea, and myalgia. 17% to 29% of patients have acute respiratory distress syndrome (ARDS). The fatality rate is estimated to be approximately 2.3%. One retrospective study estimated the R0, the average number of new infections from an infected person to a naïve population, to be 3.28 compared to WHO estimates of 1.4–2.5. Values greater than 1.0 indicate the infection will likely spread rather than diminish. R0 values estimated from later studies tend to be more reliable due to increased awareness and intervention. [4]
In an investigation of 36 patients who died from COVID-19. The mean age of the patients was 69.22 years (SD 9.64, range 50-90). 25(69.44%) patients were males, and 11 (30.56%) female. 26 (72.22%) patients had chronic diseases, mainly including hypertension, cardiovascular disease and diabetes. [6]
Patients had common clinical symptoms of fever (34 [94.44%] patients), cough (28 [77.78%] patients), shortness of breath (21 [58.33%] patients), and fatigue (17 [47.22%] patient). Chest computed tomographic scans showed that 31 (96.88%) patients had bilateral pneumonia. Most patients received antiviral therapy and antibiotic therapy, and more than half of patients received glucocorticoid therapy (25 [69.44%]). All the patients had ARDS. The median time from onset to ARDS was 11 days. One (2.78%) patient presented with acute renal injury. The median time from onset to death was 17 days. [6]
Diagnosis is by demonstration of the virus in respiratory secretions by special molecular tests. Common laboratory findings include normal/ low white cell counts with elevated C-reactive protein (CRP). The computerized tomographic chest scan is usually abnormal even in those with no symptoms or mild disease. [5]
X-ray images showed rapid progression of pneumonia and some differences between the left and right lung. In addition, the liver tissue showed moderate microvesicular steatosis and mild lobular activity, but there was no conclusive evidence to support SARS-CoV-2 infection or drug-induced liver injury as the cause. There were no obvious histological changes seen in heart tissue, suggesting that SARS-CoV-2 infection might not directly impair the heart. [2]
Lymphopenia is a common feature in the patients with COVID-19 and might be a critical factor associated with disease severity and mortality. [2] In patients recovering from COVID-19 pneumonia (without severe respiratory distress during the disease course), lung abnormalities on chest CT showed greatest severity approximately 10 days after initial onset of symptoms. [3]
Leukocytosis was detected in 26 (32%) patients and lymphocytosis in 54 (67%) patients. Concentrations of Creactive protein and serum amyloid A protein were elevated in most patients, as observed in previous betacoronavirus infections.10,11,20 In the subgroup of asymptomatic patients (group 1), concentrations of Creactive protein (6·9 mg/L) and aspartate aminotransferase (30·2 U/L) were lower than those in symptomatic patients. [4]
In a subset of patients, by the end of the first week the disease can progress to pneumonia, respiratory failure and death. This progression is associated with extreme rise in inflammatory cytokines including IL2, IL7, IL10, GCSF, IP10, MCP1, MIP1A, and TNFα. [5]
Other laboratory investigations are usually non specific. The white cell count is usually normal or low. There may be lymphopenia; a lymphocyte count <1000 has been associated with severe disease. The platelet count is usually normal or mildly low. The CRP and ESR are generally elevated but procalcitonin levels are usually normal. A high procalcitonin level may indicate a bacterial co-infection. The ALT/AST, prothrombin time, creatinine, D-dimer, CPK and LDH may be elevated and high levels are associated with severe disease. [5]
A lymphocytopenia occurred in more than 70% of patients at admission, which is a main laboratory feature in COVID-19 patients 15.17. Lymphocytopenia have been identified in the critically ill patients with SARS-CoV and MERS infection 18.19. As mentioned in previous studies, the severity of lymphocytopenia might indicate the severity of COVID-19, under the assumption of SARS-CoV-2 viral could attack and destroy the lymphocyte targetedly2. Further studies are warranted to confirm these findings. Increased levels of serum CRP, PCT, IL-6 were also found. [6]
Increased CRP, PCT concentration and decreased lymphocyte count from admission to death (Supplementary Figure 2), which may represent more prominent inflammation in severe patients. Therefore, intravenous glucocorticoids therapy, intravenous immunoglobulin therapy and interferon-alpha (α-IFN) aerosol inhalation were also used to restore homeostasis, without solid evidence. To our knowledge, there is still no specific medicine for COVID-19 till now. Clinical trials on promising regimens for COVID-19, such as remdesivir, lopinavir, and chloroquine phosphate are ongoing, which shed light on conquering the COVID-19 epidemic. [6]
Lab characteristics:
All 12 cases of the 2019 COVID-19-infected patients developed pneumonia and half of them developed ARDS. The most common laboratory abnormalities were hypoalbuminemia, lymphopenia, decreased percentage of lymphocytes (LYM) and neutrophils (NEU), elevated C-reactive protein (CRP) and lactate dehydrogenase (LDH), and decreased CD8 count. The viral load of 2019-nCoV detected from patient respiratory tracts was positively linked to lung disease severity. ALB, LYM, LYM (%), LDH, NEU (%), and CRP were highly correlated to the acute lung injury. Age, viral load, lung injury score, and blood biochemistry indexes, albumin (ALB), CRP, LDH, LYM (%), LYM, and NEU (%), may be predictors of disease severity. Moreover, the Angiotensin II level in the plasma sample from 2019-nCoV infected patients was markedly elevated and linearly associated to viral load and lung injury. Our results suggest a number of potential diagnosis biomarkers and angiotensin receptor blocker (ARB) drugs for potential repurposing treatment of COVID-19 infection. [8]
Increased levels of serum CRP, PCT, IL-6 were also found. Extreme rise in inflammatory cytokines including IL2, IL7, IL10, GCSF, IP10, MCP1, MIP1A, and TNFα. MEasured from 31 infected patients: Lymphopenia (lymphocyte count, 0.67 109/L [SD, 0.33]) occurred in 24 patients (70.59%), decreased albumin (30.18, [SD, 4.76]) in 25 patients (80.65%), elevated D-dimer (8.64 [IQR, 2.39-20]) in 27 patients (100%), and elevated lactate dehydrogenase (502.5 U/L [IQR, 410-629]) in 26 patients (100%). Nearly all of the patients have elevated CRP (106.3 mg/L [IQR, 60.83 225.3]), PCT (0.61 ng/ml [IQR, 0.16-2.10]) and IL-6 (100.6 pg/ml [IQR, 51.51-919.5]). [6]
From 81 infected patients the following values were measured (SD) [1]:
Leukocyte count, × 10⁹/L <10 68%
Lymphocyte count, × 10⁹/L ≥1.0 67%
Platelet count, × 10⁹/L ≥100 100%
Haemoglobin, ng/mL 123.9 (12.0) (SD)
C-reactive protein, mg/L 47.6 (41.8)
Serum amyloid A protein, mg/L 213.5 (177.8)
Alanine aminotransferase, U/L 46.2 (29.5)
Aspartate aminotransferase, U/L 40.8 (17.9)
Total bilirubin, µmol/L 11.9 (3.6)
Albumin, g/L 32.9 (8.1)
Glucose, mmol/L 6.4 (2.1)
Creatinine, µmol/L 75.4 (29.8)
Prothrombin time, s 10.7 (0.9)
Activated partial thromboplastin time, s 32.1 (7.6)
Thrombin time, s 28.9 (8.4)
Fibrinogen, g/L 1.5 (2.3)
D-dimers, mg/L 6.5 (0.8)
Treatment:
Although corticosteroid treatment is not routinely recommended to be used for SARS-CoV-2 pneumonia,1 according to our pathological findings of pulmonary oedema and hyaline membrane formation, timely and appropriate use of corticosteroids together with ventilator support should be considered for the severe patients to prevent ARDS development. [2] Treatment is essentially supportive; role of antiviral agents is yet to be established. Prevention entails home isolation of suspected cases and those with mild illnesses and strict infection control measures at hospitals that include contact and droplet precautions. [5]
In the case ser5ies of 99 hospitalized patients with COVID-19 infection from Wuhan, oxygen was given to 76%, non-invasive ventilation in 13%, mechanical ventilation in 4%, extracorporeal membrane oxygenation (ECMO) in 3%, continuous renal replacement therapy (CRRT) in 9%, antibiotics in 71%, antifungals in 15%, glucocorticoids in 19% and intravenous immunoglobulin therapy in 27% [15]. Antiviral therapy consisting of oseltamivir, ganciclovir and lopinavir-ritonavir was given to 75% of the patients. The duration of non-invasive ventilation was 4–22 d [median 9 d] and mechanical ventilation for 3–20 d [median 17 d]. In the case series of children discussed earlier, all children recovered with basic treatment and did not need intensive care. [5]
There is anecdotal experience with use of remdeswir, a broad spectrum anti RNA drug developed for Ebola in management of COVID-19 [27]. More evidence is needed before these drugs are recommended. Other drugs proposed for therapy are arbidol (an antiviral drug available in Russia and China), intravenous immunoglobulin, interferons, chloroquine and plasma of patients recovered from COVID-19 [21, 28, 29]. Additionally, recommendations about using traditional Chinese herbs find place in the Chinese guidelines. [5]
The ICU mortality rate among those who required non-invasive ventilation was 23 (79%) of 29 and among those who required invasive mechanical ventilation was 19 (86%) of 22. [7]
Jonathan Chun-Hei Cheung and colleagues do not recommend use of a high-flow nasal cannula or non-invasive ventilation until the patient has viral clearance. Supporting the recommendation of the authors, some points in relation to the use of high-flow nasal oxygen therapy and non-invasive ventilation in patients with COVID-19 infection: First, although exhaled air dispersion during high-flow nasal oxygen therapy and non-invasive ventilation via different interfaces is restricted, provided that there is a good mask interface fitting, not all hospitals around the world have access to such interfaces or enough personal-protective equipment of sufficiently high quality for aerosol-generating procedures, and several hospitals do not have a negative pressure isolation room. [7] Second, the fundamental pathophysiology of severe viral pneumonia is ARDS. Non-invasive ventilation is not recommended for patients with viral infections complicated by pneumonia because, although non-invasive ventilation temporarily improves oxygenation and reduces the work of breathing in these patients, this method does not necessarily change the natural disease course. Finally, the application of non-invasive ventilation in patients with COVID-19 in the ICU is controversial. Considering the above factors, clinicians might not use non-invasive ventilation for critically ill patients with ARDS due to COVID-19 until further data from the COVID-19 epidemic are available. [7]
The WHO interim guidelines made general recommendations for treatment of ARDS in this setting, including that consideration be given to referring patients with refractory hypoxemia to expert centers capable of providing extracorporeal membrane oxygenation (ECMO). [8]
ECMO is a form of modified cardiopulmonary bypass in which venous blood is removed from the body and pumped through an artificial membrane lung in patients who have refractory respiratory or cardiac failure. Oxygen is added, carbon dioxide is removed, and blood is returned to the patient, either via another vein to provide respiratory support or a major artery to provide circulatory support. ECMO is a resource-intensive, highly specialized, and expensive form of life support with the potential for significant complications, in particular hemorrhage and nosocomial infection. Recent evidence suggests that use of ECMO in the most severe cases of ARDS is associated with reduced mortality.6 There is some evidence that outcomes from ECMO are better in higher-volume centers. [8]
Furthermore, with the apparent contagiousness of this virus and the relatively high numbers of patients who require intensive care, this may prove very resource-consumptive. Countries will need to pay specific attention to the considerable investment needed to provide ECMO during this outbreak. Judgment will be needed to decide when ECMO may be worthwhile and when it may not, understanding that the risk-to-benefit ratio of performing ECMO in these circumstances is dynamic and dependent on many factors. If the mechanism of death in COVID-19 ultimately includes a substantial number of patients with septic shock or refractory multiorgan failure, then the shift away from ECMO is likely to occur earlier because the most severely ill patients in this cohort would be less likely to benefit. The higher the all-cause mortality, the less relevant ECMO becomes. [8]
Regardless, ECMO is clearly a finite resource. In a large outbreak, additional limitations to providing ECMO may include a lack of ECMO consoles or disposable equipment, suitably trained staff, or isolation rooms with the requisite infrastructure. Many materials necessary to make ECMO circuits are manufactured in China and it is conceivable that the outbreak may disrupt supply chains. [8]
Summary on COVID-19 characteristics:
Introduction:
Beginning in December, 2019, a cluster of cases of pneumonia with unknown cause was reported in Wuhan, in the Hubei province of China.1 On Jan 7, 2020, a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARSCoV2; previously known as 2019nCoV), was identified as the causative organism by Chinese facilities via deep sequencing analysis of patients’ respiratory tract samples.2,3 SARSCoV2 has been shown to infect human respiratory epithelial cells through an interaction between the viral S protein and the angiotensin converting enzyme 2 receptor on human cells; thus, SARSCoV2 possesses a strong capability to infect humans. Most of the initial cases of coronavirus disease 2019 (COVID19), the disease caused by SARSCoV2, were epidemiologically linked to exposure to Wuhan’s Huanan seafood market, where wild animals are traded. Although the market has been closed since Jan 1, 2020, as part of efforts to contain the outbreak, patients without exposure to the market but with a history of travel to Wuhan or close physical contact with a patient confirmed to have COVID19, including healthcare workers, have also been identified, suggesting strong human to human transmission. The number of cases has been increasing rapidly. [1]
Detection:
Chest CT vs. RT-PCR viral nucleic acid testing. The real-time reverse transcriptase polymerase chain reaction (RT-PCR) test for COVID-19 is believed to have high specificity but sensitivity has been reported to be as low as 60%–70%. Thus, excluding a diagnosis of COVID-19 requires multiple negative tests, with test kits in short supply or unavailable. In response to reports of lung abnormalities on CT predating conversion to positive RT-PCR, Chinese authorities initially broadened the official definition of infection to include patients with typical findings at CT, even with a first negative RT-PCR result. This broader definition has resulted in a higher number of presumptive cases of COVID-19 and an increasing role for CT in diagnosis. However, the presence of mild or no CT findings in many early cases of infection highlights the difficulties of early detection. [4]
The importance of CT for detecting COVID-19 infection continues to increase as public health authorities grapple with the clinical complexities of early diagnosis. Future challenges include distinguishing COVID-19 infection from other conditions that present with similar findings at radiography and CT. Serial CT imaging shows the progression of lung abnormalities with the development of crazy-paving and increase in consolidation, more extensive lung involvement, and slow resolution—the typical evolution of acute lung injury. The character and extent of abnormalities beyond 4 weeks remains unknown, but one can expect similarities to other acute lung injuries with resolution or residual scar. Furthermore, detailed pathologic analysis of patients infected with or who died from COVID-19 infection remains unreported. In the appropriate setting of patient exposure or in areas of endemic disease, chest CT findings have played a key role in evaluation of COVID-19 infection. [4]
The chest X-ray (CXR) usually shows bilateral infiltrates but may be normal in early disease. The CT is more sensitive and specific. CT imaging generally shows infiltrates, ground glass opacities and sub segmental consolidation. It is also abnormal in asymptomatic patients/ patients with no clinical evidence of lower respiratory tract involvement. In fact, abnormal CT scans have been used to diagnose COVID-19 in suspect cases with negative molecular diagnosis; many of these patients had positive molecular tests on repeat testing. [5]
Symptoms:
COVID-19 infection causes a severe lower respiratory tract infection with bilateral, basal and peripheral predominant ground-glass opacity, consolidation or both as the most common reported CT findings—features typical of an organizing pneumonia pattern of lung injury. These findings peak around 9–13 days and slowly begin to resolve thereafter.[4]
Most patients with lower respiratory tract infection caused by COVID-19 present with fever, cough, dyspnea, and myalgia. 17% to 29% of patients have acute respiratory distress syndrome (ARDS). The fatality rate is estimated to be approximately 2.3%. One retrospective study estimated the R0, the average number of new infections from an infected person to a naïve population, to be 3.28 compared to WHO estimates of 1.4–2.5. Values greater than 1.0 indicate the infection will likely spread rather than diminish. R0 values estimated from later studies tend to be more reliable due to increased awareness and intervention. [4]
In an investigation of 36 patients who died from COVID-19. The mean age of the patients was 69.22 years (SD 9.64, range 50-90). 25(69.44%) patients were males, and 11 (30.56%) female. 26 (72.22%) patients had chronic diseases, mainly including hypertension, cardiovascular disease and diabetes. [6]
Patients had common clinical symptoms of fever (34 [94.44%] patients), cough (28 [77.78%] patients), shortness of breath (21 [58.33%] patients), and fatigue (17 [47.22%] patient). Chest computed tomographic scans showed that 31 (96.88%) patients had bilateral pneumonia. Most patients received antiviral therapy and antibiotic therapy, and more than half of patients received glucocorticoid therapy (25 [69.44%]). All the patients had ARDS. The median time from onset to ARDS was 11 days. One (2.78%) patient presented with acute renal injury. The median time from onset to death was 17 days. [6]
Diagnosis is by demonstration of the virus in respiratory secretions by special molecular tests. Common laboratory findings include normal/ low white cell counts with elevated C-reactive protein (CRP). The computerized tomographic chest scan is usually abnormal even in those with no symptoms or mild disease. [5]
X-ray images showed rapid progression of pneumonia and some differences between the left and right lung. In addition, the liver tissue showed moderate microvesicular steatosis and mild lobular activity, but there was no conclusive evidence to support SARS-CoV-2 infection or drug-induced liver injury as the cause. There were no obvious histological changes seen in heart tissue, suggesting that SARS-CoV-2 infection might not directly impair the heart. [2]
Lymphopenia is a common feature in the patients with COVID-19 and might be a critical factor associated with disease severity and mortality. [2] In patients recovering from COVID-19 pneumonia (without severe respiratory distress during the disease course), lung abnormalities on chest CT showed greatest severity approximately 10 days after initial onset of symptoms. [3]
Leukocytosis was detected in 26 (32%) patients and lymphocytosis in 54 (67%) patients. Concentrations of Creactive protein and serum amyloid A protein were elevated in most patients, as observed in previous betacoronavirus infections.10,11,20 In the subgroup of asymptomatic patients (group 1), concentrations of Creactive protein (6·9 mg/L) and aspartate aminotransferase (30·2 U/L) were lower than those in symptomatic patients. [4]
In a subset of patients, by the end of the first week the disease can progress to pneumonia, respiratory failure and death. This progression is associated with extreme rise in inflammatory cytokines including IL2, IL7, IL10, GCSF, IP10, MCP1, MIP1A, and TNFα. [5]
Other laboratory investigations are usually non specific. The white cell count is usually normal or low. There may be lymphopenia; a lymphocyte count <1000 has been associated with severe disease. The platelet count is usually normal or mildly low. The CRP and ESR are generally elevated but procalcitonin levels are usually normal. A high procalcitonin level may indicate a bacterial co-infection. The ALT/AST, prothrombin time, creatinine, D-dimer, CPK and LDH may be elevated and high levels are associated with severe disease. [5]
A lymphocytopenia occurred in more than 70% of patients at admission, which is a main laboratory feature in COVID-19 patients 15.17. Lymphocytopenia have been identified in the critically ill patients with SARS-CoV and MERS infection 18.19. As mentioned in previous studies, the severity of lymphocytopenia might indicate the severity of COVID-19, under the assumption of SARS-CoV-2 viral could attack and destroy the lymphocyte targetedly2. Further studies are warranted to confirm these findings. Increased levels of serum CRP, PCT, IL-6 were also found. [6]
Increased CRP, PCT concentration and decreased lymphocyte count from admission to death (Supplementary Figure 2), which may represent more prominent inflammation in severe patients. Therefore, intravenous glucocorticoids therapy, intravenous immunoglobulin therapy and interferon-alpha (α-IFN) aerosol inhalation were also used to restore homeostasis, without solid evidence. To our knowledge, there is still no specific medicine for COVID-19 till now. Clinical trials on promising regimens for COVID-19, such as remdesivir, lopinavir, and chloroquine phosphate are ongoing, which shed light on conquering the COVID-19 epidemic. [6]
Lab characteristics:
All 12 cases of the 2019 COVID-19-infected patients developed pneumonia and half of them developed ARDS. The most common laboratory abnormalities were hypoalbuminemia, lymphopenia, decreased percentage of lymphocytes (LYM) and neutrophils (NEU), elevated C-reactive protein (CRP) and lactate dehydrogenase (LDH), and decreased CD8 count. The viral load of 2019-nCoV detected from patient respiratory tracts was positively linked to lung disease severity. ALB, LYM, LYM (%), LDH, NEU (%), and CRP were highly correlated to the acute lung injury. Age, viral load, lung injury score, and blood biochemistry indexes, albumin (ALB), CRP, LDH, LYM (%), LYM, and NEU (%), may be predictors of disease severity. Moreover, the Angiotensin II level in the plasma sample from 2019-nCoV infected patients was markedly elevated and linearly associated to viral load and lung injury. Our results suggest a number of potential diagnosis biomarkers and angiotensin receptor blocker (ARB) drugs for potential repurposing treatment of COVID-19 infection. [8]
Increased levels of serum CRP, PCT, IL-6 were also found. Extreme rise in inflammatory cytokines including IL2, IL7, IL10, GCSF, IP10, MCP1, MIP1A, and TNFα. MEasured from 31 infected patients: Lymphopenia (lymphocyte count, 0.67 109/L [SD, 0.33]) occurred in 24 patients (70.59%), decreased albumin (30.18, [SD, 4.76]) in 25 patients (80.65%), elevated D-dimer (8.64 [IQR, 2.39-20]) in 27 patients (100%), and elevated lactate dehydrogenase (502.5 U/L [IQR, 410-629]) in 26 patients (100%). Nearly all of the patients have elevated CRP (106.3 mg/L [IQR, 60.83 225.3]), PCT (0.61 ng/ml [IQR, 0.16-2.10]) and IL-6 (100.6 pg/ml [IQR, 51.51-919.5]). [6]
From 81 infected patients the following values were measured (SD) [1]: Leukocyte count, × 10⁹/L <10 68% Lymphocyte count, × 10⁹/L ≥1.0 67% Platelet count, × 10⁹/L ≥100 100% Haemoglobin, ng/mL 123.9 (12.0) (SD) C-reactive protein, mg/L 47.6 (41.8) Serum amyloid A protein, mg/L 213.5 (177.8) Alanine aminotransferase, U/L 46.2 (29.5) Aspartate aminotransferase, U/L 40.8 (17.9) Total bilirubin, µmol/L 11.9 (3.6) Albumin, g/L 32.9 (8.1) Glucose, mmol/L 6.4 (2.1) Creatinine, µmol/L 75.4 (29.8) Prothrombin time, s 10.7 (0.9) Activated partial thromboplastin time, s 32.1 (7.6) Thrombin time, s 28.9 (8.4) Fibrinogen, g/L 1.5 (2.3) D-dimers, mg/L 6.5 (0.8)
Treatment:
Although corticosteroid treatment is not routinely recommended to be used for SARS-CoV-2 pneumonia,1 according to our pathological findings of pulmonary oedema and hyaline membrane formation, timely and appropriate use of corticosteroids together with ventilator support should be considered for the severe patients to prevent ARDS development. [2] Treatment is essentially supportive; role of antiviral agents is yet to be established. Prevention entails home isolation of suspected cases and those with mild illnesses and strict infection control measures at hospitals that include contact and droplet precautions. [5]
In the case ser5ies of 99 hospitalized patients with COVID-19 infection from Wuhan, oxygen was given to 76%, non-invasive ventilation in 13%, mechanical ventilation in 4%, extracorporeal membrane oxygenation (ECMO) in 3%, continuous renal replacement therapy (CRRT) in 9%, antibiotics in 71%, antifungals in 15%, glucocorticoids in 19% and intravenous immunoglobulin therapy in 27% [15]. Antiviral therapy consisting of oseltamivir, ganciclovir and lopinavir-ritonavir was given to 75% of the patients. The duration of non-invasive ventilation was 4–22 d [median 9 d] and mechanical ventilation for 3–20 d [median 17 d]. In the case series of children discussed earlier, all children recovered with basic treatment and did not need intensive care. [5]
There is anecdotal experience with use of remdeswir, a broad spectrum anti RNA drug developed for Ebola in management of COVID-19 [27]. More evidence is needed before these drugs are recommended. Other drugs proposed for therapy are arbidol (an antiviral drug available in Russia and China), intravenous immunoglobulin, interferons, chloroquine and plasma of patients recovered from COVID-19 [21, 28, 29]. Additionally, recommendations about using traditional Chinese herbs find place in the Chinese guidelines. [5]
The ICU mortality rate among those who required non-invasive ventilation was 23 (79%) of 29 and among those who required invasive mechanical ventilation was 19 (86%) of 22. [7] Jonathan Chun-Hei Cheung and colleagues do not recommend use of a high-flow nasal cannula or non-invasive ventilation until the patient has viral clearance. Supporting the recommendation of the authors, some points in relation to the use of high-flow nasal oxygen therapy and non-invasive ventilation in patients with COVID-19 infection: First, although exhaled air dispersion during high-flow nasal oxygen therapy and non-invasive ventilation via different interfaces is restricted, provided that there is a good mask interface fitting, not all hospitals around the world have access to such interfaces or enough personal-protective equipment of sufficiently high quality for aerosol-generating procedures, and several hospitals do not have a negative pressure isolation room. [7] Second, the fundamental pathophysiology of severe viral pneumonia is ARDS. Non-invasive ventilation is not recommended for patients with viral infections complicated by pneumonia because, although non-invasive ventilation temporarily improves oxygenation and reduces the work of breathing in these patients, this method does not necessarily change the natural disease course. Finally, the application of non-invasive ventilation in patients with COVID-19 in the ICU is controversial. Considering the above factors, clinicians might not use non-invasive ventilation for critically ill patients with ARDS due to COVID-19 until further data from the COVID-19 epidemic are available. [7]
The WHO interim guidelines made general recommendations for treatment of ARDS in this setting, including that consideration be given to referring patients with refractory hypoxemia to expert centers capable of providing extracorporeal membrane oxygenation (ECMO). [8] ECMO is a form of modified cardiopulmonary bypass in which venous blood is removed from the body and pumped through an artificial membrane lung in patients who have refractory respiratory or cardiac failure. Oxygen is added, carbon dioxide is removed, and blood is returned to the patient, either via another vein to provide respiratory support or a major artery to provide circulatory support. ECMO is a resource-intensive, highly specialized, and expensive form of life support with the potential for significant complications, in particular hemorrhage and nosocomial infection. Recent evidence suggests that use of ECMO in the most severe cases of ARDS is associated with reduced mortality.6 There is some evidence that outcomes from ECMO are better in higher-volume centers. [8]
Furthermore, with the apparent contagiousness of this virus and the relatively high numbers of patients who require intensive care, this may prove very resource-consumptive. Countries will need to pay specific attention to the considerable investment needed to provide ECMO during this outbreak. Judgment will be needed to decide when ECMO may be worthwhile and when it may not, understanding that the risk-to-benefit ratio of performing ECMO in these circumstances is dynamic and dependent on many factors. If the mechanism of death in COVID-19 ultimately includes a substantial number of patients with septic shock or refractory multiorgan failure, then the shift away from ECMO is likely to occur earlier because the most severely ill patients in this cohort would be less likely to benefit. The higher the all-cause mortality, the less relevant ECMO becomes. [8] Regardless, ECMO is clearly a finite resource. In a large outbreak, additional limitations to providing ECMO may include a lack of ECMO consoles or disposable equipment, suitably trained staff, or isolation rooms with the requisite infrastructure. Many materials necessary to make ECMO circuits are manufactured in China and it is conceivable that the outbreak may disrupt supply chains. [8]
Abbreviations:
CRP = C-Reactive Protein / Bloodtest PCT = Porphyria cutanea tarda / Bloodtest IL-6 = Interleukin IL2 = Interleukin IL7 = Interleukin IL10 = Interleukin GCSF = Granulocyte-colony stimulating factor / Bloodtest IP10 = Interferon-inducible protein 10 / Blood or Uraine MCP1 = Monocyte chemoattractant protein-1 / urine and serum MIP1A = Macrophage inflammatory protein 1a / Serum and urinary TNFα = Tumor necrosis factor alpha / Bloodtest ARDS = Acute respiratory distress syndrome CT = Computerized Tomography RT-PCR = real-time reverse transcriptase polymerase chain reaction CXR = X-ray WHO = World Health Organization SD = Standard Deviation IQR = Interquartile range CRP = C-reactive protein ESR = Erythrocyte sedimentation rate PCT = Procalcitonin ALT/AST = alanine aminotransferase / aspartate aminotransferase CPK = Creatine phosphokinase LDH =Lactic Dehydrogenase ECMO = Extracorporeal membrane oxygenation CRRT = Continuous renal replacement therapy () ICU = Intensive care unit
References
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