Clinical Course and Risk Factors of Disease Deterioration in Critically Ill Patients with COVID-19

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began in December 2019 and rapidly spread to other provinces in China as well as other countries. In this study, 262 patients diagnosed with moderate to severe SARS-CoV-2 pneumonia in Wuhan, China, were analyzed. Data were compared between survivors and nonsurvivors. Of all the 262 patients, 23 (8.8%) patients died and 239 (91.2%) were discharged. The median age was 63.5 years and 46.9% of patients were male. The main complaints were fever (83.6%), cough (63.4%), and fatigue (49.2%) in the surviving group, while there were more complaints of dyspnea (39.1%) and shortness of breath (56.5%) in the nonsurviving group. The main comorbidities were hypertension (35.5%), diabetes mellitus (16.4%), and coronary artery disease (9.9%). Morbidity is higher in elderly patients with more comorbidities. Patients were mainly treated with nasal cannula (93.9%), while the nonsurviving group received more invasive mechanical ventilation (39.1%). Arbidol (80.9%), ribavirin (36.6%), oseltamivir (38.9%), interferon (16.4%), and ganciclovir (14.5%) were used for the antiviral treatment. In the nonsurviving group, the number of white blood cells (WBC) was significantly increased and lymphocytes were decreased, and lymphopenia was more common. The levels of aspartate transaminase (AST), brain natriuretic peptide (BNP), creatine kinase isoenzyme MB (CK-MB), lactate dehydrogenase (LDH), and C-reactive protein (CRP) were also significantly increased in the nonsurviving group. The adjusted hazard ratios (HRs) for association of known variables for all-cause mortality due to the coronavirus disease 2019 were 2.467 (95% confidence interval [CI], 1.007–6.044; p = 0.048) for shortness of breath and 1.025 (95% CI, 1.001–1.049; p = 0.042) for AST. Elderly patients with more comorbidities and complaints of dyspnea and shortness of breath had increased risk of death. Patients with lymphopenia and high levels of WBC, AST, BNP, CK-MB, LDH, and CRP may be more likely to deteriorate.

Background

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia is a newly diagnosed disease that was first discovered in Wuhan, Hubei Province, and spread rapidly to other provinces in China and around the world, reaching a pandemic level. There are three coronaviruses, SARS-CoV, Middle East respiratory syndrome coronavirus, and SARS-CoV-2, that can replicate in the lower respiratory tract and cause severe pneumonia.¹

SARS-CoV-2 belongs to the beta-coronavirus genus. Its closest relative among human coronaviruses is SARS-CoV, with 79% genetic similarity.¹ The clinical condition caused by the novel coronavirus is referred to as the coronavirus disease 2019 (COVID-19).² The COVID-19 may be asymptomatic or it may cause a wide spectrum of symptoms, such as fever, cough, running nose, sore throat, shortness of breath, mild symptoms of upper respiratory tract infection, and life-threatening sepsis.³ Previous studies have described the general epidemiological findings, clinical presentation, and clinical outcomes.^2,4 However, risk factors of disease deterioration still need to be investigated.

In this study, 262 critically ill patients with COVID-19 who were admitted to Renmin Hospital of Wuhan University were investigated to clarify their epidemiological, blood test, clinical, and therapeutic features. The data from this study will be critical for the early identification of patients who are most likely to become critically ill or benefit from intensive care treatment.

Methods

This study was done in the Renmin Hospital of Wuhan University, which was a designated hospital to treat patients with COVID-19 from January 31 to March 6, 2020. All the patients were tested positive by the nucleic acid test and transferred from other hospitals. All enrolled individuals were moderate to severe patients who met at least one of the following criteria: (1) symptoms of respiratory distress with a respiratory rate ≥30 times/min; (2) blood oxygen saturation ≤93% in resting state; (3) oxygenation index ≤300 mmHg (1 mmHg = 0.133 kPa); (4) the imaging examination of lung showing that more than 50% of the lesions progressed within 24–48 h.

This study was conducted in accordance with the amended Declaration of Helsinki. The study was approved by the Research Ethics Commission of Qilu Hospital of Shandong University and Renmin Hospital of Wuhan University, and written informed consent was obtained.

Data collection

We reviewed clinical electronic medical records, nursing records, and laboratory findings for all patients with laboratory-confirmed COVID-19.

We collected data about age, sex, chronic medical histories (hypertension, coronary artery disease (CAD), percutaneous coronary intervention, diabetes mellitus (DM), stroke, chronic obstructive pulmonary disease (COPD), and acute kidney injury), symptoms from onset to hospital admission (fever, cough, chest stuffiness, tachycardia, shortness of breath, dyspnea, fatigue, gastrointestinal complications, and conscious disturbance), vital signs, laboratory values on admission (blood routine, hepatic and kidney function, blood lipids, albumin, creatine kinase isoenzyme MB [CK-MB], brain natriuretic peptide [BNP], electrolyte, etc.), and treatment (oxygen therapy, antiviral agents, antibacterial agents, glucocorticoid, immunoglobulin, etc.).

Outcomes

The outcomes were all-cause mortality during hospitalization and discharge, which were used as instruments to divide participants into two groups: the surviving group and the nonsurviving group. Acute kidney injury was identified on the basis of serum creatinine.⁵ Hypertension was diagnosis based on medical history with systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg.⁶

Statistical analysis

Data were analyzed in R-3.6.3 (Vienna, Austria) and SPSS 23.0 (Armonk, NY). Continuous variables were expressed as median and interquartile range, and categorical variables were expressed as number and percentage (%). Statistical differences between the two groups were analyzed using t-test, while categorical variables were compared using Fisher's exact test or χ2 test. A p < 0.05 was considered statistically significant. The risk of composite endpoints and corresponding hazard ratio (HR) were calculated using the Cox proportional hazard model. Multivariable adjusted including age, gender, comorbidities, medications, and blood test was performed.

Results

Clinical characteristics on admission

All patients were residents of Wuhan city and transferred from other hospitals once diagnosed with COVID-19. Two hundred sixty-two patients had a mean age of 63.5 years, with a mortality of 8.8%. The mean age in the surviving group and nonsurviving group was 63 and 69 years, respectively. One hundred twenty-three (46.9%) patients were men, with 113 (47.3%) patients in the surviving group and 10 (43.5%) patients in the nonsurviving group, and there is no significant difference in mortality in gender.

One hundred eighty-four (70.2%) patients had comorbidities, and the most underlying chronic diseases were hypertension (35.5%), DM (16.4%), and CAD (9.9%). Compared with the surviving group, the nonsurviving group had more comorbidities. Most of the complaints of the patients were fever (83.6%), cough (63.4%), and fatigue (49.2%), while the nonsurviving group had more complaints of dyspnea (39.1%) and shortness of breath (56.5%) (Table 1).

Table 1.

Demographic and clinical findings of patients with COVID-19

	All Patients (n = 262)	Survivors (n = 239)	Nonsurvivors (n = 23)	p-Value
Age	63.5 (53–70)	63 (52–69)	69 (65–74)	0.002^*
Sex
Male	123 (46.9%)	113 (47.3%)	10 (43.5%)	0.727
Female	139 (53.1%)	126 (52.7%)	13 (56.5%)
Symptoms
Fever	219 (83.6%)	198 (82.8%)	21 (91.3%)	0.296
Cough	166 (63.4%)	148 (61.9%)	17 (73.9%)	0.255
Chest stuffiness	69 (26.3%)	60 (25.1%)	9 (39.1%)	0.145
Tachycardia	6 (2.3%)	5 (2.1%)	1 (4.3%)	0.490
Shortness of breath	68 (26%)	55 (23%)	13 (56.5%)	<0.001^*
Dyspnea	42 (16%)	34 (14.2%)	9 (39.1%)	0.002^*
Fatigue	129 (49.2%)	116 (48.5%)	13 (56.5%)	0.464
Gastrointestinal	39 (14.9%)	37 (15.5%)	2 (8.7%)	0.383
Conscious disturbance	1 (0.4%)	1 (0.4%)	0 (0%)	0.756
Comorbidities	184 (70.2%)	161 (67.4%)	23 (100%)
Hypertension	93 (35.5%)	81 (33.9%)	12 (52.2%)	0.080
CAD	26 (9.9%)	22 (9.2%)	4 (17.4%)	0.210
PCI history	8 (3.1%)	8 (3.3%)	0 (0%)	0.373
DM	43 (16.4%)	39 (15.1%)	4 (17.4%)	0.894
Stroke	7 (2.7%)	5 (2.1%)	2 (8.7%)	0.061
COPD	4 (1.5%)	4 (1.7%)	0 (0%)	0.532
AKI	3 (1.1%)	2 (0.8%)	1 (4.3%)	0.131

Data were expressed as n (%) or median (IQR).

p ＜ 0.05.

AKI, acute kidney disease; CAD, coronary artery disease; COPD, chronic obstructive pulmonary disease; DM, diabetic mellitus; IQR, interquartile range; PCI, percutaneous coronary intervention.

Laboratory findings on admission

The most common laboratory abnormalities were white blood cells (WBC), neutrophils (NEU), lymphocytes (LYM), aspartate transaminase (AST), lactate dehydrogenase (LDH), BNP, CK-MB, C-reactive protein (CRP), CD3, CD4, and CD8 T cells. Compared with the surviving group, the WBC and NEU were significantly increased in the nonsurviving group. However, in the nonsurviving group, the LYM and T cells were decreased, with a significantly decrease in CD3, CD4, and CD8, which indicated a cellular immunosuppression status. Moreover, there is also a significant difference in the AST, glucose, albumin, BNP, CRP, and CK-MB (Table 2).

Table 2.

Laboratory findings of patients with COVID-19

	Survivors (n = 239)	Nonsurvivors (n = 23)	p-Value
Biochemical
Total bilirubin (μM)	10.1 (7.5–14.0)	11.6 (10.2–18.7)	0.095
ALT (U/L)	23.0 (15.0–36.0)	24.5 (17.3–41.5)	0.378
AST (U/L)	24.0 (18.0–34.0)	33.0 (25.3–55.3)	<0.001^*
Creatinine (μM)	59.0 (49.0–74.0)	67.0 (49.0–77.3)	0.341
Glucose (mM)	5.44 (4.91–6.95)	6.1 (5.6–7.7)	0.017^*
TC (mM)	3.9 (3.4–4.6)	3.9 (3.1–4.1)	0.078
TG (mM)	1.2 (0.9–1.7)	1.4 (1.0–1.7)	0.255
HDL (mM)	0.9 (0.8–1.1)	0.8 (0.7–0.9)	0.013^*
LDL (mM)	2.4 (1.9–2.9)	2.4 (2.0–2.6)	0.232
Lpa (mg/L)	130 (78–213)	106.0 (67.3–214.8)	0.244
LDH (U/L)	241 (193–301)	454.0 (374.2–547)	<0.001^*
BNP (pg/mL)	69.94 (35.5–172.8)	539.6 (162.7–794.5)	<0.001^*
CK-MB (ng/mL)	0.92 (0.64–1.23)	2.3 (0.9–2.7)	<0.001^*
Potassium (mM)	4.0 (3.6–4.3)	4.0 (3.5–4.2)	0.608
Sodium (mM)	142.0 (139.0–144.0)	141.0 (138.2–145.5)	0.678
Albumin (g/L)	37.6 (34.6–40.3)	32.9 (30.9–35.8)	<0.001^*
C3 (g/L)	1.01 (0.87–1.15)	0.95 (0.86–1.08)	0.404
C4 (g/L)	0.24 (0.20–0.31)	0.27 (0.20–0.34)	0.954
CRP (mg/L)	38.6 (18.8–68.1)	92.4 (59.4–149.6)	<0.001^*
Hematologic
WBC (10⁹/L)	5.2 (4.1–6.7)	8.4 (6.0–12.7)	<0.001^*
Neutrophils (10⁹/L)	3.3 (2.4–4.7)	7.4 (5.1–11.7)	<0.001^*
Lymphocytes (10⁹/L)	1.22 (0.88–1.56)	0.76 (0.42–0.87)	<0.001^*
Monocytes (10⁹/L)	0.44 (0.33–0.59)	0.33 (0.27–0.63)	0.051
Hemoglobin (g/L)	122.0 (113.0–133.0)	120.5 (106.2–140.8)	0.549
Platelets (10⁹/L)	229.0 (175.0–298.0)	194.0 (158.8–232.0)	0.123
CD3 (/μL)	765 (505–1,041)	297 (142–411)	<0.001^*
CD4 (/μL)	452 (309–658)	178 (106–262)	<0.001^*
CD8 (/μL)	255 (159–371)	90 (42–156)	<0.001^*

Data were expressed as median (IQR).

p ＜ 0.05.

ALT, alanine aminotransferase; AST, aspartate transaminase; BNP, brain natriuretic peptide; CK-MB, creatine kinase isoenzyme MB; CRP, C-reactive protein; HDL, high-density lipoprotein; LDH, lactate dehydrogenase; LDL, low-density lipoprotein; Lpa, lipoprotein a; TC, total cholesterol; TG, triglyceride; WBC, white blood cells.

Supportive treatment and drugs

All patients were mainly treated with nasal cannula, while the nonsurviving group received more invasive mechanical ventilation. Arbidol (80.9%), oseltamivir (38.9%), ribavirin (36.6%), ganciclovir (14.6%), and interferon (16.4%) were used for the antivirus treatment. Moxifloxacin (69.5%) and cephalosporin (31.3%) were mainly used for antibacteria, and carbapenems (1.9%) were seldom used. None of the patients received antifungal agents. A Chinese medicine, Xuebijing Zhusheye, was also given. Moreover, 93 (35.5%) patients received glucocorticoids, and 112 (42.7%) received immunoglobulin (Table 3).

Table 3.

Interventions of patients with COVID-19

	All Patients (n = 262)	Survivors (n = 239)	Nonsurvivors (n = 23)	p-Value
Oxygen support				<0.001^*
Nasal cannula	246 (93.9%)	235 (98.3%)	11 (47.8%)
Mechanical ventilation
Noninvasive	5 (1.9%)	2 (0.8%)	3 (13.1%)
Invasive	11 (4.2%)	2 (0.8%)	9 (39.1%)
Treatment
Arbidol	212 (80.9%)	200 (83.7%)	12 (52.2%)	<0.001^*
Glucocorticoid	93 (35.5%)	80 (33.5%)	13 (56.5%)	0.027
Ribavirin	96 (36.6%)	84 (35.1%)	12 (52.2%)	0.106
Ganciclovir	38 (14.5%)	34 (14.2%)	4 (17.4%)	0.681
Immunoglobulin	112 (42.7%)	97 (40.6%)	15 (65.2%)	0.023^*
Albumin	17 (6.5%)	12 (5.0%)	5 (21.7%)	0.002^*
Cephalosporin	82 (31.3%)	68 (28.5%)	14 (60.9%)	0.001^*
Moxifloxacin	182 (69.5%)	164 (68.6%)	18 (78.3%)	0.338
Xuebijing zhusheye	59 (22.5%)	52 (21.8%)	7 (30.4%)	0.341
Interferon	43 (16.4%)	37 (15.5%)	6 (26.1%)	0.190
Oseltamivir	102 (38.9%)	91 (38.1%)	11 (47.8%)	0.360
Diuretic	13 (5.0%)	8 (3.3%)	5 (21.7%)	<0.001^*
CCB	60 (22.9%)	54 (22.6%)	6 (26.1%)	0.703
Vitamin C	74 (28.2%)	60 (25.1%)	14 (60.9%)	0.000^*
Carbapenems	5 (1.9%)	3 (1.3%)	2 (8.7%)	0.013^*
Antifungus	0	0	0	1

Data were expressed as n (%).

p ＜ 0.05.

CCB, calcium channel blockers.

Primary outcomes

In the mixed-effect Cox model using site as a random effect, after adjusting for age, gender, comorbidities, in-hospital medications, and blood test, the adjusted HRs for association of known variables for all-cause mortality due to COVID-19 were 2.467 (95% confidence interval [CI], 1.007–6.044; p = 0.048) for shortness of breath, 1.025 (95% CI, 1.001–1.049; p = 0.042) for AST, 0.301 (95% CI, 0.106–0.855; p = 0.024) for LDH (250–445), 0.037 (95% CI, 0.004–0.363; p = 0.005) for LDH (<250), and 0.258 (95% CI, 0.073–0.904; p = 0.034) for WBC (4 × 10^9–10 × 10⁹) (Table 4).

Table 4.

Hazard ratios for outcomes under mixed-effect Cox model

Parameters	Unadjusted HR (95% CI)	p	Adjusted HR (95% CI)	p
Age ≥60	2.652 (0.995–7.066)	0.051	2.371 (0.698–8.057)	0.167
Shortness of breath	3.722 (1.690–8.201)	0.001	2.467 (1.007–6.044)	0.048^*
Dyspnea	3.162 (1.397–7.158)	0.006	1.976 (0.752–5.191)	0.167
Hypertension	2.341 (1.062–5.156)	0.035	1.517 (0.518–4.441)	0.447
AST	1.037 (1.020–1.054)	<0.001	1.025 (1.001–1.049)	0.042^*
CK-MB	1.457 (1.248–1.702)	<0.001	0.973 (0.740–1.280)	0.844
LDH (reference >445)
250–445	0.118 (0.051–0.270)	<0.001	0.301 (0.106–0.855)	0.024^*
<250	0.009 (0.001–0.072)	<0.001	0.037 (0.004–0.363)	0.005^*
WBC (reference >10 × 10⁹)
4 × 109–10 × 10⁹	0.097 (0.042–0.288)	<0.001	0.258 (0.073–0.904)	0.034^*
<4 × 10⁹	0.075 (0.020–0.276)	<0.001	0.403 (0.078–2.075)	0.277

p＜0.05.

CI, confidence interval; HR, hazard ratio.

Discussion

COVID-19 is an unprecedented global threat caused by SARS-CoV-2. It began in the city of Wuhan, in Hubei Province, in December 2019 and spread throughout the world rapidly.⁷ COVID-19 can be transmitted through respiratory droplets, physical contact, and aerosols, and there is also evidence of human-to-human transmission,⁸ which may explain the sudden epidemic spreading of the virus.

In our single-center, retrospective, observational study, 262 critically ill patients with confirmed SARS-CoV-2 infection had a mortality of 8.8%, which is much higher than the mortality in other researches.^4,9 There was no difference in mortality in gender. The mean age was 63.5 years, and the mean age in the nonsurviving group was older than that in the surviving group. One hundred eighty-four (70.2%) patients had comorbidities, and the most common comorbidities were hypertension, DM, and CAD.

Previous researches have been demonstrated that there is a higher chance for patients older than 65 to progress into the severe phase.⁹ Individuals with DM, hypertension, and severe obesity are more likely to be infected and are at a higher risk for complications and death from COVID-19.^10
–12 Older people and people with comorbidities are apt to develop a dysfunctional immune response and fail to eradicate the pathogen. The exact reasons are still obscure. One underlying mechanism may be that an abnormal lung microenvironment causes dysfunctional dendritic cell maturation and migration to the lymphoid organs,¹³ and results in defective T cell activation.

In terms of clinical manifestations in our study, the common symptoms of these patients at the onset of COVID-19 were fever (83.6%), cough (63.4%), and fatigue (49.2%), while the nonsurviving group has more symptoms of dyspnea and shortness of breath, which suggested severe damage to the lung.

Since no special medication has been identified to treat COVID-19 at this time, the main treatment has been critical care treatment.¹⁴ It has been demonstrated that more than 75% of hospitalized patients with COVID-19 require supplemental oxygen therapy.³ High flow nasal cannula (HFNC) can be administered to patients who are unresponsive to conventional oxygen therapy.¹⁵ In our research, 246 (93.9%) patients were treated with nasal cannula. Compared with the surviving group, the nonsurviving group received more invasive mechanical ventilation, which suggested the severity of disease.

For patients receiving invasive mechanical ventilation, lung-protective ventilation is recommended, such as low tidal volumes, and plateau pressure <30 mm Hg.¹⁵ Moreover, a higher positive end-expiratory pressure, prone positioning, and short-term neuromuscular blockade (48 h) should also be considered. Finally, extracorporeal membrane oxygenation may be an optimal therapy for severe COVID-19.¹⁶

Previous studies have shown that ∼8% of hospitalized patients with COVID-19 have a coinfection of bacteria or fungus, but nearly 72% are treated with broad-spectrum antibiotics.¹⁷ However, in our research, most patients were mainly treated with cephalosporin or moxifloxacin, and carbapenems (1.9%) were seldom used. No patients were treated with antifungal agents in our study.

During the COVID-19 outbreak, some potential antiviral drugs were urgently used for COVID-19 patients, such as remdesivir, lopinavir and ritonavir, and arbidol. In the absence of prior evidence, most patients were also treated with various antiviral agents in our study. At present, several randomized-controlled clinical trials have been performed to verify their safety and efficacy as COVID-19 treatments.

Remdesivir, an adenine analogue, has been used for the treatment of Ebola virus and confirmed in a phase III clinical trial.¹⁸ Remdesivir showed antiviral activity of SARS-CoV-2 in vitro.¹⁹ In a study of hospitalized patients with severe COVID-19, remdesivir showed no statistically significant clinical benefits. However, patients receiving remdesivir had a faster time to clinical improvement.²⁰ In patients with severe COVID-19 without mechanical ventilation, there was no significant difference between a 5-day course and a 10-day course of remdesivir.²¹ Another clinical trial showed that remdesivir was superior to placebo in shortening the time to recovery in patients with COVID-19.²² The therapeutic efficacy and safety of these antiviral agents still need to be confirmed by more clinical researches.

The pathophysiology of COVID-19 is closely similar to that of SARS-CoV infection, with impaired inflammatory responses leading to damage to the airways and other organs.²³ Therefore, the severity of disease is closely associated with not only viral infection but also the impaired host response,²⁴ which suggested the possible effect of anti-inflammatory medications, such as glucocorticoids, chloroquine/hydroxychloroquine, and inflammatory cytokine antagonists. In our study, 93 (35.5%) patients were treated with glucocorticoids (methylprednisolone, 40–80 mg per day for 5–7 days), and the percentage (56.5%) in the nonsurviving group is much more than that in the surviving group (33.5%). Although glucocorticoids were widely used in patients with severe SARS or MERS, their use and efficacy remain unclear in the treatment of SARS-CoV-2 infection.^4,25 The data being retrospective do not exclude the possibility that the patients who received corticosteroids may have been on a more adverse trajectory before the decision to use them.

In a randomized clinical trial, for COVID-19 patients who were receiving either invasive mechanical ventilation or oxygen alone at randomization, the use of dexamethasone 6 mg daily for up to 10 days reduced the 28-day all-cause mortality.²⁶ In a retrospective cohort study of 201 COVID-19 patients with acute respiratory distress syndrome, methylprednisolone treatment reduced the risk of death.²⁷ However, some research showed no benefit from corticosteroid treatment for COVID-19 lung injury.²⁵ In a single-center study of 138 hospitalized patients with COVID-19, no effective outcomes were observed by glucocorticoid therapy in 44.9% of patients.⁴ Chloroquine/hydroxychloroquine is another candidate that can inhibit viral entry and endocytosis of SARS-CoV-2 in vitro and may be effective in vivo.^19,28

More than 200 clinical trials have been initiated, but early data have not demonstrated clear benefit.^29
–31 Therefore, the timing, efficacy, and adverse effects of anti-inflammatory medications in COVID-19 need to be further elucidated.

In our study of laboratory tests, the number of WBC was significantly increased and LYM were decreased. Moreover, lymphopenia (absolute lymphocyte count <1.0 × 10⁹/L) was more common in the nonsurviving group, which is accordance with other researches that lymphopenia is present in up to 83% of hospitalized patients with COVID-19.^1,32 Moreover, lymphocytopenia is associated with the severity of SARS-CoV-2 infection.^27,33 There are some underlying mechanisms of lymphopenia. First, SARS-CoV-2 infection may kill T lymphocyte cells. Second, the innate and the adaptive immune response to viral infection impairs lymphopoiesis and increases lymphocyte apoptosis.³ Moreover, the levels of AST, BNP, CK-MB, LDH, and CRP were also significantly increased in the nonsurviving group, which should be paid more attention to by clinicians.

This study has some limitations. First, only 262 COVID-19 patients were included. Second, some data were missing, such as blood gas test and sputum culture. Third, this is a single-center, retrospective study. Further studies are still needed.

Conclusion

In conclusion, the mortality of critically ill patients with SARS-CoV-2 pneumonia was high in our study. Elderly patients with more comorbidities and complaints of dyspnea and shortness of breath are at increased risk of death. Patients with lymphopenia and high levels of WBC, AST, BNP, CK-MB, LDH, and CRP were more likely to deteriorate. These data suggest some clinical criteria for COVID-19 patients who might be considered candidates for more aggressive gene or cell therapies.

Footnotes

Authors' Contributions

M.Z. and K.Z. participated in the study design and study conception. W.B. and K.L. performed data analysis. X.M. and W.B. recruited patients and collected data. Y.L. checked the data. W.Q. drafted the article. All authors provided critical review of the article and approved the final draft for publication.

Ethical Approval and Consent to Participate

The Research Ethics Commission of Qilu Hospital of Shandong University and Renmin Hospital of Wuhan University approved the protocol, and written informed consent was obtained.

Availability of Data and Material

The data sets used and/or analyzed during the current study are available from the corresponding author under reasonable request.

Acknowledgments

We thank Xiaofang Huang from Zhejiang University for the help in data analysis.

Author Disclosure

No competing financial interests exist.

Funding Information

This work was supported by a project funded by the China Postdoctoral Science Foundation (2018M630788) and the Shandong Provincial Natural Science Foundation (nos. ZR201807061161 and ZR2019PH007). The funding had no involvement in the study design, collection, analysis, and interpretation of data, writing of the report, and the decision to submit the article for publication.

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