Public screening for COVID-19 in Wuhan, China and beware of the antibody positive in women and tumor patients.

The novel coronavirus disease 2019 (COVID-19) has become a global health emergency. Early detection and intervention are key factors for improving outcomes in patients with COVID-19. Real-time reverse transcriptase polymerase chain reaction-based molecular assays and antibody for detecting SARS-CoV-2 in respiratory specimens are the current reference standard for COVID-19 diagnosis. Clinical implications of different specimen types for nucleic acid and antibody testing of COVID-19 in Zhongnan hospital of Wuhan University were analyzed. Compared with health groups, tumor patients had higher rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (+/-) immunoglobulin M (IgM) (+) immunoglobulin G (IgG) (+). The rate of SARS-CoV-2 (-) IgM (+) IgG (-) or SARS-CoV-2 (-) IgM (-) IgG (+) in female was significantly higher than that in male. These results can help governments to take screening measures to prevent the COVID-19 pandemic again.

Development and Validation of Predictors for the Survival of Patients With COVID-19 Based on Machine Learning.

Background: The outbreak of COVID-19 attracted the attention of the whole world. Our study aimed to explore the predictors for the survival of patients with COVID-19 by machine learning. Methods: We conducted a retrospective analysis and used the idea of machine learning to train the data of COVID-19 patients in Leishenshan Hospital through the logical regression algorithm provided by scikit-learn. Results: Of 2010 patients, 42 deaths were recorded until March 29, 2020. The mortality rate was 2.09%. There were 6,812 records after data features combination and data arrangement, 3,025 records with high-quality after deleting incomplete data by manual checking, and 5,738 records after data balancing finally by the method of Borderline-1 Smote. The results of 10 times of data training by logistic regression model showed that albumin, saturation of pulse oxygen at admission, alanine aminotransferase, and percentage of neutrophils were possibly associated with the survival of patients. The results of 10 times of data training including age, sex, and height beyond the laboratory measurements showed that percentage of neutrophils, saturation of pulse oxygen at admission, alanine aminotransferase, sex, and albumin were possibly associated with the survival of patients. The rates of precision, recall, and f1-score of the two training models were all higher than 0.9 and relatively stable. Conclusions: We demonstrated that percentage of neutrophils, saturation of pulse oxygen at admission, alanine aminotransferase, sex, and albumin were possibly associated with the survival of patients with COVID-19.

Characteristics of immune and inflammatory responses among different age groups of pediatric patients with COVID-19 in China.

BACKGROUND: Severe cases of coronavirus disease 2019 (COVID-19) among pediatric patients are more common in children less than 1 year of age. Our aim is to address the underlying role of immunity and inflammation conditions among different age groups of pediatric patients. METHODS: We recruited pediatric patients confirmed of moderate COVID-19 symptoms, admitted to Wuhan Children's Hospital from January 28th to April 1st in 2020. Patients were divided into four age groups (≤ 1, 1-6, 7-10, and 11-15 years). Demographic information, clinical characteristics, laboratory results of lymphocyte subsets test, immune and inflammation related markers were all evaluated. RESULTS: Analysis included 217/241 (90.0%) of patients with moderate clinical stage disease. Average recovery time of children more than 6 years old was significantly shorter than of children younger than 6 years (P = 0.001). Reduced neutrophils and increased lymphocytes were significantly most observed among patients under 1 year old (P < 0.01). CD19+ B cells were the only significantly elevated immune cells, especially among patients under 1 year old (cell proportion: n = 12, 30.0%, P < 0.001; cell count: n = 13, 32.5%, P < 0.001). While, low levels of immune related makers, such as immunoglobulin (Ig) G (P < 0.001), IgA (P < 0.001), IgM (P < 0.001) and serum complement C3c (P < 0.001), were also mostly found among patients under 1 year old, together with elevated levels of inflammation related markers, such as tumor necrosis factor γ (P = 0.007), interleukin (IL)-10 (P = 0.011), IL-6 (P = 0.008), lactate dehydrogenase (P < 0.001), and procalcitonin (P = 0.007). CONCLUSION: The higher rate of severe cases and long course of COVID-19 among children under 1 year old may be due to the lower production of antibodies and serum complements of in this age group.

CT Quantification of COVID-19 Pneumonia at Admission Can Predict Progression to Critical Illness: A Retrospective Multicenter Cohort Study.

Objective: Early identification of coronavirus disease 2019 (COVID-19) patients with worse outcomes may benefit clinical management of patients. We aimed to quantify pneumonia findings on CT at admission to predict progression to critical illness in COVID-19 patients. Methods: This retrospective study included laboratory-confirmed adult patients with COVID-19. All patients underwent a thin-section chest computed tomography (CT) scans showing evidence of pneumonia. CT images with severe moving artifacts were excluded from analysis. Patients' clinical and laboratory data were collected from medical records. Three quantitative CT features of pneumonia lesions were automatically calculated using a care.ai Intelligent Multi-disciplinary Imaging Diagnosis Platform Intelligent Evaluation System of Chest CT for COVID-19, denoting the percentage of pneumonia volume (PPV), ground-glass opacity volume (PGV), and consolidation volume (PCV). According to Chinese COVID-19 guidelines (trial version 7), patients were divided into noncritical and critical groups. Critical illness was defined as a composite of admission to the intensive care unit, respiratory failure requiring mechanical ventilation, shock, or death. The performance of PPV, PGV, and PCV in discrimination of critical illness was assessed. The correlations between PPV and laboratory variables were assessed by Pearson correlation analysis. Results: A total of 140 patients were included, with mean age of 58.6 years, and 85 (60.7%) were male. Thirty-two (22.9%) patients were critical. Using a cutoff value of 22.6%, the PPV had the highest performance in predicting critical illness, with an area under the curve of 0.868, sensitivity of 81.3%, and specificity of 80.6%. The PPV had moderately positive correlation with neutrophil (%) (r = 0.535, p < 0.001), erythrocyte sedimentation rate (r = 0.567, p < 0.001), d-Dimer (r = 0.444, p < 0.001), high-sensitivity C-reactive protein (r = 0.495, p < 0.001), aspartate aminotransferase (r = 0.410, p < 0.001), lactate dehydrogenase (r = 0.644, p < 0.001), and urea nitrogen (r = 0.439, p < 0.001), whereas the PPV had moderately negative correlation with lymphocyte (%) (r = -0.535, p < 0.001). Conclusions: Pneumonia volume quantified on initial CT can non-invasively predict the progression to critical illness in advance, which serve as a prognostic marker of COVID-19.

Personnel protection strategy for healthcare workers in Wuhan during the COVID-19 epidemic.

Objective: To identify the effectiveness of a personnel protection strategy in protection of healthcare workers from SARS-CoV-2 infection. Design: During the COVID-19 pandemic, 943 healthcare staff sent from Guangzhou to Wuhan to care for patients with suspected/confirmed COVID-19 received infection precaution training before their mission and were equipped with Level 2/3 personal protective equipment (PPE), in accordance with guidelines from the National Health Commission of China. We conducted a serological survey on the cumulative attack rate of SARS-CoV-2 among the healthcare workers sent to Wuhan and compared the seropositive rate to that in local healthcare workers from Wuhan and Jingzhou. Results: Serial tests for SARS-CoV-2 RNA and tests for SARS-CoV-2 immunoglobulin M and G after the 6-8 week mission revealed a zero cumulative attack rate. Among the local healthcare workers in Wuhan and Jingzhou of Hubei Province, 2.5% (113 out of 4495) and 0.32% (10 out of 3091) had RT-PCR confirmed COVID-19, respectively. The seropositivity for SARS-CoV-2 antibodies (IgG, IgM, or both IgG/IgM positive) was 3.4% (53 out of 1571) in local healthcare workers from Wuhan with Level 2/3 PPE working in isolation areas and 5.4% (126 out of 2336) in healthcare staff with Level 1 PPE working in non-isolation medical areas, respectively. Conclusions and relevance: Our study confirmed that adequate training/PPE can protect medical personnel against SARS-CoV-2.

Relationship Between Serum Severe Acute Respiratory Syndrome Coronavirus 2 Nucleic Acid and Organ Damage in Coronavirus 2019 Patients: A Cohort Study.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide and has the ability to damage multiple organs. However, information on serum SARS-CoV-2 nucleic acid (RNAemia) in patients affected by coronavirus disease 2019 (COVID-19) is limited. METHODS: Patients who were admitted to Zhongnan Hospital of Wuhan University with laboratory-confirmed COVID-19 were tested for SARS-COV-2 RNA in serum from 28 January 2020 to 9 February 2020. Demographic data, laboratory and radiological findings, comorbidities, and outcomes data were collected and analyzed. RESULTS: Eighty-five patients were included in the analysis. The viral load of throat swabs was significantly higher than of serum samples. The highest detection of SARS-CoV-2 RNA in serum samples was between 11 and 15 days after symptom onset. Analysis to compare patients with and without RNAemia provided evidence that computed tomography and some laboratory biomarkers (total protein, blood urea nitrogen, lactate dehydrogenase, hypersensitive troponin I, and D-dimer) were abnormal and that the extent of these abnormalities was generally higher in patients with RNAemia than in patients without RNAemia. Organ damage (respiratory failure, cardiac damage, renal damage, and coagulopathy) was more common in patients with RNAemia than in patients without RNAemia. Patients with vs without RNAemia had shorter durations from serum testing SARS-CoV-2 RNA. The mortality rate was higher among patients with vs without RNAemia. CONCLUSIONS: In this study, we provide evidence to support that SARS-CoV-2 may have an important role in multiple organ damage. Our evidence suggests that RNAemia has a significant association with higher risk of in-hospital mortality.

Impact of Treatment Regimens on Antibody Response to the SARS-CoV-2 Coronavirus.

The coronavirus disease 2019 (COVID-19) is widely spread and remains a global pandemic. Limited evidence on the systematic evaluation of the impact of treatment regimens on antibody responses exists. Our study aimed to analyze the role of antibody response on prognosis and determine factors influencing the IgG antibodies' seroconversion. A total of 1,111 patients with mild to moderate COVID-19 symptoms admitted to Leishenshan Hospital in Wuhan were retrospectively analyzed. A serologic SARS-CoV-2 IgM/IgG antibody test was performed on all the patients 21 days after the onset of symptoms. Patient clinical characteristics were compared. In the study, 42 patients progressed to critical illness, with 6 mortalities reported while 1,069 patients reported mild to moderate disease. Advanced age (P = 0.028), gasping (P < 0.001), dyspnea (P = 0.024), and IgG negativity (P = 0.006) were associated with progression to critical illness. The mortality rate in critically ill patients with IgG antibody was 6.45% (95% CI 1.12-22.84%) and 36.36% (95% CI 12.36-68.38%) in patients with no IgG antibody (P = 0.003). Symptomatic patients were more likely to develop IgG antibody responses than asymptomatic patients. Using univariable analysis, fever (P < 0.001), gasping (P = 0.048), cancer (P < 0.001), cephalosporin (P = 0.015), and chloroquine/hydroxychloroquine (P = 0.021) were associated with IgG response. In the multivariable analysis, fever, cancer, cephalosporins, and chloroquine/hydroxychloroquine correlated independently with IgG response. We determined that the absence of SARS-CoV-2 antibody IgG in the convalescent stage had a specific predictive role in critical illness progression. Importantly, risk factors affecting seropositivity were identified, and the effect of antimalarial drugs on antibody response was determined.

Novel biomarkers for the prediction of COVID-19 progression a retrospective, multi-center cohort study.

A pandemic designated as Coronavirus Disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is spreading worldwide. Up to date, there is no efficient biomarker for the timely prediction of the disease progression in patients. To analyze the inflammatory profiles of COVID-19 patients and demonstrate their implications for the illness progression of COVID-19. Retrospective analysis of 3,265 confirmed COVID-19 cases hospitalized between 10 January 2020, and 26 March 2020 in three medical centers in Wuhan, China. Patients were diagnosed as COVID-19 and hospitalized in Leishenshan Hospital, Zhongnan Hospital of Wuhan University and The Seventh Hospital of Wuhan, China. Univariable and multivariable logistic regression models were used to determine the possible risk factors for disease progression. Moreover, cutoff values, the sensitivity and specificity of inflammatory parameters for disease progression were determined by MedCalc Version 19.2.0. Age (95%CI, 1.017 to 1.048; P < 0.001), serum amyloid A protein (SAA) (95%CI, 1.216 to 1.396; P < 0.001) and erythrocyte sedimentation rate (ESR) (95%CI, 1.006 to 1.045; P < 0.001) were likely the risk factors for the disease progression. The Area under the curve (AUC) of SAA for the progression of COVID-19 was 0.923, with the best predictive cutoff value of SAA of 12.4 mg/L, with a sensitivity of 83.9% and a specificity of 97.67%. SAA-containing parameters are novel promising ones for predicting disease progression in COVID-19.

Tracing asymptomatic SARS-CoV-2 carriers among 3674 hospital staff:a cross-sectional survey.

BACKGROUND: Asymptomatic carriers were positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) without developing symptoms, which might be a potential source of infection outbreak. Here, we aim to clarify the epidemiologic and influencing factors of asymptomatic carriers in the general population. METHODS: In our hospital, all hospital staff have received throat swab RT-PCR test, plasma COVID-19 IgM/IgG antibodies test and chest CT examination. We analyzed the correlation between infection rates and gender, age, job position, work place and COVID-19 knowledge training of the staff. After that, all asymptomatic staff were re-examined weekly for 3 weeks. FINDINGS: A total of 3764 hospital staff were included in this single-center cross-sectional study. Among them, 126 hospital staff had abnormal findings, and the proportion of asymptomatic infection accounted for 0.76% (28/3674). There were 26 staff with IgM+, 73 with IgG+, and 40 with ground glass shadow of chest CT. Of all staff with abnormal findings, the older they are, the more likely they are to be the staff with abnormal results, regardless of their gender. Of 3674 hospital staff, the positive rate of labor staff is obviously higher than that of health care workers (HCWs) and administrative staff (P<0.05). In the course of participating in the treatment of COVID-19, there was no statistically significant difference in positive rates between high-risk departments and low-risk departments (P>0.05). The positive rate of HCWs who participated in the COVID-19 knowledge training was lower than those did not participate in early training (P <0.01). Importantly, it was found that there was no statistical difference between the titers of IgM antibody of asymptomatic infections and confirmed patients with COVID-19 in recovery period (P>0.05). During 3 weeks follow-up, all asymptomatic patients did not present the development of clinical symptoms or radiographic abnormalities after active intervention in isolation point. INTERPRETATION: To ensure the safety of resumption of work, institutions should conduct COVID-19 prevention training for staff and screening for asymptomatic patients, and take quarantine measures as soon as possible in areas with high density of population. FUNDING: The Key Project for Anti-2019 novel Coronavirus Pneumonia from the Ministry of Science and Technology, China; Wuhan Emergency Technology Project of COVID-19 epidemic, China.

Prominent Hypercoagulability Associated With Inflammatory State Among Cancer Patients With SARS-CoV-2 Infection.

Abnormal coagulation parameters and potential benefits of anticoagulant therapy in general population with novel coronavirus pneumonia (COVID-19) have been reported. However, limited data are available on cancer patients. Coagulation indexes and inflammation parameters in 57 cancer patients with SARS-CoV-2 infection with different severity were retrospectively analyzed. We found that D-dimer levels were increased in 33 patients (57.9%, median: 790 ng/mL). Compared with ordinary type patients, severe and critical ill patients had decreased MPV values (P = 0.006), prolonged PT (median: 13.3 vs. 11.5 vs. 11.4 s, P < 0.001), significant higher D-dimer levels (median: 2,400 vs. 940 vs. 280 ng/mL, P < 0.001), higher PCT levels (median: 0.17 vs. 0.055 vs. 0.045 ng/mL, P = 0.002), higher IL-6 (median: 20.6 vs. 2.3 vs. 3.0 pg/mL, P = 0.040), and decreased PaO2 (median: 68 vs. 84 vs. 96 mm Hg, P < 0.001). Importantly, three patients, one severe and two critical ill type, with increased D-dimer survived after anticoagulant therapy with continuous heparin infusion. Increased D-dimer levels positively correlated with increased PCT levels (r = 0.456, P = 0.002) and IL-6 levels (r = 0.501, P = 0.045). A negative correlation between D-dimer levels and PaO2 levels (r = -0.654, P = 0.021) were also existed. Cancer patients with COVID-19 showed prominent hypercoagulability associated with severe inflammation, anticoagulation therapy might be useful to improve the prognosis and should be immediately used after the onset of hypercoagulability.

Surface distribution of severe acute respiratory syndrome coronavirus 2 in Leishenshan Hospital in China

The global pandemic of Corona Virus Disease 2019 (COVID-19) necessitated the rapid construction of field hospitals as the main strategies to control the detrimental effects of the outbreak. Little is known about the extent of the environmental contamination of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in an urgently field hospital. A total of 66 surface samples were randomly collected from a general isolation ward and an ICU (intensive care unit) at a rapidly built field hospital (Wuhan Leishenshan Hospital) in Wuhan, China, from 12 March to 17 March 2020. The samples were used for SARS-CoV-2 detection and ATP (adenosine triphosphate) monitoring. Among these samples, 3.03% tested positive for SARS-CoV-2. The nurses' hands and nurse station in the ICU were weakly positive (CT value = 38.79;CT value = 37.56) and the ATP value of these two sites was higher than the mean value of all samples (ATP = 817;ATP = 577). The environmental cleaning and disinfection normalization bundle measures in Leishenshan hospital included air disinfection, object surface cleaning and disinfection, instrument equipment surface disinfection and hand hygiene, etc. These have been tested and were shown to be reliable and useful. Our experience can provide a useful reference in the fight against the ongoing pandemic of COVID-19.

Clinical Characteristics and Immune Injury Mechanisms in 71 Patients with COVID-19.

The outbreak of coronavirus disease 2019 (COVID-19), caused by the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a threat to global health. The mortality rate of severely ill patients in the early stage is 32.5%. The exacerbation of the condition and death of patients are closely associated with inflammatory cytokine storms, which are caused by excessive activation of the immune and complement systems as well as the coinfection of other pathogens. However, the immunological characteristics and the mechanisms underlying inflammatory storms have not been well elucidated. Here, we analyzed the clinical and immunological characteristics of 71 confirmed COVID-19 patients. Based on the National Health Commission of China (NHCC) guidelines, patients were stratified into mild and severe types. We compared the clinical and laboratory data obtained from electronic medical records between the two types. In regard to the hematological parameters, COVID-19 patients showed decreased erythrocyte count, hemoglobin, hematocrit, lymphocyte count, eosinophil count, and complement C1q, whereas neutrophils, C-reactive protein, and procalcitonin were significantly increased, especially in severe cases. We also found that CD3+ CD4+ T lymphocytes, CD3+ CD8+ T lymphocytes, CD19+ B lymphocytes, and CD16+ CD56+ NK cells in the peripheral blood of all patients were decreased. In addition, CD3+ CD8+ T lymphocytes, CD16+ CD56+ NK cells, and complement C1q in severely ill patients decreased more significantly. Additionally, interleukin 6 (IL-6) elevation was particularly prominent in all patients, especially in severe cases. These results suggest that CD3+ CD8+ T lymphocytes, CD16+ CD56+ NK cells, C1q as well as IL-6 may play critical roles in the inflammatory cytokine storm. The dysregulation of these aforementioned immune parameters, along with bacterial coinfection, were the important causes of exacerbation of the patients' condition and death. This study improves our understanding of the immune dysregulation of COVID-19 and provides potential immunotherapeutic strategies.IMPORTANCE The dysregulation of CD3+ CD8+ T lymphocytes, CD16+ CD56+ NK cells, C1q as well as IL-6, along with bacterial coinfection, were important causes of exacerbation of the patients' condition and death.

Scoring systems for predicting mortality for severe patients with COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has been widely spread and caused tens of thousands of deaths, especially in patients with severe COVID-19. This analysis aimed to explore risk factors for mortality of severe COVID-19, and establish a scoring system to predict in-hospital deaths. METHODS: Patients with COVID-19 were retrospectively analyzed and clinical characteristics were compared. LASSO regression as well as multivariable analysis were used to screen variables and establish prediction model. FINDINGS: A total of 2529 patients with COVID-19 was retrospectively analyzed, and 452 eligible severe COVID-19 were used for finally analysis. In training cohort, the median age was 66•0 years while it was 73•0 years in non-survivors. Patients aged 60-75 years accounted for the largest proportion of infected populations and mortality toll. Anti-SARS-CoV-2 antibodies were monitored up to 54 days, and IgG levels reached the highest during 20-30 days. No differences were observed of antibody levels between severe and non-severe patients. About 60.2% of severe patients had complications. Among acute myocardial injury (AMI), acute kidney injury (AKI) and acute liver injury (ALI), the heart was the earliest injured organ, whereas the time from AKI to death was the shortest. Age, diabetes, coronary heart disease (CHD), percentage of lymphocytes (LYM%), procalcitonin (PCT), serum urea, C reactive protein and D-dimer (DD), were identified associated with mortality by LASSO binary logistic regression. Then multivariable analysis was performed to conclude that old age, CHD, LYM%, PCT and DD remained independent risk factors for mortality. Based on the above variables, a scoring system of COVID-19 (CSS) was established to divide patients into low-risk and high-risk groups. This model displayed good discrimination (AUC=0·919) and calibration (P=0·264). Complications in low-risk and high-risk groups were significantly different (P<0·05). Use of corticosteroids in low-risk groups increased hospital stays by 4·5 days (P=0·036) and durations of disease by 7·5 days (P=0·012) compared with no corticosteroids. INTERPRETATION: Old age, CHD, LYM%, PCT and DD were independently related to mortality. CSS was useful for predicting in-hospital mortality and complications, and it could help clinicians to identify high-risk patients with poor prognosis. FUNDING: This work was supported by the Key Project for Anti-2019 novel Coronavirus Pneumonia from the Ministry of Science and Technology, China (grant number 2020YFC0845500).

Novel Insights Into Illness Progression and Risk Profiles for Mortality in Non-survivors of COVID-19.

Background. The outbreak of COVID-19 has attracted the attention of the whole world. Our study aimed to describe illness progression and risk profiles for mortality in non-survivors. Methods. We retrospectively analyzed 155 patients with COVID-19 in Wuhan and focused on 18 non-survivors among them. Briefly, we compared the dynamic profile of biochemical and immune parameters and drew an epidemiological and clinical picture of disease progression from disease onset to death in non-survivors. The survival status of the cohort was indicated by a Kaplan-Meier curve. Results. Of the non-survivors, the median age was 73.5 years, and the proportion of males was 72.2%. Five and 13 patients were hospital-acquired and community-acquired infection of SARS-CoV-2, respectively. The interval between disease onset and diagnosis was 8.5 days (IQR, [4-11]). With the deterioration of disease, most patients experienced consecutive changes in biochemical parameters, including lymphopenia, leukocytosis, thrombocytopenia, hypoproteinemia, as well as elevated D-dimer and procalcitonin. Regarding the immune dysregulation, patients exhibited significantly decreased T lymphocytes in the peripheral blood, including CD3+T, CD3+CD4+Th, and CD3+CD8+Tc cells. By the end of the disease, most patients suffered from severe complications, including ARDS (17/18; 94.4%), acute cardiac injury (10/18; 55.6%), acute kidney injury (7/18; 38.9%), shock (6/18; 33.3%), gastrointestinal bleeding (1/18; 5.6%), as well as perforation of intestine (1/18; 5.6%). All patients died within 45 days after the initial hospital admission with a median survivor time of 13.5 days (IQR, 8-17). Conclusions. Our data show that patients experienced consecutive changes in biochemical and immune parameters with the deterioration of the disease, indicating the necessity of early intervention.

Potential therapeutic effects of dipyridamole in the severely ill patients with COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause acute respiratory distress syndrome, hypercoagulability, hypertension, and multiorgan dysfunction. Effective antivirals with safe clinical profile are urgently needed to improve the overall prognosis. In an analysis of a randomly collected cohort of 124 patients with COVID-19, we found that hypercoagulability as indicated by elevated concentrations of D-dimers was associated with disease severity. By virtual screening of a U.S. FDA approved drug library, we identified an anticoagulation agent dipyridamole (DIP) in silico, which suppressed SARS-CoV-2 replication in vitro. In a proof-of-concept trial involving 31 patients with COVID-19, DIP supplementation was associated with significantly decreased concentrations of D-dimers (P < 0.05), increased lymphocyte and platelet recovery in the circulation, and markedly improved clinical outcomes in comparison to the control patients. In particular, all 8 of the DIP-treated severely ill patients showed remarkable improvement: 7 patients (87.5%) achieved clinical cure and were discharged from the hospitals while the remaining 1 patient (12.5%) was in clinical remission.