Nasal Spray of Neutralizing Monoclonal Antibody 35B5 Confers Potential Prophylaxis Against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Variants of Concern (VOCs): A Small-scale Clinical Trial.

BACKGROUND: SARS-CoV-2 VOCs, especially the Delta and Omicron variants, have been reported to show significant resistance to approved neutralizing monoclonal antibodies (mAbs) and vaccines. We previously identified a mAb named 35B5 that harbors broad neutralization to SARS-CoV-2 VOCs. Herein, we explored the protection efficacy of a 35B5-based nasal spray against SARS-CoV-2 VOCs in a small-scale clinical trial. METHODS: We enrolled 30 healthy volunteers who were nasally administrated with the modified 35B5 formulation. At 12, 24, 48 and 72 hours after nasal spray, the neutralization efficacy of nasal mucosal samples was assayed with pseudoviruses coated with SARS-CoV-2 Spike protein of the wild-type (WT), Alpha, Beta, Delta, or Omicron variants. RESULTS: The nasal mucosal samples collected within 24 hours after nasal spray effectively neutralized SARS-CoV-2 VOCs (including Delta and Omicron). Meanwhile, the protection efficacy was 60% effective and 20% effective at 48 and 72 hours after nasal spray, respectively. CONCLUSIONS: A single nasal spray of 35B5 formation conveys 24-hour effective protection against SARS-CoV-2 VOCs, including the Alpha, Beta, Delta, or Omicron variants. Thus, 35B5 nasal spray might be potential in strengthening SARS-CoV-2 prevention, especially in the high-risk population.

A Bispecific Antibody Targeting RBD and S2 Potently Neutralizes SARS-CoV-2 Omicron and Other Variants of Concern.

Emerging severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) variants, especially the Omicron variant, have impaired the efficacy of existing vaccines and most therapeutic antibodies, highlighting the need for additional antibody-based tools that can efficiently neutralize emerging SARS-CoV-2 variants. The use of a "single" agent to simultaneously target multiple distinct epitopes on the spike is desirable in overcoming the neutralizing escape of SARS-CoV-2 variants. Herein, we generated a human-derived IgG-like bispecific antibody (bsAb), Bi-Nab35B5-47D10, which successfully retained parental specificity and simultaneously bound to the two distinct epitopes on receptor-binding domain (RBD) and S2. Bi-Nab35B5-47D10 showed improved spike binding breadth among wild-type (WT) SARS-CoV-2, variants of concern (VOCs), and variants being monitored (VBMs) compared with its parental monoclonal antibodies (MAbs). Furthermore, pseudotyped virus neutralization demonstrated that Bi-Nab35B5-47D10 can efficiently neutralize VBMs, including Alpha (B.1.1.7), Beta (B.1.351), and Kappa (B.1.617.1), as well as VOCs, including Delta (B.1.617.2), Omicron BA.1, and Omicron BA.2. Crucially, Bi-Nab35B5-47D10 substantially improved neutralizing activity against Omicron BA.1 (IC50 = 0.15 nM) and Omicron BA.2 (IC50 = 0.67 nM) compared with its parental MAbs. Therefore, Bi-Nab35B5-47D10 represents a potential effective countermeasure against SARS-CoV-2 Omicron and other variants of concern. IMPORTANCE The new, highly contagious SARS-CoV-2 Omicron variant caused substantial breakthrough infections and has become the dominant strain in countries across the world. Omicron variants usually bear high mutations in the spike protein and exhibit considerable escape of most potent neutralization monoclonal antibodies and reduced efficacy of current COVID-19 vaccines. The development of neutralizing antibodies with potent efficacy against the Omicron variant is still an urgent priority. Here, we generated a bsAb, Bi-Nab35B5-47D10, which simultaneously targets SARS-CoV-2 RBD and S2 and improves the neutralizing potency and breadth against SARS-CoV-2 WT and the tested variants compared with their parental antibodies. Notably, Bi-Nab35B5-47D10 has more potent neutralizing activity against the VOC Omicron pseudotyped virus. Therefore, Bi-Nab35B5-47D10 is a feasible and potentially effective strategy by which to treat and prevent COVID-19.

A potent human monoclonal antibody with pan-neutralizing activities directly dislocates S trimer of SARS-CoV-2 through binding both up and down forms of RBD.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic of novel coronavirus disease (COVID-19). The neutralizing monoclonal antibodies (mAbs) targeting the receptor-binding domain (RBD) of SARS-CoV-2 are among the most promising strategies to prevent and treat COVID-19. However, SARS-CoV-2 variants of concern (VOCs) profoundly reduced the efficacies of most of mAbs and vaccines approved for clinical use. Herein, we demonstrated mAb 35B5 efficiently neutralizes both wild-type (WT) SARS-CoV-2 and VOCs, including B.1.617.2 (delta) variant, in vitro and in vivo. Cryo-electron microscopy (cryo-EM) revealed that 35B5 neutralizes SARS-CoV-2 by targeting a unique epitope that avoids the prevailing mutation sites on RBD identified in circulating VOCs, providing the molecular basis for its pan-neutralizing efficacy. The 35B5-binding epitope could also be exploited for the rational design of a universal SARS-CoV-2 vaccine.

35B5 antibody potently neutralizes SARS-CoV-2 Omicron by disrupting the N-glycan switch via a conserved spike epitope.

The SARS-CoV-2 Omicron variant harbors more than 30 mutations in the spike protein, leading to immune evasion from many therapeutic neutralizing antibodies. We reveal that a receptor-binding domain (RBD)-targeting monoclonal antibody, 35B5, exhibits potent neutralizing efficacy to Omicron. Cryo-electron microscopy structures of the extracellular domain trimer of Omicron spike with 35B5 Fab reveal that Omicron spike exhibits tight trimeric packing and high thermostability, as well as significant antigenic shifts and structural changes, within the RBD, N-terminal domain (NTD), and subdomains 1 and 2. However, these changes do not affect targeting of the invariant 35B5 epitope. 35B5 potently neutralizes SARS-CoV-2 Omicron and other variants by causing significant conformational changes within a conserved N-glycan switch that controls the transition of RBD from the "down" state to the "up" state, which allows recognition of the host entry receptor ACE2. This mode of action and potent neutralizing capacity of 35B5 indicate its potential therapeutic application for SARS-CoV-2.

A Promising and Challenging Approach: Radiologists' Perspective on Deep Learning and Artificial Intelligence for Fighting COVID-19.

Chest X-rays (CXR) and computed tomography (CT) are the main medical imaging modalities used against the increased worldwide spread of the 2019 coronavirus disease (COVID-19) epidemic. Machine learning (ML) and artificial intelligence (AI) technology, based on medical imaging fully extracting and utilizing the hidden information in massive medical imaging data, have been used in COVID-19 research of disease diagnosis and classification, treatment decision-making, efficacy evaluation, and prognosis prediction. This review article describes the extensive research of medical image-based ML and AI methods in preventing and controlling COVID-19, and summarizes their characteristics, differences, and significance in terms of application direction, image collection, and algorithm improvement, from the perspective of radiologists. The limitations and challenges faced by these systems and technologies, such as generalization and robustness, are discussed to indicate future research directions.

Sensitivity of SARS-CoV-2 Variants to Neutralization by Convalescent Sera and a VH3-30 Monoclonal Antibody.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic of novel coronavirus disease (COVID-19). Though vaccines and neutralizing monoclonal antibodies (mAbs) have been developed to fight COVID-19 in the past year, one major concern is the emergence of SARS-CoV-2 variants of concern (VOCs). Indeed, SARS-CoV-2 VOCs such as B.1.1.7 (UK), B.1.351 (South Africa), P.1 (Brazil), and B.1.617.1 (India) now dominate the pandemic. Herein, we found that binding activity and neutralizing capacity of sera collected from convalescent patients in early 2020 for SARS-CoV-2 VOCs, but not non-VOC variants, were severely blunted. Furthermore, we observed evasion of SARS-CoV-2 VOCs from a VH3-30 mAb 32D4, which was proved to exhibit highly potential neutralization against wild-type (WT) SARS-CoV-2. Thus, these results indicated that SARS-CoV-2 VOCs might be able to spread in convalescent patients and even harbor resistance to medical countermeasures. New interventions against these SARS-CoV-2 VOCs are urgently needed.

Abnormal Indexes of Liver and Kidney Injury Markers Predict Severity in COVID-19 Patients.

BACKGROUND: SARS-CoV-2 can damage not only the lungs but also the liver and kidney. Most critically ill patients with coronavirus disease 2019 (COVID-19) have liver and kidney dysfunction. We aim to investigate the levels of liver and kidney function indexes in mild and severe COVID-19 patients and their capability to predict the severity of the disease. METHODS: The characteristics and laboratory indexes were compared between patients with different conditions. We applied binary logistic regression to find the independent risk factors of severe patients. Receiver operating characteristic (ROC) analysis was used to predict the severity of COVID-19 using the liver and kidney function indexes. RESULTS: This study enrolled 266 COVID-19 patients, including 235 mild patients and 31 severe patients. Compared with mild patients, severe patients had lower albumin (ALB) and higher alanine aminotransferase (ALT), aspartate aminotransferase (AST), and urea nitrogen (BUN) (all p<0.001). Binary logistic regression analysis also identified ALB [OR=0.273 (0.079-0.947), p=0.041] and ALT [OR=2.680 (1.036-6.934), p=0.042] as independent factors of severe COVID-19 patients. Combining ALB, ALT, BUN, and LDH exhibited the area under ROC at 0.914, with a sensitivity of 86.7% and specificity of 83.0%. CONCLUSION: COVID-19 patients, especially severe patients, have damage to liver and kidney function. ALT, AST, LDH, and BUN could be independent factors for predicting the severity of COVID-19. Combining the ALB, ALT, BUN, and LDH could predict the transition from mild to severe in COVID-19 patients.

The dichotomous and incomplete adaptive immunity in COVID-19 patients with different disease severity.

The adaptive immunity that protects patients from coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is not well characterized. In particular, the asymptomatic patients have been found to induce weak and transient SARS-CoV-2 antibody responses, but the underlying mechanisms remain unknown; meanwhile, the protective immunity that guide the recovery of these asymptomatic patients is elusive. Here, we characterized SARS-CoV-2-specific B-cell and T-cell responses in 10 asymptomatic patients and 64 patients with other disease severity (mild, n = 10, moderate, n = 32, severe, n = 12) and found that asymptomatic or mild symptomatic patients failed to mount virus-specific germinal center (GC) B cell responses that result in robust and prolonged humoral immunity, assessed by GC response indicators including follicular helper T (TFH) cell and memory B cell responses as well as serum CXCL13 levels. Alternatively, these patients mounted potent virus-specific TH1 and CD8+ T cell responses. In sharp contrast, patients of moderate or severe disease induced vigorous virus-specific GC B cell responses and associated TFH responses; however, the virus-specific TH1 and CD8+ T cells were minimally induced in these patients. These results, therefore, uncovered the protective immunity in asymptomatic patients and also revealed the strikingly dichotomous and incomplete humoral and cellular immune responses in COVID-19 patients with different disease severity, providing important insights into rational design of effective COVID-19 vaccines.

Correlation between early features and prognosis of symptomatic COVID-19 discharged patients in Hunan, China.

To determine the correlation between the clinical, laboratory, and radiological findings and the hospitalization days in Coronavirus Infectious Disease-19 (COVID-19) discharged patients. We retrospectively identified 172 discharged patients with COVID-19 pneumonia from January 10, 2020, to February 28, 2020, in Hunan province. The patients were categorized into group 1 (≤ 19 days) and group 2 (> 19 days) based on the time from symptom onset to discharge. Cough during admission occurred more commonly in group 2 (68.4%) than in group 1 (53.1%, p = 0.042). White blood cell (p = 0.045), neutrophil counts (p = 0.023), Alanine aminotransferase (p = 0.029), Aspartate aminotransferase (p = 0.027) and Lactate dehydrogenase (p = 0.021) that were above normal were more common in group 2. Patients with single lesions were observed more in group 1(17.7%, p = 0.018) and multiple lesions observed more in group 2(86.8%, p = 0.012). The number of lobes involved (p = 0.008) in the CT score (p = 0.001) for each patient was all differences between the two groups with a statistically significant difference. Mixed ground-glass opacity (GGO) and consolidation appearances were observed in most patients. GGO components > consolidation appearance was more common in group 1 (25.0%) than in group 2 (8.0%) with a significant difference (0.015), GGO < consolidation was more common in group 2(71.1%, p = 0.012). From the logistic regression analysis, the CT score (OR, 1.223; 95% CI, 1.004 to 1.491, p = 0.046) and the appearance of GGO > consolidation (OR, 0.150; 95% CI, 0.034 to 0.660, p = 0.012) were independently associated with the hospitalization days. Thus, special attention should be paid to the role of radiological features in monitoring the disease prognosis.

Risk factors associated with acute respiratory distress syndrome in COVID-19 patients outside Wuhan: A double-center retrospective cohort study of 197 cases in Hunan, China.

BACKGROUND: There have been few reports on the risk factors for acute respiratory distress syndrome (ARDS) in coronavirus disease 2019 (COVID-19), and there were obvious differences regarding the incidence of ADRS between Wuhan and outside Wuhan in China. AIM: To investigate the risk factors associated with ARDS in COVID-19, and compare the characteristics of ARDS between Wuhan and outside Wuhan in China. METHODS: Patients were enrolled from two medical centers in Hunan Province. A total of 197 patients with confirmed COVID-19, who had either been discharged or had died by March 15, 2020, were included in this study. We retrospectively collected the patients' clinical data, and the factors associated with ARDS were compared by the χ² test, Fisher's exact test, and Mann-Whitney U test. Significant variables were chosen for the univariate and multivariate logistic regression analyses. In addition, literature in the PubMed database was reviewed, and the characteristics of ARDS, mortality, and biomarkers of COVID-19 severity were compared between Wuhan and outside Wuhan in China. RESULTS: Compared with the non-ARDS group, patients in the ARDS group were significantly older, had more coexisting diseases, dyspnea, higher D-dimer, lactate dehydrogenase (LDH), and C-reactive protein. In univariate logistic analysis, risk factors associated with the development of ARDS included older age [odds ratio (OR) = 1.04), coexisting diseases (OR = 3.94), dyspnea (OR = 17.82), dry/moist rales (OR = 9.06), consolidative/mixed opacities (OR = 2.93), lymphocytes (OR = 0.68 for high lymphocytes compared to low lymphocytes), D-dimer (OR = 1.41), albumin (OR = 0.69 for high albumin compared to low albumin), alanine aminotransferase (OR = 1.03), aspartate aminotransferase (OR = 1.02), LDH (OR = 1.02), C-reactive protein (OR = 1.04) and procalcitonin (OR = 17.01). In logistic multivariate analysis, dyspnea (adjusted OR = 27.10), dry/moist rales (adjusted OR = 9.46), and higher LDH (adjusted OR = 1.02) were independent risk factors. The literature review showed that patients in Wuhan had a higher incidence of ARDS, higher mortality rate, and higher levels of biomarkers associated with COVID-19 severity than those outside Wuhan in China. CONCLUSION: Dyspnea, dry/moist rales and higher LDH are independent risk factors for ARDS in COVID-19. The incidence of ARDS in Wuhan seems to be overestimated compared with outside Wuhan in China.

Effectiveness of Convalescent Plasma Therapy for COVID-19 Patients in Hunan, China.

OBJECTIVE: To investigate clinical efficacy and safety of convalescent plasma (CP) therapy in coronavirus disease 2019 (COVID-19) patients. METHODS: We included 4 severe patients and 3 critical patients. The date of admission to hospital ranged from January 30 to February 19, 2020. We retrospectively collected clinical and outcome data. Relative parameters were compared. RESULTS: After CP therapy, the symptoms and respiratory functions were improved. Median PaO2/FIO2 increased from 254 (142-331) to 326 (163-364), and dependence of oxygen supply decreased. Median time to lesion's first absorption was 5 (2-7) days, undetectable viral RNA was 11 (3.5-15.7) days. Median lymphocyte count (0.77 × 109/L vs 0.85 × 109/L) and albumin level (31g/L vs 36 g/L) were elevated, C-reactive protein (44 mg/L vs 18 mg/L), D-dimer (5.9 mg/L vs 4 mg/L) and lactate dehydrogenase (263 U/L vs 245 U/L) decreased. No obvious adverse reactions were observed. At the follow-up on June 14, 2020, 6 patients had completely recovered and one died from terminal disease. CONCLUSION: CP therapy for COVID-19 was effective and safe. Three patients who did not combine with antiviral therapy after CP also obtained viral clearance and clinical improvement. However, CP therapy failed to save the life of a terminally ill patient.

The differences of clinical characteristics and outcomes between imported and local patients of COVID-19 in Hunan: a two-center retrospective study.

BACKGROUND: The clinical characteristics and outcomes of the 2019 novel coronavirus (COVID-19) pneumonia are different in Hubei compared to other regions in China. But there are few comparative studies on the differences between imported and local patients which may provide information of the different courses of the virus after transmission. METHODS: We investigated 169 cases of COVID-19 pneumonia in two centers in Hunan Province, and divided them into two groups according to epidemiological history, "imported patients" refers to patient with a clear history of travel in Wuhan within 14 days before onset, and " local patients" refers to local resident without a recent history of travel in Wuhan, aiming to analyze the difference in clinical characteristics and outcomes between the two groups. All the epidemiological, clinical, imaging, and laboratory data were analyzed and contrasted. RESULTS: The incidence of fever on admission in imported patients was significantly higher than local patients. There was a significantly higher proportion of abnormal pulmonary signs, hypokalemia, hyponatremia, prolonged PT, elevated D-dimer and elevated blood glucose in imported patients. Compared with local patients, the proportion using antibiotics, glucocorticoids and gamma globulin were significantly higher in imported patients. The moderate type was more common in local patients, and the severe type were more frequent in imported patients. In addition, the median duration of viral clearance was longer in imported patients. CONCLUSIONS: In summary, we found that imported cases were more likely to develop into severe cases, compared with local patients and required more powerful treatments. Trial registration Registered 21st March 2020, and this study has been approved by the Medical Ethics Committee (Approved Number. 2020017).

Clinical characteristics and risk factors for severity of COVID-19 outside Wuhan: a double-center retrospective cohort study of 213 cases in Hunan, China.

AIM: To investigate clinical characteristics and identify risk factors for severity of coronavirus disease 2019 (COVID-19) pneumonia outside of Wuhan, China. MATERIALS AND METHODS: We included 213 patients with confirmed COVID-19 who had been discharged or died by 15 March 2020. We retrospectively collected epidemiological, clinical, laboratory, computed tomography imaging and outcome data. Clinical characteristics were described and relative risk factors were compared. RESULTS: Most clinical characteristics of this study were similar to those from studies in Wuhan, but there were lower mortality rate and milder severity. The median time from onset of symptoms to confirmation and hospitalization was 4 and 5 days, respectively. The median virus clearance and shedding times were 10 and 15 days, respectively. When the severe/critical group was compared with the mild/moderate group, significant risk factors included: older age; dyspnea; hypertension; poor appetite; fatigue; higher white cell count, neutrophil count, prothrombin time, creatine kinase, creatine kinase-MB, D-dimer, alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and C-reactive protein; and lower lymphocyte count and albumin (p < 0.05). In the intensive care unit (ICU) group compared with the non-ICU group, risk factors included: older age; chronic obstructive pulmonary disease (COPD); dyspnea; poor appetite; higher white cell count, D-dimer, ALT, AST and LDH; and lower lymphocyte count and albumin (p < 0.05). Independent risk factors associated with the severe/critical group were dyspnea [odds ratio (OR) = 19.48], ALT (OR = 6.02) and albumin (OR = 3.36). Independent risk factors associated with the ICU group were dyspnea (OR = 8.88), COPD (OR = 31.80), D-dimer (OR = 8.37), ALT (OR = 28.76) and LDH (OR = 9.95) (p < 0.05). CONCLUSION: The severity of COVID-19 outside Wuhan, China was milder than that within Wuhan. The clinical infective period was long, and the longest virus shedding time was 35 days. The most important risk factors were dyspnea, COPD, D-dimer, ALT, LDH and albumin.The reviews of this paper are available via the supplemental material section.

Comparative effectiveness of Lopinavir/Ritonavir-based regimens in COVID-19.

The coronavirus disease 2019 (COVID-19) is an epidemic disease caused by the Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) and spreading throughout the world rapidly. Here we evaluated the efficacy of the Lopinavir/Ritonavir (LPV/r) and its combination with other drugs in the treatment of COVID-19. We included 170 confirmed COVID-19 patients who had been cured and discharged. Their antiviral therapies were LPV/r alone or combinations with interferon (IFN), Novaferon and Arbidol. We evaluated the medication efficacy by comparing the time of the negative nucleic acid conversion and the length of hospitalization mainly. The LPV/r + Novaferon [6.00 (4.00-8.00) and 7.50 (5.00-10.00) days] had shorter time of the negative nucleic acid conversion (P = .0036) and shorter time of hospitalization (P < .001) compared with LPV/r alone [9.00 (5.00-12.00) and 12.00 (11.00-15.00) days] and LPV/r + IFN [9.00 (7.25-11.00) and 12.00 (10.00-13.50) days]. On the contrary, LPV/r + IFN [9.00 (7.25-11.00) and 12.00 (10.00-13.50) days] had shorter time of the negative nucleic acid conversion (P = .031) and shorter time of hospitalization (P < .001) compared with LPV/r + IFN +Novaferon [10.00 (8.00-11.25) and 13.50 (11.50-17.00) days] and LPV/r + IFN +Arbidol [14.00 (9.75-19.00) and 19.50 (13.25-24.00) days]. In conclusion, the combination of LPV/r and Novaferon may have better efficacy against COVID-19. However, adding IFN based on LPV/r + Novaferon or adding Arbidol based on LPV/r + IFN may not improve the efficacy.

Deep learning-based triage and analysis of lesion burden for COVID-19: a retrospective study with external validation.

Background: Prompt identification of patients suspected to have COVID-19 is crucial for disease control. We aimed to develop a deep learning algorithm on the basis of chest CT for rapid triaging in fever clinics. Methods: We trained a U-Net-based model on unenhanced chest CT scans obtained from 2447 patients admitted to Tongji Hospital (Wuhan, China) between Feb 1, 2020, and March 3, 2020 (1647 patients with RT-PCR-confirmed COVID-19 and 800 patients without COVID-19) to segment lung opacities and alert cases with COVID-19 imaging manifestations. The ability of artificial intelligence (AI) to triage patients suspected to have COVID-19 was assessed in a large external validation set, which included 2120 retrospectively collected consecutive cases from three fever clinics inside and outside the epidemic centre of Wuhan (Tianyou Hospital [Wuhan, China; area of high COVID-19 prevalence], Xianning Central Hospital [Xianning, China; area of medium COVID-19 prevalence], and The Second Xiangya Hospital [Changsha, China; area of low COVID-19 prevalence]) between Jan 22, 2020, and Feb 14, 2020. To validate the sensitivity of the algorithm in a larger sample of patients with COVID-19, we also included 761 chest CT scans from 722 patients with RT-PCR-confirmed COVID-19 treated in a makeshift hospital (Guanggu Fangcang Hospital, Wuhan, China) between Feb 21, 2020, and March 6, 2020. Additionally, the accuracy of AI was compared with a radiologist panel for the identification of lesion burden increase on pairs of CT scans obtained from 100 patients with COVID-19. Findings: In the external validation set, using radiological reports as the reference standard, AI-aided triage achieved an area under the curve of 0·953 (95% CI 0·949-0·959), with a sensitivity of 0·923 (95% CI 0·914-0·932), specificity of 0·851 (0·842-0·860), a positive predictive value of 0·790 (0·777-0·803), and a negative predictive value of 0·948 (0·941-0·954). AI took a median of 0·55 min (IQR: 0·43-0·63) to flag a positive case, whereas radiologists took a median of 16·21 min (11·67-25·71) to draft a report and 23·06 min (15·67-39·20) to release a report. With regard to the identification of increases in lesion burden, AI achieved a sensitivity of 0·962 (95% CI 0·947-1·000) and a specificity of 0·875 (95 %CI 0·833-0·923). The agreement between AI and the radiologist panel was high (Cohen's kappa coefficient 0·839, 95% CI 0·718-0·940). Interpretation: A deep learning algorithm for triaging patients with suspected COVID-19 at fever clinics was developed and externally validated. Given its high accuracy across populations with varied COVID-19 prevalence, integration of this system into the standard clinical workflow could expedite identification of chest CT scans with imaging indications of COVID-19. Funding: Special Project for Emergency of the Science and Technology Department of Hubei Province, China.

Disease severity dictates SARS-CoV-2-specific neutralizing antibody responses in COVID-19.

COVID-19 patients exhibit differential disease severity after SARS-CoV-2 infection. It is currently unknown as to the correlation between the magnitude of neutralizing antibody (NAb) responses and the disease severity in COVID-19 patients. In a cohort of 59 recovered patients with disease severity including severe, moderate, mild, and asymptomatic, we observed the positive correlation between serum neutralizing capacity and disease severity, in particular, the highest NAb capacity in sera from the patients with severe disease, while a lack of ability of asymptomatic patients to mount competent NAbs. Furthermore, the compositions of NAb subtypes were also different between recovered patients with severe symptoms and with mild-to-moderate symptoms. These results reveal the tremendous heterogeneity of SARS-CoV-2-specific NAb responses and their correlations to disease severity, highlighting the needs of future vaccination in COVID-19 patients recovered from asymptomatic or mild illness.

Finding the Best Antiviral Regimen for COVID-19: A Double-Center Retrospective Cohort Study of 207 Cases in Hunan, China.

OBJECTIVE: To compare the efficacy of 3/4-drugs' group with 1-drug's or 2-drugs' groups in coronavirus disease 2019 (COVID-19). METHODS: We included 207 patients confirmed with COVID-19. We compared the viral clearance rate and discharge rate at day 7, 14, 21 and 28, and median time of viral clearance and length of hospitalization in patients treated with 3/4, 1 or 2 drugs. RESULTS: The viral clearance rates of the 3/4-drugs group at day 7, 14 and 21 were significantly lower than those in the 1-drug's or 2-drugs' groups (P < 0.05). The median viral clearance days in 3/4-drugs group (13.5 days) were longer than 1-drug's or 2-drugs' groups (both were 9 days) (P < 0.001). The patients' discharge rates in the 3/4-drugs group at day 14 and 21 were significantly lower than that in the 1-drug's or 2 drugs' group (P < 0.05). The median length of hospitalization in the 3/4-drugs group was 17 days, which was significantly longer than 11 days in the 1-drug group and 13 days in the 2-drug group (P < 0.05). CONCLUSION: The efficacy of 1 or 2 antiviral drugs was similar in COVID-19, and 3/4-drug regimens were not associated with clinical improvement. Corticosteroid treatment and more serious disease were also risk factors for viral clearance and patients'discharge.

Factors associated with duration of viral shedding in adults with COVID-19 outside of Wuhan, China: A retrospective cohort study

Objectives To investigate factors associated with the duration of viral shedding in patients with COVID-19 outside of Wuhan. Methods In this retrospective cohort study, patients with laboratory-confirmed COVID-19 in Changsha, China were included. Clinical characteristics, laboratory findings, treatment and outcome were retrieved. Univariable and multivariable analysis were performed to explore potential factors. Results Totally 147 patients with COVID-19 were included. The median duration of viral shedding (the number of days from symptoms onset till the successive negative detection of SARS-CoV-2 RNA) was 17 days (interquartile range [IQR], 12 to 21). Multivariable Logistic regression analysis indicated that the highest temperature at admission (odds ratio [OR], 5.200;95% confidence interval [CI]: 1.190-22.726;p = 0.028) and time from symptom onset to admission (OR, 1.740;95% CI: 1.296-2.337;p < 0.001) and hospital length of stay (OR, 1.604;95% CI: 1.262-2.040;p < 0.001) were risk factors for prolonged duration of viral shedding. Conclusions This is the study with relatively large sample size that mainly focused on the duration of viral shedding and relevant factors in patients with COVID-19 outside of Wuhan, China. Potential risk factors were identified and should be taken into consideration for the strategy of quarantine of infected patients.

Clinical and radiological changes of hospitalised patients with COVID-19 pneumonia from disease onset to acute exacerbation: a multicentre paired cohort study.

OBJECTIVES: To analyse clinical and radiological changes from disease onset to exacerbation in coronavirus infectious disease-19 (COVID-19) patients. METHODS: We reviewed clinical histories of 276 patients with confirmed COVID-19 pneumonia and extracted data on patients who met the diagnostic criteria for COVID-19 severe/fatal pneumonia and had an acute exacerbation starting with mild or common pneumonia. RESULTS: Twenty-four patients were included. Of these, 8% were smokers, 54% had been to Wuhan, and 46% had comorbidities. Before acute exacerbation, elevated lactate dehydrogenase (232.9 ± 88.7) was present, and chest CT scans showed the number of involved lobes was 4 (2-5) and total CT score was 6 (2-8). Following acute exacerbation, patients were likely to have more clinical symptoms (p < 0.01) and abnormal laboratory changes (p < 0.01). The number of involved lobes and CT score after an exacerbation significantly increased to 5 (5-5) and 12 (9-14), respectively. Receiver operating characteristic (ROC) curve showed that, when the cutoff value of CT score was 5, the sensitivity and specificity for severe pneumonia were 90% and 70%, respectively. CT findings of ground glass opacity with consolidations (91.7%), bilateral distribution (100.0%), and multifocal lesion (100.0%) were features in found in patients after exacerbation. CONCLUSIONS: There are significant changes in clinical, laboratory, and CT findings in patients from disease onset to exacerbation. An increase in the number of involved lobes or an increased CT score from the baseline may predict poor clinical outcomes. Combining an assessment of CT changes with clinical and laboratory changes could help clinical teams evaluate the prognosis. KEY POINTS: • The common chest CT signs of COVID-19 pneumonia after exacerbation were ground glass opacity (GGO) with consolidation, bilateral distribution, and multifocal lesions. • An increase in number of involved lobes or an increased CT score from the baseline may predict a poor clinical outcome. • Worsened symptoms and abnormal laboratory results are also associated with poor prognosis.