Clinical and Immunological Characteristics in COVID-19 Convalescent Patients (preprint)

Objective: The immune responses of COVID-19 convalescent patients have not been well described. Methods Blood from thirty COVID-19 convalescent patients who were virus-free were collected. Their clinical laboratory findings and SARS-CoV-2-specific humoral and cellular immunity were detected. Results At 283 days after diagnosis of SARS-CoV-2 infection, the levels of clinical laboratory indicators and lymphocyte subtypes returned to normal levels. However, the ratio of memory/naive CD4+ T lymphocytes cells was greater in COVID-19 convalescent patients and severe COVID-19 convalescent patients, when compared with that in healthy blood donors (P=0.0135) and non-severe patients (P=0.0431), respectively. The levels of anti-SARS-CoV-2-IgM (P=0.014), S1-IgM (P=0.0004) and RBD-IgM (P=0.0002) in severe COVID-19 patients were all significantly greater than those in non-severe COVID-19 patients. When the serums of COVID-19 convalescent patients were diluted as 1:125, the predictive of serum neutralization capabilities were persistent in all patients. SARS-CoV-2-specific T cells were generated and maintained in majority of tested convalescent COVID-19 patients, regardless of the severity of disease in acute phase. Conclusion At 283 days after diagnosis of SARS-CoV-2 infection, specific cellular and humoral immunity against SARS-CoV-2 could be detectable. The severity of disease in acute phase cannot affect the strength of cellular and humoral immunity in convalescent phase.

Antinuclear Autoimmunity Potentially Makes the Middle-aged and Female with COVID-19 Prone to Severe Progression: A Case-control Study (preprint)

Background: Elderliness is known risk factor for severe progression of COVID-19 due to compromised immunity, however aberrant hyperactive immune response including autoimmunity might be responsible for younger patients. Methods: 162 patients tested with autoimmunological detections were enrolled, and study of “Severe” cases and “Non-severe” controls was retrospectively analyzed. Results: Multivariable analysis involving antinuclear autoimmunity manifests correlation of disease severity with middle age and attenuates the risk of age older than 65. Middle age (45≤age≤65) and female turn out to be the risk factors after hierarchical cluster analysis, before which however sex was not correlated. We find antinuclear autoimmunity to be strongly correlated with severity for the middle-aged (OR= 21.000, 95% CI 4.893- 90.126, p< 0.001) and female (OR= 16.044, 95% CI 4.717- 54.568, p< 0.001), especially for the middle-aged female (Pearson R= 0.770, p< 0.001). Incidence of symptoms fever and chest distress, and complication myocardial injury are statistically more frequent in patients with positive antinuclear antibody, compared with those negative. Severe patients with positive antinuclear antibody possess significantly shorter onset of symptoms to severity time (p= 0.021), indicating quicker progression, and interestingly, present more incidence (21%) of post-remission aggravation, compared with those negative (6%). Conclusions: The presence of antinuclear autoimmunity potentially makes COVID-19 prone to severe progression, especially for the middle-aged and female, probably even quicker.

Role of Darunavir/cobicisitat in the Treatment of COVID-19: Initial Virological and Clinical Findings (preprint)

Background: COVID-19 still become a common threat to public health.In this study, we evaluated the antiviral effects and safety of darunavir/cobicisitat (DRV/c) in patients with confirmed COVID-19. Patients and Methods: Totally 66 patients with COVID-19 infection who were admitted to Zhongnan Hospital of Wuhan University between February 3 and March 11, 2020 were collected. The patients were divided into the DRV/c group and the control group. The Primary endpoints was the time of SARS-CoV-2 nucleic acid conversion detected in respiratory specimens.Results: A total of 66 subjects with confirmed SARS-CoV-2 infection were enrolled in this study, 32 subjects were enrolled in the DRV/c group and 34 in the control group. The mean time to nucleic acid conversion (NAC) was shorter in DRV/c group. The cumulative nucleic acid conversion rate (CNACR) in the DRV/C group was higher during the first 2 weeks, but the difference was not statistically significant. The proportion of fever during hospitalization in the DRV/C group was significantly lower than that in the control group (P value 0.01). It was found that in DRV/c group NAC of patients with duration from symptom onset to admission within 3 days was significantly shorter (7.9 ± 6.7 days) than that of and above 3 days (15.9 ± 7.1 days)( P = 0.01). Conclusion: Although the combination of DRV/c and routine treatment for patients with non-severe COVID-19 can significantly reduce the proportion of fever after admission, but no significant differences were observed between the DRV/c group and the conventional therapy group, including overall time to nucleic acid conversion, safety and tolerability. 

Clinical Characteristics and Comparative Analysis of Covid-19 Patients With or Without HIV Coinfection in Wuhan, China (preprint)

Background: COVID-19 is a public health emergency that is spreading worldwide and seriously affecting global economy. Information about the impact of HIV co-infection and anti-HIV drugs on the clinical characteristics and prognosis of COVID-19 patients remains limited.Methods: In this retrospective study, the maximum body temperatures, fever duration, chest computed tomography changes and viral shedding, lymphocyte counts changes and titer of SARS-CoV-2 antibody were compared between COVID-19 patients with and without HIV infection in Zhongnan Hospital of Wuhan University from January 20th to February 14th, 2020. Results: Compared with 50 control COVID-19 patients, the two COVID-19/HIV co-infection patients had higher maximum body temperatures(40.2℃ and 40.3℃ vs 38.2℃), longer fever duration(11 days and 15 days vs 7 days), longer time of lung recovery(20 days and 24 days vs 14 days), shorter duration of viral shedding after the onset of symptoms(6 days and 4 days vs 10 days). Compared with three COVID-19 infection colleagues who had exposure history with the same COVID-19 patient, the third COVID-19/HIV co-infection patient had the same duration of viral shedding after exposure(29 days vs 29 days), lower titer of SARS-CoV-2 IgG(negative vs positive for all). Conclusion: For patients co-infected with HIV, the clinical manifestations of SARS-CoV-2 infection were diverse. The ability of those COVID-19/HIV co-infection patients with severe immunodeficiency to produce SARS-CoV-2 antibodies were weakened. The small sample in this study implied that the effects of anti-HIV drugs in prevention and treatment of COVID-19 appears to be limited.

Scoring Systems for Predicting Mortality for Severe Patients with COVID-19 (preprint)

Background: Coronavirus disease 2019 (COVID-19) has been widely spread and caused tens of thousands of deaths, mainly in patients with severe COVID-19.Methods: Patients with COVID-19 were retrospectively analyzed. Clinical characteristics were compared, and LASSO regression as well as multivariate 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. About 60.2% of severe patients had complications. Acute myocardial injury was the earliest injured organ, whereas the time from acute kidney injury 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 multivariate 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 and divided into low-risk and high-risk groups. This model displayed good discrimination (AUC=0·919) and calibration (P =0·264). The complications in low-risk and high-risk groups were significantly different. We also found that the 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 Statement: 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). Declaration of Interests: All authors declare no competing interests.Ethics Approval Statement: This study was conducted according to the principles of Helsinki and approved by the Ethics Committee of Zhongnan Hospital of Wuhan University (No.2020063).

Clinical Characteristics Hospitalized Patients with SARS-Cov-2 and HBV Co-infection (preprint)

Background & Aims The coronavirus disease 2019 (COIVD-19) caused by SARS-CoV-2 has been characterized as a pandemic, which causes a serious public health challenge in the world. A very large group of patients infected by HBV has been reported worldwide, especially in China. In order to answer whether specific treatment strategy on the patients coinfected with HBV and SARS-CoV-2, it requires profound understanding of the clinical characteristics on those patients. However, the impacts of SARS-CoV-2 infection on HBV patients remain largely unknown. Approach & Results In this retrospective investigation, we included 123 COVID-19 patients admitted to Zhongnan Hospital of Wuhan University, Wuhan, China, from January 5 to March 7, 2020. All enrolled patients are the laboratory confirmed COVID-19 pneumonia cases according to the criteria reported previously. A total of 123 patients were analyzed for their Clinical records, laboratory results including the diagnosis of HBV infection and liver function. Among 123 confirmed COVID-19 patients, the mean age was 51 years old and 59.3% were females (73/123). Fifteen were previously HBV infected patients, 66.7% of them were males (10/15), patients with HBV infection appeared to have a higher incidence of liver cirrhosis and an increased level of total bilirubin. Seven (46.7%) patients with HBV infection were defined as severe cases, while the severity rate was 24.1% for the patients without HBV infection (26/108). The mortality of patients with HBV infection was 13.3% (2/15) compared to 2.8% (3/108) for the patients without HBV infection. Conclusions SARS-CoV-2 infection may cause liver function damage in COVID-19 cases and the patients with HBV infection are likely to have more severe disease outcome.

Hypertension and Diabetes Delay the Viral Clearance in COVID-19 Patients (preprint)

Objectives: Comorbidities have significant indications for the disease outcome of COVID-19, however which underlying diseases that contribute the most to aggravate the conditions of COVID-19 patients is still largely unknown. SARS-CoV-2 viral clearance is a golden standard for defining the recovery of COVID-19 infections. To dissect the underlying diseases that could impact on viral clearance, we enrolled 106 COVID-19 patients who were hospitalized in the Zhongnan Hospital of Wuhan University, Wuhan, China between Jan 5 and Feb 25, 2020. Methodology: We comprehensively analyzed demographic, clinical and laboratory data, as well as patient treatment records. Survival analyses with Kaplan-Meier and Cox regression modelling were employed to identify factors influencing the viral clearance negatively. Results: We found that increasing age, male gender, and angiotensin-converting enzyme 2 (ACE2) associated factors (including hypertension, diabetes, and cardiovascular diseases) adversely affected the viral clearance. Furthermore, analysis by a random forest survival model pointed out hypertension, cortisone treatment, gender, and age as the four most important variables. Conclusions: We conclude that patients at old age, males, and/or having diseases associated with high expression of ACE2 will have worse prognosis during a COVID-19 infections.

The reflection on an AIDS patient with asymptomatic COVID-19 (preprint)

We reported the process of exposure, clinical characteristics, diagnosis and prognosis of an AIDS patient with asymptomatic COVID-19. In our report, we found the asymptomatic is still shedding virus for at least 29 days. Therefore, we suggested that for individuals who had close contact with diagnosed or suspected COVID-19 patients, in addition to isolation, medical observation, and further related testing if clinical symptoms appear in the observation period, it is best to collect nasopharyngeal and throat swab specimens and test for COVID-19 nucleic acid as early as possible. The purpose of this active detection is to screen out COVID-19 asymptomatic patients, and to avoid further transmission through recessive source of infection. Our findings will facilitate understanding of asymptomatic COVID-19 and improve prevention strategies against COVID-19 transmission. 

Favipiravir versus Arbidol for COVID-19: A Randomized Clinical Trial (preprint)

Background No clinically proven effective antiviral strategy exists for the epidemic Coronavirus Disease 2019 (COVID-19). Methods We conducted a prospective, randomized, controlled, open-label multicenter trial involving adult patients with COVID-19. Patients were randomly assigned in a 1:1 ratio to receive conventional therapy plus Umifenovir (Arbidol) (200mg*3/day) or Favipiravir (1600mg*2/first day followed by 600mg*2/day) for 10 days. The primary outcome was clinical recovery rate of Day 7. Latency to relief for pyrexia and cough, the rate of auxiliary oxygen therapy (AOT) or noninvasive mechanical ventilation (NMV) were the secondary outcomes. Safety data were collected for 17 days. Results 240 enrolled COVID-19 patients underwent randomization; 120 patients were assigned to receive Favipiravir (116 assessed), and 120 to receive Arbidol (120 assessed). Clinical recovery rate of Day 7 does not significantly differ between Favipiravir group (71/116) and Arbidol group (62/120) (P=0.1396, difference of recovery rate: 0.0954; 95% CI: -0.0305 to 0.2213). Favipiravir led to shorter latencies to relief for both pyrexia (difference: 1.70 days, P<0.0001) and cough (difference: 1.75 days, P<0.0001). No difference was observed of AOT or NMV rate (both P>0.05). The most frequently observed Favipiravir-associated adverse event was raised serum uric acid (16/116, OR: 5.52, P=0.0014). Conclusions Among patients with COVID-19, Favipiravir, compared to Arbidol, did not significantly improve the clinically recovery rate at Day 7. Favipiravir significantly improved the latency to relief for pyrexia and cough. Adverse effects caused Favipiravir are mild and manageable. This trial is registered with Chictr.org.cn (ChiCTR2000030254).

Clinical characteristics of four cancer patients with SARS-CoV-2 infection in Wuhan, China (preprint)

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to the outbreak of pneumonia in Wuhan, and rapidly spread throughout China. The virus is highly infectious and can infect individuals in the community, including patients in the hospital. Patients with cancer might be susceptible to the viral infection because of the immunosuppressive state cause by therapies on tumors. Case presentation: We present the clinical features of four cancer patients who were infected with SARS-CoV-2 in the past month in our hospital. One patient with uncontrolled chronic B cell lymphocytic leukemia and many other underlying diseases was killed by the virus, and the other three patients survived. Nearly all patients showed a decrease in lymphocytes including total CD3+ T cells, B cells, and natural killer cells after infection of the virus. Conclusion: This report suggests that the treatment of SARS-CoV-2 infection in cancer patients is challenged by the immunosuppressive state of these patients under chemotherapy or surgery.

Restoration of leukomonocyte counts is associated with viral clearance in COVID-19 hospitalized patients (preprint)

Background: Viral clearance is one important indicator for the recovery of SARS-CoV-2 infected patients. Suboptimal T and B cell responses can delay viral clearance in MERS and SARS patients. The role of leukomonocytes in viral clearance of COVID-19 patients is not yet well defined.Methods: From January 26 to February 28, 2020, an observational study was launched at Zhongnan Hospital of Wuhan University, Wuhan, China. We enrolled 25 laboratory-confirmed COVID-19 patients, whose throat-swab specimens were tested positive for SARS-CoV-2 infection by qRT-PCR. We comprehensively analyzed clinical records, counts of lymphocyte subsets including CD3+, CD4+, CD8+ T cells, B cells and NK cells in the patients who successfully cleared SARS-CoV-2, and compared to those that failed to, after a standardized treatment of 8-14 days. Findings: In 25 enrolled COVID-19 patients, lymphopeniawas a common feature. After the treatment, 14 patients were tested negative for SARS-CoV-2. The patients that cleared the infection had restored the numbers of CD3+, CD4+, CD8+ T cellsand B cells as compared to the still viral RNA positive patients, while the recovered patients had a higher count of leukomonocytes. Conclusions: By comparison of leukomonocytes counts in COVID-19 patients at different stages of the disease, we found that CD3+, CD4+, CD8+ T cells and B cells appear to play important roles in viral clearance. The restoration of leukomonocytes counts from peripheral blood can be used as prognosis for the recovery of an COVID-19 infection. We propose that restoration of leukomonocytes counts can be added to the COVID-19 diagnostic guidanceas a criterion for releasing and discharging patients.

Clinical characteristics of refractory COVID-19 pneumonia in Wuhan, China ;Clinical Infectious Diseases ;Oxford Academic

Background Since December 2019, novel coronavirus (SARS-CoV-2)-infected pneumonia (COVID-19) occurred in Wuhan, and rapidly spread throughout China. This study aimed to clarify the characteristics of patients with refractory COVID-19. Methods In this retrospective single-center study, we included 155 consecutive patients with confirmed COVID-19 in Zhongnan Hospital of Wuhan University from January 1st to February 5th. The cases were divided into general and refractory COVID-19 groups according to the clinical efficacy after hospitalization, and the difference between groups were compared. Results Compared with general COVID-19 patients (45.2%), refractory patients had an older age, male sex, more underlying comorbidities, lower incidence of fever, higher levels of maximum temperature among fever cases, higher incidence of breath shortness and anorexia, severer disease assessment on admission, high levels of neutrophil, aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and C-reactive protein, lower levels of platelets and albumin, and higher incidence of bilateral pneumonia and pleural effusion (P<0.05). Refractory COVID-19 patients were more likely to receive oxygen, mechanical ventilation, expectorant, and adjunctive treatment including corticosteroid, antiviral drugs and immune enhancer (P<0.05). After adjustment, those with refractory COVID-19 were also more likely to have a male sex and manifestations of anorexia and fever on admission, and receive oxygen, expectorant and adjunctive agents (P<0.05) when considering the factors of disease severity on admission, mechanical ventilation, and ICU transfer. Conclusion Nearly 50% COVID-19 patients could not reach obvious clinical and radiological remission within 10 days after hospitalization. The patients with male sex, anorexia and no fever on admission predicted poor efficacy.