ABSTRACT
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.
Subject(s)
COVID-19ABSTRACT
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.
Subject(s)
COVID-19 , Fever , Brain ConcussionABSTRACT
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.
Subject(s)
COVID-19 , FeverABSTRACT
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.
Subject(s)
COVID-19 , Pneumonia , Neoplasms , Leukemia, B-CellABSTRACT
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.
Subject(s)
COVID-19 , Severe Acute Respiratory SyndromeABSTRACT
Real time fluorescent quantitative PCR (RT-PCR) is widely used as the gold standard for clinical detection of SARS-CoV-2. However, due to the low viral load in patient throats and the limitations of RT-PCR, significant numbers of false negative reports are inevitable, which results in failure to timely diagnose, early treat, cut off transmission, and assess discharge criteria. To improve this situation, an optimized droplet digital PCR (ddPCR) was used for detection of SARS-CoV-2, which showed that the limit of detection of ddPCR is significantly lower than that of RT-PCR. We further explored the feasibility of ddPCR to detect SARS-CoV-2 nucleic acid from 77 clinical throat swab samples, including 63 suspected outpatients with fever and 14 supposed convalescents who were about to discharge after treatment, and compared with RT-PCR in terms of the diagnostic accuracy. In this double-blind study, we tested, surveyed subsequently and statistically analyzed 77 clinical samples. According to our study, 26 samples from COVID-19 patients with RT-PCR negative were detected as positive by ddPCR. No FPRs of RT-PCR and ddPCR were observed. The sensitivity, specificity, PPV, NPV, NLR and accuracy were improved from 40% (95% CI: 27-55%), 100% (95% CI: 54-100%), 100%, 16% (95% CI: 13-19%), 0.6 (95% CI: 0.48-0.75) and 47% (95% CI: 33-60%) for RT-PCR to 94% (95% CI: 83-99%), 100% (95% CI: 48-100%), 100%, 63% (95% CI: 36-83%), 0.06 (95% CI: 0.02-0.18) and 95% (95% CI: 84-99%) for ddPCR, respectively. Moreover, 14 (42.9 %) convalescents still carry detectable SARS-CoV-2 after discharge. Overall, ddPCR shows superiority for clinical diagnosis of SARS-CoV-2 to reduce the false negative reports, which could be a powerful complement to the current standard RT-PCR. It also suggests that the current clinical practice that the convalescent after discharge continues to be quarantined for at least 2 weeks is completely necessary which can prevent potential viral transmission.
Subject(s)
COVID-19 , FeverABSTRACT
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.