The unreversible reduced but persistent activated NK and CD8+ T cells in severe/critical COVID-19 during omicron pandemic in China.

As a hallmark of COVID-19 progression, lymphopenia alongside its subtle immune disturbance has been widely reported, but yet to be thoroughly elucidated. Aiming at exploring clinical immune biomarkers with accessibility in the current and acute omicron epidemic abrupted in China post-control era, we design a real-world prospective observation cohort in Peking Union Medical College Hospital to describe immunological, haematological profiles inducing lymphocyte subsets related to SARS-CoV-2 infection. In this COVID-19 cohort, we enrolled 17 mild/moderate (M/M), 24 severe (S) and 25 critical (C) patients. The dynamics of lymphocytes of COVID-19 demonstrated that the sharp decline of NK, CD8+, and CD4+ T cell counts was the main contributor to lymphopenia in the S/C group, compared to the M/M group. Expressions of activation marker CD38 and proliferation marker Ki-67 both in CD8+ T and NK cells were significantly higher in all COVID-19 patients than that in healthy donors, independent of disease severity. The subsequent analysis showed in contrast to the M/M group, NK and CD8+ T cell counts remained low-level after therapy in the S/C group. CD38 and Ki-67 expressions in NK and CD8+ T cells still stay at a high level, despite active treatment. Targeting relatively elderly patients with SARS-CoV-2 infection, severe COVID-19 features the unreversible reduction of NK and CD8+ T cells with persistent activation and proliferation, which assist clinicians in early recognizing and saving severe or critical COVID-19 patients. Given that immunophenotype, the new immunotherapy improving NK and CD8+ T lymphocyte antiviral efficiency should be considered.

Risk for newly diagnosed diabetes after COVID-19: a systematic review and meta-analysis.

BACKGROUND: There is growing evidence that patients recovering after a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may have a variety of acute sequelae including newly diagnosed diabetes. However, the risk of diabetes in the post-acute phase is unclear. To solve this question, we aimed to determine if there was any association between status post-coronavirus disease (COVID-19) infection and a new diagnosis of diabetes. METHODS: We performed a systematic review and meta-analysis of cohort studies assessing new-onset diabetes after COVID-19. PubMed, Embase, Web of Science, and Cochrane databases were all searched from inception to June 10, 2022. Three evaluators independently extracted individual study data and assessed the risk of bias. Random-effects models estimated the pooled incidence and relative risk (RR) of diabetes compared to non-COVID-19 after COVID-19. RESULTS: Nine studies with nearly 40 million participants were included. Overall, the incidence of diabetes after COVID-19 was 15.53 (7.91-25.64) per 1000 person-years, and the relative risk of diabetes after COVID-19 infection was elevated (RR 1.62 [1.45-1.80]). The relative risk of type 1 diabetes was RR=1.48 (1.26-1.75) and type 2 diabetes was RR=1.70 (1.32-2.19), compared to non-COVID-19 patients. At all ages, there was a statistically significant positive association between infection with COVID-19 and the risk of diabetes: <18 years: RR=1.72 (1.19-2.49), ≥18 years: RR=1.63 (1.26-2.11), and >65 years: RR=1.68 (1.22-2.30). The relative risk of diabetes in different gender groups was about 2 (males: RR=2.08 [1.27-3.40]; females: RR=1.99 [1.47-2.80]). The risk of diabetes increased 1.17-fold (1.02-1.34) after COVID-19 infection compared to patients with general upper respiratory tract infections. Patients with severe COVID-19 were at higher risk (RR=1.67 [1.25-2.23]) of diabetes after COVID-19. The risk (RR=1.95 [1.85-2.06]) of diabetes was highest in the first 3 months after COVID-19. These results remained after taking confounding factors into account. CONCLUSIONS: After COVID-19, patients of all ages and genders had an elevated incidence and relative risk for a new diagnosis of diabetes. Particular attention should be paid during the first 3 months of follow-up after COVID-19 for new-onset diabetes.

Profiling Early Humoral Response to Diagnose Novel Coronavirus Disease (COVID-19).

BACKGROUND: The emergence of coronavirus disease 2019 (COVID-19) is a major healthcare threat. The current method of detection involves a quantitative polymerase chain reaction (qPCR)-based technique, which identifies the viral nucleic acids when present in sufficient quantity. False-negative results can be achieved and failure to quarantine the infected patient would be a major setback in containing the viral transmission. We aim to describe the time kinetics of various antibodies produced against the 2019 novel coronavirus (SARS-CoV-2) and evaluate the potential of antibody testing to diagnose COVID-19. METHODS: The host humoral response against SARS-CoV-2, including IgA, IgM, and IgG response, was examined by using an ELISA-based assay on the recombinant viral nucleocapsid protein. 208 plasma samples were collected from 82 confirmed and 58 probable cases (qPCR negative but with typical manifestation). The diagnostic value of IgM was evaluated in this cohort. RESULTS: The median duration of IgM and IgA antibody detection was 5 (IQR, 3-6) days, while IgG was detected 14 (IQR, 10-18) days after symptom onset, with a positive rate of 85.4%, 92.7%, and 77.9%, respectively. In confirmed and probable cases, the positive rates of IgM antibodies were 75.6% and 93.1%, respectively. The detection efficiency by IgM ELISA is higher than that of qPCR after 5.5 days of symptom onset. The positive detection rate is significantly increased (98.6%) when combining IgM ELISA assay with PCR for each patient compared with a single qPCR test (51.9%). CONCLUSIONS: The humoral response to SARS-CoV-2 can aid in the diagnosis of COVID-19, including subclinical cases.

Stress and psychological impact of the COVID-19 outbreak on the healthcare staff at the fever clinic of a tertiary general hospital in Beijing: a cross-sectional study.

BACKGROUND: It is important to maintain the psychological well-being of front-line healthcare staff during the coronavirus disease 2019 (COVID-19) pandemic. AIMS: To examine COVID-19-related stress and its immediate psychological impact on healthcare staff. METHOD: All healthcare staff working in the fever clinic, from 20 January 2020 to 26 March 2020, of a tertiary general hospital were enrolled. Stress management procedures were in place to alleviate concerns about the respondents' own health and the health of their families, to help them adjust their work and to provide psychological support via a hotline. Qualitative interviews were undertaken and the Sources of Distress and the Impact of Event Scale-Revised (IES-R) were administered. RESULTS: Among the 102 participants (25 males; median age 30 years, interquartile range (IQR) = 27-36), the median IES-R total score was 3 (IQR = 0-8), and 6 participants (6.0%) scored above the cut-off on the IES-R (≥20). Safety and security were acceptable or better for 92 (90.2%) participants. The top four sources of distress were worry about the health of one's family/others at 0.88 (IQR = 0.25-1.25), worry about the virus spread at 0.50 (IQR = 0.00-1.00), worry about changes in work at 0.50 (IQR = 0.00-1.00) and worry about one's own health at 0.25 (IQR = 0.25-0.75). There was a moderate correlation between the IES-R score and the Sources of Distress score (rho = 0.501, P = 0.001). CONCLUSIONS: The stress levels of healthcare staff in the fever clinic during the COVID-19 epidemic were not elevated. Physio-psychosocial interventions, including fulfilment of basic needs, activation of self-efficacy and psychological support, are helpful and worth recommending in fighting COVID-19.

Clinical features of novel coronavirus infection patients and a feasible screening procedure

Objective: To study the clinical characteristics of novel coronavirus pneumonia (COVID-19) patients and make a feasible screening process in fever clinic.

Antiphospholipid Antibodies in Critically Ill Patients With COVID-19.

OBJECTIVE: Coagulopathy is one of the characteristics observed in critically ill patients with coronavirus disease 2019 (COVID-19). Antiphospholipid antibodies (aPLs) contribute to coagulopathy, though their role in COVID-19 remains unclear. This study was undertaken to determine the prevalence and characteristics of aPLs in patients with COVID-19. METHODS: Sera collected from 66 COVID-19 patients who were critically ill and 13 COVID-19 patients who were not critically ill were tested by chemiluminescence immunoassay for anticardiolipin antibodies (aCLs), anti-ß2 -glycoprotein I (anti-ß2 GPI) (IgG, IgM, and IgA), and IgG anti-ß2 GPI-domain 1 (anti-ß2 GPI-D1) and IgM and IgG anti-phosphatidylserine/prothrombin (anti-PS/PT) antibodies were detected in the serum by enzyme-linked immunosorbent assay. RESULTS: Of the 66 COVID-19 patients in critical condition, aPLs were detected in 31 (47% ). Antiphospholipid antibodies were not present among COVID-19 patients who were not in critical condition. The IgA anti-ß2 GPI antibody was the most commonly observed aPL in patients with COVID-19 and was present in 28.8% (19 of 66) of the critically ill patients, followed by IgA aCLs (17 of 66, or 25.8%) and IgG anti-ß2 GPI (12 of 66, or 18.2%). For multiple aPLs, IgA anti-ß2 GPI + IgA aCLs was the most common antibody profile observed (15 of 66, or 22.7%), followed by IgA anti-ß2 GPI + IgA aCL + IgG anti-ß2 GPI (10 of 66, or 15.2%). Antiphospholipid antibodies emerge ~35-39 days after disease onset. A dynamic analysis of aPLs revealed 4 patterns based on the persistence or transient appearance of the aPLs. Patients with multiple aPLs had a significantly higher incidence of cerebral infarction compared to patients who were negative for aPLs (P = 0.023). CONCLUSION: Antiphospholipid antibodies were common in critically ill patients with COVID-19. Repeated testing demonstrating medium to high titers of aPLs and the number of aPL types a patient is positive for may help in identifying patients who are at risk of developing cerebral infarction. Antiphospholipid antibodies may be transient and disappear within a few weeks, but in genetically predisposed patients, COVID-19 may trigger the development of an autoimmune condition similar to the antiphospholipid syndrome (APS), referred to as "COVID-19-induced APS-like syndrome." Long-term follow-up of COVID-19 patients who are positive for aPLs would be of great importance in understanding the pathogenesis of this novel coronavirus.

Identifying the effects of an upgraded 'fever clinic' on COVID-19 control and the workload of emergency department: retrospective study in a tertiary hospital in China.

OBJECTIVE: COVID-19 started spreading widely in China in January 2020. Outpatient fever clinics (FCs), instituted during the SARS epidemic in 2003, were upgraded to serve for COVID-19 screening and prevention of disease transmission in large tertiary hospitals in China. FCs were hoped to relieve some of the healthcare burden from emergency departments (EDs). We aimed to evaluate the effect of upgrading the FC system on rates of nosocomial COVID-19 infection and ED patient attendance at Peking Union Medical College Hospital (PUMCH). DESIGN: A retrospective cohort study. PARTICIPANTS: A total of 6365 patients were screened in the FC. METHODS: The FC of PUMCH was upgraded on 20 January 2020. We performed a retrospective study of patients presenting to the FC between 12 December 2019 and 29 February 2020. The date when COVID-19 was declared an outbreak in Beijing was 20 January 2020. Two groups of data were collected and subsequently compared with each other: the first group of data was collected within 40 days before 20 January 2020; the second group of data was collected within 40 days after 20 January 2020. All necessary data, including patient baseline information, diagnosis, follow-up conditions and the transfer records between the FC and ED, were collected and analysed. RESULTS: 6365 patients were screened in the FC, among whom 2912 patients were screened before 21 January 2020, while 3453 were screened afterward. Screening results showed that upper respiratory infection was the major disease associated with fever. After the outbreak of COVID-19, the number of patients who were transferred from the FC to the ED decreased significantly (39.21% vs 15.75%, p<0.001), and patients generally spent more time in the FC (55 vs 203 min, p<0.001), compared with before the outbreak. For critically ill patients waiting for their screening results, the total length of stay in the FC was 22 min before the outbreak, compared with 442 min after the outbreak (p<0.001). The number of in-hospital deaths of critically ill patients in the FC was 9 out of 29 patients before the outbreak and 21 out of 38 after the outbreak (p<0.05). Nineteen cases of COVID-19 were confirmed in the FC during the period of this study. However, no other patients nor any healthcare providers were cross-infected. CONCLUSION: The workload of the FC increased significantly after the COVID-19 outbreak. New protocols regarding the use of FC likely helped prevent the spread of COVID-19 within the hospital. The upgraded FC also reduced the burden on the ED.

Clinical features of 2019 novel coronavirus infection in Beijing.

BACKGROUND: A new coronavirus pneumonia caused by 2019 new coronavirus (2019-nCoV) is spreading in China. Here we summarized the patients we accepted in the fever outpatient department. METHODS: Patients with epidemiologic history, respiratory symptoms or fever were required to go to the fever clinic for screening. Patients were finally laboratory-confirmed 2019-nCoV infection by real-time reverse transcription-polymerase chain reaction (RT-PCR) using nasal and pharyngeal swabs. Epidemiologic features, clinical presentation, laboratory findings and image features were collected and analyzed. RESULTS: Totally, 16 patients were diagnosed as 2019-nCoV infection. The median age of the patients was 39.00 (35.25-55.75) years old, and the ratio of men and women was 9:7. Fifteen (93.75%) patients had clear epidemiologic history. The most common symptoms of the patients were fever (87.50%) and cough (n=8, 50.00%). The mean white blood cell count in the patients was (4.97±1.71) ×109/L, and it was lower than 4.00×109/L in 4 (25.00%) patients. The median neutrophil and lymphocyte count were 2.70 (1.84-3.27) ×109/L and (1.52±0.53) ×109/L respectively. The mean C-reactive protein level was 19.11±17.39 mg/L. Patients were likely had normal procalcitonin, creatinine, alanine aminotransferase, creatine kinase and lactate dehydrogenase levels at diagnosis. Fourteen (87.50%) patients had pneumonia in chest CT scan. CONCLUSIONS: No specific symptom was helpful in the diagnosis of 2019-nCoV infection, but relatively low WBC and lymphocyte level might be suggestive to diagnosis. Most patients had fever and pneumonia, however, there were indeed some patients without fever and pneumonia. Screening procedure should not only focus on fever patients. The origin, transmission route, key targets of the virus and mechanism of infection deserved more studies.

Characteristics of respiratory virus infection during the outbreak of 2019 novel coronavirus in Beijing.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is spreading. Here, we summarized the composition of pathogens in fever clinic patients and analyzed the characteristics of different respiratory viral infections. METHODS: Retrospectively collected patients with definite etiological results using nasal and pharyngeal swabs in a fever clinic. RESULTS: Overall, 1860 patients were screened, and 136 patients were enrolled. 72 (52.94%) of them were diagnosed as influenza (Flu) A virus infection. 32 (23.53%) of them were diagnosed as Flu B virus infection. 18 (13.24%) and 14 (10.29%) of them were diagnosed as COVID-19 and respiratory syncytial virus (RSV) infections, respectively. The COVID-19 group had a higher rate of contact with the epidemic area within 14 days and of clustering onset than other groups. Fever was the most common symptom in these patients. The ratio of fever to the highest temperature was higher in Flu A virus infection patients than in COVID-19 patients. COVID-19 patients had a lower white blood cell count and neutrophil count than Flu A virus and RSV infection groups, but higher lymphocyte count than Flu A and B virus infection groups. The COVID-19 group (83.33%) had a higher rate of pneumonia in chest CT scans than Flu A and B virus infection groups. CONCLUSIONS: Influenza viruses accounted for a large proportion of respiratory virus infection even during the epidemic of COVID-19 in Beijing. No single symptom or laboratory finding was suggestive of a specific respiratory virus; however, epidemic history was significant for the screening of COVID-19.

Significance of serology testing to assist timely diagnosis of SARS-CoV-2 infections: implication from a family cluster.

Confirmative diagnosis of SARS-CoV-2 infections has been challenged due to unsatisfactory positive rate of molecular assays. Here we identified a family cluster of SARS-CoV-2 infections, with five of six family members were SARS-CoV-2-specific immunoglobin serology testing positive, while molecular assays only detected two of this five patients even repeated twice. We comprehensively analyzed this familial cluster of cases based on the clinical characteristics, chest CT images, SARS-CoV-2 molecular detection results, and serology testing results. At last, two patients were diagnosed with COVID-19, two were suspected of COVID-19, and two were considered close contacts. Our results emphasized the significance of serology testing to assist timely diagnosis of SARS-CoV-2 infections, especially for COVID-19 close contacts screening.