ABSTRACT
Since the initial detection of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant (B.1.1.529) in November 2021 in South Africa, it has caused a rapid increase in infections globally. The Omicron variant encodes 37 amino acid substitutions in its spike protein, and early reports have provided evidence for extensive immune escape and reduced vaccine effectiveness. We assessed serum neutralizing activity in sera from Delta infection following vaccination of CoronaVac or ZF2001 and Delta infection only against SARS-CoV-2 Wuhan-Hu-1 (WA1), Beta, Delta, and Omicron. We found that sera from Delta infection only could neutralize WA1 and Delta pseudoviruses but nearly completely lost capacity to neutralize Beta and Omicron pseudoviruses. However, Delta infection following vaccination resulted in a significant increase of serum neutralizing activity against WA1, Beta, and Omicron. This study demonstrates that breakthrough infection of Delta in previously vaccinated individuals substantially induced high potency humoral immune response against the Omicron variant and other emerged variants.
Subject(s)
Coronavirus InfectionsABSTRACT
Determining the longevity of natural immunity after SARS-CoV-2 infection is critical for understanding immune protection and optimizing vaccine design. Over six months have been passed since the emergence of COVID-19 in China. We evaluated humoral and cellular responses in 418 patients six months after infection. 95.9% and 98.1% of the patients maintained SARS-CoV-2-specific IgG and neutralizing antibodies. All severe patients were positive for IgG and neutralizing antibodies and had significantly higher titers than mild and moderate patients as well as asymptomatic individuals. The patients had a more robust SARS-CoV-2-specific CD4+ T cell response than CD8+ T cells six months after infection. Unexpectedly, sustained immune activation was observed, which displayed as the evaluated proinflammatory monocytes, non-classical NK cells, CD4+ Treg cells, and activated CD4+ T cells. Our findings indicate that SARS-CoV-2 gives rise to persisting and robust protective immunity, which provides a promising sign for prevention from reinfection and vaccination strategy.Funding: This work was supported by grants from the Natural Science Foundation of China (81773494 to M.J.M.), the National Major Project for Control and Prevention of Infectious Disease of China (2017ZX10303401-006 to M.J.M.), the Special National Project on Investigation of Basic Resources of China (2019FY101502 to M.J.M.).Conflict of Interest: The authors declare no competing interests.Ethical Approval: All patients provided written informed consent. The study was conducted following the Declaration of Helsinki, and the Institutional Review Board of the Academy of Military Medical Sciences approved the study protocol (IRB number: AF/SC-08/02.46).
Subject(s)
COVID-19ABSTRACT
Recent studies have characterized the single-cell immune landscape of host immune response of coronavirus disease 2019 (COVID-19), specifically focus on the severe condition. However, the immune response in mild or even asymptomatic patients remains unclear. Here, we performed longitudinal single-cell transcriptome sequencing and T cell/B cell receptor sequencing on 3 healthy donors and 10 COVID-19 patients with asymptomatic, moderate, and severe conditions. We found asymptomatic patients displayed distinct innate immune responses, including increased CD56briCD16- NK subset, which was nearly missing in severe condition and enrichment of a new Th2-like cell type/state expressing a ciliated cell marker. Unlike that in moderate condition, asymptomatic patients lacked clonal expansion of effector CD8+ T cells but had a robust effector CD4+ T cell clonal expansion, coincide with previously detected SARS-CoV-2-reactive CD4+ T cells in unexposed individuals. Moreover, NK and effector T cells in asymptomatic patients have upregulated cytokine related genes, such as IFNG and XCL2. Our data suggest early innate immune response and type I immunity may contribute to the asymptomatic phenotype in COVID-19 disease, which could in turn deepen our understanding of severe COVID-19 and guide early prediction and therapeutics.
Subject(s)
COVID-19ABSTRACT
Background: Current information is not enough to recognize the risk factors of clinical deterioration and to make medical decisions in COVID-19 patients. Methods: A retrospective study was performed, with collecting data from medical records of COVID-19 patients in three designated hospitals from January 8, 2020 to May 6, 2020. Clinical data were analyzed between the deteriorated and the non-deteriorated patients, which was defined as either a increase of 2 categories on the modified 6-category ordinal scale, or a decline of PaO2-to-FIO2 ratio more than 100mmHg. Results: Total 238 patients with COVID-19 were selected, where 31 were deteriorated and 207 were non-deteriorated. In the deterioration group, the case fatality rate was up to 41.9%. Compared with non-deteriorated patients, the deteriorated were older (65.8[IQR 54.3-72.3] vs 54.4[41.0-66.1], p=0.004) and were more likely to have chronic medical illnesses (17[54.8%]) vs 92[44.4%]). Multivariable regression showed that three variables, neutrophil-lymphocyte ratio (NLR)≥3.66 (OR, 9.85; 95% CI, 1.68-57.57), hyponatremia (OR, 8.35; 95% CI, 1.74-40.16), and presence of ground-glass opacities with consolidation (OR, 5.84; 95% CI, 1.24-27.49) were associated with increased odds of clinical deterioration. The variable that inspiring air or traditional oxygen therapy only within 72 hours after admission, indicated a decreased odd of illness progression (OR, 0.075; 95% CI, 0.012–0.465).Conclusions: COVID-19 patients with clinical deterioration had more common extra-pulmonary organ impair in early stage and high case fatality rate. Three factors, NLR ≥3.66, hyponatremia and presence of ground-glass opacities with consolidation were determined as high risk factors in deterioration.
Subject(s)
COVID-19 , HyponatremiaABSTRACT
Background: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has now spread worldwide. This study aimed to provide a reference for comprehensive treatment, personal protection, and team management of patients with critical COVID-19. Methods: The study included critical COVID-19 cases at a single centre in Wuhan, China. We retrospectively analysed data on symptoms, laboratory tests, radiology findings, treatment, and outcomes. Air samples and environmental surface swabs in the isolation ward were tested for SARS-CoV-2.Results: Fourteen critically ill patients (mean age 62.1 years) were treated between February 4, 2020 and April 6, 2020. Less than half had underlying diseases, including hypertension (n=6, 42.9%) and diabetes (n=4, 28.6%). Laboratory tests showed decreased lymphocyte levels and increased serum ferritin and inflammatory cytokine levels. More than half of the patients received antiviral drugs, including lopinavir/ritonavir (n=10; 71.4%) and arbidol (n=6, 42.9%). Eight patients (57.1%) received convalescent plasma, and 12 (85.7%) received systemic glucocorticoids. Eleven (78.6%) received high-flow nasal cannula oxygen therapy, five (35.7%) received non-invasive positive pressure ventilation, seven (50.0%) received invasive positive pressure ventilation, and three (21.4%) received extracorporeal membrane oxygenation. By April 6, 2020, nine (64.3%) patients were discharged, four remained in hospital, and one had died. All air samples tested negative for SARS-CoV-2. Of 128 environmental surface swabs, one gastric tube swab and one anal tube swab were positive for SARS-CoV-2. All oropharyngeal swabs taken from medical staff tested negative for SARS-CoV-2.Conclusions: Individualised comprehensive treatment, appropriate personal protection, and teamwork may improve the prognosis in patients with COVID-19 who are critically ill.
Subject(s)
Stomach Neoplasms , Diabetes Mellitus , Critical Illness , Hypertension , COVID-19ABSTRACT
Background: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has now spread worldwide. This study aimed to provide a reference for comprehensive treatment, personal protection, and team management of patients with critical COVID-19. Methods: The study included critical COVID-19 cases at a single centre in Wuhan, China. We retrospectively analysed data on symptoms, laboratory tests, radiology findings, treatment, and outcomes. Air samples and environmental surface swabs in the isolation ward were tested for SARS-CoV-2.Results: Fourteen critically ill patients (mean age 62.1 years) were treated between February 4, 2020 and April 6, 2020. Less than half had underlying diseases, including hypertension (n=6, 42.9%) and diabetes (n=4, 28.6%). Laboratory tests showed decreased lymphocyte levels and increased serum ferritin and inflammatory cytokine levels. More than half of the patients received antiviral drugs, including lopinavir/ritonavir (n=10; 71.4%) and arbidol (n=6, 42.9%). Eight patients (57.1%) received convalescent plasma, and 12 (85.7%) received systemic glucocorticoids. Eleven (78.6%) received high-flow nasal cannula oxygen therapy, five (35.7%) received non-invasive positive pressure ventilation, seven (50.0%) received invasive positive pressure ventilation, and three (21.4%) received extracorporeal membrane oxygenation. By April 6, 2020, nine (64.3%) patients were discharged, four remained in hospital, and one had died. All air samples tested negative for SARS-CoV-2. Of 128 environmental surface swabs, one gastric tube swab and one anal tube swab were positive for SARS-CoV-2. All oropharyngeal swabs taken from medical staff tested negative for SARS-CoV-2.Conclusions: Individualised comprehensive treatment, appropriate personal protection, and teamwork may improve the prognosis in patients with COVID-19 who are critically ill.
Subject(s)
Stomach Neoplasms , Diabetes Mellitus , Critical Illness , Hypertension , COVID-19ABSTRACT
Background: Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2), a novel betacoronavirus, has caused an outburst of pneumonia cases in Wuhan, China. We report the production of specific IgM and IgG antibodies after the infection of SARS-CoV-2 and its implication for the diagnosis, pathology and the course of the disease as well as the recurrence of positive nucleic acid tests after discharge. Methods: Test results for SARS-CoV-2 IgM and IgG antibodies of 221 confirmed COVID-19 patients were retrospectively examined, and their clinical data were collected and analyzed based on various subgroups. SARS-CoV-2 IgM and IgG antibodies were determined with the chemiluminescence method. Findings: The concentration (S/CO) of SARS-CoV-2 IgM and IgG antibodies peaked on day 19-21 after symptom onset, with a median of 17.38 (IQR 4.39-36.4) for IgM and 5.59 (IQR 0.73-13.65) for IgG. Detection rates reached highest on day 16-18 and day 19-21 for IgM and IgG, which were 73.6% and 98.6%, respectively, with significantly higher concentration of IgG in critically ill patients than in those with mild to moderate disease (P=0.027). The concentration of the antibodies on day 16-21 is not correlated with the course or outcome of the disease (Spearman r < 0.20, P > 0.05). Nasopharyngeal swabs revealed positive SARS-CoV-2 RNA in up to 52.7% of recovered patients after discharge, whose IgG proved to be significantly lower than that of those with negative RNA results (P = 0.009). IgG and IgM were tested twice within 14 days after discharge with a 7-day interval, and the second testing of these antibodies displayed a decrease in concentration of 21.2% (IQR, 11.2%34.48%) for IgG and 23.05% (IQR, -27.96%46.13%) for IgM, without statistical significance between the patients with re-detectable positive RNA results and those with negative RNA results after discharge. However, those with positive results experienced a count decrease in lymphocyte subsets. Interpretation: The concentration of SARS-CoV-2 IgM and IgG antibodies peaked on day 19-21 after symptom onset, and antibody testing on day 16-21 is associated with increased detection rates, but the antibody concentration does not affect the course and outcome of the infection. Recovering patients with re-detectable positive SARS-CoV-2 RNA displayed lower concentration of IgG, but the downward trend of IgG during recovery indicated its limited duration of protection, and the protective effect of IgG remains to be investigated.
Subject(s)
COVID-19 , Critical Illness , Pneumonia , Severe Acute Respiratory SyndromeABSTRACT
Background: Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has recently spread worldwide partly through environmental and airborne contamination. The number of patients requiring intensive care unit (ICU)-based healthcare services exceeds the available negative-pressure isolation ICU room capacity. Some general wards of Wuhan hospitals have been temporarily converted into COVID-19 ICU wards and pose safety concerns. We explored the safety of these temporary COVID-19 ICU wards.Methods: Fifteen air samples and 128 environmental surface swabs were collected from 14 patients in 4 departments with temporary COVID-19 ICU wards. Quantitative real-time PCR (RT-PCR) methods confirmed the existence of COVID-19 pathogens.Results: Four of the 15 air samples were obtained during aerosol-generating medical procedures (1 tracheostomy, 1 high-flow nasal cannula [HFNC], 1 HFNC+nebulization, 1 non-invasive positive pressure ventilation). Five patients were administered invasive positive pressure ventilation through tracheostomy. All air samples tested negative for SARS-CoV-2 by RT-PCR. Viruses were detected on the surface of a patient’s gastric tube, and an anal tube swab tested positive. Five days later, the anal swab of the patient remained positive, although viral RNA of the nasopharyngeal swap turned negative.Conclusions: Establishing temporary isolation COVID-19 ICU wards is a safe and effective method to increase surge capacity in a hospital. SARS-CoV-2 sheds from the enteric canal after viral clearance in the respiratory tract. Reinforcing disinfection of tubes and circuits given to the patients is essential in COVID-19 isolation wards to decrease nosocomial transmission.
Subject(s)
COVID-19 , Stomach NeoplasmsABSTRACT
Background The outbreak of a novel coronavirus (2019-nCoV)–infected pneumonia (NCIP) is currently ongoing in China. Most of the critically ill patients received high flow nasal cannula (HFNC). However, the experience of HFNC in this population is lacking. Methods We retrospectively collected the NCIP patients who received HFNC in two hospital of Chongqing, China from January 1st to February 18th, 2020. The clinical characteristics were collected. Patients who required upgrading to noninvasive ventilation (NIV) were defined as HFNC failure. Results We enrolled 17 patients in this study. Of them, 7 patients (41%) experienced HFNC failure (6 required upgrading to NIV, and one to NIV and further to intubation). The HFNC failure rate was 0% (0/6), 57% (4/7) and 75% (3/4) (p =0.03 between 3 groups) in patients with PaO2/FiO2 >200, 150-200, and <150 mmHg, respectively. In the successful patients, the respiratory rate, heart rate and PaO2/FiO2 significantly improved from initiation to termination of HFNC (27±3 vs. 21±2 breaths/min, p <0.01; 86±15 vs. 76±12 beats/min, p =0.03; and 213±49 vs. 299±125 mmHg, p =0.04, respectively). However, in the unsuccessful patients, the respiratory rate and PaO2/FiO2 significantly deteriorated (22±3 vs. 25±3 breaths/min, p =0.04; and 160±27 vs. 105±24 mmHg, p =0.01, respectively). When they upgraded to NIV, the PaO2/FiO2 improved after 1-2 h of NIV (105±24 vs. 202±111 mmHg, p =0.04). In the total cohort, only PaO2/FiO2 at baseline was lower in unsuccessful patients than that in successful ones (213±49 vs. 160±27 mmHg, p =0.02). Conclusions This study firstly provides the experience of how to use HFNC in patients with NCIP. Patients with lower PaO2/FiO2 were more likely to experience HFNC failure. Among the failure patients, most of them can avoid intubation when they were ungraded to NIV.