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1.
iScience ; 25(2): 103743, 2022 Feb 18.
Article in English | MEDLINE | ID: covidwho-1611783

ABSTRACT

Information concerning the longevity of immunity to SARS-CoV-2 following natural infection may have considerable implications for durability of immunity induced by vaccines. Here, we monitored the SARS-CoV-2 specific immune response in COVID-19 patients followed up to 15 months after symptoms onset. Following a peak at day 15-28 postinfection, the IgG antibody response and plasma neutralizing titers gradually decreased over time but stabilized after 6 months. Compared to G614, plasma neutralizing titers were more than 8-fold lower against variants Beta, Gamma, and Delta. SARS-CoV-2-specific memory B and T cells persisted in the majority of patients up to 15 months although a significant decrease in specific T cells, but not B cells, was observed between 6 and 15 months. Antiviral specific immunity, especially memory B cells in COVID-19 convalescent patients, is long-lasting, but some variants of concern may at least partially escape the neutralizing activity of plasma antibodies.

2.
J Allergy Clin Immunol ; 149(1): 65-75.e8, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1474660

ABSTRACT

BACKGROUND: Young adults are now considered major spreaders of coronavirus disease 2019 (COVID-19) disease. Although most young individuals experience mild to moderate disease, there are concerns of long-term adverse health effects. The impact of COVID-19 disease and to which extent population-level immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exists in young adults remain unclear. OBJECTIVE: We conducted a population-based study on humoral and cellular immunity to SARS-CoV-2 and explored COVID-19 disease characteristics in young adults. METHODS: We invited participants from the Swedish BAMSE (Barn [Children], Allergy Milieu, Stockholm, Epidemiology) birth cohort (age 24-27 years) to take part in a COVID-19 follow-up. From 980 participants (October 2020 to June 2021), we here present data on SARS-CoV-2 receptor-binding domain-specific IgM, IgA, and IgG titers measured by ELISA and on symptoms and epidemiologic factors associated with seropositivity. Further, SARS-CoV-2-specific memory B- and T-cell responses were detected for a subpopulation (n = 108) by ELISpot and FluoroSpot. RESULTS: A total of 28.4% of subjects were seropositive, of whom 18.4% were IgM single positive. One in 7 seropositive subjects was asymptomatic. Seropositivity was associated with use of public transport, but not with sex, asthma, rhinitis, IgE sensitization, smoking, or body mass index. In a subset of representative samples, 20.7% and 35.0% had detectable SARS-CoV-2 specific B- and T-cell responses, respectively. B- and T-cell memory responses were clearly associated with seropositivity, but T-cell responses were also detected in 17.2% of seronegative subjects. CONCLUSIONS: Assessment of IgM and T-cell responses may improve population-based estimations of SARS-CoV-2 infection. The pronounced surge of both symptomatic and asymptomatic infections among young adults indicates that the large-scale vaccination campaign should be continued.


Subject(s)
COVID-19/immunology , Immunity, Cellular , Immunity, Humoral , SARS-CoV-2/immunology , T-Lymphocytes/immunology , Adult , Antibodies, Viral/immunology , Female , Follow-Up Studies , Humans , Male , Prospective Studies , Sweden
3.
Sci Rep ; 10(1): 14186, 2020 08 25.
Article in English | MEDLINE | ID: covidwho-1434143

ABSTRACT

Infections cause varying degrees of haemostatic dysfunction which can be detected by clot waveform analysis (CWA), a global haemostatic marker. CWA has been shown to predict poor outcomes in severe infections with disseminated intravascular coagulopathy. The effect of less severe bacterial and viral infections on CWA has not been established. We hypothesized that different infections influence CWA distinctively. Patients admitted with bacterial infections, dengue and upper respiratory tract viral infections were recruited if they had an activated partial thromboplastin time (aPTT) measured on admission. APTT-based CWA was performed on Sysmex CS2100i automated analyser using Dade Actin FSL reagent. CWA parameters [(maximum velocity (min1), maximum acceleration (min2) and maximum deceleration (max2)] were compared against control patients. Infected patients (n = 101) had longer aPTT than controls (n = 112) (34.37 ± 7.72 s vs 27.80 ± 1.59 s, p < 0.001), with the mean (± SD) aPTT longest in dengue infection (n = 36) (37.99 ± 7.93 s), followed by bacterial infection (n = 52) (33.96 ± 7.33 s) and respiratory viral infection (n = 13) (29.98 ± 3.92 s). Compared to controls (min1; min2; max2) (5.53 ± 1.16%/s; 0.89 ± 0.19%/s2; 0.74 ± 0.16%/s2), bacterial infection has higher CWA results (6.92 ± 1.60%/s; 1.04 ± 0.28%/s2; 0.82 ± 0.24%/s2, all p < 0.05); dengue infection has significantly lower CWA values (3.93 ± 1.32%/s; 0.57 ± 0.17%/s2; 0.43 ± 0.14%/s2, all p < 0.001) whilst respiratory virus infection has similar results (6.19 ± 1.32%/s; 0.95 ± 0.21%/s2; 0.73 ± 0.18%/s2, all p > 0.05). CWA parameters demonstrated positive correlation with C-reactive protein levels (min1: r = 0.54, min2: r = 0.44, max2: r = 0.34; all p < 0.01). Different infections affect CWA distinctively. CWA could provide information on the haemostatic milieu triggered by infection and further studies are needed to better define its application in this area.


Subject(s)
Bacterial Infections/blood , Hemostasis , Partial Thromboplastin Time/methods , Virus Diseases/blood , Aged , Aged, 80 and over , C-Reactive Protein/analysis , Dengue/blood , Disseminated Intravascular Coagulation/blood , Disseminated Intravascular Coagulation/etiology , Elective Surgical Procedures , Female , Humans , Male , Middle Aged , Procalcitonin/blood , Respiratory Tract Infections/blood
5.
Blood ; 136(Supplement 1):25-26, 2020.
Article in English | PMC | ID: covidwho-1338960

ABSTRACT

IntroductionAn increasing number of evidence have reported the association of COVID-19 with increased incidence of thrombotic events. High incidences were initially reported in critically ill COVID-19 patients, but subsequently an increased incidence was also noticed in non-critically ill general ward patients. This has led to a universal recommendation of thromboprophylaxis for all COVID-19 patients by ASH and ISTH. As the data on COVID-19 and thrombosis continue to develop and evolve, we examined the data in two aspects. Firstly, other non-SARS-CoV-2 viral respiratory infections have also been reported to be associated with thrombotic events, be it arterial or venous. Thus, we aimed to compare the thrombotic rates between these two groups of patients directly to hopefully ascertain the actual thrombotic tendency in COVID-19 infections. Secondly, global hemostatic assays such as thromboelastogram and clot waveform analysis (CWA) have been used to demonstrate hypercoagulability in COVID-19 patients, albeit in a small group of patients and only in the critically ill. Incorporating these laboratory results into the management of thromboprophylaxis in COVID-19 is an attractive notion but more data and studies are definitely needed. Here, we evaluate the dynamic changes of hemostatic assays in patients with COVID-19 to better understand the overall coagulation profiles of COVID-19 infection.MethodsWe performed a single center, retrospective cohort study. All consecutive patients admitted to our hospital between 15 January and 10 April 2020 that were tested positive for COVID-19 or other non-SARS-CoV-2 respiratory viruses were included in our study. The main coagulation assays studied were prothrombin time and activated partial thromboplastin time and its associated CWA, min1, min2 and max2.FindingsWe included a total of 181 COVID-19 patients and 165 patients with non-SARS-CoV-2 respiratory viral infections. The respiratory viruses were rhinovirus (n=65), influenza A and B (n=46), adenovirus (n=13), human coronavirus 229E/NL63/OC43 (n=15), human enterovirus (n=3), metapneumovirus (n=6), parainfluenza virus 1 to 4 (n=11), respiratory syncytial virus (n=6) and human bocavirus 1 to 4 (n=0). The median age of COVID-19 patients was 37 (interquartile range [IQR], 30.5-51 years) versus 35 (IQR, 29-51.5) in the non-SAR-CoV-2 respiratory viruses group (P=0.12). Comorbidities, assessed by Charlson score, was also not statistically different between both groups (median score 0 (IQR, 0-1) in both groups, P=0.39). Majority of our patients had relatively mild infection as reflected by the low proportions of them requiring oxygen supplementation (11.0% in COVID-19 vs 4.8% in non-SARS-COV-2, P=0.035). COVID-19 patients had longer hospital stay (7 days (IQR, 5.5-13) vs 3 days (IQR, 2-3), P<0.001) and more required ICU support (5.0% vs 1.2%, P=0.04). Mortality rate was low in both groups. We reported two (1.0 event/1000-hospital-days) and one (1.8 event/1000-hospital-day) thrombotic events amongst COVID-19 group and non-SARS-COV-2 group respectively (P=0.63). All were myocardial infarction and occurred in intensive care unit. No venous thrombotic event was noted. There was no significant difference in all the coagulation parameters throughout the course of mild COVID-19 infection (Table 1). However, CWA parameters were significantly higher in severe COVID-19 infection compared with mild disease (min1: 6.48%/s vs 5.05%/s, P<0.001;min2: 0.92%/s2 vs 0.74%/s2, P=0.033), suggesting hypercoagulability in severe COVID-19 infection (Table 2 and Figure 1). We also observed that critically ill COVID-19 patients had higher absolute CWA parameters as compared to non-SARS-CoV-2 patients, albeit in small number of patients (Table 3).ConclusionThe thrombotic rates were low in both groups and did not differ significantly between COVID-19 and Non-SARS-CoV-2 patients. Nonetheless, our analysis of hemostatic parameters demonstrated hypercoagulability in COVID-19 as a dynamic process with the risk highest when the patients are critically ill. These c anges in hemostasis could be detected by CWA. With our findings, we suggest that a more individualized thromboprophylaxis approach, considering clinical and laboratory factors, is probably preferred over universal pharmacological thromboprophylaxis for all hospitalized COVID-19 patients and warrants further research.

7.
Med (N Y) ; 2(3): 281-295.e4, 2021 03 12.
Article in English | MEDLINE | ID: covidwho-1078082

ABSTRACT

BACKGROUND: Monitoring the adaptive immune responses during the natural course of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection provides useful information for the development of vaccination strategies against this virus and its emerging variants. We thus profiled the serum anti-SARS-CoV-2 antibody (Ab) levels and specific memory B and T cell responses in convalescent coronavirus disease 2019 (COVID-19) patients. METHODS: A total of 119 samples from 88 convalescent donors who experienced mild to critical disease were tested for the presence of elevated anti-spike and anti-receptor binding domain Ab levels over a period of 8 months. In addition, the levels of SARS-CoV-2 neutralizing Abs and specific memory B and T cell responses were tested in a subset of samples. FINDINGS: Anti-SARS-CoV-2 Abs were present in 85% of the samples collected within 4 weeks after the onset of symptoms in COVID-19 patients. Levels of specific immunoglobulin M (IgM)/IgA Abs declined after 1 month, while levels of specific IgG Abs and plasma neutralizing activities remained relatively stable up to 6 months after diagnosis. Anti-SARS-CoV-2 IgG Abs were still present, although at a significantly lower level, in 80% of the samples collected at 6-8 months after symptom onset. SARS-CoV-2-specific memory B and T cell responses developed with time and were persistent in all of the patients followed up for 6-8 months. CONCLUSIONS: Our data suggest that protective adaptive immunity following natural infection of SARS-CoV-2 may persist for at least 6-8 months, regardless of disease severity. Development of medium- or long-term protective immunity through vaccination may thus be possible. FUNDING: This project was supported by the European Union's Horizon 2020 research and innovation programme (ATAC, no. 101003650), the Italian Ministry of Health (Ricerca Finalizzata grant no. GR-2013-02358399), the Center for Innovative Medicine, and the Swedish Research Council. J.A. was supported by the SciLifeLab/KAW national COVID-19 research program project grant 2020.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Viral , Humans , Immunoglobulin A , Immunoglobulin G , T-Lymphocytes
8.
Sci Rep ; 11(1): 1793, 2021 01 19.
Article in English | MEDLINE | ID: covidwho-1065942

ABSTRACT

COVID-19 caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) and other respiratory viral (non-CoV-2-RV) infections are associated with thrombotic complications. The differences in prothrombotic potential between SARS-CoV-2 and non-CoV-2-RV have not been well characterised. We compared the thrombotic rates between these two groups of patients directly and further delved into their coagulation profiles. In this single-center, retrospective cohort study, all consecutive COVID-19 and non-CoV-2-RV patients admitted between January 15th and April 10th 2020 were included. Coagulation parameters studied were prothrombin time and activated partial thromboplastin time and its associated clot waveform analysis (CWA) parameter, min1, min2 and max2. In the COVID-19 (n = 181) group there were two (1.0 event/1000-hospital-days) myocardial infarction events while one (1.8 event/1000-hospital-day) was reported in the non-CoV-2-RV (n = 165) group. These events occurred in patients who were severely ill. There were no venous thrombotic events. Coagulation parameters did not differ throughout the course of mild COVID-19. However, CWA parameters were significantly higher in severe COVID-19 compared with mild disease, suggesting hypercoagulability (min1: 6.48%/s vs 5.05%/s, P < 0.001; min2: 0.92%/s2 vs 0.74%/s2, P = 0.033). In conclusion, the thrombotic rates were low and did not differ between COVID-19 and non-CoV-2-RV patients. The hypercoagulability in COVID-19 is a highly dynamic process with the highest risk occurring when patients were most severely ill. Such changes in haemostasis could be detected by CWA. In our population, a more individualized thromboprophylaxis approach, considering clinical and laboratory factors, is preferred over universal pharmacological thromboprophylaxis for all hospitalized COVID-19 patients and such personalized approach warrants further research.


Subject(s)
COVID-19/pathology , Thrombophilia/diagnosis , Virus Diseases/pathology , Adult , COVID-19/complications , COVID-19/virology , Female , Humans , Male , Myocardial Infarction/complications , Myocardial Infarction/diagnosis , Partial Thromboplastin Time , Prothrombin Time , Retrospective Studies , Risk Factors , SARS-CoV-2/isolation & purification , Severity of Illness Index , Thrombophilia/complications , Virus Diseases/complications
11.
Infect Dis Poverty ; 9(1): 116, 2020 Aug 24.
Article in English | MEDLINE | ID: covidwho-727301

ABSTRACT

BACKGROUND: In December 2019, an outbreak of coronavirus disease (later named as COVID-19) was identified in Wuhan, China and, later on, detected in other parts of China. Our aim is to evaluate the effectiveness of the evolution of interventions and self-protection measures, estimate the risk of partial lifting control measures and predict the epidemic trend of the virus in the mainland of China excluding Hubei province based on the published data and a novel mathematical model. METHODS: A novel COVID-19 transmission dynamic model incorporating the intervention measures implemented in China is proposed. COVID-19 daily data of the mainland of China excluding Hubei province, including the cumulative confirmed cases, the cumulative deaths, newly confirmed cases and the cumulative recovered cases between 20 January and 3 March 2020, were archived from the National Health Commission of China (NHCC). We parameterize the model by using the Markov Chain Monte Carlo (MCMC) method and estimate the control reproduction number (Rc), as well as the effective daily reproduction ratio- Re(t), of the disease transmission in the mainland of China excluding Hubei province. RESULTS: The estimation outcomes indicate that Rc is 3.36 (95% CI: 3.20-3.64) and Re(t) has dropped below 1 since 31 January 2020, which implies that the containment strategies implemented by the Chinese government in the mainland of China are indeed effective and magnificently suppressed COVID-19 transmission. Moreover, our results show that relieving personal protection too early may lead to a prolonged disease transmission period and more people would be infected, and may even cause a second wave of epidemic or outbreaks. By calculating the effective reproduction ratio, we prove that the contact rate should be kept at least less than 30% of the normal level by April, 2020. CONCLUSIONS: To ensure the pandemic ending rapidly, it is necessary to maintain the current integrated restrict interventions and self-protection measures, including travel restriction, quarantine of entry, contact tracing followed by quarantine and isolation and reduction of contact, like wearing masks, keeping social distance, etc. People should be fully aware of the real-time epidemic situation and keep sufficient personal protection until April. If all the above conditions are met, the outbreak is expected to be ended by April in the mainland of China apart from Hubei province.


Subject(s)
Coronavirus Infections/epidemiology , Coronavirus Infections/transmission , Models, Statistical , Pneumonia, Viral/epidemiology , Pneumonia, Viral/transmission , Betacoronavirus/isolation & purification , COVID-19 , China/epidemiology , Coronavirus Infections/prevention & control , Disease Transmission, Infectious/prevention & control , Humans , Markov Chains , Monte Carlo Method , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , SARS-CoV-2 , Travel
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