Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 27
Filter
1.
Ann Intern Med ; 174(8): 1073-1080, 2021 08.
Article in English | MEDLINE | ID: covidwho-1456490

ABSTRACT

BACKGROUND: Assessing the evolution of SARS-CoV-2 immune response among patients receiving dialysis can define its durability in a highly clinically relevant context because patients receiving dialysis share the characteristics of persons most susceptible to SARS-CoV-2 infection. OBJECTIVE: To evaluate the persistence of SARS-CoV-2 receptor-binding domain (RBD) IgG in seroprevalent patients receiving dialysis. DESIGN: Prospective. SETTING: Nationwide sample from dialysis facilities. PATIENTS: 2215 patients receiving dialysis who had evidence of SARS-CoV-2 infection as of July 2020. MEASUREMENTS: Remainder plasma from routine monthly laboratories was used to measure semiquantitative RBD IgG index value over 6 months. RESULTS: A total of 2063 (93%) seroprevalent patients reached an assay detectable response (IgG index value ≥1). Most (n = 1323, 60%) had responses in July with index values classified as high (IgG ≥10); 1003 (76%) remained within this stratum. Adjusted median index values declined slowly but continuously (July vs. December values were 21 vs. 13; P < 0.001). The trajectory of the response did not vary by age group, sex, race/ethnicity, or diabetes status. Patients without an assay detectable response (n = 137) were more likely to be White and in the younger (18 to 44 years) or older (≥80 years) age groups and less likely to have diabetes and hypoalbuminemia. LIMITATION: Lack of data on symptoms or reverse transcriptase polymerase chain reaction diagnosis, cohort of persons who survived infection, and use of a semiquantitative assay. CONCLUSION: Despite impaired immunity, most seropositive patients receiving dialysis maintained RBD antibody levels over 6 months. A slow and continual decline in median antibody levels over time was seen, but no indication that subgroups with impaired immunity had a shorter-lived humoral response was found. PRIMARY FUNDING SOURCE: Ascend Clinical Laboratories.


Subject(s)
Antibodies, Viral/blood , COVID-19/immunology , Immunoglobulin G/blood , Protein Domains/immunology , Renal Dialysis , Spike Glycoprotein, Coronavirus/immunology , Adolescent , Adult , Aged , Aged, 80 and over , Antibodies, Neutralizing/immunology , Female , Follow-Up Studies , Humans , Male , Middle Aged , Prospective Studies , SARS-CoV-2 , Young Adult
2.
AACE Clin Case Rep ; 7(5): 288-292, 2021.
Article in English | MEDLINE | ID: covidwho-1397116

ABSTRACT

Objective: During the ongoing coronavirus disease 2019 pandemic, procalcitonin (PCT) levels have proven useful in assisting clinicians to diagnose bacterial superinfection. However, in the absence of signs of infection or at the resolution thereof, inappropriately and persistently high PCT levels may suggest and reveal the presence of other pathologies. We report a patient with severe acute respiratory syndrome coronavirus 2 pneumonia with initially elevated PCT levels that persisted during recovery, prompting the diagnosis of medullary thyroid carcinoma (MTC). Methods: A 43-year-old man presented with a 2-day history of fever, sneezing, sore throat, and dry cough. His PCT was 94 ng/mL (normal value, 0.00-0.10 ng/mL), and he was positive for severe acute respiratory syndrome coronavirus 2 RNA. Results: Empirical antibiotic therapy was administered for 7 days, but despite a clinical improvement, serum PCT remained high (84 ng/mL). Serum calcitonin (CTN) was 2120 pg/mL (normal, ≤12 pg/mL). Cytologic examination of thyroid nodules and CTN measurement of the aspiration needle washout confirmed MTC. The patient underwent total thyroidectomy with bilateral cervical lymph node dissection. Lowered CTN (986 pg/mL) and PCT (16 ng/mL) levels were observed 48 hours after surgery. A close follow-up was planned following the results of RET gene analysis. Conclusion: PCT can be a useful biochemical marker of MTC suspicion in patients with inflammatory conditions and persistently elevated PCT, even after resolution. In our case, high levels of PCT in a patient with coronavirus disease 2019 pneumonia without signs of bacterial infection led to MTC diagnosis.

4.
Open Forum Infect Dis ; 8(6): ofab205, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1261053

ABSTRACT

Background: Liver injury in patients with coronavirus disease 2019 (COVID-19) is common and prognostic. Direct viral tropism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for angiotensin-converting enzyme 2 receptors in hepatocytes may be one of the mechanisms of liver injury. We aimed to determine the role of viral persistence of SARS-CoV-2, based on cycle threshold (Ct) value, in liver injury in COVID-19. Methods: This was a territory-wide retrospective cohort study of all public hospitals in Hong Kong. Laboratory-confirmed COVID-19 was identified. Serial liver biochemistries and Ct values of SARS-CoV-2 RNA were analyzed. Results: We identified 7622 COVID-19 patients (mean age, 47 years; 48.2% male) diagnosed from March 24 to January 1, 2021, who had serial liver biochemistries and Ct values. A total of 1363 (17.9%) COVID-19 patients had alanine transferase (ALT)/aspartate aminotransferase (AST) elevations with 2 temporal patterns-early (within first 14 days of symptom onset) and late (>14 days from symptom onset). COVID-19 patients with ALT/AST elevations had a lower Ct value at admission (23 vs 25; P < .001), day 5 (24 vs 26; P < .001), and day 20 (31 vs 32; P < .001) after admission, compared with those without ALT/AST elevations. COVID-19 patients with ALT/AST elevations had a longer duration from first positive to first negative reverse transcription polymerase chain reaction test for SARS-CoV-2 (13 vs 9 days; P < .001). ALT/AST elevation and presence of diabetes were independent risk factors of viral persistence. Conclusions: Liver injury in COVID-19 is linked to a higher SARS-CoV-2 viral load during the early phase of infection, signifying a possible direct viral injury to the liver. Prolonged viral persistence of SARS-CoV-2 is associated with liver injury.

5.
Viruses ; 13(5)2021 05 12.
Article in English | MEDLINE | ID: covidwho-1227067

ABSTRACT

SARS-CoV-2 nasopharyngeal shedding contributes to the spread of the COVID-19 epidemic. Among 3271 COVID-19 patients treated at the Hospital University Institute Méditerranée Infection, Marseille, France from 3 March to 27 April 2020, tested at least twice by qRT-PCR, the median SARS-CoV-2 nasopharyngeal shedding duration was 6 days (range 2-54 days). Compared with short shedders (qRT-PCR positivity < 10 days), 34 (1.04%) persistent shedders (qRT-PCR positivity ≥ 17 days; mean ± SD: 23.3 ± 3.8 days) were significantly older, with associated comorbidities, exhibiting lymphopenia, eosinopenia, increased D-dimer and increased troponin (p < 0.05), and were hospitalized in intensive care unit in 17.7% vs. 1.1% of cases (p < 0.0001). Viral culture was positive in six persistent shedders after day 10, including in one patient after day 17, and no viral co-pathogen was detected in 33 tested patients. Persistent shedders received azithromycin plus hydroxychloroquine ≥ 3 days in 26/34 (76.5%) patients, a figure significantly lower than in short shedders (86.6%) (p = 0.042). Accordingly, mortality was 14.7% vs. 0.5% (p < 0.0001). Persistent shedding was significantly associated with persistent dyspnea and anosmia/ageusia (p < 0.05). In the context of COVID-19 treatment, including treatment with azithromycin plus hydroxychloroquine, the persistence of SARS-CoV-2 nasopharyngeal shedding was a rare event, most frequently encountered in elderly patients with comorbidities and lacking azithromycin plus hydroxychloroquine treatment.


Subject(s)
COVID-19/metabolism , Hydroxychloroquine/pharmacology , Virus Shedding/drug effects , Adult , Aged , Azithromycin/metabolism , Azithromycin/pharmacology , COVID-19/drug therapy , Comorbidity , Drug Therapy, Combination , Female , France/epidemiology , Hospitalization , Humans , Hydroxychloroquine/metabolism , Male , Middle Aged , Nasopharynx , SARS-CoV-2/drug effects , SARS-CoV-2/metabolism , SARS-CoV-2/pathogenicity
6.
J Med Virol ; 93(4): 2227-2233, 2021 04.
Article in English | MEDLINE | ID: covidwho-1217375

ABSTRACT

The coronavirus disease 2019 (COVID-19) is a pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, little is known about the durability of the antibody response during COVID-19 convalescent phase. We investigated the prevalence of anti-SARS-CoV-2 specific antibodies including immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies and the dynamic changes in antibody levels in convalescent COVID-19 patients. A total of 159 blood samples were collected from 52 recovered COVID-19 patients up to six months after symptom onset for longitudinal serological tests. The positive rate of IgG and IgM antibodies was 92.3% and 90.4% in the first month after symptom onset, and the seropositivity of IgG antibody remained high at all follow-up time points, whereas the seropositivity of IgM antibody decreased to 22.73% by the sixth months after symptom onset. The level of IgG antibody was stable, the level of IgM antibody decreased slightly in the early convalescent phase and was detected in only five patients in the sixth month after symptom onset. The level of IgG antibody was higher in the severe and critical group than in the moderate group. The anti-SARS-CoV-2 specific antibodies have a long-term persistence in convalescent COVID-19 patients, whether they have long-term protection need to be further investigated.


Subject(s)
Antibodies, Viral/blood , COVID-19/immunology , SARS-CoV-2/immunology , Adult , Antibodies, Viral/biosynthesis , Antibody Formation , COVID-19/blood , COVID-19/diagnosis , COVID-19 Testing/methods , Female , Humans , Immunoglobulin G/blood , Immunoglobulin M/blood , Male , Middle Aged , Serologic Tests/methods
7.
Turk J Urol ; 47(2): 87-97, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-1170529

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has been predominantly respiratory. This study aimed to evaluate the presence of virus in non-airborne body fluids as transmission vehicles. Medline, EMBASE, and Cochrane Library databases were searched from December 01, 2019, to July 01, 2020, using terms relating to SARS-CoV-2 and non-airborne clinical sample sources (feces, urine, blood, serum, serum, and peritoneum). Studies in humans, of any design, were included. Risk of bias assessment was performed using the Quality Assessment of Diagnostic Accuracy 2 tool. Preferred Reporting Items for Systematic Reviews & Meta-Analyses) guidelines were used for abstracting data. If ≥5 studies reported proportions for the same non-respiratory site, a meta-analysis was conducted using either a fixed or random-effects model, depending on the presence of heterogeneity. A total of 22 studies with 648 patients were included. Most were cross-sectional and cohort studies. The SARS-CoV-2 RNA was most frequently detected in feces. Detectable RNA was reported in 17% of the blood samples, 8% of the serum, 16% in the semen, but rarely in urine. Prevalence of SARS-CoV-2 in non-airborne sites varies widely with a third of non-airborne fluids. Patients with bowel and non-specific symptoms have persistence of virus in feces for upto 2 weeks after symptom resolution. Although there was a very low detection rate in urine, given the more frequent prevalence in blood samples, the presence of SARS-CoV-2 in patients with disrupted urothelium or undergoing urinary tract procedures, is likely to be higher. Healthcare providers need to consider non-airborne transmission and persistence of SARS-CoV-2 in body fluids to enable appropriate precautions to protect healthcare workers and carers.

8.
Microbes Infect ; 23(4-5): 104810, 2021.
Article in English | MEDLINE | ID: covidwho-1135522

ABSTRACT

SARS-CoV-2 as a new global threat has affected global population for one year. Despite the great effort to eradicate this infection, there are still some challenges including different viral presentation, temporal immunity in infected individuals and variable data of viral shedding. We studied 255 COVID-19 suspected individuals to assess the viral shedding duration and also the antibody development against SARS-CoV-2 among the cases. Real Time RT-PCR assay was applied to determine the virus presence and SARS-CoV-2 antibodies were evaluated using SARS-CoV-2 IgM and IgG kits. 113 patients were confirmed for COVID-19 infection. The patients were followed until negative PCR achieved. The median viral shedding among studied population was obtained 34.16 (±17.65) days which was not significantly associated with age, sex and underlying diseases. Shiver and body pain were found in prolonged form of the infection and also patients who had gastrointestinal problems experienced longer viral shedding. Moreover, IgG was present in 84% of patients after 150 days. According to this data, the median viral shedding prolongation was 34.16 days which indicates that 14 days isolation might not be enough for population. In addition, IgG profiling indicated that it is persistent in a majority of patients for nearly 6 months which has brought some hopes in vaccine efficacy and application.


Subject(s)
Antibodies, Viral/blood , COVID-19/blood , Virus Shedding , Adult , COVID-19/virology , Female , Humans , Immunoglobulin G/blood , Immunoglobulin M/blood , Iran , Male , Middle Aged , Polymerase Chain Reaction
9.
Virol Sin ; 36(5): 869-878, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1117772

ABSTRACT

Understanding the persistence of antibody in convalescent COVID-19 patients may help to answer the current major concerns such as the risk of reinfection, the protection period of vaccination and the possibility of building an active herd immunity. This retrospective cohort study included 172 COVID-19 patients who were hospitalized in Wuhan. A total of 404 serum samples were obtained over six months from hospitalization to convalescence. Antibodies in the specimens were quantitatively analyzed by the capture chemiluminescence immunoassays (CLIA). All patients were positive for the anti-SARS-CoV-2 IgM/IgG at the onset of COVID-19 symptoms, and the IgG antibody persisted in all the patients during the convalescence. However, only approximately 25% of patients can detect the IgM antibodies, IgM against N protein (N-IgM) and receptor binding domain of S protein (RBD-IgM) at the 27th week. The titers of IgM, N-IgM and RBD-IgM reduced to 16.7%, 17.6% and 15.2% of their peak values respectively. In contrast, the titers of IgG, N-IgG and RBD-IgG peaked at 4-5th week and reduced to 85.9%, 62.6% and 87.2% of their peak values respectively at the end of observation. Dynamic behavior of antibodies and their correlation in age, gender and severity groups were investigated. In general, the COVID-19 antibody was sustained at high levels for over six months in most of the convalescent patients. Only a few patients with antibody reducing to an undetectable level which needs further attention. The humoral immune response against SARS-CoV-2 infection in COVID-19 patients exhibits a typical dynamic of acquired immunity.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Viral , Convalescence , Hospitalization , Humans , Immunity, Humoral , Retrospective Studies , Spike Glycoprotein, Coronavirus
10.
Clin Microbiol Infect ; 27(2): 258-263, 2021 Feb.
Article in English | MEDLINE | ID: covidwho-1086858

ABSTRACT

OBJECTIVES: To describe the clinical evolution and predictors of symptom persistence during 2 months' follow-up in adults with noncritical coronavirus disease 2019 (COVID-19). METHODS: We performed descriptive clinical follow-up (day (D) 7, D30 and D60) of 150 patients with noncritical COVID-19 confirmed by real-time reverse transcriptase PCR at Tours University Hospital from 17 March to 3 June 2020, including demographic, clinical and laboratory data collected from the electronic medical records and by phone call. Persisting symptoms were defined by the presence at D30 or D60 of at least one of the following: weight loss ≥5%, severe dyspnoea or asthenia, chest pain, palpitations, anosmia/ageusia, headache, cutaneous signs, arthralgia, myalgia, digestive disorders, fever or sick leave. RESULTS: At D30, 68% (103/150) of patients had at least one symptom; and at D60, 66% (86/130) had symptoms, mainly anosmia/ageusia: 59% (89/150) at symptom onset, 28% (40/150) at D30 and 23% (29/130) at D60. Dyspnoea concerned 36.7% (55/150) patients at D30 and 30% (39/130) at D60. Half of the patients (74/150) at D30 and 40% (52/130) at D60 reported asthenia. Persistent symptoms at D60 were significantly associated with age 40 to 60 years old, hospital admission and abnormal auscultation at symptom onset. At D30, severe COVID-19 and/or dyspnoea at symptom onset were additional factors associated with persistent symptoms. CONCLUSIONS: Up to 2 months after symptom onset, two thirds of adults with noncritical COVID-19 had complaints, mainly anosmia/ageusia, dyspnoea or asthenia. A prolonged medical follow-up of patients with COVID-19 seems essential, whatever the initial clinical presentation.


Subject(s)
COVID-19/complications , COVID-19/epidemiology , Adult , Aged , Ageusia/epidemiology , Ageusia/etiology , Anosmia/epidemiology , Anosmia/etiology , Asthenia/epidemiology , Asthenia/etiology , COVID-19/pathology , Dyspnea/epidemiology , Dyspnea/etiology , Female , Follow-Up Studies , France/epidemiology , Humans , Male , Middle Aged , Risk Factors , SARS-CoV-2 , Symptom Assessment
11.
Int Immunopharmacol ; 90: 107271, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-1065224

ABSTRACT

To better understand humoral immunity following SARS-CoV-2 infection, 114 hospitalised COVID-19 patients with antibody monitored over 8 weeks from symptom onset were retrospectively investigated. A total of 445 serum samples were assessed via chemiluminescence immunoassay. Positive rate of virus-specific IgM reached up to over 80% from the second week to the eighth week after symptom onset, then declined quickly to below 30% in the twelfth week. Concentrations of IgG remained high for at least 3 months before subsequently declining. As compared with the non-severe group, serum IgM level from week 3 to week 8 was significantly higher among the patients with severe clinical symptoms (P = 0.012) but not IgG (P = 0.053). Serum IgM level from week 3 to week 8 was correlated with positive virus RNA test (r = 0.201, P = 0.044), albumin level (r = -0.295, P = 0.003), lactic dehydrogenase (LDH) level (r = 0.292, P = 0.003), alkaline phosphatase (ALP) level (r = 0.254, P = 0.010), C-reactive protein (CRP) level (r = 0.281, P = 0.004) during the same course, while serum IgG level was correlated with age (r = 0.207, P = 0.038). This presented results provide insight into duration of SARS-CoV-2 antibodies and interaction between the virus and host systems.


Subject(s)
Antibodies, Viral/blood , COVID-19/blood , Immunoglobulin G/blood , Immunoglobulin M/blood , SARS-CoV-2 , Aged , C-Reactive Protein/analysis , COVID-19/immunology , COVID-19/virology , Female , Hospitalization , Humans , L-Lactate Dehydrogenase/blood , Male , Middle Aged , RNA, Viral/analysis , Retrospective Studies , Serum Albumin/analysis , Severity of Illness Index
12.
Transfusion ; 61(4): 1148-1159, 2021 04.
Article in English | MEDLINE | ID: covidwho-1031042

ABSTRACT

BACKGROUND: In March 2020, the Food and Drug Administration (FDA) approved use of COVID-19 convalescent plasma (CCP) as an investigational new drug for treatment of COVID-19. Since then, collection of CCP from COVID-19-recovered patients has been implemented in donor centers nationwide. Children's Hospital Colorado rapidly put into practice a CCP collection protocol, necessitating development and implementation of assays to evaluate SARS-CoV-2 antibodies in CCP units. STUDY DESIGN AND METHODS: We evaluated 87 units of CCP collected from 36 donors over two to four sequential donations using both antigen-binding assays for SARS-CoV-2 nucleoprotein and spike antigens and a live virus focus reduction neutralization test (FRNT50 ). RESULTS: Our data show that the majority of donors (83%) had a FRNT50 titer of at least 80, and 61% had a titer of at least 160, which met the FDA's criteria for acceptable CCP units. Additionally, our data indicate that analysis of antibodies to a single SARS-CoV-2 antigen is likely to miss a percentage of seroconverters; however, these individuals tend to have neutralizing antibody titers of less than 80. There was considerable variability in the short-term, sustained antibody response, measured by neutralizing antibody titers, among our donor population. CONCLUSION: The correlation of neutralizing activity and antigen-binding assays is necessary to qualify CCP for therapeutic use. Since SARS-CoV-2 antibody levels decline in a percentage of donors, and such a decline is not detectable by current qualitative assays implemented in many laboratories, robust, quantitative assays are necessary to evaluate CCP units best suited for therapeutic infusion in COVID-19 patients.


Subject(s)
Antibodies, Neutralizing/blood , Antibodies, Viral/blood , Blood Donors , COVID-19/blood , Convalescence , SARS-CoV-2/metabolism , Animals , Chlorocebus aethiops , Female , Humans , Male , Time Factors , Vero Cells
14.
Artif Organs ; 45(7): 762-769, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-978684

ABSTRACT

Our aim was to investigate the effect of artificial liver blood purification treatment on the survival of severe/critical patients with coronavirus disease 2019 (COVID-19). A total of 101 severe and critical patients with coronavirus SARS-CoV-2 infection were enrolled in this open, case-control, multicenter, prospective study. According to the patients' and their families' willingness, they were divided into two groups. One was named the treatment group, in which the patients received artificial liver therapy plus comprehensive treatment (n = 50), while the other was named the control group, in which the patients received only comprehensive treatment (n = 51). Clinical data and laboratory examinations, as well as the 28-day mortality rate, were collected and analyzed. Baseline data comparisons on average age, sex, pre-treatment morbidity, initial symptoms, vital signs, pneumonia severity index score, blood routine examination and biochemistry indices etc. showed no difference between the two groups. Cytokine storm was detected, with a significant increase of serum interleukin-6 (IL-6) level. The serum IL-6 level decreased from 119.94 to 20.49 pg/mL in the treatment group and increased from 40.42 to 50.81 pg/mL in the control group (P < .05), indicating that artificial liver therapy significantly decreased serum IL-6. The median duration of viral nucleic acid persistence was 19 days in the treatment group (ranging from 6 to 67 days) and 17 days in the control group (ranging from 3 to 68 days), no significant difference was observed (P = .36). As of 28-day follow-up,17 patients in the treatment group experienced a median weaning time of 24 days, while 11 patients in the control group experienced a median weaning time of 35 days, with no significant difference between the two groups (P = .33). The 28-day mortality rates were 16% (8/50) in the treatment group and 50.98% (26/51) in the control group, with a significant difference (z = 3.70, P < .001). Cytokine storm is a key factor in the intensification of COVID-19 pneumonia. The artificial liver therapy blocks the cytokine storm by clearing inflammatory mediators, thus preventing severe cases from progressing to critically ill stages and markedly reducing short-term mortality.


Subject(s)
COVID-19/therapy , Cytokine Release Syndrome/prevention & control , Liver, Artificial , Plasma Exchange/instrumentation , Aged , Biomarkers/blood , COVID-19/blood , COVID-19/mortality , COVID-19/virology , Case-Control Studies , Cytokine Release Syndrome/blood , Cytokine Release Syndrome/mortality , Cytokine Release Syndrome/virology , Cytokines/blood , Female , Hospital Mortality , Host-Pathogen Interactions , Humans , Male , Middle Aged , Plasma Exchange/adverse effects , Plasma Exchange/mortality , Prospective Studies , SARS-CoV-2/pathogenicity , Severity of Illness Index , Time Factors , Treatment Outcome , Viral Load
15.
J Med Virol ; 92(10): 2227-2231, 2020 10.
Article in English | MEDLINE | ID: covidwho-935128

ABSTRACT

Patients with coronavirus disease-2019 may be discharged based on clinical resolution of symptoms, and evidence for viral RNA clearance from the upper respiratory tract. Understanding the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral clearance profile is crucial to establish a re-testing plan on discharge and ending isolation of patients. We aimed to evaluate the number of days that a patient needed to achieve undetectable levels of SARS-CoV-2 in upper respiratory tract specimens (nasopharyngeal swab and/or an oropharyngeal swab). The clearance and persistence of viral RNA was evaluated in two groups of positive patients: those who achieved two negative reverse transcription-polymerase chain reaction (RT-PCR) tests and those who kept testing positive. Patients were organized thereafter in two subgroups, mild illness patients discharged home and inpatients who had moderate to severe illness. Results from RT-PCR tests were then correlated with results from the evaluation of the immune response. The study evidenced that most patients tested positive for more than 2 weeks and that persistence of viral RNA is not necessarily associated with severe disease but may result from a weaker immune response instead.


Subject(s)
COVID-19/diagnosis , Patient Discharge/statistics & numerical data , RNA, Viral/genetics , SARS-CoV-2/genetics , Adult , Aged , Aged, 80 and over , COVID-19/immunology , COVID-19/pathology , COVID-19/virology , COVID-19 Testing/methods , Child , Convalescence , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Nasopharynx/virology , Oropharynx/virology , Retrospective Studies , Reverse Transcriptase Polymerase Chain Reaction , SARS-CoV-2/immunology , SARS-CoV-2/pathogenicity , Severity of Illness Index
17.
Sci Immunol ; 5(52)2020 10 08.
Article in English | MEDLINE | ID: covidwho-842518

ABSTRACT

We measured plasma and/or serum antibody responses to the receptor-binding domain (RBD) of the spike (S) protein of SARS-CoV-2 in 343 North American patients infected with SARS-CoV-2 (of which 93% required hospitalization) up to 122 days after symptom onset and compared them to responses in 1548 individuals whose blood samples were obtained prior to the pandemic. After setting seropositivity thresholds for perfect specificity (100%), we estimated sensitivities of 95% for IgG, 90% for IgA, and 81% for IgM for detecting infected individuals between 15 and 28 days after symptom onset. While the median time to seroconversion was nearly 12 days across all three isotypes tested, IgA and IgM antibodies against RBD were short-lived with median times to seroreversion of 71 and 49 days after symptom onset. In contrast, anti-RBD IgG responses decayed slowly through 90 days with only 3 seropositive individuals seroreverting within this time period. IgG antibodies to SARS-CoV-2 RBD were strongly correlated with anti-S neutralizing antibody titers, which demonstrated little to no decrease over 75 days since symptom onset. We observed no cross-reactivity of the SARS-CoV-2 RBD-targeted antibodies with other widely circulating coronaviruses (HKU1, 229 E, OC43, NL63). These data suggest that RBD-targeted antibodies are excellent markers of previous and recent infection, that differential isotype measurements can help distinguish between recent and older infections, and that IgG responses persist over the first few months after infection and are highly correlated with neutralizing antibodies.


Subject(s)
Antibodies, Viral/immunology , Betacoronavirus/immunology , Coronavirus Infections/epidemiology , Pneumonia, Viral/epidemiology , Protein Domains/immunology , Spike Glycoprotein, Coronavirus/immunology , Adult , Aged , Antibodies, Neutralizing/immunology , Antibodies, Viral/blood , Betacoronavirus/genetics , Biomarkers/blood , COVID-19 , Cohort Studies , Coronavirus Infections/virology , Cross Reactions , Dried Blood Spot Testing , Female , Humans , Immunoglobulin A/blood , Immunoglobulin A/immunology , Immunoglobulin G/blood , Immunoglobulin G/immunology , Immunoglobulin M/blood , Immunoglobulin M/immunology , Male , Middle Aged , Pandemics , Pneumonia, Viral/virology , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/chemistry
18.
bioRxiv ; 2020 Sep 27.
Article in English | MEDLINE | ID: covidwho-807634

ABSTRACT

Following emergence in late 2019, SARS-CoV-2 rapidly became pandemic and is presently responsible for millions of infections and hundreds of thousands of deaths worldwide. There is currently no approved vaccine to halt the spread of SARS-CoV-2 and only very few treatment options are available to manage COVID-19 patients. For development of preclinical countermeasures, reliable and well-characterized small animal disease models will be of paramount importance. Here we show that intranasal inoculation of SARS-CoV-2 into Syrian hamsters consistently caused moderate broncho-interstitial pneumonia, with high viral lung loads and extensive virus shedding, but animals only displayed transient mild disease. We determined the infectious dose 50 to be only five infectious particles, making the Syrian hamster a highly susceptible model for SARS-CoV-2 infection. Neither hamster age nor sex had any impact on the severity of disease or course of infection. Finally, prolonged viral persistence in interleukin 2 receptor gamma chain knockout hamsters revealed susceptibility of SARS-CoV-2 to adaptive immune control. In conclusion, the Syrian hamster is highly susceptible to SARS-CoV-2 making it a very suitable infection model for COVID-19 countermeasure development.

19.
J Ultrasound Med ; 40(3): 503-511, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-754787

ABSTRACT

OBJECTIVES: Coronavirus disease 2019 (COVID-19) is a viral illness caused by severe acute respiratory syndrome coronavirus 2. With the increasing number of improved and discharged patients with COVID-19, the definition of an adequate follow-up strategy is needed. The purpose of this study was to assess whether lung ultrasound (LUS) is an effective indicator of subclinical residual lung damage in patients with COVID-19 who meet discharge criteria. METHODS: We prospectively enrolled 70 consecutive patients with COVID-19 who had a prolonged hospitalization with inpatient rehabilitation between April 6 and May 22, 2020. All of the patients underwent an LUS evaluation at discharge. Data of patients with more severe disease during the acute phase (ie, required ventilatory support) were compared to those of patients with milder disease. RESULTS: Among the 70 patients with COVID-19 (22 women and 48 men; mean age ± SD, 68 ± 13 years), the LUS score before discharge was still frankly pathologic and higher in patients who had more severe disease during the acute phase compared to patients with milder disease (median [interquartile range], 8.0 [5.5-13.5] versus 2.0 [1.0-7.0]; P < .001), even when both categories met internationally defined discharge criteria. CONCLUSIONS: Lung ultrasound can identify the persistence of subclinical residual lung damage in patients with severe COVID-19 even if they meet discharge criteria. Considering the low cost, easy application, and lack of radiation exposure, LUS seems the ideal tool to be adopted in outpatient and primary care settings for the follow-up of patients with COVID-19.


Subject(s)
COVID-19/diagnostic imaging , Lung/diagnostic imaging , Ultrasonography/methods , Aged , Chronic Disease , Female , Humans , Male , Prospective Studies , Reproducibility of Results , SARS-CoV-2
20.
Math Biosci ; 328: 108438, 2020 10.
Article in English | MEDLINE | ID: covidwho-696903

ABSTRACT

Coronavirus disease 2019 (COVID-19), an infectious disease caused by the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is spreading and causing the global coronavirus pandemic. The viral dynamics of SARS-CoV-2 infection have not been quantitatively investigated. In this paper, we use mathematical models to study the pathogenic features of SARS-CoV-2 infection by examining the interaction between the virus, cells and immune responses. Models are fit to the data of SARS-CoV-2 infection in patients and non-human primates. Data fitting and numerical simulation show that viral dynamics of SARS-CoV-2 infection have a few distinct stages. In the initial stage, viral load increases rapidly and reaches the peak, followed by a plateau phase possibly generated by lymphocytes as a secondary target of infection. In the last stage, viral load declines due to the emergence of adaptive immune responses. When the initiation of seroconversion is late or slow, the model predicts viral rebound and prolonged viral persistence, consistent with the observation in non-human primates. Using the model we also evaluate the effect of several potential therapeutic interventions for SARS-CoV-2 infection. Model simulation shows that anti-inflammatory treatments or antiviral drugs combined with interferon are effective in reducing the duration of the viral plateau phase and diminishing the time to recovery. These results provide insights for understanding the infection dynamics and might help develop treatment strategies against COVID-19.


Subject(s)
Betacoronavirus , Coronavirus Infections/virology , Models, Biological , Pneumonia, Viral/virology , Adaptive Immunity , Animals , Betacoronavirus/drug effects , Betacoronavirus/genetics , Betacoronavirus/immunology , COVID-19 , Coronavirus Infections/drug therapy , Coronavirus Infections/epidemiology , Coronavirus Infections/immunology , Host Microbial Interactions/immunology , Humans , Macaca mulatta , Mathematical Concepts , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/immunology , RNA, Viral/analysis , RNA, Viral/genetics , SARS-CoV-2 , Viral Load
SELECTION OF CITATIONS
SEARCH DETAIL
...