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1.
Cell Rep Med ; 2(6): 100321, 2021 06 15.
Article in English | MEDLINE | ID: covidwho-1253745

ABSTRACT

The pathogenesis of severe coronavirus disease 2019 (COVID-19) remains poorly understood. While several studies suggest that immune dysregulation plays a central role, the key mediators of this process are yet to be defined. Here, we demonstrate that plasma from a high proportion (93%) of critically ill COVID-19 patients, but not healthy controls, contains broadly auto-reactive immunoglobulin M (IgM) and less frequently auto-reactive IgG or IgA. Importantly, these auto-IgMs preferentially recognize primary human lung cells in vitro, including pulmonary endothelial and epithelial cells. By using a combination of flow cytometry, analytical proteome microarray technology, and lactose dehydrogenase (LDH)-release cytotoxicity assays, we identify high-affinity, complement-fixing, auto-reactive IgM directed against 260 candidate autoantigens, including numerous molecules preferentially expressed on the cellular membranes of pulmonary, vascular, gastrointestinal, and renal tissues. These findings suggest that broad IgM-mediated autoimmune reactivity may be involved in the pathogenesis of severe COVID-19, thereby identifying a potential target for therapeutic interventions.


Subject(s)
Autoantibodies/immunology , COVID-19/pathology , Immunoglobulin M/immunology , Autoantibodies/blood , COVID-19/immunology , COVID-19/virology , Cell Line , Complement C4/metabolism , Critical Illness , Humans , Immunoglobulin M/blood , Intensive Care Units , Lung/metabolism , Protein Array Analysis , Proteome/analysis , SARS-CoV-2/isolation & purification
2.
Can Commun Dis Rep ; 47(4): 195-201, 2021 May 07.
Article in English | MEDLINE | ID: covidwho-1244372

ABSTRACT

BACKGROUND: Research studies comparing antibody response from coronavirus disease 2019 (COVID-19) cases that retested positive (RP) using reverse transcription polymerase chain reaction (RT-PCR) and those who did not retest positive (NRP) were used to investigate a possible relationship between antibody response and retesting status. METHODS: Seven data bases were searched. Research criteria included cohort and case-control studies, carried out worldwide and published before September 9, 2020, that compared the serum antibody levels of hospitalized COVID-19 cases that RP after discharge to those that did NRP. RESULTS: There is some evidence that immunoglobulin G (IgG) and immunoglobulin M (IgM) antibody levels in RP cases were lower compared with NRP cases. The hypothesis of incomplete clearance aligns with these findings. The possibility of false negative reverse transcription polymerase chain reaction (RT-PCR test results during viral clearance is also plausible, as concentration of the viral ribonucleic acid (RNA) in nasopharyngeal and fecal swabs fluctuate below the limits of RT-PCR detection during virus clearance. The probability of reinfection was less likely to be the cause of retesting positive because of the low risk of exposure where cases observed a 14 day-quarantine after discharge. CONCLUSION: More studies are needed to better explain the immune response of recovered COVID-19 cases retesting positive after discharge.

3.
Acad Pathol ; 8: 23742895211010247, 2021.
Article in English | MEDLINE | ID: covidwho-1228979

ABSTRACT

International travel has been a significant factor in the coronavirus disease 2019 pandemic. Many countries and airlines have implemented travel restrictions to limit the spread of the causative agent, severe acute respiratory syndrome coronavirus-2. A common requirement has been a negative reverse-transcriptase polymerase chain reaction performed by a clinical laboratory within 48 to 72 hours of departure. A more recent travel mandate for severe acute respiratory syndrome coronavirus-2 immunoglobulin M serology testing was instituted by the Chinese government on October 29, 2020. Pretravel testing for severe acute respiratory syndrome coronavirus-2 raises complications in terms of cost, turnaround time, and follow-up of positive results. In this report, we describe the experience of a multidisciplinary collaboration to develop a workflow for pretravel severe acute respiratory syndrome coronavirus-2 reverse-transcriptase polymerase chain reaction and immunoglobulin M serology testing at an academic medical center. The workflow primarily involved self-payment by patients and preferred retrieval of results by the patient through the electronic health record patient portal (Epic MyChart). A total of 556 unique patients underwent pretravel reverse-transcriptase polymerase chain reaction testing, with 13 (2.4%) having one or more positive results, a rate similar to that for reverse-transcriptase polymerase chain reaction testing performed for other protocol-driven asymptomatic screening (eg, inpatient admissions, preprocedural) at our medical center. For 5 of 13 reverse-transcriptase polymerase chain reaction positive samples, the traveler had clinical history, prior reverse-transcriptase polymerase chain reaction positive, and high cycle thresholds values on pretravel testing consistent with remote infection and minimal transmission risk. Severe acute respiratory syndrome coronavirus-2 immunoglobulin M was performed on only 24 patients but resulted in 2 likely false positives. Overall, our experience at an academic medical center shows the challenge with pretravel severe acute respiratory syndrome coronavirus-2 testing.

4.
Saudi J Biol Sci ; 28(8): 4677-4682, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1213522

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected persons could be symptomatic or asymptomatic. Asymptomatic and symptomatic patients can transmit SARS-CoV-2. This study aimed to study the humoral immune response in Saudis who are Covid-19 symptomatic and asymptomatic patients. We created three types of enzyme-linked immunosorbant assays (ELISAs) to reveal IgG and IgM antibodies (Abs) against SARS-CoV-2. The developed ELISAs were designed to detect Abs against SARS-CoV-2 N, S and N + S proteins. A number of Covid-19 symptomatic (1 5 3) and asymptomatic (84) RT-PCR-confirmed patient sera were used to evaluate the ELISAs and to determine the IgG and IgM antibody profile in those patients. The sensitivity and specificity of these ELISAs were evaluated using pre-Covid-19 pandemic serum samples. The results revealed the existence of anti-SARS-CoV-2 IgG and IgM Abs in Covid-19 symptomatic and asymptomatic Saudi persons. The use of SARS-CoV-2 N and S proteins in the same ELISA greatly increased the detectability of infection. In conclusion, the Covid-19 symptomatic and asymptomatic Saudi persons demonstrated both IgG and IgM antibody profile with higher titer in symptomatic patients. The use of N + S proteins as antibody capture antigens greatly increased the ELISA sensitivity.

5.
J Med Virol ; 93(9): 5409-5415, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1209995

ABSTRACT

Timing of detection of immunoglobulin G (IgG), immunoglobulin A (IgA), and immunoglobulin M (IgM) antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and their use to support the diagnosis are of increasing interest. We used the Gold Standard Diagnostics ELISA to evaluate the kinetics of SARS-CoV-2 IgG, IgA, and IgM antibodies in sera of 82 hospitalized patients with polymerase chain reaction (PCR)-confirmed coronavirus disease 2019 (COVID-19). Serum samples were collected 1-59 days post-onset of symptoms (PoS) and we examined the association of age, sex, disease severity, and symptoms' duration with antibody levels. We also tested sera of 100 ambulatory hospital employees with PCR-confirmed COVID-19 and samples collected during convalescence, 35-57 days PoS. All but four of the admitted patients (95.1%) developed antibodies to SARS-CoV-2. Antibodies were detected within 7 days PoS; IgA in 60.0%, IgM in 53.3%, and IgG in 46.7% of samples. IgG positivity increased to 100% on Day 21. We did not observe significant differences in the rate of antibody development in regard to age and sex. IgA levels were highest in patients with a severe and critical illness. In multiple regression analyses, only IgA levels were statistically significantly correlated with critical disease (p = .05) regardless of age, sex, and duration of symptoms. Among 100 ambulatory hospital employees who had antibody testing after 4 weeks PoS only 10% had positive IgA antibodies. The most frequently isolated isotype in sera of employees after 30 days PoS was IgG (88%). IgA was the predominant immunoglobulin in early disease and correlated independently with a critical illness. IgG antibodies remained detectable in almost 90% of samples collected up to two months after infection.


Subject(s)
Antibodies, Viral/blood , COVID-19/immunology , Immunoglobulin A/blood , Immunoglobulin G/blood , Immunoglobulin M/blood , SARS-CoV-2/immunology , Adult , Aged , Aged, 80 and over , COVID-19/blood , COVID-19/diagnosis , COVID-19/mortality , COVID-19 Serological Testing , Convalescence , Enzyme-Linked Immunosorbent Assay , Female , Humans , Male , Middle Aged , Sensitivity and Specificity , Severity of Illness Index , Survival Analysis
6.
J Orthop Sci ; 27(3): 713-716, 2022 May.
Article in English | MEDLINE | ID: covidwho-1188813

ABSTRACT

BACKGROUND: Elective orthopaedic surgery has been severely curtailed because of coronavirus disease, 2019. There is scant scientific evidence to guide surgeons in assessing the protocols that must be implemented before resuming elective orthopaedic surgery safely after the second wave of the coronavirus disease, 2019. METHODS: A retrospective review of elective orthopaedic surgeries performed between May 15, 2020, and November 20, 2020, was conducted. A screening questionnaire was used, and reverse transcription-polymerase chain reaction and severe acute respiratory syndrome coronavirus-2 immunoglobulin G and IgM antibodies testing were assessed in all admitted patients. Screening and testing data for coronavirus disease was reviewed for all patients. RESULTS: Of 592 patients tested for severe acute respiratory syndrome coronavirus-2 during the study period, 21 (3.5%) tested positive. There were 2 patients (0.3%) with positive reverse transcription-polymerase chain reaction tests, 3 (0.5%) with positive IgG and IgM antibodies, 13 (2.2%) with positive IgG antibodies, and 10 (1.7%) with positive IgM antibodies. Among these 21 patients, 20 (95.2%) were asymptomatic. CONCLUSIONS: Our findings suggest that most elective orthopaedic surgery patients with severe acute respiratory syndrome coronavirus-2 are asymptomatic. In the second wave of coronavirus disease, 2019, universal testing of all patients should be strongly considered as an important measure to prevent clusters of in-hospital transmission of the disease.


Subject(s)
COVID-19 , Orthopedic Procedures , Humans , Immunoglobulin G , Immunoglobulin M , SARS-CoV-2
7.
Am J Otolaryngol ; 42(4): 102956, 2021.
Article in English | MEDLINE | ID: covidwho-1077757

ABSTRACT

PURPOSE: Idiopathic facial palsy is called as Bell's palsy and reports showed that facial paralysis increased during COVID-19 pandemic period. There are many reports about the relationship between COVID-19 and facial paralysis but there is no prospective study. SARS-CoV-2 IgG and IgM antibodies increase in COVID-19. Our purpose is to investigate SARS-CoV-2 IgG + IgM antibody in the Bell's palsy. METHODS: Prospective cross-sectional study was planned. Patients with acute peripheral facial paralysis with no reason and diagnosed as Bell's palsy was included in the study. In order to investigate SARS-CoV-2 in the etiologies of these patients, SARS-CoV-2 IgM + IgG (total) test was studied. SARS-CoV-2 IgG + IgM was measured by using the ADVIA Centaur® test kit. Test reports result in index values and as nonreactive or reactive. The results were analyzed. RESULTS: Forty-one patients were included in the study. The average age of the patients was 41,7. 17 (41,4%) were female and 24 (58,6%) were male. 21 patients had left-sided; 20 had right-sided paralysis. SARS-CoV-2 IgG + IgM values were measured two times of the patients. First control was in the first week of facial paralysis, 10 (24,3%) positivity was found. The average index of the positive patients were 6,74 (min.1,39-max.10) in the first control and 9,585 in the second control (min.8,7-max. 10). CONCLUSION: We found that the SARS-CoV-2 IgM + IgG antibody test was positive in 24.3% of the patients with Bell's palsy. The results are higher than the seroprevalence studies conducted in asymptomatic individuals. Facial paralysis could be the only symptom of COVID-19 but further studies must be done.


Subject(s)
COVID-19/complications , Facial Paralysis/virology , SARS-CoV-2/isolation & purification , Adult , COVID-19/diagnosis , COVID-19/therapy , Cross-Sectional Studies , Female , Humans , Immunoglobulin G/blood , Immunoglobulin M/blood , Male , Middle Aged , Prospective Studies , SARS-CoV-2/immunology , Symptom Assessment
8.
Clin Infect Dis ; 72(2): 301-308, 2021 01 27.
Article in English | MEDLINE | ID: covidwho-1050133

ABSTRACT

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can be detected indirectly by measuring the host immune response. For some viruses, antibody concentrations correlate with host protection and viral neutralization, but in rare cases, antiviral antibodies can promote disease progression. Elucidation of the kinetics and magnitude of the SARS-CoV-2 antibody response is essential to understand the pathogenesis of coronavirus disease 2019 (COVID-19) and identify potential therapeutic targets. METHODS: Sera (n = 533) from patients with real-time polymerase chain reaction-confirmed COVID-19 (n = 94 with acute infections and n = 59 convalescent patients) were tested using a high-throughput quantitative immunoglobulin M (IgM) and immunoglobulin G (IgG) assay that detects antibodies to the spike protein receptor binding domain and nucleocapsid protein. Individual and serial samples covered the time of initial diagnosis, during the disease course, and following recovery. We evaluated antibody kinetics and correlation between magnitude of the response and disease severity. RESULTS: Patterns of SARS-CoV-2 antibody production varied considerably. Among 52 patients with 3 or more serial specimens, 44 (84.6%) and 42 (80.8%) had observed IgM and IgG seroconversion at a median of 8 and 10 days, respectively. Compared to those with milder disease, peak measurements were significantly higher for patients admitted to the intensive care unit for all time intervals between 6 and 20 days for IgM, and all intervals after 5 days for IgG. CONCLUSIONS: High-sensitivity assays with a robust dynamic range provide a comprehensive picture of host antibody response to SARS-CoV-2. IgM and IgG responses were significantly higher in patients with severe than mild disease. These differences may affect strategies for seroprevalence studies, therapeutics, and vaccine development.


Subject(s)
Antibody Formation , COVID-19 , Antibodies, Viral , Humans , Immunoglobulin M , Kinetics , SARS-CoV-2 , Seroepidemiologic Studies , Severity of Illness Index
9.
Clin Transl Immunology ; 9(9): e1182, 2020.
Article in English | MEDLINE | ID: covidwho-796073

ABSTRACT

OBJECTIVES: Asymptomatic and symptomatic patients may transmit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but their clinical features and immune responses remain largely unclear. We aimed to characterise the clinical features and immune responses of asymptomatic and symptomatic patients infected with SARS-CoV-2. METHODS: We collected clinical, laboratory and epidemiological records of patients hospitalised in a coronavirus field hospital in Wuhan. We performed qualitative detection of anti-SARS-CoV-2 immunoglobulin M (IgM) and immunoglobulin G (IgG) using archived blood samples. RESULTS: Of 214 patients with SARS-CoV-2, 26 (12%) were asymptomatic at hospital admission and during hospitalisation. Most asymptomatic patients were ≤ 60 years (96%) and females (65%) and had few comorbidities (< 16%). Serum levels of white and red blood cells were higher in asymptomatic than in symptomatic patients (P-values < 0.05). During hospitalisation, IgG seroconversion was commonly observed in both asymptomatic and symptomatic patients (85% versus 94%, P-value = 0.07); in contrast, IgM seroconversion was less common in asymptomatic than in symptomatic patients (31% versus 74%, P-value < 0.001). The median time from the first virus-positive screening to IgG or IgM seroconversion was significantly shorter in asymptomatic than in symptomatic patients (median: 7 versus 14 days, P-value < 0.01). Furthermore, IgG/IgM seroconversion rates increased concomitantly with the clearance of SARS-CoV-2 in both asymptomatic and symptomatic patients. At the time of virus clearance, IgG/IgM titres and plasma neutralisation capacity were significantly lower in recovered asymptomatic than in recovered symptomatic patients (P-values < 0.01). CONCLUSION: Asymptomatic and symptomatic patients exhibited different kinetics of IgG/IgM responses to SARS-CoV-2. Asymptomatic patients may transmit SARS-CoV-2, highlighting the importance of early diagnosis and treatment.

11.
Chin Med J (Engl) ; 133(20): 2410-2414, 2020 Oct 20.
Article in English | MEDLINE | ID: covidwho-730316

ABSTRACT

BACKGROUND: The coronavirus disease 2019 (COVID-19) outbreak occurred during the flu season around the world. This study aimed to analyze the impact of influenza A virus (IAV) exposure on COVID-19. METHODS: Seventy COVID-19 patients admitted to the hospital during January and February 2020 in Wuhan, China were included in this retrospective study. Serum tests including respiratory pathogen immunoglobulin M (IgM) and inflammation biomarkers were performed upon admission. Patients were divided into common, severe, and critical types according to disease severity. Symptoms, inflammation indices, disease severity, and fatality rate were compared between anti-IAV IgM-positive and anti-IAV IgM-negative groups. The effects of the empirical use of oseltamivir were also analyzed in both groups. For comparison between groups, t tests and the Mann-Whitney U test were used according to data distribution. The Chi-squared test was used to compare disease severity and fatality between groups. RESULTS: Thirty-two (45.71%) of the 70 patients had positive anti-IAV IgM. Compared with the IAV-negative group, the positive group showed significantly higher proportions of female patients (59.38% vs. 34.21%, χ = 4.43, P = 0.035) and patients with fatigue (59.38% vs. 34.21%, χ = 4.43, P = 0.035). The levels of soluble interleukin 2 receptor (median 791.00 vs. 1075.50 IU/mL, Z = -2.70, P = 0.007) and tumor necrosis factor α (median 10.75 vs. 11.50 pg/mL, Z = -2.18, P = 0.029) were significantly lower in the IAV-positive group. Furthermore, this group tended to have a higher proportion of critical patients (31.25% vs. 15.79%, P = 0.066) and a higher fatality rate (21.88% vs. 7.89%, P = 0.169). Notably, in the IAV-positive group, patients who received oseltamivir had a significantly lower fatality rate (0 vs. 36.84%, P = 0.025) compared with those not receiving oseltamivir. CONCLUSIONS: The study suggests that during the flu season, close attention should be paid to the probability of IAV exposure in COVID-19 patients. Prospective studies with larger sample sizes are needed to clarify whether IAV increases the fatality rate of COVID-19 and to elucidate any benefits of empirical usage of oseltamivir.


Subject(s)
Betacoronavirus , Coronavirus Infections/mortality , Influenza A virus , Influenza, Human/complications , Pneumonia, Viral/mortality , Adult , Aged , Antibodies, Viral/blood , COVID-19 , Female , Humans , Immunoglobulin M/blood , Influenza A virus/immunology , Male , Middle Aged , Pandemics , Retrospective Studies , SARS-CoV-2 , Severity of Illness Index
12.
J Infect Dis ; 222(2): 183-188, 2020 06 29.
Article in English | MEDLINE | ID: covidwho-245018

ABSTRACT

BACKGROUND: A novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has recently emerged and caused the rapid spread of coronavirus disease 2019 (COVID-19) worldwide. METHODS: We did a retrospective study and included COVID-19 patients admitted to Renmin Hospital of Wuhan University between 1 February and 29 February 2020. Antibody assay was conducted to detect COVID-19 envelope protein E and nucleocapsid protein N antigen. RESULTS: One hundred twelve patients were recruited with symptoms of fever, cough, fatigue, myalgia, and diarrhea. All patients underwent antibody tests. Fifty-eight (51.79%) were positive for both immunoglobulin M (IgM) and immunoglobulin G (IgG), 7 (6.25%) were negative for both antibodies, 1 (0.89%) was positive for only IgM, and 46 (41.07%) were positive for only IgG. IgM antibody appeared within a week post-disease onset, lasted for 1 month, and gradually decreased, whereas IgG antibody was produced 10 days after infection and lasted for a longer time. However, no significant difference in levels of IgM and IgG antibodies between positive and negative patients of nucleic acid test after treatment was found. CONCLUSIONS: Our results indicate that serological tests could be a powerful approach for the early diagnosis of COVID-19.


Subject(s)
Antibodies, Viral/blood , Betacoronavirus/immunology , Coronavirus Infections/diagnosis , Coronavirus Infections/immunology , Pneumonia, Viral/diagnosis , Pneumonia, Viral/immunology , Adult , Aged , COVID-19 , COVID-19 Testing , Clinical Laboratory Techniques , Disease Progression , Female , Humans , Immunoglobulin G/blood , Immunoglobulin M/blood , Male , Middle Aged , Pandemics , Retrospective Studies , Reverse Transcriptase Polymerase Chain Reaction , SARS-CoV-2 , Serologic Tests
13.
J Clin Microbiol ; 58(6)2020 05 26.
Article in English | MEDLINE | ID: covidwho-45977

ABSTRACT

We set out to investigate the interference factors that led to false-positive novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgM detection results using gold immunochromatography assay (GICA) and enzyme-linked immunosorbent assay (ELISA) and the corresponding solutions. GICA and ELISA were used to detect SARS-CoV-2 IgM in 86 serum samples, including 5 influenza A virus (Flu A) IgM-positive sera, 5 influenza B virus (Flu B) IgM-positive sera, 5 Mycoplasma pneumoniae IgM-positive sera, 5 Legionella pneumophila IgM-positive sera, 6 sera of HIV infection patients, 36 rheumatoid factor IgM (RF-IgM)-positive sera, 5 sera from hypertensive patients, 5 sera from diabetes mellitus patients, and 14 sera from novel coronavirus infection disease 19 (COVID-19) patients. The interference factors causing false-positive reactivity with the two methods were analyzed, and the urea dissociation test was employed to dissociate the SARS-CoV-2 IgM-positive serum using the best dissociation concentration. The two methods detected positive SARS-CoV-2 IgM in 22 mid-to-high-level-RF-IgM-positive sera and 14 sera from COVID-19 patients; the other 50 sera were negative. At a urea dissociation concentration of 6 mol/liter, SARS-CoV-2 IgM results were positive in 1 mid-to-high-level-RF-IgM-positive serum and in 14 COVID-19 patient sera detected using GICA. At a urea dissociation concentration of 4 mol/liter and with affinity index (AI) levels lower than 0.371 set to negative, SARS-CoV-2 IgM results were positive in 3 mid-to-high-level-RF-IgM-positive sera and in 14 COVID-19 patient sera detected using ELISA. The presence of RF-IgM at mid-to-high levels could lead to false-positive reactivity of SARS-CoV-2 IgM detected using GICA and ELISA, and urea dissociation tests would be helpful in reducing SARS-CoV-2 IgM false-positive results.


Subject(s)
Betacoronavirus/immunology , Chromatography, Affinity/methods , Clinical Laboratory Techniques/methods , Coronavirus Infections/diagnosis , Enzyme-Linked Immunosorbent Assay/methods , Immunoglobulin M/blood , Pneumonia, Viral/diagnosis , COVID-19 , COVID-19 Testing , False Positive Reactions , Humans , Pandemics , SARS-CoV-2
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