April 29, 2020

Cases of large-vessel stroke in young patients with COVID-19, and seroconversion patterns of IgM and IgG antibodies after SARS-CoV-2 infection

By Denise Baez

NEW YORK -- April 29, 2020 -- In today’s DG Alert, we cover large-vessel stroke as a presenting feature of coronavirus disease 2019 (COVID-19) in the young, and the profile and seroconversion patterns of IgM and IgG antibodies after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

According to a study published in The New England Journal of Medicine, large-vessel stroke may be another complication of COVID-19.

“Over a 2-week period from March 23 to April 7, 2020, a total of 5 patients who were younger than 50 years of age presented with new-onset symptoms of large-vessel ischaemic stroke,” wrote Thomas J. Oxley, MD, Mount Sinai Health System, New York, New York. “All 5 patients tested positive for COVID-19. By comparison, every 2 weeks over the previous 12 months, our service has treated, on average, 0.73 patients younger than 50 years of age with large-vessel stroke.”

Patient 1 was a female aged 33 years with no medical history or risk factors for stroke and a National Institutes of Health Stroke Scale (NIHSS) score of 19 on admission. Patient 2 was a male aged 37 years with no medical history or risk factors for stroke and a NIHSS score of 13 on admission. Patient 3 was a male aged 39 years with hyperlipidaemia and hypertension, and a NIHSS score of 16 on admission. Patient 4 was a male aged 44 years with undiagnosed diabetes and a NIHSS score of 23 on admission. Patient 5 was a male aged 49 years with a history of mild stroke and diabetes and a NIHSS score of 13 on admission. Patient 5 was the only patient taking medications (aspirin and atorvastatin).

All patients presented with signs and symptoms of stroke, including reduced level of consciousness, hemiplegia, and dysarthria. Patients 1, 4, and 5 had COVID-19 symptoms, including cough, fever, and lethargy.

Patient 1 was treated with apixaban; patient 2 with clot retrieval and apixaban; patient 3 with clot retrieval and aspirin; patient 4 with intravenous t-PA, clot retrieval, hemicraniectomy; and aspirin; and patient 5 with clot retrieval, stent, aspirin, and clopidogrel.

At last follow-up, patient 1 was discharged to a rehabilitation facility, patient 2 was discharged to his home, patient 3 was in the intensive care unit (intubated, sedated, with multi-organ failure), patient 4 was moved to a stroke unit, and patient 5 was discharged to a rehabilitation facility. 

“The association between large-vessel stroke and COVID-19 in young patients requires further investigation,” the authors wrote.

Of note, 2 patients -- including the youngest in the series -- delayed seeking emergency care because of fear of COVID-19. 

“Social distancing, isolation, and reluctance to present to the hospital may contribute to poor outcomes,” the authors wrote. “Two patients in our series delayed calling an ambulance because they were concerned about going to a hospital during the pandemic.”

Another study, published in Clinical Infectious Diseases, showed that the majority of patients with SARS-CoV-2 developed robust antibody responses between 17 and 23 days after illness onset, with delayed but stronger antibody responses in critical patients.

Jiuxin Qu, MD, Third People’s Hospital of Shenzhen, Shenzhen, China, and colleagues analysed data from 41 patients with confirmed SARS-CoV-2 (two back-to-back tests). Patients with mild, moderate, and severe disease were included. 

IgG and IgM antibodies against SARS-CoV-2 were measured using the iFlash-SARSCoV-2 IgG/IgM chemiluminescent immunoassay kit. According to the instructions, the sensitivity and specificity of the kits was 90% and 95% for IgG, and 80% and 95% for IgM. Combined nucleocapsid protein and spike glycoprotein were used as coated antigens to increase the sensitivity. 

Of the 41 patients, 40 (97.6%) of patients (40/41) were positive with IgG and 36 (87.8%) were positive with IgM. The median time of seroconversion after disease onset was 11 days for IgG and 14 days for IgM. On an individual basis, the seroconversion time of IgG antibody was earlier than that of IgM antibody (12.45 ± 4.36 vs 13.75 ± 4.60 days; P = 0.0019). The level of IgG antibody reached the highest concentration on day 30, while the highest concentration of IgM antibody appeared on day 18, but then began to decline.

When the researchers analysed trends in antibody production according to disease severity, the fitting curve of critically ill patients increased rapidly above the cut-off value from day 7 and peaked on day 20, while the fitting curves of the non-critical groups increased more slowly from day 5. 

Although the IgG level of those in the mild and moderate group was still rising on day 28, the IgG response of the critical group was significantly stronger than that of non-critical groups within 4 weeks after illness onset (P = 0.0001). For IgM, the fitting curve of the critical group rose above the cut-off value on day 10, peaked on day 23, and then began to decline. However, the IgM levels of non-critical groups rose above the cut-off value as early as day 5, peaked on day 16, and then decreased.

“In the majority of the patients, there were antibody responses to SARS-CoV-2 during the first 3 weeks of the disease,” the authors wrote. “The seroconversion time of IgG antibody was earlier than that of IgM antibody. The kinetics of anti-SARS-CoV-2 antibodies should be helpful in epidemiologic surveys, and especially in clinical diagnoses since the immunoassays can efficiently compensate the false negative limitations of nucleic acid testing.”

SOURCE: The New England Journal of Medicine and Clinical Infectious Diseases