Viral Kinetics and Antibody Responses in Patients with COVID-19

Abstract

Background A pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been spreading over the world. However, the viral dynamics, host serologic responses, and their associations with clinical manifestations, have not been well described in prospective cohort. Methods We conducted a prospective cohort and enrolled 67 COVID-19 patients admitting between Jan 26 and Feb 5, 2020. Clinical specimens including nasopharyngeal swab, sputum, blood, urine and stool were tested periodically according to standardized case report form with final follow-up on February 27. The routes and duration of viral shedding, antibody response, and their associations with disease severity and clinical manifestations were systematically evaluated. Coronaviral particles in clinical specimens were observed by transmission electron microscopy (TEM). Results The median duration of SARS-CoV-2 RNA shedding were 12 (3-38), 19 (5-37), and 18 (7-26) days in nasopharyngeal swabs, sputum and stools, respectively. Only 13 urines (5.6%) and 12 plasmas (5.7%) were viral positive. Prolonged viral shedding was observed in severe patients than that of non-severe patients. Cough but not fever, aligned with viral shedding in clinical respiratory specimens, meanwhile the positive stool-RNA appeared to align with the proportion who concurrently had cough and sputum production, but not diarrhea. Typical coronaviral particles could be found directly in sputum by TEM. The anti-nucleocapsid-protein IgM started on day 7 and positive rate peaked on day 28, while that of IgG was on day 10 and day 49 after illness onset. IgM and IgG appear earlier, and their titers are significantly higher in severe patients than non-severe patients (p<0.05). The weak responders for IgG had a significantly higher viral clearance rate than that of strong responders (p= 0.011). Conclusions Nasopharyngeal, sputum and stools rather than blood and urine, were the major shedding routes for SARS-CoV-2, and meanwhile sputum had a prolonged viral shedding. Symptom cough seems to be aligned with viral shedding in clinical respiratory and fecal specimens. Stronger antibody response was associated with delayed viral clearance and disease severity.

Analytical performances of a chemiluminescence immunoassay for SARS-CoV-2 IgM/IgG and antibody kinetics

“…For example, using an ELISA in-house developed method, Zhang et al found that the increase of antibody against the virus was clearly visible in almost all patients after 5 days of symptom onset, a time period that was usually considered as a transition from an early to a late period of infection [19]. Likewise, using a commercial ELISA kit from Livzon Diagnostics (China), Tan et al found a marked increase of immunoglobulins 7 days after the onset of symptoms, particularly in patients with severe disease [20]. Table 3 reports in detail the kinetics of IgM and IgG, showing that IgG requires at least 12 days to attain 100% sensitivity, whilst the highest positive rate achieved for IgM was 88% throughout the study period.…”

In Vitro Diagnostic Assays for COVID-19: Recent Advances and Emerging Trends

“…The most widely used biomarkers for the detection of SARS-CoV-2 infection in commercial immunoassays (rapid lateral flow immunoassay (LFIA) tests, automated chemiluminescence immunoassay (CLIA), manual ELISA, and other formats) are IgM and IgG antibodies produced in suspects from the 2nd week of viral infection. IgM can be detected in the patient samples from 10 to 30 days after SARS-CoV-2 infection, while IgG can be detected from 20 days onwards [13]. The IgM response occurs earlier than that of IgG, but it then decreases and disappears.…”

A systematic review of antibody mediated immunity to coronaviruses: antibody kinetics, correlates of protection, and association of antibody responses with severity of disease

“…Another study 40 suggested that weaker antibody responses to endemic HCoVs (specifically HCoV-229E) might be because these mainly infect the upper respiratory tract. Preliminary studies on SARS-CoV-2 point to a possibly contrasting pattern to MERS-CoV: while IgM antibodies appear at the same time in severe and non-severe cases, IgG appears sooner in severe cases 33 . On the other hand, neutralizing antibody titers were higher in severe cases 34 .…”

“…A comparison of a cohort of [21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40] year-olds and a cohort of ≥65 year-olds found no clear difference in incidence between the two age groups, as measured by seroconversion or PCRconfirmed, HCoV-associated respiratory illness 120 . Finally, observational studies have shown evidence of coronavirus-associated respiratory illnesses in elderly populations [121][122][123] and across all ages 124 .…”