A compromised specific humoral immune response against the SARS-CoV-2 receptor-binding domain is related to viral persistence and periodic shedding in the gastrointestinal tract

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been redetected after discharge in some coronavirus disease 2019 (COVID-19) patients. The reason for the recurrent positivity of the test and the potential public health concern due to this occurrence are still unknown. Here, we analyzed the viral data and clinical manifestations of 289 domestic Chinese COVID-19 patients and found that 21 individuals (7.3%) were readmitted for hospitalization after detection of SARS-CoV-2 after discharge. First, we experimentally confirmed that the virus was involved in the initial infection and was not a secondary infection. In positive retests, the virus was usually found in anal samples (15 of 21, 71.4%). Through analysis of the intracellular viral subgenomic messenger RNA (sgmRNA), we verified that positive retest patients had active viral replication in their gastrointestinal tracts (3 of 16 patients, 18.7%) but not in their respiratory tracts. Then, we found that viral persistence was not associated with high viral titers, delayed viral clearance, old age, or more severe clinical symptoms during the first hospitalization. In contrast, viral rebound was associated with significantly lower levels of and slower generation of viral receptor-binding domain (RBD)-specific IgA and IgG antibodies. Our study demonstrated that the positive retest patients failed to create a robust protective humoral immune response, which might result in SARS-CoV-2 persistence in the gastrointestinal tract and possibly in active viral shedding. Further exploration of the mechanism underlying the rebound in SARS-CoV-2 in this population will be crucial for preventing virus spread and developing effective vaccines.

The Spike of Concern—The Novel Variants of SARS-CoV-2

“…Interestingly, in both cases, short deletions in the supersite loop N3 were found. Given the high expression level of Ace2 in the gastrointestinal system [7], it is worth noting that active replicating virus was found in anal samples [77], suggesting that the gastrointestinal system may provide an evolution refuge for SARS-CoV-2.…”

Long-Haul COVID-19: Putative Pathophysiology, Risk Factors, and Treatments

“…determined lymphopenia and high pro-inflammatory neutrophil count as independent risk factors of COVID-19 severity and mortality(Danwang et al 2020;Malik et al 2020;Ou et al 2020).Therefore, as B-cell and T-cell lymphocytes are renewed, elevated inflammation from unresolved hyperinflammation may ensue and contribute to long-haul COVID-19(Kong et al 2020;Tavakolpour et al 2020). Moreover, decreased T-cell and B-cell numbers have been shown to correlate with persistent SARS-CoV-2 shedding, which may further perpetuate chronic immune activation in long-haul COVID-19 (F Hu et al 2020b;B. Liu et al 2020a…”

Immunoglobulin Response and Prognostic Factors in Repeated SARS-CoV-2 Positive Patients: A Systematic Review and Meta-Analysis

“…The basic characteristics of the included articles are summarized in Table 1 . Out of the 34 included articles, 33 were from China [ 12 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 ] and 1 from Italy [ 30 ]. All of the included studies were conducted during the first wave of the COVID-19 pandemic.…”