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Resolution of viral load in mild COVID-19 patients is associated with both innate and adaptive immune responses.

ABSTRACT: Over 90% of the COVID-19 patients manifest mild/moderate symptoms or are asymptomatic. Although comorbidities and dysregulation of immune response have been implicated in severe COVID-19, the host factors that associate with asymptomatic or mild infections have not been characterized. We have collected serial samples from 23 hospitalized COVID-19 patients with mild symptoms and measured the kinetics of SARS-CoV-2 viral load in respiratory samples and markers of inflammation in serum samples. We monitored seroconversion during the acute phase of illness and quantitated the amount of total IgG against the receptor-binding domain of SARS-CoV-2 and estimated the virus neutralization potential of these antibodies. Viral load decreased by day 8 in all the patients but the detection of viral RNA in saliva samples did not correlate well with viral RNA detection in nasopharyngeal/oropharyngeal swab samples. 25% of the virus-positive patients had no detectable neutralizing antibodies in the serum and in other cases, the efficiency of antibodies to neutralize SARS-CoV-2 B1.1.7 strain was lower as compared to the circulating virus isolate. Decrease in viral load coincided with increase in neutralizing antibodies and interferon levels in serum. Most patients showed no increase in inflammatory cytokines such as IL-1β or IL-6, however, elevated levels of IL-7 and other inflammatory mediators such as TNF-α and IL-8 was observed. These data suggest that most mild infections are associated with absence of inflammation coupled with an active innate immune response, T-cell activation and neutralizing antibodies.

SUBMITTER: Anantharaj A

PROVIDER: S-EPMC8687718 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The sharp increase in the proportion of asymptomatic cases and the potential risk of virus transmission have greatly increased the difficulty of controlling the COVID-19 pandemic. The individual immune response is closely associated with clinical outcomes and pathogenic mechanisms of COVID-19. However, the clinical characteristics and immunophenotyping features of immune cells of asymptomatic individuals remain somewhat mysterious. To better understand and predict the disease state and progress, we performed a comprehensive analysis of clinical data, laboratory indexes and immunophenotyping features in 41 patients with SARS-CoV-2 (including 24 asymptomatic cases and 17 symptomatic individuals). Firstly, from the perspective of demographic characteristics, the rate of asymptomatic infection was significantly higher in those with younger age. Secondly, the laboratory test results showed that some indexes, such as CRP (acute phase reaction protein), D-Dimer and fibrinogen (the marker for coagulation) were lower in the asymptomatic group. Finally, symptomatic individuals were prone to establishing a non-protective immune phenotype by abnormally decreasing the lymphocyte count and percentage, abnormally increasing the Th17 percentage and decreasing Treg percentage, which therefore cause an increase in the neutrophil/lymphocyte ratio (NLR), monocytes/lymphocytes ratio (MLR) and Th17/Treg ratio. On the other hand, asymptomatic individuals tended to establish a more effective and protective immune phenotype by maintaining a normal level of lymphocyte count and percentage and a high level of NK cells. At the same time, asymptomatic individuals can establish a relatively balanced immune response through maintaining a low level of monocytes, a relatively low level of Th17 and high level of Treg, which therefore lead to a decrease in MNKR and Th17/Treg ratio and finally the avoidance of excessive inflammatory responses. This may be one of the reasons for their asymptomatic states. This study is helpful to reveal the immunological characteristics of asymptomatic individuals, understand immune pathogenesis of COVID-19 and predict clinical outcomes more precisely. However, owing to small sample sizes, a future study with larger sample size is still warranted.

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Resolution of viral load in mild COVID-19 patients is associated with both innate and adaptive immune responses.

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