Published online: June 20, 2020
COVID-19 has emerged as the most lethal pandemic in the last century with more than 10 million cases and half a million deaths as of June 29, 2020. Certain populations such as those with advanced age or patients with other underlying diseases are highly susceptible to have severe consequences in COVID-19. Currently it remains unclear what makes these patients more susceptible to the disease. Identifying the mechanisms that lead to severe disease can potentially provide important therapeutic target to improve the disease outcomes in COVID-19.
In this study co-led by Dr. En-Qiang Qin and Dr. De Chang, both from the Chinese PLA General Hospital, and Dr. Lokesh Sharma, Dr. Charles Dela Cruz, both from Yale University investigated key contributing factors in mediating the disease severity in COVID-19. In addition, they investigated whether reactivation of virus in recovered patients as seen by qPCR in some patients represents infective viral presence in these patients. The study is published in The Journal of Allergy and Clinical Immunology: In Practice.
This study reports that persistent presence of viral infection in the throat swabs is associated with significantly severe disease. In contrast, the levels of inflammatory cytokines were not significantly elevated at early time points, suggesting elevated inflammation is a consequence of uncontrolled viral replication. Importantly, depletion of T cells, a well-known antiviral immune cell is evident within the first week of the symptom onset and these were significantly lower in the patients with persistent viral presence. This study suggest that depletion of antiviral immune cells may be a key mechanism by which SARS-CoV-2 disarms the host immune system and ensures persistent replication in the host. Uncontrolled inflammatory response, often termed as “cytokine storm” is a consequence of uncontrolled viral replication that occurs at later time points and potentially not an early contributor to the disease severity. This study highlights the important need to target the viral replication rather than the early host inflammatory response using anti-inflammatory therapies such as glucocorticoids, which should only be reserved for later stage of the disease.
Authors also attempted to culture the live virus from the throat swabs of patients in whom viral positivity was found days after confirmed negative status. This has posed a significant public health concern. The authors of this study failed to cultivate the virus, suggesting that the viral positivity on qPCR after confirmed negative results are not mediated by live infective virus, but are potentially viral remnants that are picked up by qPCR assay. These results should reassure healthcare professionals that viral reactivation after prolonged period of viral negativity is not contagious and should not pose a significant public health concern.
The Journal of Allergy and Clinical Immunology: In Practice is an official journal of the AAAAI, focusing on practical information for the practicing clinician.