COVID-19: Multiorgan Dissemination of SARS-CoV-2 Is Driven by Pulmonary Factors

Abstract

Multi-organ failure is one of the common causes of fatal outcome in COVID-19 patients. However, the pathogenetic association of the SARS-CoV-2 viral load (VL) level with fatal dysfunctions of the lungs, liver, kidneys, heart, spleen and brain, as well as with the risk of death in COVID-19 patients remains poorly understood. SARS-CoV-2 VL in the lungs, heart, liver, kidneys, brain, spleen and lymph nodes have been measured by RT qPCR using the following formula: NSARS-CoV−2/NABL1 × 100. Dissemination of SARS-CoV-2 in 30.5% of cases was mono-organ, and in 63.9% of cases, it was multi-organ. The average SARS-CoV-2 VL in the exudative phase of diffuse alveolar damage (DAD) was 60 times higher than in the proliferative phase. The SARS-CoV-2 VL in the lungs ranged from 0 to 250,281 copies. The “pulmonary factors” of SARS-CoV-2 multi-organ dissemination are the high level of SARS-CoV-2 VL (≥4909) and the exudative phase of DAD. The frequency of SARS-CoV-2 dissemination to lymph nodes was 86.9%, heart–56.5%, spleen–52.2%, liver–47.8%, kidney–26%, and brain–13%. We found no link between the SARS-CoV-2 VL level in the liver, kidneys, and heart and the serum level of CPK, LDH, ALP, ALT, AST and Cr of COVID-19 patients. Isolated detection of SARS-CoV-2 RNA in the myocardium of COVID-19 patients who died from heart failure is possible. The pathogenesis of COVID-19-associated multi-organ failure requires further research in a larger cohort of patients.

Current Updates on COVID-19 Vaccines and Therapeutics: As of June 2022

“…The coronavirus disease 2019 (COVID-19) pandemic is the hottest global topic of 2020-2022, and it shook the political, economic, cultural, and public healthcare fields worldwide. SARS-CoV-2 (SCoV2) primarily infects the upper respiratory tract and exhibits gradual dissemination to multiple organs such as the lung, liver, kidney, heart, spleen, and brain, following various symptoms after an infection period of approximately 3-5 days [1][2][3]. Although the incubation period and fatality fluctuate according to its genomic variants, SCoV2 has shown an average fatality of approximately 1.18% (cumulative deaths/cases: 6,314,972/ 535,863,950, as of June 22, 2022) over the past two years [4].…”

Pathological Findings Associated With SARS-CoV-2 on Postmortem Core Biopsies: Correlation With Clinical Presentation and Disease Course

“…The presence of elevated LDH represents cell necrosis activity and inflammation, which is what happens with DAD. In the literature, severe course and fatal outcomes of COVID-19 due to multi-organ injury are associated with high LDH ( 47 ). The relationship between tocilizumab and DAD may be a consequence of using tocilizumab in more severe patients rather than because tocilizumab is a risk factor for DAD in and of itself.…”

SARS‐CoV‐2 cellular tropism and direct multiorgan failure in COVID‐19 patients: Bioinformatic predictions, experimental observations, and open questions

“…Autopsy reports have provided evidence that the virus can directly infect the kidney cells of COVID‐19 patients (Bradley et al, 2020 ; Diao et al, 2021 ; Jansen et al, 2022 ; Liu et al, 2021 ; Menter et al, 2020 ; Müller et al, 2021 ; Odilov et al, 2021 ; Puelles et al, 2020 ). SARS‐CoV‐2 particles were isolated from an autopsied kidney and subsequently shown to infect Vero cells, thus confirming the presence of infective virus in the kidney, even under postmortem conditions (Braun et al, 2020 ).…”