COVID-19 Autopsies Reveal Underreporting of SARS-CoV-2 Infection and Scarcity of Co-infections

Abstract

Coronavirus disease 2019 (COVID-19) mortality can be estimated based on reliable mortality data. Variable testing procedures and heterogeneous disease course suggest that a substantial number of COVID-19 deaths is undetected. To address this question, we screened an unselected autopsy cohort for the presence of SARS-CoV-2 and a panel of common respiratory pathogens. Lung tissues from 62 consecutive autopsies, conducted during the first and second COVID-19 pandemic waves in Switzerland, were analyzed for bacterial, viral and fungal respiratory pathogens including SARS-CoV-2. SARS-CoV-2 was detected in 28 lungs of 62 deceased patients (45%), although only 18 patients (29%) were reported to have COVID-19 at the time of death. In 23 patients (37% of all), the clinical cause of death and/or autopsy findings together with the presence of SARS-CoV-2 suggested death due to COVID-19. Our autopsy results reveal a 16% higher SARS-CoV-2 infection rate and an 8% higher SARS-CoV-2 related mortality rate than reported by clinicians before death. The majority of SARS-CoV-2 infected patients (75%) did not suffer from respiratory co-infections, as long as they were treated with antibiotics. In the lungs of 5 patients (8% of all), SARS-CoV-2 was found, yet without typical clinical and/or autopsy findings. Our findings suggest that underreporting of COVID-19 contributes substantially to excess mortality. The small percentage of co-infections in SARS-CoV-2 positive patients who died with typical COVID-19 symptoms strongly suggests that the majority of SARS-CoV-2 infected patients died from and not with the virus.

Keywords: COVID-19; SARS-CoV-2; autopsy; bacterial co-infection; infection; mortality; respiratory failure.

FIGURE 1

Coronavirus disease 2019 (COVID-19) epidemiology and stratification of patients. (A) Weekly numbers of COVID-19 cases (black interconnected dots, right axis) and deaths (red bars, left axis) in Switzerland from March 2020 until November 2021. Blue boxes represent time windows for collection of consecutive autopsies. Source of data: Bundesamt für Gesundheit (BAG) Switzerland, December 12, 2021. (B) Partition of autopsy cohort according to COVID-19 diagnosis, SARS-CoV-2 infection, co-infection, and antibacterial treatment.

FIGURE 2

Overview of patient characteristics, clinical data, and autopsy findings of all 62 autopsies during the first (n = 25) and second (n = 37) wave of the COVID-19 pandemic. BMI, body mass index; ICU, intensive care unit.

FIGURE 3

SARS-CoV-2 organ distribution in all 28 autopsy cases with SARS-CoV-2 positive lung tissues. (A) Percentage of SARS-CoV-2 positive heart, adrenal gland, kidney, pancreas, liver and thyroid samples of all SARS-CoV-2 infected patients. Viral load in organs of (B) patients with a clinically known COVID-19 diagnosis (n = 18), and (C) unexpected SARS-CoV-2 positive cases (n = 10). Data represent median of three technical replicates, lines connect data from the same individual. Median viral loads of SARS-CoV-2 in different organs are listed in Supplementary Table 4.

FIGURE 4

Co-infections in autopsy cases. (A) Left, SARS-CoV-2 positive and right, SARS-CoV-2 negative patients. (B) Types of co-infections identified in the autopsy cohort of SARS-CoV-2 positive and negative patients. (C) Left, bacterial co-infections in individuals with antibiotic treatment. Right, bacterial co-infections in individuals without antibiotic treatment. (D) Bacterial co-infections in relation to duration of hospitalization, ICU care or mechanical ventilation.

FIGURE 5

Representative lung histology of (A) a patient with clinically known COVID-19 showing DAD with hyaline membranes, heavy inflammatory infiltration and squamous metaplasia; (B) a patient with clinically known COVID-19 showing only discrete morphological changes in his lungs; (C) a patient who was unexpectedly SARS-CoV-2 positive post mortem with bacterial co-infection and signs of acute bronchopneumonia; (D) a patient who was unexpectedly SARS-CoV-2 positive post mortem with emphysema and discrete edema, but no relevant inflammation. Scale bar, 100 μm.