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. 2020 Dec;10(2):020504.
doi: 10.7189/jogh.10.020504.

SARS-CoV-2-related pneumonia cases in pneumonia picture in Russia in March-May 2020: Secondary bacterial pneumonia and viral co-infections

Konstantin S Sharov  1
Affiliations

SARS-CoV-2-related pneumonia cases in pneumonia picture in Russia in March-May 2020: Secondary bacterial pneumonia and viral co-infections

Konstantin S Sharov. J Glob Health. 2020 Dec.

Abstract

Background: We are communicating the results of investigating statistics on SARS-CoV-2-related pneumonias in Russia: percentage, mortality, cases with other viral agents, cases accompanied by secondary bacterial pneumonias, age breakdown, clinical course and outcome.

Methods: We studied two sampling sets (Set 1 and Set 2). Set 1 consisted of results of testing 3382 assays of out-patients and hospital patients (5-88 years old) with community-acquired and hospital-acquired pneumonia of yet undetermined aetiology. Set 2 contained results of 1204 assays of hospital patients (12-94 years old) with pneumonia and COVID-19 already diagnosed by molecular biological techniques in test laboratories. The results were collected in twelve Russian cities/provinces in time range 2 March - 5 May 2020. Assays were analysed for 10 bacterial, 15 viral, 2 fungal and 2 parasitic aetiological agents.

Results: In Set 1, 4.35% of total pneumonia cases were related to SARS-CoV-2, with substantially larger proportion (18.75%) of deaths of pneumonia with COVID-19 diagnosed. However, studying Set 2, we revealed that 52.82% patients in it were also positive for different typical and atypical aetiological agents usually causing pneumonia. 433 COVID-19 patients (35.96%) were tested positive for various bacterial aetiological agents, with Streptococcus pneumoniae, Staphylococcus aureus and Haemophilus influenzae infections accounting for the majority of secondary pneumonia cases.

Conclusions: SARS-CoV-2, a low-pathogenic virus itself, becomes exceptionally dangerous if secondary bacterial pneumonia attacks a COVID-19 patient as a complication. An essential part of the severest complications and mortality associated with COVID-19 in Russia in March-May 2020, may be attributed to secondary bacterial pneumonia and to a much less extent viral co-infections. The problem of hospital-acquired bacterial infection is exceptionally urgent in treating SARS-CoV-2 patients. The risk of secondary bacterial pneumonia and its further complications, should be given very serious attention in combating SARS-CoV-2.

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Conflict of interest statement

Competing interests: The author completed the ICMJE Unified Competing Interest form (available upon request from the corresponding author) and declares no conflicts of interest.

Figures

Figure 1
Figure 1
Results of testing the broad sampling of pneumonia patients (Set 1) for different pneumonia aetiological agents. Viral agents were detected in swab samples. For Orthohantavirus, hantavirus pulmonary syndrome was detected. For different detected species of Plasmodium (P. falciparum, P. malariae, P. ovale, P. vivax) pulmonary oedema was observed. Protozoa-caused pneumonias were detected for some persons, which recently returned from epidemiologically risky areas of Africa, South Asia and Latin America. Plasmodium was detected in blood films by microscopy. Fungal agents were revealed mainly in immunocompromised persons (sputum, histology). These cases were also included in the overall pneumonia picture. Cytomegalovirus (swabs) and Escherichia coli (K1 antigen detection in blood) that were deemed to have caused pneumonias, were found only in the children and adolescents group (5-17 years). For viral pneumonia cases, tests were also made for secondary bacterial aetiological agents, with Streptococcus pneumonia (antigen detection in urine), Staphylococcus aureus (sputum/BAL, Gram cytobacterioscopy + cultural inoculation) and Haemophilus influenza of serotypes a, b, c, d, e and f (IgG antibodies to PRP antigen detection in blood + sputum/BAL cultural inoculation) infections being mainly detected (blue, cyan and green subcolumns, correspondingly). Secondary bacterial pneumonia statistics include both nosocomial and community-acquired cases. In 171 cases (5.06%), no common causative agent was identified.
Figure 2
Figure 2
In-group mortality rates in Set 1. Mortality of SARS-CoV-2-related pneumonia are further subdivided into different groups in the inset. 91.67% of lethal cases associated with COVID-19, were also related to different secondary bacterial pneumonias.
Figure 3
Figure 3
Results of testing pneumonia patients with SARS-CoV-2 (Set 2) for different viral and bacterial aetiological agents causing pneumonia. If in any of the three samples (see Methods section for a detailed explanation) bacterial agents were identified by cultural inoculation or another techniques, we counted the case in question as complicated by bacterial pneumonia. Percentage of COVID-19 patients with secondary bacterial pneumonia and different viral co-infections is shown. Escherichia coli secondary bacterial pneumonia was observed for 12-17 age group. Detection. Streptococcus pneumoniae: urine, antigen; Staphylococcus aureus: sputum/BAL, Gram cytobacterioscopy + cultural inoculation; Haemophilus influenzae of serotypes a, b, c, d, e and f: blood, IgG antibodies to PRP antigen detection, sputum/BAL, cultural inoculation; Escherichia coli: blood, K1 antigen; Mycoplasma pneumoniae: blood, IgA+IgM antibodies; swabs, multiplex RT-PCR for Mycoplasma DNA detection; Chlamydophila pneumoniae: blood, IgM antibodies; swabs, multiplex RT-PCR for DNA detection; sputum/BAL, culture inoculation; Klebsiella pneumoniae: sputum/BAL, spectrophotometry assay for detection of Kl. pneum. carbapenemase KPC+RT-PCR for bla-KPC gene; sputum/BAL, cultural inoculation + detection of indole, ornithine decarboxylase, acetone (Voges-Proskauer reaction), o-nitrophenyl-β-D-galactopyranoside synthesis malonate utilization in a broth culture; Legionela pneumophila: urine, antigen, specific buffered charcoal yeast extract (BCYE) alpha culture inoculation with cysteine and Fe4(P2O7)3; Moraxella catarrhalis: swabs, multiplex RT-PCR for DNA detection, sputum, culture inoculation; Pseudomonas aeruginosa: blood, IgG antibodies; sputum/BAL, culture inoculation in trypticase soy agar; all virus agents: multiplex RT-PCR technique.
Figure 4
Figure 4
Regression analysis of viral co-infections (left) and secondary bacterial pneumonias (right) in Set 2. Viral co-infection dependency on age is fitted with asymmetric Giddings peak function introduced by J. Calvin Giddings [34-36] (explanation in the Online Supplementary Document). Secondary bacterial pneumonia percentage grows with age and may be satisfactorily fitted with a power function: Psecond. act. pneum. = a + btc. Factors of regression quality (χred2, Radj2), coefficients and errors of regression are provided in the figure (inset tables).
Figure 5
Figure 5
The structure of Set 2. The proportion of secondary bacterial pneumonias, viral co-infections and SARS-CoV-2 pneumonias not complicated by different aetiological agents.
Figure 6
Figure 6
Proportion of community-acquired and hospital-acquired secondary bacterial pneumonias and viral co-infections in pneumonia patients tested positive for SARS-CoV-2 (Set 2).
Figure 7
Figure 7
Clinical course and outcomes for 1204 pneumonia patients tested positive for SARS-CoV-2 (Set 2). Oxygenation through Non-invasive ventilation (NIV) was applied for patients with slight degrees of respiratory failure of type 1 (hypoxemic respiratory failure). Acute respiratory distress syndrome (ARDS) and severe respiratory failure of type 1 resulted in three outcomes: fatality, recovery with lung fibrosis of different intensity or full recovery without pathological consequences for lungs. All patients with ARDS were oxygenated with the help of mechanical ventilators or extracorporeal membrane oxygenation (ECMO) apparatuses in intensive care units. The sum of column values in any of the four quintuplets is 100%.
Figure 8
Figure 8
Scatter matrix for different cases of pneumonia aetiological agents presence other than SARS-CoV-2.
Figure 9
Figure 9
Age breakdown of mortality of pneumonia patients tested positive for SARS-CoV-2 with respect to different bacterial and/or viral co-infections. The absolute number of cases is provided in the main graph, and percentage is provided in the inset. The sum of column values in any of the four quadruplets in the inset is 100%.
Figure 10
Figure 10
Scatter matrix for different age groups. 12-17 and 18-29 age groups are represented by one point, as they are statistically identical.
Figure 11
Figure 11
Different sets of people affected by SARS-CoV-2 in Russian population. Circles area proportions do not reflect with percentages of sets A-F. Current population infection rate B/A = 0.04 (official data on population mass screening) [38]. Ratio of symptomatic patients to all carriers C/B = 0.455 (our unpublished data on large sampling symptomatic study). Percentage of pneumonia COVID-19 patients in symptomatic cohort D/C = 0.13 (our unpublished data on large sampling symptomatic study). Ratio of ARDS complications in SARS-CoV-2 related pneumonia E/D = 0.147 (determined in the current study, on analysing Set 2). Mortality in cohort E F/E = 0.503 (determined in the current study, on analysing Set 2).
Figure 12
Figure 12
Change of protocols in calculating COVID-19-related mortality in Russia on 18 May 2020. Red arrow points at the date of change. Case fatality rate (CFR) = total deaths (accumulated) / total positive cases (accumulated). Official Russian statistics are taken into account [38]. Calculated regression factors, coefficients and their standard errors are presented in the insets.
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