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Background:
Systematic Review

Global Coinfections with Bacteria, Fungi, and Respiratory Viruses in Children with SARS-CoV-2: A Systematic Review and Meta-Analysis

by Saad Alhumaid 1,*, Muneera Alabdulqader 2, Nourah Al Dossary 3, Zainab Al Alawi 4, Abdulrahman A. Alnaim 5, Koblan M. Al Mutared 6, Khalid Al Noaim 5, Mohammed A. Al Ghamdi 7, Suha Jafar Albahrani 8, Abdulaziz A. Alahmari 7, Sarah Mahmoud Al Hajji Mohammed 9, Yameen Ali Almatawah 10, Omar Musa Bayameen 11, Ahmed Abdulwhab Alismaeel 11, Sherifah Khaled Alzamil 11, Samiah Ahmad Alturki 11, Zahra’a Radi Albrahim 11, Nasreen Ahmad Al Bagshi 11, Hesham Yousef Alshawareb 12, Jaafar Abdullah Alhudar 13, Qassim Abdulatif Algurairy 14, Samirah Mansour Alghadeer 15, Hassan Ali Alhadab 16, Taleb Nasser Aljubran 9, Yousif Ahmad Alabdulaly 17, Abbas Al Mutair 18,19,20,21 and Ali A. Rabaan 22,23,24add Show full author list remove Hide full author list
1
Administration of Pharmaceutical Care, Al-Ahsa Health Cluster, Ministry of Health, Al-Ahsa 31982, Saudi Arabia
2
Pediatric Nephrology Specialty, Pediatric Department, Medical College, King Faisal University, Al-Ahsa 31982, Saudi Arabia
3
General Surgery Department, Alomran General Hospital, Ministry of Health, Al-Ahsa 36358, Saudi Arabia
4
Division of Allergy and Immunology, College of Medicine, King Faisal University, Al-Ahsa 31982, Saudi Arabia
5
Department of Pediatrics, College of Medicine, King Faisal University, Al-Ahsa 31982, Saudi Arabia
6
Administration of Pharmaceutical Care, Ministry of Health, Najran 66255, Saudi Arabia
7
Department of Pediatrics, King Fahad Hospital of the University, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam 34212, Saudi Arabia
8
Division of Diabetology, Family Medicine Department, College of Medicine, King Faisal University, Al-Ahsa 36364, Saudi Arabia
9
Pharmacy Department, Prince Saud Bin Jalawi Hospital, Al-Ahsa 36424, Saudi Arabia
10
Division of Infectious Diseases and Infection Control, Pediatric Department, Maternity and Children Hospital, Ministry of Health, Al-Ahsa 36422, Saudi Arabia
11
Public Health Administration, Directorate of Health Affairs, Ministry of Health, Al-Ahsa 36441, Saudi Arabia
12
Southern Sector, Primary Care Medicine, Al-Ahsa Health Cluster, Ministry of Health, Al-Ahsa 36421, Saudi Arabia
13
Regional Medical Supply, Al-Ahsa Health Cluster, Ministry of Health, Al-Ahsa 36361, Saudi Arabia
14
Nutrition Department, King Fahad Hofuf Hospital, Ministry of Health, Al-Ahsa 36441, Saudi Arabia
15
Infection Prevention and Control Administration, Al-Ahsa Health Cluster, Ministry of Health, Al-Ahsa 36421, Saudi Arabia
16
Ambulatory Transportation Administration, Al-Ahsa Health Cluster, Ministry of Health, Al-Ahsa 36421, Saudi Arabia
17
Quality Assurance and Patient Safety Administration, Directorate of Health Affairs, Ministry of Health, Al-Ahsa 36441, Saudi Arabia
18
Research Center, Almoosa Specialist Hospital, Al-Ahsa 36342, Saudi Arabia
19
College of Nursing, Princess Norah Bint Abdulrahman University, Riyadh 11564, Saudi Arabia
20
School of Nursing, Wollongong University, Wollongong, NSW 2522, Australia
21
Department of Nursing, Prince Sultan Military College, Dhahran 34313, Saudi Arabia
22
Molecular Diagnostic Laboratory, Johns Hopkins Aramco Healthcare, Dhahran 31311, Saudi Arabia
23
College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia
24
Department of Public Health/Nutrition, The University of Haripur, Haripur 22620, Khyber Pakhtunkhwa, Pakistan
*
Author to whom correspondence should be addressed.
Trop. Med. Infect. Dis. 2022, 7(11), 380; https://doi.org/10.3390/tropicalmed7110380
Submission received: 20 October 2022 / Revised: 1 November 2022 / Accepted: 7 November 2022 / Published: 15 November 2022
(This article belongs to the Section Infectious Diseases)

Abstract

:
Background: Coinfection with bacteria, fungi, and respiratory viruses has been described as a factor associated with more severe clinical outcomes in children with COVID-19. Such coinfections in children with COVID-19 have been reported to increase morbidity and mortality. Objectives: To identify the type and proportion of coinfections with SARS-CoV-2 and bacteria, fungi, and/or respiratory viruses, and investigate the severity of COVID-19 in children. Methods: For this systematic review and meta-analysis, we searched ProQuest, Medline, Embase, PubMed, CINAHL, Wiley online library, Scopus, and Nature through the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for studies on the incidence of COVID-19 in children with bacterial, fungal, and/or respiratory coinfections, published from 1 December 2019 to 1 October 2022, with English language restriction. Results: Of the 169 papers that were identified, 130 articles were included in the systematic review (57 cohort, 52 case report, and 21 case series studies) and 34 articles (23 cohort, eight case series, and three case report studies) were included in the meta-analysis. Of the 17,588 COVID-19 children who were tested for co-pathogens, bacterial, fungal, and/or respiratory viral coinfections were reported (n = 1633, 9.3%). The median patient age ranged from 1.4 months to 144 months across studies. There was an increased male predominance in pediatric COVID-19 patients diagnosed with bacterial, fungal, and/or viral coinfections in most of the studies (male gender: n = 204, 59.1% compared to female gender: n = 141, 40.9%). The majority of the cases belonged to White (Caucasian) (n = 441, 53.3%), Asian (n = 205, 24.8%), Indian (n = 71, 8.6%), and Black (n = 51, 6.2%) ethnicities. The overall pooled proportions of children with laboratory-confirmed COVID-19 who had bacterial, fungal, and respiratory viral coinfections were 4.73% (95% CI 3.86 to 5.60, n = 445, 34 studies, I2 85%, p < 0.01), 0.98% (95% CI 0.13 to 1.83, n = 17, six studies, I2 49%, p < 0.08), and 5.41% (95% CI 4.48 to 6.34, n = 441, 32 studies, I2 87%, p < 0.01), respectively. Children with COVID-19 in the ICU had higher coinfections compared to ICU and non-ICU patients, as follows: respiratory viral (6.61%, 95% CI 5.06–8.17, I2 = 0% versus 5.31%, 95% CI 4.31–6.30, I2 = 88%) and fungal (1.72%, 95% CI 0.45–2.99, I2 = 0% versus 0.62%, 95% CI 0.00–1.55, I2 = 54%); however, COVID-19 children admitted to the ICU had a lower bacterial coinfection compared to the COVID-19 children in the ICU and non-ICU group (3.02%, 95% CI 1.70–4.34, I2 = 0% versus 4.91%, 95% CI 3.97–5.84, I2 = 87%). The most common identified virus and bacterium in children with COVID-19 were RSV (n = 342, 31.4%) and Mycoplasma pneumonia (n = 120, 23.1%). Conclusion: Children with COVID-19 seem to have distinctly lower rates of bacterial, fungal, and/or respiratory viral coinfections than adults. RSV and Mycoplasma pneumonia were the most common identified virus and bacterium in children infected with SARS-CoV-2. Knowledge of bacterial, fungal, and/or respiratory viral confections has potential diagnostic and treatment implications in COVID-19 children.

1. Introduction

Although most cases of coronavirus disease 2019 (COVID-19) in pediatric populations are mild or asymptomatic [1], the clinical spectrum of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children ranges from asymptomatic to life-threatening [2,3]. Similar to adults, coinfection with bacteria, fungi, and respiratory viruses has been described as a factor associated with more severe clinical outcomes in children with COVID-19 [4,5,6,7,8,9,10,11]. Such coinfections have been reported to increase morbidity and mortality, therefore, knowledge of bacterial, fungal, and/or respiratory viral confections has potential diagnostic and treatment implications in children infected with SARS-CoV-2. Many studies have shown that COVID-19 children may develop severe diseases, requiring intensive care admission and/or mechanical ventilation because patients rapidly develop acute respiratory distress syndrome and sepsis, leading to death from multiple organ failure [12,13,14,15,16,17,18,19,20,21,22,23]. SARS-CoV-2 is hypothesized to weaken the bodies of children to bacterial, fungal, and/or respiratory viral coinfections [24], yet the mechanism of coinfection has not been fully established, but represents a threat to the respiratory epithelium favoring bacteremia, fungaemia, and/or viraemia (see Figure 1).
There is a lack of systematic reviews and meta-analyses on the type and frequency of coinfection by bacterial, fungal, and/or respiratory viral infections and associated clinical outcomes among COVID-19 children. We aimed to identify the type and proportion of coinfections with SARS-CoV-2 and bacteria, fungi, and/or respiratory viruses, and investigate the severity of COVID-19 in these patients.

2. Methods

2.1. Design

We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PRISMA) in conducting this systematic review and meta-analysis [25]. The following electronic databases were searched: PROQUEST, MEDLINE, EMBASE, PUBMED, CINAHL, WILEY ONLINE LIBRARY, SCOPUS, and NATURE with Full Text. We used the following keywords: (“COVID-19” OR “SARS-CoV-2” OR “Severe acute Respiratory Syndrome Coronavirus 2” OR “Coronavirus Disease 2019” OR “2019 novel coronavirus”) AND (“children” OR “child” OR “paediatric” OR “pediatric” OR “infant” OR “toddler” OR “adolescent” OR “newborn”) AND (“coinfection” OR “co-infection” OR “cocirculation” OR “co-circulation” OR “coinfected” OR “co-infected” OR “co-circulated” OR “mixed” OR “concurrent” OR “concomitant”). The search was limited to papers published in English between 1 December 2019 and 1 October 2022. Based on the title and abstract of each selected article, we selected those discussing and reporting the occurrence of bacterial, fungal, and/or respiratory viral coinfection in children with COVID-19.

2.2. Inclusion–Exclusion Criteria

Inclusion criteria were as follows: (1) published case reports, case series, and cohort studies that focused on children infected with SARS-CoV-2 and bacteria, fungi, and/or respiratory viruses; (2) studies of experimental or observational design reporting the incidence of SARS-CoV-2 infection in pediatric patients with other co-pathogens; (3) language restricted to English. The exclusion criteria were as follows: (1) editorials, commentaries, case and animal studies, reviews, and meta-analyses; (2) studies that did not report data on COVID-19 in coinfected patients; (3) studies that never reported details on identified coinfected cases with SARS-CoV-2 infection; (4) studies that reported coinfection in adult COVID-19 patients; (5) studies that reported coinfection in patients with negative SARS-CoV-2 polymerase chain reaction (PCR) tests; (6) duplicate publications.

2.3. Data Extraction

Six authors (Saad Alhumaid, Muneera Alabdulqader, Nourah Al Dossary, Zainab Al Alawi, Abdulrahman A. Alnaim, and Koblan M. Al mutared) critically reviewed all of the studies retrieved and selected those judged to be the most relevant. Data were carefully extracted from the relevant research studies independently. Articles were categorized as case report, case series, or cohort studies. The following data were extracted from selected studies: authors; publication year; study location; study design and setting; number of SARS-CoV-2 children tested for co-pathogens; number of coinfected children; age; proportion of male children; patient ethnicity; number of children with bacterial, fungal, and/or respiratory viral coinfections; total organisms identified; antimicrobials prescribed; laboratory techniques for co-pathogen detection; number of children admitted to intensive care unit (ICU), placed on mechanical ventilation, and/or suffered acute respiratory distress syndrome (ARDS); assessment of study risk of bias; and final treatment outcome (survived or died). These data are noted in Table 1.

2.4. Quality Assessment

For many selected cohort studies, the Newcastle–Ottawa scale (NOS) was used to assess the risk of bias, a tool which measures quality in the three parameters of selection, comparability, and exposure/outcome, and allocates a maximum of 4, 2, and 3 points, respectively [26]. High-quality studies are scored greater than 7 on this scale, and moderate-quality studies between 5 and 7 [26]. Otherwise, quality assessment of the selected case report and case series studies was undertaken based on the modified NOS [27]. Items related to the comparability and adjustment were removed from the NOS, and items which focused on selection and representativeness of cases, and the ascertainment of outcomes and exposure, were kept [27]. Modified NOS consists of five items, each of which requires a yes or no response to indicate whether bias is likely, and these items were applied to single-arm studies [27]. Quality of the study was considered good if all five criteria were met, moderate when four were met, and poor when three or less were met. Quality assessment was performed by six authors (Khalid Al Noaim, Mohammed A. Al Ghamdi, Suha Jafar Albahrani, Abdulaziz A. Alahmari, Sarah Mahmoud Al HajjiMohammed, and Yameen Ali Almatawah) independently, with any disagreement to be resolved by consensus.

2.5. Data Analysis

The proportion of confirmed COVID-19 children with bacterial, fungal, and/or respiratory viral coinfection were examined. This proportion was further classified based on initial presentation or during the course of the illness. A random effects DerSimonian–Laird model was used, which produces wider confidence intervals (Cis) than a fixed effect model [28]. Results are illustrated using a forest plot. The Cochran’s chi-square (χ2) and the I2 statistic provided the tools for examining statistical heterogeneity [29]. An I2 value of >50% suggested significant heterogeneity [30]. To lower the source of heterogeneity, we conducted a subgroup analysis based on children’s admission to the ICU. To estimate publication bias, funnel plots and Egger’s correlation were used, and a p-value < 0.05 was considered to indicate statistical significance. All p-values were based on two-sided tests and significance was set at a p-value less than 0.05. R version 4.1.0 with the packages finalfit and forestplot was used for all statistical analyses. Figure 1 was created with BioRender.com (agreement no. NX24IV1VNB) (accessed on 14 October 2022).

3. Results

3.1. Study Characteristics and Quality

A total of 130 publications were identified (Figure 2). After scanning titles and abstracts, 67 duplicate articles were discarded. Another 33 irrelevant articles were excluded based on the titles and abstracts. The full texts of the 378 remaining articles were reviewed, and 248 irrelevant articles were excluded. As a result, we identified 130 studies that met our inclusion criteria and reported SARS-CoV-2 infection in pediatric patients with bacterial, fungal, and viral coinfection [4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82,83,84,85,86,87,88,89,90,91,92,93,94,95,96,97,98,99,100,101,102,103,104,105,106,107,108,109,110,111,112,113,114,115,116,117,118,119,120,121,122,123,124,125,126,127,128,129,130,131,132,133,134,135,136,137,138,139,140]. The detailed characteristics of the included studies are shown in Table 1. Among these, two articles were preprint versions [64,89]. There were 57 cohort [4,5,6,7,8,9,10,11,12,17,31,32,34,35,36,37,39,41,42,44,49,53,58,66,69,71,73,78,79,80,81,82,83,84,89,90,95,98,99,102,105,108,109,115,116,118,119,123,125,127,129,131,133,134,137,138,139], 52 case report [13,14,15,16,18,19,21,22,23,33,38,40,43,45,46,48,50,51,52,55,56,59,64,65,67,68,70,72,74,75,76,77,86,87,91,93,94,97,104,106,107,110,111,113,114,121,122,124,126,128,130,140], and 21 case series [20,47,54,57,60,61,62,63,85,88,92,96,100,101,103,112,117,120,132,135,136] studies. These studies were conducted in the United States (n = 23), China (n = 21), India (n = 9), Italy (n = 7), Iran (n = 7), France (n = 6), Turkey (n = 6), Spain (n = 5), Mexico (n = 4), Brazil (n = 4), Indonesia (n = 4), South Africa (n = 3), Switzerland (n = 3), Poland (n = 3), United Kingdom (n = 3), Argentina (n = 2), Saudi Arabia (n = 2), United Arab Emirates (n = 1), Portugal (n = 1), Malaysia (n = 1), Thailand (n = 1), Bulgaria (n = 1), The Netherlands (n = 1), Germany (n = 1), Lebanon (n = 1), Botswana (n = 1), Denmark (n = 1), Russia (n = 1), Pakistan (n = 1), Bangladesh (n = 1), Japan (n = 1), Greece (n = 1), and Canada (n = 1). Only four studies were conducted within multiple countries (n = 4) [53,109,118,127]. The majority of the studies were single-center [4,6,11,12,13,14,15,16,18,19,21,22,23,32,33,34,35,38,39,40,41,43,44,45,46,48,49,50,51,52,55,56,57,59,60,61,62,64,65,66,67,68,69,70,72,73,74,75,76,77,78,79,80,81,82,83,85,86,87,88,89,90,91,92,93,94,97,98,99,100,101,102,103,104,105,106,107,111,112,113,114,115,116,117,120,121,122,124,126,128,130,132,133,134,138,139,140] and only 33 studies were multicenter [5,7,8,9,10,17,20,31,36,37,42,47,53,54,58,63,71,84,95,96,108,109,110,118,119,123,125,127,129,131,135,136,137]. In some studies, concurrent infection of SARS-CoV-2 with other bacterial, fungal, and/or viral pathogens was investigated in pediatric and adult patients as the population of interest (19/130, 14.6%) [10,17,31,37,47,54,57,62,71,79,82,90,96,102,108,112,118,123,139]. The majority (n = 128) of the studies included any hospitalized patient, except for two studies that investigated potential of SARS-CoV-2 transmission in a cluster and genomic analysis of SARS-CoV-2 in a family [47,62], and two studies included only critically ill COVID-19 patients [9,18]. Eleven, four, and one studies exclusively reported on respiratory viral [10,18,31,35,61,71,73,89,101,125,140], bacterial [11,96,100,112], and fungal [90] coinfections, respectively; the remaining 114 studies reported on bacterial, fungal, and respiratory viral coinfections [4,5,6,7,8,9,12,13,14,15,16,17,19,20,21,22,23,32,33,34,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,62,63,64,65,66,67,68,69,70,72,74,75,76,77,78,79,80,81,82,83,84,85,86,87,88,91,92,93,94,95,97,98,99,102,103,104,105,106,107,108,109,110,111,113,114,115,116,117,118,119,120,121,122,123,124,126,127,128,129,130,131,132,133,134,135,136,137,138,139]. Few studies investigated the existence of COVID-19 with influenza virus type A and B only [31,101,140], Mycobacterium tuberculosis only [11,96,112], respiratory syncytial virus (RSV) only [35,61], Rhinovirus only [10,125], pneumovirus only [18], herpes simplex virus only [71], human coronavirus OC43 only [73], adenovirus only [89], Mycoplasma pneumonia only [100], and Candida species only [90]. Laboratory techniques for co-pathogen detection within studies included 52 that used real-time reverse transcription–polymerase chain reaction (RT-PCR) tests for multiple respiratory viruses [9,10,17,18,31,34,37,41,43,44,46,47,48,49,61,65,66,68,69,71,73,76,79,80,81,82,83,89,91,92,95,99,101,102,110,113,115,116,117,119,123,125,127,129,130,131,132,135,136,137,138,139], 23 that used antibody tests (immunoglobulins M and/or G) [5,8,22,23,45,52,54,56,70,72,77,78,81,85,98,100,104,108,111,120,122,133,140], 42 that used cultures (blood, urine, cerebrospinal fluid, tracheal, nasal discharge, pharyngeal swabs, wound, respiratory secretions, bronchoalveolar lavage, alveolar fluid, sputum, and pleural fluid) [5,6,11,12,13,15,16,20,21,23,38,40,42,50,51,53,55,60,63,64,74,75,84,85,87,88,90,93,96,97,105,106,107,109,112,114,118,121,124,126,128,134], 29 that used two or more laboratory methods (RT-PCR, antibody tests, and/or culture) [4,5,6,7,8,12,20,23,36,39,42,50,52,53,57,58,63,72,77,78,81,84,85,98,105,109,124,126,133], and two that did not specify their testing method [32,33]. Among the 130 included studies, 57 cohort studies were assessed using the NOS: 52 studies were found to be moderate-quality studies (i.e., NOS scores were between 5 and 7) and five studies demonstrated a relatively high quality (i.e., NOS scores > 7). All case reports and case series studies were assessed for bias using the modified NOS. Forty-nine studies were deemed to have high methodological quality, and three exhibited moderate methodological quality; Table 1.
Table 1. Summary of the characteristics of the included studies with evidence on SARS-CoV-2 and bacterial, fungal, and/or respiratory viral coinfections in children (n = 130), 2020–2022.
Table 1. Summary of the characteristics of the included studies with evidence on SARS-CoV-2 and bacterial, fungal, and/or respiratory viral coinfections in children (n = 130), 2020–2022.
Author, Year, Study LocationStudy Design, SettingNumber of SARS-CoV-2 Patients Tested for Co-Pathogens, nCoinfected Patients, nAge (Months) aMale, n (%) AND Ethnicity, n bBacterial Coinfection, nFungal Coinfection, nRespiratory Viral Coinfection, nTotal Organisms, nAntimicrobials Used, nLaboratory Techniques for Co-Pathogen DetectionAdmitted to ICU, nMechanical Ventilation, nARDS, nAssessment of Study Risk of Bias (Tool Used, Finding) and Treatment Outcome
Aggarwal et al. 2022 [31], IndiaRetrospective cohort, multicenter770412, 18, 96, and 723 (75)
AND
4 Indian
0063 Influenza A virus
3 Influenza B virus
0RT-PCR for respiratory specimens (viruses) c000(NOS, 7)
4 survived
Al Mansoori et al. 2021 [32], United Arab EmiratesRetrospective cohort, single-center177Median (IQR), 84 (0–192)Gender (not reported)
AND
Ethnicity (not reported)
2053 Rhinovirus
2 Group A Streptococcus
1 Enterovirus
1 Adenovirus
7 Not reportedRT-PCR for respiratory specimens (viruses) c
Not reported (Group A Streptococcus)
000(NOS, 6)
Treatment outcome (not reported)
Allen-Manzur et al. 2020 [33], MexicoRetrospective case report, single-center1160 (0)
AND
1 Hispanic
1001 Mycobacterium bovis1 Not reportedRT-PCR for respiratory specimens (viruses) c
Not reported (Mycobacterium bovis)
000(Modified NOS, moderate)
1 survived
Alrayes et al. 2022 [34], United StatesRetrospective cohort, single-center1313Age group 0–2: 270 (71.3%) patients (RSV coinfection)Gender (not reported)
AND
Ethnicity (not reported)
001513 RSV
1 Rhinovirus
1 Adenovirus
13 Not reportedRT-PCR for respiratory specimens (viruses) c000(NOS, 7)
13 survived
Alvares 2021 [35], BrazilRetrospective cohort, single-center326Median (IQR), 62 (33.3)
AND
6 Hispanic
0066 RSV1 Not reportedChemiluminescence for RSV111 Not reported(NOS, 6)
6 survived
Anderson et al. 2021 [4], United StatesRetrospective cohort, single-center2910Age group 168 (42–198): 10 (34.4%) patients
Age group 192 (168–204): 9 (31%) patients
Age group 102 (72–168): 10 (34.4%) patients
Gender (not reported)
AND
Ethnicity (not reported)
5062 Staphylococcus aureus
2 Escherichia coli
1 Salmonella enteritis
1 Enterovirus
1 Adenovirus
2 Rhinovirus
1 Parainfluenza virus
1 EBV
10 Not reportedRT-PCR for respiratory specimens (viruses) c
PCR assays (bacteria)
723(NOS, 8)
7 survived
3 died
Andina-Martinez et al. 2022 [36], SpainProspective cohort, multicenter921.3 and 1.81 (50)
AND
2 White (Caucasian)
1011 Bordetella pertussis
1 Metapneumovirus
2 AzithromycinRT-PCR for respiratory specimens (viruses) c
PCR assays (Mycoplasma pneumoniae, Chlamydia pneumoniae and Bordetella pertussis)
112 Not reported(NOS, 7)
2 survived
Aragón-Nogales et al. 2022 [12], MexicoProspective cohort, single-center181212 and 240 (0)
AND
2 Hispanic
1011 Pseudomonas aeruginosa
1 EBV
1 Cefotaxime
1 Ceftriaxone
RT-PCR for respiratory specimens (viruses) c
Blood culture (bacteria)
222(NOS, 7)
2 died
Arguni et al. 2022 [37], IndonesiaRetrospective cohort, multicenter12559Two patients: <12 months to <60 months
Six patients: <60 months to <216 months
Gender (not reported)
AND
8 Asian
005932 Influenza A virus
10 Adenovirus
16 Influenza B virus
1 Metapneumovirus
59 Not reportedRT-PCR for respiratory specimens (viruses) c59 Not reported59 Not reported59 Not reported(NOS, 6)
Treatment outcome (not reported)
Arslan et al. 2021 [38], TurkeyRetrospective case report, single-center11101 (100)
AND
1 White (Caucasian)
1001 MSSA1 Clindamycin
1 Ceftriaxone
Blood culture (bacteria)000(Modified NOS, high)
1 survived
Aykac et al. 2021 [39], TurkeyRetrospective cohort, single-center11537Median (IQR), 48 (12–132)Gender (not reported)
AND
37 White (Caucasian)
370437 Streptococcus pneumoniae
2 Bocavirus
1 Rhinovirus
1 Parechovirus
7 Ceftriaxone
7 Azithromycin
7 Ampicillin/sulbactam
RT-PCR for respiratory specimens (viruses) c
PCR assays (Streptococcus pneumoniae)
111(NOS, 6)
Treatment outcome (not reported)
Ayoubzadeh et al. 2021 [40], CanadaRetrospective case report, single-center111681 (100)
AND
1 Pakistani
1001 Gram-negative bacilli
1 Salmonella Typhi
1 Meropenem
1 Ampicillin
1 Amoxicillin
Blood culture (bacteria)000(Modified NOS, high)
1 survived
Berksoy et al. 2021 [41], TurkeyRetrospective
cohort, single-center
128211 patient: 5
Other patients: not reported
Gender (not reported)
AND
21 White (Caucasian)
00239 Rhinovirus
5 Metapneumovirus
4 RSV
3 Adenovirus
2 Bocavirus
21 Not reportedRT-PCR for respiratory specimens (viruses) c21 Not reported021 Not reported(NOS, 6)
Treatment outcome (not reported)
Blázquez-Gamero et al. 2021 [42], SpainRetrospective
cohort, multicenter
2721 and 3Gender (not reported)
AND
27 White (Caucasian)
3001 Streptococcus mitis
1 Escherichia coli
1 Enterobacter cloacae
2 Ampicillin
1 Gentamycin
1 3rd -generation cephalosporin
RT-PCR for respiratory specimens (viruses) c
Blood culture (bacteria)
Urine culture (bacteria)
111(NOS, 7)
2 survived
Borocco et al. 2021 [43], FranceRetrospective case report, single-center111560 (0)
AND
1 Arab
0011 EBV0RT-PCR for respiratory specimens (viruses) c000(Modified NOS, high)
1 survived
Brothers et al. 2021 [13], United StatesRetrospective case report, single-center111440 (0)
AND
1 White (Caucasian)
1101 MSSA
1 Candida glabrata
1 Clindamycin
1 Vancomycin 1 Cefepime
1 Fluconazole
1 Micafungin
Tracheal culture (bacteria)
Urine culture (urine)
111(Modified NOS, high)
1 died
Cason et al. 2022 [44], ItalyRetrospective
cohort, single-center
6417Age group <24 was the most frequent)Gender (not reported)
AND
17 White (Caucasian)
00191 Other coronaviruses (229E, NL63, and OC43)
12 Rhinovirus
4 Bocavirus
2 Adenovirus
17 Not reportedRT-PCR for respiratory specimens (viruses) c17 Not reported17 Not reported17 Not reported(NOS, 6)
Treatment outcome (not reported)
Chacón-Cruz et al. 2022 [14], MexicoRetrospective case report, single-center11841 (100)
AND
1 Hispanic
1001 Neisseria meningitidis1 Amoxicillin
1 Ceftriaxone 1 Doxycycline
PCR assays (Neisseria meningitidis)1 Not reported1 Not reported1 Not reported(Modified NOS, high)
1 died
Chen et al. 2020 [45], ChinaRetrospective case report, single-center111441 (100)
AND
1 Asian
2001 Mycoplasma pneumonia
1 Chlamydia pneumoniae
1 Mezlocillin
1 Ceftizoxime
1 Amoxicillin/clavulanic acid
Serum antibody tests (IgM, IgG)001(Modified NOS, high)
1 survived
Choudhary et al. 2022 [5], United StatesRetrospective cohort, multicenter947235Age group <60: 101 (33.9%) patients (viral coinfection)
Age group <60: 50 (16.8%) patients (bacterial coinfection)
Gender (not reported)
AND
Ethnicity (not reported)
123711375 RSV
113 Viral
123 Bacterial
7 Fungal
123 AntibioticsRT-PCR for respiratory specimens (viruses) c
Blood culture (bacteria)
Serum antibody tests (IgM, IgG)
3314235 Not reported(NOS, 8)
233 survived
2 died
Ciuca et al. 2021 [46], ItalyRetrospective case report, single-center11721 (100)
AND
1 Black
0011 Parvovirus B191 AntibioticsPCR assays (Parvovirus B19)111(Modified NOS, high)
1 survived
Danis et al. 2020 [47], FranceRetrospective case series, multicenter1211081 (100)
AND
1 White (Caucasian)
0021 Influenza A virus
1 Rhinovirus
0RT-PCR for respiratory specimens (viruses) c000(NOS, 7)
1 survived
Danley and Kent 2020 [48], United StatesRetrospective case report, single-center1141 (100)
AND
1 White (Caucasian)
0011 Adenovirus0RT-PCR for respiratory specimens (viruses) c001(Modified NOS, high)
1 survived
DeBiasi et al. 2020 [49], United StatesRetrospective cohort, single-center634Median, 115.2Gender (not reported)
AND
Ethnicity (not reported)
0052 Rhinovirus
2 RSV
1 Other coronaviruses (229E, NL63, and OC43)
4 Not reportedRT-PCR for respiratory specimens (viruses) c4 Not reported4 Not reported4 Not reported(NOS, 6)
Treatment outcome (not reported)
Demirkan and Yavuz 2021 [50], TurkeyRetrospective case reports, single-center2284 and 1560 (0)
AND
2 White (Caucasian)
0202 Fungal bezoars1 Meropenem
2 Fluconazole
RT-PCR for respiratory specimens (viruses) c
Blood culture (bacteria)
000(Modified NOS, high)
2 survived
Dhanawade et al. 2021 [51], IndiaRetrospective case report, single-center11480 (0)
AND
1 Indian
1001 Mycobacterium tuberculosis1 Ceftriaxone
1 Antibiotics
1 Isoniazid
1 Rifampicin
1 Pyrazinamide
1 Ethionamide
CSF culture (bacteria)111(Modified NOS, high)
1 survived
Di Nora et al. 2022 [52], ItalyRetrospective case report, single-center11241 (100)
AND
1 White (Caucasian)
0011 Human Herpesvirus 61 Acyclovir
1 Ceftriaxone
CSF PCR assays (viruses)
Serum antibody test (IgM)
000(Modified NOS, high)
1 survived
Dikranian et al. 2022 [53], Multi-countryRetrospective cohort, multicenter92231Age group ≤6: 136/820 (16.6%)
Age group >120 to 180: 182/820 (22.2%)
Age group >180 to 216: 189/820 (23%)
Gender (not reported)
AND
Ethnicity (not reported)
003010 Rhinovirus
5 RSV
2 Adenovirus
1 Coronavirus NL63
1 Parainfluenza-2
1 Parainfluenza-3
1 Parainfluenza-4
1 Metapneumovirus
8 Unspecified viruses
31 Not reportedRT-PCR for respiratory specimens (viruses) c
Blood culture (bacteria)
Sputum (bacteria)
2231 Not reported31 Not reported(NOS, 6)
Treatment outcome (not reported)
Diorio et al. 2020 [6], United StatesProspective cohort, single-center247Median (IQR), 60 (30–192)5 (71.4)
AND
3 White (Caucasian)
1 Hispanic
3 Black
4051 Parainfluenza 3
1 Parainfluenza 4
2 Escherichia coli
1 Enterovirus
1 Adenovirus
1 Rhinovirus
1 MRSA
1 Salmonella typhi
7 Not reportedRT-PCR for respiratory specimens (viruses) c
Blood culture (bacteria)
Urine (culture)
111(NOS, 8)
6 survived
1 died
Dong et al. 2020 [54], ChinaRetrospective case series, multicenter111281 (100)
AND
1 Asian
0011 Cytomegalovirus0Serum antibody test (IgM)000(Modified NOS, high)
1 survived
Essajee et al. 2020 [55], South AfricaRetrospective case report, single-center11310 (0)
AND
1 Black
1001 Mycobacterium tuberculosis1 Antibiotics
1 Isoniazid
1 Rifampicin
1 Pyrazinamide
1 Ethionamide
Blood culture (bacteria)001(Modified NOS, high)
1 survived
Ferdous et al. 2021 [56], BangladeshRetrospective case report, single-center11960 (0)
AND
1 Bangladeshi
0011 Dengue virus1 AntibioticsDengue NS1 antigen111(Modified NOS, high)
1 survived
Freij et al. 2020 [15], United StatesRetrospective case report, single-center11600 (0)
AND
1 Black
2001 Mycobacterium tuberculosis
1 Group A Streptococcus
1 Amoxicillin
1 Azithromycin
CSF culture (bacteria)110(Modified NOS, high)
1 died
Frost et al. 2022 [57], United StatesRetrospective case series, single-center76Median (IQR), 16 (7–30)5 (83.3)
AND
5 Hispanic
14051 Adenovirus
1 Metapneumovirus
2 Rhinovirus
1 Enterovirus
4 Streptococcus pneumoniae
5 Haemophilus influenza
3 Moraxella catarrhalis
2 Staphylococcus aureus
7 Not reportedRT-PCR for respiratory specimens (viruses) c
PCR assays (bacteria)
000(Modified NOS, high)
6 survived
Garazzino et al. 2021 [7], ItalyRetrospective cohort, multicenter51569Median (IQR), 87 (17–149)Gender (not reported)
AND
69 White (Caucasian)
3204545 Unspecified viruses
32 Unspecified bacteria
69 Not reportedRT-PCR for respiratory specimens (viruses) c
PCR assays (bacteria)
332(NOS, 7)
67 survived
2 died
Garazzino et al. 2020 [58], ItalyRetrospective cohort, multicenter16810Median (IQR), 28 (4–115)Gender (not reported)
AND
10 White (Caucasian)
10103 RSV
3 Rhinovirus
2 EBV
1 Influenza A virus
1 Other coronaviruses (229E, NL63, and OC43)
1 Streptococcus pneumoniae
10 Not reportedRT-PCR for respiratory specimens (viruses) c
PCR assays (bacteria)
222(NOS, 6)
Treatment outcome (not reported)
Goussard et al. 2020 [59], South AfricaRetrospective case report, single-center11291 (100)AND
1 Black
1001 Rifampicin-sensitive Mycobacterium tuberculosis1 Antibiotics
1 Isoniazid
1 Rifampicin
1 Pyrazinamide
1 Ethionamide
1 Amoxicillin/clavulanic acid
PCR assay for gastric aspirate (Mycobacterium tuberculosis)000(Modified NOS, high)
1 survived
Guy et al. 2022 [60], United StatesRetrospective case series, single-center66Median (IQR), 144 (42–168)5 (83.3)
AND
5 Black
1 White (Caucasian)
5001 Streptococcus intermedius
2 Prevotella species
2 Streptococcus constellatus
4 Ceftriaxone
3 Clindamycin
2 Amoxicillin/clavulanic acid
1 Penicillin
2 Metronidazole
1 Ampicillin/sulbactam
2 Vancomycin
1 Cefdinir
Nasal discharge (culture)000(Modified NOS, high)
6 survived
Halabi et al. 2022 [61], United StatesRetrospective and prospective case series, single-center1818Median (IQR), 6 (2–36)11 (61.1)
AND
Ethnicity (not reported)
002218 RSV
3 Rhinovirus
1 Parainfluenza virus
18 Not reportedRT-PCR for respiratory specimens (viruses) c922(Modified NOS, high)
Treatment outcome (not reported)
Hamzavi et al. 2020 [16], IranRetrospective case report, single-center111681 (100)
AND
1 Persian
1001 Staphylococcus aureus1 Vancomycin
1 Meropenem
Blood (culture)111(Modified NOS, high)
1 died
Hare et al. 2021 [62], United KingdomRetrospective case series, single-center71220 (0)
AND
1 White (Caucasian)
0011 Rhinovirus0RT-PCR for respiratory specimens (viruses) c000(Modified NOS, high)
1 survived
Hashemi et al. 2021 (17], IranRetrospective cohort, multicenter1055Age group 0 to 168: 5 (4.8%) patients (viral coinfection)4 (80)
AND
5 Persian
0053 Metapneumovirus
1 Bocavirus
1 Influenza A virus
5 Not reportedRT-PCR for respiratory specimens (viruses) c555(NOS, 7)
5 died
Hashemi et al. 2021 [18], IranRetrospective case reports, single-center3313, 72, and 722 (66.6)
AND
3 Persian
0033 Metapneumovirus3 Not reportedRT-PCR for respiratory specimens (viruses) c333(Modified NOS, high)
3 died
Hassoun et al. 2021 [63], United StatesRetrospective case series, multicenter86Median (IQR), 1.4 (0.5–1.6)5 (83.3)
AND
2 Black
2 White (Caucasian)
1 Hispanic
1 Indian
1065 RSV
1 Rhinovirus
1 Escherichia coli
6 AntibioticsRT-PCR for respiratory specimens (viruses) c
Urine (culture)
000(Modified NOS, high)
6 survived
He et al. 2020 [8], ChinaRetrospective cohort, multicenter154Median (IQR), 72 (36–84)3 (75)
AND
4 Asian
2202 Unspecified bacteria
2 Unspecified fungi
4 AntibioticsRT-PCR for respiratory specimens (viruses) c
Sputum (bacteria)
G assay and GM assay (fungi)
Serum antibody test (IgM)
222(NOS, 7)
2 survived
2 died
Hertzberg et al. 2020 [64], United StatesRetrospective case reports, single-center332, 24 and 602 (66.7)
AND
Ethnicity (not reported)
1022 Rhinovirus
1 Bordetella pertussis
1 AzithromycinRT-PCR for respiratory specimens (viruses) c
Blood (culture)
100(Modified NOS, moderate)
3 survived
Jarmoliński et al. 2021 [65], PolandRetrospective case report, single-center111080 (0)
AND
1 White (Caucasian)
0021 Metapneumovirus
1 RSV
1 Piperacillin/tazobactam
1 Amikacin
1 Azithromycin
1 Cefepime
1 Micafungin
1 Acyclovir
RT-PCR for respiratory specimens (viruses) c000(Modified NOS, high)
1 survived
Jiang et al. 2020 [66], ChinaRetrospective cohort, single-center161280 and 420 (0)
AND
2 Asian
1031 RSV
2 Metapneumovirus
1 Mycoplasma pneumonia
2 AntibioticsRT-PCR for respiratory specimens (viruses) c101(NOS, 7)
2 survived
Jose et al. 2021 [67], MexicoRetrospective case report, single-center11841 (100)
AND
1 Hispanic
0011 Dengue virus1 Amoxicillin
1 Trimethoprim/sulfamethoxazole
1 Clindamycin
1 3rd -generation cephalosporin
1 Ceftriaxone 1 Acyclovir
RT-PCR for respiratory specimens (viruses) c
DENV RTqPCR (dengue)
111(Modified NOS, high)
1 survived
Kakuya et al. 2020 [68], JapanRetrospective case report, single-center32132 and 602 (100)
AND
2 Asian
0021 Influenza A virus
1 Metapneumovirus
1 CeftriaxoneRT-PCR for respiratory specimens (viruses) c000(Modified NOS, high)
2 survived
Kanthimathinathan et al. 2021 [9], United KingdomRetrospective cohort, multicenter7317Median (IQR), 120 (12–156)Gender (not reported)
AND
6 White (Caucasian)
5 Asian
4 Black
64143 Pseudomonas aeruginosa
2 Klebsiella pneumoniae
1 Acinetobacter baumannii
2 Adenovirus
2 Influenza
2 Parainfluenza
2 Rhinovirus
1 Metapneumovirus
1 RSV
4 Cytomegalovirus
4 Unspecified fungi
3 Amoxicillin/clavulanic acid
1 Azithromycin
2 Clarithromycin
1 Piperacillin/tazobactam
1 Gentamicin
RT-PCR for respiratory specimens (viruses) c17710(NOS, 8)
16 survived
1 died
Karaaslan et al. 2021 [69], TurkeyRetrospective cohort, single-center937Mean ± SD, 10.99 ± 6.445 (71.4)
AND
7 White (Caucasian)
1072 Rhinovirus
2 Coronavirus NL63
1 Adenovirus
1 Mycoplasma pneumoniae
1 Rhinovirus
1 Adenovirus
7 AntibioticsRT-PCR for respiratory specimens (viruses) c000(NOS, 7)
7 survived
Karimi et al. 2020 [70], IranRetrospective case report, single-center111441 (100)
AND
1 Persian
0011 Varicella zoster virus1 AzithromycinSerum antibody tests (IgM and IgG)000(Modified NOS, high)
1 survived
Katz et al. 2022 [71], United StatesRetrospective cohort, multicenter16272 and 1201 (50)
AND
2 White (Caucasian)
0022 Herpes simplex virus2 Not reportedRT-PCR for respiratory specimens (viruses) c2 Not reported2 Not reported2 Not reported(NOS, 6)
Treatment outcome (not reported)
Kazi et al. 2021 [72], IndiaRetrospective case report, single-center1190 (0)
AND
1 Indian
0011 Dengue virus1 Ceftriaxone
1 Vancomycin
1 Doxycycline
RT-PCR for respiratory specimens (viruses) c
DENV RTqPCR (dengue)
IgM antibody test from CSF (dengue)
111(Modified NOS, high)
1 survived
Keshavarz Valian et al. 2022 [73], IranRetrospective cohort, single-center252Mean ± SD, 58.8 ± 51.6Gender (not reported)
AND
2 Persian
0022 Human coronavirus OC432 Not reportedRT-PCR for respiratory specimens (viruses) c2 Not reported2 Not reported2 Not reported(NOS, 6)
Treatment outcome (not reported)
Khataniar et al. 2022 [74], IndiaRetrospective case report, single-center111681 (100)
AND
1 Indian
1001 Mycobacterium tuberculosis1 Meropenem 1 Vancomycin
1 Ceftriaxone
1 Amikacin
1 Levofloxacin
1 Isoniazid
1 Rifampicin
1 Pyrazinamide
1 Ethionamide
CSF culture (bacteria)111(Modified NOS, high)
1 survived
Lambrou et al. 2022 [75], GreeceRetrospective case report, single-center11360 (0)
AND
1 White (Caucasian)
1001 Escherichia hermannii1 Piperacillin/tazobactam
1 Amikacin
1 Teicoplanin
1 Meropenem 1 Micafungin
Blood (culture)000(Modified NOS, high)
1 survived
Le Glass et al. 2021 [10], FranceRetrospective cohort, multicenter215958Age group <180: 25 (43.1%) patients (rhinovirus coinfection)33 (56.9)
AND
Ethnicity (not reported)
58 Not reported58 Not reported5858 Rhinovirus93 Not reportedRT-PCR for respiratory specimens (viruses) c58 Not reported58 Not reported58 Not reported(NOS, 6)
57 survived
1 died
Le Roux et al. 2020 [76], FranceRetrospective case report, single-center11101 (100)
AND
1 White (Caucasian)
0021 Varicella zoster virus
1 Rotavirus
1 Amoxicillin/clavulanic acid
1 Azithromycin
1 Acyclovir
PCR000(Modified NOS, high)
1 survived
Leclercq et al. 2021 [77], SwitzerlandRetrospective case report, single-center11961 (100)
AND
1 White (Caucasian)
1011 EBV
1 Group A Streptococcus
1 Amoxicillin
1 Cephalosporin
RT-PCR for respiratory specimens (viruses) c
Serum antibody tests (IgM, IgG)
000(Modified NOS, high)
1 survived
Lee et al. 2022 [78], United StatesRetrospective cohort, single-center162592Not reportedGender (not reported)
AND
Ethnicity (not reported)
0011156 RSV
38 Influenza A virus
11 Rhinovirus 2 Influenza B virus
2 Adenovirus
2 Parainfluenza virus
Not reportedRT-PCR for respiratory specimens (viruses) c
Serum antibody tests (IgM, IgG)
Not reportedNot reportedNot reported(NOS, 7)
Treatment outcome (not reported)
Leuzinger et al. 2020 [79], SwitzerlandRetrospective cohort, single-center164Age group ≤60: 2 (14.3%) patients (viral coinfection)
Age group ≤192: 2 (14.3%) patients (viral coinfection)
Gender (not reported)
AND
4 White (Caucasian)
0084 Rhinovirus
2 RSV
2 Parainfluenza virus (types 1–4)
4 Not reportedRT-PCR for respiratory specimens (viruses) c4 Not reported4 Not reported4 Not reported(NOS, 7)
Treatment outcome (not reported)
Li et al. 2020 [80], ChinaRetrospective cohort, single-center4015Mean ± SD, 61 ± 56Gender (not reported)
AND
15 Asian
140413 Mycoplasma pneumoniae
3 Influenza A or B virus
1 Adenovirus
1 Streptococcus pneumonia
13 Azithromycin
1 Meropenem
1 Piperacillin/tazobactam
RT-PCR for respiratory specimens (viruses) c111(NOS, 7)
15 survived
Li et al. 2021 [81], ChinaRetrospective cohort, single-center8127Mean ± SD, 76.5 ± 9.615 (55.6)
AND
27 Asian
240620 Mycoplasma pneumoniae
1 Influenza A virus
2 Influenza B virus
1 RSV
1 Adenovirus
1 Parainfluenza virus 2
3 Moraxella catarrhalis
1 Streptococcus pneumoniae
27 Not reportedRT-PCR for respiratory specimens (viruses) c
Sputum (bacteria)
Serum antibody tests (IgM, IgG)
111(NOS, 7)
27 survived
Lin et al. 2020 [82], ChinaRetrospective cohort, single-center921360 (0)
AND
1 Asian
0011 Metapneumovirus1 Not reportedRT-PCR for respiratory specimens (viruses) c1 Not reported1 Not reported1 Not reported(Modified NOS, high)
Treatment outcome (not reported)
Ma et al. 2020 [83], ChinaRetrospective cohort, single-center4544 Not reportedGender (not reported)
AND
4 Asian
0074 Mycoplasma pneumonia
2 Parainfluenza virus
1 Adenovirus
4 Not reportedRT-PCR for respiratory specimens (viruses) c333(NOS, 6)
Treatment outcome (not reported)
Mania et al. 2022 [84], PolandRetrospective cohort, multicenter1283135Median (IQR), 72 (12–156)Gender (not reported)
AND
135 White (Caucasian)
1503711 Streptococcus pneumoniae
2 Influenza A virus
2 Escherichia coli
1 Adenovirus
1 Rhinovirus
1 Bocavirus
1 RSV
1 Parainfluenza
1 Mycoplasma pneumoniae
1 Klebsiella oxytoca
2 Varicella zoster virus
3 Herpes simplex virus
25 Rotavirus, adenovirus, and norovirus
135 Not reportedRT-PCR for respiratory specimens (viruses) c
Blood, urine, and pharyngeal swabs (culture)
302(NOS, 7)
135 survived
Mannheim et al. 2020 [85], United StatesRetrospective case series, single-center104Median (IQR), 132 (84–192)Gender (not reported)
AND
Ethnicity (not reported)
2041 Mycoplasma pneumoniae
2 Adenovirus
1 Rhinovirus
1 Escherichia coli
1 Rotavirus
4 Not reportedRT-PCR for respiratory specimens (viruses) c
Serum antibody test (IgM)
Urine (culture)
400(NOS, 7)
4 survived
Mansour et al. 2020 [86], LebanonRetrospective case report, single-center11160 (0)
AND
1 Arab
1001 Streptococcus pneumoniae1 Ceftriaxone 1 MetronidazoleBlood (culture)000(Modified NOS, high)
1 survived
Marsico et al. 2022 [87], ItalyRetrospective case report, single-center11<10 (0)
AND
1 White (Caucasian)
1001 Multidrug-resistant Enterobacter asburiae1 Azithromycin
1 Vancomycin
1 Ceftazidime
1 Gentamycin
1 Meropenem
1 Aztreonam
1 Ceftazidime/avibactam
1 Fosfomycin
Blood (culture)111(Modified NOS, high)
1 survived
Mathur et al. 2022 [11], IndiaRetrospective cohort, single-center32717Mean (SD), 137 (32)9 (52.9)
AND
17 Indian
170017 Mycobacterium tuberculosis17 Not reportedBlood culture (bacteria)627(NOS, 7)
13 survived
4 died
Mithal et al. 2020 [88], United StatesRetrospective case series, single-center182<31 (50)
AND
2 Hispanic
2022 RSV
1 Streptococcus agalactiae
1 Klebsiella oxytoca
1 AntibioticsRT-PCR for respiratory specimens (viruses) c
Urine (culture)
000(Modified NOS, high)
2 survived
Mohammadi et al. 2022 [89], IranRetrospective cohort, single-center4541, 36, 72, and 1202 (50)
AND
4 Persian
0044 Adenovirus0RT-PCR for respiratory specimens (viruses) c000(NOS, 5)
4 survived
Moin et al. 2021 [90], PakistanRetrospective cohort, single-center42384≤ 180 (10–180)4 (100)
AND
4 Pakistani
0401 Candida auris
1 Candida albicans
1 Candida tropicalis
1 Candida rugosa
4 Antibiotics
4 Antifungals
Blood (culture)111(NOS, 7)
3 survived
1 died
Morand et al. 2020 [91], FranceRetrospective case report, single-center11550 (0)
AND
1 White (Caucasian)
0011 EBV0RT-PCR for respiratory specimens (viruses) c000(Modified NOS, high)
1 survived
Mulale et al. 2021 [19], BotswanaRetrospective case report, single-center1131 (100)
AND
1 Black
1001 Rifampin-sensitive Mycobacterium tuberculosis1 Ampicillin
1 Gentamicin
1 Rifampicin
1 Isoniazid
1 Pyrazinamide
1 Ethambutol
PCR assay for gastric lavage (bacteria)111(Modified NOS, high)
1 died
Ng et al. 2020 [92], United KingdomRetrospective case series, single-center8312, 0.5, and 101 (33.3)
AND
3 White (Caucasian)
0052 Adenovirus
2 Rhinovirus
1 Other coronaviruses (229E, NL63, and OC43)
1 Amoxicillin
1 Cefotaxime
1 Gentamicin
RT-PCR for respiratory specimens (viruses) c100(Modified NOS, high)
3 survived
Nieto-Moro et al. 2020 [93], SpainRetrospective case report, single-center1181 (100)
AND
1 White (Caucasian)
1001 Streptococcus pneumoniae1 Azithromycin
1 Clindamycin
1 Meropenem
1 Linezolid
Blood (culture)101(Modified NOS, high)
1 survived
Nygaard et al. 2022 [20], DenmarkRetrospective case series, multicenter2224 and 1321 (50)
AND
2 White (Caucasian)
2022 Panton-Valentine leukocidin-producing Staphylococcus aureus
1 Parainfluenza
1 Rhinovirus
1 Meropenem
1 Clindamycin
1 Amoxicillin
Blood PCR assays (viruses)
Blood, lung biopsy and CSF (culture)
111(Modified NOS, high)
2 died
Oba et al. 2020 [94], BrazilRetrospective case report, single-center1120 (0)
AND
1 Hispanic
1001 Clostridium difficile0Fecal PCR assays (bacteria)100(Modified NOS, high)
1 survived
Ogunbayo et al. 2022 [95], South AfricaRetrospective cohort, multicenter3631Median (IQR), 16 (5–29)19 (61.3)
AND
31 Black
005323 Rhinovirus
16 RSV
6 Adenovirus
8 Parainfluenza virus 3
31 Not reportedRT-PCR for respiratory specimens (viruses) c231 Not reported31 Not reported(NOS, 7)
Treatment outcome (not reported)
Palmero et al. 2020 [96], ArgentinaRetrospective case series, multicenter44Range (60–192)Gender (not reported)
AND
4 Hispanic
4004 Mycobacterium tuberculosis4 Isoniazid
4 Rifampicin
4 Pyrazinamide
4 Ethionamide
Blood culture (bacteria)111(Modified NOS, high)
3 survived
1 died
Patek et al. 2020 [97], United StatesRetrospective case report, single-center110.51 (100)
AND
1 White (Caucasian)
1001 MSSA1 Antibiotic
1 Acyclovir
Wound (culture)101(Modified NOS, high)
1 survived
Peng et al. 2020 [98], ChinaRetrospective cohort, single-center7542Mean ± SD, 72.7 ± 57.4Gender (not reported)
AND
42 Asian
310828 Mycoplasma pneumoniae
1 Moraxella catarrhalis
1 Staphylococcus aureus
1 Streptococcus pneumoniae
3 Influenza B virus
1 Influenza A virus
2 Adenoviridae 1 Cytomegalovirus
1 RSV
37 1st- or 2nd-generation cephalosporins
28 Azithromycin
RT-PCR for respiratory specimens (viruses) c
Serum antibody test (IgM) for Mycoplasma pneumoniae (only)
001(NOS, 7)
42 survived
Pigny et al. 2021 [99], SwitzerlandRetrospective cohort, single-center517Median (IQR), 50.4 (20.4–87.6)Gender (not reported)
AND
7 White (Caucasian)
0094 Rhinovirus
2 Other coronaviruses (NL63)
2 Adenovirus
1 Metapneumovirus
7 Not reportedRT-PCR for respiratory specimens (viruses) c7 Not reported7 Not reported7 Not reported(NOS, 6)
Treatment outcome (not reported)
Plebani et al. 2020 [100], ItalyRetrospective case series, single-center9436, 120, 168, and 1202 (50)
AND
4 White (Caucasian)
4004 Mycoplasma pneumonia3 Ceftriaxone
1 Cefotaxime
2 Azithromycin
1 Ampicilline/sulbactam
1 Clindamycin
Serum antibody test (IgM)4 Not reported4 Not reported4 Not reported(Modified NOS, high)
4 survived
Pokorska-Śpiewak et al. 2021 [101], PolandProspective case series, single-center1511 Not reportedGender (not reported)
AND
1 White (Caucasian)
0011 Influenza A virus0RT-PCR for respiratory specimens (viruses) c000(Modified NOS, high)
1 survived
Pucarelli-Lebreiro et al. 2022 [102], BrazilProspective cohort, single-center1059Median, 45Gender (not reported)
AND
9 Hispanic
00106 RSV
1 Influenza
2 Rhinovirus
1 Norovirus
9 Not reportedRT-PCR for respiratory specimens (viruses) c000(NOS, 7)
9 survived
Rastogi et al. 2022 [103], IndiaRetrospective case series, single-center1911080 (0)
AND
1 Indian
1001 Mycobacterium tuberculosis1 Isoniazid
1 Rifampicin
1 Pyrazinamide
1 Ethionamide
PCR assay of bronchoalveolar lavage (bacteria)000(NOS, 7)
1 survived
Ratageri et al. 2021 [104], IndiaRetrospective case report, single-center11961 (100)
AND1 Indian
0011 Dengue virus0IgM antibody test (dengue)000(Modified NOS, high)
1 survived
Raychaudhuri et al. 2021 [105], IndiaProspective cohort, single-center10243Median (IQR), 54 (4.8–90)23 (53.4)
AND
43 Indian
260124 MRSA
5 MSSA
3 CONS
3 Pseudomonas aeruginosa
1 Klebsiella pneumonia
7 Scrub typhus
5 Dengue
3 Salmonella typhi
1 Hepatitis A
1 EBV
2 RSV
1 Influenza A virus
1 Adenovirus
1 Rhinovirus
38 AntibioticsRT-PCR for respiratory specimens (viruses) c
Blood, respiratory secretions, and CSF (culture)
271514(NOS, 8)
39 survived
4 died
Rebelo et al. 2022 [21], PortugalRetrospective case report, single-center111681 (100)
AND
1 White (Caucasian)
1001 Neisseria meningitidis serogroup B1 Ceftriaxone
1 Meropenem
1 Vancomycin
Blood (culture)111(Modified NOS, high)
1 died
Said et al. 2022 [106], Saudi ArabiaRetrospective case report, single-center1110Gender (not reported)
AND
1 Arab
1001 Escherichia coli1 AntibioticUrine (culture)000(NOS, 6)
1 survived
Sanchez Solano and Sharma 2022 [107], United StatesRetrospective case report, single-center111921 (100)
AND
1 White (Caucasian)
1001 MRSA1 Ceftriaxone 1 Vancomycin
1 Clindamycin
Bronchoalveolar lavage (culture)111(Modified NOS, high)
1 survived
Santoso et al. 2021 [108], IndonesiaRetrospective cohort, multicenter9011 Not reportedGender (not reported)
AND
1 Asian
0011 Dengue virus1 Not reportedDengue NS1 antigen
IgM and IgG antibody tests (dengue)
1 Not reported1 Not reported1 Not reported(NOS, 7)
Treatment outcome (not reported)
Schober et al. 2022 [109], Multi-countryRetrospective cohort, multicenter4035445.4 (6.4–129.2)Gender (not reported)
AND
Ethnicity (not reported)
2403224 Bacterial
32 Viral
3 AzithromycinRT-PCR for respiratory specimens (viruses) c
Blood (culture)
1044(NOS, 7)
Treatment outcome (not reported)
See et al. 2020 [110], MalaysiaRetrospective case reports, multicenter41480 (0)
AND
1 Asian
0011 Influenza A virus1 PhenoxymethylpenicillinRT-PCR for respiratory specimens (viruses)c000(Modified NOS, high)
1 survived
Serrano et al. 2020 [111], SpainRetrospective case report, single-center11961 (100)
AND
1 White (Caucasian)
1001 Mycoplasma pneumonia1 Not reportedIgM and IgG antibody tests (Mycoplasma pneumonia)000(Modified NOS, high)
1 survived
Shabrawishi et al. 2021 [112], Saudi ArabiaRetrospective case series, single-center711680 (0)
AND
1 Arab
1001 Mycobacterium tuberculosis1 Ceftriaxone
1 Azithromycin
1 Isoniazid
1 Rifampicin
1 Pyrazinamide
1 Ethionamide
Blood culture (bacteria)000(Modified NOS, high)
1 survived
Shi et al. 2020 [113], ChinaRetrospective case report, single-center1131 (100)
AND
1 Asian
0011 RSV1 CeftizoximeRT-PCR for respiratory specimens (viruses) c101(Modified NOS, high)
1 survived
Sibulo et al. 2021 [114], United StatesRetrospective case report, single-center11361 (100)
AND
1 White (Caucasian)
1001 Staphylococcus epidermidis1 Vancomycin
1 Clindamycin
1 Piperacillin/tazobactam
Blood (culture)110(Modified NOS, high)
1 survived
Şık et al. 2022 [115], TurkeyRetrospective cohort, single-center14131 (100)
AND
1 White (Caucasian)
0011 Rhinovirus RT-PCR for respiratory specimens (viruses) c001(NOS, 7)
1 survived
Somasetia et al. 2020 [22], IndonesiaRetrospective case report, single-center11721 (100)
AND
1 Asian
0011 Dengue virus1 AntibioticsIgM antibody test (dengue)111(Modified NOS, high)
1 died
Sun et al. 2020 [116], ChinaRetrospective cohort, single-center3623Mean (range), 6.43 (2–12)Gender (not reported)
AND
23 Asian
23 Not reported23 Not reported23 Not reportedUnspecified number of Cytomegalovirus, EBV and Mycoplasma pneumonia15 Cefmetazole
15 Azithromycin
RT-PCR for respiratory specimens (viruses) c111(NOS, 7)
22 survived
1 died
Sun et al. 2020 [117], ChinaRetrospective case series, single-center81961 (100)
AND
1 Asian
0011 Influenza A virus1 AntibioticsRT-PCR for respiratory specimens (viruses) c111(Modified NOS, high)
1 Remained in ICU
Tadolini et al. 2020 [118], Multi-countryRetrospective cohort, multicenter49131 (100)
AND
1 Black
1001 Mycobacterium tuberculosis1 Antibiotics
1 Isoniazid
1 Rifampicin
1 Pyrazinamide
1 Ethionamide
Blood culture (bacteria)000(NOS, 7)
1 survived
Tagarro et al. 2021 [119], SpainRetrospective cohort, multicenter412Median (IQR), 36 (10.8–72)Gender (not reported)
AND
Ethnicity (Not reported)
0022 Influenza B virus2 Not reportedRT-PCR for respiratory specimens (viruses) c000(NOS, 7)
2 survived
Tan et al. 2020 [120], ChinaRetrospective case series, single-center10324, 105, and 1111 (33.3)
AND
3 Asian
4003 Mycoplasma pneumonia
1 Chlamydia pneumonia
1 AntibioticsSerum antibody test (IgM)3 Not reported3 Not reported3 Not reported(Modified NOS, high)
Treatment outcome (not reported)
Taweevisit et al. 2022 [23], ThailandRetrospective case report, single-center11671 (100)
AND
1 Asian
2141 Aspergillus species
1 Cytomegalovirus
1 Pseudomonas aeruginosa
1 Acinetobacter baumannii
1 Adenovirus
1 EBV
1 Herpes virus 4
1 AntibioticsAlveolar fluid (culture)
RT-PCR for respiratory specimens (viruses) c
Serum antibody tests (IgM and IgG)
111(Modified NOS, high)
1 died
Tchidjou et al. 2021 [121], FranceRetrospective case report, single-center111.51 (100)
AND
1 White (Caucasian)
1001 Citrobacter koseri1 Cefotaxime
1 Gentamycin
1 Amoxicillin/clavulanic acid
Urine (culture)000(Modified NOS, high)
1 survived
Tiwari et al. 2020 [122], IndiaRetrospective case report, single-center111680 (0)
AND
1 Indian
0011 Dengue virus1 Ceftriaxone
1 Azithromycin
Dengue NS1 antigen
IgM antibody test (dengue)
101(Modified NOS, high)
1 survived
Trifonova et al. 2022 [123], BulgariaRetrospective cohort, multicenter24216All patients were <192
156 (n = 1)
36 (n = 1)
Gender (not reported)
AND
16 White (Caucasian)
16 Not reported16 Not reported22 Influenza A virus16 Not reportedRT-PCR for respiratory specimens (viruses) c100(NOS, 7)
16 survived
Vanzetti et al. 2020 [124], ArgentinaRetrospective, case reports, single-center112041 (100)
AND
1 Hispanic
1001 Mycobacterium tuberculosis1 Isoniazid
1 Rifampicin
1 Pyrazinamide
1 Ethionamide
PCR assay (bacteria)
Sputum (culture)
000(Modified NOS, moderate)
1 survived
Varela et al. 2022 [125], BrazilProspective cohort, multicenter9231Median (IQR), 64.8 (24–122.4)Gender (not reported)
AND
31 Hispanic
003029 Rhinovirus
1 Enterovirus
5 AzithromycinRT-PCR for respiratory specimens (viruses) c400(NOS, 7)
31 survived
Verheijen et al. 2022 [126], The NetherlandsRetrospective case report, single-center110.030 (0)
AND
1 White (Caucasian)
1001 Staphylococcus aureus1
Flucloxacillin
RT-PCR for respiratory specimens (viruses) c
Blood (culture)
111(Modified NOS, high)
1 survived
Vidal et al. 2022 [127], Multi-countryRetrospective cohort, multicenter2912Median, 36Gender (not reported)
AND
12 White (Caucasian)
001212 Adenovirus12 Not reportedRT-PCR for respiratory specimens (viruses) c212 Not reported12 Not reported(NOS, 7)
Treatment outcome (not reported)
Vu et al. 2021 [128], United StatesRetrospective case report, single-center11481 (100)
AND
1 White (Caucasian)
1001 Streptococcus pneumonia1 Cefepime
1 Vancomycin
1 Ceftriaxone
1 Amoxicillin
Pleural fluid (culture)111(Modified NOS, high)
1 survived
Wanga et al. 2021 [129], United StatesRetrospective cohort, multicenter713113Age group <12: 37 (32.4%) patients (viral coinfection)
Age group 12–48: 41 (36.1%) patients (viral coinfection)
Gender (not reported)
AND
Ethnicity (not reported)
113 Not reported113 Not reported113113 RSV113 Not reportedRT-PCR for respiratory specimens (viruses) c113 Not reported113 Not reported113 Not reported(NOS, 6)
Treatment outcome (not reported)
Wehl et al. 2020 [130], GermanyRetrospective case report, single-center114Gender (not reported)
AND
1 White (Caucasian)
0011 Influenza A virus0RT-PCR for respiratory specimens (viruses) c000(Modified NOS, high)
1 survived
Wu et al. 2020 [131], ChinaRetrospective cohort, multicenter341972 (1.2–180.9)Gender (not reported)
AND
19 Asian
1601016 Mycoplasma pneumoniae
3 RSV
3 EBV
3 Cytomegalovirus
1 Influenza A and B virus
15 AzithromycinRT-PCR for respiratory specimens (viruses) c101(NOS, 7)
19 survived
Xia et al. 2020 [132], ChinaRetrospective case series, single-center208Median, 24Gender (not reported)
AND
8 Asian
4051 Cytomegalovirus
2 Influenza B virus
1 Influenza A virus
4 Mycoplasma pneumoniae
1 RSV
8 Not reportedRT-PCR for respiratory specimens (viruses) c000(Modified NOS, high)
8 survived
Yakovlev et al. 2022 [133], RussiaRetrospective cohort, single-center28732Median (IQR), 12 (8.4–30) (viral coinfection)
Median (IQR), 144 (90–180) (bacterial coinfection)
Gender (not reported)
AND
32 White (Caucasian)
1603411 Rhinovirus
11 Other coronaviruses (HKU-1/OC 43)
9 Mycoplasma pneumoniae
7 Chlamydia pneumoniae
4 Metapneumovirus
4 Parainfluenza virus 3
4 Parainfluenza virus 4
32 Not reportedRT-PCR for respiratory specimens (viruses) c
Serum antibody tests (IgM and IgG)
632 Not reported32 Not reported(NOS, 7)
Treatment outcome (not reported)
Zeng et al. 2020 [134], ChinaRetrospective cohort, single-center317.751 (100)
AND
1 Asian
1001 Enterobacter1 AntibioticsBlood (culture)111(NOS, 7)
1 survived
Zhang et al. 2020 [135], ChinaRetrospective case series, multicenter3416Median (IQR), 33 (10–94.2)Gender (not reported)
AND
16 Asian
90159 Mycoplasma pneumoniae
6 Influenza B virus
3 Influenza A virus
2 RSV
2 EBV
1 Parainfluenza virus
1 Adenovirus
11 Antibiotics
9 Azithromycin
RT-PCR for respiratory specimens (viruses) c000(Modified NOS, high)
16 survived
Zhang et al. 2021 [136], United StatesRetrospective case series, multicenter162Mean ± SD, 204 ± 61.3Gender (not reported)
AND
Ethnicity (not reported)
0041 Rhinovirus
1 Adenovirus
1 RSV
1 Influenza A virus
2 AntibioticsRT-PCR for respiratory specimens (viruses) c2 Not reported2 Not reported2 Not reported(Modified NOS, high)
Treatment outcome (not reported)
Zheng et al. 2020 [137], ChinaRetrospective cohort, multicenter253Median (IQR), 36 (24–108)2 (66.7)
AND
3 Asian
4023 Mycoplasma pneumoniae
2 Influenza B virus
1 Enterobacter aerogenes
1 Meropenem
1 Linezolid
RT-PCR for respiratory specimens (viruses) c111(NOS, 7)
3 survived
Zheng et al. 2020 [138], ChinaRetrospective cohort, single-center411801 (100)
AND
1 Asian
0011 Influenza B virus1 AntibioticsRT-PCR for respiratory specimens (viruses) c000(NOS, 7)
1 survived
Zhu et al. 2020 [139], ChinaRetrospective cohort, single-center25711<180Gender (not reported)
AND
11 Asian
20236 Streptococcus pneumoniae
5 Haemophilus influenzae
3 Klebsiella pneumoniae
3 Staphylococcus aureus
2 Aspergillus 1 Metapneumovirus
1 Cytomegalovirus
1 Mycoplasma pneumonia
1 Adenovirus
1 Pseudomonas aeruginosa
1 Escherichia coli
11 Not reportedRT-PCR for respiratory specimens (viruses) c000(NOS, 7)
11 survived
Zou et al. 2020 [140], ChinaRetrospective case report, single-center2228 and 1561 (50)
AND
2 Asian
0022 Influenza A virus1 CefaclorSerum antibody tests (IgM and IgG)000(Modified NOS, high)
2 survived
Abbreviations: ARDS, acute respiratory distress syndrome; CONS, coagulase-negative Staphylococcus species; CMV, Cytomegalovirus; COVID-19, coronavirus disease 2019; CSF, cerebrospinal fluid; EBV, Epstein–Barr virus; ICU, intensive care unit; IgG, immunoglobulin G; IgM, immunoglobulin M; IQR, interquartile range; MRSA, Methicillin-resistant Staphylococcus aureus; MSSA, Methicillin-susceptible Staphylococcus aureus; NOS, Newcastle–Ottawa scale; RT-PCR, real-time reverse transcription–polymerase chain reaction; RSV, respiratory syncytial virus; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; SD, standard deviation. a Data are presented as median (25th–75th percentiles), or mean ± SD. b Patients of black ethnicity include African-American, Black African, African, and Afro-Caribbean patients. c PCR assay for multiple respiratory viruses (including influenza virus types A and B, respiratory syncytial virus type A/B, human metapneumovirus, parainfluenza virus types 1–4, other coronaviruses (229E, NL63, and OC43), metapneumovirus, rhinovirus, enterovirus, adenovirus, parechovirus, and bocavirus).

3.2. Demographic, Clinical Characteristics, and Treatment Outcomes of Children with COVID-19 and Bacterial, Fungal, and/or Respiratory Viral Coinfection

The included studies comprised a total of 17,588 children with confirmed SARS-CoV-2 infection who were tested for co-pathogens, as detailed in Table 1. Among these 17,588 COVID-19 patients, bacterial, fungal, and/or respiratory viral coinfections were reported (n = 1633, 9.3%). The median patient age ranged from 1.4 months to 144 months across studies. There was an increased male predominance in pediatric COVID-19 patients diagnosed with bacterial, fungal, and/or viral coinfections in most of the studies (male gender: n = 204, 59.1% compared to female gender: n = 141, 40.9%) [6,8,10,11,16,17,18,19,21,22,23,31,35,38,40,45,46,47,48,52,54,57,59,60,61,63,64,67,68,69,70,71,74,76,77,81,90,93,95,97,104,105,107,111,113,114,117,118,121,124,128,134,137,138]. The majority of the cases belonged to White (Caucasian) (n = 441, 53.3%) [6,7,9,13,20,21,36,38,39,41,42,44,47,48,50,52,58,60,62,63,65,69,71,75,76,77,79,84,87,91,93,97,99,100,101,107,111,114,115,121,123,126,127,128,130,133], Asian (n = 205, 24.8%) [8,9,22,23,37,45,54,65,66,68,80,81,82,83,98,108,110,113,116,117,120,131,132,134,135,137,138,139,140], Indian (n = 71, 8.6%) [11,31,51,63,72,74,103,104,105,122], and Black (n = 51, 6.2%) [6,9,15,19,46,55,59,60,63,95,118] ethnicities.
COVID-19 children coinfected with bacteria, fungi, and/or respiratory viruses were reported to have received antibiotics in 77 studies [5,8,9,12,13,14,15,16,19,20,21,22,23,36,38,39,40,42,45,46,50,51,52,55,56,59,60,63,64,65,66,67,68,69,70,72,74,75,76,77,80,86,87,88,90,92,93,96,97,98,100,103,105,106,107,109,110,112,113,114,116,117,118,120,121,122,124,125,126,128,131,134,135,136,137,138,140]. The most prescribed antibiotics were azithromycin (n = 109) [9,15,36,39,64,65,70,76,80,87,93,98,100,109,112,116,122,125,131,135], 1st/2nd/3rd generation of cephalosporins (n = 66) [12,13,42,45,60,65,67,77,87,98,100,113,116,121,128,140], ceftriaxone (n = 29) [12,14,21,38,39,51,52,60,67,68,72,74,86,100,107,112,122,128], isoniazid (n = 13) [19,51,55,59,74,96,103,112,118,124], pyrazinamide (n = 13) [19,51,55,59,74,96,103,112,118,124], rifampicin (n = 13) [19,51,55,59,74,96,103,112,118,124], ethionamide (n = 12) [51,55,59,74,96,103,112,118,124], meropenem (n = 11) [16,20,21,40,50,74,75,80,87,93,137], vancomycin (n = 11) [13,16,21,60,72,74,87,107,114,128], amoxicillin/clavulanic acid (n = 9) [9,45,59,60,76,121], amoxicillin (n = 8) [14,15,20,40,67,77,92,128], clindamycin (n = 8) [13,20,38,60,67,93,100,107,114], ampicillin/sulbactam (n = 7) [39,60,100], and gentamycin (n = 6) [9,19,42,87,92,121]. There were children who were admitted to the intensive care unit (n = 214, 18.6%) [4,5,6,7,8,9,11,12,13,15,16,18,19,20,21,22,23,35,36,39,42,46,51,53,56,58,61,63,64,66,67,72,74,80,81,83,84,85,87,90,92,93,94,95,96,97,105,107,109,113,114,116,117,122,123,125,126,127,128,131,133,134,137], intubated and placed on mechanical ventilation (n = 98, 9.2%) [4,5,6,7,8,9,11,12,13,15,16,17,18,19,20,21,22,23,35,36,39,42,46,51,56,58,61,67,72,74,80,81,83,87,90,96,105,107,109,114,116,117,126,128,134,137], and suffered acute respiratory distress syndrome (n = 100, 12.5%) [4,6,7,8,9,11,12,13,16,17,18,19,20,21,22,23,39,42,45,46,48,51,55,56,58,61,66,67,72,74,80,81,83,84,87,90,93,96,97,98,105,107,109,113,115,116,117,122,126,128,131,134,137].
Clinical treatment outcomes for the COVID-19 children who were coinfected with bacteria, fungi, and/or respiratory viruses and died was documented in 43 (4.4%) cases [4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,90,96,105,116], while 931 (95.6%) of the COVID-19 cases recovered [4,5,6,7,8,9,10,11,31,33,34,35,36,38,40,42,43,45,46,47,48,50,51,52,54,55,56,57,59,60,62,63,64,65,66,67,68,69,70,72,74,75,76,77,80,81,84,85,86,87,88,89,90,91,92,93,94,95,96,97,100,101,102,103,104,105,106,107,110,111,112,113,114,115,116,118,119,121,122,123,124,125,126,128,130,131,132,134,135,137,138,139,140], and final treatment outcome was reported in one patient who remained in the intensive care unit (n = 1, %) [117].

3.3. Meta-Analysis of Bacterial, Fungal, and Respiratory Viral Coinfections in Children with SARS-CoV-2

The overall pooled proportions of COVID-19 children who had laboratory-confirmed bacterial, fungal, and respiratory viral coinfections were 4.73% (95% CI 3.86 to 5.60, n = 445, 34 studies, I2 85%, p < 0.01), 0.98% (95% CI 0.13 to 1.83, n = 17, six studies, I2 49%, p < 0.08), and 5.41% (95% CI 4.48 to 6.34, n = 441, 32 studies, I2 87%, p < 0.01), respectively; (Figure 3, Figure 4 and Figure 5).
In bacterial coinfected COVID-19 children, subgroup analysis showed some difference in the rates between all patients (patients in the ICU and non-ICU group or ICU only group); the ICU and non-ICU group showed a prevalence of 4.91% (95% CI 3.97 to 5.84, n = 431, 28 studies, I2 87%, p < 0.01), while the ICU only group showed a prevalence of 3.02% (95% CI 1.70 to 4.34, n = 14, six studies, I2 0%, p = 0.90), respectively; Figure 3.
In fungal coinfected COVID-19 children, subgroup analysis showed almost a threefold increase in the rates between all patients (patients in the ICU and non-ICU group or ICU only group); the ICU only group showed a prevalence of 1.72% (95% CI 0.45 to 2.99, n = 11, three studies, I2 0%, p = 0.63), while the ICU and non-ICU group showed a prevalence of 0.62% (95% CI 0.00 to 1.55, n = 6, three studies, I2 54%, p = 0.11), respectively; Figure 4.
However, in the respiratory viral coinfected COVID-19 children, subgroup analysis showed a slight difference in the rates between all patients (patients in the ICU and non-ICU group or ICU only group); the ICU and non-ICU group showed a prevalence of 5.31% (95% CI 4.31 to 6.30, n = 418, 28 studies, I2 88%, p < 0.01), while the ICU only group showed a prevalence of 6.61% (95% CI 5.06 to 8.17, n = 23, four studies, I2 0%, p = 0.90), respectively; Figure 5.
Funnel plots for possible publication bias for the pooled effect size to determine the prevalence of bacterial, fungal, and/or fungal coinfections in children with COVID-19 appeared asymmetrical on visual inspection, and Egger’s tests confirmed asymmetry with p-values < 0.05; Figure 6, Figure 7 and Figure 8.

3.4. Bacterial, Fungal, and Respiratory Viral Co-Pathogens in COVID-19 Children

Specific bacterial co-pathogens were reported in 71/130 (54.6%) studies, which is about 31.8% of the reported coinfections. The most common bacteria were Mycoplasma pneumoniae (n = 120), Streptococcus pneumoniae (n = 65), Mycobacterium tuberculosis (n = 31), Staphylococcus aureus (n = 12), Escherichia coli (n = 11), Haemophilus influenza (n = 10), Chlamydia pneumoniae (n = 9), and Pseudomonas aeruginosa (n = 9) (Table 2).
Fungal co-pathogens were reported in 8/130 (6.1%) studies, which is equal to only 1.4% of the reported coinfections. The most common fungal organisms were Aspergillus species (n = 3), fungal bezoars (n = 2), Candida albicans (n = 1), Candida auris (n = 1), Candida glabrata (n = 1), Candida rugosa (n = 1), and Candida tropicalis (n = 1) (Table 3).
Respiratory viral co-pathogens were reported in 88/130 (67.7%) studies, representing about 66.8% of the reported coinfections. The most common respiratory viruses were RSV (n = 342), Rhinovirus (n = 209), Influenza A virus (n = 80), Adenovirus (n = 60), Parainfluenza virus (types 1–4) (n = 29), Influenza B virus (n = 28), Metapneumovirus (n = 27), EBV (n = 14), Cytomegalovirus (n = 12), Dengue virus (n = 12), Coronaviruses (HKU-1/OC 43) (n = 11), and Bocavirus (n = 10) (Table 4).

4. Discussion

This systematic review and meta-analysis included 17,588 laboratory-confirmed COVID-19 children from 130 observational studies to estimate the prevalence of coinfections with bacteria, fungi, and/or respiratory viruses. Children with SARS-CoV-2 infection had the following prevalence of pathogen coinfections: bacterial (4.7%, 95% CI 3.8–5.6), fungal (0.9%, 95% CI 0.1–1.8), and respiratory viral (5.4%, 95% CI 4.4–6.3). COVID-19 children had higher fungal and respiratory viral coinfections in ICU units (1.7%, 95% CI 0.4–2.9 and 6.6%, 95% CI 5–8.1, respectively) than mixed ICU and non-ICU patients. However, bacterial coinfection was lower in children infected with SARS-CoV-2 in ICU group (3%, 95% CI 1.7–4.3). Children with COVID-19 seem to have a distinctly lower susceptibility to bacterial, fungal, and/or respiratory viral coinfections than adults. Our study documents that 4.7% (bacteria), 0.9% (fungal), and 5.4% (viral) of the pediatric COVID-19 population harbor microbiologically confirmed coinfections, which is much lower than the recent systematic review and meta-analysis, including 72 studies, conducted from 1 December 2019 to 31 March 2021, portraying coinfection rates of 15.9% (bacterial), 3.7% (fungal), and 6.6% (viral) in the adult COVID-19 population [141]. Lower rates of bacterial, fungal, and/or respiratory viral coinfection in children with SARS-CoV-2 infection compared to the adult COVID-19 population may have different explanations. Immunologically, children seem to have an immature receptor system, immune-system-specific regulatory mechanisms, and possible cross-protection from other common bacterial, fungal, and viral infections occurring in children [142,143]. A growing body of evidence suggests that children’s immune systems can neutralize SARS-CoV-2 because their T cells are relatively naïve and mostly untrained, and thus might have a greater capacity to respond to new viruses and eliminate SARS-CoV-2 before it replicates in large numbers [144,145,146]. Children are also the main reservoir for seasonal coronaviruses, and some researchers have suggested that antibodies for these coronaviruses might confer some protection against SARS-CoV-2 [143,146]. Moreover, children are more protected at the cellular level, as the expression of angiotensin-converting enzyme 2, which is the receptor that SARS-CoV-2 uses for host entry, is less frequently expressed in the epithelial cells of the nasal passages and lungs of younger children [147]. Otherwise, differences can be explained by the numerous different study designs to a large extent, as well as selection bias, consideration of respiratory and extra-respiratory pathogens, microbiological investigations employed, use of culture and non-culture methods, time of specimen collection, exclusion/inclusion of contaminants, climate, temporal variations in microbial epidemiology and the study population itself.
Three previous systematic reviews and meta-analyses reported on bacterial, fungal, and respiratory vial coinfections; however, these studies included mixed populations of adults and children, included a smaller number of studies (with most data for adults and very few pediatric patients), and sensitivity analysis to study the proportion of coinfection in COVID-19 children was not conducted [148,149,150]. To the best of our knowledge, this is the first and largest systematic review and meta-analysis to report exclusively on bacterial, fungal, and respiratory viral coinfection in children with COVID-19, and we pooled evidence from 130 studies, including at least Mycoplasma pneumoniae, Streptococcus pneumoniae, Mycobacterium tuberculosis, Staphylococcus aureus, RSV, rhinovirus, influenza A or B virus, adenovirus, parainfluenza virus, and metapneumovirus due to their virulence and prevalence, in an attempt to avoid measurement bias. Of the 98.6% who had additional respiratory viruses or bacteria detected, we found that the most common identified virus and bacterium in children with COVID-19 were RSV (n = 342, 31.4%) and Mycoplasma pneumonia (n = 120, 23.1%), in line with findings in two previous systematic reviews and meta-analyses, which reported that RSV and Mycoplasma pneumonia were the most commonly isolated co-pathogens in the adult population with SARS-CoV-2 infection [148,150]. RSV and Mycoplasma pneumonia cause acute respiratory tract illness in people of all ages, and all children are infected with RSV by 2 years of age [151], while approximately one-half of patients infected with Mycoplasma pneumonia are <6 years old [school-age years) [152]. RSV is the most common cause of lower respiratory tract infection in children <1 year of age [153], and bronchiolitis (up to 80% of which is caused by RSV) is a leading cause of hospital admission [154] and an important cause of death in infants and young children [155]. Mycoplasma pneumonia is the second most common cause of respiratory tract infections, and upper and lower respiratory tracts may be affected [156]. This pathogen causes a wide spectrum of illness, ranging from asymptomatic to severe community-acquired pneumonia or extrapulmonary manifestations necessitating ICU admission [157,158]. Several countries have reported that there has been a suppression of RSV and Mycoplasma pneumonia circulation, and their typical seasonality, since early 2020 due to the preventive infection control measures and non-pharmaceutical interventions against SARS-CoV-2 [159,160,161,162,163,164]. However, RSV and Mycoplasma pneumonia activity rebounded in early–mid 2021 at a fast pace, as public health restrictions and social distancing regulations were relaxed; higher hospitalization rates were reported, and most of the hospitalized children required ICU admission [165,166,167]. Although two recent studies demonstrated no association between SARS-CoV-2 and RSV coinfection and clinical severity (need or use of supplemental oxygen, ICU admission, mechanical ventilation, and mortality), the evidence was only based on three small studies [167,168]. In contrast, evidence of clinical severity regarding cases coinfected with SARS-CoV-2 and Mycoplasma pneumonia is well-established, and several studies reported such coinfection as being associated with an increase in inpatient mortality, length of hospital stay, and need for mechanical ventilation [69,100,169,170]. In children, both RSV and Mycoplasma pneumonia are similar to SARS-CoV-2; as potential triggers for a cytokine storm, leading to the development of Multisystem Inflammatory Syndrome in Children (MIS-C), they appear to play a role in the pathogenesis, and may contribute to the subsequent clinical severity of COVID-19. The cytokines tumor necrosis factor-alpha, interleukin-8, interleukin-6, and interleukin-1 beta were detected in the airway secretions of children infected with RSV and Mycoplasma pneumonia, which may act as a double whammy of respiratory pathogens and correlate with severe pathogenesis [171,172,173,174]. As coinfection with either the highly contagious RSV or Mycoplasma pneumonia and SARS-CoV-2 can modify the disease course and contribute to severity, and can cause serious compilations in children, especially those with high-risk comorbidities, healthcare workers need to consider RSV or Mycoplasma pneumonia and SARS-CoV-2 coinfection in the differential diagnosis of acute febrile illness in the endemic areas.
It is noteworthy that in the studies where the laboratory techniques for co-pathogen detection were described, a high number of bacterial and viral coinfections in children infected with SARS-CoV-2 included in our review were diagnosed serologically through the detection of immunoglobulins M and/or G. One of the easiest, most convenient, and fastest point-of-care testing to diagnose COVID-19 and other bacterial, fungal, and/or respiratory co-pathogens is by rapid serology tests; however, serology testing has been associated with many false-positive antibody test results for COVID-19 and mixed pathogens [111,175,176]. Therefore, application of serologic laboratory techniques for co-pathogen detection across all studies was likely to reveal an even higher overall coinfection proportion and high rates of anti-infective use for admitted children with SARS-CoV-2 infection to treat documented or presumed bacterial, fungal, and/or respiratory viral coinfections [177,178,179]. In line with previous studies, we identified high anti-infective use in pediatric patients with COVID-19 [177,180,181]. As the prevalence of bacterial, fungal, or respiratory viral coinfections in children with COVID-19 is not high, and anti-infectives likely provide minimal benefit as an empirical treatment, clinicians should prescribe anti-infectives wisely, and only in cases with an objective diagnosis of coinfection, as injudicious use of anti-infectives is associated with unintended consequences, such as adverse events, toxicity, resistance, Clostridioides difficile infections, risk of emergence and transmission of multidrug-resistant organisms, morbidity, and death [182,183,184,185,186,187]. Undoubtedly, coinfection in children with COVID-19 is likely to be an important modifier in the development of these abovementioned unintended consequences; however, the degree to which co-pathogens interact with SARS-CoV-2 remains unclear in many cases, and even where we know that interactions are occurring, the mechanisms are often poorly defined [188,189].
The combined pooled prevalence for fungal coinfections reported in our review in COVID-19 children is very low (0.98%). In general, very low numbers of fungal species, out of thousands of fungi, are pathogenic [190], and fungal infections in children, other than those caused by Candida species, are uncommon [191]. This can be explained by the strong natural immunity towards fungi in healthy children, and almost every invasive fungal infection that occurs in children is opportunistic [192]. In line with previous studies, all children infected with SARS-CoV-2 who were coinfected with fungi had recognized risk factors for fungaemia, such as use of central lines, malignancy, renal failure, mechanical ventilation, immunosuppression, neutropenia, solid organ transplant recipients, and use of broad-spectrum parenteral antibiotics and corticosteroids [193,194]. Fungal infections in children can be curbed by early diagnosis and timely treatment with the optimal prescription of antifungals based on culture and susceptibility tests, along with adopting appropriate hygienic and sanitization measures [195,196].

Limitations of the Study

We acknowledge that our study is not without some limitations. First, while all of the evidence discussed was based on many cohorts and case series, and some case reports, many of these were small and performed in single centers, and not necessarily generalizable to children infected with SARS-CoV-2 who had bacterial, fungal, or respiratory viral coinfections. Second, almost all studies included in this review were retrospective in design, except seven prospective studies, which could have introduced potential reporting bias due to reliance on obtaining illness histories regarding the identified pediatric cases with COVID-19 and coinfection from household members or contacts and clinical case records. Third, to asses factors associated with the clinical severity in children infected with SARS-CoV-2 who have coinfections, a larger cohort of patients is needed. Last, the study was not registered in Prospero, an international prospective register of systematic reviews, as this might have added extra work and the merit was mostly limited to the avoidance of duplication.

5. Conclusions

Children with COVID-19 seem to have distinctly lower rates of bacterial, fungal, and/or respiratory viral coinfections than adults. RSV and Mycoplasma pneumonia were the most common identified virus and bacterium in children infected with SARS-CoV-2. Knowledge of bacterial, fungal, and/or respiratory viral confections has potential diagnostic and treatment implications in COVID-19 children.

Author Contributions

S.A., M.A., N.A.D., Z.A.A. and A.A.A. (Abdulrahman A. Alnaim) contributed equally to the systematic review. S.A., A.A.M. and A.A.R. were the core team leading the systematic review. S.A., M.A., N.A.D., Z.A.A., A.A.A. (Abdulrahman A. Alnaim) and K.M.A.M. identified and selected the studies. K.A.N., M.A.A.G., S.J.A., A.A.A. (Abdulaziz A. Alahmari), S.M.A.H.M. and Y.A.A. (Yameen Ali Almatawah) conducted the quality assessment of the studies. S.A., O.M.B., A.A.A. (Ahmed Abdulwhab Alismaeel), S.K.A., S.A.A., Z.R.A., N.A.A.B., H.Y.A., J.A.A., Q.A.A., S.M.A., H.A.A., T.N.A. and Y.A.A. (Yousif Ahmad Alabdulaly) collected the data. S.A., M.A., Z.A.A., A.A.A. (Abdulrahman A. Alnaim), K.A.N., M.A.A.G., S.J.A. and A.A.A. (Abdulaziz A. Alahmari) drafted the manuscript. The corresponding author attests that all listed authors meet authorship criteria, and that no others meeting the criteria have been omitted. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

This review is exempt from ethics approval because we collected and synthesized data from previous clinical studies in which informed consent had already been obtained by the investigators.

Informed Consent Statement

Not applicable.

Data Availability Statement

Not applicable.

Acknowledgments

We would like to thank authors and their colleagues who contributed to the availability of evidence needed to compile this article. We would also like to thank the reviewers for their helpful and valuable comments and suggestions for improving the paper.

Conflicts of Interest

The authors declare that they have no competing interest.

Abbreviations

ARDS, acute respiratory distress syndrome; CMV, Cytomegalovirus; CONS, coagulase-negative Staphylococcus species; COVID-19, coronavirus disease 2019; CSF, cerebrospinal fluid; EBV, Epstein–Barr virus; ICU, intensive care unit; IgG, immunoglobulin G; IgM, immunoglobulin M; MRSA, Methicillin-resistant Staphylococcus aureus; MSSA, Methicillin-susceptible Staphylococcus aureus; NOS, Newcastle–Ottawa scale; PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses; RSV, respiratory syncytial virus; RT-PCR, real-time reverse transcription–polymerase chain reaction; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.

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Figure 1. Monoinfection with SARS-CoV-2 results in less severe form of COVID-19 and better prognosis. In contrast, SARS-CoV-2 coinfection with bacteria, fungi, and/or respiratory viruses may intensify the severity of COVID-19 and increase the expression of macrophages, T and B defensive cells that may cause the elevation of inflammatory cytokines such as tumor necrosis factor-alpha, interleukin-1, and interleukin-6 in the infected organs, leading to a hyperinflammatory response by recruiting immune cells.
Figure 1. Monoinfection with SARS-CoV-2 results in less severe form of COVID-19 and better prognosis. In contrast, SARS-CoV-2 coinfection with bacteria, fungi, and/or respiratory viruses may intensify the severity of COVID-19 and increase the expression of macrophages, T and B defensive cells that may cause the elevation of inflammatory cytokines such as tumor necrosis factor-alpha, interleukin-1, and interleukin-6 in the infected organs, leading to a hyperinflammatory response by recruiting immune cells.
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Figure 2. Flow diagram of literature search and data extraction from studies included in the systematic review and meta-analysis.
Figure 2. Flow diagram of literature search and data extraction from studies included in the systematic review and meta-analysis.
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Figure 3. Pooled estimate for the prevalence of bacterial coinfections in children with COVID-19 stratified by the ICU admission (ICU and non-ICU compared to ICU only). [4,5,6,7,8,9,12,13,20,23,32,36,39,57,58,63,64,66,69,77,80,81,84,85,88,98,105,109,131,132,133,135,137,139].
Figure 3. Pooled estimate for the prevalence of bacterial coinfections in children with COVID-19 stratified by the ICU admission (ICU and non-ICU compared to ICU only). [4,5,6,7,8,9,12,13,20,23,32,36,39,57,58,63,64,66,69,77,80,81,84,85,88,98,105,109,131,132,133,135,137,139].
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Figure 4. Pooled estimate for the prevalence of fungal coinfections in children with COVID-19 stratified by the ICU admission (ICU and non-ICU compared to ICU only). [5,8,9,13,23,139].
Figure 4. Pooled estimate for the prevalence of fungal coinfections in children with COVID-19 stratified by the ICU admission (ICU and non-ICU compared to ICU only). [5,8,9,13,23,139].
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Figure 5. Pooled estimate for the prevalence of respiratory viral coinfections in children with COVID-19 stratified by the ICU admission (ICU and non-ICU compared to ICU only). [4,5,6,7,9,12,20,23,32,36,39,57,58,63,64,66,69,77,80,81,84,85,88,98,105,109,131,132,133,135,137,139].
Figure 5. Pooled estimate for the prevalence of respiratory viral coinfections in children with COVID-19 stratified by the ICU admission (ICU and non-ICU compared to ICU only). [4,5,6,7,9,12,20,23,32,36,39,57,58,63,64,66,69,77,80,81,84,85,88,98,105,109,131,132,133,135,137,139].
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Figure 6. Funnel plot to evaluate publication bias for the pooled effect size to estimate the prevalence of bacterial coinfections in children with COVID-19 based on ICU admission.
Figure 6. Funnel plot to evaluate publication bias for the pooled effect size to estimate the prevalence of bacterial coinfections in children with COVID-19 based on ICU admission.
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Figure 7. Funnel plot to evaluate publication bias for the pooled effect size to estimate the prevalence of fungal coinfections in children with COVID-19 based on ICU admission.
Figure 7. Funnel plot to evaluate publication bias for the pooled effect size to estimate the prevalence of fungal coinfections in children with COVID-19 based on ICU admission.
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Figure 8. Funnel plot to evaluate publication bias for the pooled effect size to estimate the prevalence of respiratory viral coinfections in children with COVID-19 based on ICU admission.
Figure 8. Funnel plot to evaluate publication bias for the pooled effect size to estimate the prevalence of respiratory viral coinfections in children with COVID-19 based on ICU admission.
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Table 2. Proportion of all identified bacterial co-pathogens in children with COVID-19 (N = 520).
Table 2. Proportion of all identified bacterial co-pathogens in children with COVID-19 (N = 520).
Bacterial Pathogen TypeIdentified Number (%)
Unspecified bacteria181 (34.8)
Mycoplasma pneumoniae120 (23.1)
Streptococcus pneumoniae65 (12.5)
Mycobacterium tuberculosis31 (6)
Staphylococcus aureus12 (2.3)
Escherichia coli11 (2.1)
Haemophilus influenza10 (1.9)
Chlamydia pneumoniae9 (1.7)
Pseudomonas aeruginosa9 (1.7)
MSSA8 (1.5)
Moraxella catarrhalis7 (1.3)
Scrub typhus7 (1.3)
MRSA6 (1.1)
Salmonella typhi5 (1)
Group A Streptococcus4 (0.8)
Klebsiella pneumoniae4 (0.8)
CONS3 (0.6)
Acinetobacter baumannii2 (0.4)
Bordetella pertussis2 (0.4)
Klebsiella oxytoca2 (0.4)
Klebsiella pneumoniae2 (0.4)
Neisseria meningitidis2 (0.4)
Prevotella species2 (0.4)
Streptococcus constellatus2 (0.4)
Streptococcus agalactiae1 (0.2)
Streptococcus intermedius1 (0.2)
Streptococcus mitis1 (0.2)
Citrobacter koseri1 (0.2)
Clostridium difficile1 (0.2)
Enterobacter1 (0.2)
Enterobacter aerogenes1 (0.2)
Enterobacter cloacae1 (0.2)
Enterobacter asburiae1 (0.2)
Escherichia hermannii1 (0.2)
Gram-negative bacilli1 (0.2)
Mycobacterium bovis1 (0.2)
Salmonella enteritis1 (0.2)
Staphylococcus epidermidis1 (0.2)
Abbreviations: CONS, coagulase-negative Staphylococcus species; COVID-19, coronavirus disease 2019; MRSA, Methicillin-resistant Staphylococcus aureus; MSSA, Methicillin-susceptible Staphylococcus aureus.
Table 3. Proportion of all identified fungal co-pathogens in children with COVID-19 (N = 23).
Table 3. Proportion of all identified fungal co-pathogens in children with COVID-19 (N = 23).
Fungal Pathogen TypeIdentified Number (%)
Unspecified fungi13 (56.5)
Aspergillus species3 (13)
Fungal bezoars2 (8.7)
Candida albicans1 (4.3)
Candida auris1 (4.3)
Candida glabrata1 (4.3)
Candida rugosa1 (4.3)
Candida tropicalis1 (4.3)
Table 4. Proportion of all identified respiratory viral co-pathogens in children with COVID-19 (N = 1090).
Table 4. Proportion of all identified respiratory viral co-pathogens in children with COVID-19 (N = 1090).
Viral Pathogen TypeIdentified Number (%)
RSV342 (31.4)
Rhinovirus209 (19.2)
Unspecified viruses198 (18.2)
Influenza A virus80 (7.3)
Adenovirus60 (5.5)
Parainfluenza virus (types 1–4)29 (2.7)
Influenza B virus28 (2.6)
Metapneumovirus27 (2.5)
Rotavirus, adenovirus, and norovirus25 (2.3)
EBV14 (1.3)
Cytomegalovirus12 (1.1)
Dengue virus12 (1.1)
Coronaviruses (HKU-1/OC 43)11 (1)
Bocavirus10 (0.9)
Coronaviruses (229E, NL63, and OC43)6 (0.5)
Enterovirus5 (0.4)
Herpes simplex virus5 (0.4)
Coronavirus NL635 (0.4)
Varicella zoster virus4 (0.4)
Rotavirus2 (0.2)
Human Herpesvirus 61 (0.1)
Norovirus1 (0.1)
Parechovirus1 (0.1)
Parvovirus B191 (0.1)
Hepatitis A virus1 (0.1)
Herpes virus 41 (0.1)
Abbreviations: EBV, Epstein–Barr virus; RSV, respiratory syncytial virus.
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Alhumaid, S.; Alabdulqader, M.; Al Dossary, N.; Al Alawi, Z.; Alnaim, A.A.; Al Mutared, K.M.; Al Noaim, K.; Al Ghamdi, M.A.; Albahrani, S.J.; Alahmari, A.A.; et al. Global Coinfections with Bacteria, Fungi, and Respiratory Viruses in Children with SARS-CoV-2: A Systematic Review and Meta-Analysis. Trop. Med. Infect. Dis. 2022, 7, 380. https://doi.org/10.3390/tropicalmed7110380

AMA Style

Alhumaid S, Alabdulqader M, Al Dossary N, Al Alawi Z, Alnaim AA, Al Mutared KM, Al Noaim K, Al Ghamdi MA, Albahrani SJ, Alahmari AA, et al. Global Coinfections with Bacteria, Fungi, and Respiratory Viruses in Children with SARS-CoV-2: A Systematic Review and Meta-Analysis. Tropical Medicine and Infectious Disease. 2022; 7(11):380. https://doi.org/10.3390/tropicalmed7110380

Chicago/Turabian Style

Alhumaid, Saad, Muneera Alabdulqader, Nourah Al Dossary, Zainab Al Alawi, Abdulrahman A. Alnaim, Koblan M. Al Mutared, Khalid Al Noaim, Mohammed A. Al Ghamdi, Suha Jafar Albahrani, Abdulaziz A. Alahmari, and et al. 2022. "Global Coinfections with Bacteria, Fungi, and Respiratory Viruses in Children with SARS-CoV-2: A Systematic Review and Meta-Analysis" Tropical Medicine and Infectious Disease 7, no. 11: 380. https://doi.org/10.3390/tropicalmed7110380

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